An outbreak of hepatitis A occurred in a north Georgia trailer park served by a private well. Of 18 residents who were serosusceptible to hepatitis A virus (HAV), 16 (89%) developed hepatitis A. Well water samples were collected 3 months after illness onset in the index case and 28 days after illness onset in the last trailer park resident. Hepatitis A virus antigen (HAVAg) was detected in the samples by enzyme immunoassay from three of the five cell lines following two 30-day passages and from a fourth cell line following a third passage of 21 days.

In 1985, the authors studied the epidemiology of hepatitis B virus (HBV) in a healthy Middle Eastern population. Residents of three remote villages and urban areas of Jordan were assessed for seroprevalence of hepatitis B surface antigen (HBsAg) and HBV infection. Infection was defined as the presence of antibody to hepatitis B core antigen (total) and/or antibody to hepatitis B surface antigen, with or without HBsAg. The overall HBsAg prevalence was 9.9% and was not age-related, although significant differences were noted between the villages (range, 5.7%-12.8%). The prevalence of HBV infection was 36% and increased with age. In addition, there were differences between the villages in patterns of age-specific infection. A newly constructed socioeconomic index showed greater HBsAg prevalence in lower (14.4%) than in upper (2.4%) socioeconomic groups. A history of contact with a jaundiced person and socioeconomic status were independent risk factors for HBsAg-positive status, while contact with a jaundiced person, rural background, and age were independently related to HBV infection. There was evidence of familial clustering of HBV in two of the villages, with HBV carriers and infected children particularly aggregating around HBsAg-positive siblings. There was also a trend toward an association of HBsAg-positive children with HbsAg-positive mothers. HBV carrier prevalence correlated with family size, and HBV infection in the household increased proportionately with the number of carriers in the family. Hepatitis B e antigen was detected most frequently in children and antibody to hepatitis B e antigen in adults. Postnatal early childhood transmission through contact among children of poorer and larger families probably accounts for the high endemicity of HBV in this region.

Between January 1984 and December 1985 a large outbreak of viral hepatitis occurred in the island nation of Mauritius (population 986,000). No hepatitis epidemics had occurred there since the 1930s. The outbreak involved 2428 reported cases; however, reporting levels were thought to be extremely low. All of the island's nine geographical districts were affected, but cases were concentrated in five districts mostly in the central and northern parts of the island. The highest attack rate occurred in children aged five to nine; persons above age 14 were almost unaffected. The male:female ratio of cases was 1.1:1. Evidence to support hepatitis A virus (HAV) as the infecting agent included; (1) clinical illness was compatible with hepatitis A; (2) the age profile of cases was typical for community-wide hepatitis A outbreaks; (3) the rate of positive tests for hepatitis B surface antigen in suspected hepatitis patients did not increase during the outbreak; and (4) nine of nine clinically ill children tested were serum-positive for IgM anti-hepatitis A virus antibody. Transmission was probably by the person-to-person route; no common source was implicated. The outbreak appears to represent a transition from a 40-year pattern of endemic HAV transmission on the island to an epidemic pattern.

An experimental model of enterically transmitted non-A, non-B hepatitis (ET-NANBH) was established in tamarins (Saguinus mystax mystax) and cynomolgus macaques (Macaca fascicularis). First-passage animals were inoculated with two different stool suspensions obtained from human patients with well-defined ET-NANBH that originated from Burma and Pakistan, where epidemics of ET-NANBH occur. Both inocula contained 27- ato 34-nm-diameter viruslike particles (VLPs) that were specifically aggregated by acute-phase ET-NANBH sera. ET-NANBH was subpassaged in both tamarins and cynomolgus macaques by using pools of stool suspensions from first-passage animals. One additional passage of disease in cynomolgus macaques resulted in a significantly shortened incubation period and increased severity of disease. VLPs similar to those found in the human inocula were observed in stool specimens of first-, second-, and third-passage cynomolgus macaques and in first- and second-passage tamarins. Our findings indicate that cynomolgus macaques are particularly suitable experimental models for studies of human ET-NANBH. The 27- to 34-nm VLPs found in infected human and primate stools appear to be etiologically linked to disease.

Epidemic non-A, non-B hepatitis was diagnosed in three young Pakistani men during a 10-month period at the Los Angeles County-University of Southern California Medical Center. All three patients had recently visited or lived in Karachi, Pakistan. None had serologic markers of hepatitis B virus infection or IgM antibody (acute-phase) to hepatitis A virus. A liver biopsy from one patient showed marked cholestasis and cholangiolar transformation of hepatocytes, a pattern previously described in patients with epidemic non-A, non-B hepatitis. Immune electron microscopy of a stool specimen obtained from this patient 10 days after the onset of symptoms showed virus-like particles, 27 nm in diameter, that were specifically aggregated by antibody contained in acute-phase sera from the three Pakistani patients, from patients with non-A, non-B hepatitis in Burma and Nepal, and from an experimentally infected marmoset. Recognition of three separate cases of probable epidemic-type non-A, non-B hepatitis in patients at one institution during such a short time suggests that Pakistan is endemic for this infection and that the disease may be more commonly spread to the United States than is now presumed.

To determine if passively reported cases of acute viral hepatitis are representative of the affected population, an active surveillance system was set up that identified all persons in Pierce County, Washington, who had been diagnosed by a physician as having acute viral hepatitis in the period March 1 through August 31, 1984. In this county, this was part of an ongoing epidemiologic study of viral hepatitis that had previously included some stimulation of reporting. The active surveillance system covered all primary sources of medical care, including all private physicians who were most likely to see persons with hepatitis. Secondary sources, those that did not provide direct medical care but might be aware of new cases, were also surveyed. The results of active surveillance showed that passive reporting was about 65% complete in Pierce County. No change occurred in the number of hepatitis A cases reported, but hepatitis B cases increased by 50%, and non-A, non-B hepatitis cases increased by 138%. Most of the increase was a result of enhanced reporting from private physicians. The two risk groups most affected by underreporting were homosexual men with hepatitis B and blood transfusion recipients with non-A, non-B hepatitis. During active surveillance, the proportion of persons with hepatitis B who reported homosexual activity was 52% compared with 20% from passive surveillance. Transfusion recipients represented 24% of the non-A, non-B hepatitis reported from active surveillance compared with 9% reported from passive surveillance. Although Pierce County may not be representative of all counties in the United States, persons responsible for public health prevention programs should recognize that data acquired through passive surveillance may not accurately reflect the magnitude of the risk for specific populations or the amount of disease that can be prevented.

Between June 1, 1983 and August 30, 1984, an epidemic involving 313 cases of hepatitis A occurred in Muskingum County, Ohio. One hundred ninety-seven cases occurred in the city of Zanesville, with 34.7% of cases concentrated in two neighborhoods in the eastern part of the city. Case characteristics were similar to those reported in previous community-wide outbreaks, including a maximum attack rate among 5-9-year-olds and a very low attack rate in adults over 30 years. Case households were larger, and their members were less educated than the mean for households in the city. Forty-eight per cent of the cases reported exposures to other cases which temporally could have been the source of infection. A case-control study failed to show differences in several behavioral factors between case and control households, but did confirm that lower socioeconomic status was a risk factor for the disease. Broad use of immunoglobulin was effective in preventing clinical disease among family contacts, but did not stop the outbreak. This outbreak typifies a genre of hepatitis A epidemic transmitted from person to person in which exact routes of spread are poorly understood and control is difficult. Lower socioeconomic status may be a marker for some unidentified behaviors that promote hepatitis A transmission.

A human fecal isolate of hepatitis A virus strain HAS-15 was adapted to rapid growth in FRhK-4 cells by more than 20 7-day passages. A cell culture-derived inoculum of strain HAS-15 was used at a multiplicity of infection of 80 radioimmunofocus-forming units per cell, and a one-step growth curve was determined. Both intracellular production and supernatant release of infectious virions were evaluated. Detection of virus release into the medium directly corresponded to intracellular production of infectious virions. A classical eclipse period was not observed during the growth curve determinations; however, detectable infectious virion production was absent for approximately 20 h after infection. This 20-h period was immediately followed by a 4-day logarithmic phase of virus production. A maximum intracellular virus titer of 10(9) radioimmunofocus-forming units per ml was achieved, and this level remained essentially constant for up to 14 days after infection. The infectious virus and viral antigen produced during the growth cycle were ascertained by a radioimmunofocus assay and by a radioimmunoassay, respectively. Cell culture supernatants were negative for viral antigen as determined by the radioimmunoassay, even though as many as 10(8) hepatitis A virus radioimmunofocus-forming units per ml were found. An adsorption study was also performed with strain HAS-15 by using FRhK-4 cells. More than 99.9% of the infectious virus was adsorbed at 25 degrees C in less than 20 min.

To study the duration of antibody persistence and protection provided by the hepatitis B vaccine, we followed 773 homosexual men for five years after completion of vaccination. Among the 635 participants in whom antibody levels above 9.9 sample ratio units (SRU) developed after vaccination, 15 percent lost antibody altogether, and in another 27 percent, antibody levels declined below 10 SRU within five years. The extent of the maximal antibody response strongly predicted the persistence of protective antibody. Hepatitis B infection occurred in 55 men; 8 of these infections were clinically important (characterized by the presence of the hepatitis B surface antigen and elevation of liver-enzyme levels), and two of the patients became hepatitis B virus carriers. The long-term risk of hepatitis B infection was inversely related to the maximal antibody response to vaccine. Most severe infections occurred among those who responded poorly or had no response to the vaccination. The risk of late infection with hepatitis B in those with an initially adequate vaccine response increased markedly when antibody levels decreased below 10 SRU, but only 1 of 34 late infections resulted in viremia and liver inflammation. A second series of vaccinations induced a moderate antibody response in 50 percent of the subjects who initially had no response or a poor response; however, the persistence of antibody was poor. Both antibody loss and the risk of severe disease should be considered when booster-dose strategies for the hepatitis B vaccine are being designed.

A previously asymptomatic carrier of hepatitis B virus receiving chronic hemodialysis developed acute delta hepatitis. The patient regularly received dialysis treatments on the same machine as a parenteral drug abuser with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis whose serum was strongly positive for delta antibody. The drug abuser had a major bleeding episode that caused extensive environmental contamination 3 months before onset of illness in the index patient. No other patients receiving dialysis or staff members had evidence of delta infection. A surgeon previously infected with hepatitis B from the same parenteral drug abuser also had delta antibody. Testing for delta virus is indicated for both HBsAg-positive parenteral drug abusers and patients with hemophilia receiving chronic hemodialysis. All patients who are HBsAg- and delta-positive should receive dialysis separately from patients who are HBsAg-positive and delta-negative. Susceptible patients on dialysis and staff should receive hepatitis B vaccine to protect against both hepatitis B and delta virus infection.

A delta virus (DV) infection was experimentally transmitted to a hepatitis B chronic carrier chimpanzee. The infection was monitored by the examination of liver biopsy materials with the use of FITC-labeled human anti-delta IgG or by an indirect immunoperoxidase staining technique and by measurement of the serum alanine aminotransferase (ALT) activity. Three different antibody enzyme immunoassays (EIAs) were developed for assessment of the serologic response: 1) blocking assay, 2) IgM-specific capture assay, and 3) IgG-specific capture assay. An antigen-specific EIA was also developed for monitoring delta antigen in the serum. The results indicate that a superinfection with the DV produced a biphasic ALT response concomitant with the appearance of the delta antigen in biopsy materials. The persistence of these markers over the observation period (350 days) indicates the development of a persistent DV infection.

To determine if heterosexual activity was a risk factor for acquiring hepatitis B virus (HBV) infection, we studied attendees at a sexually transmitted disease (STD) clinic and students at a large university. Responses to self-administered questionnaires were used to exclude persons with factors known to be related to the acquisition of HBV and to determine the number of recent (past four months) and lifetime sexual partners. Serum samples were tested for hepatitis B surface antigen, antibody to hepatitis B surface antigen, and antibody to hepatitis B core antigen. For white heterosexuals in the STD group, the prevalence of HBV infection was 6% for those with fewer than five recent partners vs 21% for those with five or more partners, and 5% for those with fewer than 50 lifetime partners vs 20% for those with 50 or more partners. For black heterosexuals in the STD group, no association was found between prevalence of HBV infection and number of recent or lifetime sexual partners. For the heterosexual student group (all white), the prevalence of HBV infection was 1.5% for fewer than three recent partners vs 14% for three or more partners, and 2% for fewer than ten lifetime partners vs 7% for ten or more partners. For white heterosexuals, the risk of acquiring HBV infection increases with increasing amounts of sexual activity and may reach a level similar to that of other groups previously recognized to be at high risk of acquiring hepatitis B. (JAMA1986;256:1307-1310)

In 1981, a hepatitis B vaccine demonstration project was initiated among Yupik Eskimos of southwest Alaska to demonstrate that, under field conditions, the vaccine was safe, immunogenic, and efficacious. Laboratory tests for serologic markers of hepatitis B virus infection (HBsAg, anti-HBs, and anti-HBc) performed on sera collected in May 1981 from 3,988 residents of 17 remote Eskimo villages revealed that 2,645 (66.3%) had no evidence of hepatitis B virus infection. Because of a limited supply of vaccine, specific criteria for selection were used so that those at highest risk of infection would be immunized first. In November 1981, the first dose of vaccine was administered to 1,693 carefully selected individuals. The second dose was administered to 1,678 (99.1%) of those who received the first dose, and the final dose was administered to 1,630 persons (96.3%). Serologic follow-up showed the vaccine to be safe (0.4% experienced minor adverse reactions) and immunogenic (97.4% developed antibody). Vaccine-induced antibody levels were significantly higher for persons less than 30 years of age (p less than 0.001) and for females (p less than 0.001). Vaccine recipients were also protected from hepatitis B virus infection (p = 0.002). This public health measure proved to be feasible and effective in this remote arctic population despite difficult conditions for delivery and administration of this temperature-sensitive vaccine. This strategy for immunization is now being applied on a larger scale in Alaska as part of a program for the primary prevention of this infection and its sequelae.