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Q1: What is the likely and differential diagnosis?
The liver function abnormalities in the teacher reveal a marked increase of ALT suggesting acute hepatocellular damage. There are a wide range of causes of acute hepatitis (see box 1).
Box 1: Causes of acute hepatitis
Viral infection: hepatitis A, B, C, E, Epstein-Barr, cytomegalovirus.
Bacterial infection: leptospirosis.
Liver hypoperfusion and hypoxia.
Drug induced: antibiotics, oral contraceptive pill, phenothiazines.
Toxins: carbon tetrachloride, solvents.
Metabolic: Wilson's disease, haemochromatosis.
Autoimmune: chronic active, lupoid.
Assuming that the boy had the same illness, the most likely cause in this setting is infective viral hepatitis A (HAV). HAV is an RNA hepatovirus belonging to the family picornaviridae. HAV is an enteric infection and has a mean incubation period of 28 days (range 15–50). The likelihood of developing symptomatic infection is related to the patient's age. In children less than 6 years old, 70%–90% of infections are asymptomatic, and if illness does occur, jaundice is unusual.1 In adults, infection is usually symptomatic and variable in clinical severity, with jaundice occurring in over 70% patients affected.2 Convalescence may be prolonged over several months, but there is usually complete recovery. There was no direct contact between the teacher and school child and it is therefore likely that infection was acquired as part of an outbreak rather than by person-to-person transmission.
The incidence of HAV shows a cyclical pattern in the UK, the most recent peak year being 1992 when 7856 cases in England and Wales were reported to the Public Health Laboratory Service. In 1999, there were 1676 cases reported.3
Q2: What was the diagnostic test performed?
The diagnosis is established by detecting the presence of serum IgM antibody to the capsid proteins of HAV. These usually become detectable 5–10 days before the onset of symptoms. IgG anti-HAV, which appears after several weeks of infection, persists conferring lifelong immunity against the disease.
Q3: What are the risk factors for contracting this condition?
HAV is acquired primarily by the faeco-oral route by either person-to-person contact or ingestion of contaminated food or water. In developing countries, water borne and food borne transmission is almost universal in childhood and responsible for HAV endemicity. However, in areas of low prevalence, extensive outbreaks may occur, for example, in Shanghai in 1988, an epidemic of 300 000 cases was linked to consumption of infected clams.4
Improved sanitation in developed countries has dramatically reduced the incidence of HAV over the last 25 years; however, this leaves many adults susceptible to HAV infection. In developed countries, the most frequent source of HAV infection during community outbreaks is from person-to-person transmission between household and sexual contacts, accounting for 12%–26% of cases.5 As most children have asymptomatic or unrecognised infection, they play an important part in HAV transmission and act as a source of infection for others, for example in day care centres and close communities.6
Travellers to countries that have high endemicity of hepatitis A are at substantial risk of acquiring HAV. In 1999, 60% of the notified cases in England and Wales included a history of travel abroad before the onset of illness.3 Prospective studies suggest that the risk to non-immune travellers is 3–5/1000 per month of stay.7
Hepatitis A outbreaks have been identified in homosexual men with association noted between oral-anal contact, the incidence of other sexually transmitted diseases, and multiple partners. Intravenous drug users have higher anti-HAV seropositivity than the general population and outbreaks have been reported in these communities.
Several outbreaks of HAV have been reported in the United States and Europe among patients with clotting factors disorders receiving solvent-detergent-treated factor VIII and IX concentrates contaminated from plasma donors incubating HAV. Although not at increased risk of contracting HAV, those who have chronic liver disease are at increased risk of fulminant hepatitis A and should be considered for immunisation.
See box 2for those at risk for HAV.
Box 2: People at risk for HAV
Household or sexual partners of patient.
Those with poor sanitation and exposed to raw sewage.
Those exposed to water borne or food contamination—for example, shellfish.
Travellers to endemic areas.
Intravenous drug users.
Recipients of factor VIII and IX concentrate.
Laboratory workers in direct contact with HAV.
Residents of institutions for the mentally handicapped.
Young children and staff in nurseries.
Q4: What is the management approach to the control of this condition?
There is no specific treatment of HAV and management is supportive. HAV is a notifiable disease and should be promptly reported to the local Communicable Diseases Department. Improvements in social conditions in developed countries have reduced the incidence of HAV and consequently the proportion of the adult population who are susceptible to infection has risen. Adults are more likely to have severe illness, which increases the importance of controlling outbreaks. There are several vaccination strategies that can be used for control of outbreaks and post-exposure prophylaxis.
The current recommendation in the UK Department of Health Handbook is to provide protection through the passive transfer of antibody by use of human normal immunoglobulin (HNIG).8 When administered within two weeks after an exposure to HAV, HNIG has protective efficacy of over 85%. However, this strategy poses a number of concerns. HNIG is administered by deep intramuscular injection that can be painful, limiting its use in children and mass campaigns. It may interfere with the development of active immunity from live vaccines such as measles, mumps, and rubella. Although plasma donors are tested for blood borne viruses, there is general concern regarding the use of human blood products and the potential risk of transmissible spongiform encephalopathies.
Hepatitis A vaccine is easier to administer and, after a booster, offers up to 10 years of protection that can be use in populations with low natural immunity. It does not interfere with the immunogenicity of other vaccines. Double blind, placebo controlled studies suggest protective antibody response of between 94% and 100% at four weeks after immunisation.9,10 In one study, over 90% seronegative vaccinees developed protective IgG three to four weeks after single dose immunisation.11
Several studies have confirmed the effectiveness of HAV vaccine without HNIG in controlling outbreaks. In populations of high HAV endemicity, inactivated vaccine has been successfully used to terminate ongoing established epidemics.11,12 There has been successful use of HAV vaccine in the control of community outbreaks in schools and day centres.13–16 Although the incubation of HAV infection may be up to 50 days, a randomised controlled trial of HAV vaccine found that it was 79% efficacious in preventing development of HAV IgM positivity after post-household exposure compared with no treatment.17 No cases of HAV in vaccine recipients were reported during use of inactivated hepatitis A vaccine to terminate an outbreak.10,18 Furthermore, in chimpanzee animal models, inactivated HAV vaccine can prevent infection if given shortly after HAV exposure therefore suggesting a post-exposure prophylaxis effect in those already infected.19 In practice, however, there remains the risk that those already infected at the time of immunoprophylaxis will develop symptomatic illness, although this risk appears less with inactivated vaccine than with passive immunity by administration of HNIG.12 There have been no clinical trials of HNIG compared with inactivated HAV vaccine in prevention of HAV.
Several vaccination approaches have been used, including protecting adults alone in small outbreaks (as those most susceptible to serious illness), both adults and children, extending vaccination to household contacts or targeting those at risk by identifying serological status by measurement of salivary IgM and IgG anti-HAV.15,17
Acute HAV outbreak managed by immunisation of all adults in school and household contacts of both cases.
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