Microbiology Flashcards

Question

Neonatal and childhood infections ``` A Rubella B Syphilis C Measles D Hepatitis B E Mumps F Listeria monocytogenes G Cytomegalovirus H Haemophilus influenzae I HIV ``` 5 An 8-month old girl is seen by a paediatrician due to concerns about developmental delay. On examination cataracts are noted in both eyes. Echocardiography reveals a patent ductus arteriosus.

Answer 1

5) A Rubella (German measles; A) is a viral infection which can be congeni- tal or acquired. Congenital rubella syndrome (CRS) occurs in a develop- ing fetus if the mother has contracted rubella in her first trimester. CRS is characterized by sensorineural deafness, eye abnormalities (cataracts, glaucoma, retinopathy) and congenital heart disease (patent ductus arteriosus). Other associations include microcephaly and developmental delay. Acquired rubella is transmitted via the respiratory route. Characteristically, a rash appears on the face which spreads to the trunk and disappears after a few days. Hepatitis B (D) may be vertically transmitted from mother to child dur- ing childbirth. Mothers who are HBeAg positive are especially at risk of transmitting the virus; infection may become chronic in 20 per cent of cases. Syphilis (B) can be congenitally transmitted. Symptoms that may develop in the first few years of life include hepatosplenomegaly, rash, fever and neurosyphilis. Long-term complications include saddle-nose deformity, Higoumenakis’ sign (unilateral enlargement of the clavicle) and Clutton’s joints (symmetrical joint swelling). Cytomegalovirus (G) may be transmitted in the perinatal period from infected mothers. Presentation may include low birth weight, micro- cephaly, seizures and/or petechial rash. HIV (I) transmission may occur in utero or during birth. Infected moth- ers are advised to take Zidovudine during pregnancy; the infant is required to take Zidovudine for 6 weeks following birth.

Answer 2

1) D Listeria monocytogenes (D) is a -haemolytic anaerobic Gram-positive rod that may cause outbreaks of non-invasive gastroenteritis. Sources include refrigerated food and unpasteurized dairy products. Clinical features of listeria infection include watery diarrhoea, abdominal cramps, headaches and fever, but minimal vomiting. Listeria demonstrates ‘tumbling motility’ as a result of flagellar-driven movements. Neonates and immunocompromised patients are particularly susceptible. Invasive infection can cause more serious problems in these groups including septicaemia, meningitis and encephalitis. Salmonella typhi (E) infection, also known as enteric fever, multiplies in the Peyer’s patches of the small intestine. Clinical features include slow onset fever, constipation and splenomegaly. Rose spots are pathognomonic. Shigellae (F) are non-motile, non-hydrogen sulphide producers. The bacteria cause dysentery via invasion of mucosal cells of distal ileum and colon as well as the production of an enterotoxin, known as Shiga toxin. Campylobacter jejuni (G) are oxidase positive, non-motile bacteria. Transmission occurs via the faecal–oral route, generally due to contamination by dog faecal matter, causing a watery, foul smelling diarrhoea. Complications include Guillain–Barré syndrome and Reiter’s syndrome. Entamoeba histolytica (I) is a motile trophozite. Ingestion of the cysts leads to colonization of caecum and colon, which may cause a ‘flask-shaped’ ulcer to develop. Clinical features involve dysentery, chronic weight loss and liver abscess formation.

Answer 3

2) C Escherichia coli (C) is a Gram-negative rod-shaped bacterium that is a common cause of traveller’s diarrhoea in those returning from abroad. Transmission occurs via food and water that become contaminated with human faeces, as can swimming in contaminated lakes. Enterohaemorrhagic E. coli infection (serotype O157:H7) can lead to haemolytic uraemic syndrome (HUS), characterized by haemolytic anaemia, acute renal failure (uraemia) and a low platelet count (thrombocytopenia). Other diarrhoea-causing strains of E. coli include enterotoxigenic, enteropathogenic and enteroinvasive forms. Salmonella typhi (E) infection, also known as enteric fever, multiplies in the Peyer’s patches of the small intestine. Clinical features include slow onset fever, constipation and splenomegaly. Rose spots are pathognomonic. Shigellae (F) are non-motile, non-hydrogen sulphide producers. The bacteria cause dysentery via invasion of mucosal cells of distal ileum and colon as well as the production of an enterotoxin, known as Shiga toxin. Campylobacter jejuni (G) are oxidase positive, non-motile bacteria. Transmission occurs via the faecal–oral route, generally due to contamination by dog faecal matter, causing a watery, foul smelling diarrhoea. Complications include Guillain–Barré syndrome and Reiter’s syndrome. Entamoeba histolytica (I) is a motile trophozite. Ingestion of the cysts leads to colonization of caecum and colon, which may cause a ‘flask-shaped’ ulcer to develop. Clinical features involve dysentery, chronic weight loss and liver abscess formation.

Answer 4

3) A Vibrio cholerae (A) are comma-shaped oxidase positive bacteria, causing profuse watery diarrhoea containing no inflammatory cells on microscopy. Transmission occurs via the faecal-oral route. Vibrio cholerae colonizes the small intestinal section of the gut and secretes enterotoxin containing subunits A (active) and B (binding). B subunit binds to GM1 ganglioside on the intestinal epithelial cells. Intracellularly, there is activation of cAMP by A subunit, which causes active secretion of sodium and chloride ions; as a consequence water is lost due to the osmotic pull of NaCl. Salmonella typhi (E) infection, also known as enteric fever, multiplies in the Peyer’s patches of the small intestine. Clinical features include slow onset fever, constipation and splenomegaly. Rose spots are pathognomonic. Shigellae (F) are non-motile, non-hydrogen sulphide producers. The bacteria cause dysentery via invasion of mucosal cells of distal ileum and colon as well as the production of an enterotoxin, known as Shiga toxin. Campylobacter jejuni (G) are oxidase positive, non-motile bacteria. Transmission occurs via the faecal–oral route, generally due to contamination by dog faecal matter, causing a watery, foul smelling diarrhoea. Complications include Guillain–Barré syndrome and Reiter’s syndrome. Entamoeba histolytica (I) is a motile trophozite. Ingestion of the cysts leads to colonization of caecum and colon, which may cause a ‘flask-shaped’ ulcer to develop. Clinical features involve dysentery, chronic weight loss and liver abscess formation.

Answer 5

4)H Giardia lamblia (H) is a pear-shaped trophozite containing two nuclei, four flagellae and a suction disc. Transmission occurs via ingestion of a cyst from faecally contaminated water and food. Trophozites attach to the duodenum but do not invade. Instead, protein absorption is inhibited, drawing water into the lumen of the gastrointestinal tract. G. lamblia must be considered in travellers, hikers and homosexual men. Clinically, foul smelling non-bloody steatorrhoea is produced, with stool containing cysts visible on microscopy. Salmonella typhi (E) infection, also known as enteric fever, multiplies in the Peyer’s patches of the small intestine. Clinical features include slow onset fever, constipation and splenomegaly. Rose spots are pathognomonic. Shigellae (F) are non-motile, non-hydrogen sulphide producers. The bacteria cause dysentery via invasion of mucosal cells of distal ileum and colon as well as the production of an enterotoxin, known as Shiga toxin. Campylobacter jejuni (G) are oxidase positive, non-motile bacteria. Transmission occurs via the faecal–oral route, generally due to contamination by dog faecal matter, causing a watery, foul smelling diarrhoea. Complications include Guillain–Barré syndrome and Reiter’s syndrome. Entamoeba histolytica (I) is a motile trophozite. Ingestion of the cysts leads to colonization of caecum and colon, which may cause a ‘flask-shaped’ ulcer to develop. Clinical features involve dysentery, chronic weight loss and liver abscess formation.

Answer 6

5)B Staphylococcus aureus (B) are beta-haemolytic Gram-positive cocci arranged in grape-like clusters. In the gastrointestinal tract, S. aureus produces the exotoxin TSST-1, which acts as a superantigen causing non-specific activation of T cells and subsequent release of IL-1, IL-2 and TNF-alpha. A massive non-specific immune response follows caus- ing shock and multiple organ failure. Enterotoxin produced by bacteria causes vomiting and diarrhoea 12–24 hours after the culprit food has been consumed. Salmonella typhi (E) infection, also known as enteric fever, multiplies in the Peyer’s patches of the small intestine. Clinical features include slow onset fever, constipation and splenomegaly. Rose spots are pathognomonic. Shigellae (F) are non-motile, non-hydrogen sulphide producers. The bacteria cause dysentery via invasion of mucosal cells of distal ileum and colon as well as the production of an enterotoxin, known as Shiga toxin. Campylobacter jejuni (G) are oxidase positive, non-motile bacteria. Transmission occurs via the faecal–oral route, generally due to contamination by dog faecal matter, causing a watery, foul smelling diarrhoea. Complications include Guillain–Barré syndrome and Reiter’s syndrome. Entamoeba histolytica (I) is a motile trophozite. Ingestion of the cysts leads to colonization of caecum and colon, which may cause a ‘flask-shaped’ ulcer to develop. Clinical features involve dysentery, chronic weight loss and liver abscess formation.

Answer 7

1) I Candida albicans (I) can affect both immunocompetent and immunocompromised hosts. In the immunocompetent host, clinical features range from oral thrush (creamy-white patches with red base over mucous membranes of mouth; treated with nystatin) to vaginitis (vaginal inflammation, pruritis and discharge; speculum examination reveals patches of cottage cheese-like clumps fixed to vaginal wall). In immunocompromised patients, C. albicans infection leads to oesophagitis, characterized by odynophagia. Candidaemia can lead to severe flu-like symptoms and can be diagnosed by testing for blood -D-glucan (a component of fungal cell walls). Histoplasma capsulatum (D) is a fungus transmitted by inhaled spores; it is highly prevalent in the Mississippi River region. Although mostly subclinical, a minority of infections will proceed to a chronic progressive lung disease. Phialophora verrucosa (E) is a copper coloured soil saprophyte found on rotting wood that causes chromoblastomycosis. Infection is characterized by a warty lesion resembling a cauliflower. Tinea capitis (F) is a cutaneous dermatophyte fungal infection of the scalp leading to scaly red lesions with loss of hair. It primarily affects children. Infection is characterized by an expanding ring on the scalp. Tinea corporis (H) is also known as ringworm. It is a cutaneous dermatophyte fungal infection affecting the trunk, arms and legs. It is identified by raised red rings.

Answer 8

2)A Cryptococcus neoformans (A) is an encapsulated yeast that is transmitted via inhaled spores from pigeon droppings. It is usually asymptomatic in most cases. 75% of cases occur in immunocompromised patients, characterized by the development of sub-acute or chronic meningitis. Cryptococcal meningitis is fatal without treatment due to the associated cerebral oedema and brainstem compression. Diagnosis is made by CSF analysis with India ink stain which reveals yeast cells surrounded by a halo (polysaccharide capsule). A cryptococcal antigen test can also be used which offers higher sensitivity. Histoplasma capsulatum (D) is a fungus transmitted by inhaled spores; it is highly prevalent in the Mississippi River region. Although mostly subclinical, a minority of infections will proceed to a chronic progressive lung disease. Phialophora verrucosa (E) is a copper coloured soil saprophyte found on rotting wood that causes chromoblastomycosis. Infection is characterized by a warty lesion resembling a cauliflower. Tinea capitis (F) is a cutaneous dermatophyte fungal infection of the scalp leading to scaly red lesions with loss of hair. It primarily affects children. Infection is characterized by an expanding ring on the scalp. Tinea corporis (H) is also known as ringworm. It is a cutaneous dermatophyte fungal infection affecting the trunk, arms and legs. It is identified by raised red rings.

Answer 9

3) B Pityriasis versicolor (B) is a chronic fungal infection caused by Malassezia furfur, characterized by hypopigmentation (in patients with dark skin tones) and hyperpigmentation (in patients with pale skin tones). Spots affect the back, underarm, arms, legs, chest, neck and rarely the face. Microscopic investigation of the M. furfur with potassium hydroxide reveals a ‘spaghetti with meatballs’ appearance. Wood’s light may also reveal an orange fluorescence in some cases. Histoplasma capsulatum (D) is a fungus transmitted by inhaled spores; it is highly prevalent in the Mississippi River region. Although mostly subclinical, a minority of infections will proceed to a chronic progressive lung disease. Phialophora verrucosa (E) is a copper coloured soil saprophyte found on rotting wood that causes chromoblastomycosis. Infection is characterized by a warty lesion resembling a cauliflower. Tinea capitis (F) is a cutaneous dermatophyte fungal infection of the scalp leading to scaly red lesions with loss of hair. It primarily affects children. Infection is characterized by an expanding ring on the scalp. Tinea corporis (H) is also known as ringworm. It is a cutaneous dermatophyte fungal infection affecting the trunk, arms and legs. It is identified by raised red rings.

Answer 10

4)C Aspergillus flavus (C) is a fungus that commonly grows on stored grains and can cause a spectrum of disease. Allergic reaction in the airways may cause allergic broncho-pulmonary aspergillosis (ABPA) which occurs due to an IgE mediated type I hypersensitivity reaction leading to bronchospasm and eosinophilia. Infection in pre-formed lung cavities (for example in TB patients) may lead to a fungal ball visible on chest X-ray (aspergilloma). Invasive aspergillosis is a chronic necrotizing infection that may occur in neutropenic patients (chemotherapy) or patients with end stage AIDS (CD4 count <50). Strains may produce the carcinogen aflatoxin, which has a strong association with hepatocellular carcinoma. Histoplasma capsulatum (D) is a fungus transmitted by inhaled spores; it is highly prevalent in the Mississippi River region. Although mostly subclinical, a minority of infections will proceed to a chronic progressive lung disease. Phialophora verrucosa (E) is a copper coloured soil saprophyte found on rotting wood that causes chromoblastomycosis. Infection is characterized by a warty lesion resembling a cauliflower. Tinea capitis (F) is a cutaneous dermatophyte fungal infection of the scalp leading to scaly red lesions with loss of hair. It primarily affects children. Infection is characterized by an expanding ring on the scalp. Tinea corporis (H) is also known as ringworm. It is a cutaneous dermatophyte fungal infection affecting the trunk, arms and legs. It is identified by raised red rings.

Answer 11

5) G Sporothrix schenckii (Rose garderner’s disease; G) is a fungus found in soil and plants that causes sporotrichosis. A prick by thorns causes nodular lesions to appear on the surface of the skin. Initially the lesions will be small and painless; left untreated they become ulcerated. Infection may also spread to joints, bone and muscle by this route. Inhalation of spores may lead to pulmonary disease and systemic infection may lead to central nervous system involvement. Treatment options include itraconazole, fluconazole and oral potassium iodide. Histoplasma capsulatum (D) is a fungus transmitted by inhaled spores; it is highly prevalent in the Mississippi River region. Although mostly subclinical, a minority of infections will proceed to a chronic progressive lung disease. Phialophora verrucosa (E) is a copper coloured soil saprophyte found on rotting wood that causes chromoblastomycosis. Infection is characterized by a warty lesion resembling a cauliflower. Tinea capitis (F) is a cutaneous dermatophyte fungal infection of the scalp leading to scaly red lesions with loss of hair. It primarily affects children. Infection is characterized by an expanding ring on the scalp. Tinea corporis (H) is also known as ringworm. It is a cutaneous dermatophyte fungal infection affecting the trunk, arms and legs. It is identified by raised red rings.

Answer 12

1) I Mycobacterium tuberculosis (I) may lead to a subacute or chronic meningitis. Symptoms are non-specific, including fever, headache and confusion. Focal signs may be present as a result of a cerebral granuloma. A tuberculous granuloma that occurs in the cortex of the brain, subsequently rupturing into the subarachnoid space, is termed a Rich focus. Diagnosis of tuberculous meningitis involves a lumbar puncture; the CSF appears colourless and characteristically has high protein, low glucose and raised lymphocyte levels. Nucleic acid amplification tests as well as imaging studies (CT and MRI) can be useful in the diagnostic work-up. Listeria monocytogenes (D) is a Gram-positive bacillus. Infection usually occurs in neonates, the immunocompromised and elderly. Manifestations include meningitis, encephalitits, pneumonia and septicaemia. Escherichia coli (F) is a Gram-negative bacillus. The K1 antigen of the bacterium as well as a lack of circulating IgM are responsible for severe meningitis in neonates. Streptococcus pneumoniae (G) is a Gram-positive alpha-haemolytic diplococcus. It is the most common cause of meningitis in adults together with N. meningitides. Borrelia burgdorferi (H) is a Gram-negative zoonotic spirochaete that causes Lyme disease. In the late stages of disease the patient will experience arthritis, peripheral neuropathy and/or encephalopathy.

Answer 13

2) C Leptospira interrogans (C) causes leptospirosis (also known as Weil’s syndrome). Transmission occurs via contact with animals. Leptospira are thin aerobic spirochaetes that are tightly coiled. The first stage of infection is known as the leptospiramic phase, during which the patient suffers non-specific symptoms such as fever, headache, malaise and photophobia. In the second immune phase, IgM antibodies have formed and meningitis, liver damage (causing jaundice) and renal failure may develop. CSF examination will reveal a raised white cell count. The microscopic agglutination test is considered the gold standard for diagnosing leptospirosis. Listeria monocytogenes (D) is a Gram-positive bacillus. Infection usually occurs in neonates, the immunocompromised and elderly. Manifestations include meningitis, encephalitits, pneumonia and septicaemia. Escherichia coli (F) is a Gram-negative bacillus. The K1 antigen of the bacterium as well as a lack of circulating IgM are responsible for severe meningitis in neonates. Streptococcus pneumoniae (G) is a Gram-positive alpha-haemolytic diplococcus. It is the most common cause of meningitis in adults together with N. meningitides. Borrelia burgdorferi (H) is a Gram-negative zoonotic spirochaete that causes Lyme disease. In the late stages of disease the patient will experience arthritis, peripheral neuropathy and/or encephalopathy.

Answer 14

3) A Neisseria meningitides (meningococcus; A) is a Gram-negative diplococ- cus. Infants aged 6 months to 2 years are most at risk as well as large numbers of adults living in close quarters. Virulence factors include its capsule (antiphagocytic), endotoxin (lipopolysaccharide causes haemor- rhage from blood vessels resulting in characteristic petechiae in menin- gococcaemia) and IgA1 protease (destroys IgA). Neisseria meningitides can lead to meningitis (headache, photophobia and neck stiffness) and meningococcaemia (signs of sepsis with spreading petechial rash). Neisseria meningitides is grown best on Thayer–Martin VCN media (only allows Neisseria species to grow). Listeria monocytogenes (D) is a Gram-positive bacillus. Infection usually occurs in neonates, the immunocompromised and elderly. Manifestations include meningitis, encephalitits, pneumonia and septicaemia. Escherichia coli (F) is a Gram-negative bacillus. The K1 antigen of the bacterium as well as a lack of circulating IgM are responsible for severe meningitis in neonates. Streptococcus pneumoniae (G) is a Gram-positive alpha-haemolytic diplococcus. It is the most common cause of meningitis in adults together with N. meningitides. Borrelia burgdorferi (H) is a Gram-negative zoonotic spirochaete that causes Lyme disease. In the late stages of disease the patient will experience arthritis, peripheral neuropathy and/or encephalopathy.

Answer 15

4)E Cryptococcus neoformans (E) is a polysaccharide encapsulated yeast that causes a subacute or chronic meningoencephalitis. It is transmitted by inhalation (the source of which is pigeon droppings). Cryptococcus neoformans is usually asyptomatic, but can be pathogenic in immunocompromised patients such as those with HIV. As well as meningitis, C. neoformans can also cause pneumonia, skin ulcers and bone lesions. Diagnosis is made by examination of CSF; India ink staining reveals yeast cells with a surrounding halo. Cryptococcal antigen test is, however, a more sensitive test. Listeria monocytogenes (D) is a Gram-positive bacillus. Infection usually occurs in neonates, the immunocompromised and elderly. Manifestations include meningitis, encephalitits, pneumonia and septicaemia. Escherichia coli (F) is a Gram-negative bacillus. The K1 antigen of the bacterium as well as a lack of circulating IgM are responsible for severe meningitis in neonates. Streptococcus pneumoniae (G) is a Gram-positive alpha-haemolytic diplococcus. It is the most common cause of meningitis in adults together with N. meningitides. Borrelia burgdorferi (H) is a Gram-negative zoonotic spirochaete that causes Lyme disease. In the late stages of disease the patient will experience arthritis, peripheral neuropathy and/or encephalopathy.

Answer 16

5) B Herpes simplex virus 2 (HSV-2; B) is the most common cause of viral meningitis of all the herpes family. HSV-2 is transmitted via sexual contact or via the mother during birth. The virus infects mucosal epithelial cells or lymphocytes; retrograde transport occurs from peripheral nerves to ganglion. Viral causes of meningitis can be diagnosed on examination of CSF; it appears colourless, with a raised lymphocyte level, moderately raised protein and normal glucose concentration. Recurrent aseptic meningitis (Mollaret’s meningitis) can be caused by both HSV-1 and HSV-2. Listeria monocytogenes (D) is a Gram-positive bacillus. Infection usually occurs in neonates, the immunocompromised and elderly. Manifestations include meningitis, encephalitits, pneumonia and septicaemia. Escherichia coli (F) is a Gram-negative bacillus. The K1 antigen of the bacterium as well as a lack of circulating IgM are responsible for severe meningitis in neonates. Streptococcus pneumoniae (G) is a Gram-positive alpha-haemolytic diplococcus. It is the most common cause of meningitis in adults together with N. meningitides. Borrelia burgdorferi (H) is a Gram-negative zoonotic spirochaete that causes Lyme disease. In the late stages of disease the patient will experience arthritis, peripheral neuropathy and/or encephalopathy.

Answer 17

1)D Zidovudine (D) is a nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of HIV/AIDS (as well as prevention of vertical transmission from infected mothers). Tx is commenced once the CD4 count <350 copies/μL. Zidovudine works by inhibiting the action of the enzyme reverse transcriptase, preventing the conversion of HIV RNA to DNA, which consequently cannot be incorporated into the host DNA. SE: anaemia, neutropenia, hepatic and cardiac dysfunction as well as myopathy. The standard tx regimen = 2 nucleoside reverse transcriptase inhibitors (NRTIs) and a non-nucleoside reverse transcriptase inhibitor (NNRTI; Efivarenz) or a protease inhibitor (PI; Ritonavir). Lamivudine (F) is an NRTI (analogue of cytidine). It leads to the inhibition of reverse transcriptase and is therefore effective for the treatment of hepatitis B and HIV. Efavirenz (G) is an NNRTI used in the treatment of HIV. The drug causes inhibition of the reverse transcription enzyme. Ritonavir (H) is a protease inhibitor used in the management of HIV. Ritonavir inhibits viral assembly by preventing the cleavage of proteins that belong to newly formed virions. Amantidine (I) is an M2 ion channel inhibitor preventing the uncoating of influenza virions and therefore inhibiting entry into susceptible cells.

Answer 18

2)C Interferon- (IFN- C) is a protein that is used in the treatment of hepatitis B; it potentiates the immune system to fight active viral infection. IFN- acts on the JAK-STAT pathway; IFN- binds to the IFN- receptor, causing phosphorylation of STAT1 and STAT2, which subsequently form a complex with IRF9 (a transcription factor), leading to the synthesis of anti-viral proteins. A NRTI and IFN- is the standard treatment for hepatitis B infection. Pegylated-IFN- is used in the treatment of hepatitis C; similar to IFN- , the addition of polyethylene glycol increases the half life of the drug. Lamivudine (F) is an NRTI (analogue of cytidine). It leads to the inhibition of reverse transcriptase and is therefore effective for the treatment of hepatitis B and HIV. Efavirenz (G) is an NNRTI used in the treatment of HIV. The drug causes inhibition of the reverse transcription enzyme. Ritonavir (H) is a protease inhibitor used in the management of HIV. Ritonavir inhibits viral assembly by preventing the cleavage of proteins that belong to newly formed virions. Amantidine (I) is an M2 ion channel inhibitor preventing the uncoating of influenza virions and therefore inhibiting entry into susceptible cells.

Answer 19

3)B Oseltamivir (B) is a viral neuraminidase inhibitor used in the treatment of influenza. Osteltamivir is in fact a pro-drug; once metabolized in the liver the active form GS4071 is produced. Once a newly formed influen- za virion is produced, the surface viral protein haemagglutinin is bound to sialic acid receptors along the upper respiratory tract. Neuraminidase is normally responsible for cleaving the haemagglutinin–sialic acid receptor bond, hence facilitating the release of newly formed virions. Therefore, inhibiting neuraminidase activity prevents further viral replication. Gancyclovir (E) is a 2 ́-deoxyguanosine analogue used in the treatment of cytomegalovirus (CMV) infection. It is the first line drug for the prophylaxis of CMV in bone marrow transplant patients. 2 ́-deoxy- guanosine is phosphorylated to the triphosphate form, which prevents viral DNA polymerase from elongating viral DNA and therefore inhibits CMV replication. Gancyclovir can cause bone marrow toxicity; it may therefore be prescribed together with granulocyte-colony stimulating factor (G-CSF). Gancyclovir is also used in the treatment of human herpes virus 6 (HHV-6) and Epstein–Barr virus infection. Acyclovir (A) is a guanosine analogue anti-viral drug used primarily in the treatment of herpes simplex virus infections (HSV-1 and HSV-2). It is converted to acyclo-guanosine monophosphate (acyclo-GMP) by viral thymidine kinase. Acyclo-GMP is further phosphorylated to acycloguanosine triphosphate (acyclo-GTP). Acyclo-GTP is incorporated into the viral DNA strand, terminating the chain and stopping DNA polymerase from functioning. Aciclovir is also indicated for the treatment of varicella zoster, Epstein–Barr virus and cytomegalovirus infections (with decreasing efficacy). Lamivudine (F) is an NRTI (analogue of cytidine). It leads to the inhibition of reverse transcriptase and is therefore effective for the treatment of hepatitis B and HIV. Efavirenz (G) is an NNRTI used in the treatment of HIV. The drug causes inhibition of the reverse transcription enzyme. Ritonavir (H) is a protease inhibitor used in the management of HIV. Ritonavir inhibits viral assembly by preventing the cleavage of proteins that belong to newly formed virions. Amantidine (I) is an M2 ion channel inhibitor preventing the uncoating of influenza virions and therefore inhibiting entry into susceptible cells.

Answer 20

1. Sputum culture A 24 year-old Asian man presents with a persistent cough. A sputum sample is taken and cultured on Lowenstein–Jensen medium, appearing as brown, granular colonies after several weeks. The organism implicated is: ``` A Coxiella burnetti B Streptococcus pneumoniae C Mycobacterium tuberculosis D Legionella pneumophilia E Mycobacterium leprae ```

Answer 21

E Vibrio cholerae (E) causes profuse watery diarrhoea and vomiting. It can in fact be one of the most rapidly fatal infectious illnesses if not treated, because of the severe dehydration causing circulatory shock. The bacteria produce a toxin which has an A and a B subunit. It is the A subunit which activates a G protein and results in the production of cAMP, which initiates the secretion of Na+, K+, Cl-, and HCO3- into the small intestine lumen. Most people only have a mild illness which simply resembles other diarrhoeal illnesses. Sometimes the diarrhoea is profuse and is known colloquially as ‘rice-water’ stools because of its appearance. The diagnosis is predominantly clinical, but if stool culture is performed the classical appearance will be of curved shaped, oxidase-positive organisms. You can remember this as the Cholera Comma! Rehydration therapy forms the mainstay of treatment. Hepatitis A (A) can cause diarrhoea in travellers to developing countries, but the stools are not ‘rice-water’, and the organisms would not be demonstrated on microscopy as above. The more common symptoms are flu-like, and for this reason it can be mistaken for influenza. Jaundice can also develop with tender hepatomegaly. Treatment is mainly supportive – there is no specific anti-viral for hepatitis A. Clostridium difficile (B) is an anaerobic, Gram-positive rod that produces enterotoxins and cytotoxins. It can cause antibiotic-associated diarrhoea. A severe form is known as pseudomembranous colitis, of which a complication is toxic megacolon. Diagnosis is usually by demonstrating the presence of the Clostridium difficile toxin in faeces using cell-culture assay or immunoassay. Enterocolitis caused by Yersinia enterocolitica (C) is also characterized by fever, abdominal pain and diarrhoea. It is a Gram-negative rod, so would not result in the comma-shaped organisms found here. It is normally self-limiting. Campylobacter jejuni (D) is a common cause of gastroenteritis. Whilst vomiting is not a prominent feature, the diarrhoea that occurs can be bloody. Sources can include unpasteurized milk and meat – remember this as the food and drink you might take with you camping! It is a Gram-negative bacterium that is also oxidase positive, but has a corkscrew rather than a comma appearance. Diagnosis is made by stool culture. It is usually self-limiting, but sometimes oral erythromycin is used for treatment. The oxidase test mentioned in the question is used to determine if bacteria produce a certain type of oxidase enzyme. Important oxidase positive organisms that sometimes appear in questions are: Pseudomonas, Neisseria, Campylobacter, Helicobacter, Moraxella, Vibrio, and Legionella. This can be remembered using the mnemonic: ‘Pu.N.C.H. Me Very Lightly!’

Answer 22

A Leishmaniasis is transmitted by phlebotomine sandflies and occurs in Africa, America & Middle East. Visceral leishmaniasis (A) is aka ‘Kala-azar’, and the most common clinical features include fever and splenomegaly. Hepatomegaly, skin hyperpigmentation and dry warty skin occur less frequently, and bone marrow invasion can result in pancytopenia. It can be mistaken for malaria, which is dangerous as it can be fatal if left untreated. L. donovani and L. infantum are thought to cause the disease in Africa, Asia and Europe, whilst L. chagasi is implicated in South America. The most common form of leishmaniasis is called cutaneous leishmaniasis (B), where an itchy papule develops at the bite site and develops into an ulcer with raised edges. Local lymphadenopathy can also occur, but the lesion usually heals within 8 months leaving a depigmented scar. The organisms implicated are L. major and L. tropica. Mucocutaneous leishmaniasis (C) can produce destructive and disfiguring facial lesions, and so is the most feared form of cutaneous leishmaniasis. It may begin in the same way as the cutaneous form, but years later ulceration can appear in mucous membranes leading to mutilation of those areas. It is most often caused by L. braziliensis. A single ulcer caused by L. major or L. tropica may be left to heal spontaneously, but otherwise the firstline drug for leishmaniasis is a pentavalent antimonial such as sodium stibogluconate. Malaria (D) can present with non-specific flu-like symptoms, but hyperpigmentation of the skin is not a feature. Hepatosplenomegaly can occur however, and other clinical features might include malaise, headache, vomiting or diarrhoea. Malaria should be considered as the most likely diagnosis in a patient with a fever returning from an endemic area. Schistosomiasis (E), also known as bilharzia, is transmitted by blood flukes. An itchy rash, known as ‘swimmer’s itch’, may develop at the site where the vectors penetrate the skin. They may then migrate to the liver, causing ‘Katayama fever’ with clinical features such as fever, rash, myalgia and sometimes hepatosplenomegaly. Following maturation in the liver, the flukes migrate to either mesenteric veins causing intestinal schistosomiasis, or to the urinary tract leading to urinary schistosomiasis. Hepatosplenomegaly can occur, but again the dry warty skin lesions described are not usually a feature.

Answer 23

D The picture described is consistent with cutaneous leishmaniasis, the most common form of leishmaniasis. An itchy, scaly papule develops at the bite site and develops into a crusty ulcer with raised edges. Local lymphadenopathy can also occur, but the lesion usually heals within 8 months leaving a depigmented scar called an oriental sore. The organisms implicated are Leishmania major (D) and L. tropica. You can remember this if you picture lots of skin lesions cropping up in travellers from the ‘major tropics’! It is found in many countries, ranging from South America to the Middle East. Diagnosis can be by Giemsa staining of slit skin smears, or from tissue aspirated from the ulcer. The organism can be cultured on Novy–Macneal–Nicolle medium as described in the question. The other forms of leishmaniasis are visceral and mucocutaneous. Visceral leishmaniasis aka ‘Kala-azar’= fever and splenomegaly. Hepatomegaly, skin hyperpigmentation and dry warty skin occur less frequently. Leishmania donovani (C) and L. infantum are thought to cause the disease in Africa, Asia and Europe, whilst L. chagasi is implicated in South America. Mucocutaneous leishmaniasis can produce destructive and disfiguring facial lesions, and so is the most feared form of cutaneous leishmaniasis. It may begin in the same way as the cutaneous form, but years later ulceration can appear in mucous membranes leading to mutilation of those areas. It is most often caused by L. braziliensis (E). Toxoplasma gondii (A) is a protozoal disease, for which the cat family is the definitive host. It can infect humans by eating undercooked meat or from contact with cat faeces. Like other protozoa they become trophozites in the gut and spread to the brain, eyes and lungs. It would not normally cause an ulcer, and cannot be cultured in Novy–Macneal– Nicolle medium. Most infections are asymptompatic in immunocom- petent hosts, but in the immunocompromised or in fetuses affected via pregnant mothers the consequences can be fatal. In AIDS patients it can have neurological manifestations such as cranial nerve palsies, meningo-encephalitis and focal neurological deficits secondary to a space-occupying lesion. In the eyes it can cause chorioretinitis. Characteristically a CT scan may show ring enhancing lesions with sur- rounding oedema. If you can picture the ‘O’s in tOxOplasmosis jumping out at you like rings on a CT scan, you should be able to recall this important diagnostic fact! Treponema pallidum (B) = syphilis. The first stage of syphilis presents with a papule which ulcerates to become a painless chancre. This may be associated with regional lymphadenopathy that is also painless. This fact often crops up in exam questions and can be remembered by thinking of the word ‘syphilis’ corresponding to the 2 Ss found in painless! This organism also cannot be grown as described, but diagnosis would be by dark ground microscopy or serology of anti-treponemal antibodies.

Answer 24

D The Brucella species are Gram-negative, rod shaped, intracellular bacteria that cause a highly contagious zoonosis known as brucellosis (D). The causative agent in cattle is B. abortis, but in dogs it is B. canis. Infection in cattle can lead to miscarriages, hence the name ‘abortis’. Infection is usually contracted from unsterilized milk, cheese or meat. Clinical features of brucellosis can include a long history of undulating fevers, arthralgia and myalgia, weight loss, fatigue, lymphadenopathy, sacroilitis and depression. Many cases present as pyrexia of unknown origin. Hepatomegaly and/or splenomegaly can sometimes be found on examination. You can remember these by picturing an old man called Bruce, walking with a stick due to his back and muscle pain (arthralgia, myalgia, sacroilitis), feeling down (depression), looking thin (anorexia), sweating (fevers), and with lots of protruding lumps (hepatosplenomegaly and lymphadenopathy)! Draw this picture, label it with these features and it will be easier to remember! The most common diagnostic method is serum agglutination for antibodies. Antibiotics that can be used for treatment include doxycylcine and gentamicin for approximately 6 weeks, though streptomycin and rifampicin are other agents that are used. Because the bacteria are intracellular, usually >1 antibiotic is needed and relapse is common. Whilst tuberculosis (B) can cause drenching sweats, it would not typically cause lower back pain and certainly would not be treated with doxycycline. Do not forget the treatment for TB can be remembered as RIPE: Rifampicin, Isoniazid, Pyrazinamide and Ethambutol. The last two drugs, pyrazinamide and ethambutol, are usually only used for the first 2 months. The features of brucellosis and influenza (C) are not dissimilar, but influenza would usually have an incubation period of 1–4 days. Note also the history of working on a farm: any unusual facts like this are not red herrings, but are usually put in to help guide you to the right answer! Treatment of influenza would not be with doxycycline, but is usually symptomatic. Typhoid (E) is caused by Salmonella typhi, and again can present with non-specific features like brucellosis. However, there are a few unusual clinical features of typhoid --> mnemonic A.B.C.C.D.E: Abdominal distension, Bradycardia, Cough, Constipation, Diarrhoea and Erythematous rose spots. Antibiotics of choice in the treatment of typhoid are the quinolones such as ciprofloxacin for 2 weeks.

Answer 25

E Borrelia burgdorferi (E) is a Gram-negative bacterium that causes Lyme disease. It is a spirochaete, which is the name for a group of bacteria that are helically coiled in shape. Lyme disease is actually thought to be the most common vector borne disease in England and Wales. It is named after a town called Lyme in Connecticut, where the disease was first seen. The vector is a tick called the Ixodes tick, which can be found on deer and rodents. Lyme disease is a multisystemic disorder which has three main stages: the local stage, disseminated stage and a late stage. The local stage involves a characteristic skin lesion called erythema chronicum migrans, usually appearing 7–10 days after the initial infection. It usually starts off as a red macule or papule, and approximately 1 week later expands to leave a target appearance with an area of central fading. Other symptoms at this stage are usually constitutional, such as a fever and headache. The somewhat unusual features of the next stage can be remembered using the word PEACH: Peripheral neuropathy, Erythema chronicum migrans (persists in this stage), Arthritis, Cranial nerve palsies and Heart block. Finally, the late stage can include persistent arthritis and chronic encephalitis. Treatment is with oral antibiotics, usually doxycycline. The rash would not be in keeping with any of the other organisms listed. Herpes simplex (A) causes an acute viral disease. Type 1 is primarily responsible for oral–facial lesions, whereas Type 2 is responsible for genital disease – remember this as Type 2 requires 2 people to lead to the disease! Several anti-virals can be effective in treating the disease, particularly acyclovir. The Epstein–Barr virus (B) is also one of the herpes viruses, and is responsible for causing infectious mononucleosis. A rash is not typically a feature of this disease, but sometimes the virus can cause erythema multiforme. This rash usually consists of itchy papules, which may evolve into target lesions. Streptococcus pyogenes (C) is a Gram-positive bacterium responsible for many conditions, including impetigo and rheumatic fever. The rash in rheumatic fever is known as erythema marginatum, which can be easily confused with erythema chronicum migrans of Lyme disease. A good way to remember which is which is to picture a person sucking a Lyme and getting a ‘chronic migraine’ from doing so! In terms of appearance, erythema marginatum consists of pink ring lesions which usually occur on the trunk, arms and legs but with facial sparing. Treponema pallidum (D) is another spirochaete, like Borrelia burgdorferi, but is the organism responsible for causing syphilis. The skin lesion with syphilis is called a chancre, and is classically a painless ulcer with sharp borders.

Answer 26

A The patient in this question is presenting with septic arthritis. Other differentials might include gout or pseudogout, but it is paramount to consider septic arthritis as it is a rheumatalogical emergency! Typical features are like those described in the question: the patient is often pyrexial, the joint is swollen and painful with limited range of movement, and the skin overlying the joint is warm and erythematous. Classically the patient will refuse to move the joint at all. The most important investigation is an aspirate of the joint: the fluid aspirated may appear purulent and have a high neutrophil count. The most common cause of septic arthritis in young, sexually active adults is Neisseria gonorrhoeae (A). A Gram-stain of this aspirate would reveal Gram-negative diplococci. It is less likely for this organism to lead to joint destruction than a staphylococcal arthritis. The two forms of disseminated gonoccocal infection are the septic arthritis form (as described in this case), and the bacteraemic form. Other clinical features of the bacteraemic form might include a migratory polyarthralgia and a vesicular or papular rash. Staphyloccocus aureus (B) is the most common causative organism in older patients. A Gram-stain of the joint aspirate would reveal Gram-positive cocci. It is thought that a septic arthritis infected with this organism is more likely to be destructive than a gonoccocal arthritis, and a joint can be destroyed within 24 hours if left untreated. Haemophilus influenzae (C) is a Gram-negative bacterium that used to be the most common cause of septic arthritis in children, but is not typically found in adults. Streptococcus viridans (D) is an alpha haemolytic, optochin resistant streptococcus that does not typically cause septic arthritis. It is, how- ever, the most common cause of sub-acute bacterial endocarditis.

Answer 27

E The patient in this question is presenting with septic arthritis, and the most likely cause given the joint aspiration findings of Gram-negative diplococci is Neisseria gonorrhoeae. The British National Formulary (BNF) advises the use of intravenous cefotaxime for 4–6 weeks (E) if gonococcal arthritis or a Gram-negative infection is suspected. The BNF is a good source of information for looking up the latest guidelines regarding antibiotic treatment regimens for common types of infection. Cefotaxime is a third generation cephalosporin. Cephalosporins are part of the beta-lactam group of antibiotics which work by inhibiting cell wall synthesis. The penicillins are also part of this group. There are different generations of cephalosporins, with those of later generations having increasing Gram-negative but decreasing Gram-positive cover. Cefotaxime is also used to treat meningitis and gonorrhoea. Some of the other commonly used third generation cephalosporins are ceftizoxime and ceftriaxone – you can remember these because they all have a ‘t’ in their names, just like in ‘third’ generation. If a staphylococcal cause of septic arthritis is suspected, IV flucloxacillin for 4–6 weeks (B) would be the preferred regimen. Flucloxacillin is a narrow spectrum beta-lactam antibiotic, used to treat infections caused by Gram-positive organisms. Some bacteria, such as Staphylococcus aureus, produce an enzyme called beta-lactamase which renders this class of antibiotics ineffective. However, flucloxacillin is beta-lactamase stable, and so is used to treat staphylococcal infections. It is ineffective against MRSA, in which case vancomycin is preferred. Oral flucloxacillin (A) or IV therapy of only 2–4 weeks’ treatment (C) would not be sufficient to clear the infection in this case. IV flucloxacillin and vancomycin (D) together would not be needed.

Answer 28

A The HBsAg positive indicate that the patient has hepatitis B, and the HBeAg indicates that it is highly infectious (A). The anti-HBc IgG is also a marker that it is a chronic infection. The different hepatitis B surface antigens and antibodies can become quite confusing, but are often asked about in exam questions. Here is a summary of what you should know: --> HBsAg – The ‘s’ stands for surface, and refers to a protein on the surface of the virus. It is the first detectable antigen to appear after someone has been infected, and can be positive in acute or chronic disease. Patients who still carry this antigen after 6 months are termed hepatitis carriers. It is this antigen that is used to make the hepatitis B vaccine --> Anti-HBs – This is an IgG antibody that appears after the host has cleared the infection, and indicates recovery. It is also found in a person who has been vaccinated against hepatitis B (D) --> HBeAg – the ‘e’ antigen is often used as a marker of infectivity, as it is only found in the blood when the virus is actively replicating. If you find this hard to remember, think of the ‘e’ standing for ‘eek! I’m infectious!’ If the patient was not infectious (B), this would not be present --> Anti-HBc IgM – this indicates that the patient has recently been infected with hepatitis B, and is a marker of acute infection (C) --> Anti-HBc IgG – this is produced in response to the core antigen, and often persists for life. You can remember this as the ‘c’ standing for ‘chronicity’, as it is the difference between IgM and IgG antibod- ies which can tell you whether the infection is acute or chronic. And to remember which way round it is, think of ‘My Gosh, he’s chron- ic!’ If the patient was immune from natural infection (E), HBsAg would not be positive, but anti-HBc IgG would be.

Answer 29

D Remember from the previous question that the anti-HBs antibody appears after the host has cleared the infection, and indicates recovery. It is also found in a person who has been vaccinated against hepatitis B (D). If you get an exam question which only has the anti-HBs positive, think of vaccination! Levels of this antibody are measured to see if the patient has responded adequately to the vaccine. The patient has not got hepatitis (E) nor is he highly infectious (A) given that HBsAg and HbeAg are negative. HBsAg can be negative in the case of a resolved infection (C), but you would expect to see some marker of previous infection such as anti-HBc IgG, which usually persists for life. It is much more likely that the patient has been vaccinated than it is to be a false positive result (B)!

Answer 30

B Broad spectrum antibiotics, such as those used for pneumonia, can eradicate a patient’s normal gut flora and therefore increase their susceptibility to Clostridium difficile infection. This is particularly true of penicillin derivatives (as was most likely used to treat her pneumonia), clindamycin, and third generation cephalosporins. It classically presents with profuse watery diarrhoea, usually of acute onset. The most common time for it to occur is 4–9 days after the antibiotics are started, but it can occur up to 2 months after discontinuing treatment. Clostridium difficile is a Gram-positive, anaerobic rod-shaped bacterium. The gold standard for diagnosis is detection of the C. difficile toxin in a stool sample. The two most feared complications are pseudomembranous colitis and toxic megacolon. Pseudomembranous colitis is essentially an acute, severe colitis, which is named as such because of the formation of ‘pseudomembranes’ on the mucosa of the colon. These are thought to be composed of exudative material produced from the bacterium. Toxic megacolon can also be a complication of inflammatory bowel disease. The colon becomes severely distended, and clinical features include pyrexia, severe abdominal pain and bloating. First line treatment for infection with C. difficile is oral metronidazole, with a suggested duration of treatment of 10–14 days (B). Metronidazole is classified as a nitroimidazole antibiotic, and is particularly useful for the treatment of anaerobic organisms and protozoa. You can remember three of the key organisms it is used to treat by remembering that ‘Met is out to G.E.T you difficult bugs!’ (Giardia, Entamoeba, Trichomonas and C. difficile). Patients are usually advised to avoid consuming alcohol whilst taking this antibiotic because of the potential reaction that can occur characterized by nausea, shortness of breath, flushing and vomiting. The course of treatment should be at least 10–14 days, so 7 would not suffice (A). Whilst the patient must be isolated and rehydrated adequately, this alone would not be enough (C). IV metronidazole is not necessary in the first instance (D), unless the patient had a life- threatening infection. Co-amoxiclav (E), otherwise known as augmentin, is not used to treat C. difficile infections.

Answer 31

B This patient’s repeated diarrhoea may be caused by persistent infection with Clostridium difficile (spore germination), new infection or resistant bacteria. Current guidelines recommend the use of a repeat course of metronidazole for the treatment of recurrent C. difficile infection (B). As explained previously, a 7-day course of metronidazole (A) is not considered a sufficient duration of treatment to eradicate the bacte- rium. Again, isolation and IV fluid resuscitation (C) is necessary but not adequate as a single measure in the management of this woman. Intravenous metronidazole (D) is only needed if a patient is not responding to vancomycin, the infection is life-threatening, or for patients with ileus. Oral vancomycin for 10–14 days (E) is given for: - Third or subsequent episodes - Severe infection - Infection not responding to metronidazole - Patients who cannot tolerate metronidazole Vancomycin is classified as a glycopeptide antibiotic. Its mechanism of action is to inhibit cell wall synthesis in Gram-positive bacteria, and it is not effective for Gram-negative bacteria. You can remember this if you picture an ambulance ‘Van’ with a big red cross (for Gram-positive) on the side! Because it cannot pass through the lining of the intestine, it is usually given intravenously. However, in the case of Clostridium difficile infection we give it orally, as this stays in the gut where it is needed. One rare but important side effect you might hear about is ‘red man syndrome’, a reaction to the drug which consists of a sudden onset ery- thematous, pruritic rash over the face, neck and upper torso. To remember this fact, picture the driver of the red cross van emerging very angry, with a bright red face!

Answer 32

B The key here is the rapidly progressive condition in a relatively young patient. He shows the characteristic sudden decline in cognitive function, combined with the presence of myoclonic jerks and the lack of positive investigation results so far. This is highly suggestive of sporadic Creutzfeldt–Jakob disease (CJD), the name given to a common group of prion diseases. The word prion is derived from the words ‘protein’ and ‘infection’, and it so follows that a prion is a highly infectious agent composed of protein. 3 different forms of CJD: 1) Sporadic CJD (80%) 2) Acquired (<5%: Kuru, variant CJD, iatrogenic CJD 3) Genetic (15%): Gerstmann–Straussler–Sheinker syndrome, familial fatal insomnia clinical features of sporadic CJD are rapid dementia at a mean age of 65 years, and LMN signs, akinetic mutism (a clinical state of not speaking or moving), myoclonus, and cortical blindness. This can be remembered as the ‘demented L.A.M.B’. In terms of the pathology behind sporadic CJD, the characteristic feature found at autopsy in these patients is known as spongiform vacuolation (essentially the presence of many round vacuoles in the grey matter). This is not unique to sporadic CJD, but unlike in other forms of dementia, such as Alzheimer’s disease, there is no associated brain atrophy. This may be because the disease progresses so rapidly. Ix: electroencephalogram (B), abnormal in 2/3rd of patients and demonstrates generalized triphasic sharp wave complexes. Do not confuse this with an electrocardiogram (ECG) (C), which would not be diagnostic in this case. An MRI brain (A) may show increased signal in the basal ganglia, but would not be the best investigation here. An USS of both carotids (D) is a useful test if investigating a transient ischaemic attack (TIA) to look for carotid stenosis, but this is not relevant with this patient. Finally, a tonsillar biopsy (E), is a useful diagnostic test for variant CJD (for which it has 100% sensitivity and specificity), but not for sporadic CJD.

Answer 33

B The lumbar puncture in CJD is used to analyze the CSF for a protein named ‘14-3-3’ (B). Note that routine analysis of the CSF is normal in CJD, therefore looking at levels of protein, glucose and polymorphs (A) would not be useful to distinguish between possible causative agents of the clinical features as it is in meningitis. ‘14-3-3’ is a term for a large group of proteins which have different functions in eukaryotic cells, such as in cell signalling. However, its measurement in CJD is a time consuming process, and as it is a normal neuronal protein it can be released into the CSF as a result of many other normal neuronal insults. It is therefore not a specific finding (C), and the test can be positive in other conditions such as a recent stroke, viral encephalitis or a subarachnoid haemorrhage. The 14-3-3 protein is present in both variant and sporadic CJD, therefore (D) is incorrect. Variant CJD has several important differences from sporadic CJD: 1) It typically occurs in younger patients (median age of onset 26 years) than sporadic CJD 2) The median survival time is approximately 14 months, compared to 4 months for sporadic CJD 3) Psychiatric features may dominate in the initial stages, before neurological features such as ataxia, myoclonus, chorea, dementia and peripheral sensory symptoms appear 4) The MRI in variant CJD shows the ‘positive pulvinar sign’ (enhanced signal of nuclei in the thalamus) 5) The classical EEG findings are often absent in the variant form 6) A tonsillar biopsy is sensitive and specific in the variant form, but is not a useful test in the sporadic form (E).

Answer 34

D In this context, the two most immediately worrying diagnoses for the onset of an acute headache are a subarachnoid haemorrhage and bacterial meningitis as both of these may be fatal if rapid intervention does not occur. A LP can be used to differentiate between the different aetiological agents of meningitis as follows: Rather than trying to remember specific numbers, try to remember the normal features and then the main differentiating factors between each agent: - -> Bacterial meningitis typically has a very high neutrophil count, with a high protein & low glucose - -> Viral meningitis typically has a very high lymphocyte count - -> TB meningitis has similar features to viral meningitis in terms of cell types found in the CSF, but has a particularly high protein Using this, the easiest way to tell what the cause of the patient’s headache is in this scenario is the high lymphocyte count found in LP. This, combined with its clear appearance and slightly high protein content, indicates that the most likely cause is viral meningitis (D). A bacterial meningitis (C) is more likely to look turbid in appearance and would not have a predominant lymphocytosis, whilst a meningitis caused by TB (E) would usually have a higher protein content. LP in a subarachnoid haemorrhage (A) may be normal, or may have an increased number of red blood cells. The CSF is also examined for the presence of xanthochromia – this is the term for the yellowish appearance seen when red blood cells enter the CSF and are broken down. The presence of pyrexia combined with LP results clearly points towards excluding a simple tension headache (B).

Answer 35

E This patient is presenting with features suggestive of spontaneous bacterial peritonitis (SBP), which is a form of peritonitis in the absence of a contiguous source of infection. This usually results from the develop- ment of portal hypertension in patients with chronic liver disease. This group of patients are particularly susceptible as they are often immunocompromised. The pyrexia and tachycardia, in conjunction with the clinical features of abdominal tenderness and ascites, make this the most likely diagnosis in this patient. Other typical clinical features might include nausea, vomiting, confusion, general malaise or features of hepatic encephalopathy. In approximately 15% of patients SPB can be asymptomatic. A prompt diagnostic paracentesis is needed to make the diagnosis, and SPB is confirmed by the presence of: (1) Ascitic fluid WCC of 500 cells/mm3 (2) or Neutrophil count of >250 cells/mm3 Do not confuse a diagnostic paracentesis with a therapeutic paracentesis (A): in the latter the purpose is to remove the fluid, for example to relieve abdominal pressure or in the case of respiratory compromise. This may be appropriate later, but only once SBP has been excluded from the results of a diagnostic paracentesis or treated. The most common organisms isolated in patients with SBP include E. coli, Gram-positive cocci and enterococci. Although local antibiotic guidelines may differ, of the options listed cefotaxime (E) is one of the most extensively studied and has been proven to be effective. It is usually given for at least 5 days. Other third generation cephalosporins such as ceftriaxone can also be used. Amoxicillin (D) would not provide sufficient cover against Gram-negative organisms. Whilst analgesia and close observation are also important measures (B), the high risk of mortality in SBP necessitates prompt antibiotic treatment. Spironolactone (C) is used for the treatment of uncomplicated ascites, but initial antibiotic treatment would take precedence in the case of SBP.

Answer 36

D Hepatitis C is a single stranded RNA virus that is similar in structure to the ‘flaviviruses’. It can cause a slowly progressive disease of the liver that is frequently asymptomatic and which cannot be vaccinated against. Routes of transmission include: 1) blood products (before 1991, when screening of blood donors for the disease was introduced) 2) IVDU 3) sexual transmission 4) vertical transmission 5) less commonly: needle-stick injuries, tattoos Acute hepatitis occurs in ~20% of patients following exposure to the virus. The symptoms = mild, such as malaise, arthralgia, jaundice and lethargy. Others may remain asymptomatic. Up to 85% of patients this may persist and cause chronic infection, and ~20% of these will develop liver cirrhosis in 20 years. There are 6 different genotypes of the virus. The most common in the UK is genotype 1 (40–50%), genotypes 2 and 3 are responsible for another 40–50%, and the remainder is due to genotypes 4, 5 and 6. It has been found that genotype 1 is associated with a poorer response to anti-viral treatment (with interferon and ribavarin) than the other genotypes, so the answer here is (D). In fact, the recommended duration for combination therapy is 24 weeks for people with the 2nd and 3rd genotypes, but 48 weeks for genotypes 1, 4, 5, and 6. Patients with hepatitis C who develop cirrhosis have ~1–2% annual risk of developing hepatocellular carcinoma. Alpha-feto protein is the main tumour marker for this cancer, but its levels do not influence response to treatment (E). Similarly, the length of time between contracting the disease and being diagnosed (A), the route by which she contracted the disease (B), or her liver function test results (C) do not impact her response as significantly as the viral genotype does. A liver biopsy is also often performed and is thought to be the most accurate way to obtain information about the severity of the liver disease. It is thought that the severity of the fibrosis can also help to predict which patients are more likely to respond to antiviral treatment.

Answer 37

D There are several different tests which are helpful in investigating the disease: 1 Hepatitis C RNA PCR (D) – This can be used to differentiate between a current and past infection. A quantitative test to detect the number of hepatitis C RNA particles (called the ‘viral load’) can also be performed. This can be very useful to detect a patient’s response to the anti-viral treatment. Therefore, this is the best diagnostic test for hepatitis C. 2 Anti-hepatitis C antibodies (B) – a positive test would indicate exposure to the disease, but results should be interpreted with caution because it cannot distinguish between current or past infection. In addition, it can take up to 3 months for these antibodies to appear after exposure, so an initial negative test can be misleading. It has also been suggested that a weakly positive test might actually be a false positive, so this is not the best diagnostic test. However, it may be performed initially, and if the patient has two positive results a hepatitis C RNA PCR is used to confirm the diagnosis. 3 Viral genotyping (E) – this is used to determine the genotype of virus present. The most common, genotype 1, is less likely to respond to treatment than genotypes 2 or 3 and requires longer therapy. 4 Liver biopsy (A) – this would be the most accurate means of determining the stage and severity of liver damage caused by the virus, and may be useful to assess the patient’s likelihood to respond to treatment. However, it would be performed after the suspected diagnosis has been confirmed. 5 Alanine aminotransferase levels (ALT) (C) – this is not a diagnostic test, but can be useful aid in the initial stages of confirming the diagnosis. The ALT to AST (aspartate aminotransferase) ratio is typically <1 in liver damage caused by hepatitis, whereas if it is >2 this is more suggestive of alcoholic liver disease. You can remember this because AST is indicative of Smirnoff drinking, whereas ALT is indicative of viraL aetiology!

Answer 38

C Human African trypanosomiasis is also known as sleeping sickness, and is an infection transmitted by the tsetse fly in sub-Saharan Africa. There are 2 main types: 1) Trypanosoma brucei gambiense (B) is found in west and central Africa, is responsible for over 95% of cases, and causes a chronic infection. It can take months or even years for symptoms to appear. You can remember this as gambiense causes a gradual infection. 2) Trypanosoma brucei rhodesiense (C) is found in south and eastern Africa, accounts for under 5% of cases, and causes an acute infection with symptoms appearing over a few weeks or months. You can remember this as rhodesiense causes a rapid infection. As this patient’s symptoms appeared 3 months after returning from his travels, this is more likely to be the causative agent here. A subcutaneous chancre can develop at the site where the tsetse fly bites, and symptoms such as fevers, weakness, arthralgia and headache can then appear. Posterior cervical lymphadenopathy can also occur, especially with T. brucei gambiense. This is known as Winterbottom’s sign. Later the parasite can cross the BBB resulting in neurological features such as disturbance of the sleep cycle, ataxia, behavioural changes and psychiatric disturbance. Treatment is with drugs such as pentamidine and suramin in the early stages. Plasmodium falciparum (A) is an organism responsible for causing malaria. Whilst it should be considered in all patients with a fever returning from an endemic area, the changes in behaviour and sleep disturbance described in this patient make this a less likely cause. Trypanosoma cruzi (D) causes Chagas disease, carried by the reduviid bug. Chronic infection can appear weeks to years after the initial infection, affecting the cardiac and GIT systems. Leishmania infantum (E) is responsible for leishmaniasis, features include fever, hepatosplenomegaly and lymphadenopathy. Again, it is less likely to cause behavioural changes and sleep is unlikely to be affected.

Answer 39

B Trypanosoma cruzi is responsible for causing Chagas disease, a potentially life-threatening disease which is spread by reduviid bugs (B) in Brazil. These are also known as ‘kissing bugs’. A red nodule, called a chagoma, can appear at the site of the bite. There are 2 forms of the disease: acute and chronic. In the acute phase, patients may experience non-specific symptoms such as fever, lethargy, diarrhoea, and vomiting. A characteristic feature, but one which occurs in less than 50 per cent of cases, is a purplish swelling of the eyelids (called Romana’s sign). To put this all together, picture Tom Cruise (Trypanosoma cruzi) starring in a gladiator film as a Roman (Romana’s sign) wearing purple sunglasses (swollen eyelids) and being kissed (kissing bugs) by lots of fans ‘ready with their video cameras’ (reduviid!) The chronic phase can occur even years after the initial bite, and typically affects the heart and GIT. You can remember its effects by thinking of it causing both dilatation and dysfunction in three organs: in the heart (dilatation = dilated cardiomyopathy, dysfunction = arrhythmias), in the colon (dilatation = megacolon, dysfunction = constipation) and in the oesophagus (dilatation = mega oesophagus, dysfunction = dysphagia). Bennzimidazole or nifurtimox are effective medications used to treat this disease. The tsetse fly (A) is responsible for causing human African trypano- somiasis, also known as sleeping sickness, in sub-Saharan Africa. The clinical features of this disease can include changes to the sleep–wake cycle and psychiatric disturbance. The sandfly (C) transmits Leishmania species in Africa, America and the Middle East. The Aedes mosquito (D) is a type of mosquito that causes Dengue fever. The Ixodes tick (E), also known as the ‘deer tick’, transmits the organism responsible for causing Lyme disease. None of these vectors would cause the spectrum of clini- cal features described in this patient.

Answer 40

A Current guidelines in the UK recommend the following antibiotic treatment for pulmonary tuberculosis: - Isoniazid and rifampicin for 6 months - Pyrazinamide and ethambutol for the first 2 months The purpose of the initial phase where all four drugs are taken together is to rapidly reduce the number of bacteria and prevent drug resistant bacteria emerging. Culturing TB can take several weeks, so treatment is started without waiting for the culture results if clinical features or histopathology results are highly suggestive. Streptomycin (D) is an aminoglycoside that is rarely used in the UK, but may be used in the initial phase if it has been shown that the organism is resistant to isoniazid. It is not usually necessary to continue all four drugs after 2 months (E). The continuation phase consists of rifampicin and isoniazid alone for 2 months. A good way to remember is R.I.P.E (rifampicin, isonizaid, pyrazinamide, ethambutol), with the first two letters given for 6 months, and the last two letters on the end of the word dropping off after 2 months! Answers (B) and (C) are therefore incorrect. In the case of tuberculous meningitis, direct spinal cord involvement, and for resistant organisms a longer course of treatment may be necesarry. A corticosteroid such as dexamethasone should be started at the same time as anti-tuberculosis therapy in meningeal or pericardial tuberculosis.

Answer 41

E Tx for pulmonary TB usually consists of two phases – an initial phase with rifampicin, isoniazid, pyrazinamide and ethambutol for 2 months, and then a continuation phase with rifampicin and isoniazid only for 4 months. Streptomycin and ethambutol are two anti-tuberculous drugs which should preferably be avoided in patients with renal impairment (E). If they have to be used the dosage should be reduced and the plasma drug concentration closely monitored. A patient’s renal function should be checked routinely before anti-tuberculous medication is started. The side effect that is particularly worrying with the use of ethambutol is its ocular toxicity, and this is more likely in renal impairment as it is renally excreted. This can present with changes in visual acuity, colour blindness and restriction of visual fields. Therefore a patient’s visual acuity should be assessed with a Snellen chart prior to starting treatment, and they should be strongly advised to stop the medication and seek advice if they become aware of any change in their vision. This side effect does not occur with rifampicin (D). Liver function should be tested in everyone before starting antituberculous therapy, as isoniazid, rifampicin and pyrazinamide are all hepatotoxic (A). Further checks are not needed unless the patient has pre-existing liver disease, is alcohol dependent or develops symptoms of liver disease. Rifampicin can commonly cause a transient disturbance to liver function tests in the first 2 months, but this does not usually necessitate any changes to the treatment regimen. The only common side effect of isoniazid is a peripheral neuropathy. This can be remembered by ‘isoniazid causes a sensory neuropathy’. Pyridoxine (vitamin B6) is not given routinely as a prophylactic measure in patients using isoniazid, but may be given in those with pre-existing risk factors such as diabetes, alcohol dependence and HIV (C). Ethambutol does not cause a peripheral neuropathy (B).

Answer 42

C This scenario is characteristic of Guillan–Barrè syndrome. If you remember that this disease is also known as AIDP – acute inflammatory demyelinating polyradiculopathy – you can remember the underlying pathology more easily. It is usually triggered by an infection, and it is thought that a suppressed T-cell response results in an immunological reaction that targets the peripheral nerves. The triggering infection is most commonly Campylobacter jejuni but other common causes can include Mycoplasma pneumoniae and viruses such as CMV and influenza. key clinical features: (1) An antecedent infection (2) Sudden progressive muscle weakness within ~3 weeks of the onset of the original infection (3) The muscle weakness evolving rapidly over 1–3 weeks (4) The weakness is often symmetrical, and usually begins distally and ascends over time (5) Cranial nerves can also be affected, most commonly presenting as a unilateral facial weakness (6) Reflexes are usually absent (7) Sensory abnormalities are not a common feature The key worrying features of this disease: (1) Autonomic involvement – with tachycardia, fluctuating BP and arrhythmias (2) Respiratory involvement – which can lead to type 2 respiratory failure Treatment is usually supportive, but intravenous immunoglobulin therapy for 5 days or plasma exchange has been shown to be effective. Polio (A) would not characteristically have an antecedent diarrhoeal infection, and facial weakness is less likely. The paralytic phase would not typically have an ascending pattern of weakness, and fasciculations prior to paralysis are an important feature. Lyme disease (B) can cause facial weakness, but you would normally expect a question pointing you to this diagnosis to mention the characteristic target rash of erythema chronicum migrans. The somewhat unusual features of the second stage of Lyme disease can be remembered using the word PEACH: Peripheral neuropathy, Erythema chronicum migrans (persists in this stage), Arthritis, Cranial nerve palsies and Heart block. Haemolytic uraemic syndrome (D) is a triad remembered by the phrase ‘He’s (haemolytic) got your (uraemia) MAT (the triad of microangiopathic haemolytic anaemia, acute renal failure and thrombocytopenia). Cases that feature diarrhoea often occur in children, and are usually caused by E. coli O157. The neurological features described here would not normally be associated with this syndrome. Influenza (E) is again not likely to manifest with this characteristic neurological pattern of symptoms.

Answer 43

D Malaria should always be considered as a diagnosis in a patient pre- senting with a fever from an endemic country – mainly Africa, South and Central America, Asia and the Middle East. It is transmitted by the female Anopheles mosquito. 5 types as listed below. differentiated clinically according to the pattern of the fever they cause. Each of the different members of the Plasmodium genus results in a different periodicity of fever. ‘Tertian’ malaria means that the fever occurs every 3 days (i.e. days 1, 3 and 5 and so on) and ‘quartan’ malaria means it occurs every fourth day (i.e. days 1, 4, 7 and so on), as in this case. P. malariae (D) causes quartan malaria, so is the correct answer here. This type of malaria is said to be benign, and is the least common form found in the UK. The following table summarizes the features of the different types of malaria: It is worth remembering that malaria does not usually cause a rash or lymphadenopathy, so think again if these are featured in a question on a fever in a returning traveller! O/E: anaemia, jaundice and hepatosplenomegaly.

Answer 44

C Malaria has a complex life cycle, with two phases. The ‘erthrocytic’ phase involves red blood cells, whereas the ‘exoerthryocytic phase’ involves the liver. The basic stages are: (1) An infected mosquito injects sporozites (A) from its saliva into a person’s blood stream when it bites (2) These enter the blood stream and are taken to the liver where they infect hepatocytes (3) Here they multiply for a varying period of time, and then differentiate to form haploid merozites (C). These have a ‘signet ring’ appearance. Schizonts (B) are oval-shaped inclusions that contain the merozoites. Note that P. vivax and P. ovale sporozoites may not develop into merozites immediately, but can form hypnozoites (D) that remain dormant in the liver (4) The merozites escape from the liver into the blood stream and infect red blood cells – the erythrocytic phase (5) They multiply further in the erythrocytes, and will be released from them at intervals. The waves of fever the patient experiences correspond to when the merozites are released from the erythrocytes (6) Some of the merozoites develop into sexual forms of the parasite, called male and female gametocytes (E). When a mosquito bites an infected human, it ingests the gametocytes which form gametes inside the mosquito (7) These then fuse to form oocytes and then sporozites – ready to inject into a person.

Answer 45

E All patients with falciparum malaria should be admitted to hospital initially, so answers (A) and (B) are automatically excluded. Children should be kept in for at least 24 hours, and infants, pregnant women and the elderly need to be closely monitored because they can deteriorate rapidly. The treatment options then depend on whether the malaria is uncomplicated or complicated. Uncomplicated malaria can be treated with one of the following: 1 Oral quinine plus doxycycline for 5–7 days (E) 2 Co-artem (artemetherelumefantrine) for 3 days 3 Atovaquone–proguanil (Malarone) for 3 days Therefore the correct answer here is (E). Giving paracetamol without anti-malarials would not be adequate, so clearly (C) is not suitable. Chloroquine and mefloquine (B) are not recommended for the treatment of falciparum malaria in the UK. Oral treatment would suffice in an uncomplicated case of falciparum malaria such as this, but in a severe case the first line anti-malarial used in the UK is IV quinine (D). IV artesunate may also be considered in the case of very severe disease instead of or in addition to quinine, but this is not always widely available. The treatment for non-falciparum malaria is quite different. In uncomplicated infection, chloroquine is used initially followed by a 2-week course of primaquine. The choloroquine treats the parasites in the eryth- rocytes only, thus primaquine is still needed to kill the hypnozoites that remain latent in the liver. Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease, and anti-malarial drugs can cause acute haemolysis in these patients. The drugs thought to be particularly troublesome are primaquine and choloroquine, but others may be dangerous at high doses. For this reason glucose-6-phosphate dehydrogenase levels are checked in patients before starting anti-malarial treatment.

Answer 46

A The most reliable way to diagnose malaria is via a blood film, and traditionally a thick and thin blood film are requested. Most people remember this fact, but not the reason behind it! Thick films are better than thin films at picking up lower levels of infection, but thin films allow the specific species to be identified. Both types of films are used together to make the diagnosis. In the erythrocytic life cycle of the malarial parasite, disc-like granulations can be seen at the edge of the cell using an electron microscope. These are known as Maurer’s clefts, and are found in falciparum malaria (A). They are thought to be used by the parasite for protein sorting and export. They are larger and coarser than the Schuffner’s dots seen with P. vivax (B) and P. ovale (C). These are punctuate granulations again seen under the microscope in erythrocytes invaded by the tertian malaria parasite. These two structures are worth remembering for exam questions! P. malariae (D) causes ‘quartan’ malaria, meaning the fever occurs every fourth day (i.e. days 1, 4, 7 and so on). P. knowlesi (E) is much less common, and mainly occurs in southeast Asia (such as in Borneo). Maurer’s clefts and Schuffner’s dots would not typically be found in infection with these species.

Answer 47

C Infective endocarditis can be classified into two broad categories: acute and sub-acute. Acute infective endocarditis is less common, and the most likely causative agent is Staphylococcus aureus (C). It can affect both normal and abnormal valves, and can typically be found in intravenous drug users, such as the patient described. The tricuspid valve is most commonly affected in these cases, which can easily be remembered as this is the first valve that the bacteria will encounter following injection into a vein. Therefore, (C) is the correct answer in this case. The other category of infective endocarditis is the sub-acute form, which is more common. It is most often caused by Streptococcus viridans (A), and usually occurs on damaged valves. Patients typically present with an insidious onset of fevers, night sweats, and weight loss. Other clinical features can result from emboli, such as cerebral emboli causing a stroke, or less commonly recurrent pulmonary emboli in right sided endocarditis. If asked about the signs of endocarditis, steer away from mentioning the rare eponymous signs first! You can remember the signs as rules of two: two signs in the hands include clubbing and splinter haemorrhages, two signs in the abdomen are splenomegaly and microscopic haematuria, and two signs elsewhere can include new or changing heart murmurs and embolic phenomena. Remember that the most common valves to be affected are the aortic and mitral valves. Fungi such as Candida albicans (B) are a much less common cause of endocarditis. They can also be found in intravenous drug users, but this is much less likely than Staphylococcus aureus. They can include Aspergillus and Candida species, and usually cause a sub-acute picture. Strep. bovis (D) has also been implicated as a rarer cause of infective endocarditis, and is part of the natural flora of the bowel. If found in a patient with endocarditis, a colonoscopy may be important as its presence is associated with colonic malignancies. The HACEK organisms consist of a Gram-negative group which includes Haemophilus parainfluenzae, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens and Kingella (E). They typically result in a culture negative endocarditis. Whilst all of the above answers are possible, the single best answer is Staphylococcus aureus because the patient is an intravenous drug user and has developed an acute form of the disease.

Answer 48

D Acyclovir (D) is a guanosine analogue that causes obligate chain ter- mination when it attaches to DNA. It is phosphorylated by the enzyme thymidine kinase found in viruses, which is far more effective than the cellular thymidine kinase for this process. This means that normal cells which are not infected by the virus are not affected as much by acyclovir, as there is no viral thymidine kinase present. The acyclovir monophosphate which then forms is further phosphorylated to a diphosphate and then to a triphosphate by the cellular thymidine kinase. This triphosphate potently inhibits viral DNA polymerase, leading to chain termination. It is effective against the herpes viruses, for example herpes simplex and herpes zoster which causes shingles. Foscarnet (A) is a pyrophosphate analogue used for the treatment of CMV, and works by inhibiting viral DNA polymerase via a different mechanism to acyclovir. It can also be used for herpes zoster, but is usually a second line if the infection is resistant to acyclovir. It does not require phosphorylation by viral thymidine kinase. Lamivudine (B) is used for the treatment of hepatitis B and HIV, not shingles. It is a cytidine analogue, and acts as a potent nucleoside analogue reverse transcriptase inhibitor. Cidofovir (C) works by inhibiting viral DNA polymerase, and is used for cytomegalovirus retinitis. It is not dependent on phosphorylation by viral enzymes in the way acyclovir is. Ganciclovir (E) is thought to be the drug of choice for treating cytomegalovirus infections. Unlike acyclovir it is also phosphorylated by uninfected cells, so it is more toxic in comparison.

Answer 49

A The current UK immunization schedule is as follows: - Two months: Hib/IPV/DTaP/PCV - Three months: Hib/IPV/DTaP/Men C - Four months: Hib/IPV/DTaP/PCV/Men C - Twelve months: Hib/Men C - Thirteen months: MMR/PCV - Three years four months old or soon after: MMR/DTaP/IPV - 13–18 years: Booster Diptheria and tetanus/IPV DTap stands for diphtheria, tetanus and acellular pertussis, and IPV is the inactivated poliovirus vaccine. This can be challenging to remember but is often asked about in exams. One way of remembering it is this: H = Hib, I = IPV, D = DTaP, P = PCV, Men = Men C, M = MMR: - Two months: H.I.De your little baby Please. - Three months: the first three as above, but meningitis C instead of PCV - Four months: all the above - Twelve months: now we want to H.I.De them from Men. C?! - Thirteen months: MMR/Please! - Three years four months old or soon after: things are starting to D.I.M now so we need to booster it! - 13–18 years: I’D like my teenager to go back for a jab!

Answer 50

B The most common cause of a urinary tract infection in all groups of patients is Escherichia coli (B). Do not be misled by the fact that the patient is a young, sexually active woman. The E. coli bacterium is a lactose-fermenting Gram-negative rod. It has various properties that aid its pathogenesis: a flagellum to enable it to move upstream, fimbrae so that it can adhere to the urothelium, and haemolysin to form pores in white blood cells. It also has a protective capsule called the K-antigen. The other lactose fermenting organisms are Klebsiella and Enterobacter, whilst non-lactose fermenting organisms include Proteus and Pseudomonas. Lactose fermenting organisms turn MacConkey agar pink, whereas non-lactose fermenters do not. Useful investigations for urinary tract infections can include a urine dipstick to look for nitrites and leukocytes, and urine cultures looking for a bactiuria of greater than 105 colony forming units. Enterobacter (A) is less commonly implicated in urinary tract infections. They are Gram-negative, lactose-fermenting, rod-shaped bacteria. They tend to cause opportunistic infections in immunocompromised hosts, so it is unlikely to be the causative agent here. Klebsiella (C) is also a Gram-negative, non-motile, lactose-fermenting organism. Patients that are immunocompromised or have indwelling catheters are at increased risk of Klebsiella infections. Staphylococcus saphrophyticus (D) is a Gram-positive cause of urinary tract infections. It is the second most common cause of urinary tract infections in young, sexually active women after E. coli. It is coagulase positive like other staphylococcal species, but catalase negative unlike S. aureus. Proteus mirabilis (E) is an example of a non-lactose fermenting bacterium. It is not a likely cause of this patient’s UTI, but is more common in young boys and hospitalized patients. It has the ability to split urea into ammonia, which raises the pH of the urine. This predisposes to the formation of phos- phate stones, particularly staghorn calculi.

Answer 51

C Giardia lamblia (C) is a flagellated protozoan parasite which causes giardiasis. It attaches to the small bowel wall, but does not invade it. If you can remember this fact, you will find it easier to remember that it interferes with absorption, and so leads to the classic symptoms of weight loss, flatulence, chronic diarrhoea and bloating, as in the patient in this question. Because it does not invade the small bowel wall, the diarrhoea is not bloody but it is watery. Microscopy of a stool sample may show a pear-shaped protozoan. If you imagine a pear making you feel very bloated, you will remember this fact which often crops up in questions! Very rarely, a string test may be done if other methods to detect the parasites fail but there is still a high index of clinical suspi- cion. A gelatine capsule attached to a long string is swallowed, with the end of the string remaining outside the mouth and taped to the patient’s cheek. It remains in place for about 4–6 hours, before the end is exam- ined under the microscope. Treatment of giardiasis is typically oral metronidazole. Bacillus cereus (A) causes food poisoning with vomiting and sometimes diarrhoea, usually from re-heated food such as rice. The symptoms appear quite quickly, within a couple of hours of consumption. The bacteria produce spores, which are activated by changes in temperature (such as re-heating or refrigerating food) to produce heat-labile and heat-stabile toxins. The patient in question has no vomiting, no history of eating re-heated food and has unusual symptoms of flatulence and bloating which would not normally be associated with this infection. Salmonella enteritidis (B) is an important cause of food poisoning, usu- ally from contaminated meat and eggs. Do not confuse this with enteric fevers which are systemic illnesses caused by Salmonella typhi and paratyphi. The incubation period is 12–48 hours, after which the patient may present with nausea, vomiting and malaise, after which follows abdominal pain and diarrhoea. This can occasionally become bloody. Most cases are self limiting within approximately 3 days. Again the patient in the question does not fit this picture. Entamoeba histolytica (D) causes amoebic dysentery. Trophozites invade the bowel wall and lead to classical ‘flask shaped ulcers’, causing bloody diarrhoea. Trophozites can enter the portal vein and lead to liver abscesses too. The entamoeba cysts classically have four nuclei. One way to remember these somewhat obscure facts that appear in exam questions is to picture four runners ‘ent-ering’ a race, and the winner gets a silver flask! Cryptosporidium parvum (E) is a parasite that causes acute, watery diarrhoea which is not usually bloody. This is of particular concern in immunocompromised patients, such as those with AIDS, where the severe dehydration can be fatal.

Answer 52

1)A Amoxicillin (A) is a beta-lactam antibiotic which inhibits enzymes responsible for cell wall synthesis, leading to osmotic lysis of the bacteria. As a result, -beta-lactams are ineffective against bacteria that lack cell walls such as Mycoplasma spp. and Chlamydia spp. In this case, amoxicillin is the best choice antibiotic to treat mild community acquired pneumonia. It is also useful in the treatment of urinary tract infection (UTI), Listeria meningitis, endocarditis prophylaxis and protection against Streptococcus pneumoniae in asplenic patients. Major side effects can be divided into allergic (anaphylaxis) and non-allergic (Steven–Johnson syndrome) consequences. Doxycycline (B) is a tetracycline antibiotic that interferes with protein synthesis by binding to the 30S ribosomal subunit. It is used in COPD exacerbations, sexually transmitted infections (gonorrhoea and chlamydia) and acne. Co-amoxiclav IV (augmentin; C) is the combination of amoxicillin and clavulinic acid (beta-lactamase inhibitor). It is usually prescribed when beta-lactamase-producing strains are suspected and other treatment has failed. Meropenem (D) is a broad-spectrum carbapenem antibiotic which is used in the management of severely sick patients, usually in intensive care. It is resistant to beta-lactamase, including extended spectrum beta-lactamase producing bacteria. Chloramphenicol (E) acts on 50S ribosomes to inhibit protein synthesis. It is used in cases of Rocky Mountain spotted fever. Side effects include aplastic anaemia.

Answer 53

2)I Flucloxacillin (I) is a beta-lactam antibiotic that is especially effective against Gram-positive bacteria that produce beta-lactamase, for example S. aureus. Just like amoxicillin, flucloxacillin inhibits cell wall synthesis. Indications for its use include staphylococcal skin infections such as cellulitis (in this case), folliculitis and mastitis as well as pneumonia (adjunct), osteomyelitis, septic arthritis, endocarditis and prophylaxis in surgery. A rare side effect of flucloxacillin is cholestatic jaundice which may develop weeks after treatment is stopped. Doxycycline (B) is a tetracycline antibiotic that interferes with protein synthesis by binding to the 30S ribosomal subunit. It is used in COPD exacerbations, sexually transmitted infections (gonorrhoea and chlamydia) and acne. Co-amoxiclav IV (augmentin; C) is the combination of amoxicillin and clavulinic acid (beta-lactamase inhibitor). It is usually prescribed when beta-lactamase-producing strains are suspected and other treatment has failed. Meropenem (D) is a broad-spectrum carbapenem antibiotic which is used in the management of severely sick patients, usually in intensive care. It is resistant to beta-lactamase, including extended spectrum beta-lactamase producing bacteria. Chloramphenicol (E) acts on 50S ribosomes to inhibit protein synthesis. It is used in cases of Rocky Mountain spotted fever. Side effects include aplastic anaemia.

Answer 54

3)H Trimethoprim (H) is an inhibitor of folate metabolism; it impairs syn- thesis of DNA by interfering with folic acid metabolism. It is used in the treatment of uncomplicated UTIs. Trimethoprim should be used with cau- tion in patients with megaloblastic anaemia due to its interaction with folate. SE: thrombocytopenia, megalo- blastic anaemia and hyperkalaemia (via antagonism of sodium channels in the distal convoluted tubule of nephrons). Trimethoprim combined with another folate inhibitor, sulphamethoxazole, forms co-trimoxazole, which is used in the treatment of Pneumocystis jirovecii infection. Doxycycline (B) is a tetracycline antibiotic that interferes with protein synthesis by binding to the 30S ribosomal subunit. It is used in COPD exacerbations, sexually transmitted infections (gonorrhoea and chlamydia) and acne. Co-amoxiclav IV (augmentin; C) is the combination of amoxicillin and clavulinic acid (beta-lactamase inhibitor). It is usually prescribed when beta-lactamase-producing strains are suspected and other treatment has failed. Meropenem (D) is a broad-spectrum carbapenem antibiotic which is used in the management of severely sick patients, usually in intensive care. It is resistant to beta-lactamase, including extended spectrum beta-lactamase producing bacteria. Chloramphenicol (E) acts on 50S ribosomes to inhibit protein synthesis. It is used in cases of Rocky Mountain spotted fever. Side effects include aplastic anaemia.

Answer 55

3)H Trimethoprim (H) is an inhibitor of folate metabolism; it impairs syn- thesis of DNA by interfering with folic acid metabolism. It is used in the treatment of uncomplicated UTIs. Trimethoprim should be used with cau- tion in patients with megaloblastic anaemia due to its interaction with folate. SE: thrombocytopenia, megalo- blastic anaemia and hyperkalaemia (via antagonism of sodium channels in the distal convoluted tubule of nephrons). Trimethoprim combined with another folate inhibitor, sulphamethoxazole, forms co-trimoxazole, which is used in the treatment of Pneumocystis jirovecii infection. Doxycycline (B) is a tetracycline antibiotic that interferes with protein synthesis by binding to the 30S ribosomal subunit. It is used in COPD exacerbations, sexually transmitted infections (gonorrhoea and chlamydia) and acne. Co-amoxiclav IV (augmentin; C) is the combination of amoxicillin and clavulinic acid (beta-lactamase inhibitor). It is usually prescribed when beta-lactamase-producing strains are suspected and other treatment has failed. Meropenem (D) is a broad-spectrum carbapenem antibiotic which is used in the management of severely sick patients, usually in intensive care. It is resistant to beta-lactamase, including extended spectrum beta-lactamase producing bacteria. Chloramphenicol (E) acts on 50S ribosomes to inhibit protein synthesis. It is used in cases of Rocky Mountain spotted fever. Side effects include aplastic anaemia.

Answer 56

4)G Vancomycin (G) is the drug of choice in cases of methicillin-resistant Staphylococcus aureus infections (MRSA). Vancomycin is a glycopeptide antibiotic that inhibits cell wall synthesis. It is too large to traverse the cell wall of Gram-negative bacteria and hence is primarily targeted to Gram-positive bacteria. Side effects include renal failure, ototoxicity, blood disorders, rash and anaphylaxis. Due to the potential side effects, serum drug levels must be monitored. Vancomycin is also a second-line antibiotic in the treatment of Clostridium difficile infection. Doxycycline (B) is a tetracycline antibiotic that interferes with protein synthesis by binding to the 30S ribosomal subunit. It is used in COPD exacerbations, sexually transmitted infections (gonorrhoea and chlamydia) and acne. Co-amoxiclav IV (augmentin; C) is the combination of amoxicillin and clavulinic acid (beta-lactamase inhibitor). It is usually prescribed when beta-lactamase-producing strains are suspected and other treatment has failed. Meropenem (D) is a broad-spectrum carbapenem antibiotic which is used in the management of severely sick patients, usually in intensive care. It is resistant to beta-lactamase, including extended spectrum beta-lactamase producing bacteria. Chloramphenicol (E) acts on 50S ribosomes to inhibit protein synthesis. It is used in cases of Rocky Mountain spotted fever. Side effects include aplastic anaemia.

Answer 57

5)F Cefotaxime (F) is a third generation cephalosporin and is the drug of choice in treating Neisseria meningitidis, which is the most common cause of meningitis in the UK. Cefotaxime is a beta-lactam antibiotic and therefore inhibits cell wall synthesis. If meningitis is suspected in the community, the patient should be started on benzyl-penicillin until they are transferred to a secondary care unit. Cefotaxime is also useful in the treatment of pyelonephritis, sepsis secondary to hospital acquired pneu- monia and soft tissue infections. Doxycycline (B) is a tetracycline antibiotic that interferes with protein synthesis by binding to the 30S ribosomal subunit. It is used in COPD exacerbations, sexually transmitted infections (gonorrhoea and chlamydia) and acne. Co-amoxiclav IV (augmentin; C) is the combination of amoxicillin and clavulinic acid (beta-lactamase inhibitor). It is usually prescribed when beta-lactamase-producing strains are suspected and other treatment has failed. Meropenem (D) is a broad-spectrum carbapenem antibiotic which is used in the management of severely sick patients, usually in intensive care. It is resistant to beta-lactamase, including extended spectrum beta-lactamase producing bacteria. Chloramphenicol (E) acts on 50S ribosomes to inhibit protein synthesis. It is used in cases of Rocky Mountain spotted fever. Side effects include aplastic anaemia.

Answer 58

4)E Gancyclovir (E) is a 2 ́-deoxyguanosine analogue used in the treatment of cytomegalovirus (CMV) infection. It is the first line drug for the prophylaxis of CMV in bone marrow transplant patients. 2 ́-deoxy- guanosine is phosphorylated to the triphosphate form, which prevents viral DNA polymerase from elongating viral DNA and therefore inhibits CMV replication. Gancyclovir can cause bone marrow toxicity; it may therefore be prescribed together with granulocyte-colony stimulating factor (G-CSF). Gancyclovir is also used in the treatment of human herpes virus 6 (HHV-6) and Epstein–Barr virus infection. Lamivudine (F) is an NRTI (analogue of cytidine). It leads to the inhibition of reverse transcriptase and is therefore effective for the treatment of hepatitis B and HIV. Efavirenz (G) is an NNRTI used in the treatment of HIV. The drug causes inhibition of the reverse transcription enzyme. Ritonavir (H) is a protease inhibitor used in the management of HIV. Ritonavir inhibits viral assembly by preventing the cleavage of proteins that belong to newly formed virions. Amantidine (I) is an M2 ion channel inhibitor preventing the uncoating of influenza virions and therefore inhibiting entry into susceptible cells.

Answer 59

5)A Acyclovir (A) is a guanosine analogue anti-viral drug used primarily in the treatment of herpes simplex virus infections (HSV-1 and HSV-2). It is converted to acyclo-guanosine monophosphate (acyclo-GMP) by viral thymidine kinase. Acyclo-GMP is further phosphorylated to acycloguanosine triphosphate (acyclo-GTP). Acyclo-GTP is incorporated into the viral DNA strand, terminating the chain and stopping DNA polymerase from functioning. Aciclovir is also indicated for the treatment of varicella zoster, Epstein–Barr virus and cytomegalovirus infections (with decreasing efficacy). Lamivudine (F) is an NRTI (analogue of cytidine). It leads to the inhibition of reverse transcriptase and is therefore effective for the treatment of hepatitis B and HIV. Efavirenz (G) is an NNRTI used in the treatment of HIV. The drug causes inhibition of the reverse transcription enzyme. Ritonavir (H) is a protease inhibitor used in the management of HIV. Ritonavir inhibits viral assembly by preventing the cleavage of proteins that belong to newly formed virions. Amantidine (I) is an M2 ion channel inhibitor preventing the uncoating of influenza virions and therefore inhibiting entry into susceptible cells.

Answer 60

Nevirapine In 1999, the HIVNET 012 team reported exciting preliminary results that single-dose nevirapine prophylaxis for mother and baby significantly lowered HIV-1 infection risk at 14–16 weeks compared with controls who received short-course zidovudine prophylaxis. For preventing HIV mother-to-child transmission and for a discussion on pegylated Interferon vs not pegylated, and interferon alpha vs beta vs gamma, see attached file.

Answer 61

Nevirapine In 1999, the HIVNET 012 team reported exciting preliminary results that single-dose nevirapine prophylaxis for mother and baby significantly lowered HIV-1 infection risk at 14–16 weeks compared with controls who received short-course zidovudine prophylaxis. For preventing HIV mother-to-child transmission and for a discussion on pegylated Interferon vs not pegylated, and interferon alpha vs beta vs gamma, see attached file.

Answer 62

1) C Hepatitis B virus (HBV; C) is a dsDNA virus that is prevalent in sub-Saharan Africa. It is transmitted via sexual contact, contaminated blood products, intravenous drug use as well as vertical transfer from mother to child during child birth. The virus has an incubation period of 2–6 months with 80% of infections remaining acute and 20% becoming chronic with risk of cirrhosis and hepatocellular carcinoma. HBV antigens include HBsAg (surface antigen), HBcAg (core antigen) and HBeAg (soluble antigen). Cytomegalovirus (CMV; D) can be transmitted vertically from contaminated blood products and transplant organs (50% risk of infection in seropositive donor and seronegative recipient). It is especially prevalent in the immunocompromised. Hepatitis D virus (HDV; E) is a helical ssRNA virus that requires hepatitis B co-infection. HDV produces an acute-on-chronic picture in HBV patients and puts them at higher risk of cirrhosis and subsequent liver failure. Hepatitis C virus (HCV; G) is a ssRNA virus that is transferred via contaminated blood products and vertically from mother to child during birth. 20% remain acute, while 80% become chronic. Human herpes virus 8 (HHV-8; H) is transmitted primarily via saliva as well as semen to a lesser extent. It causes Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease.

Answer 63

2) A Human immunodeficiency virus (HIV; A) possesses ssRNA as well as enzymes (reverse transcriptase, integrase and protease) in its core. HIV is transmitted via sexual intercourse, blood products, IVDU and vertically from mother to child. HIV infects CD4+ T cells; within the cell the RNA undergoes reverse transcription to make DNA which is integrated into the host DNA; the virus then becomes latent or buds to infect further. AIDS (CD4+ count <200) defining illnesses include bacterial (Mycobacterium avium-intracellulare, TB), fungal (Candida albicans oesophagitis), protozoal (Pneumocystis jerovicci) and viral infections as well as certain cancers (Kaposi’s sarcoma). Cytomegalovirus (CMV; D) can be transmitted vertically from contaminated blood products and transplant organs (50% risk of infection in seropositive donor and seronegative recipient). It is especially prevalent in the immunocompromised. Hepatitis D virus (HDV; E) is a helical ssRNA virus that requires hepatitis B co-infection. HDV produces an acute-on-chronic picture in HBV patients and puts them at higher risk of cirrhosis and subsequent liver failure. Hepatitis C virus (HCV; G) is a ssRNA virus that is transferred via contaminated blood products and vertically from mother to child during birth. 20% remain acute, while 80% become chronic. Human herpes virus 8 (HHV-8; H) is transmitted primarily via saliva as well as semen to a lesser extent. It causes Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease.

Answer 64

3) B Epstein–Barr virus (EBV; B) primarily infects B lymphocytes, binding via a complement receptor. Transmission involves person-to-person transfer through close contact. EBV is associated with glandular fever (infectious mononucleosis) which causes pharyngitis, lymphadenopathy, fever, splenomegaly and hepatomegaly. Rare sequelae include thrombocytopenia and erythema multiforme. EBV can also cause Hodgkin’s lymphoma (latent reactivation of EBV), Burkitt’s lymphoma and nasopharyngeal cancers. It is diagnosed on blood film (atypical lymphocytes), monospot test (positive heterophil antibody test) and/or EBV antibodies in the blood. Cytomegalovirus (CMV; D) can be transmitted vertically from contaminated blood products and transplant organs (50% risk of infection in seropositive donor and seronegative recipient). It is especially prevalent in the immunocompromised. Hepatitis D virus (HDV; E) is a helical ssRNA virus that requires hepatitis B co-infection. HDV produces an acute-on-chronic picture in HBV patients and puts them at higher risk of cirrhosis and subsequent liver failure. Hepatitis C virus (HCV; G) is a ssRNA virus that is transferred via contaminated blood products and vertically from mother to child during birth. 20% remain acute, while 80% become chronic. Human herpes virus 8 (HHV-8; H) is transmitted primarily via saliva as well as semen to a lesser extent. It causes Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease.

Answer 65

4) I Influenza virus (I) is part of the orthomyxoviridae group of viruses and causes epidemics of influenza annually. The influenza virus causes primary pneumonia as well as delayed secondary bacterial pneumonia and otitis media in immunocompromised patients. It is a spherical virion with haemagglutinin (HA) and neuraminidase (NA) glycoproteins on the surface. HA binds to sialic acid receptors present in the upper respiratory tract; viral RNA is subsequently inserted into the host cell and HA is cleaved by clara cell tryptase. NA cleaves neuraminic acid, a component of protective mucin; as a result the protective barrier is disrupted exposing sialic acid receptor sites beneath. NA also has a role facilitating the release of newly formed influenza virions. Cytomegalovirus (CMV; D) can be transmitted vertically from contaminated blood products and transplant organs (50% risk of infection in seropositive donor and seronegative recipient). It is especially prevalent in the immunocompromised. Hepatitis D virus (HDV; E) is a helical ssRNA virus that requires hepatitis B co-infection. HDV produces an acute-on-chronic picture in HBV patients and puts them at higher risk of cirrhosis and subsequent liver failure. Hepatitis C virus (HCV; G) is a ssRNA virus that is transferred via contaminated blood products and vertically from mother to child during birth. 20% remain acute, while 80% become chronic. Human herpes virus 8 (HHV-8; H) is transmitted primarily via saliva as well as semen to a lesser extent. It causes Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease.

Answer 66

5) F Varicella zoster virus (VZV; F) is a droplet-spread herpes virus that causes chickenpox in children and shingles in adults. Chickenpox = fever, malaise and a rash (erythematous base with fluid top) that spreads over the body. Complications include secondary bacterial infection and encephalitis. VZV remains dormant in the dorsal root ganglia & may reactivate in states of immunosuppression. The most common symptom is neuralgia which occurs in a dermatomal distribution; other manifestations include encephalitis, Guillain–Barré syndrome, facial palsy and progressive outer retinal necrosis. Cytomegalovirus (CMV; D) can be transmitted vertically from contaminated blood products and transplant organs (50% risk of infection in seropositive donor and seronegative recipient). It is especially prevalent in the immunocompromised. Hepatitis D virus (HDV; E) is a helical ssRNA virus that requires hepatitis B co-infection. HDV produces an acute-on-chronic picture in HBV patients and puts them at higher risk of cirrhosis and subsequent liver failure. Hepatitis C virus (HCV; G) is a ssRNA virus that is transferred via contaminated blood products and vertically from mother to child during birth. 20% remain acute, while 80% become chronic. Human herpes virus 8 (HHV-8; H) is transmitted primarily via saliva as well as semen to a lesser extent. Causes Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease.