Infectious diseases

Question 1

How is hepatitis A transmitted?

Answer 1

Faeco-oral. Often in travellers or those in institutions. Also shellfish

Question 2

How do you interpret Hep A serology?

Answer 2

IgM signifies recent infection

IgG remains detectable for life.

Question 3

What is the clinical course of Hep A?

Answer 3

Incubation 2-6 weeks
Symptoms - prodromal fever, malaise, anorexia, nausea and arthralgia, with jaundice +/- hepatomegaly, splenomegaly and lymphadenopathy.
Usually self limiting. Rarely, fulminant hepatitis occurs.

Question 4

What immunisation is available for Hep A?

Answer 4

Passive immunisation with normal human immunoglobulin gives immunity to those at risk.
Active immunisation is with an inactivated protein derived from HAV.

Question 5

What sort of virus is Hep B?

Answer 5

DNA virus

Question 6

How is hep B spread?

Answer 6

Blood products, IVDU
Sexual intercourse
Direct contacts
Vertical transmission

Question 7

Where is hepatitis B endemic?

Answer 7

Far East, Africa and Mediterranean.

Question 8

What are some of the extrahepatic symptoms of hep B?

Answer 8

Urticaria, arthralgia, fever, cryoglobulinaemia and other immune-complex mediated conditions such as arteritis or glomerulonephritis

Question 9

What are the significance of HBsAg, HBeAg and HBV DNA?

Answer 9

HBsAg - can be present in acute or chronic infection
HBeAg - acute hep B with high infectivity
HBV DNA - implies viral replication. Levels indicate response to treatment.

Question 10

What do the different Hep B antibodies mean?

Answer 10

Anti-HBs - immunity to HBV, previous exposure/vaccination
Anti-HBe - seroconversion
Anti-HBc IgM - acute hep B (high titre), chronic hep B (low titre)
IgG - past exposure to hep B

Question 11

What is the clinical course of hepatitis B?

Answer 11

The majority of patients recover completely.
Fulminant hepatitis occurs in up to 1%
Some patients go on to develop chronic hepatitis, cirrhosis and HCC, or have inactive chronic HBV infection.

Question 12

What investigations would you do to diagnose hepatitis C?

Answer 12

LFT
Anti-HCV antibodies - ELISA
qHCV RNA PCR
Recombinant immunoblot assay
Liver biopsy if HCV-PCR positive to assess liver damage and need for treatment.

Question 13

What is the clinical course of hep C?

Answer 13

Early infection is often mild/asymptomatic. 85% develop chronic infection; 20-30% get cirrhosis within 20 years. A few get HCC.

Question 14

How is hepatitis C treated?

Answer 14

Combination therapy, comprising PEG-interferon alpha-A and ribavirin, is recommended for the treatment of chronic hep C.

Question 15

What is the significance of hepatitis D?

Answer 15

It is an incomplete RNA virus which only exists with HBV and spreads with HBV. When present, it increases the risk of acute hepatic failure and cirrhosis.

Question 16

What do you know about hepatitis E?

Answer 16

RNA virus which is similar to HAV. It is enterally transmitted and common in Indo China.

It causes a high mortality in pregnancy (20%) from fulminant hepatitis.

Prevention and control depend on good sanitation and hygiene.

Question 17

What tests would you do for suspected TB?

Answer 17

Latent TB - Mantoux testing and interferon-gamma testing (Quantiferon TB gold/T-spot-TB)

Active TB - CXR showing suspicious features, sputum samples (x3, with one morning sample) - send for MC&S for acid-fast bacilli. if sputum cannot be obtained, consider bronchoscopy and lavage.

Active non-respiratory TB - try to get the relavant sample and send for MC&S for AFB.

Question 18

How is TB treated?

Answer 18

TB is treated in 2 phases - an initial phase using 4 drugs and a continuation phase using 2 drugs in fully sensitive cases.

In the initial phase, 4 drugs are used. These are rifampicin, isoniazid, pyrazinamide and ethambutol.

Streptomycin is rarely used in the UK but can be used if isoniazid resistance is confirmed.

After the initial phase, treatment is continued for a further 4 months with isoniazid and rifampicin. Longer treatment is necessary for meningitis, direct spinal cord involvement and for resistant organisms which may also require modification of the regimen.

Question 19

Before starting TB treatment, which tests should be performed?

Answer 19

LFTs - rifampicin, isoniazid and pyrazinamide can all cause liver toxicity.

U&Es - streptomycin and ethambutol should preferably be avoided in patients with renal impairment, but if used the dose should be reduced and the plasma-drug concentration monitored.

Visual acuity and colour vision should be started before starting ethambutol.

Question 20

What side effects should you warn the patient of before starting rifampicin?

Answer 20

Common: often causes transient disturbance of liver function with elevated serum transaminases. Occasionally causes more serious liver toxicity. Also causes body secretions to become orange.

Occasional: six toxicity syndromes have been recognised: influenza-like, abdominal and respiratory symptoms, shock, renal failure and thrombocytopenic purpura.

Rifampicin induces hepatic enzymes which accelerate the metabolism of several drugs including oestrogens, corticosteroids, phenytoin, sulphonylureas and anticoagulants.

Question 21

What are the side effects of isoniazid?

Answer 21

Common: peripheral neuropathy, which is more likely to occur when there are pre-existing risk factors such as diabetes, alcohol dependence, chronic renal failure, malnutrition and HIV infection. Pyridoxine 10mg daily can be given prophylactically from the start of treatment.

Question 22

What is the side effect of pyrazinamide?

Answer 22

Severe liver toxicity may occasionally occur.

Question 23

What are the side effects of ethambutol?

Answer 23

Visual disturbances in the form of loss of acuity, colour blindness and restriction of visual fields. Early discontinuation of the drug is almost always followed by recovery of eyesight.

Question 24

What are the stages of HIV infection?

Answer 24

Acute - often asymptomatic

Seroconversion - may be accompanied by a transient illness 2-6 weeks after exposure: fever, malaise, myalgia, pharyngitis, maculopapular rash or meningoencephalitis.

AIDS-related complex - later, constitutional symptoms develop, with fever, night sweats, diarrhoea, weight loss and minor opportunistic infections. This is regarded as a prodrome to AIDS.

AIDS - characterised by CD4 count <200 x 10^6/L and the presence of an indicator disease.

Question 25

What investigations would you do to test for HIV?

Answer 25

Serum HIV-Ab by ELISA, usually confirmed by Western blot.

In case of recent infection, HIV-Ab might be negative. In this case, check HIV RNA (PCR) or core p24 antigen or plasma or repeating ELISA at 6 weeks and 3 months.

Question 26

Which tests should you do once you have made a diagnosis of HIV?

Answer 26

Tuberculin

Toxoplasma, CMV, hep B/C and syphilis serology

Question 27

What is the chief life-threatening infection in AIDS?

Answer 27

PCP = pneumocystis pneumonia

Question 28

What is the treatment for PCP pneumonia?

Answer 28

High dose co-trimoxazole, with each dose preceded by prednisolone.

Primary prophylaxis of co-trimoxazole can be given if CD4<200. Secondary prevention is essential after first attack.

Question 29

What are the features of PCP pneumonia in a patient with AIDS?

Answer 29

Gradual onset. Characterised by fever, cough, dyspnoea progressing over days to weeks.

Common findings: fever, tachypnoea and crepitations, but normal chest exam in 50%. Hypoxia occurs with progression of PCP.

CXR normal in up to 25% of patients. The commonest radiographic abnormalities are diffuse, bilateral, interstitial or alveolar infiltrates.

Question 30

How would you definitively diagnose PCP pneumonia?

Answer 30

Requires visualisation of the cystic or trophic forms in respiratory secretions.

Sputum induction is the initial step in the attempt to obtain an adequate specimen, but in many cases,bronchoalveolar lavage specimens are required to make the diagnosis. Infrequently, tissue biopsy may be required.

Question 31

What is toxoplasmosis and how is it transmitted?

Answer 31

It is caused by the intracellular protozoan Toxoplasma gondii. It infects via the gut (in poorly cooked meat), lung or broken skin via infected cysts. In humans, the oocytes release trophozoites which migrate widely with a predeliction for eye, brain and muscle.

Infection is lifelong and may be reactivated by HIV.

50% in the UK have been infected by 70 years.

Question 32

Where is the commonest site for toxoplasmosis reactivation?

Answer 32

CNS –> cerebral abscess

Question 33

What are the clinical features of toxoplasmic encephalitis? What would you see on CT?

Answer 33

Headache, confusion, fever, focal neurological signs, seizures, dull affect due to global encephalitis or raised ICP.

On CT, there are usually multiple ring-shaped contrast-enhancing CNS lesions with a predeliction for basal ganglia.

Question 34

What are the extracerebral manifestations of toxoplasmosis and how do they present?

Answer 34

Pneumonitis - fever, dyspnoea and non-productive cough. CXR typically has reticulonodular infiltrates and may be indistinguishable from PCP. Diagnose with bronchoalveolar lavage.

Chorioretinitis - eye pain and reduced visual acuity. On fundoscopy, there are raised, yellow-white cottony lesions in a non-vascular distribution.

Question 35

What investigations would you do to confirm toxoplasmosis?

Answer 35

Acute infection is confirmed by a 4-fold rise in Ab-titre over 4 weeks or specific IgM (unreliable if HIV positive). A definitive diagnosis of TE requires a compatible clinical syndrome, identification of mass lesions by brain imaging and detection of the organism in a biopsy. However, most clinicians would prefer to treat a seropositive patient and only do a biopsy if symptoms do not improve.

Question 36

How would you treat toxoplasmosis?

Answer 36

Pyrimethamine and sulfadizine and leucovorin.

Question 37

What is Kaposi’s sarcoma?

Answer 37

An angioproliferative disorder that requires infection with human herpes virus 8. It causes multicentric neoplasms derived from capillary endothelial cells or from fibrous tissue –> purple papules or plaques on skin and mucosa.

Question 38

How might Kaposi’s sarcoma present in an AIDS patient? How would you treat?

Answer 38

Gut, skin and lung lesions. Lung KS may present as dyspnoea and haemoptysis. Bowel KS may present with nausea and abdominal pain.

Treatment is by optimising HAART. Radiotherapy can be considered for skin lesions, as can chemotherapy.

Question 39

How is cryptococcal meningitis diagnosed?

Answer 39

Clinical features of chronic meningitis.

High index of suspicion if CD4 count is low. LP –> raised ICP and CSF culture to confirm and India Ink staining. Also testing for cryptococcal antigen in serum and CSF.

Question 40

How is cryptococcal meningitis treated?

Answer 40

Amphotericin B IV for 14 days
Fluconazole
Normalising ICP by repeated LPs and shunts might help.

Give secondary prophylaxis with fluconazole until CD4>150 and cryptococcal antigen negative.

Question 41

What are the different classes of anti-retroviral agents in HAART?

Answer 41

Nucleoside and nucleotide reverse transcriptase inhibitors e.g. zidovudine and limivudine

Non-nucleoside RT inhibitors e.g. nevirapine

Protease inhibitors

Integrase strand transfer inhibitors

CCR5 antagonists

Question 42

Describe a HAART regimen.

Answer 42

Most regimens contain 2 NRTIs and either a PI, NNRTI or an integrase inhibitor. The exact regimen takes into account a patient’s comorbid condition, the characteristics of a virus, drug availability and cost and practicalities.