GUM - Viral STIs

Question 1

What is herpes simplex virus?

Answer 1

There are two strains of the herpes simplex virus (HSV) in humans: HSV-1 and HSV-2. Whilst it was previously thought HSV-1 accounted for oral lesions (cold sores) and HSV-2 for genital herpes it is now known there is considerable overlap.

Question 2

What symptoms does HSV cause?

Answer 2

• primary infection: may present with a severe gingivostomatitis
• cold sores
• painful genital ulceration (cf. syphilis where lesions are non painful)

Question 3

How is HSV infection managed?

Answer 3

gingivostomatitis: oral aciclovir, chlorhexidine mouthwash
cold sores: topical aciclovir although the evidence base for this is modest
genital herpes: oral aciclovir. Some patients with frequent exacerbations may benefit from longer term aciclovir.

Salt water bathing is also useful.

Question 4

How should HSV be managed during pregnancy?

Answer 4

Elective caesarean section at term is advised if a primary attack of herpes occurs during pregnancy at greater than 28 weeks gestation.

Women with recurrent herpes who are pregnant should be treated with suppressive therapy and be advised that the risk of transmission to their baby is low.

Question 5

What virus causes genital warts?

Answer 5

Genital warts (also known as condylomata accuminata) are a common cause of attendance at genitourinary clinics. They are caused by the many varieties of the human papilloma virus HPV, especially types 6 & 11. It is now well established that HPV (primarily types 16,18 & 33) predisposes to cervical cancer.

Question 6

How do genital warts present?

Answer 6

Small (2 - 5 mm) fleshy protuberances (cauliflower appearance) which are slightly pigmented
May bleed or itch

Question 7

How are congenital warts managed?

Answer 7

• topical podophyllum or cryotherapy are commonly used as first-line treatments depending on the location and type of lesion. Multiple, non-keratinised warts are generally best treated with topical agents whereas solitary, keratinised warts respond better to cryotherapy
• imiquimod is a topical cream which is generally used second line
• genital warts are often resistant to treatment and recurrence is common although the majority of anogenital infections with HPV clear without intervention within 1-2 years

Question 8

How is hepatitis B transmitted?

Answer 8

Hepatitis B is a double-stranded DNA hepadnavirus and is spread through exposure to infected blood or body fluids, including vertical transmission from mother to child. The incubation period is 6-20 weeks.

Question 9

What are the clinical features of hepatitis B infection?

Answer 9

Features of hepatitis B include fever, jaundice and elevated transaminases (AST and ALT). Remember, transaminases are located in hepatocytes and are released following cell damage. ALP and GGT are found in duct epithelium and are usually raised first following obstruction.

The illness tends to start insidiously, with fever and anorexia. Jaundice (darkening of urine and lighter stools) is only seen in 10% of patients. Majority are detected by deranged LFTs.

Question 10

What are the complications of hepatitis B infection?

Answer 10

chronic hepatitis (5-10%)
fulminant liver failure (1%)
hepatocellular carcinoma
glomerulonephritis
polyarteritis nodosa
cryoglobulinaemia

Question 11

Which groups are at risk of hepatitis B infection and should be immunised?

Answer 11

At risk groups who should be vaccinated include: healthcare workers, intravenous drug users, sex workers, close family contacts of an individual with hepatitis B, individuals receiving blood transfusions regularly, chronic kidney disease patients who may soon require renal replacement therapy, prisoners, chronic liver disease patients.

Most schedules give 3 doses of the vaccine with a recommendation for a one-off booster 5 years following the initial primary vaccination.

Question 12

What factors suggest a poor response to hepatitis B vaccine?

Answer 12

Around 10-15% of adults fail to respond or respond poorly to 3 doses of the vaccine. Risk factors include age over 40 years, obesity, smoking, alcohol excess and immunosuppression.

Question 13

What is HBsAg? What does its presence imply?

Answer 13

Hepatitis B surface antigen (HBsAg) is a surface protein found in excess in hepatitis B and circulates in the blood. It is the first marker to appear in acute hepatitis infection and causes the production of anti hepatitis B surface antibodies (anti-HBs).

HBsAg normally implies acute disease (present for 1-6 months). If HBsAg is present for longer than 6 months then this implies chronic disease (i.e. infective).

The key thing to remember is that HBsAg = ongoing infection, either acute or chronic (if longer than 6 months).

Question 14

What does the presence of anti-HBs suggest?

Answer 14

The presence of anti hepatitis B surface antigen antibodies suggests immunity (either exposure or immunisation). If exposure is from previous infection then anti-HBc are also present. If from vaccination, anti-HBc is not present. It is negative in chronic disease.

Question 15

What is anti-HBc?

Answer 15

The hepatitis B core antigen (HBcAg) is not found in the blood but antibody to it (anti-HBc) appears early in illness. Anti-HBc is initially IgM type, with IgG appearing later and persisting.

Anti-HBc = caught, i.e. negative if immunised

Question 16

What is HBeAg?

Answer 16

HbeAg results from breakdown of core antigen from infected liver cells as is therefore a marker of infectivity. It appears only transiently at the outset of the illness and is followed by the production of antibody (anti-HBe).

Question 17

What hepatitis B serology suggests previous immunisation?

Answer 17

previous immunisation: anti-HBs positive, all others negative

Question 18

What serology suggests previous hepatitis B (>6 months ago), not a carrier?

Answer 18

anti-HBc positive (IgG), HBsAg negative

Question 19

What hepatitis serology would suggest carrier status?

Answer 19

previous hepatitis B, now a carrier: anti-HBc positive, HBsAg positive

Question 20

How should viral load be interpreted?

Answer 20

HBV-DNA can be measured by PCR in the blood. Viral loads are usually >105 copies/mL in the presence of active viral replication, as indicated by the presence of e antigen. In contrast, in those with low viral replication, HBsAg- and anti-HBe-positive, viral loads are usually <105 copies/mL. High viral loads are also found in e antigen-negative chronic hepatitis, which occurs in the Far East and is due to a mutation.

Question 21

What is the natural history of hepatitis B infection?

Answer 21

There is an initial immunotolerant phase with
high levels of virus and normal liver biochemistry. An immunological response to the virus then occurs, with elevation in serum transaminases, which causes liver damage: chronic hepatitis. If this response is sustained over many years and viral clearance does not occur promptly, chronic hepatitis may result in cirrhosis. In individuals who mount a successful immunological response, viral load falls, HBe antibody develops and there is no further liver damage. Some individuals may subsequently develop HBV-DNA mutants, which escape from immune regulation, and viral load again rises with further chronic hepatitis. Mutations in the core protein result in the virus’s inability to secrete HBe antigen despite high levels of viral replication; such individuals have HBeAg negative chronic hepatitis.

Question 22

How is hepatitis B managed?

Answer 22

Pegylated interferon-alpha used to be the only treatment available. It reduces viral replication in up to 30% of chronic carriers. A better response is predicted by being female, < 50 years old, low HBV DNA levels, non-Asian, HIV negative, high degree of inflammation on liver biopsy.

Whilst NICE still advocate the use of pegylated interferon firstl-line other antiviral medications are increasingly used with an aim to suppress viral replication (not in a dissimilar way to treating HIV patients)
examples include tenofovir and entecavir.

Question 23

How common is chronic hepatitis B? What treatment is available?

Answer 23

This develops in 5–10% of acute cases and is lifelong. No drug is consistently able to render patients HBsAg-negative.

Lamivudine and tenofovir are both effective, but viral mutations causing resistance commonly develop. Tenofovir also has anti-HIV efficacy, so monotherapy should be avoided in HIV co-infected patients to prevent HIV antiviral drug resistance. Interferon alfa is most effective in patients with low viral load and high transami- nases, in whom it acts by augmenting a native immune response. Interferon is contraindicated in the presence of cirrhosis, as it may precipitate liver failure. Longer-acting pegylated interferons, which can be given once weekly, have been evaluated in both HBeAg- positive and HBeAg-negative chronic hepatitis.

Question 24

How can hepatitis B infection be prevented?

Answer 24

Individuals are most infectious when markers of continuing viral replication, such as HBeAg, and high levels of HBV-DNA are present in the blood. HBV-DNA can be found in saliva, urine, semen and vaginal secretions. The virus is about ten times more infectious than hepatitis C, which in turn is about ten times more infectious than HIV. Recombinant hepatitis B vaccines containing HBsAg are avail- able which are capable of producing active immunisation in 95% of normal individuals. Infection can also be prevented or minimised by the IM injection of hyperimmune serum globulin prepared from blood containing anti-HBs. This should be given within 24 hrs, or at most a week, of exposure to infected blood in circumstances likely to cause infection (e.g. needlestick injury, contamination of cuts or mucous membranes).

Question 25

What are the important features of hepatitis B during pregnancy?

Answer 25

• all pregnant women are offered screening for hepatitis B
• babies born to mothers who are chronically infected with hepatitis B or to mothers who’ve had acute hepatitis B during pregnancy should receive a complete course of vaccination + hepatitis B immunoglobulin
• studies are currently evaluating the role of oral antiviral treatment (e.g. Lamivudine) in the latter part of pregnancy
• there is little evidence to suggest caesarean section reduces vertical transmission rates
• hepatitis B cannot be transmitted via breastfeeding (in contrast to HIV)

Question 26

What is hepatitis C?

Answer 26

Hepatitis C is likely to become a significant public health problem in the UK in the next decade. It is thought around 200,000 people are chronically infected with the virus. At risk groups include intravenous drug users and patients who received a blood transfusion prior to 1991 (e.g. haemophiliacs).

It is caused by hepatitis C virus which is an RNA flavivirus. Incubation period is 6-9 weeks.

Question 27

How is hepatitis C transmitted?

Answer 27

The risk of transmission during a needle stick injury is about 2%.
The vertical transmission rate from mother to child is about 6%. The risk is higher if there is coexistent HIV
breast feeding is not contraindicated in mothers with hepatitis C.
The risk of transmitting the virus during sexual intercourse is probably less than 5%.

Question 28

What are the clinical features of hepatitis C infection?

Answer 28

After exposure to the hepatitis C virus less than 20% of patients develop an acute hepatitis

Complications:

1) chronic infection (80-85%) - only 15-20% of patients will clear the virus after an acute infection and hence the majority will develop chronic hepatitis C
2) cirrhosis (20-30% of those with chronic disease)
3) hepatocellular cancer
4) cryoglobulinaemia
5) porphyria cutanea tarda (PCT): it is increasingly recognised that PCT may develop in patients with hepatitis C, especially if there are other factors such as alcohol abuse

Question 29

How is chronic hepatitis C infection managed?

Answer 29

Treatment depends on genotype:

• currently a combination of pegylated interferon-alpha, ribavirin and a a protease inhibitor (e.g. boceprevir, simeprevir and telaprevir) is used
• cure rates are now approaching 90%, including for some strains which have been previously difficult to treat
• the aim of treatment is sustained virological response (SVR), defined as undetectable serum HCV RNA six months after the end of therapy

Question 30

What are the complications of hepatitis C treatment?

Answer 30

Ribavirin - side-effects: haemolytic anaemia, cough. Women should not become pregnant within 6 months of stopping ribavirin as it is teratogenic

Interferon alpha - side-effects: flu-like symptoms, depression, fatigue, leukopenia, thrombocytopenia