Week 7 - Microbiology and Infection 2 Flashcards
How is clostridium difficile infection treated?
- Stop precipitating antibiotics broad spectrum
- Oral metronidazole (mild - 0 severity markers), oral vancomycin (severe >1 severity markers or no improvement after 5 days metronidazole)
- Refractory recurrent disease may require faecal transplant
List the defining symptoms of systemic inflammatory response syndrome (SIRS)
Sweats, chills, rigors, malaise, tachypnoea RR>20/minute, tachycardia >90bpm, hypotension (patients may appear well perfused despite hypotension)
How is drug-resistance testing used in HIV?
Drug-resistance testing identifies which, if any, HIV medicines won’t be effective against a persons HIV - helps to determine which HIV medicines to include in an HIV treatment regimen
How can MDR-TB be diagnosed?
May be detected rapidly using molecular testing - gene Xpert
What causes HIV brain disease?
- Consequence of unrecognised/untreated infection and marked immunodeficiency (opportunistic infections) or lifestyle
- Encephalitis (ARVs)
- Dementia
- Neuro-syphilis (secondary or tertiary)
- Opportunistic
- Tuberculosis, cryptococcus, toxoplasmosis
- JCV (John Cunningham virus) - progressive multi-focal leuco-encephalopathy
What is point of care testing? How is it used in diagnosis of viral infections?
Cobas Liat system
- ‘Lab in a tube’
- Test for flu A, B and RSV using gargle from patient
- Takes 20 minutes
- Used on wards
When is a lumbar puncture contraindicated?
Brain shift
Rapid GCS reduction
Respiratory/cardiac compromise
Severe sepsis
Rapidly evolving rash
Infection at LP site
Coagulopathy (including INR >1.5, platelets <40, DOAC, therapeutic LMWH)
What complications can arise as a result of norovirus infection?
- Significant proportion of childhood hospitalisation - usually due to dehydration
- Illness in hospital outbreaks lasts longer with an increased risk of mortality (underling illness)
- In elderly increased post-infection complications
- Chronic diarrhoea and virus shedding in both solid organ transplant patients and bone marrow transplant patients
- Shedding for up to 2 years - can still infect others
Which patient groups are most likely to present with pulmonary TB?
- Typical main group who present with TB currently in Glasgow
- Likely have acquired infection as a child in the 1940s and 50s when TB was more common
- Only 10% of those infected go on to show clinical disease, can remain dormant and only be active due to reduced immunity due to age and alcohol ingestion
- Patients who grew up or visit areas of the world where TB is prevalent - most places in the developing world
- Rare in people on holiday, more significant in those staying for prolonged periods e.g. with friends and family
- Strong association between pulmonary TB and infection with HIV - test for HIV in all those infected with TB
Why is under 5 mortality important statistically?
Under 5 mortality rate is a good indicator of health of a population - shows changes rapidly (acute index)
List the most common sites of infections in febrile neutropaenic patients with haematological malignancy
- Bloodstream
- Mouth and pharynx - mucositis, ulceration of oesophagus
- Skin and soft tissues - axilla, perianal area
- Respiratory tract
- Gastrointestinal tract
- Urinary tract
- Other sites
What are the doctor/patient barriers to HIV testing?
- Patient barriers
- May not think they are at risk
- Worried regarding confidentiality, stigma, immigration issues
- Don’t have to inform GP but may compromise care of patient if not
- Employment issues, may fear they will lose their job especially if healthcare worker
- Doesn’t prevent you from doing any jobs - even surgery (have to be on treatment and prove HIV is well controlled)
- Can’t travel to some countries (may effect occupation) - may have to hide diagnosis
- Criminalisation issues
- Criminalisation of transmission
- Insurance
- Doesn’t stop you from getting mortgage, life insurance etc. (have to prove you’re on treatment and well controlled)
- Doctor barriers
- May not think of testing or be aware of clinical indications for testing
- May assume patient is not at risk
- Fear of embarrassing or offending patient especially if taking sexual history
- Lack of time
- Perceived lack of counselling skills
- Logistic issues to get result back to patient
Define fever
Pyrexia temperature >38 or hypothermia <36 OR >37.5 on 2 occasions 30 minutes apart
How should an unwell child be clinically assessed?
Take a good history:
- Fever - durations and measurement
- Assessment of severity
- Localising symptoms
- Causation
Is the patient well/unwell?
Should I be acting now or do I have time to observe?
- Infant:
- Severity indicated by:
- Feeding/vomiting
- How much are they feeding? How often? How does this compare to normal intake?
- Crying
- Sleeping
- Do they have to be woken to feed? Are they lethargic?
- Smiling
- Localising symptoms - difficult due to lack of communication
- Diarrhoea not always relevant in young babies - can just be systemic response to infection
- Causation - e.g. sick contacts (likely to have contracted from close family)
- Feeding/vomiting
- Severity indicated by:
- Child:
- Severity indicated by
- Feeding
- Activity levels
- Drowsiness
- Localising symptoms
- Cough, coryza (nasal inflammation), vomiting, diarrhoea, rash, dysuria, headache, sore ears/throat
- Causation - nursery contacts etc.
- Severity indicated by
Which viruses causing gastroenteritis affect which specific populations?
Norovirus/sapovirus (calciviridae) - can affect all ages and healthy individuals but often most serious in young and elderly
Rotavirus/adenovirus/astrovirus - affects mainly children under 2 years, elderly and immunocompromised
Describe the outbreak of SARS-CoV
- Emerged in China in 2002
- Source - bats, civet cats
- May 2003 - 29 countries reported SARS-CoV cases to WHO, 8,096 people infected, fatality rate 9.5%
- Contained in 2003 (human chain of transmission broken)
- 3 cases of accidental release by labs which had stored strains in 2004
- No new cases reported since 2004
How is cryptococcal meningitis treated?
- Treatment - antifungals
- Amphotericin B and flucytosine
- Fluconazole
- Paradoxical worsening with ARVs in HIV
Which pathogens most commonly cause lower respiratory tract infections in
a) Neonates
b) Young infants
c) Infants and young children
d) Older children
a) Neonates
- Group B streptococcus (usually an innocuous benign group in healthy adults)
- E coli
- Respiratory viruses
- Enteroviruses
b) Young infants - still some maternal Ig so protected from bacterial pathogens (half life 6 weeks - 3 months)
- Respiratory viruses
- Enteroviruses
- Chlamydia
c) Infants and young children
- Streptococcus pneumonia
- Respiratory viruses
d) Older children
- Mycoplasma pneumonia
- Streptococcus pneumonia
- Respiratory viruses
Describe the features of the common cold
- Usually self diagnosed
- Onset 1-3 days after innoculation
- Symptoms
- Sore ‘scratchy’ throat
- Rhinorrhoea
- Nasal obstruction
- Persists for approx. 1 week
Describe high risk and low risk neutropaenia
Low risk neutropaenia = <0.5 x 109/L for <7 days with no organ failure/comorbidities
High risk neutropaenia = <0.1 x 109/L for >7 days
List the neurological HIV indicator conditions
- AIDS defining conditions
- Cerebral toxoplasmosis
- Primary cerebral lymphoma
- Cryptococcal meningitis
- Progressive multifocal leucoencephalopathy
- Other conditions where HIV testing should be offered
- Aseptic meningitis/encephalitis
- Cerebral abscess
- Space occupying lesion of unknown cause
- Guillain-Barre syndrome
- Transverse myelitis
- Peripheral neuropathy
- Dementia
- Leucoencephalopathy
How is scabies diagnosed and treated?
- Diagnosis made on clinical appearance
- Treatment
- Permethrin 5% OR malathion 0.5%
- Wash off after 24 hours
- Wash contaminated clothes at 50 degrees
- Permethrin 5% OR malathion 0.5%
List the investigations which should be undertaken in suspected meningitis
- History and exam
- Anyone presenting with a headache - look at their throat, check lymph nodes
- Young people with group A strep can present with headache and neck pain (swelling of lymph nodes)
- If they have signs of infection in the throat (e.g. white spots) - can rule out meningitis
- Blood cultures (can do blood PCR for pneumococcus/meningococcus)
- Throat culture, viral gargle
- FBC, Ues, LFTs, CRP
- Lumbar puncture - most important investigation, examination of CSF
- Cell count, gram stain, culture and PCR
- Protein and glucose
- Viral PCR
What type of bacteria are helicobacter pylori?
Gram -ve spiral shaped bacilli
Microaerophilic, urease-positive
Describe the physical barriers which contribute to the immune response
- Principal barriers against microbial invasion
- Skin
- Conjunctivae
- Mucous membranes
- Gut
- Respiratory tract
- GU tract
- Constantly in contact with the environment
- Skin features
- Desquamates
- Dry
- pH = 5-6
- Temperature - 5 degrees lower
- Secretory IgA in sweat
How can the transmission of vibrio cholerae be controlled?
Clean drinking water supply and proper sanitation are key preventative measures
What complications can occur as a result of the common cold?
- Otitis media in 30% of children
- Sinusitis
- Severe infections in suceptible groups
- Elderly
- Immunocompromised
- Asthma, COPD, CF
How is mycoplasma genitalium treated?
- Treatment not indicated unless symptoms or partner has symptoms
- Treatment depends on antibitoic resistance (high levels of resistance)
How is active TB treated?
Four drug treatment:
- Rifampicin 6 months
- Isoniazid 6 months
- Ethambutol 2 months
- Pyrazinamide 2 months
Describe the structure of HIV
- Roughly spherical, with a diameter of about 120nm, around 60 times smaller than a RBC but large for a virus
- 2 copies of positive single-stranded RNA that codes for the virus’s nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein
- RNA tightly bound to nucleocapsid proteins, p7 and enzymes needed for the development of the virion such as reverse transcriptase, proteases, ribonuclease and integrase
- Matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of the virion particle
Describe the pathogenesis of enteropathogenic E. coli
Initial adherence via pili, followed by formation of characteristic attaching and effacing lesion mediated by intimin protein and Tir (translocation intimin receptor) with disruption of intestinal microvilli
Describe the epidemiology of clostridium difficile infection
Predominantly affects the elderly
Major cause of healthcare associated infections
How do influenza pandemics occur?
- ANTIGENIC SHIFT - segmented genome
- Avian flu and human flu infect same cell, both replicate, progeny can be mixture of genetic segments –> new virus = reassortment virus
- Pigs are ideal host for antigenic shift of flu
- Avian flu requires alpha 2,3 salicylic acid receptor
- Human flu requires alpha 2,6 salicylic acid receptor (in upper respiratory tract)
- Pigs have a mixture of alpha 2,3 and 2,6 salicylic acid receptors in their upper respiratory tract, can easily be infected with both
How long is the incubation period of shigella? How long does the infection last?
Incubation 1-3 days
Duration 2-7 days
How should pathogens be identified in prosthetic joint infections?
- What microbiology grow relates directly to what is sent to the lab
- Tissue or pus or fluid is always preferable to a surface swab
- Diagnosis of a prosthetic joint infection depends on macroscopic appearance, histopathology and microbiology
- Watch out for contaminants - can happen at any time in the sample collection/lab processing
- Need 5 samples aseptically taken from different locations to give sensitivity and specificity
Describe cell mediated immunity
- T cells mediate three principal functions - help, suppression and cytotoxicity
- T-helper cells stimulate the immune response of other cells (i.e. T cells stimulate B cells to produce antibodies)
- T-suppressor cells play an inhibitory role and control the level and quality of the immune response
- Cytotoxic T cells recognise and destroy infected cells and activate phagocytes to destroy pathogens they have taken up
What are the signs/symptoms of pharyngeal chlamydia?
Usually asymptomatic
Describe the prevalence of chronic granulomatous disease
Commonest of rare inherited disorders - 1/200,000
X-linked most common
How is influenza treated?
Neuraminidase Inhibitors:
- Dosage in adults for treatment of uncomplicated influenza
- Oseltamivir 75mg PO twice daily for 5 days
- Zanamivir 10mg INH twice daily for 5 days
- Can give IV if multi-organ failure
- Can be used for prophylaxis if given within 48 hours of exposure
What is the main cause of bronchiolitis?
- Respiratory syncytial virus (RSV) is main cause of bronchiolitis
- 35 million cases/year
- Common in children <2y/o
- One of the main causes of nosocomial infection
Describe the pharmacological treatment of HIV
- Highly active antiretroviral therapy
- Usually ‘triple therapy’
- 2 nucleoside reverse transcriptase inhibitors + 1 drug from another class
- Combination pills available - only need to take 1 per day
- Guided by patient choice/comorbidities/interactions/drug resistance
Classes of ARVs:
- Nucleoside reverse transcriptase inhibitors
- Non-nucleoside reverse transcriptase inhibitors
- Integrase inhibitors - few drug interactions/side effects
- Protease inhibitors
- Other e.g. CCR5 entry inhibitor
List the symptoms of vibrio cholerae infection
- Severe, profuse, non-bloody, watery diarrhoea (rice water stool)
- Profound fluid loss and dehydration precipitates hypokalaemia, metabolic acidosis, hypovolaemic shock and cardiac failure
- Untreated mortality 30-40%
Describe the surgical treatment options for prosthetic joint infections
- DAIR to leave the infected join in
- Debride, antibiotics, implant retained
- If prosthesis infection is acute (<30 days since insertion), then it is still mechanically functional and can be kept in but infected tissues should be debrided and the joint washed out to reduce the burden of infection then IV antibiotics started for 4-6 weeks
- Before 30 days - biofilm unlikely to have developed
2.Take the infected joint out
- If the infection occurs over 30 days since surgery (biofilm likely to have developed) then it may no longer be fully functional and may need removed
- Removal involves taking out the prosthesis and all cement (can’t heal if foreign body retained)
- Options
- Girdlestone procedure - joint fused, very limited movement
- One stage revision - put a new prosthetic in during the same operation as removing the infected one
- Two stage revision - delay putting in a new one until treated the existing infection for 4-6 weeks
What were the initial causes of HIV thought to be?
- All male, all homosexual
- Related to sexual activity?
- CMV related?
- Drug use?
- Environmental? Sauna related?
What percentage of prosthetic joint infections develop from local spread of infection?
60-80%
How can local tumours impact immunity?
- Tumours may cause local organ dysfunction
- Obstruction leads to infection
- Lung is particularly susceptible
- CNS tumours/spinal cord compression –> loss of cough/swallow reflex, incomplete bladder emptying –> infection
How does HIV cause illness?
- HIV infects cells in the immune system such as T helper cells, macrophages and dendritic cells
- All these cells carry CD4 receptors which allow HIV entry
- HIV infection causes depletion of CD4 helper cells by:
- Direct viral killing of cells
- Apoptosis of uninfected ‘bystander cells’
- CD8+ cytotoxic T cell killing of infected CD4+ cells
- Abnormal B cell activation resulting in excess/inappropriate immunoglobulin production
- Once CD4+ cells fall below a critical level (<200), the person is at risk of opportunistic infections and some cancers
How can Shigella be diagnosed in a clinical lab?
Use XLD plates
Describe empirical antibiotic treatment of patients with neutropaenic fever
- Patient is a stem cell transplant/solid organ transplant recipient or recieving chemotherapy for acute leukaemia
- Has sepsis, septic shock or NEWS >7
- Critical risk - first line IV meropenem, IV amoxicillin and IV vancomycin (if true penicillin/beta-lactam allergy IV amikacin, IV vancomycin and IV ciprofloxacin)
- Doesn’t have sepsis, septic shock or NEWS >7
- High risk - IV piperacillin/tazobactam, IV gentamicin and IV vancomycin (allergy - IV gentamicin, IV vancomycin and IV ciprofloxacin)
- Has sepsis, septic shock or NEWS >7
- Patient is not a stem cell transplant/solid organ transplant recipient or recieving chemotherapy for acute leukaemia
- Has sepsis, septic shock or NEWS >7
- High risk - IV piperacillin/tazobactam, IV gentamicin and IV vancomycin (allergy - IV gentamicin, IV vancomycin and IV ciprofloxacin)
- Doesn’t have sepsis, septic shock or NEWS >7
- Standard risk - IV piperacillin/tazobactam +/- IV vancomycin (allergy - IV gentamicin and IV vancomycin)
- Has sepsis, septic shock or NEWS >7
Describe the clinical features of rotavirus
- Incubation period 1-3 days
- Clinical manifestations depend on if it is the 1st infection or reinfection
- Symptoms of rotavirus
- Watery diarrhoea
- Abdominal pain
- Vomiting
- Loss of electrolytes leading to dehydration
- Symptoms usually last 3-7 days (longer than norovirus)
- 1st infection after age 3 months is usually the most severe
- Protected before age 3 months by maternal antibodies
- Hospital outbreaks in paediatric wards common
Describe the epidemiology of enterpathogenic E. coli
Sporadic cases and outbreaks of diarrhoea in infants and children
Cause of some cases of traveller’s diarrhoea
How does secondary syphilis present clinically?
- 3 months - 2 years post infection
- Occurs in 25% of patients
- Usually generalised rash affects palms and soles
- Muco-cutaneous lesions, condylomata lata/lymphadenopathy and fever
- Less commonly - patchy alopecia, anterior uvetitis, meningitis, cranial nerve palsies (blurred vision, hearing loss, tinnitus, vision loss - can be irreversible), hepatitis, splenomegaly, periostitis, arthritis and glomerulonephropathies
Why do seasonal flu epidemics occur?
- During replication of the virus mutations often occur in the Hemagglutinin and Neuraminidase protein-coding genes
- Mutations in the HA and NA genes cause structural changes to the HA and NA surface proteins - antibodies can no longer recognise the virus
- Gradual process - antigenic drift
- Seasonal epidemics occur when the antigenic drift has occurred to such an extent that the immune system struggles to fight the virus (approx. same length of time every year - epidemics in winter)
List the disease/therapies which suppress humoral immunity
- Bruton agammaglobulinaemia (commonest of rare primary disorders)
- Antibody production reduced in lymphoproliferative disorders
- CLL, multiple myeloma
- Usually preserved in acute leukaemia
- Intensive radiotherapy and chemotherapy will ultimately cause hypogammaglobulinaemia
Can you be vaccinated against norovirus?
NO - due to the incomplete understanding of immunity and the fact norovirus can’t be cultured there have been issues with creating a vaccine
What is the global impact of gastrointestinal infections?
- Major cause of morbidity and mortality
- Resource poor countries - 2 million deaths in children under 5 per year
- Developed world morbidity and economic loss
How does tertiary syphilis present clinically?
- Can take 8-15 years to develop - expect to see more in the future following the 2003 epidemic
- Neurosyphilis
- Many variations of neurological symptoms including cognitive
- Always think syphilis with neurological symptoms
- Cardiovascular syphilis
- Aortic valve disease, aortic aneurysm, aortitis
- Gummatous syphilis - skin/bony lesions
What are the complications of chlamydia?
- Women = pelvic inflammatory disease
- Pelvic pain/fever/dyspareunia
- 16% untreated women will develop PID (= complicated chlamydia)
- Tubal infertility (1-20% of PID cases)
- Many women worry about infertility in chlamydia - if they have uncomplicated chlamydia can reassure that infertility is not a risk
- Ectopic pregnancy
- Fitz-Hugh-Curtis syndrome (peri-hepatitis)
- Epididymo-orchitis
- Male infertility likely associated but insufficient evidence
Describe the tests which can be used in the diagnosis of TB
Mantoux Reaction:
- Determine if someone has been exposed to mycobacteria - doesn’t differentiate between active and latent disease, doesn’t distinguish from non-TB mycobacteria
- Tuberculin injected intradermally and read 48-72 hours later
- Those who have been exposed to the bacteria are expected to mount an immune response in the skin containing the bacterial proteins
- Reaction read by measuring the diameter of induration (palpable raised, hardened area) across the forearm in mm
- Erythema should not be measured
- Positive result depends on presence of risk factors e.g. 5mm positive in HIV+, 10mm positive in IVDUs, 15mm positive in those with no known risk factors for TB
Interferon gamma release assays
- Blood samples taken, exposure of blood lymphocytes to highly specific TB antigens
- Exposure causes lymphocytes (specifically CD4 and CD8 T cells) to produce interferon gamma, in the presence of TB infection
Describe the clinical features of listeria monocytogenes
- Median incubation period 3 weeks
- Duration of illness 1-2 weeks
- Initial flu-like illness, with or without diarrhoea
- Majority of cases present with severe systemic infection
- Septicaemia
- Meningitis
What type of bacteria are listeria monocytogenes?
Gram +ve coccobacilli
List the other HIV indicator conditions
- Conditions where HIV testing should be offered
- Mononucleosis-like syndrome (primary HIV infection)
- Pyrexia of unknown origin
- Any lymphadenopathy of unknown cause
- Any sexually transmitted infection
What virology tests are used to diagnose HIV?
- HIV antibody test
- Traditional method for diagnosis
- Most patients develop antibodies within 6-8 weeks, almost 100% at 3 months (3 month window period for HIV testing)
- An ELISA test is performed first then confirmed with Western Blot
- ELISA is an enzyme linked immunosorbent assay which uses an antigen-antibody reaction to generate a signal and result
- Western blot uses gel electrophoresis to demonstrate specific HIV proteins
- HIV p24 antigen testing - more recent
- Used with a confirmatory antibody test
- Detects p24 protein which is present on the surface of the virus
- Can be positive as early as 3 weeks (much shorts window period)
- Early HIV infection can give negative antibody test but positive antigen test
What is the significance of avian influenza?
- Natural reservoir for influenza A virus is aquatic birds
- Flu in birds based on pathogenicity in chickens
- Highly pathogenic avian influenza
- Low pathogenic avian influenza
- Prior to 1997 avian influenza infection in humans not considered serious
- Have since had avian influenza outbreaks
What type of bacteria are shigella?
Gram negative bacilli
Member of the Enterobacteriales family
Non-lactose fermenters (useful in differential media)
When should a CT be done in suspected meningitis?
- CT to exclude mass lesion/mass effect, gross cerebral oedema
- Doesn’t exclude raised intracranial pressure
- CT before LP if
- GCS <12
- CNS signs
- Papilloedema
- Immunocompromised
- Seizure
- Antibiotics pre-CT scan
- Don’t CT everyone because of delay in giving antibiotics
- If doing a CT need to give antibiotics pre-scan
What is the most common bacterial cause of meningitis in Scotland?
Meningococcus
Describe the types of infection causes by bacillus cereus and how they are transmitted
- Emetic disease
- Typically associated with fried rice
- Spores survive boiling
- If rice is bulk cooled and stored prior to frying, the spore germinate, multiply and re-sporulate
- Heat stable toxin survives further frying
- Diarrhoeal disease
- Spores in food survive cooking, germinate and organisms multiply in food
- Ingested organisms produce a heat-labile toxin in the gut with similar mode of action to cholera toxin
What effect does delaying antibiotic administration have?
6hr delay - 30% mortality
8hr+ delay - 80%
Significant increased risk of mortality if delay antibiotics
Describe the types of adenovirus
>50 serotypes causing range of illnesses
Adenovirus 40 & 41 cause gastroenteritis
At what time of year do campylobacter outbreaks most commonly occur?
Marked seasonal peaks in May/September
Often peaks in BBQ season - chicken not cooked properly
Define dysentery
Dysentery = inflammatory disorder of large intestine, blood and pus in the stools, usually with abdominal pain and fever
What happens to the new reassortment virus following an influenza pandemic?
Once pandemic has occurred - becomes seasonal flu through antigenic drift
Describe the epidemiology of HIV in the UK
- Number of HIV diagnoses declining
- Number AIDS at HIV diagnosis slowly declining
- Number of HIV-related deaths approx. the same
- New diagnosis rates MSM > heterosexual > injected drug use
- 200-300 cases newly diagnosed in Scotland per year
Describe the transmission of rotavirus
- Low infectious dose (10-100 virus particles)
- Mainly person to person via faeco-oral or fomites
- Food and water borne spread possible
- Spread via respiratory droplets is speculated
How is intra-cerebral toxoplasmosis diagnosed?
Multiple enhancing lesions (basal ganglia)
IgG and IgM (blood), PCR (CSF)
Describe the clinical presentation of prosthetic joint infection
- Pain
- Effusion
- Warm joint
- Fever and systemic symptoms
- If has a prosthetic joint, may also have:
- Loosening on X-ray
- Discharging sinus - blind-ended tract that extends from surface to underlying tissue
- Mechanical dysfunction
Describe the organisation of the intact defence system
- Innate defence mechanisms
- Integument
- Resisdent flora - colonisation resistance
- Complement
- Lysozme
- Acute phase reactants
- Phagocytes - macrophages + neutrophils
- Spleen
- NK cells
- Adaptive immune response
- Humoral - B cells (neutralisation, complement activation, opsonisation)
- Cellular - T cells (help macrophages, help B cells, kill virus-infected cells)
Describe the epidemiology of shigella infection
- Mainly associated with diarrhoeal disease in children
- S dystenteriae in developing world
- Large outbreaks can occur
- Recent outbreaks associated with MSM (men who have sex with men)
How does impaired nutritional status impact immunity?
- Anorexia, nausea and vomiting, mucositis, metabolic derangements –> compromised integrity of host defenses
- Iron deficiency reduces microbial capacity of neutrophils and T cell function
List the common viral causes of acute bronchitis
- RSV
- Human metapneumovirus
- Influenza
- Adenovirus
Describe the spread of HIV from Africa
- First confirmed HIV cases in Africa - 1959/60 in the Democratic Republic of the Congo, old samples tested
- HIV introduced to Haiti by an unknown individual or individuals who contracted it in the DRC in approx 1966
- Mini-epidemic followed, and in 1969 another individual brought HIV from Haiti to the US
- Vast majority of cases of AIDS outside sub-Saharan Africa can be traced back to that single unknown person
- Virus entered male gay community in the USA, where a combination of sexual promiscuity and high transmission rates associated with anal intercourse allowed it to spread explosively
- Long incubation period before illness, so HIV was not noticed for years
- By 1981 and the first reported cases of AIDS, the prevalence of HIV infection in some communities >5%
What are the expected infection rates of prosthetic joints?
- Hip surgery 0.3-2%
- Knee surgery <4%
- Knees more prone to getting infection
What is PCR? How is it used in diagnosis of viruses?
Polymerase chain reaction is a molecular biology technique which amplifies a specific DNA sequence generating multiples copies
It is a very sensitive and specific technique for diagnosing viruses, overtaking viral culture, serology and IHC
Which group are most affected by haemophilus influenza infection?
Highest incidence in under 5s
Asymptomatic carriage pre-vaccine was 4% in children
How is norovirus treated?
Symptomatic therapy
- Oral &/or IV fluids
- Antispasmodics - abdominal cramps
- Analgesics
- Antipyretics
How long is the incubation period of campylobacter? How long does the infection last?
Incubation 2-5 days
Duration 2-10 days
Describe the life cycle of HIV and drugs which are targetted to specific points in this life cycle
- Replication cycle takes 1-2 days
- Virus binds to CD4 cell receptor (target of Fusion inhibitor/R5 inhibitor)
- Virus released into cell
- RNA of virus reverse transcribed (using reverse transcriptase enzyme) to DNA, two strands of DNA produced (target of nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor)
- DNA enters nucleus, integrated into host DNA (target of integrase inhibitors)
- DNA transcribed to RNA, translated to viral proteins
- Virus released to infect other cells (target of protease inhibitors)
What are the risk factors for prosthetic joint infections following a primary arthroscopy?
- Rheumatoid arthritis
- Diabetes mellitus
- Poor nutritional status
- Obesity
- Concurrent UTI
- Steroids
- Malignancy
Define revision arthroplasty
Re-operating on an artificial joint
Describe granuloma formation in TB
- The tuberculous granuloma is a compact, organized aggregate of epithelioid cells — macrophages that have undergone a specialized transformation to have tightly interdigitated cell membranes that link adjacent cells
- Epithelioid cells can be highly phagocytic but in some cases do not contain bacteria at all
- Granuloma macrophages can also fuse into multinucleated giant cells or differentiate into foam cells, which are characterized by lipid accumulation
- Foam cells have been noted to be most frequently located at the rim of the necrotic centre of a mature tuberculous granuloma
- The consequences of these changes are not well understood, but in general foam cells and multinucleated giant cells have been reported to contain only a few bacteria, if any, bacteria are most commonly present in the central necrotic areas in which dead and dying macrophages can be seen
- Many other cell types also populate the granuloma, such as neutrophils, dendritic cells, B and T cells, natural killer (NK) cells, fibroblasts and cells that secrete extracellular matrix components
- The epithelial cells surrounding the granuloma are now thought to participate in its formation also
How is syphilis diagnosed?
- If chancre - dark ground microscopy/viral PCR swab (even though it is bacterial)
- Bloods for antibody
- 3 month window period
- Stays positive even after completed treatment
- Rapid plasma reagin
- Quantitative marker
List the developments which have increased the success of solid organ transplantation
- Optimal tissue typing
- Donor evaluation
- Organ procurement
- Surgical technique
- Tailored immunosuppressive regimen
- Prevention of infection
List the respiratory HIV indicator conditions
- AIDS-defining conditions
- Tuberculosis
- Pneumocystis
- Other conditions where HIV testing should be offered
- Bacterial pneumonia
- Aspergillosis
What are the signs/symptoms of rectal chlamydia?
- Usually asymptomatic
- Can present with proctitis
- Rectal pain
- PR discharge
- Rectal bleeding
- Tenesmus
- Constipation
- Lymphogranuloma venereum (LGV) sub-type often presents as proctitis
- Can also have lymphadenopathy/ulcer disease
What causes gonorrhoea?
- Bacterial
- Caused by gram-negative diplococcus N. gonorrhoeae
- Infects mucous membranes of urethra, endocervix, rectum, pharynx and conjunctiva
- Inoculation through secretions from one mucous membrane to another
What impact does vaccine coverage have on child mortality?
Where vaccine coverage low, child mortality high
Describe the structure of rotavirus
- Family: Reoviridae
- Double stranded, non-enveloped RNA virus
- Tougher, resistant to drying out, can be passed on more effectively
- 5 predominant strains, G1-4, G9
- Can also be classified by species A-H
- G group is from VP7 protein and P group is from VP4 protein
- G1 accounts for >70% of infections
- 11 strands of RNA so potential for much antigenic variation
- RNA replication is very error-prone
- Stable in environment and fairly resistant to hand washing
List the main symptoms of acute HIV infection
- First 1-2 months after infection
- Systemic
- Weight loss
- Fever
- Pharyngitis
- Mouth
- Sores
- Thrush
- Oesophagus - sores
- Muscles - myalgia
- Liver and spleen enlargement
- Central
- Malaise
- Headache
- Neuropathy
- Lymph nodes - lymphadenopathy
- Skin - rash (maculopapular)
- Gastric
- Nausea
- Vomiting
How are salmonella identified in clinical labs?
XLD plates used most commonly, salmonella appear as black colonies
How do anogenital spread?
Most likely to spread when warts present but can have asymptomatic transmission
What outcomes are possible if septic arthritis goes untreated?
- Untreated joint infection =
- Loss of cartilage –> osteoarthritis in later life (reduced quality of life)
- Severe sepsis –> septic shock –> death
- Should be treated as a medical emergency
Describe primary prevention of bacterial meningitis
- Haemophilus influenzae type B, pneumococcus and meningococcus vaccine given at 2 months, three months, four months and 12-13 months
- Meningococcus booster quadrivalent vaccine given at age 14 - MenACWY
- More strains emerge when mixing with different populations e.g. in further education
Special Cases:
- Travel to Sub-Saharan Africa and other high prevalence areas (Pilgrims) - ACWY recommended
- Asplenia, complement deficiency - Men boosters with Men B and ACWY, HIB and pneumococcus
- Cochlear implants - pneumococcus booster
What should the initial investigations be in suspected malaria?
Full Blood Count, Liver Function tests, Urea and Electrolytes
At least 3 malaria blood films or rapid diagnostic tests (RDTs) over 2 days
Blood cultures
HIV Test
Urine and stool culture and microscopy
Serology +/- PCR for dengue, other arbovirus infections, Rickettsia and others pathogens
CXR and ultrasound of liver and spleen
Describe the pathogenesis of clostridium difficile infection
- Infection requires disruption of the normal ‘protective’ gut flora
- Most commonly due to antibiotic therapy
- Can also be due to cytotoxic therapy
- Proton pump inhibitor use may be an additional risk factor
How is CSF glucose used in meningitis diagnosis?
If CSF glucose less than 50% blood glucose (need to take bloods right after LP) more likely to be bacterial, fungal or tuberculosis
Which pathogens commonly cause infections following solid organ transplantation?
- Community-acquired pathogens
- Bacterial - pneumococcus, listeria, salmonella, legionella
- Viruses - influenza, parainfluenza, RSV
- Nosocomial infections
- Especially early post-transplant and if ventilated or prolonged length of stay
- Resistant gram +ve and gram -ve bacteria, C diff associated disease, fungi
- Donor-derived infections
- Latent
- TB, syphillis, viruses (HIV, hepatitis B, CMV)
- Active bloodstream infection at procurement
- Staphylococci, pneumococci, salmonella, E. Coli
- Latent
- Reactivation of infections
- M tuberculosis
- Viruses - HSV, VZV, CMV
- Opportunistic pathogens
- Aspergillus, pneumocystis
How can the transmission of clostridium botulinum be controlled?
Proper manufacturing controls in canning industry
Hygienic food preparation
Proper cooking
Refrigerated storage
List the symptoms of shigella infection
- Dysentery - blood and pus in faeces
- Initially watery diarrhoea followed by bloody diarrhoea
- Marked, cramping abdominal pain
- Vomiting is uncommon
- Fever is usually present
How is TB infection spread?
- Spread by coughing, sneezing, talking
- Usually close contact spread - live in same household, enclosed spaces e.g. public transport
When should you consider taking a sexual history/perform a sexual health screen?
Anyone presenting with symptoms of:
- Vaginitis - change in discharge, dysuria, change in menstrual bleeding
- Urethritis - penile discharge, dysuria, meatal discomfort
- Epididymo-orchitis - swollen, painful testicle
- Pelvic inflammatory disease - pelvic pain, fever, change in discharge, dyspareunia
- Proctitis - rectal discharge/pain/bleeding
- Ulcer/lumps on genitals
- Possible syphillis - esp. rash (look at hands/feet)
- Possible HIV seroconversion
And asymptomatic patients in certain settings - screening request etc.
List the symptoms of campylobacter infection
- Bloody diarrhoea
- Cramping abdominal pain
- Not usually vomiting
- Fever
Describe the structural features of norovirus
- Family: Calciviridae
- Non-enveloped, single stranded RNA virus
- Non-enveloped viruses more tough, don’t dry out on surfaces so can be passed on easier
- Five genogroups - only 3 affect humans (GI, GII and GIV)
- G3 bovine, G5 mice
- Genogroups divided into at least 32 genotypes
- Most common in the UK is the GII-4 strain
Is there a vaccine available for adenovirus?
No vaccine for adenovirus 40 + 41
There is for adenovirus 4/7 - respiratory infection, used by US military
How do new pathogens emerge?
- Pathogenicity determinants often on mobile genetic elements
- Bacteriophages
- Plasmids
- Transposons
- Pathogenicity traits often grouped together in large integrons or pathogenicity islands
- Frequently also contain antibiotic resistance genes
- Refractory to treatment
- Selective advantage
- Many of the pathogens have evolved from gut flora
- Existing pathogens can acquire new pathogenicity traits
Describe drug-drug interactions in ART
- Including some topical/inhaled drugs
- Often class-specific
- Often mediated by CYP450 - induction/inhibition
- Reduce or increase drug levels
- E.g. PPIs, statins, antipsychotics - QTc
What are the common viral causes of the common cold?
- Rhinovirus
- Coronavirus
- Parainfluenza virus
- Human metapneumovirus
- Adenovirus
- RSV
- Influenza
Describe the pathogenesis of MERS-CoV
- Develop infection within 12 days of exposure
- Disease progression
- Prodrome - flu-like illness (transmission unlikely)
- Acute illness - dyspnoea, vomiting, diarrhoea, chest pain, cough (transmission)
- Fulminant illness - ARDS, renal failure, multi-organ failure (transmission)
Describe the transmission of campylobacter infection
- Large animal reservoir (poultry, cattle, sheep, rodents and wild birds)
- Infection transmitted via contaminated food (esp. poultry), milk or water
- Person-to-person spread rare
- Large point source outbreaks uncommon (doesn’t multiply in food)
- 70% of raw retail fresh (not frozen) chicken is contaminated with Campylobacter
How is adenovirus treated?
Supportive treatment
Give an example of a bacteria with lactose fermenting colonies
E. Coli
List the symptoms of apical TB disease
- Cough
- Sputum
- Haemoptysis
- Weight loss
- Night sweats
How do conjugate vaccines aid immunisation?
- Plain polysaccharide antigens (e.g. strep pneumonia) do not stimulate the immune system as broadly as protein antigens such as tetanus or influenza
- Therefore, production from such vaccines is not long-lasting and response in infants and young children is poor
- Some polysaccharide vaccines have been enhanced by conjugation - where the polysaccharide antigen is attached to a protein carrier (e.g. Hiv and MenC vaccines) giving better immunological memory
- Immunogenic in babies (relatively)
Describe the clinical features of clostridium difficile infection
Mild to severe with abdominal pain
Severe cases may develop pseudomembranous colitis
Fulminant cases may progress to colonic dilatation and perforation
Severe cases may be fatal
Relapses are common and may be multiple
How do prosthetic joint infections differ from native septic arthritis?
Very different environment from native joint, potential for different organisms to grow
Often occurs in elderly patients with co-morbidities, poor nutrition etc. so can be difficult to manage
Define gastroenteritis
Gastroenteritis = inflammation of the stomach and intestinal epithelium, characterised by GI symptoms including nausea, vomiting, diarrhoea and abdominal discomfort
How is CSF protein used in meningitis diagnosis?
Normal - suggests not tuberculosis or fungal cause
Can get normal with viral meningitis
High - any cause
Define complicated influenza
Complicated influenza = infection that requires hospital admission
List the signs of pneumococcal meningitis
- Neurological signs
- 65% focal signs
- 24% seizures
- 22% VIII palsy - hearing loss/damage
- Other signs of pneumococcal infection - community acquired pneumonia, ENT, endocarditis
Define osteomyelitis
Progressive infection of bone characterised by death of bone and the formation of sequestra
Sequestra = replacement tissue for bone, not as strong, not able to deal with stresses on tissue as well
Define pseudo-arthrosis
Allowing two bones to articulate against one another but without a joint e.g. Girdlestone, done in patients with no other treatment viable
Describe the aetiology of meningitis in the UK
- In 42% diagnosed with meningitis (inflammatory CSF) a cause is not identified
- When a specific diagnosis is made, the cause is usually viral (36%)
- 15% bacterial
- Rarer causes seen in immunocompromised or those from other countries
How can child mortality due to pneumonia be reduced?
- Community case identification and management of severe pneumonia by oral antibiotics delivered through community health workers
- Recognise basic clinical signs - fever, cough, tachypnoea, hyperinflation, intercostal recession and make antibiotics available to administer
How is the population of immunocompromised patients changing?
Increasing population of often profoundly immunocompromised patients due to:
- Improved survival at extremes of life - premature babies and elderly
- Improved cancer treatment
- Developments in transplant techniques
- Developments in intensive care
- Management of chronic inflammatory conditions
- Steroids
- Profound inflammatory modulators
- Taken by lots of people for many reasons
How is phthirus pubis treated?
Malathion 0.5% or Permethrin 1% cream
What are the additional roles of the laboratory in viral respiratory infections?
- Resistance
- Epidemiology
- Vaccine effectiveness studies
- Sequence analysis of circulating influenza strains
- Outbreak investigation
What is the treatment for syphilis?
Treatment - Benzathine penicillin (not much drug resistance)
Describe the epidemiology of meningitis
Sub-Saharan Africa carries the highest burden of bacterial meningitis
Incidence of meningitis highest in children, especially <1yr old - unvaccinated
Disease of children + poverty
What causes intra-cerebral toxoplasmosis?
Toxoplasma gondii - raw beef (France, Africa)
Commonly seen in immunocompromised (HIV)
Define MDR-TB
Resistance to both rifampicin and isoniazid
Describe the pathogenesis of clostridium botulinum infection
Absorbed toxins spread via bloodstream and enter peripheral nerves where they cause neuromuscular blockage at the synapses
Describe the clinical presentation of TB
- Pulmonary 90%
- Cough/haemoptysis
- Shortness of breath
- Constitutional symtoms
- Fever, chills
- Night sweats
- Fatigue
- Loss of appetite, weight loss
- Lymphadenopathy
- CNS
- Meningitis - neck stiffness, headache, photophobia
- Eyes
- Choroiditis, blurred vision, red eyes
- CVS
- Constrictive pericarditis
- Chest pain
- Shortness of breath
- Renal
- Dysuria
- Haematuria
- GI
- Ileocaecal - abdominal pain, mass in RIF, perionteal
- Distended abdomen and ascites
- Skeletal
- If occurs in the spine = Potts disease
- Arthitis and osteomyelitis
- Joint/bone pain localised swelling
- Skin
- Lupus vulgaris - brown plaques which can ulcerate and can occur at muscocutaneous junction
Give examples of viruses which replicate in the gut but do not cause diarrhoea/vomiting
- Many viruses replicate in the gut but most do NOT cause diarrhoea and vomiting
- E.g. Poliovirus (and all other enteroviruses)
- Adenoviruses other than types 40 & 41
- Hepatitis A/E
Describe the pathogenesis of neutropaenic fever in cancer patients
- Effect of chemotherapy on mucosal barriers (translocation) and immune system
- Impact on host defenses of the underlying malignancy
–> Neutropaenia, abnormal antibody production, T cell defects (+ organ dysfunction, nutritional status, IV access devices and concurrent illness)
What are the risk factors for prosthetic joint infections following revision arthroscopy?
- Prior joint surgery
- Prolonged operating room time
- Pre-op infection (teeth, skin, UTI)
What type of bacteria are clostridium botulinum?
Anaerobic, spore-forming gram +ve bacilli
Define resection arthroplasty
Taking the disease joint out and putting in an artificial one
How can viral gastroenteritis be diagnosed?
- Most of these viruses can’t be cultured
- Previously detected using EM or ELISA
- All are detected by PCR which detects the DNA or RNA
- Children/elderly/immunocompromised - test for all viruses
- Normally healthy adults - test for norovirus
- Testing done in Virology lab
- Samples - vomit or stool
Why is non-adherence common in TB treatment? What is the effect? How can this be prevented?
- Rapid clinical improvement
- Patient feels better – stops meds
- Also often live chaotic lives - homeless, drug users etc.
- Risk of generating drug resistance
- Important even at the end of treatment
- Directly observed treatment/video observed treatment can be used
When is HAART indicated?
Initiated at a CD4 count of 350 or lower, although it can be started at higher CD4 counts if the patient is symptomatic
How are enterotoxigenic E. Coli tested for?
No differential media available
Test liquid cultures for production of toxins by immunoassays - not routinely done
What are the criteria for a diagnosis of AIDS?
- Evidence of an AIDS defining illness
- The term AIDS is no longer used within clinical practice due to the connotations of a palliative disease
- AIDS is an epidemiological term - coined by the CDC in America in the 1980s to describe the outbreak of an illness in New York/San Francisco in gay men dying of PCP
- AIDS = if had positive HIV test and opportunistic infection, and denoted a 6 month life expectancy
- Often doctor and patient knowledge of HIV is 15 years out of date - AIDS is no longer clinically relevant as HIV+ have a normal life expectancy with ART
- Advanced HIV is a preferred term
Describe the body’s natural barriers to GI infection
- Mouth
- Lysozyme
- Stomach
- Acid pH
- Small intestine
- Mucous
- Bile
- Secretory IgA
- Lymphoid tissue (Peyer’s patches)
- Epithelial turnover
- Normal flora
- Large intestine
- Epithelial turnover
- Normal flora
List diseases/therapies which suppress cellular immunity
- DiGeorge syndrome (primary deficiency, rare) - failure of proliferation of T cells
- Malignant lymphoma
- Cytotoxic chemotherapy
- Extensive irradiation
- Immunosuppressive drugs
- Corticosteroids
- Cyclosporin - immunosuppressant used to prevent organ rejection
- Tacrolimus - more portent that cyclosporin
- Alemtuzumab - anti-CD52 monoclonal
- Rituximab - anti-CD20 monoclonal
- Purine analogues e.g. fludarabine - causes profound lymphopaenia
- Allogenic stem cell transplantation especially if GVHD (treated w steroids)
- Infections - HIV, mycobacterial infections, measles, EBV, CMV
- Infections - viruses, mycobacteria, fungi, protozoa
How is active TB diagnosed?
- Acid fast bacteria in respiratory or other sample
- Microbiology
- Histopathology
- M tuberculosis growth in cultures - liquid or LJ culture medium
- Clinical and/or radiological diagnosis
- TB immunology - not validated for latent TB
- Without microbiological diagnosis, difficult to determine resistance
- Get samples prior to starting treatment
In neutropaenic fever which additional antimicrobials should be added for specific infection risks?
- IV vancyomycin - recent infection with MRSA, MRSA colonised (current or previous), suspected central line infection or signs of skin/soft tissue infection
- IV clarithromycin - community acquired pneumonia suspected and atypical cover required (check drug interactions)
- IV metronidazole - history of true penicillin/beta-lactam allergy with suspected intra-abdominal sepsis
- Previous ESBL infection or known ESBL carrier use a carbapenem in place of piperacillin/tazobactam
- Consider possibility of opportunistic infection such as PCP or reactivation of previous infection e.g. CMV, VZV
Define neutropaenia
Defined as <0.5 x 10^9/L or <1.0 x 10^9/L and falling
Describe the symptoms and causes of pharyngitis
- Symptoms - sore throat and pharyngeal inflammation
- Viral infections 25% to 45% all cases
- Nasal symptoms = viral
- No nasal symptoms = bacterial
- Many different viral pathogens including
- Adenovirus (12-23% cases)
- Rhinovirus
- Influenza
- Parainfluenza
- Not just caused by respiratory viruses
- 82% occurrence in infectious mononucleosis - Epstein Barr Virus (EBV), saliva spread
- HIV seroconversion illness
- Herpes simplex virus - usually evidence of oral lesions
Where are the under 5 mortality highest and lowest? Why?
- Highest in Somalia (180 per 1,000), Mali, Burkina Faso (Sub-Saharan Africa, Southeast Asia, Middle East)
- Africa 4.2 million, SE Asia 2.4 million
- Poverty, poor sanitation, warfare, poorly developed healthcare system etc. risk factors for high under 5 mortality
- Lots of mortality in neonates (0-30 days old)
- Lowest in Singapore (2.6 per 1,000), Slovenia, Sweden
Who should be treated for gonorrhoea?
- Positive test result
- Clinical suspicion (certain circumstances)
- Recent or ongoing sexual contact with gonorrhoea
What investigations should be done in a patient with suspected GI infection?
Blood tests (FBC, U&E, blood film - HUS), sigmoidoscopy, abdominal X-ray/CT
Explain the importance of risk assessment of prosthetic infection prior to joint surgery
Risk assessment allows targeting of intervention - nutritional supplements, stop smoking, tight diabetes control, weight loss, monitor steroid use etc.
What are the goals for TB treatment in the UK?
20% reduction in TB incidence by 2020 (compared w/ 2015)
35% reduction in TB deaths by 2020 (compared w/ 2015)
List the short term side-effects of ART
- Rash
- Hypersensitivity (Abacavir and Nevirapine)
- CNS side effects (Efavirenz) - sleep disturbance, vivid dreams, mood changes
- GI side effects
- Renal
- Hepatic
Describe the pathogenesis of vibrio cholerae
Flagellae and mucinase facilitate penetration of intestinal mucous
Attachment to mucosa by specific receptors
Diarrhoea due to production of a potent protein exotoxin
List the causes of viral meningitis
- Enterovirus most common
- HSV 2 (sexually transmitted) > VZV > HSV 1
- HIV (seroconversion)
- Mumps
- Unidentified - common
Define XDR-TB
MDR-TB + additional resistance to fluoroquinolone and one of the injectables (amikacin, kanamycin, capreomycin)
Describe the population of M. Tuberculosis in infected individuals
- Tuberculosis sufferers previously considered to have heterogeneous populations of M. Tuberculosis
- 4 populations proposed
- Actively growing organisms (killed mainly by isoniazid)
- Semi-dormant organisms inhibited by an acid environment (killed mainly by pyrazinamide)
- Semi-dormant organisms with spurts of active metabolism (killed preferentially by rifampicin)
- Completely dormant organisms (not killed by standard drugs)
What are the key investigations which should be undertaken in suspected septic arthritis?
- Blood cultures
- Joint aspirate (gram, microscopy for crystals and culture)
- Need meticulous aseptic technique when taking joint aspirate - don’t want to introduce and organism into a healthy joint
- Differential includes gout - crystals
- FBC
- CRP - inflammation
- Imaging
In which cancer patients is neutropaenic fever likely to develop?
5-10% solid tumours receiving cytotoxic chemotherapy
20-25% non-leukaemic haematological malignancies
85-95% acute leukaemias receiving induction chemotherapy
How is mycoplasma genitalium diagnosed?
NAAT - urine/self-taken vaginal swab
Describe the transmission of salmonella
- Found in wide range of warm and cold blooded animals
- Only S. typhi and S. paratyphi cause enteric fever (typhoid and paratyphoid), do not have animal reservoir
- Acquired via contaminated food, especially pork, poultry and other meat and milk/dairy products
- Waterborne infection less common
- Large foodborne outbreaks can occur
- Secondary spread via person-to-person transmission may be a feature
How is clostridium perfringens transmitted?
Spores and vegetative cells ubiquitous in soil and animal gut
Contaminated foodstuff (usually meat products)
Often involves bulk-cooking of stews, meat pies
Spores survive cooking, germinate and organisms multiply in cooling food
Food inadequately re-heated to kill organisms
What are the problems associated with anogenital warts?
Itch/aesthetic usually only problems
List the types of respiratory samples which can be used for PCR diagnosis
Nasal pharyngeal swab
Throat swab
Gargle
Sputum
Endotracheal aspirate
Bronchoalveolar lavage
List the complications of rotavirus
- Severe chronic diarrhoea
- Dehydration
- Electrolyte imbalance
- Metabolic acidosis
- Immunodeficient children may have more severe or persistent disease
List the risk factors for pneumococcal meningitis
- 70% underlying disorder
- Middle ear disease
- Head injury (CSF leak)
- Neurosurgery
- Alcohol
- Immunosuppression (HIV)
What type of bacteria are campylobacter?
- Curved gram -ve bacilli
- Microaerophilic and thermophilic (multiplies at 42 degrees)
- culture on Campylobacter selective agar
- C. jejuni most important species - 90%
What are the key strains of avian influenza which have significance in humans?
- A/H5N1
- A/H7N9
- A/H9N2
- A/H7N7
What type of bacteria is clostridium difficile?
Anaerobic, spore forming gram +ve bacilli
In a total hip arthroscopy, what are the most common causative organisms of a prosthetic joint infection?
- Staphylococcus aureus
- Coagulase-negative staphylococci (normally found on skin, breach in skin allows entry to joint, very ‘sticky’, can create biofilm so hard to get rid of)
- Streptococci
- Gram negative bacilli
- Anaerobic organisms
- Enterococcus
- Culture negative - grow nothing
- Polymicrobial (mixed)
What type of virus is the influenza virus?
Orthomyxovirus - segmented RNA genome - separate strands of genes, code for different proteins
Describe the transmission of listeria monocytogenes
- Infection associated with contaminated foods, especially unpasteurised milk and soft cheeses, pate, cooked meats, smoked fish and coleslaw
- Can multiply at 4 degrees
Define neutropaenic sepsis/febrile neutropaenia
- Neutrophil count <0.5 or <1 x 109/L if recent chemotherapy (usually within 10 days but can persist for up to 21 days)
- Plus fever/hypothermia or SIRS or sepsis/septic shock
Describe the use of PEP
PEP - Post exposure prophylaxis
- Take if had exposure which might put you at risk of HIV
- Take within 72 hours
- 28 days
- Available from sexual health/A&E
- Based on exposure type and risk of contact
How is helicobacter pylori transmitted?
Though to be faecal-oral or oral-oral
Humans are only reservoir
Infection acquired in childhood and persists life long unless treated
How is the risk of sexual transmission of HIV increased?
Risks increased by high HIV viral load, trauma (including sexual assault), co-existing STIs, ulcerative conditions i.e. herpes simplex/syphilitic chancre and if the index male is uncircumcised
Describe the transmission of clostridium botulinum
- Spores and vegetative cells ubiquitous in soil and animal GIT
- Produces powerful heat-labile protein neurotoxin (types A, B + E cause human disease)
- Foodborne botulism - pre-formed toxin in food, commonly associated with improperly processed canned foods
- Infant botulism - organisms germinate in gut of babies fed honey containing spores, and toxins are produced in the gut
- Wound botulism - organisms implanted in wound produce toxins, seen in IVDU
How is MDR-TB treated?
- 18 months - 2 years of treatment
- Drugs associated with significant adverse event profiles
- Injectable agents with risk of HIV and other BBV transmission
- Pyrazinamide + 4 second line agents during intensive phase
- Fluoroquinolone
- 2nd live injectable - nephrotoxicity
- Ethionamide or prothionamide
- Cycloserine or p-aminosalicylic acid
- Duration of intensive phase >8 months
- Total duration >20 months if not previously treated for MDR TB
- Study shows no different between short and long term regimen (9 months vs 2 years)
Define viral latency
Viral latency is a state of reversibly non-productive infection of individual cells
How is intra-cerebral tuberculosis treated?
Steroids
Paradoxical worsening with treatment usual
Rx for one year (rifampicin, isoniazid, ethambutol, pyrazinamide) + steroids
How does HIV resistance develop?
- As HIV multiples in the body, the virus sometimes mutates and produces variations of itself - variations that develop while on HIV medication can lead to drug-resistant stains of HIV
- HIV medicines that previously controlled a person’s HIV are not effective against new, drug-resistant HIV (can’t prevent the drug-resistant HIV from multiplying), can cause HIV treatment to fail
- A person can be initially infected with drug-resistant HIV or develop drug-resistant HIV after starting HIV medicines
Describe the pathogenesis of enterohaemorrhagic E. Coli infection
Attaching and effacing lesion (similar to EPEC)
Production of Shiga-like toxins, structural and functional analogue of shigella dysenteriae toxin (sometimes strains called STEC - Shiga-toxin producing EC - or VTEC - verotoxin-producing EC - because toxins are toxic for cultured vero cells)
List the sources of GI infection
- Many GI infections are zoonotic - transmitted by cross contamination from animal
- Symptomatic animals
- Economic cost e.g. Salmonella Dublin
- Asymptomatic shedders
- E.g. reptiles and salmonella carriage, E. coli 0157 in cattle
- Symptomatic animals
- Human carriers important for some e.g. typhoid
- Environmental sources
- Contamination of soil and produce e.g. Listeria, E. Coli 0157
List the common viral causes of bronchioloitis
- RSV
- Human metapneumovirus
- Parainfluenza virus
- Rhinovirus
- Coronavirus
- Influenza
- Human bocavirus
List the infections which occur as the natural course of HIV infection progresses (untreated)
As CD4 count falls/years after onset of HIV infection =
- Thrush
- Oral hairy leukoplakia
- Tuberculosis
- Pneumocystis carinii pneumonia
- Histoplasmosis
- Coccidioidomycosis
- Cryptotococcosis
- Toxoplasmosis
- Atypical herpes simplex virus disease
- Cryptosporidioisis
- Cytomegalovirus disease
- Mycobacterium avium complex disease
Describe the infection caused by astrovirus
Cause less severe gastroenteritis than other enteric pathogens
Infection usually as sporadic cases but can be outbreaks, usually in younger children
In which age groups is acute osteomyelitis most common?
Acute osteomyelitis more common in children than adults
What are the challenges with ART?
- Good adherence essential - drug resistance
- Psychological impact - taking medication everyday is constant reminder of diagnosis
- Short term side-effects
- Longer term toxicities
- Drug-drug interactions
How does invasive HiB disease most commonly present?
- Most common presentation of invasive HiB disease is meningitis, frequently accompanied by
- Bacteraemia 60%
- Epiglottitis 15%
- Bacteraemia 10%
- Pneumonia, cellulitis
How are anogenital warts diagnosed and managed?
- Clinical diagnosis
- Advice:
- Reassure high prevalence and benign
- No requirement for partner notification but condoms reduce transmission
- Many people clear virus
- Smoking/hair removal
- Smoking makes treatment more difficult - impairs immune response
- Hair removal makes spread more likely, should avoid with visible warts
- Treatment:
- Cryotherapy
- Topical treatments: podophyllotoxin/imiquimod
- Surgical excision (rarely required)
- Variable success
Define arthrosis
A joint
Which groups are at higher risk of viral gastroenteritis?
- Children under age 5
- Old age people especially in nursing home
- Immunocompromised
Describe the action of live attenuated vaccines
- To produce an immune response, the live organism must replicate (grow) in the vaccinated individual over a period of time (days-weeks)
- Usually promote a full, long lasting immune response after 1-2 doses
- Vaccine virus is weakened or ‘attenuated’ but a mild form of the disease may rarely occur
- MMR, VZV, intranasal influenza
- Not to be given to immunocompromised individuals
How can clostridium difficile infection be controlled?
- Antimicrobial stewardship
- Remember that any antibiotic therapy will disturb the normal gut flora to some extent
- Avoid/stop unnecessary antimicrobial treatment
- Restrictive antibiotic formularies to minimise use of ‘high risk’ antibiotics
- Cephalosporins
- Fluoroquinolones
- Clindamycin
- Co-amoxiclav
- Remember that any antibiotic therapy will disturb the normal gut flora to some extent
- Infection prevention and control measures
- Source isolation
- Hand hygiene - need to wash hands with soap and water not just alcohol gel
- Use of personal protective equipment (PPE)
- Cleaning/disinfection with hypochlorite disinfectants
Describe antibody mediated immunity
- When a B cell encounters an antigen that it recognises, the B cell is stimulated to proliferate and produce large numbers of lymphocytes secreting an antibody to this antigen
- Replication and differentiation of B cells into plasma cells is regulated by contact with the antigen and by interactions with T cells
Why is it important to consider tuberculosis in vertebral discitis?
Tuberculosis can present with discitis
What are the blood markers tested in HIV?
- HIV viral load
- Can be up to >10 million
- The aim of treatment is to achieve and maintain an ‘undetectable viral load’
- Undetectable means below 200 copies/ml
- In Scotland, we measure to <40 copies/ml
- CD4
- Calculated from total lymphocyte count
- HIV negative - 400-1600 per mm3
- Risk of opportunistic infection increases sharply below 200/mm3
Test routinely in those with HIV
What causes cryptococcal meningitis?
Dissemination of fungus from pulmonary infection
Usually in immunocompromised (HIV)
Which organisms can cause infection in neutropaenia?
- Gram positive cocci
- Staph aureus
- Coagulase negative staphylococci
- Viridans streptococci
- Enterococci
- Anaerobes
- Bacteroides spp.
- Clostridia spp.
- Gram negative bacilli
- E coli
- Pseudomonas aeruginosa
- Klebsiella pneumoniae
- Enterobacter spp.
- Fungi
- Candida spp.
- Aspergillus spp.
Describe the pathogenesis of osteomyelitis
- Haematogenous spread
- Contiguous spread
- Overlying infection (e.g. cellulitic ulcer, diabetic feet)
- Trauma (compound fracture)
- Surgical inoculation
Describe the four species of Plasmodia responsible for human malaria in terms of clinical features, treatments and geographical distribution?
P. falciparum – Worldwide distribution, most important cause of malaria and the main cause of severe malaria and nearly all fatalities, no dormant liver infection, drug resistance +++. Commonest.
P. vivax - Worldwide but most commonly Asian subcontinent, persistent liver infection, can result in relapse months after initial infection, some Chloroquine resistance in SE Asia. Second most common.
P. ovale - Usually West Africa, persistent liver infection, can relapse. No drug resistance
P. malariae – Worldwide (Africa), 10% occur > 1 year after infection, no dormant liver infection, No drug resistance
Patients with confirmed non-falciparum malaria may be treated as outpatients with Chloroquine. Vivax and ovale infection require additional treatment with Primaquine to eradicate the liver stage infection to prevent relapse.
Vivax + ovale can be dormant in liver then reactivate many years later – treat with chloroquine to get rid of parasitaemia.
Describe the antibiotic prophylaxis used for joint replacement surgery
- No benefit to support >24 hours antibiotics
- No trial evidence to support antibiotic impregnated cement
- Single pre-op dose cephalosporin reduces risk of deep wound infection by 1.8%
- Single pre-op dose and two post op doses reduce risk of deep wound infection by 2.9%
- Should be given 30-60mins before skin incision
- Evidence supports the use of cephalosporin (plus vancomycin or teicoplanin if MRSA colonised) in prevention of PJI (but not C. difficile)
What is the under 5 mortality rate in the UK?
4.5% - steadily declining by 1% per year
