Hepatitis A is the most common cause of acute hepatitis in the United States, as reported to the Centers for Disease Control and Prevention (CDC) and shown for 1998 in Fig. 2 and 310. The numbers of hepatitis A cases reported in 1996 and 1997 were substantially higher (31,032 and 30,021, respectively); there are no data for 1999 at this time. The latest data from the Viral Hepatitis Surveillance Program (1993) indicate that contact with a person infected with hepatitis A is the most common identifiable source of infection (22%), with day care centers the possible source in 17%, international travel in 6%, homosexual activity in 5%, injection drug use in 2%, and a food- or waterborne outbreak suspected in 2% (www.cdc.gov/nciod/diseases/hepatitis/h96surve.htm). The largest percentage of infected persons, however, have no identifiable source (47%).
Besides accounting for 22% of attributed sources (website cited above), personal contact with an unidentified source shedding HAV is likely to explain many or all of the cases with no identifiable risk factor. In Salt Lake County, Utah, 98 of 390 (25%) household contacts of 167 persons without identified risk factors demonstrated serologic evidence of recent hepatitis A infection (C. Staes, T. Schlenker, I. Risk, L. Bogdanow, K. Cannon, R. Winn, H. Harris, C. Shapiro, A. Pavia, and B. Bell, Clin. Infect. Dis. 25:411, 1997, abstract). The highest rate of retrospectively diagnosed recent hepatitis A was in children who were of 81 [47%] household contacts in this age group). Young children are often asymptomatic when infected with hepatitis A 99, 226 and, with their less scrupulous hygiene, may serve as a source of infection.
The virus is hardy, surviving on human hands and inanimate objects (fomites) 163. Studies indicate that viral particles are excreted fecally during clinical illness 223 and that fecal excretion can be prolonged, as determined by detection of viral nucleic acids (by RT-PCR amplification) for 3 to 11 months 126, 269. In a neonatal intensive care unit outbreak of nosocomial hepatitis A, there was prolonged excretion of virus by neonates, as evidenced by detection of viral protein and nucleic acid for 4 to 5 months after initial identification of infection 213. Furthermore, in a large-scale field trial of the efficacy of a formalin-inactivated hepatitis A vaccine, HAV RNA was detected in stool collected 61 to 90 days after onset of illness in 16 of 19 cases of infection in the control group 125. The infectivity of fecal material was not demonstrated in any of these cases. However, taken together, these observations reinforce the need for rigorous personal hygiene in the prevention of transmission. The prolonged excretion of infectious virus plus the hardiness of the virus may well explain the continued occurrence of sporadic cases of hepatitis A in developed countries as well as the endemicity in underdeveloped countries.
Food-Borne Hepatitis A
One of the earliest documented outbreaks of hepatitis A associated with consumption of contaminated material was the demonstration of a rising titer of specific antibody in members of a family who contracted acute hepatitis after eating mussels 68. The largest known modern epidemic of hepatitis A was also from consumption of contaminated seafood. In Shanghai, China, 292,301 cases of acute hepatitis were attributed to eating raw clams 100. Oysters 49, 64 and cockles 183 have also been implicated. HAV may survive for extended periods of time in seawater. Viral nucleic acids were detectable 232 days after being seeded in artificial seawater, whereas they were only detectable for 35 days in cell culture 18. Consequently, the filtering of seawater by bivalves, with the potential for retaining infectious HAV particles resulting from fecal contamination, can lead to the transmission of infection to those who consume the seafood without adequate cooking. Spread of hepatitis A has been reported in the United States and Europe following consumption of contaminated lettuce 212, ice slush beverages 27, frozen strawberries 11, 121, 179, and salad food items 155, 192. The global movement of food items that cannot be heated for viral inactivation may be a major cause of outbreaks in developed countries in the future. The recent multistate outbreak of hepatitis A 121 following the illegal use of non-U.S. produce in school lunches 109 illustrates the problem.
In the United States, waterborne transmission of hepatitis A accounts for only a fraction of cases. In one small outbreak, HAV contaminated well water 32. A swimming pool with potential sewage contamination was implicated as the common source in another 157. Hepatitis A is considered an occupational hazard for sewage workers in some countries 65 but not in Israel or the United States 150, 247. HAV was detected in the final effluent from wastewater treatment plants in the Mediterranean 71, demonstrating a potential source for seafood contamination. Waterborne transmission is less important in the spread of hepatitis A than person-to-person contact. In contrast, hepatitis E, particularly in epidemic form, appears to be transmitted by waterborne outbreaks.
Nosocomial Hepatitis A
Transmission of hepatitis A from hospitalized patients with unsuspected disease to staff is well recognized 93. For example, an adult patient with diarrhea after an elective cholecystectomy 94, premature infants 135 with prolonged viral excretion 213, burn patients incubating HAV in hospital 72, and a patient who was immunodeficient and negative for HAV antibodies 41 have all been sources of nosocomial infection. One example of nosocomial spread emphasizes the natural life cycle of the virus. A patient with an overdose and trauma from a motor vehicle accident had a T-tube draining bile during the incubation phase of hepatitis A. The bile was the only apparent source of infection in five cases of nosocomial hepatitis A 101. Vertical transmission is rare 74, 146 but was the apparent source of hepatitis A in a nursery outbreak 258.
Parenteral Hepatitis A Transmission
Once considered rare outside experimental studies 218, parenteral transmission of hepatitis A complicating transfusion of blood and blood products has now been reported many times. Blood from a single donor who became ill 1 week after donation transmitted disease to 11 recipient neonates and thence secondarily to an additional 44 persons 180. Transmission associated with platelet and plasma donation processing 170 and anticancer immunotherapy reagents 259 has also been documented. More recently, identical HAV sequences were detected in clotting factor concentrates and hemophiliac recipients in Italy 159. The solvent-detergent method of viral inactivation was considered inadequate for nonenveloped viruses such as HAV. In late 1995, a similar outbreak occurred in the United States 7. Vapor heating of clotting factor concentrates is experimentally effective in eradicating infective HAV 25.
The other group at risk for HAV infection by parenteral transmission is the injection drug-using population 4, 97. Hepatitis A can also be potentially spread within this group by contamination from rectally carried drugs 237 as well as by unsanitary living conditions, crowding, and lack of the necessary personal hygiene to prevent infection. Approximately 40 to 50% of injection drug users in northern Europe are anti-HAV positive 136, and in Scandinavia and France the seropositive rate is significantly higher than in a matched control population 117, 216, 256, 261. At Johns Hopkins Hospital, seropositive rates were more than twice as high in injection drug users (66%) as in homosexual men (27%) and correlated with poverty 254. Targeting this group for vaccination to prevent HAV infection may decrease their infection rates in the future.
Although early seroprevalence studies of hepatitis A did not demonstrate increased positivity in homosexual men 238, two prospective studies of seroconversion clearly document a high rate of ongoing infection 50, 53. More recently, hepatitis A outbreaks among homosexual men were reported in the United States and abroad 5, 110, 236. Higher seroprevalence rates of hepatitis A infection are associated with oral-anal contact regardless of sexual orientation 23, not with homosexuality per se 254.