Infectious Diseases Flashcards
What are the genetic mechanism by which bacteria develop resistance to antibiotics?
Bacteria gain genes that encode for proteins that confer protection with the following mechanisms:
- Gene ‘mutation’
- Gene ‘acquisition’ from another bacterial species
What genetic package do bacteria use to exchange genetic information to gain resistance?
Plasmids.
Plasmids are circular segments of DNA separate to bacterial chromosome and are easily spread from bacteria-to-bacteria.
Think of it as a transferrable resistance package.
What is the usual route of transmission for Giardia lamblia?
Faeco-oral.
What are the typical clinical manifestations of Giardia lamblia?
Obvious: nausea, diarrhoea and abdominal pain.
Less obvious: steatorrhoea
Giardia makes your poo float!
True/False: Giardia lamblia infections are always symptomatic.
False.
Often asymptomatic, carriers secrete cysts in their stools.
How is Giardia lamblia diagnosed?
Stool MCS +/- duodenal aspirates or biopsy.
What is the treatment of hookworm infections?
Mebendazole
What is the treatment of Giardia lamblia?
Metronidazole
Pasteurisation of milk has reduced the incidence of which pathogen?
Brucella (from cows)
What type of bacteria is Brucella?
Gram negative bacillus - fastidious (from cows)
What are the clinical manifestations of Brucella?
- Non-specific: fever, malaise, arthralgia and depression.
- 35% with hepatosplenomegaly
Are leucocytes increased or decreased with Brucellosis?
Leucopenia (75% of cases)
What animal is associated with Toxoplasma infection in humans?
Cats
True/False: Toxoplasma infections can cause eye complications.
True.
Many:
- Focal choroidoretinitis
- Granulomatous uveitis
- Optic atrophy
- Retinal detachment
- Cataract
- Posterior uveitis
- Glaucoma
What are the clinical manifestation of diphtheria (Corynebacterium diphtheriae)?
Non-specific:
- Fever and sore throat
- Cervical LNs
More specific:
- Adherent grayish pharyngeal membrane
- Potential cardiac and nerve toxicity
What is the treatment of diphtheria?
Expedient diphtheria antitoxin +/- Benzylpenicillin.
Febrile patient recently returned from overseas has a sore throat and on inspection has a grossly inflamed and membranous pharyngitis.
What are the DDx?
Most commonly EBV, however in a returned overseas traveller Diphtheria is a DDx.
When should ‘vaccination’ occur in the following scenarios involving splenectomy:
- Elective splenectomy
- Emergency splenectomy
- Unvaccinated splenectomised patient
- Immunosuppressed patient from chemotherapy/radiotherapy
- Elective splenectomy = 2 week pre-op to ensure optimal antibody response
- Emergency splenectomy = ASAP
- Unvaccinated splenectomised patient = ASAP
- Immunosuppressed patient from chemotherapy/radiotherapy = delayed for 6m with interim prophylactic Abx
Treatment-naive patient with HIV is about to be commenced on HAART, she is diagnosed with TB.
When should TB treatment commence (before or after HAART)?
TB treatment to occur PRIOR to initiation of HAART.
What is the significance of HLA-B*5701 in HIV?
- Associate with long-term non-progressive chronic HIV-1 infection (good prognosis)
- HIV-specific Cytotoxic T-lymphocytes are restricted by this allele
- Able to control viraemia below detectable levels (<50 RNA copies/mL plasma) WITOUT antiviral therapy.
- May cause hypersensitivity reaction (SJS/TENS/SLE) if Abacavir (NRTI) given in HL-B*5701 positive patients.
What conditions is Tenofovir indicated for ?
What are the 2 side effects of Tenofovir (NRTI)?
Indications:
- HIV-1 infection
- Chronic Hep B
SEs: renal impairment and osteoporosis
Patient is diagnosed with malaria with plasmodium vivax.
What treatment is used to eliminate dormant liver hypnozoites?
Primaquine
An asymptomatic patient has a positive Quantiferon gold test, negative CXR and is from a South-East Asian country of origin with evidence of a previous BCG vaccine.
What is the diagnosis?
What is the treatment?
Latent TB
Single-agent isoniazid
NB: Quantiferon test is NOT affected by BCG vaccinations
SE-Asian patient with newly diagnosed AML is noted to positive interferon-gamma release assay (IGRA).
What is the immune mechanism that mediates this?
IGRA tests T-cell or peripheral monocyte response to M. tuberculosis antigens.
What are the live attenuated viruses?
Clue: very bimpy
VR-BIMPY (very bimpy):
Varicella Rotavirus (PO) BCG (TB) Influenza (nasal) MMR (measle/mumps/rubella) Polio Yellow fever
NB: mode of administration is important, IM influenza is ok for the immunocompromised.
What are the clinical features of acute rheumatic fever (4)?
Obvious: fever, polyarthritis
Less obvious: prolonged PR interval, subcutaneous nodules
The rate of recurrence of C. Difficile infection is higher in which of the following populations:
- Community-acquired
- Hospital-acquired
Neither, they are the same.
N. Meningitides:
- What type of organism?
- T/F: found in normal nasopharyngeal flora.
- What type of organism?
gram NEGATIVE diplococci
- T/F: found in normal nasopharyngeal flora.
True
Give examples of ‘diplococci’:
- Gram positive (SE)
- Gram negative (HB-MAN)
- Gram positive
Strep. peumonia
Enterococcus
2. Gram negative Haemophilus Brucella Maroxella catarrhalis Actinobacter N. meningitidis
Post-CABG patient is found to have Mycobacterium Chimaera surgical site infection several months post-op after requiring a Sorin heater-cooler unit intra-op.
What 3 antimicrobials are indicated?
M. Chimaera (non-TB pulmonary infection) typically occurs greater than 3 months post-op.
- Azithromycin or Clarithromycin
- Rifabutin
- Ethambutol
NB: ARE you treated?
T/F: Mycobacterium Other Than Tuberculosis (MOTT) is a rare complication of patients treated with infliximab for rheumatological or inflammatory bowel disease.
True.
In a patient with a MOTT infection as a complication of infliximab treatment for IBD, what might occur with withdrawal of infliximab treatment?
IRIS (Immune reconstitution inflammatory syndrome).
What is Strongyloidiasis?
Infection with Strongyloides Stercolaris (worm) often from contact with its filariform larvae form from soil or faeces.
What is the ‘life cycle’ of Strongyloides Stercolaris?
The following process takes 3-4 weeks:
- Filariform larvae penetrates the skin and migrates via blood to the lung alveoli.
- Larvae ascend the tracheobronchial tree and are swallowed.
- Larvae mature to adult worms and burrow into the duodenum and jejunum and may live up to 5 years.
- Female worms produce eggs which form infectious ‘rhabdiform larvae’ that develop within the GIT and pass in the faeces.
What is the spectrum of clinical features in a patient with Strongyloides?
‘Asymptomatic eosinophilia’ in immunocompetent to ‘Disseminated hyperinfection syndrome’ in immunocompromised.
How is Strongyloidiasis diagnosed?
Serology and 2 concentrated stool samples for rhabdiform larvae +/- duodenal fluid if clinical suspicion remains.
What is the treatment of uncomplicated Strongyloidiasis?
Ivermectin (200mcg/kg daily) for 2 days.
What is the treatment of complicated Strongyloidiasis i.e. disseminated hyperinfection syndrome?
Extended Ivermectin (200mcg/kg daily) for 5-7 days +/- Albendazole.
Which areas of the world is Strongyloides endemic?
- Tropical and subtropical regions.
- Southeastern states of U.S.
What is is the clinical spectrum of clinical features of Dengue fever?
‘Self-limited’ dengue fever to ‘Dengue hemorrhagic fever with shock syndrome’.
What does classic dengue fever entail?
How long does it last?
- Acute febrile illness associated with headache, retro-orbital pain, marked muscle/joint pain +/- macular papular rash.
- Fevers lasts 5-7 days (long) - sometimes referred to as ‘breakback’ fever.
What are the 4 cardinal features of Dengue haemorrhagic fever?
- Fever
- Vascular permeability leading to plasma leakage (low albumin/effusions)
- Haemorrhagic manifestations (mucosal/GI-bleed)
- Thrombocytopenia (less than 100 x10^3/mm^3)
Which of the 4 cardinal features of Dengue haemorrhagic fever is most specific and life-threatening?
Does this correlate to periods of pyrexia?
- ‘Vascular permeability’ leading to plasma leakage that occurs over 24-48h is the most specific and dangerous.
- Plasma leakage often occurs during period of deferescence (apyrexia)
T/F: In Dengue haemorrhagic fever, plasma leakage and haemorrhage are ‘always’ concomitant.
False.
They may occur together, but may also occur alone.
What type of virus causes Dengue fever?
How many serotypes?
Flavivirus with 4 serotypes: DENV-1, DENV-2, DENV-3, DENV-4.
Which mosquito is the vector for Dengue fever?
Aedes agypti
What percentage of the following is fatal?
- All cases of Dengue haemorrhagic fever
- Treated cases of Dengue haemorrhagic fever
- Untreated Dengue haemorrhagic fever
% Fatal:
- All cases of Dengue haemorrhagic fever = 2.5%
- Treated cases of Dengue haemorrhagic fever = 1%
- Untreated Dengue haemorrhagic fever = 20%
During the acute phase of Dengue fever, which diagnostic tests are most appropriate in the following time-line:
- Less than 3 days from onset of fever?
- Greater than 3 days from onset of fever?
- IgM serology +/- Dengue viral RNA or NS1 antigen (if IgM is negative i.e. risk of false negative)
- IgM serology
In which period of illness may the IgM serology of Dengue fever yield a false negative?
First 6 days.
Patient is suspected of Dengue fever, however IgM serology on day 5 is noted to be negative. What test should be done next?
- Convalescent IgM serology at days 10-14
- IgM serology may yield a false negative in the first 6 days.
What is the rationale behind the development of a tetravalent vaccine (contains all 4 serotypes) for Dengue virus?
- There are 4 serotypes of Dengue virus (DENV 1-4)
- Exposure or vaccine immunisation from one serotype confers longterm immunity from that serotype and a short-lived immunity to the other serotypes.
- Previous exposure to other serotypes increases the risk of Dengue haemorrhagic fever when contracting a different serotype (remains a low risk at 2-4%)
- A tetravalent vaccine leading to tetravalent immunity therefore obviates this risk of severe infection.
What are the 4 Dengue-endemic regions?
- Asia
- Central America
- South America
- Caribbean
What is the WHO I-IV grading system for ‘clinical features’ of Dengue Haemorrhagic Shock (DHS)?
DHS I = fever, plasma leakage, evidence of haemorrhage
DHS II = DHS I + spontaneous bleeding
DHS III = DHS II + hypotension
DHS IV = DHS III + no BP/pulse
What are the principles of management of Dengue Haemorrhagic Shock?
- IVF (monitor haematocrit, aim for decrease)
- +/- PRBC (monitor haematocrit)
- Consider dialysis or plasmaphoresis if NOT improved with above.
Patient is suspected of bacterial meningitis. Given the following gram stain appearance, with bacteria might be suggested?
- Gram negative diplococci
- Gram positive cocci
- Gram positive diplococci
- Gram positive rods and coccobacilli
- Small pleomorphic gram negative coccobacilli
- Gram negative diplococci = Neisseria meningitidis
- Gram positive cocci = Staph. aureus
- Gram positive diplococci = Strep. pneumonia
- Gram positive rods and coccobacilli = Listeria monocytogenes
- Small pleomorphic gram negative coccobacilli = H. influenza
What is the appearance on gram stain of the following pathogens:
- H. influenza
- Neisseria meningitidis
- Listeria monocytogenes
- Strep. pneumonia
- Staph. aureus
- H. influenza = small pleomorphic gram negative coccobacilli
- Neisseria meningitidis = gram negative diplococci
- Listeria monocytogenes = gram positive rods and coccobacilli
- Strep. pneumonia = gram positive diplococci
- Staph. aureus = gram positive cocci
Gram stain suggests gram POSITIVE cocci in clusters.
What is the likely pathogen?
Staphylococcus
Gram stain suggests gram POSITIVE cocci in chains
What are the 2 likely pathogens?
Streptococcus and Enterococcus
Gram stain suggests gram POSITIVE bacilli in palisades
What are the 4 likely pathogens?
CLaMP:
Corynebacterium
Listeria
Mycobacterium (acid-fast)
Propionobacterium
Gram stain suggests gram POSITIVE bacilli that are spore-bearing, large and uniform.
What are the 2 likely pathogens?
BC:
Bacillus
Clostridium
Gram stain suggests gram POSITIVE bacilli that are filamentous with extensive branching.
What are the 3 likely pathogens?
SAN:
Streptomyces
Actinomyces
Norcardia (partially acid-fast)
Gram stain suggests gram POSITIVE bacilli that are filamentous with absent or rudimentary branching.
What is the likely pathogen?
Lactobacillus
Gram stain suggests gram NEGATIVE diplococci.
What is the likely pathogen?
Neisseria
Gram stain suggests gram NEGATIVE bacilli that are cocco-bacilli.
What are the 4 likely pathogens?
BBHL:
Bordetella
Brucella
Haemophilus
Legionella
Gram stain suggests a gram negative cocci and Neisseria is suspected.
Microbiologically, how is N. gonorrhoeae and N. meningitidis differentiated.
N. gonorrhoeae = glucose +
N. meningitidis = glucose + / maltose +
Gram stain suggests gram NEGATIVE bacilli that are lactose positive.
Name 3 fast fermenters and 2 slow fermenters.
Fast fermenters (KEE): Klebsiella, E. coli, Enterobacter
Slow fermenters (CS): Citrobacter, Serratia
Gram stain suggests gram NEGATIVE bacilli that are lactose negative and oxidase POSITIVE.
What are the 2 likely pathogens?
VP:
Vibrio
Pseudomonas
Gram stain suggests gram NEGATIVE bacilli that are lactose negative and oxidase NEGATIVE.
Name 2 urease positive and 2 urease negative pathogens.
Urease positive (HP): H. pylori, Proteus
Urease negative (CS): Campylobacter, Salmonella
What is the lifetime incidence of VZV (Varicella Zoster VIrus) reactivation leading to herpes zoster?
20-30%
To prevent VZV reactivation in an immunocompromised patient, in which 2 scenarios is vaccination indicated in household contacts?
- Vaccination of persons greater than 50yrs who are household contacts of immunocompromised.
- Vaccination of persons less than 50yrs who are household contacts of immunocompromised if they have not been exposed or immunised with VZV.
T/F: Vaccination of a less than 50 year old household contact of an immunocompromised patient is NEVER required.
False.
Household contact should be vaccinated unless they have been previously exposed or vaccinated.
In which age group is compulsory VZV vaccination most efficacious is prevent herpes zoster and post-herpatic neuralgia in unvaccinated individuals?
A. 50-59 yrs
B. 60-69 yrs
C. 70-79 yrs
D. greater than 80 years
A. 50-59 yrs - NO benefit
B. 60-69 yrs - most benefit
C. 70-79 yrs - some benefit
D. greater than 80 years - some benefit (least)
T/F: Moxifloxacin and ciprofloxacin do NOT penetrate into the CSF and therefore is NOT used in meningitis.
False - both do.
Which antibiotic is Listeria monocytogenes resistant to?
Cephalosporins
Prior to considering HIV Pre-exposure Prophylaxis (PrEP) administration, which 4 clinical eligibility criteria need to be met?
- Negative HIV test result using 4th-generation Ag/Ab test within 7 days of starting PrEP
- No signs or symptoms of acute HIV infection
- Normal renal function (eGFR >60 mL/min/1.73 m2)
- No contraindicated medications (renal impairment that increases serum concentrations of tenofovir and emtricitabine)
What is the drug regimen for HIV Pre-exposure Prophylaxis (PrEP)?
- Daily continuing oral dose of coformulated tenofovir and emtricitabine.
- Patients require PrEP for 7 days before high levels of protection are achieved for both vaginal and rectal exposure to HIV
What are the 7 steps of the HIV viral cycle?
- Binding/Attachment – HIV binds to CD4 receptor on CD4 cells
- Fusion – HIV envelope and CD4 membrane fuse to release HIV into cell
- Reverse Transcription (RT) - HIV uses RT (HIV enzyme) to convert HIV RNA to HIV DNA
- Integration – HIV DNA enters the nucleus and integrase (HIV enzyme) inserts HIV DNA to DNA of CD4 cell
- Replication – HIV DNA uses CD4 machinery to make ‘long’ chains of HIV proteins and HIV RNA
- Assembly – new HIV protein and HIV RNA move to cell surface to form immature (non-infectious) HIV
- Budding – newly formed immature (non-infectious) HIV buds away from host CD4 cell then protease (HIV enzyme) breaks up the ‘long’ protein chains to form smaller HIV proteins. These combine to form mature (infectious) HIV
What is the MOA of tenofovir and emtricitabine?
Both NRTI:
tenofovir (NRTI) = nucleoside reverse transcriptase inhibitor (purine - adenosine analogue)
emtricitabine (NRTI) = nucleoside reverse transcriptase inhibitor (pyrimidine - cytidine analogue)
Where do the 6 HIV drug classes act within in the HIV viral cycle?
- Binding/Attachment – CCR5 antagonist
- Fusion – Fusion inhibitors
- Reverse Transcription (RT) - NRTIs and NNRTIs
- Integration – Integrase inhibitors
- Replication – nil
- Assembly – nil
- Budding – Protease inhibitors
How might ALL of the HIV drugs be remembered for MCQs?
Binding/Attachment = CCR5 antagonist (Maraviroc)
Fusion = Fusion inhibitors (Enfuviritide)
Reverse Transcription = NRTIs and NNRTIs (includes many and Abacavir)
Integration = Integrase inhibitors (Raltegravir)
Budding = Protease inhibitors (the other …vir)
So, just 4 to remember really…
In MSM, which of the following situations warrants HIV PrEP (pre-exposure prophylaxis):
- Rectal gonorrhoea within the past 3m
- Methamphetamine use within past 3m
- Rectal chlamydia within the past 3m
ALL of them.
T/F: an uncircumcised male, having more that 1 episode of unprotected anal intercourse where the serostatus of partner was not known should offered HIV PrEP.
True
In a patient with HIV, with what CD4+ T-cell count should prophylaxis against Mycobacterium avian complex be commenced?
CD4+ count < 50 cells/uL
What are the functions for the following toll like receptors (TLR)?
- TLR 1
- TLR 2
- TLR 3
- TLR 4
- TLR 5
- TLR 1 - bind extracellular BACTERIAL lipopeptides and pedtidoglycans
- TLR 2 - bind extracellular lipopeptides and pedtidoglycans
- TLR 3 - binds intracellular dsRNA from viruses
- TLR 4 - binds extracellular lipopolysaccharides promoting macrophage activation and cytokine storm
- TLR 5 - binds extracellular bacterial flagellin
MBL (mannose binding lectin) binds to a range of sugars found on pathogens.
Which pathogens have these sugars on their surface?
Most: Bacteria / Viruses / Fungi / Protozoa / Yeast
What are the live vaccines?
MOBY-VRT
MOBY-VRT:
M - MMR
O - oral polio
B - BCG
Y - yellow fever
V - varicella
R - rotavirus
T - oral typhoid
What are the 3 scenarios that live vaccines are contraindicated?
- > 20mg/d Prednisone
- HIV CD4 < 200
- TNF-alpha Rx
At what CD4 count should HIV patients be commenced on HAART therapy?
Any.
START trial suggest CD4 > 500 benefit from therapy.
Why are the following HAART regimens no longer recommended as first-line therapy:
- Tenofovir/Emtricitabine/Efavirenz
- Tenofovir/Emtricitabine/boosted Atazanavir
- Tenofovir/Emtricitabine/Efavirenz - neuropsychiatric AE
2. Tenofovir/Emtricitabine/boosted Atazanavir - Atazanavir related hyperbilirubinaemia
What are the new first line HAART regimens (2)?
Comment on pill burden of each.
- Tenofovir/Emtricitabine/boosted Darunavir (3 pills)
2. Abacavir/Lamivudine/Dolutegravir (1 pill only)
T/F: Tigecycline is a broad-spectrum Abx, but does NOT treat Peudomonas aeruginosa.
True.
