In most developing countries, infection occurs in childhood asymptomatically, or with a mild illness. The latter infections may be detectable only through laboratory tests of liver function. Onset of illness in adults in non-endemic areas is usually abrupt, with fever, malaise, anorexia, nausea and abdominal discomfort, followed within a few days by jaundice. The disease varies in clinical severity from a mild illness lasting 1–2 weeks to a severely disabling disease lasting several months. Prolonged, relapsing hepatitis for up to 1 year occurs in 15% of cases; no chronic infection is known to occur. Convalescence is often prolonged. In general, severity increases with age, but complete recovery without sequelae or recurrences is the rule. Reported case fatality is normally low, 0.1%–0.3%; it can reach 1.8% for adults over 50. Persons with chronic liver disease have an elevated risk of death from fulminant hepatitis A.
Hepatitis A virus (HAV), a 27-nanometer picornavirus (positive-strand RNA virus). It has been classified as a member of the family Picornaviridae.
Demonstration of IgM antibodies against hepatitis A virus (IgM anti-HAV) in the serum of acutely or recently ill patients establishes the diagnosis. IgM anti-HAV becomes detectable 5–10 days after exposure. A 4-fold or greater rise in specific antibodies in paired sera, detected by commercially available EIA, also establishes the diagnosis. If laboratory tests are not available, epidemiological evidence may provide support for the diagnosis. HAV RNA can be detected in blood and stools of most persons during the acute phase of infection through nucleic acid amplification methods, but these are not generally used for diagnostic purposes.
Person-to-person by the fecal-oral route. The infectious agent is found in feces, reaches peak levels the week or two before onset of symptoms, and diminishes rapidly after liver dysfunction or symptoms appear, which is concurrent with the appearance of circulating antibodies to HAV.
Common source outbreaks have been related to contaminated water; food contaminated by infected food handlers, including foods not cooked or handled after cooking; raw or undercooked mollusks harvested from contaminated waters; and contaminated produce such as lettuce and strawberries. Several outbreaks have been associated with injecting and non-injecting drug use. Transmission through transfusion of blood and clotting factor concentrates obtained from viremic donors during incubation has been reported, albeit rarely.
Average 28–30 days (range 15–50 days).
Studies of transmission in humans and epidemiological evidence indicate that maximum infectivity occurs during the latter half of incubation and continues for a few days after onset of jaundice (or during peak aminotransferase activity in anicteric cases). Most cases are probably noninfectious after the first week of jaundice, although prolonged viral excretion (up to 6 months) has been documented in infants and children. Chronic shedding of HAV in feces does not occur.
Humans, rarely chimpanzees and other primates.
General. Low incidence of manifested disease in infants and preschool children suggests that mild and anicteric infections are common. Homologous immunity after infection probably lasts for life.
Worldwide, geographic areas can be characterized by high, intermediate, or low levels of endemicity. Levels of endemicity are related to hygienic and sanitary conditions. In areas of high endemicity, adults are usually immune and epidemics of HA are uncommon. Improved sanitation in many parts of the world is leaving many young adults susceptible, and the frequency of outbreaks is increasing. In industrialized countries, disease transmission is most frequent among household and sexual contacts of acute cases, and occurs sporadically in day care centers with children in diapers/nappies, among travelers to countries where the disease is endemic, among injecting drug users, and among men who have sex with men. Because most children have asymptomatic or unrecognized infections, they play an important role in HAV transmission and serve as a source of infection for others. Where environmental sanitation is poor, infection is common and occurs at an early age. In some southeastern Asian areas, over 90% of the general population has serological evidence of prior HAV infection, vs. a rate of 33% in industrialized countries.
Epidemics often evolve slowly, cover wide geographic areas, and last many months; common source epidemics may evolve rapidly. During some outbreaks, day care center employees or attenders, men with multiple male sex partners and injecting drug users may be at higher risk than the general population. In about half the cases no source of infection is identified. The disease is most common among school-age children and young adults. In recent years, community-wide outbreaks have accounted for most disease transmission, although common source outbreaks due to food contaminated by food handlers and contaminated produce continue to occur and require intensive public health efforts to control. These outbreaks are usually associated with contamination of food by an HAV-infected food handler during preparation, or with food (e.g. shellfish, raw produce) contaminated before entering the food chain. Outbreaks have been reported among susceptible persons working with nonhuman primates raised in the wild.
a) Educate the public about proper sanitation and personal hygiene, with special emphasis on careful hand-washing and sanitary disposal of feces.
b) Provide proper water treatment and distribution systems and sewage disposal.
c) There are at least 4 inactivated vaccines on the market, all in line with the WHO recommendations. The dose of vaccine, vaccination schedule, ages for which the vaccine is licensed, and whether there is a pediatric and adult formulation all vary by manufacturer, and no vaccine is licensed for use in children under 1. Clinical trials have shown these vaccines to be safe, immunogenic and efficacious. Protection against clinical hepatitis A may begin in some persons as soon as 14–21 days after a single dose of vaccine, and nearly all have protective levels of antibody by 30 days after receiving the first dose of vaccine. A second dose is felt to be necessary for long-term protection. Depending on the level of HAV endemicity, it may in some cases be cost-effective to screen for HAV antibody prior to immunization.
d) WHO has issued recommendations for the use of hepatitis A vaccine. In industrialized countries with low endemicity and with high rates of disease in specific high-risk populations, vaccination of these populations against hepatitis A may be recommended. High-risk groups include the following: a) persons at increased risk for HAV infection or its consequences (chronic liver disease or clotting factor disorders; men who have sex with men; injecting drug users; all susceptible persons traveling to or working in countries where HAV is endemic; persons who work with HAV infected primates or with HAV in research laboratory settings); b) children in communities with consistently elevated rates of hepatitis A.
Close personal contacts (e.g. household, sexual) of hepatitis A patients should be given post-exposure prophylaxis with hepatitis A vaccine, preferably simultaneously with IG within 2 weeks of last exposure given at a separate injection site. Recommendations for hepatitis A vaccination in outbreak situations depend on the epidemiology of hepatitis A in the community and the feasibility of rapid implementation of a widespread vaccination program. The use of hepatitis A vaccine to control community-wide outbreaks has been most successful when vaccination is started early in the course of the outbreak and with high coverage of multiple-age cohorts.
e) Although day care centers can be the source of outbreaks of hepatitis A in some communities, disease within those centers commonly reflects extended transmission in the community. Management of day care centers should stress measures to minimize the possibility of fecal-oral transmission, including thorough hand-washing after every diaper/nappy change and before eating. If one or more hepatitis A cases are associated with a center, or if cases are recognized in two or more households of attenders, hepatitis A vaccine, possibly in combination with IG, should be administered to the staff and attenders. The same should be considered for family contacts of children in diapers/nappies attending centers where outbreaks occur and cases are recognized in 3 or more families.
f) All susceptible travelers to intermediate or highly endemic areas, including Africa, the Middle East, Asia, eastern Europe and Central and South America should be given hepatitis A vaccine prior to departure, possibly together with IG if departure takes place in less than 1 week. If used, IG in a single dose of 0.02 ml/kg, or 2 ml for adults, is recommended for expected exposures of up to 3 months; for more prolonged exposures, 0.06 ml/kg or 5 ml should be given and repeated every 4–6 months if exposure continues (only if vaccine administration is contraindicated).
g) Hepatitis A vaccine should be considered for all populations with increased risk of hepatitis A infection, such as men who have sex with men, injecting drug users and persons who work with HAV-infected primates or HAV in a research laboratory setting.
h) Raw oysters, clams and other shellfish are risky for a variety of infections including hepatitis, and should only be consumed if it can be ascertained that they are from a non-contaminated area. Otherwise, all such items should be heated to a temperature of 85°–90°C (185°–194°F) for 4 minutes or steamed for 90 seconds before eating. In endemic areas, travelers should take only hot or bottled beverages and hot, well-cooked food.
a) Report to local health authority: Obligatory in some countries, although not required in many others; Class 2.
b) Isolation: For proven hepatitis A, enteric precautions during the first 2 weeks of illness, but no more than 1 week after onset of jaundice; the exception is an outbreak in a neonatal intensive care setting, where prolonged enteric precautions must be considered.
c) Concurrent disinfection: Sanitary disposal of feces, urine and blood.
d) Quarantine: Not applicable.
e) Immunization of contacts: Active immunization should be given as soon as possible, but no later than 2 weeks after exposure. Passive immunization with IG (IM), 0.02 ml/kg of body weight, should be given as soon as possible after exposure, but also within 2 weeks. Because hepatitis A cannot be reliably diagnosed on clinical presentation alone, serological confirmation of HAV infection in index patients by IgM anti-HAV testing should be obtained before post-exposure prophylaxis of contacts. Persons who have received 1 dose of hepatitis A vaccine at least 1 month prior to exposure do not need IG.
Hepatitis A vaccine and IG are not indicated for contacts in the usual office, school or factory settings. Hepatitis A vaccine should be given to previously unimmunized persons in the situations listed below, preferably together with IG administered concurrently at a separate injection site:
i.) Close personal contacts, including household, sexual, drug using and other close personal contacts
ii.) Attenders at day care centers if one or more cases of hepatitis A are recognized in children or employees or if cases are recognized in 2 or more households of attenders—prophylaxis may be given to classroom contacts of an index case
iii.) In a common source outbreak, if a food handler is diagnosed with hepatitis A, hepatitis A vaccine and IG should be administered to other food handlers in the same establishment. Hepatitis A vaccine and IG is usually not offered to patrons; this may be considered if (i) food handlers were involved in the preparations of foods that were not heated; (ii) deficiencies in personal hygiene are noted or the food handler has had diarrhea; and (iii) the hepatitis A vaccine and IG can be given within 2 weeks after last exposure.
f) Investigation of contacts and source of infection: Search for missed cases and maintain surveillance of contacts in the patient's household or, in a common source outbreak, surveillance of people exposed to the same risk.
g) Specific treatment: None.
a) Determine mode of transmission (person-to-person or common vehicle) through epidemiological investigation; identify the population exposed. Eliminate common sources of infection.
b) Effective use of hepatitis A vaccine in community-wide outbreak situations requires the initiation of immunization early in the course of the outbreak and the rapid achievement of high (approximately 70% at least) first-dose vaccine coverage levels. Specific outbreak control measures must be tailored to the characteristics of hepatitis A epidemiology and of the existing hepatitis A immunization program, if any, in the community. Immunization of older children who have not previously received vaccine should be accelerated in communities with ongoing programs of routine hepatitis A immunization for young children; target immunization should be undertaken for groups or areas (age groups, risk groups, census tracts) where local surveillance and epidemiological data show the highest rates. In outbreak settings such as day care, hospitals, institutions and schools, routine use of hepatitis A vaccine is not warranted. These immunization programs may reduce disease incidence only in the group(s) targeted.
c) Make special efforts to improve sanitary and hygienic practices to eliminate fecal contamination of foods and water.
d) Outbreaks in institutions may warrant mass prophylaxis with hepatitis A vaccine and IG.
Hepatitis A is a potential problem in large collections of susceptible people with overcrowding, inadequate sanitation and water supplies; if cases occur, increased efforts should be exerted to improve sanitation and safety of water supplies. Mass administration of hepatitis A vaccine, which should be carefully planned, is not a substitute for environmental measures.
Source: Heymann (Ed.). (2008). Control of Communicable Diseases Manual, 19th edition. Washington, DC: American Public Health Association.