Infection Flashcards
COVID-19?
infectious disease caused by the novel coronavirus SARS-CoV-2, first identified in Wuhan, China, in late 2019. It has led to a global pandemic with significant morbidity and mortality.
COVID-19 presents with?
wide spectrum of clinical manifestations, from asymptomatic to severe respiratory failure and multi-organ dysfunction.
Cause of COVID-19?
Causative Agent: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Transmission of COVID-19?
Primarily via respiratory droplets
Contact with contaminated surfaces
Aerosol transmission in certain settings
Pathophysiology of COVID-19?
Virus binds to the ACE2 receptor on host cells, facilitating entry and replication
Causes a range of immune responses from mild inflammation to cytokine storm
Predominantly affects the respiratory system but can involve multiple organ systems
Clinical features of COVID-19?
Common: Fever, cough, fatigue, loss of taste or smell, myalgia
Severe: Shortness of breath, chest pain, confusion, bluish lips or face
Other: Gastrointestinal symptoms (nausea, diarrhoea), dermatological manifestations
COVID-19 disease course?
Incubation period: 2-14 days, median 5 days
Mild to moderate illness: Majority of cases
Severe illness: Occurs in approximately 14% of cases, characterised by hypoxia and pneumonia
Critical illness: Approximately 5% of cases, involving respiratory failure, shock, and multi-organ dysfunction
COVID-19 incubation period?
2-14d, median 5d
Diagnosis of COVID-19?
Testing=
Reverse transcription polymerase chain reaction (RT-PCR): GOLD STANDARD for diagnosis, detects viral RNA
Antigen Tests: Useful for rapid diagnosis but less sensitive than RT-PCR
Serological Tests: Detect antibodies, used for assessing past infection and immune response
- CXR: May show bilateral infiltrates
- CT: More sensitive, can reveal ground-glass opacities and consolidation
COVID-19= what does CXR and CT show?
- CXR: May show bilateral infiltrates
- CT: More sensitive, can reveal ground-glass opacities and consolidation
COVID-19 gold standard for diagnosis?
Reverse transcription polymerase chain reaction (RT-PCR): detects viral RNA
Mx of COVID-19?
- general measures= isolation to prevent transmission; supportive- hydration, antipyretics, O2 therapy
- pharmacological Tx
- supportive care
Mx of COVID-19= supportive care?
Oxygen Therapy: Nasal cannula, high-flow nasal oxygen, non-invasive ventilation
Mechanical Ventilation: For patients with refractory hypoxia
Extracorporeal Membrane Oxygenation (ECMO): In cases of severe ARDS
Mx of COVID-19= pharmacological Tx?
Antivirals= Remdesivir for hospitalised patients requiring oxygen
Corticosteroids= Dexamethasone for hospitalised patients requiring oxygen
Immunomodulators= Baricitinib or tocilizumab in selected cases with systemic inflammation / requiring higher levels of oxygen
COVID-19= prevention and vaccination?
Vaccination is the cornerstone of prevention, with several vaccines approved for use in the UK (e.g., Pfizer-BioNTech, Moderna, AstraZeneca)
Booster doses recommended to maintain immunity, especially in vulnerable populations
Non-pharmacological interventions: Mask-wearing, hand hygiene, social distancing
Prognosis of COVID-19?
Prognostic Factors:
- Age, comorbidities (e.g., cardiovascular disease, diabetes, obesity), and severity of respiratory involvement
- Early intervention and supportive care improve outcomes
Outcomes:
- Recovery in mild to moderate cases usually within 2-6 weeks
- Long-term sequelae (Long COVID) in some patients, including fatigue, dyspnoea, cognitive impairment
Coronavirus disease (COVID-19) definition?
infectious disease caused by a novel betacoronavirus known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2).
‘Acute COVID-19’?
signs and symptoms of infection consistent with COVID-19 for up to 4 weeks
‘Ongoing symptomatic COVID-19’?
signs and symptoms of COVID-19 infection from 4–12 weeks
‘Post-COVID-19 syndrome’?
signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis.
‘Longer term effects of COVID-19’ or ‘long COVID’ ?
signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 4 weeks, and are not explained by an alternative diagnosis.
Risk factors for severe infection of COVID-19?
increasing age, male sex, co-morbidities, health and social care workers, and Black and Asian ethnic groups.
Cx of COVID-19?
acute respiratory distress syndrome; venous thromboembolism; acute myocardial or kidney injury; and sepsis.
When to suspect COVID-19?
Fever or chills.
A new, continuous cough; breathlessness.
A loss or change to sense of smell or taste.
Fatigue; muscle aches and pains; headache.
Sore throat; blocked or runny nose.
Loss of appetite; diarrhoea; nausea and/or vomiting.
If a person has suspected or confirmed COVID-19, assessment for severe illness includes identifying:
Severe breathlessness; haemoptysis; hypoxia.
Cyanosis; feeling cold and clammy; pale or mottled skin.
Collapse or syncope.
New confusion; drowsiness.
Reduced urine output.
If a person has suspected COVID-19 and hospital admission is not needed, management includes advice to:
Take a lateral flow test if a person is at highest risk of becoming seriously ill.
Try to stay at home and avoid contact with other people, for all other people.
Self-manage symptoms and consider self-monitoring at home.
If a person has suspected or confirmed COVID-19, hospital admission should be arranged if the person:
Is moderately or severely unwell.
Has a suspected acute or life-threatening complication.
If a person has confirmed COVID-19 and hospital admission is not needed, management includes advice:
About antibody and antiviral treatments for people at highest risk of becoming seriously ill.
To try to stay at home and avoid contact with other people, for all other people.
To self-manage symptoms and consider self-monitoring at home.
To notify any confirmed case to the local health protection team.
Advice for all people to live safely with COVID-19 includes
Getting vaccinated, ensuring adequate ventilation, good hygiene, and when to consider wearing a face covering or mask.
Accessing mental health support, if needed.
Entry requirements and travel warnings when travelling abroad.
Support at work, self-employment and benefits.
Hypoxia (reduced oxygen saturation levels measured by pulse oximetry) levels in COVID-19?
92% or less in room air in adults (suggests severe hypoxia).
> 4% lower than usual levels (suggests severe hypoxia).
93–94% in room air in adults (suggests moderate hypoxia).
below 91% in room air at rest in children and young people aged 17 years and under (suggests severe hypoxia).
Consider using ‘exertion oximetry’ tests (such as the 40-step walk and one-minute sit-to-stand tests) if oxygen saturation is at least 93% and the person is aged 65 years or more and/or at highest risk of serious illness, to assess for oxygen desaturation on exercise — a 3% or greater reduction in oxygen saturation level is considered significant.
If the person has been in close contact with a person with COVID-19:
If they are a household or overnight contact of a person who has had a positive COVID-19 test result, advise that it can take up to how long for infection to develop?
10d
Advise on common new or ongoing symptoms after COVID-19, and expected recovery times.
Reassure that for most people symptoms resolve by
12w
People with the following clinical conditions are at highest risk of getting seriously ill from COVID-19 infection
Down’s syndrome or other chromosomal disorders known to affect immune competence.
Certain types of solid cancer, and/or received or receiving treatment for certain types of cancer.
Haematological diseases (such as some forms of leukaemia, lymphoma, myeloma, myelodysplastic syndrome, myelofibrosis, sickle cell disease) and recipients of haematological stem cell transplant.
Renal disease (including renal transplant recipients, non-transplant renal patients who are immunosuppressed, chronic kidney disease [CKD] stage 4 or 5).
Liver disease (some forms of cirrhosis especially decompensated liver disease, liver transplant recipients, liver disease on immunosuppressive therapy).
Other solid organ transplant recipients.
Immune-mediated inflammatory disorders (including people taking some forms of immunotherapy, biologics, JAK-inhibitors, corticosteroids, uncontrolled or clinically active disease, major organ involvement).
Immune deficiencies (including common variable immune deficiency, severe combined immunodeficiency).
HIV or AIDS (if immunosuppressed, have uncontrolled or untreated HIV, or acute presentation of AIDS-defining diagnosis).
Rare neurological and neurodisability conditions (multiple sclerosis, motor neurone disease, myasthenia gravis, or Huntington’s disease)
COVID-19= In the UK, the following vaccines targeting the S protein have been authorized for supply….
Two vaccines use an mRNA platform (Pfizer BioNTech BNT162b2 vaccine, Comirnaty®) and Moderna mRNA-1273 COVID-19 vaccine (Spikevax®). These vaccines have no whole or live virus involved, and the vaccines cannot cause disease. The mRNA naturally degrades after a few days.
- Comirnaty 3 micrograms/dose mRNA COVID-19 vaccine is licensed for use in infants and children aged 6 months to 4 years.
Two vaccines use an adenovirus vector (AstraZeneca COVID-19 ChAdOx1-S vaccine/Vaxzevria®) and COVID-19 Janssen Ad26.COV2-S (recombinant, less widely used). The adenovirus is modified so it cannot replicate in human cells, and cannot cause disease.
The recommended vaccines for the autumn 2024 campaign are monovalent products containing mRNA for the spike protein of the JN.1 sub-lineage of the Omicron variant strain of the SARS-CoV-2 virus. What are they?
18 years and over:
- Moderna mRNA (Spikevax) vaccine 50 micrograms , or
- Pfizer-BioNTech mRNA (Comirnaty) vaccine 30 micrograms
12 to 17 years:
- Pfizer-BioNTech mRNA (Comirnaty) vaccine 30 micrograms
5 to 11 years:
- Pfizer-BioNTech mRNA (Comirnaty) vaccine 10 micrograms
6 months to 4 years.
- Pfizer-BioNTech mRNA (Comirnaty) vaccine 3 micrograms
Prolonged symptoms of COVID-19 is or is not a contraindication to COVID-19 vaccine.
NOT
but active illness is
Common or very common adverse effects of COVID-19 vaccines?
Local injection site reactions, such as pain, swelling, redness, tenderness; fatigue; headache; chills; myalgia; arthralgia; fever.
Lymphadenopathy (in the axillary, supraclavicular, or cervical areas on the ipsilateral side to injection).
COVID-19 vaccines are what?
black triangle drugs, and any adverse reactions should be reported to the Medicines and Healthcare products Regulatory Agency (MHRA) using the Coronavirus Yellow Card reporting site.
Rare or uncommon potential adverse effects of COVID-19 vaccines?
Myocarditis and pericarditis
Vaccine-induced immune thrombocytopenia and thrombosis (VITT)
Acute disseminated encephalomyelitis (ADEM) — extremely rare cases have been reported following vaccination with the AstraZeneca vaccine, although a causal relationship has not been established. Cases with fatal outcome have been reported.
Guillain-Barré syndrome
Capillary leak syndrome
Transverse myelitis
Dizziness
Paraesthesia and hypoaesthesia
Recommended COVID-19 vaccines for pregnant women?
If she is over the age of 18 years, the Pfizer BioNTech or Moderna vaccines should be offered.
If she is under the age of 18 years, the Pfizer BioNTech vaccine should be offered.
If she has already received a dose of the AstraZeneca vaccine, she can complete the course with the same vaccine or an mRNA vaccine.
If a woman finds out she is pregnant after she has started a course of vaccine:
She may complete vaccination during pregnancy, and should complete vaccination at the recommended interval.
If a woman is breastfeeding:
Advise there is no known risk associated with a non-live COVID-19 vaccine while breastfeeding.
There is no evidence for any safety concerns with the co-administration of COVID-19 vaccine with other vaccines, and interference between inactivated vaccines with different antigenic content is likely to be limited.
Be aware that co-administration may make the attribution of adverse effects more difficult.
Be aware that administration of Novavax COVID-19 vaccine should be separated from administration of …..
influenza vaccine by at least 7 days.
Viral warts?
common and do not require treatment unless painful, unsightly or a patient is requesting treatment for a persistent wart.
Prognosis of viral warts?
Most of them will resolve spontaneously within months or at most within 2 years. In adults it can take up to 10 years.
Gangrene?
death of body tissue due to a lack of blood supply, infection, or both
Where does gangrene commonly affect?
anywhere but commonly in the extremities, such as the toes, fingers, feet, and hands
Why is gangrene a medical emergency that requires prompt diagnosis and Tx?
to prevent further tissue loss, systemic infection, and potentially life-threatening complications
Pathophysiology of gangrene?
involves the interruption of blood supply, leading to tissue ischaemia and necrosis
The pathophysiology of gangrene involves the interruption of blood supply, leading to tissue ischaemia and necrosis. This can occur due to what?
Arterial occlusion: Atherosclerosis, thrombosis, or embolism can obstruct blood flow.
Infection: Bacteria, especially in wet and gas gangrene, can exacerbate tissue necrosis through toxin production.
Trauma: Severe injuries can compromise blood supply and introduce pathogens.
Chronic conditions: Diabetes mellitus and other chronic diseases can predispose individuals to gangrene by impairing vascular function and immune response.
Types of gangrene?
1) Dry gangrene
2) Wet gangrene
3) Gas gangrene (Clostridial myonecrosis)
4) Necrotising fasciitis
Types of gangrene= dry gangrene- cause?
chronic ischaemia, usually due to peripheral arterial disease (PAD).
Types of gangrene= dry gangrene- appearance?
Characterised by dry, shrivelled, and blackened tissue (‘mummified’).
Clear demarcation between healthy and necrotic tissue.
Typically painless due to nerve damage.
Types of gangrene= dry gangrene- prognosis?
Often develops slowly and is usually not associated with infection.
Types of gangrene= wet gangrene- cause?
Results from a sudden lack of blood supply combined with bacterial infection.
Types of gangrene= wet gangrene- appearance?
Swollen, moist, and blistered tissue with a foul odour.
Rapid spread and marked systemic symptoms such as fever and malaise.
Severe pain and erythema around the affected area.
Types of gangrene= wet gangrene- prognosis?
Progresses rapidly and can lead to systemic sepsis.
Types of gangrene= gas gangrene (Clostridial myonecrosis)- cause?
Caused by infection with Clostridium bacteria, which produce gas and toxins.
Types of gangrene= gas gangrene (Clostridial myonecrosis)- appearance?
Severe pain and swelling at the site of infection.
Crepitus due to gas production by Clostridium bacteria.
Rapid onset of systemic symptoms, including tachycardia, hypotension, and shock.
Types of gangrene= gas gangrene (Clostridial myonecrosis)- prognosis?
Requires urgent medical intervention due to rapid progression and high mortality.
Types of gangrene= necrotising fasciitis?
A severe form of gangrene involving the fascia and subcutaneous tissues.
Types of gangrene= necrotising fasciitis- cause?
Caused by mixed bacterial infections, often including Streptococcus pyogenes and Staphylococcus aureus.
Types of gangrene= necrotising fasciitis- appearance?
Intense pain disproportionate to the visible signs.
Rapid progression of erythema, swelling, and tissue necrosis.
Systemic signs of sepsis, such as fever, tachycardia, and hypotension
Mx of gangrene requires what?
urgent intervention to control infection, restore blood supply, and remove necrotic tissue
Key Mx strategies of gangrene?
- surgical intervention
- antibiotic therapy
- supportive care
- hyperbaric oxygen therapy
Mx of gangrene= surgical intervention?
Debridement: Surgical removal of necrotic tissue to prevent the spread of infection.
Amputation: In severe cases, partial or complete amputation of the affected limb may be necessary.
Revascularisation: Procedures such as angioplasty or bypass surgery to restore blood flow in cases of arterial occlusion.
Mx of gangrene= antibiotic therapy?
Empirical broad-spectrum antibiotics initially, followed by targeted therapy based on culture results.
For gas gangrene, high-dose penicillin and clindamycin are often recommended.
Mx of gangrene= antibiotic therapy recommended for gas gangrene?
high-dose penicillin and clindamycin
Mx of gangrene= supportive care?
Management of systemic symptoms, including fluid resuscitation, pain control, and nutritional support.
Monitoring and treatment of comorbid conditions such as diabetes and cardiovascular disease.
Mx of gangrene= hyperbaric oxygen therapy?
Used in some cases of gas gangrene to enhance oxygen delivery to ischaemic tissues and inhibit anaerobic bacterial growth.
Why is diarrhoea common in pts with HIV?
may be due to the effects of the virus itself (HIV enteritis) or opportunistic infections
Possible causes of diarrhoea in pts with HIV?
Cryptosporidium + other protozoa (most common)
Cytomegalovirus
Mycobacterium avium intracellulare
Giardia
Most common cause of diarrhoea in pts with HIV?
Cryptosporidium
Cryptosporidium causing diarrhoea in pts with HIV?
an intracellular protozoa and has an incubation period of 7 days
Presentation is very variable, ranging from mild to severe diarrhoea
Cryptosporidium causing diarrhoea in pts with HIV= staining?
A modified Ziehl-Neelsen stain (acid-fast stain) of the stool may reveal the characteristic red cysts of Cryptosporidium.
Cryptosporidium causing diarrhoea in pts with HIV= Tx?
difficult, with the mainstay of management being supportive therapy (nitazoxanide is licensed in the US for immunocompetent patients)
Mycobacterium avium intracellulare causing diarrhoea in pts with HIV?
an atypical mycobacteria seen with the CD4 count is below 50. Typical features include fever, sweats, abdominal pain and diarrhoea. There may be hepatomegaly and deranged LFTs. Diagnosis is made by blood cultures and bone marrow examination.
Mycobacterium avium intracellulare causing diarrhoea in pts with HIV= Mx?
rifabutin, ethambutol and clarithromycin
Mycobacterium avium intracellulare causing diarrhoea in pts with HIV= diagnosis?
may be hepatomegaly and deranged LFTs
Diagnosis is made by blood cultures and bone marrow examination
Kaposi’s sarcoma= caused by what?
HHV-8 (human herpes virus 8)
Kaposi’s sarcoma= presentation?
purple papules or plaques on the skin or mucosa (e.g. gastrointestinal and respiratory tract)
skin lesions may later ulcerate
respiratory involvement may cause massive haemoptysis and pleural effusion
Pt with HIV:
- purple papules or plaques on the skin or mucosa (e.g. gastrointestinal and respiratory tract)
- skin lesions may later ulcerate
- respiratory involvement may cause massive haemoptysis and pleural effusion
Kaposi’s sarcoma
Kaposi’s sarcoma= Mx?
radiotherapy + resection
Kaposi’s sarcoma more common in who?
pt with HIV
HIV= Antiretroviral therapy (ART) involves a combination of what?
at least three drugs, typically two nucleoside reverse transcriptase inhibitors (NRTI) and either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)
HIV= Antiretroviral therapy (ART)- the combination of drugs decreases what?
viral replication but also reduces the risk of viral resistance emerging
HIV= it is now recommended that patients start ART when?
as soon as they have been diagnosed with HIV, rather than waiting until a particular CD4 count, as was previously advocated.
HIV Mx= entry inhibitors?
maraviroc (binds to CCR5, preventing an interaction with gp41), enfuvirtide (binds to gp41, also known as a ‘fusion inhibitor’)
prevent HIV-1 from entering and infecting immune cells
HIV Mx= Nucleoside analogue reverse transcriptase inhibitors (NRTI)?
examples: zidovudine (AZT), abacavir, emtricitabine, didanosine, lamivudine, stavudine, zalcitabine, tenofovir
general NRTI side-effects: peripheral neuropathy
tenofovir: used in BHIVAs two recommended regime NRTI. Adverse effects include renal impairment and ostesoporosis
zidovudine: anaemia, myopathy, black nails
didanosine: pancreatitis
HIV Mx= Nucleoside analogue reverse transcriptase inhibitors (NRTI) general side effects?
peripheral neuropathy
HIV Mx= Nucleoside analogue reverse transcriptase inhibitors (NRTI)- tenofovir?
used in BHIVAs two recommended regime NRTI. Adverse effects include renal impairment and ostesoporosis
HIV Mx= Nucleoside analogue reverse transcriptase inhibitors (NRTI)- zidovudine?
anaemia, myopathy, black nails
HIV Mx= Nucleoside analogue reverse transcriptase inhibitors (NRTI)- didanosine?
pancreatitis
HIV Mx= Non-nucleoside reverse transcriptase inhibitors (NNRTI)?
examples: nevirapine, efavirenz
side-effects: P450 enzyme interaction (nevirapine induces), rashes
HIV Mx= Protease inhibitors (PI)?
examples: indinavir, nelfinavir, ritonavir, saquinavir
side-effects: diabetes, hyperlipidaemia, buffalo hump, central obesity, P450 enzyme inhibition
indinavir: renal stones, asymptomatic hyperbilirubinaemia
ritonavir: a potent inhibitor of the P450 system
HIV Mx= Protease inhibitors (PI)- side effects?
diabetes, hyperlipidaemia, buffalo hump, central obesity, P450 enzyme inhibition
HIV Mx= Protease inhibitors (PI)- indinavir?
renal stones, asymptomatic hyperbilirubinaemia
HIV Mx= Protease inhibitors (PI)- ritonavir?
a potent inhibitor of the P450 system
HIV Mx= Integrase inhibitors?
block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell
examples: raltegravir, elvitegravir, dolutegravir
HIV Mx= Integrase inhibitors examples?
raltegravir, elvitegravir, dolutegravir
HIV focal neurological lesions= Toxoplasmosis?
accounts for around 50% of cerebral lesions in patients with HIV
constitutional symptoms, headache, confusion, drowsiness
HIV focal neurological lesions= Toxoplasmosis- CT findings?
single or multiple ring enhancing lesions, mass effect may be seen
HIV focal neurological lesions= Toxoplasmosis- Mx?
sulfadiazine and pyrimethamine
HIV focal neurological lesions= Primary CNS lymphoma?
accounts for around 30% of cerebral lesions
associated with the Epstein-Barr virus
HIV focal neurological lesions= Primary CNS lymphoma- CT findings?
single or multiple homogenous enhancing lesions
HIV focal neurological lesions= Primary CNS lymphoma- Tx?
involves steroids (may significantly reduce tumour size), chemotherapy (e.g. methotrexate) + with or without whole brain irradiation. Surgical may be considered for lower grade tumours
HIV focal neurological lesions= Differentiating between toxoplasmosis and lymphoma is a common clinical scenario in HIV patients. It is clearly important given the vastly
different treatment strategies.
HIV focal neurological lesions= Toxoplasmosis vs Primary CNS lymphoma?
Lymphoma= Single lesion; Solid (homogenous) enhancement; Thallium SPECT positive
Toxoplasmosis=
Multiple lesions, Ring or nodular enhancement, Thallium SPECT negative
TB= single enhancing lesion
HIV focal neurological lesions= Tuberculosis?
much less common than toxoplasmosis or primary CNS lymphoma
HIV focal neurological lesions= Tuberculosis- CT findings?
single enhancing lesion
HIV general neurological disease= encephalitis?
may be due to CMV or HIV itself
HSV encephalitis but is relatively rare in the context of HIV
HIV general neurological disease= encephalitis- CT findings?
oedematous brain
HIV general neurological disease= Cryptococcus?
most common fungal infection of CNS
headache, fever, malaise, nausea/vomiting, seizures, focal neurological deficit
HIV general neurological disease= Cryptococcus- CSF findings?
high opening pressure
elevated protein
reduced glucose
normally a lymphocyte predominance but in HIV white cell count many be normal
India ink test positive
HIV general neurological disease= Cryptococcus- CT findings?
meningeal enhancement, cerebral oedema
HIV general neurological disease= Cryptococcus- what is a typical presentation?
meningitis is typical presentation but may occasionally cause a space-occupying lesion
HIV general neurological disease= most common fungal infection of CNS?
Cryptococcus
HIV general neurological disease= Progressive multifocal leukoencephalopathy (PML)?
widespread demyelination
due to infection of oligodendrocytes by JC virus (a polyoma DNA virus)
HIV general neurological disease= Progressive multifocal leukoencephalopathy (PML)- symptoms?
subacute onset : behavioural changes, speech, motor, visual impairment
HIV general neurological disease= Progressive multifocal leukoencephalopathy (PML)- CT findings?
single or multiple lesions, no mass effect, don’t usually enhance.
MRI is better - high-signal demyelinating white matter lesions are seen
HIV general neurological disease= AIDS dementia complex?
caused by HIV virus itself
symptoms: behavioural changes, motor impairment
HIV general neurological disease= AIDS dementia complex- CT findings?
cortical and subcortical atrophy
most common cause of oesophagitis in patients with HIV?
Oesophageal candidiasis
HIV= Oesophageal candidiasis generally seen in who?
generally seen in patients with a CD4 count of less than 100
HIV= Oesophageal candidiasis?
most common cause of oesophagitis in patients with HIV
HIV= Oesophageal candidiasis symptoms?
dysphagia and odynophagia
HIV= Oesophageal candidiasis Tx?
1st line treatments= Fluconazole and itraconazole
HIV= some infections and other disorders may be encountered by pts with HIV according to what?
CD4 count
HIV= List 4 infections/disorders may be likely if CD4 count 200 - 500 cells/mm³?
Oral thrush
Shingles
Hairy leukoplakia
Kaposi sarcoma
HIV= infections/disorders may be likely if CD4 count 200 - 500: oral thrush secondary to?
Candida albicans
HIV= infections/disorders may be likely if CD4 count 200 - 500: shingles secondary to?
herpes zoster
HIV= infections/disorders may be likely if CD4 count 200 - 500: hairy leukoplakia secondary to?
EBV
HIV= infections/disorders may be likely if CD4 count 200 - 500: Kaposi sarcoma secondary to?
HHV-8
HIV= List 5 infections/disorders may be likely if CD4 count 100-200 cells/mm³?
Cryptosporidiosis
Cerebral toxoplasmosis
Progressive multifocal leukoencephalopathy
Pneumocystis jirovecii pneumonia
HIV dementia
HIV= infections/disorders may be likely if CD4 count 100-200: Cryptosporidiosis?
Whilst patients with a CD4 count of 200-500 may develop cryptosporidiosis the disease is usually self-limiting and similar to that in immunocompetent hosts
HIV= infections/disorders may be likely if CD4 count 100-200: Progressive multifocal leukoencephalopathy secondary to what?
JC virus
HIV= List 4 infections/disorders may be likely if CD4 count 50-100 cells/mm³?
Aspergillosis
Oesophageal candidiasis
Cryptococcal meningitis
Primary CNS lymphoma
HIV= infections/disorders may be likely if CD4 count 50-100: aspergillosis secondary to what?
Aspergillus fumigatus
HIV= infections/disorders may be likely if CD4 count 50-100: oesophageal candidiasis secondary to what?
Candida albicans
HIV= infections/disorders may be likely if CD4 count 50-100: primary CNS lyphoma secondary to what?
EBV
HIV= List 2 infections/disorders may be likely if CD4 count <50 cells/mm³?
Cytomegalovirus retinitis
Mycobacterium avium-intracellulare infection
HIV= infections/disorders may be likely if CD4 count <50: Cytomegalovirus retinitis?
Affects around 30-40% of patients with CD4 < 50 cells/mm³
HIV= What affects around 30-40% of patients with CD4 < 50 cells/mm³?
Cytomegalovirus retinitis
Pneumocystis carinii is now referred to as…
Pneumocystis jiroveci, the term Pneumocystis carinii pneumonia (PCP) is still in common use
HIV= Pneumocystis jiroveci pneumonia?
an unicellular eukaryote, generally classified as a fungus but some authorities consider it a protozoa
most common opportunistic infection in AIDS
most common opportunistic infection in AIDS?
Pneumocystis jiroveci
HIV= all pts with CD4 count <200 should have what?
PCP prophylaxis (Pneumocystis jiroveci)
HIV= Pneumocystis jiroveci pneumonia features?
dyspnoea
dry cough
fever
very few chest signs
HIV= Pneumocystis jiroveci pneumonia (PCP) common Cx?
Pneumothorax
HIV= Pneumocystis jiroveci pneumonia (PCP) extrapulmonary manifestations?
rare (1-2%)
hepatosplenomegaly
lymphadenopathy
choroid lesions
HIV= Pneumocystis jiroveci pneumonia (PCP) Ix?
CXR: typically shows bilateral interstitial pulmonary infiltrates but can present with other x-ray findings e.g. lobar consolidation. May be normal
exercise-induced desaturation
sputum often fails to show PCP, bronchoalveolar lavage (BAL) often needed to demonstrate PCP (silver stain shows characteristic cysts)
HIV= Pneumocystis jiroveci pneumonia (PCP) Ix- CXR shows what?
typically shows bilateral interstitial pulmonary infiltrates but can present with other x-ray findings e.g. lobar consolidation. May be normal
HIV= Pneumocystis jiroveci pneumonia (PCP) Ix- sputum often fails to show PCP, bronchoalveolar lavage (BAL) often needed to demonstrate PCP. Results?
silver stain shows characteristic cysts
HIV= Pneumocystis jiroveci pneumonia (PCP) Mx?
co-trimoxazole
IV pentamidine in severe cases
steroids if hypoxic (if pO2 < 9.3kPa then steroids reduce risk of respiratory failure by 50% and death by a third)
aerosolized pentamidine is an alternative treatment for Pneumocystis jiroveci pneumonia but is less effective with a risk of pneumothorax
Renal involvement in HIV patients may occur as a consequence of what?
Tx or the virus itself
Renal involvement in HIV= Protease inhibitors such as indinavir can precipitate what?
intratubular crystal obstruction
HIV-associated nephropathy (HIVAN)= Tx?
Antiretroviral therapy
If a patient is already taking antiretroviral therapy (which should be all HIV-diagnosed patients) adherence should be checked.
HIV-associated nephropathy (HIVAN)= 5 key features?
massive proteinuria resulting in nephrotic syndrome
normal or large kidneys
focal segmental glomerulosclerosis with focal or global capillary collapse on renal biopsy
elevated urea and creatinine
normotension
Pt with HIV
massive proteinuria resulting in nephrotic syndrome
normal or large kidneys
focal segmental glomerulosclerosis with focal or global capillary collapse on renal biopsy
elevated urea and creatinine
normotension
HIV-associated nephropathy (HIVAN)
HIVAN stands for what?
HIV-associated nephropathy
HIV-associated nephropathy (HIVAN)= there is massive proteinuria resulting in what?
nephrotic syndrome
HIV-associated nephropathy (HIVAN)= what is shown on renal biopsy?
focal segmental glomerulosclerosis with focal or global capillary collapse
HIV seroconversion is symptomatic in 60-80% of patients and typically presents as what?
glandular fever-type illness
glandular fever-type illness in HIV pt?
HIV seroconversion
HIV seroconversion= Increased symptomatic severity is associated with what?
poorer long-term prognosi
HIV seroconversion= typically occurs when?
3-12w after infection
HIV seroconversion= features?
sore throat
lymphadenopathy
malaise, myalgia, arthralgia
diarrhoea
maculopapular rash
mouth ulcers
rarely meningoencephalitis
HIV replication stages?
1) Fusion of HIV to host cell surface
2) HIV RNA, reverse transcriptase, integrase and other viral proteins enter the host cell
3) Viral DNA is formed by reverse transcription
4) Viral DNA is transported across the nucleus and integrates into the host DNA
5) New viral RNA is used as genomic RNA and to make viral proteins
6) New viral RNA and proteins move to cell surface and a new immature HIV forms
7) The virus matures by protease releasing individual HIV proteins
HIV seroconversion?
period when the body produces antibodies to fight the HIV virus
Seroconversion can be mild (not notice it), mistaken for the flu, or severe enough to require hospitalization
period when someone with HIV is most infectious
After seroconversion, most people feel well and don’t have symptoms for several years
However, the virus is still active and damaging the immune system
Diagnosis and screening for HIV?
combination tests (HIV p24 antigen and HIV antibody) are now standard
if the combined test is positive it should be repeated to confirm the diagnosis
some centres may also test the viral load (HIV RNA levels) if HIV is suspected at the same time
Diagnosis of HIV= HIV antibodies?
may not be present in early infection, but most people develop antibodies to HIV at 4-6 weeks but 99% do by 3 months
usually consists of both a screening ELISA (Enzyme Linked Immuno-Sorbent Assay) test and a confirmatory Western Blot Assay
Diagnosis of HIV= p24 antigen?
a viral core protein that appears early in the blood as the viral RNA levels rise
usually positive from about 1 week to 3 - 4 weeks after infection with HIV
Diagnosis of HIV= what is the standard test?
combination tests (HIV p24 antigen and HIV antibody)
if the combined test is positive it should be repeated to confirm the diagnosis
some centres may also test the viral load (HIV RNA levels) if HIV is suspected at the same time
Diagnosis of HIV= testing for HIV in asymptomatic patients should be done at?
4 weeks after possible exposure
Diagnosis of HIV= after an initial negative result when testing for HIV in an asymptomatic patient, offer what?
repeat test at 12w
Main tests available to test for HIV?
- HIV antibody
- HIV antibody and antigen
- HIV RNA (qualitative or quantitative)
Main tests available to test for HIV= HIV antibody?
enzyme-linked immunosorbent assays (ELISAs) are often used for screening
Western blot was previously used as a confirmation test but HIV-1/HIV-2
differentiation assays are now more commonly used
most people develop antibodies to HIV at 4-6 weeks but 99% do by 3 months
Main tests available to test for HIV= HIV antibody and HIV antigen?
often referred to as ‘fourth-generation’ tests
p24 antigen can be detected as early as 2-3 weeks after exposure
the sensitivity of these fourth-generation tests approaches 100% for patients with chronic HIV infection
now the first-line test for HIV screening of asymptomatic individuals or patients with signs and symptoms of chronic infection
Main tests available to test for HIV= first-line test for HIV screening of asymptomatic individuals or patients with signs and symptoms of chronic infection?
HIV antibody and HIV antigen
Main tests available to test for HIV= HIV RNA (qualitative or quantitative)?
not routinely used for screening/testing
however, may be useful for diagnosis of neonatal HIV infection and screening blood donors
Human immunodeficiency virus (HIV) is what?
retrovirus that preferentially infects and destroys cells of the immune system, in particular the CD4 cells (a class of T lymphocyte).
How is HIV transmitted?
from infected body fluids:
Through sexual activity.
Vertically from mother to child — during pregnancy, childbirth, or through breastfeeding.
By inoculation — via a contaminated needle, instrument, blood, or blood product; through direct exposure of mucous membranes or an open wound to infected bodily fluids; or by a human bite that breaks the skin.
Primary HIV infection (PHI) or HIV seroconversion illness often presents with?
a flu-like illness in the first few weeks following infection and can be mild or severe.
- The person is highly infectious during PHI.
Progression of HIV infection involves?
An asymptomatic stage once symptoms of PHI resolve — some people progress rapidly to advanced HIV infection or AIDS (acquired immunodeficiency syndrome) within 1–2 years, while others may remain immunocompetent more than 10 years later.
Advanced HIV infection occurs when the number of CD4 cells is very low (less than 200 cells per microlitre) and certain opportunistic infections (such as pneumocystis pneumonia) or malignancies (such as Kaposi’s sarcoma) develop.
The possibility of HIV infection should be considered whenever a person presents with one or more alerting features:
Common symptoms or infections that are unusually severe, prolonged, recurrent, or unexplained.
Persistent enlarged lymph nodes other than in the inguinal area.
Conditions related to immunosuppression.
Glandular fever-like illness.
Lifestyle and social risk factors for contracting HIV, such as living in, working in, or coming from a high prevalence area; men who have sex with men; and injecting drug users.
HIV testing should be offered in primary care when?
- As part of routine antenatal care.
- If the person requests a test, has a risk factor for HIV, or has another sexually transmitted infection.
- To people newly registering at a practice or having a blood test if they have not had an HIV test in the past 12 months, in areas where the prevalence of diagnosed HIV is greater than 2 in 1000.
- To people presenting with symptoms of PHI or longstanding HIV infection.
- Some HIV-related conditions such as pneumocystis pneumonia or cryptococcal meningitis can be life threatening and require urgent admission or referral to secondary care.
Management of HIV is complex and is carried out by specialist HIV services in secondary care. It involves what?
Antiretroviral therapy (ART) is initiated and monitored in secondary care — ART can be associated with serious or life-threatening adverse effects that may present in primary care.
What must be done before ART is prescribed for HRT?
ART can also have serious or life-threatening interactions with many drugs commonly prescribed in primary care — before prescribing, drug interactions should be checked in the British National Formulary, the online database of HIV drug interactions, or with an HIV specialist.
Prognosis of HIV?
ART has improved the prognosis of HIV/AIDS significantly — people living with HIV who are adherent and clinically responding to ART can expect a normal or near-normal life span.
ART stands for?
antiretroviral therapy
Potential occupational or sexual exposure to HIV is a medical emergency — what should be done?
urgent referral for consideration of post-exposure prophylaxis is required.
Primary HIV infection or HIV seroconversion illness occurs in the
first few weeks following infection with HIV (usually between 10 days and 6 weeks) and can be mild or severe.
Clinical features associated with primary HIV infection develop in over 60% of people, can be non-specific, and include:
Fever, sore throat, maculopapular rash, malaise, lethargy, arthralgia, myalgia, lymphadenopathy, and oral, genital or perianal ulcers.
Less commonly, headache, meningitis, cranial nerve palsies, diarrhoea, and weight loss.
Conditions associated with longstanding HIV infection can be subtle and people may remain well for some time before developing another condition. Consider HIV if a person has had more than one of the following in the past 3 years, or has had conditions that are severe or resistant to treatment….
- constitutional symptoms= flu-like symptoms; fever; weight loss; sweats; lymphadenopathy
- Opportunistic respiratory infections
- neurological and visual problems
- increased risk of malignancy
- skin conditions
- oral conditions
- GI conditions
- genital conditions= severe or difficult-to-treat genital candida, genital herpes, or genital warts
- haematological= unexplained abnormalities on full blood count such as neutropenia, anaemia, thrombocytopenia, or other blood dyscrasias.
Conditions associated with longstanding HIV infection= respiratory conditons?
Opportunistic respiratory infections such as pneumocystis pneumonia (PCP), tuberculosis, bacterial lower respiratory tract infections; and occasionally Kaposi’s sarcoma or lymphomas can result in symptoms including cough, sweats, breathlessness, and weight loss.
Conditions associated with longstanding HIV infection= respiratory conditions: PCP?
life-threatening condition that can be difficult to identify at onset and is typically insidious over several weeks.
Symptoms include fever (in most but not all people), persistent dry cough of a few weeks’ duration, increasing breathlessness, decreasing exercise tolerance, chest discomfort, and difficulty in taking a full breath.
Signs include fine crackles (although the chest may be clear, especially in early infection) and a drop in oxygen saturation on exertion.
PCP can be fatal if diagnosed late.
Conditions associated with longstanding HIV infection= respiratory conditions: Tuberculosis (TB) and atypical mycobacterial disease?
TB is a common presenting condition in HIV. Atypical mycobacterial disease (such as Mycobacterium avium intracellulare) is less common and is associated with advanced HIV infection.
Symptoms may include fever, night sweats, weight loss, fatigue, diarrhoea, and abdominal pain.
Conditions associated with longstanding HIV infection= neuro and visual conditions?
- Cryptococcal meningitis — may present as subacute meningitis with headache and fever, acute confusional state, or cranial nerve palsies. Typical symptoms and signs of meningism may be absent.
- Cerebral toxoplasmosis — occurs owing to reactivation of previous toxoplasmosis infection. May present with confusion, headache, personality change, fever, fits, and focal neurological signs.
- Cerebral lymphoma (in advanced HIV disease)=
May present with confusion, lethargy, personality change, headache, fever, fits, and focal neurological signs. - Cytomegalovirus (CMV) retinitis= occurs owing to reactivation of previously acquired infection and can lead to loss of vision.
Prognosis improves with earlier diagnosis.
Symptoms include floaters (due to inflammatory cells in the vitreous), reduced vision, flashing lights, and scotomas.
HIV= can lead to loss of vision.
Prognosis improves with earlier diagnosis.
Symptoms include floaters (due to inflammatory cells in the vitreous), reduced vision, flashing lights, and scotomas.
Cytomegalovirus (CMV) retinitis
HIV infection is associated with increased risk of malignancy including?
Lymphoma
Kaposi’s sarcoma
Cervical ca
HIV= increased risk of ca: lymphoma?
Can present with weight loss, fevers, night sweats, lymphadenopathy, and abdominal masses (lymph nodes, hepatomegaly, or splenomegaly).
HIV= increased risk of ca: Kaposi’s sarcoma?
Kaposi’s sarcoma is the most common tumour in people with HIV infection and typically presents with dark purple or brown intradermal skin lesions that look like bruises but feel firmer.
Tumours may occur anywhere on the skin or oropharynx — infiltration of the lungs or gut is rare but can be life threatening.
HIV= increased risk of ca: cervical ca?
Abnormal cervical cytology may be a marker for underlying HIV infection.
Conditions associated with longstanding HIV infection= skin conditions?
Kaposi’s sarcoma
Fungal skin and nail infections
Viral infections such as herpes simplex (especially if the ulcers are unusually large or persistent), molluscum contagiosum, shingles (especially if more than one dermatome is affected), and warts.
Bacterial infections such as impetigo and folliculitis.
Seborrhoeic dermatitis and psoriasis
Conditions associated with longstanding HIV infection= oral conditions?
Oral candidiasis= Typically presents with thick white plaques covering the buccal mucosa that can be scraped off. Soreness of the mouth or pain on swallowing (odynophagia) may also be present.
Aphthous ulcers
Oral hairy leukoplakia
Kaposi’s sarcoma= Most often affects the hard and soft palate, gingiva, and dorsal tongue with plaques or tumours of variable colour from non-pigmented to brownish-red or purple.
Gingivitis= Causes swelling and erythema of the gum margins that are usually painful and bleed on tooth brushing or flossing.
Dental abscess= Typically presents with rapid onset of severe dental pain and may be associated with an unpleasant taste in the mouth, fever, and malaise.
Conditions associated with longstanding HIV infection= oral conditions- oral hairy leukoplakia?
Typically presents as asymptomatic corrugated whitish, hairy patches on the side of the tongue that cannot be scraped off (in contrast to oral candidiasis) and is pathognomic of immunosuppression.
Conditions associated with longstanding HIV infection= GI conditions?
Oesophageal candidiasis=
Symptoms include retrosternal pain or dysphagia. Oral candidiasis is also likely to be present
Diarrhoea= very common and may be persistent and mild or acute and severe.
Infection due to bacteria, protozoa (such as Cryptosporidium), mycobacteria, or viruses; malignancy (such as non-Hodgkin’s lymphoma or Kaposi’s sarcoma), or the direct effects of HIV can all result in diarrhoea.
Often no specific causative organism is identified.
Hep B and C= Co-infection with hepatitis B or C is common and increases the risk of cirrhosis and hepatocellular carcinoma.
What to do if HIV test comes back positive?
The laboratory is likely to telephone the result through and ask for a repeat sample.
Emphasize the positive aspects — effective treatment can help prevent HIV-related illness and ensure that infection is not transmitted to contacts or in pregnancy.
Explain the referral process — for further information, see the section on New diagnosis of HIV.
Discuss concerns and sources of support.
Arrange follow up within the next few days as the person is likely to have additional questions.
An indicator condition is any medical condition associated with an undiagnosed HIV seroprevalence ≥1 per 1000.
There are two categories of indicator conditions?
Conditions that would be AIDS defining in an individual living with HIV.
Non-AIDS-defining conditions associated with an undiagnosed HIV seroprevalence >1 per 1000.
HIV= Condoms should still be used even if?
Antiretroviral therapy (ART) is taken regularly and viral load suppressed.
The person’s partner is also HIV positive (to prevent drug-resistant strains from being transferred).
HIV= Pre-exposure prophylaxis (PrEP)?
combination of two antiretroviral drugs that are taken before and after sex to reduce the risk of HIV acquisition – it is offered on a case by case basis to HIV-negative people who are at high risk of HIV and who do not always use condoms.
Signpost to a sexual health clinic people who may be eligible for PrEP — baseline HIV testing, counselling on risks and benefits, support to improve adherence, and regular HIV and STI screening is required.
Contraceptive choice for women with HIV may be complicated by potential drug interactions with ART — seek specialist advice….
Oral contraceptives and patches may have reduced effectiveness with some ART combinations.
Long-acting reversible contraceptives such as the copper intrauterine device (Cu-IUD), the levonorgestrel-releasing intrauterine system (IUS), or depot medroxyprogesterone acetate (DMPA) injection do not appear to be affected by enzyme-inducing drugs.
Emergency contraception for women with HIV?
A Cu-IUD is the recommended method of emergency contraception except in women with a CD4 less than 200 cells per microlitre and detectable HIV RNA (owing to potential higher risk of infection post procedure).
If progesterone-only emergency contraception is used, a doubling of the standard dose may be advised (off-label).
Fertility and assisted conception in pt with HIV?
Specialist fertility services input is recommended for all couples who wish to conceive where one or both partners are living with HIV.
Options vary depending on concordance, treatment, and viral suppression and may include donor insemination, sperm washing, or self insemination.
Care should be provided through antenatal multi-disciplinary team including an HIV specialist, obstetrician, specialist midwife, and paediatrician.
Risk of transmitting HIV from mother to child in pregnancy can be reduced from around 20% to less than 1% by:
Taking ART during pregnancy.
Using ART at the time of delivery, together with a short course of ART for the newborn baby.
Vaginal delivery for women on ART who have an undetectable viral load or elective Caesarean section for others.
Avoidance of breastfeeding — be aware that avoidance of breastfeeding may lead to problems with speculation about, or even disclosure of, the mother’s HIV status. Advice and support should be available.
HIV= If the person is not attending specialist services regularly?
Confirm that the patient has capacity to make decisions.
Explore their reasons for not attending — problems such as fear of being recognized at a local clinic may be addressed by changing to a geographically different service.
Reinforce the benefits of attending specialist care.
Consider, after discussion with the person’s specialist and the local laboratory, assessing immunity by checking a CD4 count in primary care.
Discuss with the person’s specialist the option of prophylactic treatment against some opportunistic infections such as pneumocystis pneumonia.
Death as a direct result of HIV-infection is uncommon since the introduction of effective antiretroviral therapy (ART). End-stage advanced HIV disease usually occurs in people who…
present late or have co-morbidities.
In people taking ART it can be more difficult to identify terminal illness — immunity may recover following a change in treatment regimen but the risk of overwhelming infection remains until this happens.
Close communication between secondary and primary care services is particularly important.
The following conditions are considered to be AIDS defining when they occur in people living with HIV:
Neoplasms:
Cervical cancer.
Non-Hodgkin lymphoma.
Kaposi’s sarcoma.
Bacterial infections:
Mycobacterium tuberculosis, pulmonary or extrapulmonary.
Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary.
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary.
Pneumonia, recurrent (two or more episodes in 12 months).
Salmonella septicaemia, recurrent.
Viral infections:
Cytomegalovirus retinitis.
Cytomegalovirus, other (except liver, spleen, glands).
Herpes simplex, ulcer(s) more than 1 month/bronchitis/pneumonitis.
Progressive multifocal leukoencephalopathy.
Parasitic infections:
Cerebral toxoplasmosis.
Cryptosporidiosis diarrhoea, more than 1 month.
Isosporiasis, more than 1 month.
Atypical disseminated leishmaniasis.
Reactivation of American trypanosomiasis (meningoencephalitis or myocarditis).
Fungal infections:
Pneumocystis pneumonia (PCP).
Candidiasis, oesophageal.
Candidiasis, bronchial/tracheal/pulmonary.
Cryptococcosis, extrapulmonary.
Histoplasmosis, disseminated/extrapulmonary.
Coccidioidomycosis, disseminated/extrapulmonary.
Penicilliosis, disseminated.
The immediate treatment of a site exposed to potentially HIV-infected bodily fluids is to clean it thoroughly:
Skin and skin wounds should be washed with soap and water, and mucous membranes irrigated with water. Squeezing the wound to express blood is not recommended.
Eyes should be irrigated with saline or water before and after removing contact lenses.
Puncture wounds should be encouraged to bleed freely, but should not be sucked. Small wounds and punctures may also be cleansed with an antiseptic, for example an alcohol-based hand hygiene solution.
Exposure to HIV is a medical emergency and requires prompt treatment with
course of antiretroviral therapy (ART).
Exposure to HIV= Direct the person immediately to an HIV/sexual health clinic or an Accident and Emergency department for consideration of post-exposure prophylaxis following sexual exposure (PEPSE) if:
They are an uninfected sexual partner of a person known to have HIV, to prevent infection after sex without a condom or where the condom has split.
PEP is generally no longer recommended if the HIV-positive partner is adherent to ART and has been confirmed as having a sustained (more than 6 months) undetectable plasma HIV viral load (less than 200 copies/ml).
They have had unprotected sex with a person in a high-risk group for HIV whose infection status is not known.
PEPSE may be offered to victims of sexual assault depending on risk assessment.
HIV= PEPSE can be initiated if the person presents within
72 hours of exposure and should be given as early as possible (ideally within 24 hours of exposure).
Follow up should be arranged by the prescribing team — HIV testing is recommended 8–12 weeks after exposure.
All people seeking PEPSE should be advised to attend for future regular sexual health checks.
Correlation of CD4 count (cells per microlitre) with risk of HIV-related opportunistic infections and cancers= 500 and below?
Little risk of infections
Hodgkin’s lymphoma
Cervical cancer
Correlation of CD4 count (cells per microlitre) with risk of HIV-related opportunistic infections and cancers= 400 and below?
Bacterial skin infections
Recurrent bacterial chest infections
Tuberculosis
Oropharyngeal candida
Fungal infections
Seborrhoeic dermatitis
Direct HIV effects= Lymphadenopathy, Sweats
Correlation of CD4 count (cells per microlitre) with risk of HIV-related opportunistic infections and cancers= 350 and below?
Oral hairy leukoplakia
Shingles
Pneumocystis pneumonia
Persistent herpes simplex infection
Non-Hodgkin’s lymphoma
Direct HIV effects= weight loss
Correlation of CD4 count (cells per microlitre) with risk of HIV-related opportunistic infections and cancers= 200 and below?
Oesophageal candida
Histoplasmosis
Cryptococcal meningitis
Cerebral toxoplasmosis
Cryptosporidiosis
ca= Kaposi’s sarcoma
Direct HIV effects= diarrhoea, wasting
Correlation of CD4 count (cells per microlitre) with risk of HIV-related opportunistic infections and cancers= 100 and below?
Cytomegalovirus infections
Atypical mycobacterium infections
ca= Primary cerebral lymphoma
Direct HIV effects= dementia
MRSA stands for what?
Methicillin-resistant Staphylococcus aureus
MRSA was one of the first organisms which highlighted what?
dangers of hospital acquired infections
Who should be screened for MRSA?
all patients awaiting elective admissions (exceptions include day patients having terminations of pregnancy and ophthalmic surgery. Patients admitted to mental health trusts are also excluded)
from 2011 all emergency admissions will be screened
How should a pt be screened for MRSA?
nasal swab and skin lesions or wounds
the swab should be wiped around the inside rim of a patient’s nose for 5 seconds
the microbiology form must be labelled ‘MRSA screen’
Suppression of MRSA from a carrier once identified?
nose: mupirocin 2% in white soft paraffin, tds for 5 days
skin: chlorhexidine gluconate, od for 5 days. Apply all over but particularly to the axilla, groin and perineum
The following antibiotics are commonly used in the treatment of MRSA infections?
vancomycin
teicoplanin
linezolid
MRSA= Some strains may be sensitive to antibiotics but they should not generally be used alone because resistance may develop, eg?
rifampicin
macrolides
tetracyclines
aminoglycosides
clindamycin
Relatively new antibiotics such as linezolid, quinupristin/dalfopristin combinations and tigecycline have activity against MRSA but should be reserved for?
resistant cases
Staphylococcus aureus?
bacterium that colonizes the skin, nose, or gut of up to a third of the general population — it usually lives on intact skin harmlessly, but can cause infection if invasion through the skin or deeper tissues occurs.
Where does staph aureus usually live?
lives on intact skin harmlessly, but can cause infection if invasion through the skin or deeper tissues occurs.
Meticillin-resistant S. aureus (MRSA)?
strains of S. aureus that have developed resistance to a number of commonly used antibiotics.
Healthcare-associated MRSA (HA-MRSA)?
strains of MRSA identified in people who have had contact with healthcare services — they can present in hospital or in the community
There are no clinical features specific to MRSA infection — MRSA can cause the same spectrum of disease as any other strain of S. aureus including?
Skin and soft tissue infections (such as boils, folliculitis, impetigo, cellulitis, and necrotising fasciitis).
Urinary tract infection.
Pneumonia and bronchiectasis.
Joint and bone infections (such as osteomyelitis and septic arthritis).
Sepsis and toxic shock syndrome.
Infective endocarditis.
MRSA should be suspected in all people presenting with potential staphylococcal infection, in particular if:
They have risk factors for MRSA (such as recent hospitalization, previous MRSA infection or colonization, nursing home contact, antibiotic use, chronic illness, surgical wounds, open ulcers, intravenous lines, or urinary catheters).
There is no response to first line antibiotics.
They have recurrent skin or soft tissue infections or a chronic non-healing ulcer.
Diagnosis of MRSA is based on?
thorough clinical assessment supported by confirmatory laboratory results from swabs of exudate (from lesions or wounds), urine samples, or sputum samples.
What should be followed in all cases of MRSA (whether a person is known to be infected or colonized with MRSA or not)?
Appropriate infection control measures (in line with local policy) along with careful communication between healthcare professionals.
Urgent assessment in secondary care should be arranged if a person has suspected or confirmed MRSA and ?
clinical features of severe or complicated infection or they require surgical intervention
Treatment of uncomplicated infections where MRSA is suspected or confirmed (such as antibiotics and wound care) should be?
discussed with a microbiologist or the local infection-control team.
Routine treatment with oral or topical antibiotics is not advised, unless directed by microbiology.
Follow up (after 48 hours, or sooner if worsening) is recommended to monitor for signs of complications (such as sepsis) and to ensure infection is resolving.
Decolonization is not routinely required for asymptomatic carriers of MRSA in the community but may be indicated if?
the person has risk factors (such as a wound or invasive device, or is resident in a care home).
There are no clinical features specific to meticillin-resistant Staphylococcus aureus (MRSA) infection — MRSA can cause the same spectrum of disease as other strains of S. aureus, including?
skin & soft tissue infections
bone and joint infection
pneumonia
UTI
endocarditis
sepsis
Giardiasis?
caused by the flagellate protozoan Giardia lamblia.
It is spread by the faeco-oral route.
Giardiasis RFs?
foreign travel
swimming/drinking water from a river or lake
male-male sexual contact
Giardiasis features?
often asymptomatic
non-bloody diarrhoea= steatorrhoea
bloating, abdominal pain
lethargy
flatulence
weight loss
malabsorption and lactose intolerance can occur
Ix for Giardiasis?
stool microscopy for trophozoite and cysts: sensitivity of around 65%
stool antigen detection assay: greater sensitivity and faster turn-around time than conventional stool microscopy methods
PCR assays are also being developed
Tx for giardiasis?
metronidazole
H1N1 influenza aka?
swine flu
H1N1 influenza (swine flu) outbreak?
first observed in Mexico in early 2009. In June 2009, the WHO declared the outbreak to be a pandemic.
The H1N1 virus?
subtype of the influenza A virus and the most common cause of flu in humans. The 2009 pandemic was caused by a new strain of the H1N1 virus.
What groups are particularly at risk of H1N1 influenza?
patients with chronic illnesses and those on immunosuppressants
pregnant women
young children under 5 years old
H1N1 influenza features?
flu-like illness:
fever greater than 38ºC
myalgia
lethargy
headache
rhinitis
sore throat
cough
diarrhoea and vomiting
H1N1 influenza= minority of pts may go on to develop what?
an acute respiratory distress syndrome which may require ventilatory support
H1N1 influenza= 2 main Tx available?
Oseltamivir (Tamiflu) (oral)
Zanamivir (Relenza) (inhaled or IV)
H1N1 influenza= Tx- Oseltamivir (Tamiflu)?
oral medication
a neuraminidase inhibitor which prevents new viral particles from being released by infected cells
common side-effects include nausea, vomiting, diarrhoea and headaches
H1N1 influenza= Tx- Zanamivir (Relenza)?
inhaled medication (or IV)
also a neuraminidase inhibitor
may induce bronchospasm in asthmatics
Features of influenza?
fever greater than 38ºC
myalgia
lethargy
headache
rhinitis
sore throat
cough
diarrhoea and vomiting
Influenza= consider prescribing antiviral treatment for influenza if all of the following apply….
1) The patient is in an at-risk group or is felt to be at risk of developing a serious complication
2) There is circulating influenza nationally- this would mean typically the winter months
3) The patient is able to start treatment within 48 hours from the onset of symptoms
Influenza= who is classed as at-risk group or is at risk of developing a serious Cx?
> 65 years old
pregnant women
chronic disease of respiratory, cardiac, renal, hepatic or neurological nature
diabetes
immunosuppression
morbid obesity.
Antivirals for influenza if indicated?
First line: oseltamivir
Second line: zanamivir
Antivirals for influenza if indicated= 1st line?
oseltamivir
Antivirals for influenza if indicated= 2nd line?
zanamivir
Influenza is an acute respiratory illness caused by?
RNA viruses of the family Orthomyxoviridae (influenza viruses)
How many times of influenza?
3
3 types of influenza?
A
B
C
Influenza A?
occurs more frequently and is more virulent. It is responsible for local outbreaks, larger epidemics, and pandemics.
Influenza B?
often co-circulates with influenza A during the yearly outbreaks. Generally, influenza B causes less severe clinical illness, although it can still be responsible for outbreaks.
Influenza C?
usually causes a mild or asymptomatic infection similar to the common cold
Influenza usually occurs in the UK during when?
winter months; typically between December and March
Cx of influenza?
Acute bronchitis.
Pneumonia.
Exacerbations of asthma and chronic obstructive pulmonary disease.
Otitis media.
Sinusitis.
Influenza presents with symptoms appearing around…
2d after exposure
Uncomplicated influenza signs and symptoms include?
coryza, nasal discharge, cough, fever, gastrointestinal symptoms, headache, malaise, myalgia, arthralgia, ocular symptoms, and sore throat
Complicated influenza is defined by?
signs and symptoms that require hospital admission, involve the lower respiratory tract or central nervous system, or cause significant exacerbation of an underlying medical condition.
Mx of influenza?
For otherwise healthy people, antiviral drugs (oseltamivir or zanamivir) are not usually recommended, unless they are at risk of developing serious complications.
Mx of influenza= what antiviral is prescribed?
oseltamivir should be prescribed if the national surveillance schemes indicate that influenza virus is circulating, and the person can start treatment within 48 hours.
When are antivirals indicated for influenza?
if ‘at risk’ group antiviral, if the national surveillance schemes indicate that influenza virus is circulating, and the person can start treatment within 48 hours of the onset of symptoms (36 hours in the case of zanamivir in children).
People considered to be in an ‘at risk’ group include:
- Those with chronic respiratory, heart, kidney, liver, or neurological disease; diabetes mellitus; or those who are obese or immunosuppressed.
- Those over the age of 65 years.
- Women who are pregnant (or women up to 2 weeks postpartum).
- Children aged under 6 months.
Mx of people with influenza if antivirals not needed?
drink adequate fluids, take paracetamol or ibuprofen to relieve symptoms, rest, and stay off work or school until the worst symptoms have resolved (usually about 1 week).
Influenza= Post-exposure prophylaxis with an antiviral drug should be started if all of the following apply?
The national surveillance scheme indicates that influenza is circulating.
The person has been in close contact with a person (in the same household or residential setting) who has had recent symptoms of influenza.
The person is in an ‘at risk’ group and has not been effectively immunized against influenza.
The person is able to start treatment within 48 hours of this contact (for oseltamivir) or 36 hours of this contact (for zanamivir).
Influenza= Urgent admission to hospital should be considered?
A complication such as pneumonia occurs.
The person has a concomitant disease that may be affected by influenza (for example, type 1 diabetes).
There is suspicion of a serious illness other than influenza (for example meningitis).
Diagnosis of influenza can only be confirmed by laboratory testing, although the probability that an influenza-like illness is caused by influenza is higher if…..
influenza is known to be circulating and if a person has a high fever
Rapid testing for influenza should be undertaken in all people with?
complicated influenza (although often this takes place in hospital).
Initiation of antiviral treatment should not be delayed while awaiting laboratory confirmation.
Laboratory testing to confirm or exclude influenza is particularly important if …
an individual develops symptoms despite antiviral prophylaxis, or has a persistent infection despite antiviral treatment, to identify the potential development of antiviral resistance.
Symptoms of influenza appear when?
abruptly, around 2d after exposure
Complicated influenza is suggested by….
Signs and symptoms that require hospital admission.
Presence of a lower respiratory tract infection (hypoxaemia, dyspnoea, and lung infiltrate).
Central nervous system involvement.
Significant exacerbation of an underlying medical condition.
Symptoms of influenza-like illness can be different in infants and children and may include?
Cervical adenopathy.
Conjunctival erythema.
Diarrhoea and vomiting — GI symptoms are more common in children than in adults.
Fatigue.
Fever (typically 38–40°C) — children can have a higher maximum temperature. They may also present with undifferentiated fever or febrile seizures.
Hyperaemia of oropharynx.
Irritability.
Laryngotracheobronchitis (croup), bronchiolitis, or bronchitis.
Myalgia or myositis — this can affect the calf muscles and be severe. It is a more common complication in children compared to adults.
Tachypnoea.
Mx of influenza= For uncomplicated influenza in people who were previously healthy?
no antiviral treatment is normally indicated, unless the person is at serious risk of developing serious complications from influenza, then prescribe oral oseltamivir.
Mx of influenza= For uncomplicated influenza in people who are in an at risk group (including women who are pregnant), but are not severely immunosuppressed?
prescribe oral oseltamivir. Do not wait for laboratory confirmation.
Mx of influenza= For uncomplicated influenza in people who are severely immunosuppressed, and the dominant strain has: A lower risk of oseltamivir resistance (for example, A [H3N2] influenza B)?
prescribe oral oseltamivir
Mx of influenza= For uncomplicated influenza in people who are severely immunosuppressed, and the dominant strain has: a higher risk of oseltamivir resistance (for example, A [H1N1])?
prescribe inhaled zanamivir, or if this is unsuitable or inappropriate, prescribe oral oseltamivir and follow up.
Advice to help manage influenza?
To drink adequate fluids to avoid dehydration.
To take paracetamol or ibuprofen for symptomatic relief.
To rest in bed if they feel fatigued.
To stay off work or school if they feel unable to attend — for most people, about 1 week will be adequate.
That fever and associated systemic symptoms of uncomplicated influenza usually resolve after about 1 week, although some symptoms (such as cough and fatigue) may persist for up to 2 weeks after resolution of fever.
About the symptoms of complicated influenza and to seek medical advice should their condition deteriorate.
Prophylaxis is normally not considered in at-risk groups who have been vaccinated against seasonal influenza at least …
14d before exposure
Prescribe an antiviral drug for post-exposure prophylaxis if all of the following circumstances apply?
- The national surveillance scheme indicates that influenza is circulating.
- The person has been exposed to a person (in the same household or residential setting) with an influenza-like illness.
- The person is in an ‘at risk’ group and has not been adequately protected by vaccination, that is= They have not been vaccinated since the previous influenza season; The vaccination is not well matched to the circulating strain; There has been less than 14 days between vaccination and date of contact with influenza.
- The person is able to start treatment within 48 hours of this contact (for oseltamivir) or 36 hours of this contact (for zanamivir). (after these times it is off label so get specialist advice)
If post-exposure prophylaxis is indicated, prescribe oral oseltamivir or inhaled zanamivir (as appropriate).
For people at risk of complicated influenza (including pregnant women, but excluding severely immunosuppressed people and children aged under 5 years), prescribe:
Oral oseltamivir once daily for 10 days if the identified strain in the index case or dominant circulating strain is lower risk for oseltamivir resistance (for example, influenza A [H3N2], influenza B), or is known to be higher risk for oseltamivir resistance (for example, influenza A [H1N1]).
Inhaled zanamivir daily for 10 days if the person has been exposed to suspected or confirmed oseltamivir-resistant influenza.
If post-exposure prophylaxis is indicated, prescribe oral oseltamivir or inhaled zanamivir (as appropriate).
For severely immunosuppressed adults and children aged 5 years and over, prescribe:
Oral oseltamivir once daily for 10 days if the identified strain in the index case or dominant circulating strain is lower risk for oseltamivir resistance (for example influenza A [H3N2] and influenza B).
Inhaled zanamivir daily for 10 days if the identified strain in the index case or dominant circulating strain is higher risk for oseltamivir resistance (for example, influenza A [H1N1]), or if this is unsuitable or inappropriate, prescribe oral oseltamivir once daily for 10 days.
Inhaled zanamivir daily for 10 days if the person has been exposed to suspected or confirmed oseltamivir-resistant influenza. If this is unsuitable or inappropriate seek specialist advice.
If post-exposure prophylaxis is indicated, prescribe oral oseltamivir or inhaled zanamivir (as appropriate).
For children aged under 5 years in at risk groups, including severely immunocompromised children:
Prescribe oral oseltamivir once daily for 10 days if the identified strain in the index case or dominant circulating strain is lower risk for oseltamivir resistance (for example, influenza A [H3N2], influenza B), or is known to be higher risk for oseltamivir resistance (for example, influenza A [H1N1]).
If the child has been exposed to suspected or confirmed oseltamivir-resistant influenza, seek specialist advice.
If post-exposure prophylaxis is indicated, prescribe oral oseltamivir or inhaled zanamivir (as appropriate).
What else?
Arrange for the person to receive influenza immunization if this has not already been done in the present influenza season.
Note: the efficacy of the vaccine may be reduced if it is administered within 2 weeks of use of an influenza antiviral agent.
Inform the person that although antiviral drugs help prevent influenza, they are not completely effective. Provide advice about symptomatic treatment and when to seek medical attention if influenza develops.
Malaria is a disease caused by?
Plasmodium protozoa
Malaria is a disease caused by Plasmodium protozoa which is spread by?
female Anopheles mosquito
Malaria= 4 different species that cause malaria?
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Most common cause of malaria (nearly all episodes of severe malaria)
Plasmodium falciparum
Most common cause of ‘benign’ malaria?
Plasmodium vivax (most common)
also
Plasmodium ovale
Plasmodium malariae
Protective factors from malaria?
- sickle cell trait
- G6PD deficiency
- HLA-B53
- absence of Duffy antigens
Life cycle of the malaria parasite?
1) the mosquito ingests the parasite during blood feeding
2) the mosquito injects the parasite when it bites the human
3) sporozoites to human liver cell then into human blood cell
4) sexual stage= male and female gametocytes form
5) early mosquito stages= gametes to zygote to ookinete
6) oocyst, grows and releases sporozoites
repeats
Commonest, and most severe, type of malaria?
Falciparum malaria
Falciparum malaria typically presents how?
with symptoms suggestive of a flu-like illness.
The classical triad of symptoms includes paroxysms of fever, chills, and sweating.
These symptoms may occur every 48 hours corresponding to the erythrocytic cycle of the Plasmodium falciparum parasite.
Fever is often high, intermittent, and may be accompanied by rigors.
Initial manifestations can be non-specific and include malaise, headache, and myalgia, which might be mistaken for a viral syndrome.
Falciparum malaria= triad of symptoms?
paroxysms of fever, chills, and sweating
Falciparum malaria= triad of symptoms (paroxysms of fever, chills, and sweating) typically occur every 48hrs corresponding to what?
the erythrocytic cycle of the Plasmodium falciparum parasite
Falciparum malaria= fever?
The hallmark of malaria, typically cyclical, often accompanied by sweating and sometimes rigors.
often high, intermittent, and may be accompanied by rigors
Falciparum malaria= initial manifestations?
non-specific and include malaise, headache, and myalgia, which might be mistaken for a viral syndrome
Falciparum malaria= general features?
- Fever
- GI
- Resp
- MSK
- Neuro
- Cardiovascular
- Haematological
- Renal
Falciparum malaria= general features- GI?
anorexia, nausea, vomiting, and abdominal pain are frequent
diarrhoea can occasionally be a feature, more commonly in children
patients may exhibit mild jaundice and occasional pruritus
Falciparum malaria= general features- resp?
Cough and, in some cases, mild tachypnoea may occur, though primary respiratory complications are rare in non-severe cases.
Falciparum malaria= general features- MSK?
Generalised body aches and joint pains are common.
Falciparum malaria= general features- neuro?
headache is prominent and often severe.
dizziness and sleep disturbances may also be observed.
Falciparum malaria= general features- cardiovascular?
Tachycardia may be evident, and although hypotension is more typical of severe malaria, it can occasionally be seen in non-severe cases as well.
Falciparum malaria= general features- haematological?
thrombocytopaenia is the most significant haematological finding and can occur in the absence of severe disease.
mild anaemia may also be present.
Falciparum malaria= general features- renal?
While acute kidney injury is associated with severe malaria, non-severe cases might show mild to moderate increases in creatinine or blood urea nitrogen levels.
Feature of severe falciparum malaria?
schizonts on a blood film
parasitaemia > 2%
hypoglycaemia
acidosis
temperature > 39 °C
severe anaemia
complications
Cx of severe falciparum malaria?
cerebral malaria: seizures, coma
acute renal failure: blackwater fever, secondary to intravascular haemolysis, mechanism unknown
acute respiratory distress syndrome (ARDS)
hypoglycaemia
disseminated intravascular coagulation (DIC)
Mx of uncomplicated falciparum malaria?
strains resistant to chloroquine are prevalent in certain areas of Asia and Africa
artemisinin-based combination therapies (ACTs) as first-line therapy
- examples include artemether plus lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, artesunate plus sulfadoxine-pyrimethamine, dihydroartemisinin plus piperaquine
Mx of complicated falciparum malaria?
a parasite counts of more than 2% will usually need parenteral treatment irrespective of clinical state
intravenous artesunate is now recommended by WHO in preference to intravenous quinine
if parasite count > 10% then exchange transfusion should be considered
shock may indicate coexistent bacterial septicaemia - malaria rarely causes haemodynamic collapse
most common cause of non-falciparum malaria?
Plasmodium vivax, with Plasmodium ovale and Plasmodium malariae accounting for the other cases
Plasmodium vivax is often found in?
Central America and the Indian Subcontinent whilst Plasmodium ovale typically comes from Africa
Malaria=
Plasmodium knowlesi?
another non-falciparum species which causes clinical pathology, found predominantly in South East Asia
Features of non-falciparum malaria?
general features of malaria: fever, headache, splenomegaly
Plasmodium vivax/ovale: cyclical fever every 48 hours.
Plasmodium malariae: cyclical fever every 72 hours
Plasmodium malariae: is associated with nephrotic syndrome.
Non-falciparum malria= Ovale and vivax malaria have a hypnozoite stage and may therefore…
relapse following treatment
Tx of non-falciparum malaria?
in areas which are known to be chloroquine-sensitive then WHO recommend either an artemisinin-based combination therapy (ACT) or chloroquine
in areas which are known to be chloroquine-resistant an ACT should be used
ACTs should be avoided in pregnant women
patients with ovale or vivax malaria should be given primaquine following acute treatment with chloroquine to destroy liver hypnozoites and prevent relapse
Malaria?
life-threatening illness caused by infection of red blood cells by Plasmodium parasites.
Transmission of malaria to humans occurs through the bite of infected female Anopheles mosquitoes.
Species of Plasmodium that cause malaria in humans?
Plasmodium falciparum — responsible for the majority of malaria related deaths worldwide.
Plasmodium vivax and Plasmodium ovale — these species have dormant liver stages which can cause ‘relapses’ of malaria months or years after initial infection.
Plasmodium malariae — if untreated can cause lifelong chronic infection.
Plasmodium knowlesi — a malaria parasite of monkeys in South-East Asia which can cause severe and sometimes fatal illness in humans.
Prognosis of malaria?
if identified promptly, appropriate treatment is given, and no organ dysfunction has occurred, most people make a rapid and complete recovery. If malaria treatment is delayed or inappropriate, severe or fatal malaria can develop.
Suspect malaria in anyone who?
anyone who has returned from or previously visited an area endemic for malaria who is unwell or has a fever or history of fever, regardless of malaria chemoprophylaxis.
Most missed malaria infections are misdiagnosed as non-specific viral infections, influenza, gastroenteritis, or hepatitis.
The clinical features of malaria are non-specific and include:
Fever, sweats, and/or chills — absence of fever does not exclude the possibility of malaria.
Headache.
Confusion.
General malaise, lethargy, and fatigue — somnolence is more common in children than in adults.
Myalgia and arthralgia.
Gastrointestinal disturbance (such as nausea, abdominal pain, vomiting, and diarrhoea).
Anorexia, poor feeding in children.
Jaundice.
Sore throat, cough, lower respiratory tract symptoms, and respiratory distress.
Symptoms of severe malaria include:
Impaired conscious level, seizures, or prostration (inability to stand or sit).
Renal impairment (may present with oliguria).
Acidosis (may present with acidotic breathing).
Hypoglycaemia — common in pregnant women.
Respiratory distress which may be due to pulmonary oedema or acute respiratory distress syndrome (ARDS) – common in pregnant women.
Severe anaemia (may present with pallor).
Spontaneous bleeding/disseminated intravascular coagulation.
Shock.
Sepsis – more common in pregnant women.
Haemoglobinuria — falciparum can cause severe haemolysis with dark red urine (‘blackwater fever’).
Malaria is a medical emergency and immediate admission should be arranged for:
People with suspected severe or complicated malaria.
People with suspected falciparum malaria.
Pregnant women.
Children.
People who are older than 65 years of age.
All other people suspected of having malaria should be discussed urgently with
infectious disease specialist — where capacity exists for close clinical and parasitological monitoring, clinicians experienced in the management of malaria may treat adults with malaria as outpatients.
All cases of malaria must be
notified to Public Health England
Risk of severe malaria:
Severe malaria is more likely in children, pregnant women, older people, and immunocompromised people (for example those with splenectomy or HIV/AIDS).
Treatment of malaria depends on a variety of factors including…
species of Plasmodium parasite, severity of infection, tolerability of specific drugs, and patterns of drug resistance.
Anti-malarial medications are associated with
neurological and psychiatric symptoms
Artesunate-type drugs are more efficacious and better tolerated in pregnancy than quinines
Treatment failures are rare but have been noted and clinicians should be aware of the possibility
Antimalarial drug options for malaria?
Artesunate=
Parenteral artesunate is used to treat severe or complicated malaria; Intravenous artesunate can cause haemolysis and follow-up blood tests are required.
Quinine= may be used initially to treat severe or complicated malaria if artesunate is unavailable.
Artemisinin combination therapy (ACT)=
ACT may be used to treat uncomplicated malaria and is the preferred treatment for mixed infection.
Atovaquone-proguanil=
may be used to treat uncomplicated falciparum malaria if ACT is unavailable.
Quinine plus doxycycline=
may be used to treat uncomplicated falciparum malaria if ACT is unavailable.
Doxycycline should not be given to children younger than 12 years of age.
Chloroquine= may be used to treat uncomplicated P. malariae, P. ovale, P. knowlesi, and most cases of P. vivax malaria but use depends upon patterns of resistance and tolerance.
Primaquine= only currently effective drug for the eradication of hypnozoites (dormant parasites which persist in the liver after treatment of P. vivax and P. ovale). It is contraindicated in pregnancy and breastfeeding.
Malaria= what is essential before treatment with primaquine is started?
Screening for G6PD deficiency is essential before treatment with primaquine is started as it can cause haemolysis in G6PD deficient individuals, which can be fatal. It is contraindicated in pregnancy and breastfeeding.
Meningitis= Ix?
LP
if contraindicated (any signs of raised ICP) then blood cultures and PCR for meningococcus
Meningitis: when is LP contraindicated?
any signs of raised ICP:
- focal neuro signs
- papilloedema
- signif bulging of fontanelle
- disseminated intravascular coagulation
- signs of cerebral herniation
Mx of meningitis?
1) Abx
2) Dexamethasone in all <3m or if LP shows certain features
3) Fluids- Tx any shock
4) Cerebral monitoring= mechanical ventilation if resp impairment
5) public health notification and Abx prophylaxis of contacts
Abx choice for meningitis?
> 3m= IV cefotaxime (or ceftriaxone)
<3m or >50= IV amoxicillin (or ampicillin) + IV cefotaxime
When should dexamethasone be given to pts with meningitis?
if <3m
or
if LP shows= frankly purulent CSF; WBC >1000/microlitre; raised CSF WBC with protein conc >1g/litre; bacteria on gram stain
Abx prophylaxis for contacts of meningitis?
ciprofloxacin (preferred) or rifampicin
Causes of meningitis if 0-3m
Group B Streptococcus (most common cause in neonates)
E. coli
Listeria monocytogenes
Most common cause of meningitis in neonates?
group B strep
Causes of meningitis in 3m-6yrs?
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae
Causes of meningitis in 6yrs-60yrs?
Neisseria meningitidis
Streptococcus pneumoniae
Causes of meningitis in >60yrs?
Streptococcus pneumoniae
Neisseria meningitidis
Listeria monocytogenes
Causes of meningitis in immunosuppressed?
Listeria monocytogenes
Cx of meningitis?
sensorineural hearing loss (most common)
seizures
focal neurological deficit
infective= sepsis, intracerebral abscess
pressure= brain herniation, hydrocephalus
Most common cause of meningitis?
sensorineural hearing loss
Pts with meningococcal meningitis are at risk of what?
Waterhouse-Friderichsen syndrome (adrenal insufficiency secondary to adrenal haemorrhage).
Pts with meningococcal meningitis are at risk of Waterhouse-Friderichsen syndrome- what is this?
(adrenal insufficiency secondary to adrenal haemorrhage)
CSF analysis in meningitis= bacterial findings?
1) cloudy
2) glucose low (<1/2 plasma)
3) protein high (>1g/l)
4) white cells= 10-5000 polymorphs/mm3
5) opening pressure= high (>20)
CSF analysis in meningitis= viral findings?
1) clear/cloudy
2) glucose normal (60-80% of plasma glucose)
3) protein normal/high
4) white cells= 15-1000 lymphocytes/mm3
5) opening pressure= normal/high
CSF analysis in meningitis= TB findings?
1) slight cloudy, fibrin web
2) glucose low (<1/2 plasma)
3) protein high (>1g/l)
4) white cells= 30-300 lymphocytes/mm3
5) opening pressure= high
CSF analysis in meningitis= fungal findings?
1) cloudy
2) glucose low (<1/2 plasma)
3) protein high (>1g/l)
4) white cells= 20-200 lymphocytes/mm3
5) opening pressure= high/very high
What is sometimes used in Ix TB meningitis?
The Ziehl-Neelsen stain is only 20% sensitive in the detection of tuberculous meningitis and therefore PCR is sometimes used (sensitivity = 75%)
What viral cause of meningitis has a low glucose level not normal?
mumps and herpes encephalitis
CSF:
1) cloudy
2) glucose low (<1/2 plasma)
3) protein high (>1g/l)
4) white cells= 20-200 lymphocytes/mm3
5) opening pressure= high/very high
fungal meningitis
CSF:
1) slight cloudy, fibrin web
2) glucose low (<1/2 plasma)
3) protein high (>1g/l)
4) white cells= 30-300 lymphocytes/mm3
5) opening pressure= high
TB meningitis
CSF:
1) clear/cloudy
2) glucose normal (60-80% of plasma glucose)
3) protein normal/high
4) white cells= 15-1000 lymphocytes/mm3
5) opening pressure= normal/high
viral meningitis
CSF:
1) cloudy
2) glucose low (<1/2 plasma)
3) protein high (>1g/l)
4) white cells= 10-5000 polymorphs/mm3
5) opening pressure= high (>20)
bacterial meningitis
The investigation and management of suspected bacterial meningitis are usually…
intertwined given the potential negative impact of delayed antibiotic treatment
If patients are in a pre-hospital setting (for example a GP surgery) and meningococcal disease is suspected then do what?
give IM benzylpenicillin as long as doesn’t delay transit to hospital
All suspected meningitis cases should be…
urgently transferred to hospital
Meningitis= steps in Ix and Mx?
1) A to E approach
2) senior review if any warning signs
3) consider LP
4) Mx
Meningitis= steps in Ix and Mx: 1) A to E?
Airway
Breathing
Circulation
Disability: GCS, ; focal neurological signs; seizures; papilloedema;
Meningitis= steps in Ix and Mx: 2) senior review if what warning signs are present?
examples:
rapidly progressive rash
poor peripheral perfusion
respiratory rate < 8 or > 30 / min or pulse rate < 40 or > 140 / min
pH < 7.3 or WBC< 4 *109/L or lactate > 4 mmol/L
GCS < 12 or a drop of 2 points
poor response to fluid resuscitation
Meningitis= steps in Ix and Mx: 3) deciding whether/when to do LP?
delay if contraindicated
LPs require an aseptic technique and are potentially technical difficult - this means they make take time and delay other treatment
on the other hand, having a CSF sample can be very useful in confirming the diagnosis and guiding antibiotic treatment
as always, patient safety means that if there is any doubt IV antibiotics should be given as a priority
Meningitis= steps in Ix and Mx: when should LP be delayed?
signs of severe sepsis or a rapidly evolving rash
severe respiratory/cardiac compromise
significant bleeding risk
signs of raised intracranial pressure= focal neurological signs; papilloedema; continuous or uncontrolled seizures; GCS ≤ 12
Meningitis= steps in Ix and Mx: 4) categories of Mx?
Mx of pts without indication for delayed LP
Mx of pts with signs of raised intracranial pressure
Mx of pts with signs of severe sepsis or rapidly evolving rash
Mx of meningitis in pts without indication for delayed LP?
1) IV access= bloods and blood cultures
2) LP within 1hr (if not start Abx)
3) IV Abx
4) IV dexamethasone
CT not normally indicated
Meningitis= what if LP is not indicated for delay (so is done)?
if this cannot be done within the first hour, IV antibiotics should be given after blood cultures have been taken
Meningitis= IV dexamethasone?
consider adjunctive Tx with dexamethasone (particularly if pneumococcal meningitis suspected in adults), preferably starting before or with first dose of antibacterial, but no later than 12 hours after starting antibacterial; avoid dexamethasone in septic shock, meningococcal septicaemia, or if immunocompromised, or in meningitis following surgery
Meningitis= IV dexamethasone- when to NOT give?
avoid dexamethasone in septic shock, meningococcal septicaemia, or if immunocompromised, or in meningitis following surgery’
Meningitis Mx= in pt with signs of raised ICP?
1) get critical care input
2) secure airway + high-flow oxygen
3) IV access → take bloods and blood cultures
4) IV dexamethasone
5) IV antibiotics
6) arrange neuroimaging
Meningitis Mx= in pts with signs of severe sepsis or rapidly evolving rash?
1) get critical care input
2) secure airway + high-flow oxygen
3) IV access → take bloods and blood cultures
4) IV fluid resuscitation
5) IV antibiotics as above
Meningitis= bloods that are taken should be tested for what?
full blood count
renal function
glucose
lactate
clotting profile
CRP
Meningitis= if an LP has been performed what should the CSF be tested for?
glucose, protein, microscopy and culture
lactate
meningococcal and pneumococcal PCR
enteroviral, herpes simplex and varicella-zoster PCR
consider investigations for TB meningitis
Initial empirical Abx therapy in meningitis?
3m-50yrs= IV cefotaxime (or ceftriaxone)
<3m= IV cefotaxime + amoxicillin (or ampicillin)
> 50yrs= IV cefotaxime (or ceftriaxone) + amoxicillin (or ampicillin)
Abx for Meningococcal meningitis?
IV benzylpenicillin or cefotaxime (or ceftriaxone)
Abx for Pneumococcal meningitis?
IV cefotaxime (or ceftriaxone)
Abx for Meningitis caused by Haemophilus influenzae?
IV cefotaxime (or ceftriaxone)
Abx for Meningitis caused by Listeria?
IV amoxicillin (or ampicillin) + gentamicin
If the patient has a history of immediate hypersensitivity reaction to penicillin or to cephalosporins the BNF recommends using what Abx in meningitis?
chloramphenicol
Meningitis=
Prophylaxis needs to be offered to who?
households and close contacts of patients affected with meningococcal meningitis. Prophylaxis should also be offered to people who have been exposed to respiratory secretion, regardless of the closeness of contact.
Meningitis risk to contacts?
risk to contacts is highest in the first 7 days but persists for at least 4 weeks
people who have been exposed to a patient with confirmed bacterial meningitis should be given prophylactic antibiotics if they have close contact within…
7d before onset
What else should be offered to close contacts of meningitis as well as prophylactic Abx?
meningococcal vaccination should be offered to close contacts when serotype results are available, including booster doses to those who had the vaccine in infancy
Prophylaxis for pneumococcal meningitis?
no prophylaxis is generally needed.
There are however exceptions to this. If a cluster of cases of pneumococcal meningitis occurs the HPA have a protocol for offering close contacts antibiotic prophylaxis.
Meningitis?
inflammation of the leptomeninges and the cerebrospinal fluid of the subarachnoid space
Viral meningitis?
inflammation attributed to a viral agent
Viral vs bacterial meningitis severity?
viral may be considered to be a more benign condition and is much more common. Approximately 3,000 cases of confirmed viral meningitis are reported yearly, however, the actual number of cases is likely to be much higher, as patients often do not present to medical services.
Causes of viral meningitis?
non-polio enteroviruses e.g. coxsackie virus, echovirus
mumps
herpes simplex virus (HSV), cytomegalovirus (CMV), herpes zoster viruses
HIV
measles
RFs for viral meningitis?
patients at the extremes of age (< 5 years and the elderly)
immunocompromised, e.g. patients with renal failure, with diabetes
intravenous drug users
CP of viral beningitis?
common features:
- headache
- evidence of neck stiffness
- photophobia (often milder than the photophobia experienced by a patient with bacterial meningitis)
- confusion
- fevers
less common features:
- focal neurological deficits on examination
- seizures: suggests a meningoencephalitis
What should be done in pts to confirm diagnosis of viral meningitis?
LP
viral PCR may demonstrate and underlying organism
LP findings in viral meningitis?
Opening Pressure= 10 - 20 cm³ H²O (10 - 20 cm³ H²O)
Cell count= 10-300 cells/µL (0 - 5 cells/µL)
Cell differential= Lymphocytes (0 - 5 cells/µL lymphocyte-predominant)
Glucose= 2.8 - 4.2 mmol/L or 2/3 serum glucose mmol/L ( 2.8 - 4.2 mmol/L or 2/3 paired serum glucose mmol/L)
Protein= 0.5 - 1 g/dL (0.15 - 0.45 g/L)
Mx of viral meningitis?
whilst awaiting the results of the LP, Tx should be supportive and if there is any question of bacterial meningitis or of encephalitis, the patient should be commenced on broad-spectrum Abx with CNS penetration e.g. ceftriaxone and aciclovir intravenously.
This is particularly the case if the patient has risk factors e.g. elderly,
immunocompromised
generally speaking, viral meningitis is self-limiting, with symptoms improving over the course of 7 - 14 days and complications are rare in immunocompetent patients
aciclovir may be used if the patient is suspected of having meningitis secondary to HSV
What may be used if pt is suspected of having meningitis secondary to HSV?
aciclovir
if there is any question of bacterial meningitis or of encephalitis, the patient should be commenced on what?
broad-spectrum antibiotics with CNS penetration e.g. ceftriaxone and aciclovir intravenously.
This is particularly the case if the patient has risk factors e.g. elderly, immunocompromised
Bacterial meningitis is a life-threatening condition that can affect all ages, but is most common in…
babies and children
Bacterial meningitis transmission occurs through what?
close contact, droplets, or direct contact with respiratory secretions
Prognosis of bacterial meningitis?
With prompt and adequate antimicrobial treatment and supportive therapy, the outcome of acute bacterial meningitis is excellent.
The case-fatality rates for bacterial meningitis are 4–10% in children and 25% in adults.
Complications are more common following what type of meningitis?
pneumococcal meningitis and occur in about 30% of people compared with 7% with meningococcal meningitis.
Factors that affect prognosis of bacterial meningitis?
Age — fatality rates are higher at extremes of age.
The causative organism.
Presence of comorbidities.
Severity at presentation.
Bacterial meningitis should be strongly suspected in people with all the symptoms in the red flag combinations:
Fever.
Headache.
Neck stiffness.
Altered level of consciousness or cognition (including confusion or delirium).
Meningococcal disease should be strongly suspected in people with any of these red flag symptoms:
Haemorrhagic, non-blanching rash with lesions larger than 2 mm (purpura).
Rapidly progressive and/or spreading non-blanching petechial or purpuric rash.
Any symptoms and signs of bacterial meningitis.
Type of rash pt MAY get in meningitis?
Haemorrhagic, non-blanching rash with lesions larger than 2 mm (purpura).
Rapidly progressive and/or spreading non-blanching petechial or purpuric rash.
CP of bacterial meningitis?
Non-specific symptoms: fever, nausea and vomiting, lethargy, irritable or unsettled mood, refusal of food and drink, headache, muscle ache or joint pain, and respiratory symptoms such as a cough.
More specific symptoms and signs: stiff neck, altered mental state (confusion, delirium and drowsiness, impaired consciousness), non-blanching rash, back rigidity, bulging fontanelle (in children younger than 2 years of age), photophobia, Kernig’s sign, Brudzinski’s sign, coma, paresis, focal neurological deficit, and seizures.
stiff neck, altered mental state (confusion, delirium and drowsiness, impaired consciousness), non-blanching rash, back rigidity, bulging fontanelle (in children younger than 2 years of age), photophobia, Kernig’s sign, Brudzinski’s sign, coma, paresis, focal neurological deficit, and seizures
bacterial meningitis
GP= Intravenous or intramuscular ceftriaxone or benzylpenicillin should be given to people with strongly suspected:
Bacterial meningitis if there is likely to be a clinically significant delay in transfer to hospital.
Meningococcal disease as soon as possible, unless this will delay transfer to hospital.
S&S of bacterial meningitis in babies, children and young people?
Fever, headache, neck stiffness, and altered level of consciousness or cognition (including confusion or delirium)
Fever and neck stiffness are less common in babies.
Headache and neck stiffness are harder to identify in babies and young children
Bulging fontanelle In babies and young children with an open fontanelle
Fever, headache, neck stiffness and altered level of consciousness or cognition are the red flag combination for bacterial meningitis
Fever is less common in babies
Ask the child or young person (or their family members or carers) if they have taken antipyretics, because this may make fever harder to identify
Ask the child or young person (or their family members or carers) if they have taken antipyretics, because this may make ill appearance harder to identify
Non-blanching petechial or purpuric rash= Mainly in meningococcal disease; Check all over the body and look for petechiae in the conjunctivae; May be difficult to see on brown, black or tanned skin
Pale, mottled skin or cyanosis
Irritability, lethargy
agitated, aggressive or subdued. Ask family members or carers about changes in the child or young person’s behaviour
Weak, high-pitched or continuous cry
Babies and children and young people with cognitive impairment or communication difficulties may not be able to report headache
Tachypnoea, apnoea, and grunting. Non-specific signs of illness, including sepsis and meningitis in babies
S&S of bacterial meningitis in adults?
Fever is less common in older adults
Headache and neck stiffness are harder to identify in adults with cognitive impairment
Neck stiffness is harder to identify in adults with dementia or arthritis
Altered level of consciousness or cognition may be missed in young adults and older adults
Non-blanching petechial or purpuric rash= Mainly in meningococcal meningitis and meningococcal disease (with or without meningococcal meningitis). Check all over the body and look for petechiae in the conjunctivae. May be difficult to see on brown, black or tanned skin
Pale, mottled skin or cyanosis. May be difficult to see on brown, black or tanned skin.
Lethargy in older adults.
Bacterial meningitis may be missed in older adults with delirium or altered consciousness.
In young people and young adults, altered behaviour may be incorrectly assumed to be caused by alcohol or substance misuse, and bacterial meningitis can be missed as a result.
Bacterial meningitis= neck stiffness may be harder to identify in who?
adults with cognitive impairment, communication difficulties, dementia or arthritis
children and young people with cognitive impairment or communication difficulties
Describe meningitis rash?
Non-blanching petechial or purpuric rash
Non-blanching petechial or purpuric rash is mainly in what?
meningitis caused by meningococcal bacteria (Neisseria meningitidis)
this type can lead to meningococcal septicemia (meningococcemia)
Fever in meningitis?
Ask the person (or their family members or carers) if they have taken antipyretics, because this may make fever harder to identify
Fever is a particular concern for babies at the following levels:
39°C or higher in children aged 3 to 6 months
38°C or higher in children younger than 3 months
Children and young people with bacterial meningitis commonly present with?
non-specific symptoms and signs, including fever, vomiting, irritability, reduced feeding in babies, and upper respiratory tract symptoms. These may be difficult to distinguish from other viral infections.
Some children with bacterial meningitis present with seizures.
Children and young people with more specific symptoms and signs are more likely to have what type of meningitis?
bacterial meningitis or meningococcal septicaemia, and the symptoms and signs may become more severe and more specific over time.
Classical signs of meningitis (neck stiffness, bulging fontanelle, high pitched cry) are often absent in who?
infants with bacterial meningitis.
Meningitis= When a non-blanching rash is present, it may appear as a?
Petechial rash (red or purple non-blanching macules smaller than 2 mm in diameter).
Purpuric (haemorrhagic) rash (spots larger than 2 mm in diameter) — this may be absent in the early phase of the illness and may initially be blanching or macular in nature.
How to assess meningitis rash?
Examine the whole body systematically (including nappy areas) for rash and unusual skin colour — particularly for non-blanching rashes and petechiae.
Advise to look for any changes in the rash, as it can change from blanching to non-blanching.
Consider checking for non-blanching rashes using the ‘glass test’.
Be aware that the glass test should not be used solely for diagnosing bacterial meningitis and meningococcal septicaemia.
A rash may be hard to detect on brown, black or tanned skin (even when using the glass test). Check paler areas of the body (such as the soles of the feet or palms of the hands) or the conjunctivae or palate.
Glass test for meningitis?
This involves pressing the side of a glass or tumbler firmly against the rash to see if the rash fades or loses colour under pressure. A petechial or purpuric rash does not fade.
Be aware that the glass test should not be used solely for diagnosing bacterial meningitis and meningococcal septicaemia.
The risk of meningococcal disease is high in a child or young person with petechiae if:
The petechiae start to spread.
The rash becomes purpuric.
There are signs of bacterial meningitis.
There are signs of meningococcal septicaemia.
The child or young person appears unwell.
meningococcal disease vs meningococcal septicemia?
Meningococcal septicaemia is a type of blood poisoning that is caused by the same type of bacteria that cause the most common form of bacterial meningitis.
Meningococcal meningitis and septicaemia are together known as meningococcal disease.
Meningitis= features of shock?
Capillary refill time of more than 2 seconds, cold hands and feet.
Unusual skin colour.
Tachycardia and/or hypotension.
Respiratory symptoms or breathing difficulty.
Leg pain.
Toxic/moribund state.
Altered mental state/decreased conscious level.
Poor urine output.
Dose of IM benxylpenicillin for meningitis presentation in GP?
Children aged 1-11 months — 300 mg.
Children aged 1–9 years — 600 mg.
Adults and children aged 10 years or over — 1200 mg.
Dose of IM ceftriaxone (if benzylpenicillin not given) for meningitis presentation in GP?
Children aged 1 month–11 years (body-weight up to 50 kg) — 80 mg/kg (intramuscularly). Maximum dose 2000 mg.
Children 9–11 years (body-weight 50 kg and above) — 2000 mg.
Adults and children aged 12–17 years — 2000 mg.
Necrotising fasciitis?
rapidly spreading, life-threatening bacterial infection that destroys skin, fat, and muscle tissue. It is commonly referred to as a “flesh-eating disease.”
medical emergency
Necrotising fasciitis is difficult to…
recognise in the early stages
Necrotising fasciitis can be classified according to what?
the causative organism
type 1 & type 2
Necrotising fasciitis type 1?
caused by mixed anaerobes and aerobes (often occurs post-surgery in diabetics). This is the most common type
Necrotising fasciitis type 2?
caused by Streptococcus pyogenes
Necrotising fasciitis RFs?
skin factors: recent trauma, burns or soft tissue infections
diabetes mellitus=
the most common preexisting medical condition; particularly if the patient is treated with SGLT-2 inhibitors
intravenous drug use
immunosuppression
Necrotising fasciitis most commonly affected site?
the perineum (Fournier’s gangrene)
Fournier’s gangrene?
necrotising fasciitis affecting he perineum
Features of necrotising fasciitis?
acute onset
pain, swelling, erythema at the affected site
often presents as rapidly worsening cellulitis with pain out of keeping with physical features
extremely tender over infected tissue with hypoaesthesia to light touch
skin necrosis and crepitus/gas gangrene are late signs
fever and tachycardia may be absent or occur late in the presentation
Late signs of necrotising fasciitis?
skin necrosis and crepitus/gas gangrene
necrotising fasciitis often presents with what?
rapidly worsening cellulitis with pain out of keeping with physical features
Mx of necrotising fasciitis?
urgent surgical referral debridement
intravenous antibiotics
Prognosis of necrotising fasciitis?
average mortality of 20%
Who to speak to for notifiable diseases?
The ‘Proper Officer’ at the Local Health Protection Team needs to be notified. They in turn will notify the Health Protection Agency on a weekly basis.
HIV notified different.
In April 2010 the following diseases were removed from the list of notifiable diseases?
Dysentery
Ophthalmia neonatorum
Leptospirosis
Relapsing fever
List of notifiable diseases?
Acute encephalitis
Acute infectious hepatitis
Acute meningitis
Acute poliomyelitis
Anthrax
Botulism
Brucellosis
Cholera
COVID-19
Diphtheria
Enteric fever (typhoid or paratyphoid fever)
Food poisoning
Haemolytic uraemic syndrome (HUS)
Infectious bloody diarrhoea
Invasive group A streptococcal disease
Legionnaires Disease
Leprosy
Malaria
Measles
Meningococcal septicaemia
Mumps
Plague
Rabies
Rubella
Severe Acute Respiratory Syndrome (SARS)
Scarlet fever
Smallpox
Tetanus
Tuberculosis
Typhus
Viral haemorrhagic fever (VHF)
Whooping cough
Yellow fever
Neutropenic sepsis?
relatively common complication of cancer therapy, usually as a consequence of chemotherapy
When does neutropenic sepsis commonly occur?
7-14d after chemotherapy
How is neutropenic sepsis defined?
neutrophil count of < 0.5 * 109 in a patient who is having anticancer treatment and has one of the following:
- a temperature higher than 38ºC or
- other signs or symptoms consistent with clinically significant sepsis
neutrophil count of < 0.5 * 109 in a patient who is having anticancer treatment and has one of the following:
- a temperature higher than 38ºC or
- other signs or symptoms consistent with clinically significant sepsis
diagnosis?
neutropenic sepsis
Cause of neutropenic sepsis?
coagulase-negative, Gram-positive bacteria are the most common cause, particularly Staphylococcus epidermidis
this is probably due to the use of indwelling lines in patients with cancer
Neutropenic sepsis prophylaxis?
if it is anticipated that patients are likely to have a neutrophil count of < 0.5 * 109 as a consequence of their treatment they should be offered a fluoroquinolone
Mx of neutropenic sepsis?
antibiotics must be started immediately, do not wait for the WBC
following this initial treatment patients are usually assessed by a specialist and risk-stratified to see if they may be able to have outpatient treatment
Mx of neutropenic sepsis= initial empirical Abx therapy?
piperacillin with tazobactam (Tazocin)
many units add vancomycin if the patient has central venous access but NICE do not support this approach
Mx of neutropenic sepsis= following empirical tazocin Abx, if pt is still febrile and unwell after 48hrs then?
alternative antibiotic such as meropenem is often prescribed +/- vancomycin
if patients are not responding after 4-6 days the Christie guidelines suggest ordering investigations for fungal infections (e.g. HRCT), rather than just starting therapy antifungal therapy blindly
there may be a role for G-CSF in selected patients
What is neutropenic sepsis?
potentially life-threatening complication of neutropenia. It is defined as a temperature of greater than 38°C or any symptoms and/or signs of sepsis, in a person with an absolute neutrophil count of 0.5 x 109/L or lower.
Febrile neutropenia?
most common complication of anticancer treatment, and describes the presence of fever in a person with neutropenia.
Neutropenic sepsis= There are multiple possible causes of neutropenia such as?
cytotoxic chemotherapy and other immunosuppressive drugs, stem cell transplantation, infections, bone marrow disorders such as aplastic anaemia and myelodysplastic syndromes, and nutritional deficiencies.
The risk of infection and/or sepsis increases with severe and/or prolonged neutropenia, and a rapid decline in neutrophil count.
Possible complications of neutropenic sepsis include?
death, organ failure, invasive and atypical infection, coagulopathy, encephalopathy and delirium, and long term physical, psychological and/or cognitive sequelae.
A diagnosis of neutropenic sepsis should be suspected in any person with known neutropenia or risk factors for neutropenia, and/or risk factors for neutropenic sepsis, who becomes unwell. For example, if the person?
Has confirmed infection, or symptoms or signs indicating possible infection (may be minimal, atypical, or absent).
Has a temperature greater than 38°C (may be afebrile or have a low temperature).
Has clinical features of possible sepsis (may be minimal, atypical, or absent).
Appears unwell or there is concern from a relative or carer that there is a change in appearance or behaviour.
Urgent assessment of a person with suspected neutropenic sepsis should include:
Evaluation for physiological symptoms and signs to identify the risk of serious complications.
Management of a person with suspected neutropenic sepsis
should include implementation of the ‘Sepsis Six’ bundle of care within the first hour following recognition of sepsis by:
Arranging emergency transfer to hospital (usually by 999 ambulance) if the person is critically unwell.
Arranging emergency transfer to the local oncology or haematology unit, or medical assessment unit, if the person is clinically stable, depending on local referral pathways.
Management of a person with a confirmed diagnosis of neutropenic sepsis following hospital discharge should include:
Liaising with the person’s specialist if there is any uncertainty or concern regarding the clinical presentation, such as persistent fever.
Providing advice on the nature of sepsis, what to expect during recovery after sepsis, and sources of information and support.
Providing information on how and when to seek specialist advice on any symptoms or concerns, and when to seek emergency care, for example if there is fever, signs of infection, or the person is feeling unwell.
Assessing and managing any complications following sepsis.
Neutropenic sepsis= Chills, shivers, rigors, and/or a temperature greater than 38°C.
Note: people with neutropenic sepsis may not present with fever and may instead present with….
hypothermia. In addition, medication such as corticosteroids may mask an elevated temperature.
Sepsis?
life-threatening organ dysfunction caused by dysregulated host response to an infection
Sepsis definition?
life-threatening organ dysfunction caused by a dysregulated host response to infection
Septic shock?
a more severe form sepsis, technically defined as ‘in which circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone’
Sepsis vs septic shock?
sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection
septic shock: a more severe form sepsis, technically defined as ‘in which circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone’
Sepsis= Adult patients outside of ICU with suspected infection are identified as being at heightened risk of mortality if they have….
quickSOFA (qSOFA) score meeting >= 2 of the following criteria: respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100mmHg or less
Sepsis= qSOFA score?
Respiratory rate > 22/min
Altered mentation
Systolic blood pressure < 100 mm Hg
Within an ICU setting a full SOFA score is often used.
Sepsis= what does the qSOFA score mean?
Adult patients outside of ICU with suspected infection are identified as being at heightened risk of mortality if they have quickSOFA (qSOFA) score meeting >= 2
Sepsis= red flag criteria?
Responds only to voice or pain/ unresponsive
Acute confusional state
Systolic B.P <= 90 mmHg (or drop >40 from normal)
Heart rate > 130 per minute
Respiratory rate >= 25 per minute
Needs oxygen to keep SpO2 >=92%
Non-blanching rash, mottled/ ashen/ cyanotic
Not passed urine in last 18 h/ UO < 0.5 ml/kg/hr
Lactate >=2 mmol/l
Recent chemotherapy
Sepsis= amber flag criteria?
Relatives concerned about mental status
Acute deterioration in functional ability
Immunosuppressed
Trauma/ surgery/ procedure in last 6 weeks
Respiratory rate 21-24
Systolic B.P 91-100 mmHg
Heart rate 91-130 OR new dysrhythmia
Not passed urine in last 12-18 hours
Temperature < 36ºC
Clinical signs of wound, device or skin infection
Sepsis= What needs to be identified and treated and the patient supported regardless of the cause or severity?
the underlying cause
Clearly, the underlying cause of the patient’s sepsis needs to be identified and treated and the patient supported regardless of the cause or severity. If however any of the red flags are present then what should be started straight away?
sepsis 6
Sepsis 6?
1) Give oxygen
2) Take blood cultures
3) Give broad spectrum Abx
4) Give IV fluid challenge= bolus of 500ml crystalloid (saline) over less than 15mins
5) Measure serum lactate
6) Measure hourly urine output
septic shock: a more severe form sepsis, technically defined as ‘in which circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone’.
these patients can be clinically identified by what?
a vasopressor requirement to maintain a MAP ≥ 65mmHg and serum lactate >2mmol/L in the absence of hypovolemia
To help identify and categorise patients the Sequential (Sepsis-Related) Organ Failure Assessment Score (SOFA) is increasingly used. The score grades….
abnormality by organ system and accounts for clinical interventions. However, laboratory variables, namely, PaO2, platelet count, creatinine level, and bilirubin level, are needed for full computation.
Sepsis SOFA score= PaO2 /FI O2?
score 0= >400
score 1= <400
score 2= <300
score 3= <200
score 4= <100
Sepsis SOFA score= Platelets x103 microlitres?
score 0= >150
score 1= <150
score 2= <100
score 3= <50
score 4= <20
Sepsis SOFA score= Bilirubin µmol/L?
score 0= 20
score 1= 20-32
score 2= 33-101
score 3= 102-204
score 4= >204
Sepsis SOFA score= Cardiovascular?
score 0= MAP >70mmHg
score 1= MAP 70mmHg
score 2= Dopamine <5 or dobutamine (any dose)
score 3= Dopamine 5.1-15
or epinephrine 0.1
or norepinephrine 0.1
score 4= Dopamine >15 or
epinephrine >0.1
or norepinephrine >0.1
Sepsis SOFA score= GCS?
score 0= 15
score 1= 13-14
score 2= 10-12
score 3= 6-9
score 4= <6
Sepsis SOFA score= Creatinine µmol/L?
score 0= <110
score 1= 110-170
score 2= 171-299
score 3= 300-440
score 4= >440
Sepsis SOFA score= Urine output ml/day?
score 0= >500
score 1= >500
score 2= >500
score 3= <500
score 4= <200
Sepsis SOFA score= what score reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection?
2 or more
Sepsis= Even patients presenting with modest dysfunction can deteriorate further, emphasizing the seriousness of this condition and the need for…
prompt and appropriate intervention, if not already being instituted
Definition of sepsis?
syndrome defined as life-threatening organ dysfunction due to a dysregulated host response to infection
Septic shock definition?
subset of sepsis, which describes circulatory, cellular, and metabolic abnormalities that are associated with a greater risk of mortality than sepsis alone
Sepsis is thought to be what type of response?
multifactorial response to an infecting pathogen that may be amplified by host factors (such as genetics, age, and co-morbidities), the pathogen (type, virulence, and burden), and the environment.
Most common sites of infection that lead to sepsis?
respiratory, gastrointestinal, renal, and genitourinary tracts
RFs for sepsis?
extremes of age; people who are frail, immunocompromised, or immunosuppressed; people who have had recent trauma or surgery; people with a breach in skin integrity; and women who are pregnant, are post-partum, or have had a recent termination of pregnancy or miscarriage
Cx of sepsis?
organ failure, recurrent or secondary infection, and death
When should sepsis be considered?
any person presenting with:
- Symptoms or signs indicating possible infection causing significant illness or deterioration. These may be non-specific and non-localized, such as general malaise, agitation, or behavioural change.
- One or more risk factor(s) for sepsis, and who looks unwell.
- Concern from a relative or carer that there is a change in appearance or behaviour.
Urgent assessment for pt with sepsis should include?
Evaluation for physiological symptoms and signs to identify markers of increased risk of severe illness or death.
Use of a sepsis risk stratification tool to assess the risk of clinical deterioration from sepsis.
Mx of suspected sepsis may include= 999 to hospital if pt is….
high risk of severe illness or death from sepsis, or moderate-to-high risk in certain clinical situations
Mx of suspected sepsis may include= managing in primary care when?
if they are at high risk of severe illness or death from sepsis, but transfer of care to hospital would be unnecessarily burdensome or inappropriate, for example people who are very frail or approaching the end of life
they are at low risk of severe illness or death from sepsis, and providing safety-netting information.
Mx of suspected sepsis may include= managing what?
any underlying condition and arranging follow-up in primary care, if there are any moderate-to-high risk criteria for severe illness or death from sepsis, and a definitive diagnosis has been identified, and this can be treated in primary care.
Management of a person with a confirmed diagnosis of sepsis following hospital discharge may include:
Providing the person and/or carers with advice on the nature of sepsis, what to expect during recovery, and sources of information and support.
Assessing and managing any complications following sepsis, such as anxiety and/or post-traumatic stress disorder; persistent fatigue; or chronic pain.
People with sepsis may present with non-specific, non-localized clinical features — for example, general malaise, agitation, or behavioural change.
Older children vs infants & neonates?
Older children may present with a focus of infection, while infants and neonates usually present with non-specific symptoms and signs.
Pt with sepsis may not present with raised core temp, but may present with what…
lowered core temp
Hypotension is a presenting feature in 40% of people with sepsis, but be aware that…
normal blood pressure does not exclude sepsis.
High vs moderate to high risk criteria?
High risk of severe illness or death from sepsis if they meet any of the relevant high risk criteria.
Moderate to high risk of severe illness or death from sepsis if they meet any of the relevant moderate to high risk criteria.
High risk criteria for sepsis in child under 5?
No response to social cues; Appears ill to a healthcare professional; Does not wake, or if roused does not stay awake; Weak high pitched or continuous cry
Resp:
- any=
Grunting; Apnoea; Oxygen saturation of less than 90% in air or increased oxygen requirement over baseline
- <1yrs= RR 60+
- 1-2yrs= RR 50+
- 3-4yrs= RR 40+
Circulation:
- any= HR <60
- <1yrs= HR 160+
- 1-2yrs= HR 150+
- 3-4yrs= HR 140+
Skin=
Mottled or ashen appearance; Cyanosis of skin, lips, or tongue; Non-blanching rash of skin or purpric rash
Temp:
- any= <36C
- <3m= 38C+
Moderate to high risk criteria for sepsis in child under 5?
Not responding normally to social cues; No smile; Wakes only with prolonged stimulation; Decreased activity; Parent or carer concern that child is behaving differently from usual
Resp:
- Oxygen saturation of less than 92% in air or increased oxygen requirement over baseline; Nasal flaring
- <1yr= RR 50-59
- 1-2yrs= RR 40-49
- 3-4yrs= RR 35-39
Circulation:
- Capillary refill time of 3 seconds or more; Reduced urine output; For catheterized patients, passed less than 1 ml/kg of urine per hour
- <1yrs= HR 150-159
- 1-2yrs= HR 140-149
- 3-4yrs= HR 130-139
Skin:
- Pallor of skin, lips, or tongue
Temp:
- 3-6m= 39C +
Other= leg pain, cold hands or feet
High risk criteria for sepsis in child 5-11yrs?
Objective evidence of altered behaviour or mental state; Appears ill to a healthcare professional; Does not wake or if roused does not stay awake
Resp:
- any= Oxygen saturation of less than 90% in air or increased oxygen requirement over baseline
- 5yrs= RR 29+
- 6-7yrs= RR 27+
- 8-11yrs= RR 25+
Circulation:
- any= HR <60
- 5yrs= HR 130+
- 6-7yrs= HR 120+
- 8-11yrs= HR 115+
Skin= Mottled or ashen appearance; Cyanosis of skin, lips, or tongue; Non-blanching rash of skin
Moderate to high risk criteria for sepsis in child 5-11yrs?
Not behaving normally; Decreased activity; Parent or carer concern that the child is behaving differently from usual
Resp:
- any= Oxygen saturation of less than 92% in air or increased oxygen requirement over baseline
- 5yrs= RR 24-28
- 6-7yrs= RR 24-26
- 8-11yrs= RR 22-24
Circulation:
- any= Capillary refill time of 3 seconds or more; Reduced urine output; For catheterized patients, passed less than 1 ml/kg of urine per hour
- 5yrs= HR 120-129
- 6-7rs= HR 110-119
- 8-11yrs= HR 105-114
Tympanic T <36
Leg pain; cold hands or feet
High risk criteria for sepsis in children 12-15yrs?
Objective evidence of new altered mental state
Resp= Raised respiratory rate: 25 breaths per minute or more; New need for oxygen (40% FiO2 or more) to maintain saturation more than 92% (or more than 88% in known chronic obstructive pulmonary disease)
BP= Systolic blood pressure 90 mmHg or less or systolic blood pressure more than 40 mmHg below normal
Circulation= Raised heart rate: more than 130 beats per minute; Not passed urine in previous 18 hours; For catheterized patients, passed less than 0.5 ml/kg of urine per hour
Mottled or ashen appearance; Cyanosis of skin, lips, or tongue; Non-blanching petechial or purpuric rash
Moderate to high risk criteria for sepsis in children 12-15yrs?
History from patient, friend, or relative of new onset of altered behaviour or mental state; History of acute deterioration of functional ability; Impaired immune system (illness or drugs including oral steroids); Trauma, surgery, or invasive procedures in the last 6 weeks
RR 21-24
Systolic blood pressure 91–100 mmHg
Raised heart rate: 91–130 beats per minute (for pregnant women 100–130 beats per minute) or new onset arrhythmia; Not passed urine in the past 12–18 hours; For catheterized patients, passed 0.5–1 ml/kg of urine per hour
Tympanic temperature less than 36°C
Signs of potential infection, including redness, swelling, or discharge at surgical site or breakdown of wound
Bloods in sepsis?
Blood gas including glucose and lactate measurement — hypoglycaemia may result from depleted glycogen stores; hyperglycaemia may result from the stress response to sepsis; hyperlactataemia is a non-specific indicator of cellular or metabolic stress and is a marker of illness severity, with a higher level predictive of higher mortality rates.
Blood culture — ideally done before antibiotic administration, to identify a primary bacteraemia.
FBC — white cell count may be high or low; thrombocytopenia may indicate disseminated intravascular coagulation (DIC).
CRP — may indicate infection and/or inflammation.
Creatinine, urea, and electrolytes — may indicate dehydration and/or acute kidney injury.
LFTs — increased bilirubin or alanine aminotransferase (ALT) levels may indicate cholestasis or other liver dysfunction.
Clotting screen — if abnormal may indicate coagulopathy/DIC.
Urine analysis and culture, CXR, and additional investigations depending on the person’s clinical presentation — this may allow identification of the source of infection, pathogen(s) and sensitivities, and subsequent tailoring and/or de-escalation of antibiotic therapy if appropriate. Source control to eliminate a focus of infection may be possible, such as abscess drainage, debridement of infected tissue, removal of infected devices or foreign bodies, or surgery.RP
Sepsis Mx= Transfer to critical care may be needed to assess the need for…..
central venous access and initiation of inotropes (increase cardiac output by increasing cardiac contractility) or vasopressors (increase blood pressure by increasing peripheral vascular resistance), to maintain perfusion pressure.
Staphylococcal toxic shock syndrome?
severe systemic reaction to staphylococcal exotoxins, the TSST-1 superantigen toxin.
It came to prominence in the early 1980s following a series of cases related to infected tampons.
Staphylococcal toxic shock syndrome= came to prominence in the early 1980s following a series of cases related to what?
infected tampons
Staphylococcal toxic shock syndrome= Centers for Disease Control and Prevention diagnostic criteria?
fever: temperature > 38.9ºC
hypotension: systolic blood pressure < 90 mmHg
diffuse erythematous rash
desquamation of rash, especially of the palms and soles
involvement of three or more organ systems: e.g. gastrointestinal (diarrhoea and vomiting), mucous membrane erythema, renal failure, hepatitis, thrombocytopenia, CNS involvement (e.g. confusion)
Mx of Staphylococcal toxic shock syndrome?
removal of infection focus (e.g. retained tampon)
IV fluids
IV antibiotics
Surgical site infections may occur following what?
breach in tissue surfaces and allow normal commensals and other pathogens to initiate infection.
They are a major cause of morbidity and mortality.
Surgical site infections (SSI) comprise up to ….% of all healthcare-associated infections and at least 5% of patients undergoing surgery will develop an SSI as a result.
20%
In many cases of surgical site infection, the organisms come from what?
pts own body
In many cases, the organisms are derived from the patient’s own body. Measures that may increase the risk of surgical site infection (SSI) include what?
Shaving the wound using a razor (disposable clipper preferred)
Using a non-iodine impregnated incise drape if one is deemed to be necessary
Tissue hypoxia
Delayed administration of prophylactic antibiotics in tourniquet surgery
Prevent surgical site infection preop?
Don’t remove body hair routinely
If hair needs removal, use electrical clippers with a single-use head (razors increase infection risk)
Abx prophylaxis if:
- placement of prosthesis or valve
- clean-contaminated surgery
- contaminated surgery
Use local formulary:
- Aim to give single-dose IV antibiotic on anaesthesia
- If a tourniquet is to be used, give prophylactic antibiotics earlier
Prevent surgical site infection preop- when to give Abx?
Abx prophylaxis if:
- placement of prosthesis or valve
- clean-contaminated surgery
- contaminated surgery
Use local formulary:
- Aim to give single-dose IV antibiotic on anaesthesia
- If a tourniquet is to be used, give prophylactic antibiotics earlier
Surgical site infection prevention intraoperatively?
Prepare the skin with alcoholic chlorhexidine (Lowest incidence of SSI)
Cover surgical site with dressing
A recent meta analysis has confirmed that administration of supplementary oxygen does not reduce the risk of wound infection. In contrast to previous individual RCTs
Wound edge protectors do not appear to confer benefit
Surgical site infection: prevention post op?
Tissue viability advice for management of surgical wounds healing by secondary intention.
Hepatitis A?
typically a benign, self-limiting disease, with a serious outcome being very rare
Hepatitis A= incubation period?
2-4w
Hepatitis A= type of virus?
RNA picornavirus
Hepatitis A= transmission?
faecal-oral spread, often in institutions
Hepatitis A= does it cause chronic disease?
no
Hepatitis A= features?
- flu-like prodrome
- abdominal pain: typically right upper quadrant
- tender hepatomegaly
- jaundice
- deranged liver function tests
- flu-like prodrome
- abdominal pain: typically right upper quadrant
- tender hepatomegaly
- jaundice
- deranged liver function tests
?hep A
Hepatitis A= Cx?
rare and there is no increased risk of hepatocellular ca
Hepatitis A= immunisation?
an effective vaccine is available
after the initial dose a booster dose should be given 6-12 months later
Hepatitis A= who should be vaccinated (based on Green book guidelines)?
men who have sex with men
people travelling to or going to reside in areas of high or intermediate prevalence, if aged > 1 year old
people with chronic liver disease
patients with haemophilia
injecting drug users
individuals at occupational risk: laboratory worker; staff of large residential institutions; sewage workers; people who work with primates
Hepatitis B= type of virus?
double-stranded DNA hepadnavirus
Hepatitis B= how is it spread?
exposure to infected blood or body fluids, including vertical transmission from mother to child
Hepatitis B= incubation period?
6-20w
Hepatitis B= features?
fever, jaundice, elevated liver transaminases
Hepatitis B= Cx?
chronic hepatitis (5-10%).
fulminant liver failure (1%)
hepatocellular carcinoma
glomerulonephritis
polyarteritis nodosa
cryoglobulinaemia
‘Ground-glass’ hepatocytes may be seen on light microscopy?
chronic hepatitis due to hep B
Hep B causing chronic hepatitis may show what on light microscopy?
‘Ground-glass’ hepatocytes
Hepatitis B= who is vaccinated?
- children at 2,3 & 4m
- a risks groups
Hepatitis B= at risks groups that should be vaccinated?
healthcare workers, intravenous drug users, sex workers, close family contacts of an individual with hepatitis B, individuals receiving blood transfusions regularly, chronic kidney disease patients who may soon require renal replacement therapy, prisoners, chronic liver disease patients
Hepatitis B= vaccine contains what?
HBsAg adsorbed onto aluminium hydroxide adjuvant and is prepared from yeast cells using recombinant DNA technology
Hepatitis B= how effective is the vaccine?
around 10-15% of adults fail to respond or respond poorly to 3 doses of the vaccine. Risk factors include age over 40 years, obesity, smoking, alcohol excess and immunosuppression
Hepatitis B= when is testing for anti-HBs recommended?
only recommended for those at risk of occupational exposure (i.e. Healthcare workers) and patients with chronic kidney disease. In these patients anti-HBs levels should be checked 1-4 months after primary immunisation
Hepatitis B= Anti-HBs level (mIU/ml) >100?
Indicates adequate vaccine response, no further testing required. Should still receive booster at 5 years
Hepatitis B= Anti-HBs level (mIU/ml) 10-100?
Suboptimal response to vaccine - one additional vaccine dose should be given. If immunocompetent no further testing is required
Hepatitis B= Anti-HBs level (mIU/ml) <10?
Non-responder to vaccine. Test for current or past infection. Give further vaccine course (i.e. 3 doses again) with testing following. If still fails to respond then HBIG would be required for protection if exposed to the virus.
Management of hepatitis B?
pegylated interferon-alpha used to be the only treatment available
NICE still advocate the use of pegylated interferon firstl-line other antiviral medications are increasingly used with an aim to suppress viral replication (not in a dissimilar way to treating HIV patients)
examples include tenofovir, entecavir and telbivudine (a synthetic thymidine nucleoside analogue)
Hepatitis B= Mx?
pegylated interferon-alpha
Hepatitis B= Mx- how does pegylated interferon-alpha work?
reduces viral replication in up to 30% of chronic carriers
Hepatitis B= Mx with pegylated interferon-alpha, a better response to Tx is predicted in who?
female, < 50 years old, low HBV DNA levels, non-Asian, HIV negative, high degree of inflammation on liver biopsy
Hepatitis B= who are offered screening for hep B?
all pregnant women
Hepatitis B= babies born to mothers who are chronically infected with hepatitis B or to mothers who’ve had acute hepatitis B during pregnancy should receive what?
complete course of vaccination + hepatitis B immunoglobulin
studies are currently evaluating the role of oral antiviral treatment (e.g. Lamivudine) in the latter part of pregnancy
there is little evidence to suggest caesarean section reduces vertical transmission rates
Hepatitis B= can it be transmitted via breastfeeding?
NO
(HIV can)
Hepatitis B serology= HBsAg stands for?
hep B surface antigen
Hepatitis B serology= HBsAg is what?
the first marker to appear and causes the production of anti-HBs
Hepatitis B serology= first marker to appear?
HBsAg
Hepatitis B serology= HBsAg normally means what?
acute disease (present for 1-6m)
Hepatitis B serology= what usually means acute disease (present for 1-6m)?
HBsAg
Hepatitis B serology= what implies chronic disease (i.e. infective)?
HBsAg present for >6m
Hepatitis B serology= HBsAg present for >6m means what?
chronic disease (i.e. infective)
Hepatitis B serology= Anti-HBs stands for?
Hepatitis B surface antibody
Hepatitis B serology= Anti-HBs means what?
implies immunity (either exposure or immunisation); negative in chronic disease
Hepatitis B serology= Anti-HBs in chronic disease?
negative
Hepatitis B serology= what indicates immunity (either exposure or immunisation) and is negative in chronic disease?
Anti-HBs
Hepatitis B serology= Anti-HBc stands for?
Hepatitis B core antibody
Hepatitis B serology= Anti-HBc means what?
previous (or current) infection.
IgM anti-HBc appears during acute or recent hepatitis B infection and is present for about 6 months. IgG anti-HBc persists
Hepatitis B serology= Anti-HBc IgA and IgG?
IgM anti-HBc appears during acute or recent hepatitis B infection and is present for about 6 months. IgG anti-HBc persists
Hepatitis B serology= what indicates previous (or current) infection?
Anti-HBc
Hepatitis B serology= HbeAg stands for?
Hepatitis B virus (HBV) e antigen
is a small polypeptide, which exists in a free form in the serum of individuals during the early phase of hepatitis B infection, soon after hepatitis B virus surface antigen (HBsAg) becomes detectable.
Hepatitis B serology= HbeAg means wha?
results from breakdown of core antigen from infected liver cells as is, therefore, a marker of infectivity. Marker of HBV replication and infectivity
Hepatitis B serology= wha is a marker of HBV replication and infectivity?
HbeAg
Hepatitis B serology= previous immunisation results?
anti-HBs positive, all others negative
Hepatitis B serology= previous hepatitis B (> 6 months ago), not a carrier?
anti-HBc positive, HBsAg negative
Hepatitis B serology=
previous hepatitis B, now a carrier?
anti-HBc positive, HBsAg positive
Hepatitis B serology= way to remember?
HBsAg = ongoing infection, either acute or chronic if present > 6 months
anti-HBc = caught, i.e. negative if immunized
It is thought how many people are chronically infected with hep C?
200,000 in UK
Hepatitis C= at risk groups?
intravenous drug users and patients who received a blood transfusion prior to 1991 (e.g. haemophiliacs)
Hepatitis C= type of virus?
RNA flavivirus
Hepatitis C= incubation period?
6-9w
Hepatitis C= transmission?
IVDU most common
the risk of transmission during a needle stick injury is about 2%
the vertical transmission rate from mother to child is about 6%. The risk is higher if there is coexistent HIV
the risk of transmitting the virus during sexual intercourse is probably less than 5%
Hepatitis C= can mothers with hep C still breastfeed?
yes
Hepatitis C= is there a vaccine?
no
Hepatitis C= features after expsoure?
only 30% have features
- transient rise in serum aminotransferaes/jaundice
- fatigue
- arthralgia
Hepatitis C= Ix?
HCV RNA Ix of choice for acute infection
whilst patients will eventually develop anti-HCV antibodies it should be remembered that patients who spontaneously clear the virus will continue to have anti-HCV antibodies
Hepatitis C= prognosis?
around 15-45% of patients will clear the virus after an acute infection (depending on their age and underlying health) and hence the majority (55-85%) will develop chronic hepatitis C
Hepatitis C= chronic hep C?
persistence of HCV RNA in the blood for 6m
Hepatitis C= potential Cx of chronic hep C?
rheumatological problems: arthralgia, arthritis
eye problems: Sjogren’s syndrome
cirrhosis (5-20% of those with chronic disease)
hepatocellular cancer
cryoglobulinaemia: typically type II (mixed monoclonal and polyclonal)
porphyria cutanea tarda (PCT): it is increasingly recognised that PCT may develop in patients with hepatitis C, especially if there are other factors such as alcohol abuse
membranoproliferative glomerulonephritis
Hepatitis C= Mx of chronic infection- Tx depends on what?
the viral genotype so this should be tested prior to Tx
Hepatitis C= Mx of chronic infection- how effective is Tx?
clearance rates of around 95%
Hepatitis C= Mx of chronic infection- aim of Tx?
sustained virological response (SVR) defined as undetectable serum HCV RNA 6m after the end of therapy
Hepatitis C= Mx of chronic infection- the aim of Tx is to achieve a sustained virological response (SVR), what does this mean?
undetectable serum HCV RNA 6m after the end of therapy
Hepatitis C= Mx of chronic infection?
combination of protease inhibitors (e.g. daclatasvir + sofosbuvir or sofosbuvir + simeprevir) with or without ribavirin are used
Hepatitis C= Mx of chronic infection- what are the complications of treatment: ribavirin?
side-effects: haemolytic anaemia, cough.
Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic
Hepatitis C= Mx of chronic infection- what are the complications of treatment: interferon alpha (no longer recommended)?
side-effects: flu-like symptoms, depression, fatigue, leukopenia, thrombocytopenia
Hepatitis C & pregnancy= are women screened for hep C in the antenatal period?
no
Hepatitis C & pregnancy= vertical transmission risk?
vertical transmission rate from mother to child is about 6%.
The risk is higher if there is a high viral load or coexistent HIV
Hepatitis C & pregnancy= Mx- no definitive guidelines for Mx but based on expert reviews….
standard drug therapy cannot be used in pregnancy due to concerns about teratogenicity
HCV-positive pregnant women should be monitored throughout pregnancy
HCV RNA and LFTs should be done as early as possible into prenatal care to assess the risk of transmission and degree of liver disease
if pruritic or they develop jaundice, suspect intrahepatic cholestasis of pregnancy and perform LFTs.
invasive procedures should be minimised in mother and fetus to prevent vertical transmission
not routine to offer c-section
Hepatitis C & pregnancy= what increases the risk of passing on the virus?
exposure to maternal blood eg. due to perineal tears
Hepatitis C & pregnancy= can women breastfeed?
yes
Hepatitis D= type of virus?
single stranded RNA (it is an incomplete virus)
requires hepatitis B surface antigen to complete its replication and transmission cycle.
Hepatitis D= how is it transmitted?
similar to hep B- exchange of bodily fluids (through blood-to-blood contact or sexual contact)
Hepatitis D= what is it?
an incomplete RNA virus that requires hepatitis B surface antigen to complete its replication and transmission cycle.
Hepatitis D= pts may be infected with what at the same time as hep D?
hep B
Hepatitis D= what is needed to complete its replication and transmission cycle?
hep B
Hepatitis D= co-infection definition?
Hepatitis B and Hepatitis D infection at the same time.
Hepatitis D= superinfection definition?
A hepatitis B surface antigen positive patient subsequently develops a hepatitis D infection.
Hepatitis D= superinfection (have hep B then get hep D) is associated with what?
high risk of fulminant hepatitis (acute liver failure), chronic hepatitis and cirrhosis
Hepatitis D= diagnosis?
Diagnosis is made via reverse polymerase chain reaction of hepatitis D RNA
Hepatitis D= Tx?
Interferon but poor evidence base.
Hepatitis E= type of virus?
RNA hepevirus
Hepatitis E= how is it spread?
faecal-oral route
Hepatitis E= incubation period?
3-8w
Hepatitis E= where is it common?
Central and South-East Asia, North and West Africa and Mexico
Hepatitis E= causes a similar disease to what?
hep A but carries a significant mortality (about 20%) during pregnancy
Hepatitis E= does it cause chronic disease?
does not cause chronic disease or an increased risk of hepatocellular cancer
Hepatitis E= is there a vaccine?
currently in development but not yet in widespread use
Definition of hep A?
inflammation of the liver caused by infection with the hepatitis A virus. Transmission is through the faecal-oral route.
Is hep A common?
uncommon in the UK and usually presents as sporadic cases, community-wide outbreaks (from person-to-person transmission), or point-of-source outbreaks (related to contaminated food).
What hepatitis causes chronic liver disease?
B and C
Prognosis of hep A?
usually a self-limiting illness with a good prognosis — unlike hepatitis B and C, it does not cause chronic liver disease.
Complications include relapsing hepatitis (in about 15% of infected symptomatic people) and, rarely, acute liver failure (in less than 0.1% of people).
The clinical features of acute hepatitis A are common to all forms of viral hepatitis, and are characterized by different phases:
The prodromal phase includes flu-like symptoms, gastrointestinal symptoms (such as anorexia, nausea, vomiting, and abdominal right upper quadrant discomfort), and occasionally headache, cough, pharyngitis, constipation, diarrhoea, itch, and urticaria. There may be no specific signs on examination.
The icteric phase includes jaundice, pale stools, and dark urine (if there is cholestasis); pruritus; fatigue; anorexia; nausea; and vomiting — symptoms often improve once jaundice occurs. Hepatomegaly, splenomegaly, lymphadenopathy, and hepatic tenderness may be present on examination.
The convalescent phase includes malaise and hepatic tenderness.
Confirmed Hep A is defined by what?
Meeting the clinical case definition and having IgM and IgG antibodies to hepatitis A.
Having hepatitis A RNA (HAV RNA) detected regardless of clinical features.
Being asymptomatic with no recent history of immunisation, but having anti-HAV IgM in oral fluid or serum, and having an epidemiological link to a confirmed hepatitis A case.
Management of a person with confirmed or probable hepatitis A infection includes?
Admission to hospital if they are severely unwell.
Provision of symptomatic supportive care if admission is not indicated.
Notifying the local Health Protection Unit promptly.
Providing information and advice about hepatitis A, including the need to avoid alcohol during the acute illness.
Offering referral to a genito-urinary medicine clinic or drug rehabilitation centre, if appropriate.
Arranging follow up and monitoring liver function and prothrombin time, at a frequency dependent on clinical judgement, the person’s symptoms, and liver function test results.
Advising the person to seek medical attention if their symptoms worsen.
Prevention of transmission of hepatitis A involves advising:
The person to avoid work, school, or nursery, until they are no longer infectious (typically 7 days after the onset of jaundice or 7 days after the onset of symptoms if there is no history of jaundice).
The person and all close contacts about thorough hand washing after using the toilet, changing nappies, and helping with child toileting; ensuring good general personal hygiene; avoiding handling food; thorough hand washing before food preparation; practising safe sex until they are no longer infectious; and avoiding sharing drug paraphernalia.
People at high risk of hepatitis A infection should be offered…
hepatitis A vaccination if they are not already immune
Hep A= The clinical features of the icteric phase of hepatitis (usually lasts 1–3 weeks but can be more prolonged) include:
Jaundice, pale stools, and dark urine if cholestasis — jaundice may occur in 70-80% of infected adults.
Pruritus — common in the icteric phase.
Fatigue, anorexia, nausea, and vomiting — symptoms often improve once jaundice occurs.
Hepatomegaly and right upper quadrant tenderness — often present on examination; hepatomegaly may occur in up to 80% of symptomatic people. Splenomegaly and lymphadenopathy occur less commonly.
The clinical features of the convalescent phase of hepatitis A may include…
malaise, anorexia, muscle weakness, and hepatic tenderness.
Recovery usually takes about a month in young people but may take up to 6 months in others.
Complications are more likely in people with pre-existing liver disease and older people.
Hepatitis A does not cause chronic liver disease and following clearance of infection lifelong immunity is acquired.
HAV-IgM antibodies are typically present…
HAV-IgG….
HAV-IgM antibodies are typically present 5-10 days before the onset of symptoms, peak within a month of illness, and usually remain positive for 45-60 days but can persist for 6 months or more.
HAV-IgG antibodies are typically detectable at or just before the onset of symptoms and then persist to provide lifelong immunity.
Positive HAV-IgM, and positive HAV-IgG
acute hepatitis A infection is likely.
Hep A= A high IgG reactivity and a moderate level of IgM
suggests hepatitis A infection in the recent past rather than current acute infection.
Positive HAV-IgM, and negative HAV-IgG
gM result may be a false positive.
Negative HAV-IgM, and positive HAV-IgG
uggests past hepatitis A infection or immunity from previous vaccination.
Hep A= Serology results should be interpreted in the broader context of…
Timing of illness onset —if serology is taken in the first 5 days after the onset of symptoms, there is a small risk of a false negative result — serology should be repeated.
The age of the person — false IgM results are more likely in older people, a group likely to have had hepatitis A in childhood.
Co-morbidities — HAV IgM serology may not be reliable in patients who are significantly immunocompromised — consider referring for HAV PCR.
Risk factors for hepatitis A.
Results of liver function tests (see below)
LFTs in hep A?
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may be significantly increased (usually between 500 and 10,000 IU/L).
Bilirubin may be elevated (usually between 85.5 and 171 micromols/L, but can reach up to 500 micromols/L).
Alkaline phosphatase is generally less than 2x the upper limit of normal, but higher if there is cholestasis.
Prothrombin time may be prolonged (3 seconds or more suggests severe hepatitis and 50 seconds or more suggests acute liver failure).
The usual schedule for monovalent hepatitis A vaccines is a single dose (provides protection for up to 12 months) and then
a booster dose 6-12 months later if the person remains at long-term risk of contracting hepatitis A.
For pregnant women with acute hepatitis A infection, inform the midwifery/obstetric team of the diagnosis and advise the woman that…
Infection in early pregnancy is not thought to increase the risk of congenital malformation in the infant.
They may be at increased risk of preterm labour if infection occurs in the second or third trimester and should seek urgent medical advice if symptoms develop or they are concerned.
Breastfeeding is not known to pose a specific risk — thorough hand washing and personal hygiene should be maintained.
Hep A Mx= Follow-up at least every 1 to 2 weeks…
Consider more frequent follow-up if the person is symptomatic, and/or has jaundice, and depending on the results of liver function tests).
Repeat liver function tests until amino-transferase levels are normal (usually 4–12 weeks).
Seek specialist advice if the person has significantly abnormal liver function tests or coagulation screen, or if liver function appears to be worsening.
Advise the person to seek medical attention if symptoms worsen (particularly if they include vomiting and dehydration) and to be aware of the signs of hepatic decompensation (change in personality or level of consciousness).
Admit the person to hospital if they become severely unwell.
If a person presents who has been in contact with someone with known hepatitis A infection…
Contact the local Health Protection Unit (HPU) immediately, who will advise on further management if the person has not previously received the hepatitis A vaccine.
This may include giving hepatitis A vaccination and/or arranging for the administration of human normal immunoglobulin, depending on the timing and circumstances of contact, as well as other factors including the person’s age and co-morbidities.
Hepatitis B is an infectious disease of the liver caused by the hepatitis B virus (HBV) — transmission occurs through…
transmission occurs through contact with infected blood or body fluids.
In areas of low endemicity (such as the UK), most HBV infections are acquired in adulthood through sexual transmission or sharing of contaminated injecting drug use equipment.
In areas of high endemicity, HBV infection is predominantly acquired through perinatal transmission or horizontal transmission among young children.
Hepatitis B can be acute or chronic.
In England, the prevalence of chronic HBV is estimated to be 0.45% — most chronic HBV infections in the UK are acquired where?
overseas in endemic countries prior to arrival in the UK.
Most acute HBV infections in the UK are acquired through sexual transmission and injecting drug use.
Diagnosis of acute infection of hep B is based on detection of…
hepatitis B surface antigen (HBsAg) and IgM antibodies to hepatitis B core antigen (anti-HBc).
CP of hep B?
Children, in particular infants and younger children, are usually asymptomatic during acute infection.
Up to a third of adults develop symptoms (which may include fever, malaise, right upper quadrant abdominal pain and jaundice) with acute infection.
Jaundice occurs in about 10% of younger children and in 30-50% of adults.
When present, symptoms usually last between 1 and 6 weeks.
Hepatitis B surface antigen (HBsAg) is cleared in around 95% of immunocompetent adults. Fulminant hepatitis occurs in fewer than 1% of people but can be fatal.
Chronic hepatitis B is defined as
persistence of HBsAg for six months or more after acute infection with hepatitis B virus.
Chronic hep B= Chronic infection develops in
90% of infants infected perinatally (if not vaccinated); 20-50% of children infected between one and five years of age and about 5% of immunocompetent adults.
Most people with chronic hepatitis B infection are asymptomatic.
Approximately 20-25% of people with chronic HBV infection develop progressive liver disease, which can lead to cirrhosis and increased risk of hepatocellular cancer.
Hepatitis B immunisation should be offered to:
Infants, as part of the routine childhood immunisation programme.
People at high risk of exposure to the virus or complications of the disease.
People potentially exposed to HBV through accidental inoculation (such as needlestick or other ‘sharp’, bites, or scratch injuries) or contamination of mucous membranes or non-intact skin — hepatitis B immunoglobulin (HBIG) prophylaxis may also be indicated.
Babies born to pregnant women living with Hepatitis B — HBIG prophylaxis may also be indicated.
Management of a person with hepatitis B infection includes…
Admission if severely unwell.
Referral to a liver specialist for further investigation, treatment (where indicated) and follow-up.
Offering symptomatic supportive treatment (rest, pain relief, and treatment of nausea and itch) if needed while the person is awaiting referral.
Notifying the Health Protection Unit.
Offering advice on avoidance of alcohol and prevention of transmission of infection.
Offering referral to a genito-urinary medicine clinic and/or drug rehabilitation agency, if appropriate.
CP of hep B= acute infection?
A prodromal illness that includes fever, arthralgia, or a rash (that may appear about 2 weeks before the onset of jaundice, then resolves).
Non-specific malaise (which may be profound), fatigue, nausea, and poor appetite.
Right upper quadrant abdominal pain.
Jaundice (with dark urine and/or pale stools if cholestasis is present) — occurs in about 10% of younger children and in 30-50% of adults.
Extrahepatic manifestations such as glomerulonephritis, vasculitis, and polyarteritis.
CP of hep B= chronic infection?
there are often no physical signs or symptoms. After many years of infection, depending on the severity and duration, signs of chronic liver disease may develop, such as:
Spider naevi.
Finger clubbing.
Jaundice.
Palmar erythema.
Hepatosplenomegaly.
In severe cases thin skin, bruising, ascites, liver flap, and encephalopathy.
Hep B CP= what to be aware of?
Acute hepatitis B infection is asymptomatic in almost all infants and children and 10-50% of adults.
Fulminant hepatitis is a rare complication of acute hepatitis B infection (affects less than 1% of people). If present, however, it can progress rapidly to life-threatening liver failure with coagulopathy, encephalopathy, and cerebral oedema.
LFTs in acute hep b vs chronic?
In acute hepatitis B:
- ALT and AST levels may be significantly increased (usually between 500 and 10,000 IU/L).
- Bilirubin may be elevated (can reach up to 500 micromols/L).
- ALP is usually less than twice the upper limit of normal but can be higher in the presence of cholestasis.
- Prothrombin time may be prolonged (5 seconds or more suggests severe hepatitis and 50 seconds or more suggests acute liver failure).
In chronic hepatitis B:
- For most, the only indicator is a mildly elevated serum AST level; in many, liver enzymes will be normal.
Diagnosis of hepatitis B virus (HBV) is based upon the presence of what?
serological markers (antigens and antibodies) in plasma or serum
Hepatitis B Surface Antigen (HBsAg)?
indicates presence of viral envelope and suggests that the person is infectious. It rises during the incubation period and may be cleared early in the course of the disease. It is undetectable in around 10% of people by the time the test is performed. Chronic HBV infection is indicated by the persistence of serum HBsAg for more than 6 months.
Hepatitis B e antigen (HBeAg)?
detectable in the serum during both the early phases of acute infection and some chronic infections. Usually associated with relatively high levels of virus replication. People with chronic HBV tend to be more infectious if HBeAg is detected. If HBeAg has been cleared, anti-HBe is usually detected, and infectivity is lower.
Antibody to HBeAg (Anti-HBe)?
present following clearance of HBeAg from the plasma. Disappearance of HBeAg, development of anti-HBe, and a decline in HBV-DNA, indicates control of viral replication and predict resolution of acute hepatitis B.
Antibody to HBcAg (anti-HBc)?
indicates current or previous HBV infection. Appears at the onset of symptoms in acute infection and generally persists for life. May be absent very early in acute infection.
IgG antibody to hepatitis core antigen (anti-HBc IgG)?
generally persists for life and is indicative of past infection.
IgM antibody to hepatitis core antigen (anti-HBc IgM)?
indicates recent (within the last six months) HBV infection. Quantification may be useful to distinguish between acute and chronic infection. It is usually replaced gradually by immunoglobulin G (IgG) anti-HBc.
Antibody to HBsAg (anti-HBs)?
indicates recovery from and immunity to HBV. Anti-HBs without anti-HBc is a marker of immunisation. Anti-HBs is quantified to measure vaccination response.
Other tests for hep B other than serology (presence of antigens and antibodies)?
Additional tests include quantification of HBV DNA (often referred to as HBV viral load), and HBV core avidity testing:
High levels of HBV DNA are associated with a greater risk of progression to cirrhosis and hepatocellular cancer.
Core avidity testing can differentiate between acute and chronic core IgM infection.
Hep B steps to test?
Initial testing should ideally include (at least) HBsAg and anti-HBc.
Further tests (such as Hepatitis B e antigen, or antibody status (anti-HBe); HBV DNA level; IgM antibody to hepatitis B core antigen (anti-HBc IgM) may be required depending on the findings.
Positive HBsAg and positive anti-HBc IgM confirm an acute infection, particularly if supported by clinical suspicion and raised ALT.
Positive HBsAg and anti-HBc (total or IgG) but negative anti-HBc IgM confirm a chronic infection.
Different combinations of antibodies and antigens, alongside other findings, can indicate the phase of a chronic infection which is used in determining appropriate treatment options.
Hepatitis B serology:
HBsAg= +
Anti-HBs= -
HBeAg= +
Anti-HBe= -
Anti-HBcc= +
IgM anti-HBc= +
HBV DNA= +
ALT= elevated
Acute hep B
Hepatitis B serology:
HBsAg= -
Anti-HBs= +/-
HBeAg= -
Anti-HBe= +/-
Anti-HBcc= +
IgM anti-HBc= -
HBV DNA= -
ALT= normal
immunity following infection
Hepatitis B serology:
HBsAg= -
Anti-HBs= +
HBeAg= -
Anti-HBe= -
Anti-HBcc= -
IgM anti-HBc= -
HBV DNA= -
ALT= normal
immunity due to vaccination
Hepatitis B serology:
HBsAg= +
Anti-HBs= -
HBeAg= +/-
Anti-HBe= +/-
Anti-HBcc= +
IgM anti-HBc= -
HBV DNA= +
ALT= elevated
Chronic hep B - active
Hepatitis B serology:
HBsAg= +
Anti-HBs= -
HBeAg= -
Anti-HBe= +
Anti-HBcc= +
IgM anti-HBc= -
HBV DNA= undetectable or low
ALT= normal
Chronic hep B- inactive carrier
Fees for Hepatitis B vaccination?
Hepatitis B vaccine is not routinely available free of charge.
People requesting vaccination against hepatitis B in relation to travel abroad may be charged.
Vaccination indicated for treatment (for example, following a human bite) or to address a lifestyle-related risk (such as injected drug use) must be offered free of charge.
Combination hepatitis A and B vaccines must be offered free of charge, but should only be used where protection against both illnesses is clinically indicated.
Where a person is at occupational risk of hepatitis B, it is the responsibility of their employer (or themselves if self-employed) to arrange and fund immunization.
Hep B= If treatment of nausea is required, options include:
Metoclopramide (for people aged over 20 years for a maximum duration of treatment 5 days) or cyclizine, if liver impairment is mild.
Hep B= If treatment of itch is required, options include:
Simple measures (such as maintaining a cool, well-ventilated environment, wearing loose clothing, and avoiding hot baths or showers).
Chlorphenamine at night — avoid in severe liver impairment.
Ensure pregnant women (and women planning to become pregnant) with acute or chronic hepatitis B infection are aware that:
The infant should be immunised against hepatitis B from birth — there is a 90% risk of the infant contracting hepatitis B unless immunisation takes place at birth.
There may be an increased risk of preterm delivery and low infant birth weight.
Breastfeeding is safe providing the infant has been immunised.
Ensure hepatitis serology is repeated after 6 months in all people found to be HBsAg positive to detect or exclude chronic hepatitis B infection.
All people with chronic hepatitis B infection require regular
regular review by a liver specialist. The frequency of monitoring depends on a number of factors, such as serology results (which collectively indicate the phase of disease), the person’s age, and whether they are taking antiviral drugs. Specialist follow-up is required to:
- Monitor serology.
- Screen for complications including hepatocellular cancer.
- Assess the person’s need for treatment on an ongoing basis (depending on the findings of any tests and assessments).
Antivirals initiated in secondary care may subsequently be prescribed in primary care as part of a shared care arrangement.
Refer all people found to be HBsAg positive to
hepatologist, gastroenterologist or infectious disease specialist (depending on local service provision), to consider the need for additional treatment, follow up, and monitoring.
Hep B= While awaiting referral:
Advise the person to:
Seek medical attention urgently if symptoms worsen (particularly if they include vomiting and dehydration) or do not improve within 4 weeks and to be aware of the signs of hepatic decompensation such as confusion or change in level of consciousness.
Avoid drinking alcohol as this can increase the risk of cirrhosis and hepatocellular cancer in people with chronic hepatitis B.
Take steps to minimize the risk of transmission to partners and contacts. The person should:
- Avoid sharing items that might be contaminated with small amounts of blood (such as toothbrushes, razors, and scissors).
- Avoid unprotected sexual intercourse.
- Avoid sharing needles and other drug-injecting equipment. For further information on injecting drug use, see the CKS topic on Opioid dependence.
- Not donate blood or semen, or carry an organ donor card.
Be aware that treatments that affect the immune system (such as chemotherapy or immunosupressants) can cause recurrence and they may need prophylaxisis while on these medications.
Hepatitis C infection is a
slow, progressive disease of the liver caused by the hepatitis C virus (HCV). It is an important, underdiagnosed, and undertreated cause of morbidity and mortality in the UK.
HCV causes both acute and chronic infection= acute vs chronic?
Acute infection refers to the period immediately following incubation to within 6 months of acquiring infection.
Chronic infection follows acute infection in about 55–85% of people, and refers to the continued presence of HCV 6 months or more after acquiring infection.
HCV is transmitted by?
contact with infected blood.
Parenteral spread accounts for the majority of cases in the UK, through sharing of needles or other injecting paraphernalia, blood transfusion (pre 1990s), re-use or inadequate sterilization of medical equipment, needlestick injury, and exposure to infected blood by other means (for example sharing a razor with an infected person).
Less common routes include sexual transmission and vertical transmission (from mother to baby).
Complications of chronic hepatitis C infection include…
cirrhosis, liver failure, and hepatocellular carcinoma.
Testing for hepatitis C should be offered or considered if there are:
Risk factors for hepatitis C.
Clinical features of possible HCV infection, such as fatigue, arthralgia, and jaundice.
Abnormal liver function tests.
HCV infection is diagnosed with …
antibody test (which indicates if a person has ever been infected with HCV) and HCV ribonucleic acid (RNA) test (to check if HCV infection is active and for genotype analysis).
If hepatitis C is suspected in an immunocompetent person, blood should be tested for HCV antibodies.
If the antibody test is positive, or in immunocompromised people, blood should be tested for HCV RNA.
A person has active hepatitis C if they have a positive HCV antibody test and positive HCV RNA test.
if a person has suspected acute hepatitis C infection then
Same-day assessment or immediate specialist advice should be sough
if a person has suspected chronic hepatitis C infection then…
Urgent referral to a specialist should be arranged for ongoing management and monitoring.
who should be notified about cases of suspected acute viral hepatitis.
The local Health Protection Team
Primary care management of a person with hepatitis C includes:
Ensuring the person is attending specialist appointments.
Offering sources of information and support.
Advising on measures to reduce the risk of disease progression, such as reducing alcohol consumption and stopping smoking.
Advising on measures to prevent the spread of the infection, such as not sharing razors, toothbrushes, toiletries, or other items that may be contaminated with blood.
Advising on the risk of sexual transmission, which is greater in people with multiple partners, in people co-infected with HIV, and with risky sexual practices (for example anal sex).
Encouraging the person to inform injecting or sexual contacts, so that they can be tested for hepatitis C.
Monitoring for adverse effects of specialist drug treatment (for example hypoglycaemia).
Offering people at continued risk of a blood-borne infection immunization against hepatitis A and B.
Hep C= Clinical features may include?
Non-specific fatigue, myalgia, anxiety, depression, poor memory or concentration (may be indicative of chronic hepatitis C infection).
Nausea and vomiting.
Right upper quadrant abdominal pain.
Jaundice (with dark urine and/or pale stools if cholestasis).
Signs of chronic liver disease (in advanced chronic hepatitis C).
Note that only 25–35% of people experience symptoms in the early stages of infection, and infection occurs after an incubation period. Therefore, a person may not connect their present symptoms to the time of risk exposure.
The following people will usually be routinely screened by specialist services for hep C?
People who intend to donate blood or organs/tissue.
People with end-stage chronic kidney disease requiring renal replacement therapy.
Healthcare workers who perform invasive or exposure-prone procedures (for example surgeons).
Is routine screening of pregnant women for HCV infection recommended?
no
However, testing is recommended if the woman is at increased risk for HCV infection.
They should be tested at their prenatal visits.
If the initial results in pregnant women with on-going risk factors for hepatitis C infection are negative, this should be repeated later on in the third trimester.
Offer hepatitis screening to asymptomatic people who are at high risk of hepatitis C virus (HCV) infection, such as…
People who have ever injected drugs.
People who received a blood transfusion before 1991 or blood products before 1986, when screening of blood donors for hepatitis C infection, or heat treatment for inactivation of viruses were introduced.
People born or brought up in a country with an intermediate or high prevalence (2% or greater) of chronic hepatitis C, including Africa, Asia, the Caribbean, Central and South America, Eastern and Southern Europe, the Middle East, and the Pacific islands.
Babies born to mothers infected with hepatitis C.
Prisoners, including young offenders.
Looked-after children and young people, including those living in care homes.
People living in hostels for the homeless or sleeping on the streets.
HIV-positive men who have sex with men.
Close contacts of someone known to be chronically infected with hepatitis C, including family members, close friends, household contacts, or sexual partners.
Consider testing people who are at increased risk of HCV infection, particularly if they have non-specific or unexplained symptoms and signs.
This includes?
People who have ever snorted or smoked drugs (such as cocaine), particularly if they have shared straws or pipes.
People who are at risk through sharing of contaminated items, such as razors or toothbrushes.
Healthcare workers who have been accidentally exposed to blood where there is a risk of hepatitis C (for example needlestick injuries).
People who have received medical, cosmetic, or dental treatment (or any other invasive treatment) in countries where hepatitis C is common and infection control may be poor (including people who have received blood transfusion products that have not been screened for hepatitis C).
People who have had tattoos, body piercing, acupuncture, or electrolysis, where unsterilized equipment may have been used (especially consider tattooing and piercing received in the UK before the mid 1980s or in other countries at any time).
People who have tested positive for hepatitis B or HIV — HIV-positive men who have sex with men should be offered regular testing for hepatitis C.
HCV infection is diagnosed with…
an antibody test (which indicates if a person has ever been infected with HCV) and HCV ribonucleic acid (RNA) test (to check if HCV infection is active and for genotype analysis).
HCV infection is diagnosed with an antibody test (which indicates if a person has ever been infected with HCV) and HCV ribonucleic acid (RNA) test (to check if HCV infection is active and for genotype analysis).
In immunocompetent people….
send a plain (clotted) blood sample for testing for antibodies to HCV. Detection of antibodies indicates resolved or current HCV infection.
If the antibody test is positive, test a second blood sample to confirm the diagnosis. Consider taking an additional blood sample at the same time as the first sample if venepuncture is difficult (for example if the person injects drugs).
If the antibody test is negative, consider repeating it (especially if the person is at high risk of infection). Repeat the antibody test at an appropriate time if the last risk exposure occurred within the 3–6 month ‘window period’ of the test, as it can take at least 3 months for antibodies to become detectable. Seek specialist advice if there is uncertainty about the optimal time to repeat the test.
HCV infection is diagnosed with an antibody test (which indicates if a person has ever been infected with HCV) and HCV ribonucleic acid (RNA) test (to check if HCV infection is active and for genotype analysis). If the antibody test is positive, or in immunocompromized people….
If the HCV RNA test is positive, send a repeat sample for confirmation. A positive HCV RNA result means the person has current infection with active hepatitis C, which will require specialist antiviral treatment.
If the HCV RNA result is negative, repeat the test after a period of 6 months. If the negative result is confirmed, this means the person has a previously resolved HCV infection, but they are not immune to future HCV infection. Give information and advice on measures to prevent re-infection.
HCV infection is diagnosed with an antibody test (which indicates if a person has ever been infected with HCV) and HCV ribonucleic acid (RNA) test (to check if HCV infection is active and for genotype analysis). If a healthcare professional has, or may have, sustained an occupational exposure to HCV (for example, from a needlestick injury)….
Advise that they will need HCV antibody testing at 12 and 24 weeks, and HCV RNA testing at 6, 12, and 24 weeks. This should be arranged through their Occupational Health department.
HCV infection is diagnosed with an antibody test (which indicates if a person has ever been infected with HCV) and HCV ribonucleic acid (RNA) test (to check if HCV infection is active and for genotype analysis). If the person has equivocal results, or there is uncertainty in the interpretation of results…
seek specialist advice
HCV infection is diagnosed with an antibody test (which indicates if a person has ever been infected with HCV) and HCV ribonucleic acid (RNA) test (to check if HCV infection is active and for genotype analysis). If the person tests negative for HCV but remains at increased risk of infection…
offer annual testing for HCV.
People with hepatitis C virus (HCV) infection should be under the care of a
hepatologist or specialist gastroenterologist.
If acute hepatitis C virus (HCV) infection is suspected (hepatitis C antibody positive with clinical features of acute hepatitis and/or a likely recent source of transmission is identified):
Arrange a same-day assessment or seek immediate specialist advice.
If chronic HCV infection is suspected (hepatitis C antibody positive and ribonucleic acid positive with no clinical features of acute hepatitis):
Arrange an urgent referral. Confirm the person’s address and telephone number at the time of referral, and use the practice’s address for correspondence if necessary, for example if the person frequently changes address, has an insecure address, or is homeless.
All people under specialist services for hepatitis C management should be offered integrated multidisciplinary care (including specialist nurse input) to maximise their uptake of, and retention in, services and to provide ongoing monitoring and support.
Around 15–45% of people with acute hepatitis C virus (HCV) infection will…
spontaneously clear the virus within 6 months of infection without any treatment
Hep C spontaneuous resolution?
(defined as loss of HCV ribonucleic acid [RNA] within the first 6 months) occurs, no antiviral treatment is necessary
Mx of acute hep C?
If spontaneous resolution (defined as loss of HCV ribonucleic acid [RNA] within the first 6 months) occurs, no antiviral treatment is necessary [BASHH, 2017a].
If needed, treatment should be started promptly. There is clear evidence that treatment given during the acute phase is more likely to clear infection and reduces the risk of chronic HCV infection and progression of liver disease than treatment in the chronic phase [BASHH, 2017a]. Treatment should be the same as for chronic infection [BMJ, 2019].
All people with chronic HCV infection should be considered for antiviral therapy, which is always initiated by a specialist….
The goal of treatment is to eradicate the virus, achieve a sustained virological response (SVR), and prevent disease progression [Ahmad, 2017; BMJ, 2019]. SVR (undetectable HCV RNA in the blood 12 weeks after treatment completion) is considered equivalent to a cure.
The treatment regimen and duration will depend on the HCV genotype, viral load, severity of liver disease, prior HCV treatment history, the presence of comorbidities, and the person’s ability to tolerate treatment.
Interferon-based treatment regimens are no longer recommended for HCV infection [Ahmad, 2017], as direct-acting antivirals (DAAs) are now considered first-line treatment. DAAs target different stages in the HCV lifecycle and are successful for over 90% of people with HCV infection.
The treatment is usually a once daily, oral tablet regimen for either 8 or 12 weeks and is most effective when given before the onset of cirrhosis.
DAAs are well tolerated with minimal adverse effects and result in high rates of SVR.
Specialist investigations are carried out to assess the state of infection and the progression of liver disease in hep C. These may include?
Blood tests may include:
Viral load — to assess response to treatment.
Clotting studies — clotting may be affected if there is significant liver damage.
Autoantibodies — which are non-specific markers for autoimmune disease.
Transient elastography can be offered to diagnose cirrhosis. If unsuitable, liver biopsy can be offered.
Liver ultrasound is carried out in people with advanced fibrosis or cirrhosis to screen for hepatocellular cancer. Ultrasound cannot accurately assess the degree of inflammation or liver fibrosis, or predict the prognosis.
Liver biopsy may be considered in individual cases, for example to assess the extent of liver damage caused by inflammation, fibrosis, or cirrhosis; to identify iron overload; and to exclude other causes of liver damage.
Follow up for hep C in primary care?
Ensure the person is attending specialist appointments, and provide appropriate support if needed to help the person attend.
Provide the person with sources of information and support on hepatitis C and its treatment.
Monitor the person for adverse effects of specialist treatment, and manage appropriately.
- Hypoglycaemia — monitor glucose levels closely in people with diabetes during treatment with direct-acting antivirals (DAAs), particularly within the first 3 months of treatment, and modify diabetes treatment when necessary. Concurrent treatment with antidiabetic drugs may result in symptomatic hypoglycaemia.
- Fluctuations of international normalised ratio (INR) — monitor INR closely in people on anticoagulant treatment and, if necessary, adjust the dose of the anticoagulant. Changes in liver function due to treatment with DAAs may result in fluctuations of INR values.
Give the person ongoing lifestyle advice to reduce the risk of disease progression, such as stopping smoking.
Offer all people at continued risk of a blood-borne infection immunization against hepatitis A and B (available free on the NHS for this indication).
Amoebiasis?
caused by Entamoeba histolytica (an amoeboid protozoan) and spread by the faecal-oral route.
It is estimated that 10% of the world’s population is chronically infected.
Infection can be asymptomatic, cause mild diarrhoea or severe amoebic dysentery. Amoebiasis also causes liver and colonic abscesses.
Amoebic dysentery?
profuse, bloody diarrhoea
there may be a long incubation period
stool microscopy may show trophozoites if examined within 15 minutes or kept warm (known as a ‘hot stool’)
Amoebic dysentery Tx?
oral metronidazole
a ‘luminal agent’ (to eliminate intraluminal cysts) is recommended usually as well e.g. diloxanide furoate
Amoebic liver abscess?
usually a single mass in the right lobe (may be multiple). The contents are often described as ‘anchovy sauce’
Amoebic liver abscess features?
fever
right upper quadrant pain
systemic symptoms e.g. malaise
hepatomegaly
Amoebic liver abscess Ix?
ultrasound
serology is positive in > 95%
Amoebic liver abscess Mx?
oral metronidazole
a ‘luminal agent’ (to eliminate intraluminal cysts) is recommended usually as well e.g. diloxanide furoate
Anthrax?
caused by Bacillus anthracis, a Gram positive rod. It is spread by infected carcasses.
It is also known as Woolsorters’ disease.
Bacillus anthracis produces a tripartite protein toxin
- protective antigen
- oedema factor: a bacterial adenylate cyclase which increases cAMP
- lethal factor: toxic to macrophages
Features of anthrax?
causes painless black eschar (cutaneous ‘malignant pustule’, but no pus)
typically painless and non-tender
may cause marked oedema
anthrax can cause gastrointestinal bleeding
Mx of anthrax?
initial management of cutaneous anthrax is ciprofloxacin
further treatment is based on microbiological investigations and expert advice
Recommended Abx for exacerbations of chronic bronchitis?
Amoxicillin or tetracycline or clarithromycin
Recommended Abx for uncomplicated CAP?
Amoxicillin (Doxycycline or clarithromycin in penicillin allergic, add flucloxacillin if staphylococci suspected e.g. In influenza)
Recommended Abx for pneumonia possibly caused by atypical pathogens?
Clarithromycin
Recommended Abx for HAP?
Within 5 days of admission: co-amoxiclav or cefuroxime
More than 5 days after admission: piperacillin with tazobactam OR a broad-spectrum cephalosporin (e.g. ceftazidime) OR a quinolone (e.g. ciprofloxacin)
Recommended Abx for lower UTI?
Trimethoprim or nitrofurantoin. Alternative: amoxicillin or cephalosporin
Recommended Abx for acute pyelonephritis?
Broad-spectrum cephalosporin or quinolone
Recommended Abx for acute prostatitis?
Quinolone or trimethoprim
Recommended Tx for impetigo?
Topical hydrogen peroxide, oral flucloxacillin or erythromycin if widespread
Recommended Abx for cellulitis?
Flucloxacillin (clarithromycin, erythromycin or doxycycline if penicillin-allergic)
Recommended Abx for cellulitis near the eyes or nose?
Co-amoxiclav (clarithromycin, + metronidazole if penicillin-allergic)
Recommended Abx for erysipelas?
Flucloxacillin (clarithromycin, erythromycin or doxycycline if penicillin-allergic)
Recommended Abx for animal or human bite?
Co-amoxiclav (doxycycline + metronidazole if penicillin-allergic)
Recommended Abx for mastitis during breast feeding?
Flucloxacillin
Recommended Abx for throat infections?
Phenoxymethylpenicillin (erythromycin alone if penicillin-allergic)
Recommended Abx for sinusitis?
Phenoxymethylpenicillin
Recommended Abx for otitis media?
Amoxicillin (erythromycin if penicillin-allergic)
Recommended Abx for otitis externa?
Flucloxacillin (erythromycin if penicillin-allergic)
combined topical antibiotic and corticosteroid is generally used for mild/moderate cases of otitis externa
Recommended Abx for periapical or periodontal abscess?
Amoxicillin
Recommended Abx for Gingivitis: acute necrotising ulcerative?
Metronidazole
Recommended Abx for gonorrhoea?
Intramuscular ceftriaxone
Recommended Abx for chlamydia?
Doxycycline or azithromycin
Recommended Abx for PID?
Oral ofloxacin + oral metronidazole
or
intramuscular ceftriaxone + oral doxycycline + oral metronidazole
Recommended Abx for syphilis?
Benzathine benzylpenicillin or doxycycline or erythromycin
Recommended Abx for bacterial vaginosis?
Oral or topical metronidazole or topical clindamycin
Recommended Abx for c diff?
First episode: oral vancomycin
Second or subsequent episode of infection: oral fidaxomicin
Recommended Abx for Campylobacter enteritis?
Clarithromycin
Recommended Abx for salmonella (non-typhoid)?
Ciprofloxacin
Recommended Abx for shigellosis?
Ciprofloxacin
Antibiotics: protein synthesis inhibitors= list some?
aminoglycosides
tetracyclines
chloramphenicol
clindamycin
macrolides
Antibiotics: protein synthesis inhibitors= aminoglycosides MOA?
Binds to 30S subunit causing misreading of mRNA
Antibiotics: protein synthesis inhibitors= aminoglycosides adverse effects?
Nephrotoxicity, Ototoxicity
Antibiotics: protein synthesis inhibitors= tetracyclines adverse effects?
Discolouration of teeth, photosensitivity
Antibiotics: protein synthesis inhibitors= tetracyclines MOA?
Binds to 30S subunit blocking binding of aminoacyl-tRNA
Antibiotics: protein synthesis inhibitors= chloramphenicol MOA?
Binds to 50S subunit, inhibiting peptidyl transferase
Antibiotics: protein synthesis inhibitors= chloramphenicol adverse effects?
Aplastic anaemia
Antibiotics: protein synthesis inhibitors= clindamycin adverse effects?
common cause of c diff
Antibiotics: protein synthesis inhibitors= clindamycin MOA?
Binds to 50S subunit, inhibiting translocation (movement of tRNA from acceptor site to peptidyl site)
Antibiotics: protein synthesis inhibitors= macrolides MOA?
Binds to 50S subunit, inhibiting translocation (movement of tRNA from acceptor site to peptidyl site)
Antibiotics: protein synthesis inhibitors= macrolides adverse effects?
Nausea (especially erythromycin), P450 inhibitor, prolonged QT interval
Antibiotics: protein synthesis inhibitors= macrolides commonly used in who?
pts who are allergic to penicillin
Antibiotics: protein synthesis inhibitors= macrolides examples?
Azithromycin
Clarithromycin
Erythromycin
Fidaxomicin
Antibiotics: protein synthesis inhibitors= tetracyclines examples?
doxycycline
lymecycline
Antibiotics: protein synthesis inhibitors= aminoglycosides examples?
gentamicin, tobramycin, amikacin, neomycin, plazomicin, paromomycin, and streptomycin
Antifungal agents= list some?
azoles
amphotericin B
terbinafine
griseofulvin
flucytosine
caspofungin
nystatin
Antifungal agents= Azoles MOA?
Inhibits 14α-demethylase which produces ergosterol
Antifungal agents= Azoles adverse effects?
P450 inhibition
Liver toxicity
Antifungal agents= Azoles examples?
Clotrimazole
Fluconazole
Itraconazole
Drug class is metrondiazole?
Abx (NOT ANTIFUNGAL)
Antifungal agents= Amphotericin B MOA?
Binds with ergosterol forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl) leakage
Antifungal agents= Amphotericin B adverse effects?
Nephrotoxicity, flu-like symptoms, hypokalaemia, hypomagnaseamia
Antifungal agents= Amphotericin B used for?
systemic fungal infections
Antifungal agents= Terbinafine MOA?
Inhibits squalene epoxidase
Antifungal agents= Terbinafine commonly used in?
oral form to treat fungal nail infections
Antifungal agents= Griseofulvin MOA?
Interacts with microtubules to disrupt mitotic spindle
Antifungal agents= Griseofulvin adverse effects?
Induces P450 system, teratogenic
Induces P450 system meaning?
When a substance “induces” the P450 system, it essentially triggers the body to produce more of these enzymes, increasing their activity level.
This can be clinically important because if a person takes multiple medications, one of which induces the P450 system, it can lead to decreased effectiveness of other drugs that are metabolized by the same enzymes.
Antifungal agents= Flucytosine MOA?
Converted by cytosine deaminase to 5-fluorouracil, which inhibits thymidylate synthase and disrupts fungal protein synthesis
Antifungal agents= Flucytosine adverse effects?
vomiting
Antifungal agents= Caspofungin?
Inhibits synthesis of beta-glucan, a major fungal cell wall component
Antifungal agents= Caspofungin adverse effects?
Flushing
Antifungal agents= nystatin MOA?
Binds with ergosterol forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl) leakage
Antifungal agents= nystatin can only be used how?
As very toxic can only be used topically (e.g. for oral thrush)
Aspergilloma?
a mycetoma (mass-like fungus ball) which often colonises an existing lung cavity (e.g. secondary to tuberculosis, lung cancer or cystic fibrosis).
Aspergilloma features?
Usually asymptomatic but features may include
cough
haemoptysis (may be severe)
Aspergilloma Ix?
chest x-ray containing a rounded opacity. A crescent sign may be present
high titres Aspergillus precipitins
Bacillus cereus?
gram-positive rod, which is highly adaptable to extremes of pH and oxygen levels. It is chiefly associated with food poisoning but may also be associated with nosocomial infection in the immunocompromised.
Bacillus cereus found where?
Due to its relative environmental resilience, members of the B. cereus group are almost ubiquitous in nature: they are found in soil, fresh water and salt water. They also frequently considered a transient commensal organism in the human GI tract. Isolates have even been found in disinfectant alcohol hand gel.
B. cereus is often considered a contaminant when grown from a blood culture or other sterile site, but is also a significant cause of infection in immunosuppressed patients, intravenous drug users and neonates.
Bacillus cereus commonly causes what?
Significant exposures to B. cereus occur most commonly in the context of food poisoning. Under-cooked or reheated rice is most classically associated with B. cereus . The bacterial exotoxin cereulide is stable at for short periods of very high temperatures such as in stir frying.
Under-cooked or reheated rice is most classically associated with…
Bacillus cereus
B. cereus causes two distinct food poisoning syndromes?
An emetic syndrome resulting from ingestion of the heat-stable toxin cereulide. Disease can occur from toxin ingestion even if the bacteria are killed during cooking. Symptoms typically occur between 0.5 and 6 hours of ingestion. Diarrhoea symptoms may also occur.
A diarrhoeal syndrome associated with separate exotoxins such as haemolysin BL. Patients typically complain of crampy abdominal pain and diarrhoea. Usual onset time 8-16 hours.
Symptoms typically resolve within 24 hours in both syndromes.
In immunosuppressed patients: bacteraemia, endocarditis, musculoskeletal and CNS infection may occur.
Bacillus cereus Mx?
rarely required for food poisoning syndrome. Most strains produce beta-lactamase and vancomycin is suggested as the empiric antibiotic of choice in some guidelines.
Clostridium botulinum (Botulism)?
gram positive anaerobic bacillus
7 serotypes A-G
produces botulinum toxin, a neurotoxin which irreversibly blocks the release of acetylcholine
may result from eating contaminated food (e.g. tinned) or intravenous drug use
neurotoxin often affects bulbar muscles and autonomic nervous system
Clostridium botulinum (Botulism) features?
patient usually fully conscious with no sensory disturbance
flaccid paralysis
diplopia
ataxia
bulbar palsy
Clostridium botulinum (Botulism) Tx?
botulism antitoxin and supportive care
antitoxin is only effective if given early - once toxin has bound its actions cannot be reversed
Cat scratch disease?
generally caused by the Gram negative rod Bartonella henselae
Cat scratch disease features?
fever
history of a cat scratch
regional lymphadenopathy
headache, malaise
Cholera is caused by what?
by Vibro cholerae - Gram negative bacteria
contaminated water
Cholera features?
profuse ‘rice water’ diarrhoea
dehydration
hypoglycaemia
Cholera Mx?
oral rehydration therapy
antibiotics: doxycycline, ciprofloxacin
Gram-positive cocci examples?
staphylococci + streptococci (including enterococci)
Gram-negative cocci examples?
Neisseria meningitidis + Neisseria gonorrhoeae, also Moraxella catarrhalis
Gram-positive rods (bacilli) examples?
mnemonic = ABCD L
Actinomyces
Bacillus anthracis (anthrax)
Clostridium
Diphtheria: Corynebacterium diphtheriae
Listeria monocytogenes
Gram-negative rods (bacilli) examples?
Escherichia coli
Haemophilus influenzae
Pseudomonas aeruginosa
Salmonella sp.
Shigella sp.
Campylobacter jejuni
Classify types of bacteria into gram +ve and -ve cocci and bacilli (rods)?
Gram-positive cocci = staphylococci + streptococci (including enterococci)
Gram-negative cocci = Neisseria meningitidis + Neisseria gonorrhoeae, also Moraxella catarrhalis
Gram-positive rods (bacilli) = ABCD L
Actinomyces
Bacillus anthracis (anthrax)
Clostridium
Diphtheria: Corynebacterium diphtheriae
Listeria monocytogenes
Remaining organisms are Gram-negative rods, e.g.:
Escherichia coli
Haemophilus influenzae
Pseudomonas aeruginosa
Salmonella sp.
Shigella sp.
Campylobacter jejuni
Clostridia type of bacteria?
gram-positive, obligate anaerobic bacilli.
List examples of Clostridia?
C. perfringens:
- produces α-toxin, a lecithinase, which causes gas gangrene (myonecrosis) and haemolysis
- features include tender, oedematous skin with haemorrhagic blebs and bullae. Crepitus may present on palpation
C. botulinum:
- typically seen in canned foods and honey
prevents acetylcholine (ACh) - release leading to flaccid paralysis
C. difficile:
- causes pseudomembranous colitis, typically seen after the use of broad-spectrum antibiotics
- produces both an exotoxin and a cytotoxin
C. tetani:
- produces an exotoxin (tetanospasmin) that prevents the release of glycine from Renshaw cells in the spinal cord causing a spastic paralysis
Cryptosporidiosis?
commonest protozoal cause of diarrhoea in the UK. Two species, Cryptosporidium hominis and Cryptosporidium parvum account for the majority cases.
Cryptosporidiosis is more common in immunocompromised patients (e.g. HIV) and young children.
Cryptosporidiosis features?
watery diarrhoea
abdominal cramps
fever
in immunocompromised patients, the entire gastrointestinal tract may be affected resulting in complications such as sclerosing cholangitis and pancreatitis
Cryptosporidiosis diagnosis?
stool: modified Ziehl-Neelsen stain (acid-fast stain) of the stool may reveal the characteristic red cysts of Cryptosporidium
Cryptosporidiosis Mx?
is largely supportive for immunocompetent patients
if the patient has HIV and is not on antiretroviral therapy then this should be started and often will be enough to resolve the infection
nitazoxanide may be used for immunocompromised patients
rifaximin is also sometimes used for immunocompromised patients/patients with severe disease
Cutaneous larva migrans?
dermatological condition prevalent in tropical and subtropical regions, largely attributable to cutaneous penetration and subsequent migration of nematode larvae, primarily from the Ancylostoma genus (e.g. Ancyclostoma braziliense). Typically, the transmission vectors are faecal-contaminated soil or sand, posing significant risks to individuals with a history of barefoot beach visits or direct soil contact.
CP of Cutaneous larva migrans?
intensely pruritic, ‘creeping’, serpiginous, erythematous cutaneous eruption that advances over time. Symptoms can last for weeks to months, potentially leading to secondary bacterial infection due to excessive scratching. Diagnosis is typically clinical, based on exposure history and characteristic skin manifestations.
Tx of Cutaneous larva migrans?
anthelmintic agents, such as ivermectin or albendazole. Topical therapy with thiabendazole can also be effective, although it’s generally less preferred due to a lower efficacy rate and higher side effect profile.
Prevention of Cutaneous larva migrans?
largely involve patient education about appropriate protective measures, particularly avoiding direct skin contact with potentially contaminated soil. Given the zoonotic nature of cutaneous larva migrans, public health measures for animal defecation control can also contribute to reducing the prevalence of this condition.
Cytomegalovirus (CMV)?
one of the herpes viruses. It is thought that around 50% of people have been exposed to the CMV virus although it only usually causes disease in the immunocompromised, for example people with HIV or those on immunosuppressants following organ transplantation.
Cytomegalovirus (CMV) pathophysiology?
infected cells have a ‘Owl’s eye’ appearance due to intranuclear inclusion bodies
Cytomegalovirus (CMV) patterns of disease?
Congenital CMV infection
CMV mononucleosis
CMV retinitis
CMV encephalopathy
CMV penumonitis
CMV colitis
Cytomegalovirus (CMV) only causes disease in who?
in the immunocompromised, for example people with HIV or those on immunosuppressants following organ transplantation.
Congenital CMV?
features include growth retardation, pinpoint petechial ‘blueberry muffin’ skin lesions, microcephaly, sensorineural deafness, encephalitiis (seizures) and hepatosplenomegaly
CMV mononucleosis?
infectious mononucelosis-like illness
may develop in immunocompetent individuals
CMV retinitis?
common in HIV patients with a low CD4 count (< 50)
presents with visual impairment e.g. ‘blurred vision’. Fundoscopy shows retinal haemorrhages and necrosis, often called ‘pizza’ retina
IV ganciclovir is the treatment of choice
CMV encephalopathy?
seen in patients with HIV who have low CD4 counts
Dengue fever?
viral infection that can progress to viral haemorrhagic fever (other examples include yellow fever, Lassa fever, Ebola).
Dengue fever aetiology?
dengue virus is a RNA virus of the genus Flavivirus
transmitted by the Aedes aegypti mosquito
incubation period of 7 days
Dengue fever can be classified how?
dengue fever:
without warning signs
with warning signs
severe dengue (dengue haemorrhagic fever)
Dengue fever CP?
fever
headache (often retro-orbital)
myalgia, bone pain and arthralgia (‘break-bone fever’)
pleuritic pain
facial flushing (dengue)
maculopapular rash
haemorrhagic manifestations e.g. positive tourniquet test, petechiae, purpura/ecchymosis, epistaxis
‘warning signs’ include:
abdominal pain
hepatomegaly
persistent vomiting
clinical fluid accumulation (ascites, pleural effusion)
Severe dengue (dengue haemorrhagic fever) CP?
this is a form of disseminated intravascular coagulation (DIC) resulting in:
thrombocytopenia &
spontaneous bleeding
around 20-30% of these patients go on to develop dengue shock syndrome (DSS)
Dengue fever Ix?
typically blood results=
leukopenia, thrombocytopenia, raised aminotransferases
diagnostic tests:
- serology
- nucleic acid amplification tests for viral RNA
- NS1 antigen test
Dengue fever Tx?
entirely symptomatic e.g. fluid resuscitation, blood transfusion etc
no antivirals are currently available
Diphtheria is caused by what?
Gram positive bacterium Corynebacterium diphtheriae
Diphtheria pathophysiology?
releases an exotoxin encoded by a β-prophage
exotoxin inhibits protein synthesis by catalyzing ADP-ribosylation of elongation factor EF-2
Diphtheria toxin commonly causes a ‘diphtheric membrane’ on tonsils caused by necrotic mucosal cells. Systemic distribution may produce necrosis of myocardial, neural and renal tissue
Diphtheria possible presentations?
recent visitors to Eastern Europe/Russia/Asia
sore throat with a ‘diphtheric membrane’ - grey, pseudomembrane on the posterior pharyngeal wall
bulky cervical lymphadenopathy
- may result in a ‘bull neck’ appearanace
neuritis e.g. cranial nerves
heart block
Diphtheria Ix?
culture of throat swab: uses tellurite agar or Loeffler’s media
Diphtheria Mx?
intramuscular penicillin
diphtheria antitoxin
only DNA virus that is not double-stranded?
parovirus
DNA viruses= herpesviruses: structure, envelope and examples/importance?
Double-stranded, linear
Enveloped
Herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus
DNA viruses= hepadnavirus: structure, envelope and examples/importance?
Double-stranded, circular
Enveloped
Hepatitis B virus
DNA viruses= Adenovirus: structure, envelope and examples/importance?
Double-stranded, linear
Naked
Common cold, conjunctivitis
DNA viruses= Parovirus: structure, envelope and examples/importance?
Single-stranded, linear
Naked
Parvovirus B19
DNA viruses= Papillomavirus: structure, envelope and examples/importance?
Double-stranded, circular
Naked
HPV
DNA viruses= Poxvirus: structure, envelope and examples/importance?
Double-stranded, linear
Enveloped
Smallpox, molluscum contagiosum
DNA viruses= Polyomavirus: structure, envelope and examples/importance?
Double-stranded, circular
Naked
JC virus (progressive multifocal leukoencephalopathy)
Types of DNA viruses?
HHAPPPPy! - Hepadna; Herpes; Adeno; Pox; Parvo; Papilloma; Polyoma
Ebola virus?
part of the Filoviridae virus family and causes a rare but often fatal disease. The average fatality rate during previous outbreaks is 50%. The most recent outbreak in West Africa is the largest known outbreak, mainly centred around Guinea, Sierra Leone and Liberia.
How is ebola virus spread?
through human-to-human transmission via direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people, and with surfaces and materials (e.g. bedding, clothing) contaminated with these fluids. This puts healthcare workers at particular risk and appropriate precautions should be taken.
CP of ebola virus?
The incubation period is 2 to 21 days, and patients are not infectious until they develop symptoms.
First symptoms are the sudden onset of fever fatigue, muscle pain, headache and sore throat. This is followed by vomiting, diarrhoea, rash, symptoms of impaired kidney and liver function, and in some cases, both internal and external bleeding.
Consider Ebola virus in the following patients:
Ebola should be suspected in patients presenting to primary care services who have a fever of 37.5°C OR have a history of fever in the past 24 hours AND have recently visited any of the affected areas (see maps) within the previous 21 days
OR
Have a fever of 37.5°C OR have a history of fever in the past 24 hours AND have cared for/come into contact with body fluids of/handled clinical specimens (blood, urine, faeces, tissues, laboratory cultures) from an individual or laboratory animal known or strongly suspected to have VHF.
Mx of ebola?
If a patient reports these symptoms over the telephone, they should be advised not to attend the surgery. If they do attend the surgery then they should be isolated in a single room to limit contact with staff/other patients. If the GP elicits the possibility of VHF during their consultation, they should avoid further physical contact and keep the patient isolated in their room. In all of these cases PHE should be contacted for further advice.
Enteric fever (typhoid/paratyphoid) = types?
The Salmonella group contains many members, most of which cause diarrhoeal diseases. They are aerobic, Gram-negative rods which are not normally present as commensals in the gut.
Typhoid and paratyphoid are caused by Salmonella typhi and Salmonella paratyphi (types A, B & C) respectively. They are often termed enteric fevers, producing systemic symptoms such as headache, fever, arthralgia.
Enteric fever (typhoid/paratyphoid) = transmission?
typhoid is transmitted via the faecal-oral route (also in contaminated food and water)
Enteric fever (typhoid/paratyphoid) = features?
initially systemic upset (headache, fever, arthralgia)
relative bradycardia
abdominal pain, distension
constipation: although Salmonella is a recognised cause of diarrhoea, constipation is more common in typhoid
rose spots: present on the trunk in 40% of patients, and are more common in paratyphoid
Enteric fever (typhoid/paratyphoid) = Cx?
osteomyelitis (especially in sickle cell disease where Salmonella is one of the most common pathogens)
GI bleed/perforation
meningitis
cholecystitis
chronic carriage (1%, more likely if adult females)
Enteroviruses?
positive-sense single stranded RNA viruses. The family contains the Coxsackievirus, echovirus and rhinovirus as well as others. It is the most common cause of viral meningitis in the adult population but can cause a range of different diseases, in both adults and children. Although the range of diseases caused by these viruses is broad, notable disease entities include Hand, Foot and Mouth disease, herpangina and pericarditis.
Malignancies associated with EBV infection?
Burkitt’s lymphoma
Hodgkin’s lymphoma
nasopharyngeal carcinoma
HIV-associated central nervous system lymphomas
Non-malginant condition associated with EBV infection?
hairy leukoplakia
Giardiasis?
caused by the flagellate protozoan Giardia lamblia. It is spread by the faeco-oral route.
Giardiasis RFs?
foreign travel
swimming/drinking water from a river or lake
male-male sexual contact
Giardiasis features?
often asymptomatic
non-bloody diarrhoea
steatorrhoea
bloating, abdominal pain
lethargy
flatulence
weight loss
malabsorption and lactose intolerance can occur
Giardiasis Ix?
stool microscopy for trophozoite and cysts: sensitivity of around 65%
stool antigen detection assay: greater sensitivity and faster turn-around time than conventional stool microscopy methods
PCR assays are also being developed
Giardiasis Tx?
metronidazole
Gram-positive bacteria will turn…
purple/blue following the gram staining. Microscopy will then reveal the shape, either cocci or rods.
Identifying gram-positive bacteria= Rods (bacilli)?
Actinomyces
Bacillus antracis
Clostridium
Corynebacterium diphtheriae
Listeria monocytogenes
Identifying gram-positive bacteria= Cocci?
makes catalase: Staphylococci
does not make catalase: Streptococci
Identifying gram-positive bacteria= Staphylococci?
makes coagulase: S. aureus
does not make coagulase: S. epidermidis (novobiocin sensitive), S. saprophyticus (novobiocin resistant)
Identifying gram-positive bacteria= Streptococci?
partial haemolysis (green colour on blood agar): α-haemolytic
complete haemolysis (clear): β-haemolytic
no haemolysis: γ-haemolytic
Identifying gram-positive bacteria= α-haemolytic streptococci?
optochin sensitive: S. pneumoniae
optochin resistant: Viridans streptococci
Identifying gram-positive bacteria= β-haemolytic streptococci?
bacitracin sensitive: Group A: S. pyogenes
bacitracin resistant: Group B: S. agalactiae
When to recommend to get flu vaccine?
between september and early november as flue season typically starts middle of november
Types of flu virus?
A, B and C
A and B most common
Who gets the flu vaccine?
Children, elderly and at risk groups.
Remember that the type of vaccine given routinely to children and the one given to the elderly and at risk groups is different (live vs. inactivated) - this explains the different contraindications
A new NHS influenza vaccination programme for children was announced in 2013. There are three key things to remember about the children’s vaccine:
it is given intranasally
the first dose is given at 2-3 years, then annually after that
it is a live vaccine (cf. injectable vaccine below)
children who were traditionally offered the flu vaccine (e.g. asthmatics) will now be given intranasal vaccine unless this is inappropriate, for example if they are immunosuppressed. In this situation the inactivated, injectable vaccine should be given
only children aged 2-9 years who have not received an influenza vaccine before need 2 doses
it is more effective than the injectable vaccine
Contraindications to flu vaccine?
immunocompromised
aged < 2 years
current febrile illness or blocked nose/rhinorrhoea
current wheeze (e.g. ongoing viral-induced wheeze/asthma) or history of severe asthma (BTS step 4)
egg allergy
pregnancy/breastfeeding
if the child is taking aspirin (e.g. for Kawasaki disease) due to a risk of Reye’s syndrome
Side-effects of flu vaccine?
blocked-nose/rhinorrhoea
headache
anorexia
Flu vaccine =
Current vaccines are trivalent and consist of…
two subtypes of influenza A and one subtype of influenza B.
The Department of Health recommends annual influenza vaccination for all people older than 65 years, and those older than 6 months if they have:
chronic respiratory disease (including asthmatics who use inhaled steroids)
chronic heart disease (heart failure, ischaemic heart disease, including hypertension if associated with cardiac complications)
chronic kidney disease
chronic liver disease: cirrhosis, biliary atresia, chronic hepatitis
chronic neurological disease: (e.g. Stroke/TIAs)
diabetes mellitus (including diet controlled)
immunosuppression due to disease or treatment (e.g. HIV)
asplenia or splenic dysfunction
pregnant women
adults with a body mass index >= 40 kg/m²
Other at risk individuals include:
- health and social care staff directly involved in patient care (e.g. NHS staff)
- those living in long-stay residential care homes
- carers of the elderly or disabled person whose welfare may be at risk if the carer becomes ill (at the GP’s discretion)
The influenza vaccine= important things to know
it is an inactivated vaccine, so cannot cause influenza. A minority of patients however develop fever and malaise which may last 1-2 days
should be stored between +2 and +8ºC and shielded from light
contraindications include hypersensitivity to egg protein.
in adults the vaccination is around 75% effective, although this figure decreases in the elderly
it takes around 10-14 days after immunisation before antibody levels are at protective levels
Invasive aspergillosis?
systemic Aspergillus infection (Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus) that is a leading cause of death in immunocompromised patients.
Invasive aspergillosis RFs?
HIV
Leukaemia
Following broad-spectrum antibiotics
Lemierre’s syndrome?
infectious thrombophlebitis of the internal jugular vein.
It most often occurs secondary to a bacterial sore throat caused by Fusobacterium necrophorum leading to a peritonsillar abscess. A combination of spread of the infection laterally from the abscess and compression lead to thrombosis of the IJV.
Lemierre’s syndrome CP?
Patients will present with a history of bacterial sore throat followed by neck pain, stiffness and tenderness (may be mistaken for meningitis) and systemic involvement (fevers, rigors, etc). Septic pulmonary emboli may also occur.
Leprosy?
a granulomatous disease primarily affecting the peripheral nerves and skin. It is caused by Mycobacterium leprae.
Features of leprosy?
patches of hypopigmented skin typically affecting the buttocks, face, and extensor surfaces of limbs
sensory loss
What determines the type of leprosy a pt will develop?
The degree of cell mediated immunity
Types of leprosy= Low degree of cell mediated immunity → ???
lepromatous leprosy (‘multibacillary’)
- extensive skin involvement
- symmetrical nerve involvement
Types of leprosy= High degree of cell mediated immunity → ???
tuberculoid leprosy (‘paucibacillary’)
- limited skin disease
- asymmetric nerve involvement → hypesthesia
- hair loss
Mx of leprosy?
WHO-recommended triple therapy: rifampicin, dapsone and clofazimine
Leptospirosis?
caused by the spirochaete Leptospira interrogans (serogroup L. icterohaemorrhagiae), classically being spread by contact with infected rat urine.
Leptospirosis epidemiology?
leptospirosis is commonly seen in questions referring to sewage workers, farmers, vets or people who work in an abattoir
however, on an international level, leptospirosis is far more common in the tropics so should be considered in the returning traveller
Leptospirosis= what should always be considered in high-risk patients with hepatorenal failure?
Weil’s disease
Leptospirosis features?
the early phase is due to bacteraemia and lasts around a week:
- may be mild or subclinical
- fever
- flu-like symptoms
- subconjunctival suffusion (redness)/haemorrhage
second immune phase may lead to more severe disease (Weil’s disease):
- acute kidney injury (seen in 50% of patients)
- hepatitis: jaundice, hepatomegaly
- aseptic meningitis
Leptospirosis Ix?
serology: antibodies to Leptospira develop after about 7 days
PCR
culture=
growth may take several weeks so limits usefulness in diagnosis; blood and CSF samples are generally positive for the first 10 days; urine cultures become positive during the second week of illness
Leptospirosis Mx?
mild-moderate disease: doxycycline or azithormycin
severe disease: IV benzylpencillin
Metronidazole?
type of antibiotic that works by forming reactive cytotoxic metabolites inside the bacteria.
Metronidazole adverse effects?
disulfiram-like reaction with alcohol
increases the anticoagulant effect of warfarin
Nematodes= types?
Ancylostoma braziliense
Strongyloides stercoralis
Toxocara canis
Nematodes= Ancylostoma braziliense?
most common cause of cutaneous larva migrans
common in Central and Southern America
Nematodes= Strongyloides stercoralis?
acquired percutaneously (e.g. walking barefoot)
causes pruritus and larva currens - this has a similar appearance to cutaneous larva migrans but moves through the skin at a far greater rate
abdo pain, diarrhoea, pneumonitis
may cause Gram
negative septicaemia due carrying of bacteria into bloodstream
eosinophilia sometimes seen
management: thiabendazole, albendazole. Ivermectin also used, particularly in chronic infections
Nematodes= Toxocara canis?
commonly acquired by ingesting eggs from soil contaminated by dog faeces
commonest cause of visceral larva migrans
other features: eye granulomas, liver/lung involvement
Non-gonococcal urethritis (NGU, sometimes referred to as non-specific urethritis)?
term used to describe the presence of urethritis when a gonococcal bacteria are not identifiable or the initial swab.
A typical case would be a male who presented to a GUM clinic with a purulent urethral discharge and dysuria.
A swab would be taken in clinic, microscopy performed which showed neutrophils but no Gram-negative diplococci (i.e. no evidence of gonorrhoea).
Clearly, this patient requires immediate treatment prior to waiting for the Chlamydia test to come back and hence an initial diagnosis of NGU is made.
Non-gonococcal urethritis (NGU, sometimes referred to as non-specific urethritis)= causes?
No cause is found in around half of cases. Possible causative organisms include:
Chlamydia trachomatis
most common cause
Mycoplasma genitalium
thought to cause more symptoms than Chlamydia
less common causes:
- Ureaplasma urealyticum
- Trichomonas vaginalis
- Escherichia coli
Non-gonococcal urethritis (NGU, sometimes referred to as non-specific urethritis)= Mx?
contact tracing
the BNF and British Association for Sexual Health and HIV (BASHH) both recommend either oral azithromycin or doxycycline
Norovirus?
also known as the winter vomiting bug, is one of the most common causes of gastroenteritis in the UK according to NHS England.
1 in 5 cases of infectious gastroenteritis are caused by norovirus, with 685 million cases per year worldwide.
Norovirus- type of virus?
It is a genus that encompasses a range of non encapsulated RNA virus species
Norovirus symptoms?
Develop within 15 - 50 hours of infection (quoted from the European Centre of Disease Control and Prevention), with patients experiencing nausea, vomiting, and diarrhoea, which may be accompanied by headaches, low-grade fevers, and myalgia.
The majority of patients experience both vomiting and diarrhoea
10 - 22% reported a headache and up to 47% of patients reported fevers (Clinical Microbiology Reviews, Norovirus, January 2015)
Norovirus transmission?
Faecal-oral route, with the virus becoming aerosolized when the patient vomits or when a toilet containing infected bodily fluids (vomit or faeces) is flushed.
Viral particles are transmitted directly to surrounding potential hosts and to surrounding surfaces, from which they can be transmitted by cross-contamination (for example a patient visitor touching the patient environment, then eating without first washing their hands).
Infection may also be transmitted from an infected individual in the process of direct physical contact, or contact with food preparation.
The virus enters the cell via host receptor-mediated endocytosis and replicates in the small intestine.
Norovirus is highly contagious, the European Centre of Disease Control and Prevention estimates that only 10 - 100 viral particles are required to cause an active infection.
Norovirus is not at present considered to be a notifiable disease in the UK.
Limiting transmission of norovirus?
Isolation of infected strongly recommended where possible, particularly in areas where the risk of person to person transmission is high, for example, in hospitals schools, and care facilities
Good hand hygiene using soap and water is essential
Alcohol hand gel has been shown to be less effective in reducing transmission
Diagnosis of norovirus?
Clinical history and stool culture viral PCR (polymerase chain reaction).
Norovirus differential diagnoses?
Features most suggestive of norovirus include sudden onset vomiting, relatively short duration of symptoms and contact with others with similar symptoms.
Rotavirus, E. coli and Salmonella infections will all cause similar clinical pictures, however, there are some important differentiating features.
Salmonella infection has an incubation period of 6 - 72 hours and is often the result of contact with contaminated animal products, for example, unpasteurized eggs or milk. Unlike norovirus, salmonella gastroenteritis can cause bloody diarrhoea and patients often have a high fever.
Rotavirus gastroenteritis causes symptoms very similar to those of norovirus, but predominantly affects children under the age of 5 years.
E. coli infection, like Norovirus, causes vomiting and diarrhoea but has a longer incubation period (between 3-4 days but can be up to 10 days following pathogen exposure) and unlike Norovirus, E Coli infection commonly causes severe abdominal cramping and frequently causes bloody diarrhoea.
Norovirus resolution and potential Cx?
The infection is self-limiting in immunocompetent patients and symptoms generally resolve within 72 hours
Dehydration and electrolyte imbalances may arise as a result of vomiting and diarrhoea, leading to significant morbidity and mortality and patients should be managed supportively with rehydration and electrolyte supplementation where necessary.
Pseudomonas aeruginosa?
an aerobic Gram-negative rod. It causes a number of clinically important infections in humans:
- chest infections (especially in cystic fibrosis)
- skin: burns, wound infections, ‘hot tub’ folliculitis
- otitis externa (especially in diabetics who may develop malignant otitis externa)
- urinary tract infections
Pseudomonas aeruginosa lab features?
Gram-negative rod
non-lactose fermenting
oxidase positive
Pseudomonas aeruginosa pathophysiology?
produces both an endotoxin (causes fever and shock) and exotoxin A (inhibits protein synthesis by catalyzing ADP-ribosylation of elongation factor EF-2)
Pyrexia of unknown origin (PUO)?
a prolonged febrile illness with temperatures exceeding 38.3°C on several occasions over a period of at least 3 weeks, with no established diagnosis after one week of inpatient investigation.
Pyrexia of unknown origin (PUO) classification?
Classical PUO: Often related to infections, malignancies, or non-infectious
inflammatory diseases.
Hospital-acquired PUO: Fevers that develop in hospitalized patients, commonly due to nosocomial infections, thromboembolic diseases, or drug fevers.
Neutropenic PUO: Observed in neutropenic patients, typically those undergoing chemotherapy, where febrile episodes are predominantly due to infections.
HIV-associated PUO: In patients with HIV, where fever can be attributed to various opportunistic infections, malignancies, or HIV itself.
Pyrexia of unknown origin (PUO) causes?
Infections (30%):
- Tuberculosis
- Abscess
Malignancies (20%)
- Lymphoma
- Hypernephroma
- Leukaemia
- Atrial myxoma
Non-infectious inflammatory diseases
-Systemic lupus erythematosus
- Temporal arteritis
- Rheumatoid arthritis.
Miscellaneous (50%)
- Drug fevers
- Factitious fever
Pyrexia of unknown origin (PUO) diagnostic approach?
History and physical examination: Focus on travel history, occupational exposures, animal exposures, past medical history, and medication use.
Laboratory tests: Initial tests include full blood count, ESR/CRP, HIV test, blood cultures, urine analysis, and chest radiography.
Imaging: CT scans, MRI, and PET scans to identify hidden abscesses, malignancies
Biopsies and specialised tests: Depending on the clinical suspicion, targeted biopsies, bone marrow examination
Pyrexia of unknown origin (PUO) Mx?
Many patients can undergo evaluation in an outpatient setting given the prolonged nature of the symptoms
Empirical antibiotic therapy is generally not used, unless the patient is suspected of having a potentially life-threatening infection
Pyrexia of unknown origin (PUO) prognosis?
Up to 50% of patients with classic FUO remain without a diagnosis after extensive evaluation
The majority who remain undiagnosed have a good prognosis
Q fever?
caused by Coxiella burnetii, a rickettsia. The source of infection is typically an abattoir, cattle/sheep or it may be inhaled from infected dust
Features of Q fever?
typically prodrome: fever, malaise
causes pyrexia of unknown origin
transaminitis
atypical pneumonia
endocarditis (culture-negative)
Mx of Q fever?
doxycycline
Rabies?
viral disease that causes an acute encephalitis. The rabies virus is classed as a RNA rhabdovirus (specifically a lyssavirus) and has a bullet-shaped capsid. The vast majority of cases are caused by dog bites but it may also be transmitted by bat, raccoon and skunk bites.
How serious is rabies?
If untreated then nearly always fatal.
Rabies is estimated to still kill around 25,000-50,000 people across the world each year. The vast majority of the disease burden falls on people in poor rural areas of Africa and Asia. Children are particularly at risk.
Rabies pathophysiology?
After entry, the virus replicates in muscle tissue near the site of the bite before entering the peripheral nervous system. It then travels up to the central nervous system, where it causes encephalitis, leading to severe neurological symptoms. The virus eventually reaches the salivary glands, facilitating transmission.
Features of rabies?
prodrome: headache, fever, agitation
hydrophobia: water-provoking muscle spasms
hypersalivation
Negri bodies: cytoplasmic inclusion bodies found in infected neurons
Mx of rabies?
now considered to be ‘no risk’ of developing rabies following an animal bite in the UK and the majority of developed countries. Following an animal bite in at-risk countries:
- the wound should be washed
- if an individual is already immunised then 2 further doses of vaccine should be given
- if not previously immunised then human rabies immunoglobulin (HRIG) should be given along with a full course of vaccination. If possible, the dose should be administered locally around the wound
RSV associated condition?
bronchiolitis
Parainfluenza virus associated condition?
croup
Rhinovirus associated condition?
common cold
Influenza virus associated condition?
flu
strep pneumoniae associated condition?
most common cause of CAP
Haemophilus influenzae associated condition?
CAP
Most common cause of bronchiectasis exacerbations
Acute epiglottitis
Staph aureus associated condition?
pneumonia, esp following influenza
Mycoplasma pneumoniae associated condition?
Atypical pneumonia
Flu-like symptoms classically precede a dry cough. Complications include haemolytic anaemia and erythema multiforme
Legionella pneumophilia associated condition?
Atypical pneumonia
Classically spread by air-conditioning systems, causes dry cough. Lymphopenia, deranged liver function tests and hyponatraemia may be seen
Pneumocystis jiroveci associated condition?
Common cause of pneumonia in HIV patients. Typically patients have few chest signs and develop exertional dyspnoea
Mycobacterium tuberculosis associated condition?
Causes tuberculosis. A wide range of presentations from asymptomatic to disseminated disease are possible. Cough, night sweats and weight loss may be seen.
Rifampicin?
an antibiotic which is used to treat a variety of infections. It is frequently used to treat tuberculosis (in combination with other medications).
Rifampicin can also be used for prophylaxis in those who have had close contact with tuberculosis or meningitis.
Rifampicin MOA?
inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA
Rifampicin adverse effects?
potent CYP450 liver enzyme inducer
hepatitis
orange secretions
flu-like symptoms
Way to remember RNA viruses?
‘CALL PICO and FLAVA. There’s a RETRO TOGA party with lots of CORONAs’
Only double-stranded RNA virus?
Reoviridae
List some RNA viruses?
Reoviridae
Picornaviridae
Caliciviridae
Togaviridae
Arenaviridae
Flaviviridae Orthomyxoviridae
Paramyxoviridae
Bunyaviridae
Rhabdoviridae
Filoviridae
Coronaviridae
Hepeviridae
RNA viruses: family= Reoviridae
structure, envelope, capsid symmetry, examples?
Reoviridae
Double-stranded, linear
Naked
Icosahedral Reovirus, Rotavirus
RNA viruses: family= Picornaviridae
structure, envelope, capsid symmetry, examples?
Single-stranded +, linear
Naked
Icosahedral
Enterovirus, Rhinovirus, Poliovirus, Coxsackie
RNA viruses: family= Caliciviridae
structure, envelope, capsid symmetry, examples?
Single-stranded +, linear
Naked
Icosahedral
Norwalk virus
RNA viruses: family= Togaviridae
structure, envelope, capsid symmetry, examples?
Single-stranded +, linear
Enveloped
Icosahedral
Rubella virus
RNA viruses: family= Arenaviridae
structure, envelope, capsid symmetry, examples?
Single-stranded -, circular Enveloped
Helical
Lymphocytic choriomeningitis virus
RNA viruses: family= Flaviviridae
structure, envelope, capsid symmetry, examples?
Single-stranded +, linear
Enveloped
Icosahedral
Dengue virus, Hepatitis C virus, Yellow fever virus
RNA viruses: family= Orthomyxoviridae
structure, envelope, capsid symmetry, examples?
Single-stranded -, linear
Enveloped
Helical
Influenzavirus A, Influenzavirus B, Influenzavirus C,
RNA viruses: family= Paramyxoviridae
structure, envelope, capsid symmetry, examples?
Single-stranded -, linear
Enveloped
Helical
Measles virus, Mumps virus, Respiratory syncytial virus
RNA viruses: family= Bunyaviridae
structure, envelope, capsid symmetry, examples?
Single-stranded -, circular
Enveloped
Helical
California encephalitis virus, Hantavirus
RNA viruses: family= Rhabdoviridae
structure, envelope, capsid symmetry, examples?
Single-stranded -, linear
Enveloped
Helical
Rabies virus
RNA viruses: family= Filoviridae
structure, envelope, capsid symmetry, examples?
Single-stranded -, linear
Enveloped
Helical
Ebola virus, Marburg virus
RNA viruses: family= Coronaviridae
structure, envelope, capsid symmetry, examples?
Single-stranded +, linear
Enveloped
Helical
Corona virus
RNA viruses: family= Hepeviridae
structure, envelope, capsid symmetry, examples?
Single-stranded +, linear
Naked
Icosahedral
Hepatitis E virus
Schistosomiasis (bilharzia)?
a parasitic flatworm infection.
The three main species of schistosome are S. mansoni, S. japonicum and S. haematobium.
Schistosomiasis (bilharzia)= acute infection symptoms?
Acute symptoms typically only develop in people who travel to endemic areas, as they don’t have any immunity to the worms.
Acute manifestations may include:
- swimmers’ itch
- acute schistosomiasis syndrome (Katayama fever)=
fever, urticaria/angioedema, arthralgia/myalgia, cough, diarrhoea, eosinophilia
Schistosomiasis (bilharzia)= chronic infections: Schistosoma haematobium?
These worms deposit egg clusters (pseudopapillomas) in the bladder, causing inflammation. The calcification seen on x-ray is actually calcification of the egg clusters, not the bladder itself.
Depending on the site of these pseudopapillomas in the bladder, they can cause an obstructive uropathy and kidney damage.
Schistosomiasis (bilharzia)= chronic infections: Schistosoma haematobium- presentation?
This typically presents as a ‘swimmer’s itch’ in patients who have recently returned from Africa. Schistosoma haematobium is a risk factor for squamous cell bladder cancer.
Features:
- frequency
- haematuria
- bladder calcification
Schistosomiasis (bilharzia)= chronic infections: Schistosoma haematobium- Ix?
for asymptomatic patients serum schistosome antibodies are generally preferred
for symptomatic patients the gold standard for diagnosis is urine or stool microscopy looking for eggs
Schistosomiasis (bilharzia)= chronic infections: Schistosoma haematobium- Mx?
single oral dose of praziquantel
Schistosomiasis (bilharzia)= chronic infections: Schistosoma mansoni and Schistosoma japonicum?
These worms mature in the liver and then travel through the portal system to inhabit the distal colon. Their presence in the portal system can lead to progressive hepatomegaly and splenomegaly due to portal vein congestion.
These species can also lead to complications of liver cirrhosis, variceal disease and cor pulmonale.
Schistosomiasis (bilharzia)= chronic infections: Schistosoma intercalatum and Schistosoma mekongi?
These are less prevalent than the other three forms, but are both attributed to intestinal schistosomiasis.
What is an abscess?
collection of pus encapsulated by a pyogenic membrane.
A spinal epidural abscess (SEA)?
a collection of pus that is superficial to the dura mater (of the meninges) that cover the spinal cord. It is an emergency requiring urgent investigation and treatment to avoid progressive spinal cord damage.
A spinal epidural abscess (SEA)- how do they form?
In SEA, bacteria enters the spinal epidural space by contiguous spread from adjacent structures (e.g. discitis), haematogenous spread from concomitant infection (e.g. bacteraemia from IVDU), or by direct infection (e.g. spinal surgery).
Immunosuppression is another major risk factor, which may be caused by congenital immune disorders, acquired immune disorders (such as HIV, diabetes or alcoholism or by iatrogenic means (e.g. chemotherapy or steroids).
A spinal epidural abscess (SEA)- cause?
most typically bacterial and the most common causative micro-organism is Staphylococcus aureus
A spinal epidural abscess (SEA)- presentation?
fever
back pain
focal neurological deficits according to the segment of the cord affected.
A spinal epidural abscess (SEA)- Ix?
Bloods (including inflammatory markers, HIV, Hep B, Hep C, and preoperative blood tests (coagulation and group and screen))
Blood cultures
Infection screen (including chest x-ray and urine culture): If the primary source of infection is not clear, a wide search for sources requires investigations including echocardiography and dental x-rays.
MRI whole spine (the entire spine is imaged since skip lesions may be present)
A spinal epidural abscess (SEA)- Mx?
All patients will require a long-term course of antibiotics which is at first broad spectrum but maybe later refined based on culture results. Patients with large or compressive abscesses, patients with significant or progressive neurological deficits or those who are not responding to antibiotics alone are considered for surgical evacuation of the abscess.
Staphylococci?
common type of bacteria that are often found normal commensal organisms but may also cause invasive disease
Staphylococci- 3 main facts?
Gram-positive cocci
facultative anaerobes
produce catalase
Staphylococci= 2 main types?
Staphylococcus aureus
Staphylococcus epidermidis
Staphylococci= Staphylococcus aureus?
- Coagulase-positive
- Causes skin infections (e.g. cellulitis), abscesses, osteomyelitis, toxic shock syndrome
Staphylococci= Staphylococcus epidermidis?
- Coagulase-negative
- Cause of central line infections and infective endocarditis
Streptococci?
gram-positive cocci
Streptococci can be divided into what types?
alpha and beta haemolytic types
Streptococci= Alpha haemolytic streptococci (partial haemolysis)?
The most important alpha haemolytic Streptococcus is Streptococcus pneumoniae (pneumococcus). Pneumococcus is a common cause of pneumonia, meningitis and otitis media. Another clinical example is Streptococcus viridans
Streptococci= Beta haemolytic streptococci (complete haemolysis)- These can be subdivided into groups?
A-H
Only groups A, B & D are important in humans.
Streptococci= Beta haemolytic streptococci (complete haemolysis)- group A?
most important organism is Streptococcus pyogenes
responsible for erysipelas, impetigo, cellulitis, type 2 necrotizing fasciitis and pharyngitis/tonsillitis
immunological reactions can cause rheumatic fever or post-streptococcal glomerulonephritis
erythrogenic toxins cause scarlet fever
Streptococci= Beta haemolytic streptococci (complete haemolysis)- group B?
Streptococcus agalactiae may lead to neonatal meningitis and septicaemia
Streptococci= Beta haemolytic streptococci (complete haemolysis)- group D?
Enterococcus
Strongyloides stercoralis?
a human parasitic nematode worm. The larvae are present in soil and gain access to the body by penetrating the skin. Infection with Strongyloides stercoralis causes strongyloidiasis.
Strongyloides stercoralis= features?
diarrhoea
abdominal pain/bloating
papulovesicular lesions where the skin has been penetrated by infective larvae e.g. soles of feet and buttocks
larva currens: pruritic, linear, urticarial rash
if the larvae migrate to the lungs a pneumonitis similar to Loeffler’s syndrome may be triggered
Strongyloides stercoralis= Tx?
ivermectin and albendazole are used
Sulfonamides MOA?
class of drug that work by inhibiting dihydropteroate synthetase
Antibiotic sulfonamides?
sulfamethoxazole
sulfonamides= co-trimoxazole?
a combination of sulfamethoxazole + trimethoprim that is used in the management of Pneumocystis jiroveci pneumonia
sulfadiazine
sulfisoxazole
examples of non-antibiotic sulfonamides?
sulfasalazine
sulfonylureas
Adverse effects of co-trimoxazole (sulfonamides) include?
hyperkalaemia
headache
rash (including Steven-Johnson Syndrome)
Organisms causing common surgical infections?
Staphylococcus aureus
Streptococcus pyogenes
Escherichia coli
Campylobacter jejuni
Helicobacter pylori
Organisms causing common surgical infections= Staphylococcus aureus?
Facultative anaerobe
Gram-positive coccus
Haemolysis on blood agar plates
Catalase positive
20% population are long term carriers
Exo and entero toxin may result in toxic shock syndrome and gastroenteritis respectively
Ideally treated with penicillin although many strains now resistant through beta-lactamase production. In the UK less than 5% of isolates are sensitive to penicillin.
Resistance to methicillin (and other antibiotics) is mediated by the mec operon, essentially penicillin binding protein is altered and resistance to this class of antibiotics ensues
Common cause of cutaneous infections and abscesses
Organisms causing common surgical infections= Streptococcus pyogenes?
Gram-positive, forms chain like colonies, Lancefield Group A Streptococcus
Produces beta haemolysis on blood agar plates
Rarely part of normal skin microflora
Catalase negative
Releases a number of proteins/ virulence factors into host including hyaluronidase, streptokinase which allow rapid tissue destruction
Releases superantigens such as pyogenic exotoxin A which results in scarlet fever
Remains sensitive to penicillin, macrolides may be used as an alternative.
Organisms causing common surgical infections= Escherichia coli?
Gram-negative rod
Facultative anaerobe, non-sporing
Wide range of subtypes and some are normal gut commensals
Some subtypes such as 0157 may produce lethal toxins resulting in haemolytic-uraemic syndrome
Enterotoxigenic E-Coli produces an enterotoxin (ST enterotoxin) that results in large volume fluid secretion into the gut lumen (Via cAMP activation)
Enteropathogenic E-Coli binds to intestinal cells and cause structural damage, this coupled with a moderate (or in the case of enteroinvasive E-Coli significant) invasive component produces enteritis and large volume diarrhoea together with fever.
They are resistant to many antibiotics used to treat gram positive infections and acquire resistance rapidly and are recognised as producing beta-lactamases
Organisms causing common surgical infections= Campylobacter jejuni?
Curved, Gram-negative, non-sporulating bacteria
One of the commonest causes of diarrhoea worldwide
Produces enteritis which is often diffuse and blood may be passed
Remains a differential for right iliac fossa pain with diarrhoea
Self-limiting infection so antibiotics are not usually advised. However, the quinolones are often rapidly effective.
Organisms causing common surgical infections= Helicobacter pylori?
Gram-negative, helix-shaped rod, microaerophilic
Produces hydrogenase that can derive energy from hydrogen released by intestinal bacteria
Flagellated and mobile
Those carrying the cag A gene may cause ulcers
It secretes urease that breaks down gastric urea> Carbon dioxide and ammonia> ammonium>bicarbonate (simplified!) The bicarbonate can neutralise the gastric acid.
Usually, colonises the gastric antrum and irritates resulting in increased gastrin release and higher levels of gastric acid. These patients will develop duodenal ulcers. In those with more diffuse H-Pylori infection, gastric acid levels are lower and ulcers develop by local tissue damage from H-Pylori- these patients get gastric ulcers.
Diagnosis may be made by serology (approx. 75% sensitive). Biopsy urease test during endoscopy probably the most sensitive.
In patients who are colonised 10-20% risk of peptic ulcer, 1-2% risk gastric cancer, <1% risk MALT lymphoma.
Tetanus?
caused by the tetanospasmin exotoxin released from Clostridium tetani. Tetanus spores are present in soil and may be introduced into the body from a wound, which is often unnoticed. Tetanospasmin prevents the release of GABA,
In developed countries, tetanus may be seen in intravenous drug users.
Tetanus= features?
prodrome fever, lethargy, headache
trismus (lockjaw)
risus sardonicus: facial spasms
opisthotonus (arched back, hyperextended neck)
spasms (e.g. dysphagia)
Tetanus= Mx?
supportive therapy including ventilatory support and muscle relaxants
intramuscular human tetanus immunoglobulin for high-risk wounds (e.g. compound fractures, delayed surgical intervention, significant degree of devitalised tissue)
metronidazole is now preferred to benzylpenicillin as the antibiotic of choice
prodrome fever, lethargy, headache
trismus (lockjaw)
risus sardonicus: facial spasms
opisthotonus (arched back, hyperextended neck)
spasms (e.g. dysphagia)
?tetanus
Tetracyclines?
class of antibiotics which are commonly used in clinical practice.
Tetracyclines= examples?
doxycycline
tetracycline
doxycycline
tetracycline
are examples of what?
tetracyclines
Tetracyclines= MOA?
protein synthesis inhibitors
binds to 30S subunit blocking binding of aminoacyl-tRNA
Tetracyclines= mechanism of resistance?
increased efflux of the bacteria by plasmid-encoded transport pumps, ribosomal protection
Tetracyclines= indications?
acne vulgaris
Lyme disease
Chlamydia
Mycoplasma pneumoniae
Tetracyclines= adverse effects?
discolouration of teeth: therefore should not be used in children < 12 years of age
photosensitivity
angioedema
black hairy tongue
Tetracyclines= can they be given to pregnant women?
should not be given to women who are pregnant or breastfeeding due to the risk of discolouration of the infant’s teeth.
Toxoplasma gondii (Toxoplasmosis)?
an obligate intracellular protozoan that infects the body via the gastrointestinal tract, lung or broken skin. It’s oocysts release trophozoites which migrate widely around the body including to the eye, brain and muscle. The usual animal reservoir is the cat, although other animals such as rats carry the disease.
Toxoplasmosis= features in immunocompetent pts?
Most infections are asymptomatic. Symptomatic patients usually have a self-limiting infection, often having clinical features resembling infectious mononucleosis (fever, malaise, lymphadenopathy). Other less common manifestations include meningoencephalitis and myocarditis.
Toxoplasmosis= Ix and Mx in immunocompetent pts?
Serology is the investigation of choice.
No treatment is usually required unless the patient has a severe infection or is immunosuppressed.
Toxoplasmosis= HIV/immunosuppressed pts?
Cerebral toxoplasmosis accounts for around 50% of cerebral lesions in patients with HIV:
- constitutional symptoms, headache, confusion, drowsiness
- CT: usually single or multiple ring-enhancing lesions, mass effect may be seen
- management: pyrimethamine plus sulphadiazine for at least 6 weeks
Immunosuppressed patients may also develop a chorioretinitis secondary to toxoplasmosis.
Congenital toxoplasmosis?
Congenital toxoplasmosis is due to transplacental spread from the mother. It causes a variety of effects to the unborn child including
neurological damage:
- cerebral calcification
- hydrocephalus
- chorioretinitis
ophthalmic damage:
- retinopathy
- cataracts
Trimethoprim?
antibiotic, mainly used in the management of urinary tract infections
Trimethoprim MOA?
interferes with DNA synthesis by inhibiting dihydrofolate reductase
may, therefore, interact with methotrexate, which also inhibits dihydrofolate reductase
Trimethoprim adverse effects?
myelosuppression
transient rise in creatinine: trimethoprim competitively inhibits the tubular secretion of creatinine resulting in a temporary increase which reverses upon stopping the drug
trimethoprim blocks the ENaC channel in the distal nephron, causing a hyperkalaemic distal RTA (type 4). It also inhibits creatinine secretion, often leading to an increase in creatinine by around 40 points (but not necessarily causing AKI)
Trimethoprim= why does it cause a transient rise in creatinine?
competitively inhibits the tubular secretion of creatinine resulting in a temporary increase which reverses upon stopping the drug
trimethoprim blocks the ENaC channel in the distal nephron, causing a hyperkalaemic distal RTA (type 4). It also inhibits creatinine secretion, often leading to an increase in creatinine by around 40 points (but not necessarily causing AKI)
Trimethoprim in pregnancy?
Teratogenic risk in first trimester (folate antagonist). Manufacturers advise avoid during pregnancy.
Trypanosomiasis?
Two main form of this protozoal disease are recognised - African trypanosomiasis (sleeping sickness) and American trypanosomiasis (Chagas’ disease).
Trypanosomiasis= African trypanosomiasis, or sleeping sickness- features?
Two forms of African trypanosomiasis, or sleeping sickness, are seen - Trypanosoma gambiense in West Africa and Trypanosoma rhodesiense in East Africa. Both types are spread by the tsetse fly. Trypanosoma rhodesiense tends to follow a more acute course. Clinical features include:
Trypanosoma chancre - painless subcutaneous
nodule at site of infection
intermittent fever
enlargement of posterior cervical lymph nodes
later: central nervous system involvement e.g. somnolence, headaches, mood changes, meningoencephalitis
Trypanosomiasis= African trypanosomiasis, or sleeping sickness- Mx?
early disease: IV pentamidine or suramin
later disease or central nervous system involvement: IV melarsoprol
Trypanosomiasis= American trypanosomiasis, or Chagas’ disease?
caused by the protozoan Trypanosoma cruzi.
The vast majority of patients (95%) are asymptomatic in the acute phase although a chagoma (an erythematous nodule at site of infection) and periorbital oedema are sometimes seen.
Chronic Chagas’ disease mainly affects the heart and gastrointestinal tract
myocarditis may lead to dilated cardiomyopathy (with apical atophy) and arrhythmias
gastrointestinal features includes megaoesophagus and megacolon causing dysphagia and constipation
Trypanosomiasis= American trypanosomiasis, or Chagas’ disease- Mx?
treatment is most effective in the acute phase using azole or nitroderivatives such as benznidazole or nifurtimox
chronic disease management involves treating the complications e.g., heart failure
Vancomycin?
a glycopeptide antibiotic used in the treatment of Gram-positive infections, particularly methicillin-resistant Staphylococcus aureus (MRSA).
Vancomycin= MOA?
inhibits cell wall formation by binding to D-Ala-D-Ala moieties, preventing polymerization of peptidoglycans
Vancomycin= mechanism of resistance?
alteration to the terminal amino acid residues of the NAM/NAG-peptide subunits (normally D-alanyl-D-alanine) to which the antibiotic binds
Vancomycin= adverse effects?
nephrotoxicity
ototoxicity
thrombophlebitis
red man syndrome; occurs on rapid infusion of vancomycin
Yellow fever?
Type of viral haemorrhagic fever (also dengue fever, Lassa fever, Ebola).
zoonotic infection: spread by Aedes mosquitos
incubation period = 2 - 14 days
Yellow fever= features?
may cause mild flu-like illness lasting less than one week
classic description involves sudden onset of high fever, rigors, nausea & vomiting. Bradycardia may develop. A brief remission is followed by jaundice, haematemesis, oliguria
if severe jaundice, haematemesis may occur
Councilman bodies (inclusion bodies) may be seen in the hepatocytes
Mx of venom allergy?
Broadly speaking, the management of venom allergy in the acute phase is supportive.
Anaphylaxis should be managed with intramuscular adrenaline, intravenous steroids and intravenous anti-histamines as required. Oxygen and nebulised bronchodilators may also be required.
People who’ve had a systemic reaction to an insect bite should be referred to an allergy specialist.
Venom immunotherapy (VIT) is considered to be one of the most effective immunotherapies in use and may be recommended for patients with a history of a previous reaction which presented with airway and/or haemodynamic compromise and raised levels of venom-specific immunoglobulin E on either skin prick or in vitro testing.
Testing for venom allergy is recommended in who?
any patient with a history of a systemic reaction causing airway compromise or
haemodynamic instability.
It may also be beneficial in patients with a history of a systemic cutaneous reaction where the allergen is felt to be difficult to avoid e.g. an allergy to bee stings in a beekeeper.
Patients with a history of a systemic reaction should be provided with a self-management plan, including guidance on the use of anti-histamines and adrenaline auto-injectors.
Patients should also be advised to wear a medical alert device.
Venom allergy:
The British Society for Allergy and Clinical Immunology guidance advises that VIT should not be performed in patients without demonstrable venom-specific IgE or in those with a recent history of anaphylaxis or systemic reaction….
Repeat allergy testing should be considered in those with a clear reaction history but no evidence of a venom-specific IgE.
A baseline tryptase level should also be performed to exclude indolent mastocytosis (relevant because this may predict subsequent systemic reactions during the course of immunotherapy also should prompt further tests to exclude systemic mastocytosis or monoclonal mast cell activation syndrome).
Research suggests that ‘VIT is 95-100% and about 80% successful in preventing systemic reactions in wasp and bee sting allergy respectively…(and) has been shown to induce a clinically significant improvement in health-related QOL (quality of life) in patients with anaphylactic reactions as well as generalized non-life-threatening responses to yellow jacket stings…’
Interferons (IFN)?
cytokines released by the body in response to viral infections and neoplasia.
They are classified according to cellular origin and the type of receptor they bind to.
IFN-alpha and IFN-beta bind to type 1 receptors whilst IFN-gamma binds only to type 2 receptors.
Interferon-alpha?
produced by leucocytes
antiviral action
useful in hepatitis B & C, Kaposi’s sarcoma, metastatic renal cell cancer, hairy cell leukaemia
adverse effects include flu-like symptoms and depression
bind to type 1 receptors
Interferon-beta?
produced by fibroblasts
antiviral action
reduces the frequency of exacerbations in patients with relapsing-remitting MS
bind to type 1 receptors
Interferon-gamma?
predominately natural killer cells. Also by T helper cells
weaker antiviral action, more of a role in immunomodulation particularly macrophage activation
may be useful in chronic granulomatous disease and osteopetrosis
bind to type 2 receptors
What divides hypersensitivity reactions into 4 types?
Gell and Coombs classification
Gell and Coombs classification of hypersensitivity reactions= Type I?
anaphylactic
Gell and Coombs classification of hypersensitivity reactions= Type I (anaphylactic) mechanism and examples?
Antigen reacts with IgE bound to mast cells
- Anaphylaxis
- Atopy (e.g. asthma, eczema and hayfever)
Gell and Coombs classification of hypersensitivity reactions= Type II?
Cell bound
Gell and Coombs classification of hypersensitivity reactions= Type II (cell bound) mechanism and examples?
IgG or IgM binds to antigen on cell surface
- Autoimmune haemolytic anaemia
- ITP
- Goodpasture’s syndrome
- Pernicious anaemia
- Acute haemolytic transfusion reactions
- Rheumatic fever
- Pemphigus vulgaris / bullous pemphigoid
Gell and Coombs classification of hypersensitivity reactions= Type III?
Immune complex
Gell and Coombs classification of hypersensitivity reactions= Type III (immune complex) mechanism and examples?
Free antigen and antibody (IgG, IgA) combine
- Serum sickness
- Systemic lupus erythematosus
- Post-streptococcal glomerulonephritis
- Extrinsic allergic alveolitis (especially acute phase)
Gell and Coombs classification of hypersensitivity reactions= Type IV?
Delayed hypersensitivity
Gell and Coombs classification of hypersensitivity reactions= Type IV (delayed hypersensitivity) mechanism and examples?
T-cell mediated
- Tuberculosis / tuberculin skin reaction
- Graft versus host disease
- Allergic contact dermatitis
- Scabies
- Extrinsic allergic alveolitis (especially chronic phase)
- Multiple sclerosis
- Guillain-Barre syndrome
Gell and Coombs classification of hypersensitivity reactions= recently a Type V has been added, what is this?
Antibodies that recognise and bind to the cell surface receptors.
This either stimulating them or blocking ligand binding
- Graves’ disease
- Myasthenia gravis
What type of hypersensitivity reaction is anaphylaxis?
1
What type of hypersensitivity reaction is asthma?
1
What type of hypersensitivity reaction is pernicious anaemia?
2
What type of hypersensitivity reaction is rheumatic fever?
2
What type of hypersensitivity reaction is SLE?
3
What type of hypersensitivity reaction is post-steptococcal glomerulonephritis?
3
What type of hypersensitivity reaction is allergic contact dermatitis?
4
What type of hypersensitivity reaction is MS?
4
What type of hypersensitivity reaction is graves and myasthenia gravis?
5 (just added)
Way to remember the types of hypersensitivity reactions?
ACID
Anaphylactic-Type 1
Cell bound- Type 2
Immune Complex- Type 3
Delayed hypersensitivity- Type 4
How many types of immunoglobulin are there in the body?
5
Name the 5 types of immunoglobulin?
IgG
IgA
IgM
IgD
IgE
Immunoglobulins= IgG frequency and shape?
75%
monomer
Immunoglobulins= IgA frequency and shape?
15%
monomer/dimer
Immunoglobulins= IgM frequency and shape?
10%
pentamer
Immunoglobulins= IgD frequency and shape?
1%
monomer
Immunoglobulins= IgE frequency and shape?
0.1%
monomer
Most abundant immunoglobulin?
IgG
but IgA most commonly produced in the body (blood concs lower than IgG)
What is immunoglobulin IgG?
- Enhance phagocytosis of bacteria and viruses
- Fixes complement and passes to the fetal circulation
- Most abundant isotype in blood serum
What is immunoglobulin IgA?
- IgA is the predominant immunoglobulin found in breast milk. It is also found in the secretions of digestive, respiratory and urogenital tracts and systems
- Provides localized protection on mucous membranes
- Most commonly produced immunoglobulin in the body (but blood serum concentrations lower than IgG.)
- Transported across the interior of the cell via transcytosis
Predominant immunoglobulin found in breast milk?
IgA
What is immunoglobulin IgM?
- First immunoglobulins to be secreted in response to an infection
- Fixes complement but does not pass to the fetal circulation
- Anti-A, B blood antibodies (note how they cannot pass to the fetal circulation, which could of course result in haemolysis)
Pentamer when secreted
What is immunoglobulin IgD?
- Role in immune system largely unknown
- Involved in activation of B cells
What is immunoglobulin IgE?
- Mediates type 1 hypersensitivity reactions
- Synthesised by plasma cells
- Binds to Fc receptors found on the surface of mast cells and basophils
- Provides immunity to parasites such as helminths
- Least abundant isotype in blood serum
What immunoglobulin enhances phagocytosis of bacteria and viruses?
IgG
What immunoglobulin in found in secretions of digestive, resp and urogenital tracts & provides localised protection on mucous membranes?
IgA
What is the first immunoglobulin to be secreted in response to an infection?
IgM
What immunoglobulin is involved in the activation of B cells?
IgD
What immunoglobulin mediates type 1 hypersensitivity reactions?
IgE
What immunoglobulin is synthesised by plasma cells?
IgE
Neonatal sepsis occurs when?
a serious bacterial or viral infection in the blood affects babies within the first 28 days of life
Neonatal sepsis is characterised into what?
early-onset (EOS, within 72 hours of birth) and late-onset (LOS, between 7-28 days of life) sepsis, with each category tending to have a distinct group of causes and common presentations
Prognosis of neonatal sepsis?
account for 10% of all neonatal mortality and therefore must be promptly identified and managed to prevent significant consequences, as untreated, the mortality can be very high.
Epidemiology of neonatal sepsis?
Male:female incidence 1:1
Incidence of neonatal sepsis: 1-5 per 1000 live births
* Term neonates: 1-2 per 1000 live births
* Late pre-term infants: 5 per 1000 live births
* Birth weight <2.5kg: 0.5 per 1000 live births
Black race is an independent risk factor for group B streptococcus-related sepsis
Neonatal infection is present in 8 per 1000 live births (note: this is the incidence of neonatal infection, not yet necessarily progressed to neonatal sepsis), and is the key factor which leads to subsequent….
life-threatening sepsis
Most common cause of neonatal sepsis (2/3rds)?
group B strep (GBS) and E.coli
Main cause of early-onset neonatal sepsis (within 72hrs of birth)?
GBS infection (75%)
Infective causes in early-onset sepsis are usually due to transmission of pathogens from the mother to the neonate during delivery
Cause of late-onset neonatal sepsis (7-28 days of life)?
usually occurs via the transmission of pathogens from the environment post-delivery, this is normally from contacts such as the parents or healthcare workers
Infective causes are more commonly coagulase-negative staphylococcal species such as Staphylococcus epidermidis, Gram-negative bacteria such as Pseudomonas aeruginosa, Klebsiella and Enterobacter, and fungal species
Less common causes of neonatal sepsis?
Staphylococcus aureus
Enterococcus
Listeria monocytogenes
Viruses including herpes simplex and enterovirus
RFs for neonatal sepsis?
Mother who has had a previous baby with GBS infection, who has current GBS colonisation from prenatal screening, current bacteruria, intrapartum temperature ≥38ºC, membrane rupture ≥18 hours, or current infection throughout pregnancy
Premature (<37 weeks): approximately 85% of neonatal sepsis cases are in premature neonates
Low birth weight (<2.5kg): approximately 80% are low birth weight
Evidence of maternal chorioamnionitis
Presentation of neonatal sepsis?
subacute onset of….
Respiratory distress (85%)= Grunting, Nasal flaring, Use of accessory respiratory muscles, Tachypnoea
Tachycardia: common, but non-specific
Apnoea (40%)
Apparent change in mental status/lethargy
Jaundice (35%)
Seizures (35%): if cause of sepsis is meningitis
Poor/reduced feeding (30%)
Abdominal distention (20%)
Vomiting (25%)
Temperature: not usually a reliable sign as the temperature can vary from being raised, lowered or normal
Term infants are more likely to be febrile
Pre-term infants are more likely to be hypothermic
The clinical presentation can vary from very subtle signs of illness to clear septic shock
Frequently, the symptoms will be related to the source of infection (e.g. pneumonia + respiratory symptoms, meningitis + neurological symptoms)
Signs of resp distress in neonatal sepsis (85%)?
Grunting
Nasal flaring
Use of accessory respiratory muscles
Tachypnoea
Temperature in neonatal sepsis?
not usually a reliable sign as the temperature can vary from being raised, lowered or normal
Term infants are more likely to be febrile
Pre-term infants are more likely to be hypothermic
Ix for neonatal sepsis?
Blood culture: this will usually establish the diagnosis, as the sensitivity for septicaemia is around 90%. Should usually obtain two blood cultures if possible to distinguish from contamination, however one culture is still sufficient depending on hospital protocol
Full blood examination: neonatal sepsis is often associated with abnormal neutrophil counts (both neutrophilia and neutropenia), however in neonates, parameters on full blood examination are usually not always useful for diagnosis, rather may help to exclude healthy neonates
C-reactive protein: not useful for diagnosis, but sequential assessment will help to guide management and patient progress with treatment. CRP will usually be raised, and a persistently normal level is likely to exclude neonatal sepsis
Blood gases: metabolic acidosis is particularly concerning for neonatal sepsis, particularly a base deficit of ≥10 mmol/L
Urine microscopy, culture and sensitivity: rarely positive in EOS, more useful in LOS. Will show signs of infection (e.g. raised leukocytes, positive culture, haematuria, proteinuria) if urinary tract infection is the source of sepsis
Lumbar puncture: particularly if there is concern of meningitis as the source of sepsis based on clinical features, however many hospitals will require lumbar puncture as part of a septic screen in any baby below the age of 28 days
What signs on blood gas is particularly concerning in neonatal sepsis?
metabolic acidosis esp if a base deficit of ≥10 mmol/L
Mx of neonatal sepsis?
early identification and treatment
IV benzylpenicillin with gentamicin as a first-line regimen for suspected or confirmed neonatal sepsis
- The exception to this is if microbiological surveillance data reveal local bacterial resistance patterns, in which case an alternative antibiotic should be considered
Maintaining adequate oxygenation status
Maintaining normal fluid and electrolyte status: severely ill neonates may require volume and/or vasopressor support. Body weight needs to be measured daily for accurate assessment of fluid status
Prevention and/or management of hypoglycaemia
Prevention and/or management of metabolic acidosis
Duration of Abx in neonatal sepsis?
- CRP should be re-measured 18-24 hours after presentation in babies given antibiotics to monitor ongoing progress and guide duration of therapy
- The evidence suggests that antibiotics can be ceased at 48 hours in neonates who have CRP of <10 mg/L and a negative blood culture at presentation and at 48 hours
- In all other neonates, the duration of antibiotic treatment will depend on the ongoing investigations and clinical picture, this will involve specialist decision making. Normally, in neonates with culture-proven sepsis, duration will be approximately 10 days
Neonatal sepsis= how to monitor fluid status in very ill neonates who may require volume and/or vasopressor support?
body weight measured daily
Abx 1st line for suspected or confirmed neonatal sepsis?
IV benzylpenicillin + gentamicin
unless microbiological surveillance data reveal local bacterial resistance patterns, in which case an alternative antibiotic should be considered
