Infectious disease Flashcards
what is TB?
Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis that most commonly affects the lungs.
**common exam question involves a patient coughing u sputum that grows acid-fast bacilli that stain red with Zeihl- neelsen staning - this is mycobacterium tuberculosis and the diagnosis of TB
what is the pathophysiology of TB?
Primary tuberculosis
A non-immune host who is exposed to M. tuberculosis may develop primary infection of the lungs. A small lung lesion known as a Ghon focus develops. The Ghon focus is composed of tubercle-laden macrophages. The combination of a Ghon focus and hilar lymph nodes is known as a Ghon complex
In immunocompotent people the intially lesion usually heals by fibrosis. Those who are immunocompromised may develop disseminated disease (miliary tuberculosis).
Latent - infected but no clinical or X ray signs of active TB, non-infectious, may persist for years.
Secondary (post-primary) tuberculosis
If the host becomes immunocompromised the initial infection may become reactivated. Reactivation generally occurs in the apex of the lungs and may spread locally or to more distant sites. Possible causes of immunocomprise include:
immunosuppressive drugs including steroids
HIV
malnutrition
The lungs remain the most common site for secondary tuberculosis. Extra-pulmonary infection may occur in the following areas:
central nervous system (tuberculous meningitis - the most serious complication)
vertebral bodies (Pott’s disease)
cervical lymph nodes (scrofuloderma)
renal
gastrointestinal tract
what are the risk factors for TB?
Known contact with active TB
Immigrants from areas of high TB prevalence
People with relatives or close contacts from countries with a high rate of TB
Immunosuppression due to conditions like HIV or immunosuppressant medications
Homeless people, drug users or alcoholics
what is the BCG vaccine?
The BCG vaccine involves an intradermal infection of live attenuated (weakened) TB. It offers protection against severe and complicated TB but is less effective at protecting against pulmonary TB.
Prior to the vaccine patients are tested with the Mantoux test and given the vaccine only if this test is negative. They are also assessed for the possibility of immunosuppression and HIV due to the risks related to a live vaccine.
who is the BCG vaccine offered to?
BCG vaccine is offered to patients that are at higher risk of contact with TB:
Neonates born in areas of the UK with high rates of TB
Neonates with relatives from countries with a high rate of TB
Neonates with a family history of TB
Unvaccinated older children and young adults (< 35) who have close contact with TB
Unvaccinated children or young adults that recently arrived from a country with a high rate of TB
Healthcare workers
what are the clinical features of pulmonary TB?
cough with or without haemoptysis lethargy fever or night sweats weight loss lymphadenopathy erythema nodosum
what are the symptoms of TB meningitis?
headache, drowsiness fever vomiting meningism worsening over 1-3 weeks CNS signs - papilloedema, CN palsies
how would TB present if spread to the lymph nodes?
cervical lymphadentis - scrofula
painless neck mass -no signs of infection (cold)
how would GU TB present?
frequency, dysuria, loin/back pain, haematuria sterile pyuria (puss in urine)
how would bone TB present?
vertebral collapse and potts vertebra
spinal pain
how would skin TB present?
lupus vulgaris (jelly-like nodules)
how would peritoneal TB present?
abdo pain
GI upset
ascites
how would adrenal TB present?
addisons disease
what are the investigations for TB?
- require specialst stains like the Ziehl-Neelsen stain
- there are two tests for an immune resonse to TB caused by previous, latent or active TB - the mantoux test an interferon-gamma release assay
- in patients where active disease is suspected a chest x-ray and cultures are used to suport the diagnosis
what is the mantoux test?
The Mantoux test is used to look for a previous immune response to TB. This indicates possible previous vaccination, latent or active TB.
This involves injecting tuberculin into the intradermal space on the forearm. Tuberculin is a collection of tuberculosis proteins that have been isolated from the bacteria. The infection does not contain any live bacteria.
Injecting the tuberculin creates a bleb under the skin. After 72 hours the test is “read”. This involves measuring the induration of the skin at the site of the injection. NICE suggest considering an induration of 5mm or more a positive result. After a positive result they should be assessed for active disease.
what is the interferon-gamma release assays?
This test involves taking a sample of blood and mixing it with antigens from the TB bacteria. In a person that has had previous contact with TB the white blood cells have become sensitised to those antigens and they will release interferon-gamma as part of an immune response. If interferon-gamma is released from the white blood cells then this is considered a positive result.
The IGRA test is used in patients that do not have features of active TB but do have a positive Mantoux test to confirm a diagnosis of latent TB.
what would xrays show at different stages of TB?
Primary TB may show patchy consolidation, pleural effusions and hilar lymphadenopathy
Reactivated TB may show patchy or nodular consolidation with cavitation (gas filled spaces in the lungs) typically in the upper zones
Disseminated Miliary TB give a picture of “millet seeds” uniformly distributed throughout the lung fields
TIP: Disseminated miliary TB gives quite a characteristic appearance on a chest xray. This makes it a popular spot diagnosis in exams so it is worth looking at some pictures and remembering this.
should cultures be done for TB?
Performing a bacterial culture and collecting a sample of the bacteria is very useful prior to starting treatment. This allows testing the bacteria for resistance to antibiotics. Unfortunately cultures can take several months to grown an organism. Treatment is usually started whilst waiting for the culture results.
There are several ways to collect cultures:
Sputum. 3 samples should be collected and tested. If they are not producing sputum then hypertonic saline can be used to induce sputum that can be collected. They might require bronchoscopy with lavage to collect sputum samples.
Mycobacterium blood cultures. These require special blood culture bottle.
Lymph node aspiration or biopsy
how is active TB managed?
initial phase - first 2 months (RIPE)
- rifampicin
- isoniazid
- pyrazinamide
- ethambutol
Continuation phase - next 4 months
Rifampicin
Isoniazid
how do you manage TB meningitis?
Patients with meningeal tuberculosis are treated for a prolonged period (at least 12 months) with the addition of steroids (dexamethasone)
how do you manage latent TB?
The treatment for latent tuberculosis is 3 months of isoniazid (with pyridoxine) and rifampicin OR 6 months of isoniazid (with pyridoxine)
Base the choice of regimen on the person’s clinical circumstances. Offer:
3 months of isoniazid (with pyridoxine) and rifampicin to people younger than 35 years if hepatotoxicity is a concern after an assessment of both liver function (including transaminase levels) and risk factors
6 months of isoniazid (with pyridoxine) if interactions with rifamycins are a concern, for example, in people with HIV or who have had a transplant.
who may require directly obsrived therapy when on TB treatmet?
Directly observed therapy with a three times a week dosing regimen may be
indicated in certain groups, including:
homeless people with active tuberculosis
patients who are likely to have poor concordance
all prisoners with active or latent tuberculosis
what are the side effects of TB treatments?
Rifampicin can cause red/orange discolouration of secretions like urine and tears. It is a potent inducer of cytochrome P450 enzymes therefore reduces the effect of drugs metabolised by this system. This is important for medications such as the contraceptive pill.
Isoniazid can cause peripheral neuropathy. Pyridoxine (vitamin B6) is usually co-prescribed prophylactically to reduce the risk of peripheral neuropathy.
Pyrazinamide can cause hyperuricaemia (high uric acid levels) resulting in gout.
Ethambutol can cause colour blindness and reduced visual acuity.
Rifampicin, isoniazid and pyrazinamide are all associated with hepatotoxicity
TIP: A common exam question starts with “a patient has recently started treatment for tuberculosis. They noticed … Which medication is most likely to be implicated?” It is worth remembering the common side effects to help you answer these questions. They start feeling numbness or unusual sensations in their fingertips or feet: isoniazide (“I’m-so-numb-azid”). They noticed difficulty recognising colours: ethambutol (“eye-thambutol”). They noticed their urine or tears are orange or red: rifampicin (“red-an-orange-pissin’”).
how do you perform a gram stain?
A gram stain is used as a quick way to check a sample under the microscope to look for bacteria. It involves two main steps:
Add a crystal violet stain which binds to molecules in the thick peptidoglycan cell wall in gram positive bacteria turning them violet.
Then add a counterstain (such as safranin) which binds to the cell membrane in bacteria that don’t have a cell wall (gram negative bacteria) turning them red/pink.
whar are gram positive cocci?
stahylococcus
streptococcus
enterococcus
what are gram positive rods?
Use the mnemonic “corney Mike’s list of basic cars”:
Corney – Corneybacteria Mike’s – Mycobacteria List of – Listeria Basic – Bacillus Cars – Nocardia
what are gram positive anaerobes?
Use the mnemonic “CLAP”:
C – Clostridium
L – Lactobacillus
A – Actinomyces
P – Propionibacterium
what are gram negative bacteria?
Neisseria meningitis Neisseria gonorrhoea Haemophilia influenza E. coli Klebsiella Pseudomonas aeruginosa Moraxella catarrhalis
what are atypical bacteria ?
The definition of atypical bacteria is that they cannot be cultured in the normal way or detected using a gram stain. Atypical bacteria are most often implicated in pneumonia.
The atypical bacteria that cause atypical pneumonia can be remembered using the mnemonic “legions of psittaci MCQs”:
Legions – Legionella pneumophila Psittaci – Chlamydia psittaci M – Mycoplasma pneumoniae C – Chlamydydophila pneumoniae Qs – Q fever (coxiella burneti)
what is MRSA?
MRSA refers to staphylococcus aureus bacteria that have become resistant to beta-lactam antibiotics such as penicillins, cephalosporins and carbapenems
whar are ESBLs?
ESBLs are bacteria that have developed resistance to beta-lactam antibiotics. They produce beta lactamase enzymes that destroy the beta-lactam ring on the antibiotic. They can be resistant to a very broad range of antibiotics.
ESBLs tend to be e. coli or klebsiella and typically cause urinary tract infections but can also cause other infections such as pneumonia.
They are usually sensitive to carbapenems such as meropenem or imipenem.
what antibiotics inhibit cell wall synthesis?
Antibiotics with a beta-lactam ring
Penicillin
Carbapenems such as meropenem
Cephalosporins
Antibiotics without a beta-lactam ring
Vancomycin
Teicoplanin
what antibiotics inhibit folic acid metabolism?
Bacteria produce their own folic acid in a series of steps. This chain starts with para-aminobenzoic acid (PABA), which is directly absorbed in to the cell across the cell membrane. PABA is then converted to dihydrofolic acid (DHFA), then tetrahydrofolic acid (THFA) and finally folic acid.
Antibiotics can be used to disrupt steps along this chain:
Sulfamethoxazole blocks the conversion of PABA to DHFA
Trimethoprim blocks the conversion of DHFA to THFA
Co-trimoxazole is a combination of sulfamethoxazole and trimethoprim
what kind of bacteria does metronidazole work on?
The reduction of metronidazole into its active form only occurs in anaerobic cells. When partially reduced metronidazole inhibits nucleic acid synthesis. This is why metronidazole is effective against anaerobes and not aerobes.
what antibiotics inhibit protein synthesis by targeting the ribosome?
Macrolides such as erythromycin, clarithromycin and azithromycin Clindamycin Tetracyclines such as doxycycline Gentamicin Chloramphenicol
what is sepsis and septic shock?
sepsis is a condition where the body launches a large immune response to an infection that causes systemic inflammation and affects the functioning organs of the body
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
what is the pathophysiology of sepsis?
The bacteria or other pathogens are recognised by macrophages, lymphocytes and mast cells. These cells release vast amounts of cytokines like interleukins and tumor necrosis factor to alert the immune system of an invader. These cytokines activate other parts of the immune system. This immune activation leads to further release of chemicals such as nitrous oxide that causes vasodilation. This full immune response causes inflammation throughout the body.
Many of these cytokines cause the endothelial lining of blood vessels to become more permeable. This causes fluid to leak out of the blood and in to the extracellular space leading to oedema and a reduction in intravascular volume. The oedema around blood vessels creates a space between the blood and the tissues reducing the amount of oxygen that reaches the tissues.
Activation of the coagulation system leads to deposition of fibrin throughout the circulation further compromising organ and tissue perfusion. It also leads to consumption of platelets and clotting factors as they are being used up to form the clots within the circulatory system. This leads to thrombocytopenia, haemorrhages and an inability to form clots and stop bleeding. This is called disseminated intravascular coagulopathy (DIC).
Blood lactate rises due to hypoperfusion of tissues that starves the tissues of oxygen causing them to switch to anaerobic respiration. A waste product of anaerobic respiration is lactate.
what are the risk factors for sepsis?
Any condition that impacts the immune system or makes the patient more frail or prone to infection is a risk factor for developing sepsis:
- Very young or old patients (under 1 or over 75 years)
- Chronic conditions such as COPD and diabetes
- Chemotherapy, immunosuppressants or steroids
- Surgery or recent trauma or burns
- Pregnancy or peripartum
- Indwelling medical devices such as catheters or central lines
what score is used to pick up the signs of sepsis?
The National Early Warning Score (NEWS) is used in the UK to pick up the signs of sepsis. This involves checking physical observations and their consciousness level:
Temperature Heart rate Respiratory rate Oxygen saturations Blood pressure Consciousness level
how does sepsis present?
high temp
heart rate increase
increased resp rate
oxygen sats
BP
Signs of potential sources such as cellulitis, discharge from a wound, cough or dysuria
Non-blanching rash can indicate meningococcal septicaemia
Reduced urine output
Mottled skin
Cyanosis
Arrhythmias such as new onset atrial fibrillation
what is usually the first sign of sepsis?
tachypnoea
how do elderly patients with sepsis usually present?
Elderly patients often present with confusion or drowsiness or simply “off legs”
why do you have to be careful with neutropenic or immuocompromised people when thinking about sepsis?
Neutropenic or immunosuppressed patients may have normal observations and temperature despite being life threatening unwell
what investigations would you perform for sepsis?
Arrange blood tests for patients with suspected sepsis:
Full blood count to assess cell count including white cells and neutrophils
U&Es to assess kidney function and for acute kidney injury
LFTs to assess liver function and for possible source of infection
CRP to assess inflammation
Clotting to assess for disseminated intravascular coagulopathy (DIC)
Blood cultures to assess for bacteraemia
Blood gas to assess lactate, pH and glucose
Additional investigations can be helpful in locating the source of the infection:
Urine dipstick and culture
Chest xray
CT scan if intra-abdominal infection or abscess is suspected
Lumbar puncture for meningitis or encephalitis
what score is used to identify patients at heightened risk of mortality related to sepsis?
quickSOFA - if outside of ICU
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
Within an ICU setting a full SOFA score is often used
»> 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.
what are the red and amber flat criteria for sepsis?
RED FLAG
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
AMBER
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
if there are any red flag signs for sepsis what should be started straight away?
‘sepsis six’ should be started straight away:
- Administer oxygen: Aim to keep saturations > 94% (88-92% if at risk of CO2 retention e.g. COPD)
- Take blood cultures
- Give broad spectrum antibiotics
- Give intravenous fluid challenges: NICE recommend a bolus of 500ml crystalloid over less than 15 minutes
- Measure serum lactate
- Measure accurate hourly urine output
what is neutropenic sepsis?
neutropenic sepsis isa very important medical emergency. It is sepsis in a patient with a low neutrophle count less than 1 x 10^9/L
Have a low threshold for suspecting neutropenic sepsis in patients taking immunosuppressants or medications that may cause neutropenia. Treat any temperature above 38C as neutropenic sepsis in these patients until proven otherwise. They are at high risk of death from sepsis as their immune system cannot adequately fight the infection. They need emergency admission and careful management.
Each local hospital will have a neutropenic sepsis policy. Treatment is with immediate broad spectrum antibiotics such as piperacillin with tazobactam (tazocin). The other aspects of management are essentially the same as for sepsis however extra precaution needs to be taken. Time is precious so don’t delay antibiotics while waiting for investigation results.
what drugs may cause neutropenia?
Anti-cancer chemotherapy
Clozapine (schizophrenia)
Hydroxychloroquine (rheumatoid arthritis)
Methotrexate (rheumatoid arthritis)
Sulfasalazine (rheumatoid arthritis)
Carbimazole (hyperthyroidism)
Quinine (malaria)
Infliximab (monoclonal antibody use for immunosuppression)
Rituximab (monoclonal antibody use for immunosuppression)
what is influenza?
The influenza virus is an RNA virus. There are three types: A, B and C, of which A and B are the most common. The A type has different H and N subtypes and you may hear about different strains, for example H1N1 (swine flu) and H5N1 (avian flu). Outbreaks typically occur during the winter.
who is the influenza vaccine offered to?
those at higher risk of developig flu: aged over 65 young children pregnant woman chronic health conditions such as asthma, COPD, heart failure and diabetes healthare workers and carers
how does the flu present ?
fever coryzal symptoms lethargy and fatigue anorexia muscle and joint aches headache dry cough sore throuat
how is the flu usually diagnosed?
usually treatment is started based on hisotry, risk factors and clinical presentation however viral nasal or throat swabs can be sent to lab for PCR analysis
how should you manage the flu?
Health patients not at risk of complications just need fluids and rest
those at risk of complications can have medications
- oral oseltamivir 75mg twice a day for 5 days
or
- inhaled zanamivir 10 mg twice daily for 5 days
however these tretaments must be started withing 48 h hours of onset of symptoms to be effective
Post-exposure prophylaxis can be given to higher risk patients such as those with chronic diseases or immunosuppression within 48 hours of close contact with influenza. This aims to minimise the risk of developing flu and complications.
Oral oseltamivir 75mg once daily for 10 days
Inhaled zanamivir 10mg once daily for 10 days
whatr are the complications of influnza?
Otitis media, sinusitis and bronchitis Viral pneumonia Secondary bacteria pneumonia Worsening of chronic health conditions such as COPD and heart failure Febrile convulsions (young children) Encephalitis
how is influeza spread?
droplets
what is the incubation period of influenza?
1-4 days
how long is influeza infective for?
1 day before symptoms start and 7 days after
what are the basics of HIV?
HIV is an RNA retrovirus. HIV-1 is most common type. HIV-2 is rare outside West Africa. The virus enters and destroys the CD4 T helper cells. An initial seroconversion flu like illness occurs within a few weeks of infection. The infection is then asymptomatic until it progresses and the patient becomes immunocompromised and develops AIDS defining illnesses and opportunistic infections potentially years later
how is HIV spread?
unprotected anal, vaginal or oral sexual activity
mother to child at any stage of pregnancy, birth or breast feeding - vertical transmission
mucous membrane, blood or open wound exposure to infected blood or bodily fluids such as sharing needles, needle stick injuries or blood splashed in the eye
whar are some AIDs defining illnesses?
There is a long list of AIDS defining illnesses associated with end stage HIV infection where the CD4 count has dropped to a level that allows for unusual opportunistic infections and malignancies to appear. Some examples are:
Kaposi’s sarcoma Pneumocystis jirovecii pneumonia (PCP) Cytomegalovirus infection Candidiasis (oesophageal or bronchial) Lymphomas Tuberculosis
what are the different tests for HIV?
Antibody blood test. This is the typical test used in hospitals to screen for HIV. There is an option for patients to self sample by requesting a kit online and posting a sample of their blood to get tested for the antibody.
PCR testing for the p24 antigen tests directly for this HIV antigen in the blood and can be positive before the antibody test.
PCR testing for the HIV RNA levels tests directly for the quantity of the HIV virus in the blood and gives a viral load.
how is HIV monitored?
CD4 count
This is a count of the number of CD4 cells in the blood. These are the cells destroyed by the HIV virus. The lower the count the higher the risk of opportunistic infection.
500-1200 cells/mm3 is the normal range
Under 200 cells/mm3 is considered end stage HIV / AIDS and puts the patient at high risk of opportunistic infections
Viral Load (VL) Viral load is the number of copies of HIV RNA per ml of blood. “Undetectable” refers to a viral load below the labs recordable range (usually 50 – 100 copies/ml). The viral load can be in the hundreds of thousands in untreated HIV.
how is HIV managed?
a combination of antiretroviral therapy (ART) medications.
Some regimes involve only a single combination tablet once per day that has the potential to completely suppress the infection.
Specialist blood tests can establish the resistance of each HIV strain to different medications to help tailor treatment.
BHIVA guidelines (2015) recommend a starting regime of 2 NRTIs (e.g. tenofovir and emtricitabine) plus a third agent.
The aim of treatment is to achieve a normal CD4 count and undetectable viral load. As a general rule when a patient has normal CD4 and undetectable VL on ART treat their physical health problems (e.g. routine chest infections) as you would an HIV -ve patient. When prescribing be aware and check interactions any medication might have with the HIV therapy.
Highly Active Anti-Retrovirus Therapy (HAART) Medication Classes
Protease Inhibitors (PIs)
Integrase Inhibitors (IIs)
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Entry Inhibitors (EIs)
Prophylactic co-trimoxazole (Septrin) is given to patients with CD4 < 200/mm3 to protect against pneumocystis jirovecii pneumonia (PCP).
HIV infection increases the risk of developing cardiovascular disease. Patients with HIV have close monitoring of cardiovascular risk factors and blood lipids and appropriate treatment (such as statins) to reduce their risk of developing cardiovascular disease.
Yearly cervical smears are required for women. HIV predisposes to developing cervical human papillomavirus (HPV) infection and cervical cancer so female patients need close monitoring to ensure early detection of these complications.
Vaccinations should be up to date including annual influenza, pneumococcal (every 5-10 years), hepatitis A and B, tetanus, diphtheria and polio. Patients should avoid live vaccines.
what are examples of enrtry inhibitors?
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
what are examples of 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
what are examles of Non-nucleoside reverse transcriptase inhibitors (NNRTI)?
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
examples: nevirapine, efavirenz
side-effects: P450 enzyme interaction (nevirapine induces), rashes
what are examples of Protease inhibitors (PI)?
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
what are examples of integrase inhibitors?
Integrase inhibitors
examples: raltegravir, elvitegravir, dolutegravir
what are the focal neurological complications of HIV?
toxoplasmosis
Primary CNS lymhoma
tuberculosis
what are the features of toxoplasmosis and how is it managed?
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: sulfadiazine and pyrimethamine
what are the features of primary CNS lymhoma and what is the management?
Primary CNS lymphoma
accounts for around 30% of cerebral lesions
associated with the Epstein-Barr virus
CT: single or multiple homogenous enhancing lesions
treatment generally 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
how can you differentiate between toxoplasmosis and primary CNS lymphoma is HIV patients?
Differentiating between toxoplasmosis and lymphoma is a common clinical scenario in HIV patients. It is clearly important given the vastly different treatment strategies.
TOXOPLASMOSIS
Multiple lesions
Ring or nodular enhancement
Thallium SPECT negative
LYMPHOMA
Single lesion
Solid (homogenous) enhancement
Thallium SPECT positive
what are the generalised neuro complications of HIV?
Encephalitis
may be due to CMV or HIV itself
HSV encephalitis but is relatively rare in the context of HIV
CT: oedematous brain
Cryptococcus
most common fungal infection of CNS
headache, fever, malaise, nausea/vomiting, seizures, focal neurological deficit
CSF: high opening pressure, India ink test positive
CT: meningeal enhancement, cerebral oedema
meningitis is typical presentation but may occasionally cause a space occupying lesion
Progressive multifocal leukoencephalopathy (PML)
widespread demyelination
due to infection of oligodendrocytes by JC virus (a polyoma DNA virus)
symptoms, subacute onset : behavioural changes, speech, motor, visual impairment
CT: single or multiple lesions, no mass effect, don’t usually enhance. MRI is better - high-signal demyelinating white matter lesions are seen
AIDS dementia complex
caused by HIV virus itself
symptoms: behavioural changes, motor impairment
CT: cortical and subcortical atrophy
what opportunistic infections can occur with a CD4 count of 200-500 cell/mm^3?
Oral thrush Secondary to Candida albicans
Shingles Secondary to herpes zoster
Hairy leukoplakia Secondary to EBV
Kaposi sarcoma Secondary to HHV-8
what opportunistic infections can occur with a CD4 count of 100-200 cell/mm^3?
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
Cerebral toxoplasmosis
Progressive multifocal leukoencephalopathy- Secondary to the JC virus
Pneumocystis jirovecii pneumonia
HIV dementia
what opportunistic infections can occur with a CD4 count of 50-100 cell/mm^3?
Aspergillosis Secondary to Aspergillus fumigatus
Oesophageal candidiasis Secondary to Candida albicans
Cryptococcal meningitis
Primary CNS lymphoma Secondary to EBV
what opportunistic infections can occur with a CD4 count of <50 cell/mm^3?
Cytomegalovirus retinitis Affects around 30-40% of patients with CD4 < 50 cells/mm³
Mycobacterium avium-intracellulare infection
what is Kaposi’s sarcoma?
caused by HHV-8 (human herpes virus 8)
presents as 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
radiotherapy + resection
what is Pneumocystis jiroveci pneumonia?
Whilst the organism Pneumocystis carinii is now referred to as Pneumocystis jiroveci, the term Pneumocystis carinii pneumonia (PCP) is still in common use
Pneumocystis jiroveci is an unicellular eukaryote, generally classified as a fungus but some authorities consider it a protozoa
PCP is the most common opportunistic infection in AIDS
all patients with a CD4 count < 200/mm³ should receive PCP prophylaxis
Features dyspnoea dry cough fever very few chest signs
Pneumothorax is a common complication of PCP.
Extrapulmonary manifestations are rare (1-2% of cases), may cause
hepatosplenomegaly
lymphadenopathy
choroid lesions
Investigation
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)
Management
co-trimoxazole
IV pentamidine in severe cases
aerosolized pentamidine is an alternative treatment for Pneumocystis jiroveci pneumonia but is less effective with a risk of pneumothorax
steroids if hypoxic (if pO2 < 9.3kPa then steroids reduce risk of respiratory failure by 50% and death by a third)
what is the post-exposure prophylaxis for HIV?
Post exposure prophylaxis can be used after exposure to HIV to reduce the risk of transmission. It is not 100% effective and must be commenced within a short period (less than 72 hours). The sooner it is started the better. A risk assessment about the probability of developing HIV should be balanced against the side effects of post exposure prophylaxis.
It involves a combination of ART therapy. The current regime is Truvada (emtricitabine / tenofovir) and raltegravir for 28 days.
HIV tests should be done initially but also a minimum of 3 months after exposure to confirm a negative status. Individuals should abstain from unprotected activity for a minimum of 3 months until confirmed negative.
what is HSV?
herpes simplex virus
there are two main strains HSV1 and HSV2. It was previously thought that HSV1 was oral and HSV2 was genital but not thought that they overlap.
less commonly primary or recurrent HSV infections may also present at other sites with neurological, ocular, hepatic or respiratory complications
what are the symptoms of herpes?
- dysuria in woman
- lymphadenopathy
- genital ulcer
- oral ulcer
- they may have tingling sensation
- primary infection may present with severe gingivostmatitis
what are the risk factors for herpes?
HIV infection
immunosupressive medicaions
high risk sexual behaviour
what investigations would you perform for hepres?
- viral culture (when lesions are present)
- HSV PCR
- glycoprotein G-based type specific serology (gG! and gG2)
what are some differential diagnosis for herpes?
symphilis chancroid contact dermatitis rheumatological fisease crohns/UC scabies fixed drug erruption squamous cell carcinome shingles
how do you manage herpes?
if they have gingivostomatitis - oral aciclovir, chlorhexidine mouthwash
genital herpes - oral aciclovir, valaciclovir or famiciclovir plus symptomatic treatment (paracetamol, ibuprofen or lidocaine topical)
for oral herpes - oral aciclovir, valaciclovir or famciclovir plus symptomatic treatment
if pregnant give antiviral prophylaxsis at 36 weeks
what are the features of HSV encephalitis?
fever, headache, psychiatric symptoms, seizures, vomiting
focal features - aphasia
peripheral lesions (cold sores) have no relation to the resence of HSV encephalitis
*typically affects the temporal and inferior frontal lobes
what investigations would you perform for HSV encephalitis?
CSF - lymphocytosis, elevated protein
PCR for HSV
CT - medial temporal and inferior frontal changes (e.g. haemorrhages)
MRI
EEG - lateralised periodic discharges at 2 Hz
how is HSV encephalitis managed?
IV aciclovir
what is syphilis?
syphilis is an STI caused by spirochaete treponema pallidum characterised by primary, secondary and tertiary stages
what is the incubation period of syphilis ?
9-90 days
what are the primary features of syphilis?
chancre - painless ulcer at the site of sexual contact
local non-tender lymphadenopathy
(often not seen in woman as the lesion may be on the cervix )
what are secondary features of syphilis?
they occur 6-10 weeks after primary infection
- systemic symptoms - fevers, lymphadenopathy
- rash on trunk, palms and soles
- buccal snail track ulcers
- condylomata lata (painless warty lesions of the genitalia)
what are the tertiary features of syphilis?
Tertiary features gummas (granulomatous lesions of the skin and bones) ascending aortic aneurysms general paralysis of the insane tabes dorsalis Argyll-Robertson pupil
what are the congenital features of syphilis?
Features of congenital syphilis
blunted upper incisor teeth (Hutchinson’s teeth), ‘mulberry’ molars
rhagades (linear scars at the angle of the mouth)
keratitis
saber shins
saddle nose
deafness
what are the investigations for syphilis?
- serum venereal disease research laboratory (VDRL) test - is positive but will become negative after treatment (it is a cardiolipin test)
- serum treponema pallidum haemagglutination (TPHA) test - this will be postive but will remain positive after treatment
other options
- dark field microscopy of swab from lesion - will show coiled spirochaete bacterium with a corkscrew apprearance and motility
- serum treponemal enzyme immunoassay will be positive
- serum TPPA will be positive
what may cause a false positive cardiolipin test (TPHA) for syphilis?
pregnancy SLE anti-phospholidpid syndrome TB leprosy malaria HIV
how is syphilis managed?
IM benzylpenicillin - 1.8g IM single dose if allergic to penicillin alternative is doxycyclne
the Jarisch-Herxheimer reaction is sometimes seen following treatment
fever, rash, tachycardia after the first dose of antibiotic
in contrast to anaphylaxis, there is no wheeze or hypotension
it is thought to be due to the release of endotoxins following bacterial death and typically occurs within a few hours of treatment
No treatment is needed other than antipyretics if required
