Path - Microbiology Flashcards

Question

Which statement is true of variant Creutzfeld-jacob disease? A. The disease mainly affects elderly people B. vCJD is more rapidly progressive than sporadic CJD C. The initial symptoms are always neurological D. An MRI typically shows the pulvinar sign E. EEG is usually abnormal

Answer 1

D. An MRI typically shows the pulvinar sign Variant CJD occurs in younger people (median onset is 26) and is slower progressing than sCJD. It usually presents with psychiatric symptoms (anxiety, paranoia, hallucinations, dysphoria) and neurological symptoms appear later (peripheral neuropathy, ataxia, myoclonus, chorea, dementia). Signs of vCJD include: a positive tonsillar biopsy (100% sensitive and specific in vCJD), increased signal form the pulvinar nuclei in the posterior thalamus on MRI (pulvinar sign), and florid plaques seen on biopsy. All bar one patients who have been known to contract vCJD have had the methyinine-methyinine polymorphism at codon 129 of the PRNP gene. It is not known why this association exists.

Answer 2

A. The vast majority of cases of variant CJD have been found to be MM at codon 129 of the PRNP gene All but one case

Answer 3

A. Benzylpenicillin This is most probably a case of bacterial pharyngitis, as indicated by a high centor score, as a score of 3-4 indicates a 32-56% chance of a Streptococcal cause. As a result, benzylpenicillin should be given for 10 days.

Answer 4

C. Consider ICU admission and give I.V. co-amoxiclav with clarithromycin A CURB-65 score would be used to calculate the predicted mortality, and by extension the severity of this patient's disease. Confusion - new onset, defined by an AMTS of 8 or less Urea - Serum conc. > 7mmol/L Respiratory rate - >30 breaths per minute Blood pressure - less than 90 systolic or 60 diastolic 65 - aged 65 or over This patient has a CURB-65 score of 4 and so should be given I.V. co-amoxiclav with clarithromycin and should be admitted to ITU. A score of 0 or 1 indicates possible home-based care, 2 indicates hospital-based care, and 3 or more indicates ITU admission. It is important to monitor for sepsis and remember the Sepsis 6: ``` Monitor urine output Take blood cultures Serial lactate measurements Give oxygen Give empirical antibiotics Give I.V. saline ```

Answer 5

C. Hepatitis C This is a clinical picture of a woman with acute-on-chronic liver failure (also known as decompensated liver failure) as indicated by ascites (low albumin), spider naevi and palmar erythema (high oestrogens as the liver can no longer metabolise them). The seafood is a red herring (badoom cha) because though that could infect this patient with hepatitis A, it is a self-limiting illness that could not cause this extent of damage. This woman most likely contracted hepatitis C from contaminated blood products given when she gave birth to her first child, as this was before the advent of hepatitis C screening in the UK (1991).

Answer 6

A. Because ceftriaxone is not effective against Listeria Ceftriaxone is a third generation cephalosporins with good Gram positive and negative cover, but does not protect against Listeria, an important cause of meningitis in newborns and immunocompromised patients. Cheese may be contaminated with Listeria, and is an important clue in the history.

Answer 7

E. Flucloxacillin Benzylpenicillin, piperacillin, and amoxicillin are all antibiotics of the penicillin class which are sensitive to beta-lactamase. Tazobactam is a beta-lactamase inhibitor which is given along with piperacillin, but which is not itself an antibiotic. Flucloxacillin is a member of the penicillin class, but is resistant to beta-lactamase.

Answer 8

D. Cryptococcus neoformans Cryptococcus neoformans is a cause of meningitis usually seen only in HIV+ patients. It is well-known for causing a particularly high opening pressure on LP. Cryptococcus neoformans is a fungus that can be stained for using the India Ink stain.

Answer 9

C. Unknown INR prior to procedure ``` Unless there is a known clotting issue, this is not a contraindication. Some of the main contraindications to LP are: GCS reduction below 12 Continuous or uncontrolled seizures Focal neurology Papilloedema Infection at LP site Cardiac/ respiratory compromise Thrombocytopenia/ clotting abnormalities An extensive or spreading purpuric rash (i.e. one which indicates DIC which will derange clotting and make the procedure unsafe) ```

Answer 10

C. Typhoid When considering fever in the returning traveller, malaria and typhoid are the most common diagnoses and the most important to remember. Typhoid is caused by Salmonella typhi (though an essentially identical disease - paratyphoid - is caused by Salmonella paratyphi). Typhoid causes constant high fevers, headache, cough, malaise, and constipation (NOT DIARRHOEA), and features an insidious onset. More distinctive features include rose spots (small red macules caused by bacterial emboli), relative bradycardia (Faget's sign - the pairing of relative bradycardia with fever as usually a febrile patient would be tachycardic), intestinal haemorrhages resulting from colonisation of Peyer's patches, and intestinal perforation. S. typhi has flagella and so is motile. As a result, it can spread throughout the body and so typhoid can be picked up on blood cultures, where it will appear as a Gram negative rod. It can also lie dormant within the gallbladder, which is how the original 'Typhoid Mary' had recurrent disease.

Answer 11

D. Pneumocystis jiroveci PCP used to stand for Pneumocystis carinii pneumonia, and is still used though the organism has been re-named Pneumocytsis jiroveci. PCP is an AIDS-defining illness and features a non-productive cough along with SOB, fever and generic pneumonia/ infection signs. The presentation is generally insidious, and may feature a normal or non-specific CXR. A CXR may feature perihilar fine reticular shadowing, but a CT chest may be more helpful and may feature perihilar ground glass opacities particularly in the apical regions of the lungs. Decreased exercise tolerance or reduced oxygen saturations on exercise are classic of PCP. Standard treatment is with Co-trimoxazole (trimethoprim with sulphamexothazole). The urinary antigen tests mentioned are for pneumococcal and legionella species. each test has very high specificity, but sensitivity of only around 60%, nevertheless negative tests suggest those options are less likely. NB: PCP increases the risk of a pneumothorax

Answer 12

E. Dengue fever Dengue fever is caused by a single-stranded RNA flaviviridae virus spread by the Aedes mosquito. Infection with the virus may cause either Dengue fever or Dengue haemorrhagic fever. It is a disease endemic to the tropics, and is classified as a neglected tropical disease, and is an important differential when considering fever in the returning traveller. Primary infection usually causes Dengue fever (secondary infection may also cause it) which is characterised by fever, severe headache (especially retro-orbital), myalgia, arthralgia, anorexia, abdominal discomfort, and perhaps a maculopapular rash. The fever may be biphasic (saddleback fever) though this is relatively uncommon. Dengue haemorrhagic fever may feature the symptoms above, but will include some of: petechiae/ echymoses, epistaxis, bleeding from the gums, internal bleeding leading to circulatory compromise. Reduced platelet count is a defining feature of Dengue haemorrhagic fever, but may also be present in regular Dengue fever. Joint pain is common, and can be used to differentiate Dengue from Chikungunya, an arbovirius which may present similarly, but which features much worse debilitating joint pain. There are four serotypes of Dengue fever, and infection with one generally confers immunity against that serotype but not the others. The big problem with Dengue fever, is that subsequent infection with another serotype results in a more severe infection. The pathogenesis of this is not fully understood, but it is known that antibodies against one serotype somehow enhance infection by another, and that the immune system plays a significant role in the pathogenesis of haemorrhagic fever. This is relatively rare (affecting only 2-4% of patients with secondary Dengue infection) but highly dangerous. NB: Dengue fever often is asymptomatic or causes mild, vague symptoms (particularly in young children) in the same way that Polio is usually asymptomatic or mild, but can still be dangerous. The prevalence of Dengue infection means that it still exerts a significant disease burden worldwide. NB: The rash in this question is a combination of non-blanching and blanching because the patient has developed a petechial rash in addition to the blanching maculopapular rash of Dengue fever.

Answer 13

B. HIV seroconversion illness Seroconversion refers to the time when the immune system begins to create antibodies to a pathogen. In patients with HIV this may be accompanied by a brief and self-resolving flu-like illness. This occurs roughly between 3-12 weeks after infection but varies from person to person. Influenza and mononucleosis are good differentials for this illness, though the diarrhoea and time frame since exposure are more suggestive of seroconversion illness. Seroconversion illness only occurs in ~50% of patients. Cryptosporidium and toxoplasmosis are parasitic diseases which should not cause significant disease in immunocompetent hosts. In immunocompromised patients cryptosporidium may cause severe diarrhoeal disease (and can cause mild symptoms in immunocompetent patients), and toxoplasma causes widespread infection but particularly affects the CNS causing abscesses and encephalitis (toxoplasmosis is one of the most common opportunistic infections in HIV/AIDS).

Answer 14

E. Measles Measles is an extremely infectious viral disease. It is covered by the MMR vaccine which confers a 93% or 97% rate of protection depending on whether one or two doses are given (according to CDC). The MMR vaccine is very effective, but confers a lower rate of protection against mumps (78-88%). The classic presentation of mumps is a high fever with the three C's: conjunctivitis, coryza (upper respiratory symptoms - rhinitis essentially), and cough. This initial phase lasts around three days and begins after a 10-14 day incubation period. During the initial phase, Koplik spots may appear - white spots on the buccal mucosa. After the initial phase the classic measles maculopapular rash appears, starting around the hairline and moving caudally.

Answer 15

D. Immune reconstitution Immune reconstitution inflammatory syndrome (IRIS) occurs when a patient with a low CD4 count has opportunistic infection, and is then started on anti-retroviral therapy. As the immune system reconstitutes it may cause either an unmasking or a paradoxical IRIS. In unmasking IRIS, the immune system creates an inflammatory response against a previously unknown opportunistic infection, causing the normal symptoms of the disease. In paradoxical IRIS, there is an inflammatory response causing relapse of symptoms of a prior infection that has already been treated (blood cultures are often sterile). The purple skin plaques mentioned are Kaposi's sarcomas - a cancer caused by HHV8 which only appears in immunocompromised patients - and hairy leukoplakia (white plaque on the side of the tongue which cannot be wiped away) which also indicates an immunocompromised state.

Answer 16

A. Encephalitis The acronym for causes of a ring-enhancing lesion on a head CT scan is MAGICAL DR: M - metastasis A - abscess (e.g. toxoplasmosis) G - glioblastoma I - infarct (subacute phase), inflammation (tuberculoma, neurocystericosis - tapeworm infection of CNS) C - contusion A - AIDS-related CNS disease L - lymphoma (ring-enhancing appearance more common in immunocompromised) D - Demyleinating disease (classically produces an incomplete ring) R - radiation necrosis, resolving haematoma

Answer 17

C. 200 CD4 count is used to monitor the competence of HIV patients' immune systems, and the lower it drops, the more opportunistic infections may take hold and they more severe these infections will be. Viral load correlates inversely with CD4 count. HIV infection is comprised of three phases: eclipse, acute, and chronic. During the eclipse phase, the virus spreads and begins to infect cells, establishing a viral reservoir. In the acute phase, the immune system begins to produce antibodies to HIV which may cause a brief seroconversion illness (generic flu-like symptoms). Viral load rapidly peaks in the acute phase, and this is the first time HIV can be detected on a blood test. Viral load rapidly decreases to a point known as the 'set-point' which is important in prognosis, and from there chronic infection ensues with steady CD4 loss and progression to AIDS. This is a link to an excellent Nature review article on HIV with some very good diagrams: https://www.nature.com/articles/nrdp201535#Sec12

Answer 18

E. CD4 and co-receptors The primary receptor for HIV is CD4, but co-receptors are also required for entry, most often the chemokine receptors CXCR4 and CCR5. Although HLA molecules are not important for the entry of HIV into host cells, they are important in mediating immunity, as certain HLA I (and to a lesser extent HLA II) subtypes are enriched in the naturally immune population (<1% infected people).

Answer 19

B. They are secreted through bile Beta lactams are renally excreted, and so an altered dose should be considered in patients with renal impairment.

Answer 20

A. Chloramphenicol Macrolides (clarithromycin), glycopeptides (vancomycin, teicoplanin), and oxazolidinones (Linezolid) are not generally active against Gram negative organisms. Whilst more advanced penicillins have increasing Gram negative coverage, benzylpenicillin is very narrow-spectrum and is not useful against Gram negative organisms.

Answer 21

``` 1 - D. Allogenic stem cell transplant recipients 2 - B. Advanced HIV patients 3 - A. Solid organ transplant recipients 4 - E. Cytotoxic chemotherapy patients 5 - C. Patients on long-term steroids ``` Although all of these patients will be more vulnerable to opportunistic viral infections, those who have received allogenic bone marrow transplants are most heavily immunosuppressed (although long-term, these patients' immunosuppression can be tapered off more than in solid organ recipients).

Answer 22

D. Widespread purple papular lesions on the skin of a man who has been steadily declining Varicella-Zoster virus (VZV) usually infect children, giving them the relatively harmless disease of chicken pox. VZV is a member of the herpes virus family (HHV3) and lies dormant in nerve ganglia after initial infection. It can reactivate later in life (particularly in the elderly) to cause shingles - a particularly painful vesicular rash that is confined to a dermatome. In the immunocompromised VZV is a much more significant problem. Whilst it is generally true that - in a significantly immunocomproimised patient - any pathogen can infect any system, there are certain diseases that are particularly associated with VZV infection. These include pneumonitis (A), acute retinal necrosis (B), cerebral vasculopathy leading to stroke (C), purpura fulminans - acquired protein S deficiency resulting from VZV infection and leading to intravascular thrombosis and haemorrhage into the skin (E). 'D' describes Kaposi's sarcoma - purple/brown papules or plaques that can only appear in the immunocompromised, and are classically associated with AIDS. Kaposi's sarcoma is caused by HHV8, not VZV.

Answer 23

A. Post-transplant lymphoproliferative disease - 3. EBV B. Retinitis - 5. CMV C. Progressive multifocal leukoencephalopathy - 1. JC virus D. Multi-dermatomal shingles - 2. VZV E. Haemorrhagic cystitis - 4. BK virus BK virus is a polyoma virus associated with haemorrhagic cystitis in bone marrow transplant patients, and nephropathy in renal transplant patients

Answer 24

D. HBV sAg (-), HBV core Ab (+), HBV sAb (+) Since the past infection was cleared, there should be no surface antigen remaining. The significance of the presence of core antibodies is that the vaccine for hepatitis B only causes production of surface antibodies, therefore the presence of core antibodies helps differentiate cleared infection from vaccinated.

Answer 25

B. New tricuspid regurgitation with a fever of 38.5 and Janeway lesions and Osler nodes on the hands Although realistically you would strongly suspect infective endocarditis in every one of these cases, the Duke criteria are very specific in terms of what does and does not confirm it. The Duke criteria is as follows: To definitely diagnose infective endocarditis you must have either: Pathological evidence (histology showing vegetations) Or Clinical evidence Clinical evidence is divided into major and minor criteria. To confirm the diagnosis you need 2 major criteria, or 1 major and 3 minor criteria, or 5 minor criteria. Major criteria: 1) Evidence of microorganisms in the blood NB: if S. viridans, S. bovis, HACEK group, S. aureus, enterococci, then only two separate cultures are needed. If other organisms are detected, then either two samples >12 hours apart are needed, or all 3 or the majority of 4 samples have to be positive 2) Evidence of endocardial involvement (signs on echocardiogram or new valvular regurgitation) Minor criteria: 1) Predisposing heart condition or IVDU 2) Fever ≥ 38 3) Vascular events e.g. septic pulmonary emboli, Janeway lesions, intracranial haemorrhage 4) Immune events e.g. Roth spots, Osler's nodes, glomerulonephritis 5) Cultures or biochemical evidence of infection that does not meet the major criteria 6) Echo findings indicating infective endocarditis but not sufficient to meet the major criteria Luke Moore says to learn this in his PUO lecture

Answer 26

C. Age of 37 It is a good rule of thumb that people do not get giant cell arteritis below the age of 50

Answer 27

B. HIV test All patients would ideally get an HIV test on admission to hospital, especially for PUO.

Answer 28

E. EBV IgM EBV PCR is useful and can be done (and is conceivably a correct answer), but is expensive and ideally not used in this case. Although the heterophile antibody test is useful and widely used, it may also be positive in CMV infection: EBV IgM is more specific. You can't generally culture viruses.

Answer 29

A. Rifampicin - 4. Enzyme inducer B. Isoniazid - 2. Peripheral neuropathy C. Pyrazinimide - 1. Non-gout arthralgia D. Ethambutol - 3. Optic neuritis Rifampicin also causes red secretions (urine, sweat, tears) Isoniazid must be given with B6 to combat the peripheral neuropathy Pyrazinimide can trigger gout, but can also cause nont gout-arthralgia Ethambutol also causes red-green colour blindness All four can cause GI disturbance and liver toxicity, though pyrazinimide most commonly causes it, so baseline liver function tests must be carried out. Find Northwick quiz

Answer 30

E. Mycoplasma pneumoniae Mycoplasma pneumoniae is one of the most common causes of community-acquired pneumonia in children and young adults, and is still a significant cause in adults. It is an atypical organism, i.e. it does not have a cell wall, so beta lactams will not be effective against it. Instead, an antibiotic that targets protein production (e.g. a tetracycline or macrolide) will be needed. Mycoplasma pneumoniae typically presents insidiously, with a persistent dry cough and malaise. It can eventually produce severe pneumonia as it has in this patient. Cold agglutinins are the big key in mycoplasma infection: it triggers an autoimmune reaction which agglutinates and lyses RBCs.

Answer 31

``` Falciparum Ovale Vivax Malariae Knowlesi ```

Answer 32

1) Because the life cycle of Plasmodium vivax and ovale include a hypnozoite stage in the liver. The parasite lies dormant within the liver and are not affected by the initial course of chloroquine. However a two-week course of primaquine can kill the hypnozoites; without it, the patient will experience recurrent malaria. 2) G6PD test, because primaquine can trigger serious haemolytic anaemia in patients who are G6PD deficient

Answer 33

E) Malaria The three key differentials of fever in the returning traveller are malaria, dengue fever, and typhoid. Amongst them, malaria is comfortably the most common, and if it is falciparum malaria it can be very dangerous.

Answer 34

D. I.V. artesunate I.V. artesunate has been proven to reduce mortality by 34.7% compared to quinine (SEAQAMAT trial) and so is the best choice for severe falciparum malaria, as indicated by the high parasitaemia. Definition of severe malaria varies by country and organisation, but 20% is severe by any standards. Although artesunate is ideal, it is a specialist drug which is not always available, in which case I.V. quinine should be the second drug of choice. Co-artem and malarone are oral treatments for falciparum malaria. Quinine can be used, but is generally avoided as it has more side-effects. NB: hypoglycaemia is an important and dangerous complication of malaria which should not be forgotten, though its pathophysiology is unclear.

Answer 35

B. Campylobacter jejuni ETEC, C. jejuni, and E. histolytica may all cause diarrhoea, but ETEC causes traveller's diarrhoea - not bloody diarrhoea, though enterohaemorrhagic E. coli (EHEC - the best known serotype being 0157:H7 which can cause haemolytic-uraemic syndrome) can. E. histolytica is unlikely in this case because it is not endemic to the UK, though it is found in North and South America and Asia. S. typhi and paratyphi cause typhoid and paratyphoid (clinically they are essentially the same) which features constipation, not diarrhoea. The organisms most associated with bloody diarrhoea are the CHESS organisms: ``` Campylobacter Haemorrhagic E. coli Entamoeba histolytica Salmonella enteredis Shigella ```

Answer 36

D. Doxycycline This is a history of pneumonia caused by L. pneumophilia, an atypical organism. The atypical organisms in pneumonia lack a cell wall, so penicillins (amoxicillin in co-amoxiclav and piperacillin in tazocin) are not effective. An antibiotic is needed which affects protein synthesis: either a tetracycline or a macrolide. Macrolides are first line, but are not an option here, so a tetracycline (doxycycline) is the best option. Other atytpical organisms include Chlamydia psitticai, Mycoplasma pneumoniae, and Coxiella burnetti. These organisms carry a particularly high risk of extra-pulmonary involvement, and will often be more chronic and insidious than typical pneumonia. Although malignancy could be a differential here, it is not the most likely diagnosis. It should be remembered that both mesothelioma and small cell lung cancer can be associated with hyponatraemia, however the CXR in this case makes it unlikely.

Answer 37

B. Empyema Empyema is a collection of pus in the pleural cavity, and can behave like an abscess in that it won't necessarily respond to antibiotics alone and will need draining. The failure to respond to antibiotics could also indicate MRSA, mesothelioma, or TB, but the history doesn't suggest any of these.

Answer 38

It is metabolised to its active form by viral thymidine kinase (and other kinases subsequently) and so won't become active in non-infected cells. When resistance to aciclovir arises, it is almost always through a mutation in viral thymidine kinase (95% of cases) whereas mtuations in viral DNA polymerase are rare (5%).

Answer 39

The presence of squamous epithelial cells in an MSU would imply the sample was incorrectly taken. The initial stream should wash away any epithelial cells along with any bacteria colonising the urethra. These bacteria are not a pathological issue as they are not in the bladder, which is why the sample should be mid-stream, so the only bacteria collected have come from the bladder. The presence of squamous epithelial cells reduces the validity of the sample. The sample is also unlikely to be valid if the culture shows mixed bacterial growth, as in >95% of cases there is only a single organism responsible for a UTI.

Answer 40

E. Chlamydia trachomatis A little known fact is that Chlamydia trachomatis is the most common infectious cause of blindness in the world. Though usually though of as an STD, C. trachomatis can be spread from faeces by the musca sorbens fly, and by hand-eye transmission between people. The infection causes inflammation of the inner eyelid. Repeated infections cause the eyelid to scar and turn inwards, leading to corneal scarring and blindness.

Answer 41

B. Performing the HIV test without consent would breach B’s article 8 rights The four main articles of the Human Rights Act relevant to healthcare are 2, 3, 5, and 8.These are the right to life, prohibition of torture, right to liberty, and right to a private life. Article 8 is the right which protects a patient's right to confidentiality and to refuse treatment, and so is the most relevant in this case.

Answer 42

Certain haematological malignancies (e.g. myelofibrosis, CML, hairy cell leukaemia) Chronic malaria Leishmaniasis Gaucher disease

Answer 43

C. Adenovirus Adenovirus is considered to be a particularly big problem in bone marrow transplant recipients, especially young ones. It can cause disseminated disease and is a significant cause of mortality (~25% overall for untreated asymptomatic patients, but 50% for pneumonia, and 80% for disseminated disease).

Answer 44

B. A high chance of curing chronic infection using ribavirin and sofosbuvir Hepatitis C causes chronic infection more often than hepatitis B, and yet treatment (e.g. with sofosbuvir and ribavirin - B) has a ~90% cure rate. Conversely, though it causes chronic infection in <5% people, hepatitis B is not curable. Both viruses can be transmitted through contact with infected blood. Hepatitis C can also be transmitted vertically from mother to baby, or through sexual practices (particularly those leading to blood exposure), but these are rarer. Hepatitis B is most commonly spread from mother to baby at birth (perinatal) but may also be spread through bodily fluids (e.g. sexually). Blood transfusions before September 1991 were not screened for hepatitis in the UK, so this should be considered in a person who may be presenting with sequelae of chronic hepatitis. Both viruses can lead to cirrhosis and liver cancer (C). It is known that children in the first year of life who become infected with hepatitis B have a 80-90% chance of establishing a chronic infection, compared to 30-50% of children < 6, or 5% of adults. Accordingly, 'D' is true of hepatitis B, not C. The incubation periods of both viruses are similar and hugely variable, from a few weeks to 6 months, hence 'E' is not useful for discriminating between the viruses.

Answer 45

E. Pulmonary aspergillosis Aspergillus is generally not an issue in immunocompetent patients, but this individual has recently received an allogenic BMT and so will be heavily immunosuppressed (though with time the immunosuppression for BMT can be significantly tapered off). The major clue to this being aspergillosis is the presence of the 'Halo sign' on CT: a ground glass opacity surrounding a pulmonary nodule caused by haemorrhage. The halo sign is not totally specific, but classically indicates invasive aspergillosis.

Answer 46

B. Proteus mirabalis This would be defined as a complicated UTI, because it occurs on a background of obstruction and hydronephrosis. Proteus species are a major cause of UTI in patients with structural abnormalities to their urinary tract, though E. coli is still the most common cause. Klebsiella is also a common cause of UTIs.

Answer 47

C. Clear fluid, high lymphocytes, normal glucose, slightly raised protein, PCR positive for enterovirus This is essentially just a question of what is the most common cause of meningitis. Viral meningitis is the most common, and it is most commonly caused by echoviruses or coxsackie viruses - i.e. non-polio enteroviruses. See the CDC page for more info: https://www.cdc.gov/meningitis/viral.html

Answer 48

D. Staphylococcus saprophyticus S. saprophyticus is a Gram positive coagulase negative coccus, and is the second most common cause of UTI in young women after E. coli. The urine dipstick result (if assumed to be a valid sample and read correctly) makes the presence of E. coli less likely because of the absence of nitrites. Nitrites are produced from nitrates in the urine by Gram negative bacteria, therefore if the causative organism is Gram positive, nitrites will be negative but leukocytes will be positive.

Answer 49

1. Tsetse fly - C. Trypanosoma brucei 2. Sandfly - D. Leishmania 3. Aedes mosquito - B. Dengue fever virus/ Chikungunya fever virus 4. Anopheles mosquito - A. Malaria 5. Ixodes tick - E. Borrelia burgdorferi NB: As a rule the Aedes mosquito bits during the day, and the Anopholes mosquito bites at night

Answer 50

B. Klebsiella pneumoniae K. pneumoniae is a less common organism in pneumonia cases, but is seen in those with underlying conditions (e.g. T2DM), and especially in alcoholics. Once established, Klebsiella has a high mortality rate and can rapidly prove fatal. NB: the important nosocomial pathogens are the ESKAPE ones: ``` Enterococcus faecium Staphylococcus aureus Klebsiella pneumoniae Acinetobacter baumannii Pseudomonas aeruginosa Enterobacter species (does not include E. coli) ``` (the first three are Gram+, while the last three are Gram-)

Answer 51

A. Subacute bacterial endocarditis, Streptococcus viridans Streptococcus viridans is an alpha-haemolytic Gram+ coccus which is usually a harmless commensal of the mouth. However during dental procedures it can enter the blood, and can cause subacute endocarditis, a more insidious form of bacterial endocarditis. As it is more chronic, subacute endocarditis is more likely to cause the classic signs of endocarditis (including nail clubbing). The signs of endocarditis can be remembered using the mnemonic 'FROM JANE': ``` Fever Roth spots Osler's nodes Murmur Janeway lesions Anaemia Nail bed haemorrhage Emboli (causing stroke, PE, haematuria from renal damage) ```

Answer 52

A. Measles R0 is the average number of healthy people to which one infected individual will pass on an infection. Ebola has an R0 of only 2, SARS and HIV have an R0 of 4, Mumps has an R0 of 10, and Measles is ludicrously contagious with a R0 of 18.

Answer 53

C. Amoebiasis ``` As a rule, there are 5 main organisms that cause bloody diarrhoea - the CHESS organisms: Campylobacter jejuni Haemolytic E. coli Entamoeba histolytica Shigella Salmonella enterica ``` Entamoeba histolytica infection is an important cause of fever in the returning traveller, and typically will cause a fever whose origin cannot be traced, until a liver abscess is found. Entamoeba histolytica initially causes bloody diarrhoea, but once it enters the bloodstream it spreads to the liver and establishes an abscess. This may well cause swinging fevers due to intermittent bactaraemia, and so may be difficult to distinguish from malaria. Risk factors include institutionalisation, being male, being MSM (men who have sex with men), and travel in endemic areas.

Answer 54

D. Cytomegalovirus Though sensorineural hearing loss is included in the classic triad of Rubella syndrome (along with eye and heart abnormalities e.g. cataracts and PDA), cytomegalovirus is the most common non-genetic cause of sensorineural hearing loss in children. Furthermore, Rubella is far less likely to cause abnormalities if a pregnant woman is infected after 20 weeks, meaning that the abnormality in this question is more likely to be due to cytomegalovirus. NB: HSV is most likely to be transmitted from mother to baby if the mother is infected within 6 weeks of delivery, as there is not time to produce antibodies. Therefore there is a high risk of transmission during vaginal birth, so a C-section is recommended.

Answer 55

B. Herpes simplex Whilst herpes simplex may cause intrauterine infection (which leads to fairly standard eye, skin, and brain abnormalities) only 5% of infections are transmitted in utero. 85% are transmitted during birth, and particular risk factors for this are prolonged rupture of membranes and vaginal birth. Type of maternal infection is also a significant risk factor; if the mother has never been infected with herpes before, she has a 57% chance of passing the infection to the neonate. Herpes simplex is most likely to be transmitted to the neonate if the mother is infected within 6 weeks of her delivery, as this does not allow time for the formation of protective antibodies which reduce transmission. Once infected, 45% of neonates develop localised skin, eye, and mouth (SEM) disease. Around 30% will develop CNS disease (which may also feature SEM involvement), and 25% will develop disseminated disease. Disseminated disease may cause a range of complications including pneumonitis, DIC, hepatitis, and frequently CNS involvement, and even with antiviral treatment is associated with major mortality (~30%) and long term neurological sequelae (~17%). Whilst VZV can cause significant infection in neonates, 90% of women in developed countries are immune by the time they are pregnant, and neonates are only considered significantly vulnerable if the mother is infected within 7 days before or after birth, as there is no time for transfer of passive immunity via antibodies to the neonate. VZV may cause a congenital syndrome but this is fairly uncommon. NB: In >20% of cases, the neonate will not display the classic skin lesions associated with adult herpes simplex infection, so their absence does not exclude infection.

Answer 56

E. Bacillus cereus Bacillus cereus is classically associated with rice and produces two toxins: a heat-labile one which causes diarrhoeal illness, and a heat-stable one which causes emetic illness. In this case the bacteria have been killed by the thorough reheating of the rice, but the heat-stable emetic toxin has remained and caused the rapid-onset nausea and vomiting.

Answer 57

C. Pear-shaped trophozoites with 4 flagella and 2 nuclei Giardiasis is a protozoan infection causing a malabsorptive diarrhoea - hence the pale, foul-smelling stools (steathorrea) and weight loss. Risk factors include MSM (men who have sex with men), being institutionalised in a mental hospital, and travel to an endemic region.

Answer 58

E. Rubella VZV only 0.5%, peaks at 2% between 13-20 weeks HSV: vulnerable in 3rd trimester, particularly if infected within 6 weeks of birth, low rates of transmission in utero Parvovirus ~33% before 20 weeks Cytomegalovirus, though the most common congenital infection, 30-40% transmission Rubella carries 20% chance of fetal loss, and 90% surviving pregnancies develop congenital Rubella syndrome

Answer 59

B. Shigella dysenteriae Along with norovirus, shigella is considered to have the lowest infective dose of any enteric pathogen, and so can very easily spread between hosts.

Answer 60

D. Efficacy is believed to be extremely high No RCT for PEP efficacy can be conducted because of the obvious ethical issues, but the CDC released a review of 6 observational studies in 2016 which revealed a failure rate of only 0.5%. Even in the cases where PEP 'failed' it is though that other factors were responsible and this was not truly down to failure of the medication. https://www.aidsmap.com/about-hiv/how-effective-post-exposure-prophylaxis-pep

Answer 61

Wild birds e.g. ducks Influenza A viruses are the most significant from a public health perspective as they tend to cause pandemics. This is because they are present in a wide variety of reservoirs and have a strong presence within those reservoir populations. B and C flu viruses cause seasonal flu but have less of a reservoir so don't tend to cause pandemics

Answer 62

C. The influenza virus requires activation by host cell proteases that are only expressed in the respiratory tract Haemagglutinin is a viral protein that is essential for its entry into host cells. Haemagglutinin is produced as a precursor by the virus, which must be cleaved by a host protease to become active. The majority of influenza viruses require a very specific protease to perform this action: human airway tryptase. However influenza viruses may undergo mutations allowing them to be cleaved by proteases found elsewhere in the host body. The avian H5 and H7 subtypes are well known for this property and can kill bird very quickly. They may be transmitted into humans where they cause severe disseminated disease and viraemia because the virus has the ability to replicate anywhere - they are no longer restricted by their tropism. High viral load in the blood drives production of inflammatory cytokines and leads to cytokine storm, which in turn triggers systemic inflammatory responses e.g. ARDS. It is for this reason that infection with certain subtypes of avian flu (e.g. H5 and H7) are associated with high mortality.

Answer 63

Novel antigenicity Ability to replicate within the human respiratory tract Effective transmission between humans

Answer 64

A switch in affinity of haemagglutinin from the alpha-2,3 to the alpha-2,6 variant of sialic acid An increase in virion stability conferred by adaptation to a lower pH environment An increase in the neuraminidase stalk length

Answer 65

Because the virus bore antigenic similarities to an influenza virus circulating between 1920-1940

Answer 66

B. A purified fraction containing HA and NA of an inactivated virus Vulnerable children are given the live attenuated quadrivalent vaccine

Answer 67

Thymic infection reduces production of new T-cells Incomplete reverse transcript production stimulates inflammation and cell death Direct cytopathogenicity of HIV replication Generalised activation of immune response?

Answer 68

E. Memory CD4 cells Memory CD4+ cells are especially vulnerable to HIV infection because they highly express CCR5 (a co-receptor for HIV entry into cells). Memory CD4+ cells act as a reservoir for HIV infection.

Answer 69

A. Colistin Colistin is a last-ditch treatment for multi-drug resistant Gram negative infections

Answer 70

Lyme disease *Taken from 2017 paper

Answer 71

I.V. Artesunate Malaria Treatment Guide: Non-falciparum - Chloroquine + Primaquine ``` Falciparum: Mild (parasitaemia <2%, reasonably well): Quinine *OR* Co-Artem *OR* Malarone ``` Severe: I.V. Artesunate I.V. Quinine if Artesunate unavailable *Taken from 2017 paper

Answer 72

A. Tsetse fly *Taken from 2017 paper

Answer 73

Give her VZIG NB: shingles doesn't count *Taken from 2017 paper

Answer 74

Malaria *Taken from 2017 paper

Answer 75

1. 74 year old woman with Gram + bacilli in CSF - F. L. monocytogenes 2. Man with meningitis Gram + diplococci - B. S. pneumoniae 3. Young woman with following CSF results: normal glucose, raised lymphocytes, slightly raised protein - A. Herpes simplex virus 4. 2 day old baby with gram negative rods in CSF - D. E. coli 5. Young guy with meningitis and Gram negative diplococci - E. N. meningitidis * Taken from 2017 paper

Answer 76

1. A young woman develops diarrhoea whilst travelling abroad through rural India - Escherichia Coli 2. A man develops foul-smelling diarrhoea and cramping pain 5 days after eating chicken at a barbecue - Campylobacter 3. A man presents with vomiting 10 hours after going out for a meal at a Chinese buffet restaurant with a lot of rice - Bacillus Cereus 4. Woman has had some surgery which required antibiotics, and now has profuse watery diarrhoea - Clostridium Difficile 5. A ward sister gets diarrhoea, and patients on the ward have been ill recently with the same symptoms - Norovirus 6. An MSM man who has just returned from travelling has been experiencing particularly foul-smelling greasy diarrhoea for the past two weeks - Giardia 7. A 3 year old unvaccinated child develops vomiting and diarrhoea - Rotavirus NB: Question 2 is a little unfair because this could very reasonably be Salmonella, but Campylobacter is generally acknowledged to be a slightly more common cause of gastroenteritis *Modified from 2017 paper

Answer 77

1. What is the treatment of choice for Listeria meningitis? - Amoxicillin 2. Which antibiotic would be used for a mild CAP (CURB65 of 0 or 1) - Amoxicillin 3. Which antibiotic would be used for a severe HAP - Tazocin 2. Which antibiotic should be used to treat Strep pharyngitis? - Phenoxymethylpenicllin/ penicillin V 3. Which antibiotic would you prescribe for a young women with cystitis caused by fully sensitive E-Coli? - Trimethoprim 4. Which antibiotic would you use for cellulitis with MRSA? - Vancomycin 5. Which antibiotic would you use to treat someone who has cellulitis with an MSSA? - Flucloxacillin * Modified from 2017 paper

Answer 78

Aciclovir (oral or I.V. depending on severity)

Answer 79

``` Attachment and fusion Reverse transcription Integration Transcription Protein synthesis Assembly and exit Maturation ```

Answer 80

Memory CD4+ T-cells are more easily infected than other cells T-cell depletion allows higher loads of other pathogens causing widespread immune activation Activated cells are more susceptible to HIV infection so this helps the virus proliferate and spread There is gradual depletion of memory CD4+ T-cells Even after initiation of successful HAART, immunological memory has been shown to be depleted

Answer 81

Reverse transcriptase and RNA polymerase

Answer 82

Two nucleoside reverse transcriptase inhibitors (NRTIs) + one of: A protease inhibitor *OR* A non-nucleoside reverse transcriptase inhibitor *OR* An integrase inhibitor Integrase inhibitors prevent integration of the viral DNA into the host genome (post-reverse transcription) Protease inhibitors block cleaving of HIV proteins which is an essential step in maturing the new virion so it may infect other cells

Answer 83

C. Viral load after primary infection peak settles This is known as the viral burden 'set point' and is correlated with clinical outcome, with so-called 'elite controllers' having very low viral load set points.

Answer 84

D. CD4+ count The screening test is ELISA The confirmatory test is a Western blot analysis (electrophoresis) Plasma viral load is quantified using PCR Drug resistance analysis is done using either cell culture or viral genome sequencing NB: All these investigations would be carried out in a new HIV patient, and would be done in the order they are written in this question

Answer 85

Around 1/3

Answer 86

B. B Because it has only recently been included in routine vaccination.

Answer 87

Prematurity

Answer 88

D. I.V. benzylpenicillin + gentamicin This is the standard treatment for neonatal sepsis, and is chosen because benzylpenicillin treats Group B Strep infection (most common cause), and gentamicin treats E. coli infection (2nd most common cause). 'B' is the correct treatment for meningitis in a child under 3 months old - ceftriaxone is avoided because it can cause biliary sludging in these children.

Answer 89

Group B Streptococcus *Taken from 2017 paper

Answer 90

Coagulase negative Staph e.g. epidermidis

Answer 91

Entero-toxigenic Escherichia coli

Answer 92

CCR5 mutation *Taken from 2019 paper

Answer 93

Bartonella henselae *Taken from 2019 paper

Answer 94

1. CMV retinitis - Ganciclovir 2. HSV meningitis - Aciclovir 3. Adult with Varicella-Zoster infection - Aciclovir 4. Child with respiratory syncitial virus - Ribavirin 5. Asthmatic with flu - Oseltamivir 6. Hepatitis B where the patient wants to try for a cure - Interferon-alpha 7. RSV prevention in a vulnerable child - Palivizumab 8. CMV infection in a bone marrow transplant patient pre-graft - Foscarnet 9. Must be taken with probenecid - Cidofovir 10. May be taken on its own in patients with resistant CMV - Foscarnet 10. Can be given for post-transplant lymphoproliferative disease - Rituximab 11. Should be given to a non-immune pregnant woman with chicken pox contact within 10 days - VZIG * Modified from 2019 paper

Answer 95

C. Aciclovir resistance in HSV is most commonly mediated by mutations in the viral thymidine kinase 95% of cases of aciclovir resistance are due to mutation in the viral thymidine kinase gene (which also confers resistance to ganciclovir), and this almost exclusively arises in immunocompromised patients. The other 5% of cases are due to mutations in viral DNA polymerase. Mutations in the UL97 protein kinase gene are responsible for resistance of CMV against gancilcovir.

Answer 96

A. Oseltamavir directly inhibits the influenza neuraminidase Oseltamivir and Zanamivir are both direct neuraminidase inhibitors; Zanamivir is given via a dry powder inhaler or nebuliser, and Oseltamivir (Tamiflu) is given orally. By binding to influenza neuraminidase, these drugs prevent viral escape from infected cells, thereby limiting their ability to further infect the host.

Answer 97

E. I.V. aciclovir Fever, mental state changes, and seizures are highly suggestive of encephalitis, the most common causative organism of which is herpes simplex virus. The treatment for this is a few weeks of I.V. aciclovir.

Answer 98

NS5A inhibitors - '...asvirs' Polymerase inhibitors - '...buvirs' Protease inhibitors - '...previrs'

Answer 99

1. A previously well 22 year old with cough productive of rusty coloured sputum - Streptococcus pneumoniae 2. A 40 year old man just returned from abroad with a dry cough, malaise, and hyponatraemia - Legionella pneumoniae 3. A 45 year old presented to GP with flu symptoms which resolve, 2 weeks later is admitted with bacterial pneumonia - Streptococcus pneumoniae 4. A 62 year old alcoholic man with an upper lobe cavitating pneumonia - Klebsiella pneumoniae 5. A 74 year old who presented with SOB, fever, and pleuritic chest pain and who has failed to respond to broad spectrum antibiotics - Empyema 6. A 15 year old with a dry cough, myalgia, fever, and headache. CXR is normal and other kids at school have similar symptoms - Mycoplasma pneumoniae 7. A 22 year old neutropenic chemotherapy patient with ongoing fevers unresponsive to antibiotics or antivirals, but with interstitial CT changes - Aspergillus fumigatus 8. A 70 year old woman admitted for confusion caused by a UTI develops pneumonia whilst in hospital - Enterobacteriaceae 9. A 56 year old man presents with cough, haemoptysis and CXR shows a LLL pneumonia. Sputum culture grows Gram- cocco-bacilli - Haemophilus influenzae 10. A 21 year old Ecuadorean man presents with a few weeks' history of cough weight loss, CXR shows RUZ shadowing - Mycobacterium tuberculosis 11. A known IVDU who desaturates upon exercise - Pneumocystis jirovecii 12. An 18 year old chemotherapy patient whose CXR shows the 'Halo' sign - Aspergillus fumigatus * Modified from 2016, 2017, 2018, and 2019 paper i.e. this question comes up, so learn it

Answer 100

Neisseria meningitidis *Taken from 2017 paper

Answer 101

A. Cephalosporin with anti-pseudomonal activity - Ceftazidime B. Broad spectrum, no anti-pseudomonal activity, usually given with a beta lactamase inhibitor - Amoxicillin C. A glycopeptide used to treat MRSA - Teicoplanin D. A protein synthesis inhibitor used to treat Pseudomonal infections but which has no activity against anaerobes - Gentamicin E. Abx of the Macrolide/lincosamide/streptogrammin group used to treat some atypical pneumonias - Clarithromycin F. A DNA synthesis inhibitor used to treat Pseudomonal infections but which has little activity against anaerobes - Ciprofloxacin

Answer 102

It is a poor sample and was not properly taken mid-stream *Taken from 2019 paper

Answer 103

Ceftriaxone *Taken from 2019 paper

Answer 104

Listeria monocytogenes Amoxicillin is added to cover for Listeria

Answer 105

A. Auramine Auramine staining is faster than staining with ZN (though accuracy is operator dependent) so it is used as a screening test, and Ziehl-Neelson is used for more formal diagnosis.