Hepatitis B virus infection in Thai children.

We studied hepatitis B virus (HBV) transmission among 7416 Thai children from 148 schools in Kamphaeng Phet province, a rural part of northern Thailand. Their age ranged from 2 to 16 years (median 9 years). Between May 1991 and June 1992, 61 of 2593 (2.4%) in the cohort of susceptible children acquired anti-HBc immunoglobulin. Forty-seven of the 148 schools had children who acquired anti-HBc. School seroconversion rates to anti-HBc varied from 0% to 23%. There was no correlation between percent of carriers in schools and percent of anti-HBc acquisition. Of the 61 children who acquired anti-HBc, eight (13%) became HBsAg carriers but only two were symptomatic, for a clinical to subclinical infection ration of 1 : 30. One of the two symptomatic children became an HBsAg carrier. Three (38%) of the eight who were persistently antigenemic developed antibody to hepatitis B virus e antigen. Males were 2.5 times (95% CI 1.4-4.3) more likely to acquire anti-HBc than females. Risk factors for acquisition of HBc in Thailand over a 9-month period were examined in a subset of 2412 susceptible children and later in a case-control study of 22 children who acquired anti-HBc and 59 age and sex-matched controls. Risks for acquiring anti-HBc were male gender and a history of bleeding gums. In comparing this study to an earlier pilot study among 9848 children from the same area in Thailand, the yearly antibody acquisition rate to anti-HBc among Thai children dropped from 5.7% in 1989 to 2.4% in 1992. A random sample of children in the pilot study showed that 16% were HBsAg positive and 27% had anti-HBc at the beginning of the study. 34% had markers for either anti-HBc or HBsAg. 12% were repeatedly positive for HBsAg a year later.

Causes of death and unintentional injury among schoolchildren in Thailand.

Few prospective studies of mortality among children in developing countries have been published. Here we quantify and describe mortality and injury morbidity among a cohort of schoolchildren in rural Southeast Asia. Deaths among a cohort of 40,119 schoolchildren in Thailand were prospectively monitored over a two year period from January 1991. Additionally, data were collected with a questionnaire from a subset of 6,378 children asking them to recall all injuries over a one-year period. There were 40 deaths for an annual incidence of 50/100,000. Fifty percent of all deaths were due to injury; 25% to infectious diseases. Sixty percent of the injury deaths were due to motor vehicles and 35% to drowning. Sixty-six percent of the children reported one or more accidents. The leading categories of non-fatal injuries, in decreasing order, were: animal bite, puncture wound, burn, near-drowning, fall from a height. Boys experienced more injuries than girls for almost every type of injury. Injuries are replacing infectious diseases as the most important cause of deaths in developing countries. Additional public health initiatives to reduce childhood accidents may be warranted.

High prevalence of hepatitis G viremia among kidney transplant patients in Thailand.

Patients receiving kidney transplants (KT) are at high risk for blood borne viral infections. To determine the prevalence of a recently discovered hepatitis G virus (HGV) in this patient group, reverse transcription-polymerase chain reaction (RT-PCR) employing primers derived from the NS5 region of the viral genome was utilized. HGV RNA was detected in 40 of 94 KT patients (43%), as compared to 3 of 69 healthy subjects (4.3%). Cocirculation of HGV and hepatitis C virus (HCV) RNA was detected in 12 patients (13%). Comparison of patients with and without HGV revealed that the former had received hemodialysis before transplantation for a significantly longer duration than the latter (28 vs. 17 months, respectively; P < 0.05). The amount of blood transfused and mean levels of liver enzymes, including alkaline phosphatase, alanine transaminase, and aspartate transaminase, were the same in both groups. Sequence analysis of 275-base pair DNA clones obtained from 2 patients revealed approximately 92% sequence homology to the published HGV and GB virus C sequences. These results suggested that HGV infection among Thai KT patients was high and the role of HGV in causing liver disease remains to be determined.

Rates of hepatitis E virus infection and disease among adolescents and adults in Kathmandu, Nepal.

To determine hepatitis E virus (HEV) infection and disease rates in the Kathmandu Valley of Nepal, serum was collected from 757 healthy Nepalese (ages 12-48 years) during March and September 1992 and September 1993. At each visit, reports of interval illness were obtained. Sera were examined for IgG to HEV, using a commercially available kit. Seroconversion was used as a marker for HEV infection, and an episode of hepatitis E was defined as a history of jaundice with seroconversion. Seroprevalence ranged from 16% to 31% and increased with age, whereas both infection and disease rates decreased with age. Infection and disease rates were as high as 99/1000 and 45/1000 person-years, respectively. These results highlight the importance of sporadic hepatitis E as a public health problem among adolescents and young adults in this region.

Herpes simplex virus type-2, cytomegalovirus and Epstein-Barr virus infection in acute non A to E hepatitis Thai patients.

A significant number of acute non A to E hepatitis cases are reported in Thailand every year, and the etiologies of these cases are unknown. Members of the herpesviridae family have been reported to cause either a self limited or fatal hepatitis in a small proportion of patients in other parts of the world. To determine whether herpesviruses may play a role in acute non A to E hepatitis, sera from 32 acute hepatitis patients without markers for acute hepatitis A to E virus infection were examined for IgM to herpesvirus type 2 (HSV-2), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) using commercially available assays. IgM to HSV-2 was detected in four sera, IgM to CMV was detected in one serum, and IgM to EBV was detected in one serum. All of the acute non A to E hepatitis patients recovered and none had underlying conditions associated with impaired immunity. These results suggest that herpesviruses should be considered in the differential diagnosis for Thai patients with hepatitis.

Protective antibody after a 'one dollar' hepatitis B vaccine.

The seropositivity rate of anti-HBs after hepatitis B vaccines, "Hepavax B", a one-dollar per dose vaccine produced by Korean Green Cross Corporation, Korea which were widely distributed and used for the first few years in the National Expanded Program on Immunization in Thailand were assessed in children who regularly came for immunization at the Well Baby Clinic at the Children's Hospital between June to December 1994. The schedule for hepatitis B immunization is at birth, 2 and 6 months of age. The seropositivity rate of anti-HBs at 6 months after the last dose were 86.3% and 87.7% at 12 months which was comparable to the seropositivity rate after other more expensive hepatitis B vaccines at 2 years (88.1%). This result should convince people that a one-dollar hepatitis B vaccine, "Hepavax" is immunogenic and expected to be as effective as other expensive hepatitis B vaccines. The marked reduce in the cost of hepatitis B vaccines will enable us to prevent and ultimately control of worldwide hepatitis B infections in the future.

Etiology of acute non-A, B, C hepatitis in Thai patients: preliminary study.

To better characterize the etiology of acute non-A, B, C hepatitis, 24 sera from 50 acute hepatitis without acute markers for hepatitis A, B, and C were examined for acute markers for the hepatitis E virus (HEV), cytomegalovirus (CMV), herpes simplex virus type 2 (HSV-2), and Epstein-Barr virus. Immunoglobulin M (IgM) specific for HEV, HSV-2, and CMV was detected using ELISA and total Ig specific to EBV was determined by standard indirect immunofluorescence. IgM to CMV was not observed in sera from any of the patients; whereas, IgM to HEV was detected in sera from 2 patients and IgM to HSV-2 was detected in 5 of 24 acute hepatitis patients. In addition, high titer of antibody was found in 2 of the patients. This results indicate that HSV-2 and HEV circulate in Thailand and are responsible for a small proportion of non-A, B, C hepatitis in Thailand.

Outbreak of hepatitis A in a college traced to contaminated water reservoir in cafeteria.

A sharp but short outbreak of hepatitis A occurred in a college during September and October 1992. The epidemic pattern suggested a common source. The attack rate of clinically recognizable hepatitis A was 8% all cases were HAV IgM positive. Among 31 students with minor symptoms but without jaundice 8 (26%) were also HAV IgM positive, as were 8 (10%) of 77 totally asymptomatic students tested. A case control study of eating and drinking habits of the students showed no other significant differences other than that 45 of 56 cases and 18 of 34 controls interviewed had filled their water glasses by dipping them in a overflow water reservoir. This gives an odds ratio of 3.8. The reservoir was heavily contaminated with coliform bacteria and the residual chlorine was at lower than standard concentration, whereas other water resources were clean. It is suggested that the reservoir had been contaminated with hepatitis A virus by somebody with fecally contaminated hands a couple of weeks prior to the beginning of the outbreak.

Age-specific prevalence of hepatitis A antibody in Thai children.

Age-specific prevalence of anti-HAV was determined for 3 groups of children whose mean ages were 12.6, 20.7 and 52.5 months. There were 41, 43 and 99 children in the respective age groups. All children were healthy, from middle to low socioeconomic families in Bangkok and vicinity. None of the children in the two younger age groups had anti-HAV antibody while 2 of 99 children in the oldest age group did. One of them resided in central Bangkok (Amphoe Dusit) and the other in Nonthaburi Province. The overall prevalence of anti-HAV in children under 5 years old was 1.1%. This demonstrates that hepatitis A transmission rates in Bangkok are very low when compared to ten years ago when prevalence rates were as high as 50-65%. From this study hepatitis A vaccine is recommended for 4-5 years old children in Bangkok. We need more epidemiologic data concerning hepatitis A transmission in Thailand before we can consider hepatitis A immunization for the whole country.

Viremia, fecal shedding, and IgM and IgG responses in patients with hepatitis E.

Viremia, fecal shedding and antibody responses to hepatitis E virus (HEV) infections are poorly understood. To better characterize HEV infections, these responses were examined in 67 patients with acute markers for hepatitis E who were admitted to the Infectious Disease Hospital in Kathmandu, Nepal in 1993. A single stool and multiple sera from each patient were examined using polymerase chain reaction to detect HEV RNA. Sera were also examined for antibodies to HEV. Viremia, fecal shedding, and IgM and IgG to HEV were detected in 93%, 70%, 79%, and 87% of 67 patients, respectively. Viremia or fecal shedding (or both) were detected in 14 patients from whom IgM and IgG to HEV were not detected. Viremia lasted at least 2 weeks in nearly all subjects and at least 39 days in 1 subject. Our results suggest that viremia is a common occurrence in patients infected with HEV.

Short report: relative risk of hepatitis A and E among foreigners in Nepal.

Sera from two groups of patients in Nepal with acute hepatitis were examined for the presence of antibodies to the hepatitis A, B, C, and E viruses to determine the etiology of viral hepatitis. The first group consisted of 43 consecutive acute hepatitis patients presenting at a clinic for tourists and foreign residents in Kathmandu from January 1987 to June 1988. The other group consisted of 95 consecutive acute hepatitis patients admitted during the same period at a hospital used predominantly by adult Nepalese residents of Kathmandu. Hepatitis A was diagnosed in 39 (91%) of the foreign patients and in one of the 95 Nepalese patients, whereas hepatitis E was diagnosed in four of the 43 foreign patients and in 90 (95%) of the Nepalese patients. No cases of hepatitis B or C were identified in either group, nor were any cases of dual infection with the hepatitis A virus (HAV) and hepatitis E virus (HEV) identified. These results suggest that in the Kathmandu Valley, hepatitis A is the predominant form of hepatitis among foreigners, hepatitis E is the predominant form of hepatitis among adult Nepalese, and both HAV and HEV are endemic to the Kathmandu Valley.

Protection against hepatitis A by an inactivated vaccine.

OBJECTIVE: To evaluate the safety and efficacy of a new inactivated hepatitis A vaccine. DESIGN: Double-blind randomized controlled trial stratified by community. SETTING: Community-based in Thailand. STUDY PARTICIPANTS: A total of 40,119 children, aged 1 to 16 years, attending 148 primary schools: 38,157 (95%) entered surveillance a mean of 138 days after receiving vaccine dose 1; 33,586 (84%) completed the controlled trial of 532 days; and 31,075 (81%) received crossover vaccine and remained under surveillance until day 844. INTERVENTION: Participants received hepatitis A vaccine or control hepatitis B vaccine starting January 7, 1991 (doses in months 0, 1, and 12), and crossed over to the alternate vaccine 18 months later. MAIN OUTCOME MEASURE: Cases of hepatitis A (symptoms, alanine aminotransferase levels of 45 U/L or higher, and IgM to hepatitis A virus) were identified by evaluating school absences of 2 or more days. RESULTS: There were no serious adverse reactions despite administration of more than 109,000 doses of hepatitis A vaccine. Among initially seronegative recipients of two doses of hepatitis A vaccine, the proportion with 20 mIU/mL or more of antibody to hepatitis A virus before and 5 months after a 1-year booster was 94% and 99%, respectively. Of 6976 episodes of illness during the controlled trial, there were 40 cases of hepatitis A; 38 were in the control group. Of the 40 cases, six, all in controls, occurred after the 1-year booster dose. Following two doses of hepatitis A vaccine (days 138 through 386), protective efficacy was 94% (95% confidence interval, 79% to 99%); cumulative efficacy including the postbooster period (days 138 to 532) was 95% (95% confidence interval, 82% to 99%). The two hepatitis A vaccine recipients who had symptomatic infections (257 and 267 days after dose 1) appeared to have been partially protected since their illnesses were brief and associated with only slight increases in alanine aminotransferase. CONCLUSIONS: Inactivated hepatitis A vaccine is safe; when administered in two doses, it protects against hepatitis A for at least 1 year.

Solid-phase antibody capture hemadsorption assay for detection of hepatitis A virus immunoglobulin M antibodies.

A solid-phase antibody capture hemadsorption (SPACH) assay was developed to detect hepatitis A virus (HAV)-specific immunoglobulin M (IgM) antibodies in sera from humans recently infected with hepatitis. The assay is performed with microtiter plates coated with anti-human IgM antibodies to capture IgM antibodies from the test sera. HAV-specific IgM antibody is detected by the addition of HAV hemagglutinating antigen and goose erythrocytes. Hemadsorption of erythrocytes to antigen-antibody complexes attached to the solid phase indicate the presence of IgM antibodies. The SPACH assay was compared to a commercial radioimmunoassay and was found to be equally or more sensitive and specific for the detection of HAV IgM antibodies. The SPACH assay is an alternative, rapid assay that doesn't require hazardous substrates or radioactivity for the detection of HAV-specific antibodies.

The declining transmission of hepatitis A in Thailand.

Hepatitis A antibody was almost universal among Thai children 10-15 years ago. To assess whether transmission of hepatitis A among Thai children had declined, contemporary antibody prevalence and seroconversion rates were determined. Antibody prevalence in 1987-1988 among children in Bangkok declined since 1977 for all ages studied, most markedly among young children. Among 453 low-income urban schoolchildren, there were no seroconversions over a 10- to 12-month period (95% confidence interval [CI] for incidence, 0-0.8%). Antibody prevalence among rural children also declined between 1985 and 1989, though rates were higher than those in Bangkok. Antibody prevalence differed by community. The annual rural infection rate was 1.1% (CI, 0.8%-1.6%). The pattern of rural hepatitis A transmission was focal. Increased numbers of susceptible children in Thailand, where hepatitis A virus still circulates, sets the stage for rising rates of symptomatic disease in adults.

Factors relating to transmission of viral hepatitis in a United States military population stationed in Thailand.

To determine the incidence of clinical and inapparent hepatitis in a US military population stationed in Thailand, the authors prospectively studied a cohort of 326 men during one year. Clinical hepatitis A occurred in one man (clinical attack rate = 3.1/1000 men/year), and clinical hepatitis B was found in four men (clinical attack rate = 12.3/1000 men/year). No non-A, non-B hepatitis was identified. There was no serologically identified inapparent hepatitis A but inapparent hepatitis B occurred in 17 men. The apparent/inapparent ratio for hepatitis B was 1:4.25. Serotype analysis suggested that hepatitis B virus largely originated from Thai contacts, although 23% of cases were derived from western sources. To determine the relative contribution of 16 statistically significant (out of 67 studied) behavioral variables to the transmission of HBV, a factor analysis and a multivariate correlation analysis were employed. Factor analysis indicated that social and sexual contact with the indigenous population, including prostitutes, residence within the Thai community and marijuana use were behavioral areas that were associated with the acquisition of hepatitis B. Residence in the Thai community during the first four-month period in Thailand, sexual contact with a prostitute during the third four-month period, and ever having maintained a Thai mistress were found to be significant and independent risk factors by multiple regression analysis.

Age-specific prevalence of hepatitis A virus antibody in Thailand.

Serum specimens drawn at random from three geographically defined populations of healthy Thais were tested for antibody to the hepatitis A virus (anti-HAV) by radioimmunoassay. A total of 746 specimens were tested. The age by which 50 per cent were antibody positive was 4-5 years for residents of an urban Bangkok housing project, 8-9 years for rural villagers, and 10-11 years for urban Bangkok government school pupils. Overall, specimens from 97 per cent of Thai adults 16 years of age or older were anti-HAV positive. These data suggest widespread distribution of HAV in Thailand.

Experimental transmission of hepatitis B virus by semen and saliva.

The ability of human semen and saliva to transmit hepatitis B virus (HBV) by parenteral and nonparenteral routes was studied. Semen, donated by a hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen (HBeAg)-positive carrier, was administered to one gibbon by subcutaneous inoculation and to another by intravaginal instillation. Both developed HBsAg, followed by the development of antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc). Saliva from two donors who were HBsAg- and HBeAg-positive was pooled and administered subcutaneously to two gibbons and orally to five others. The animals inoculated subcutaneously developed HBsAg followed by anti-HBs, but none of the gibbons exposed orally developed evidence of HBV infection. Thus, semen and saliva of HBsAg carriers can be infectious, and venereal transmission of HBV by semen can occur. Transmission of HBV in saliva can also occur through breaks in the skin, but experimental transmission of HBV by saliva administered orally has not been accomplished.

Hepatitis B in the rural tropics.

The prevalence of HBSAg in a cross-sectional serosurvey of a rural Thai village was nearly 8%. The corresponding antibody prevalence was approximately 35%. The prevalence of antigenaemia was significantly higher for adult males than for adult females. Possible dynamics of hepatitis B virus transmission in this rural village are explored, but tend to rely on a differential handling of antigenaemia by males and females. A considerable proportion of the hepatitis B virus exposure appears to be associated with malaria prophylaxis programmes.