First documented outbreak of hepatitis E virus transmission in Java, Indonesia.

A suspected hepatitis outbreak occurred in Bondowoso District, East Java Province, Indonesia, in March-May 1998. An investigation was initiated in April 1998, involving a retrospective review of hospital records, a community-based cross-sectional study, and a health service-based case detection and household follow-up. Sera and epidemiological information were collected from 962 individuals: 235 from 3 outbreak-affected communities along the same rural stretch of river, 101 from community controls living distant from the river, 151 cases detected in health centres, 141 family members of the cases, and 334 subjects from neighbouring families. The prevalence of acute hepatitis E virus (HEV), based on anti-HEV IgM, total antibody (Ig) to HEV and polymerase chain reaction (PCR), was significantly (P < 0.00001) higher (52.4%) among the outbreak communities than among the community controls (3%). The background prevalence of HEV, based on anti-HEV IgG, was also significantly (P < 0.00001) higher (47%) among the outbreak communities than among the community controls (3%). None of the 476 sera screened for anti-HAV (hepatitis A virus) IgM was positive. These results indicate that HEV was the aetiological agent responsible for the outbreak. The overall attack rate (AR) for the 3 outbreak-affected communities surveyed was 19%, with AR determined on the basis of clinically recognized, acute jaundice illness. The usage of river water as primary source for bathing, human-waste disposal, and drinking purposes differed significantly (P < 0.00001) between the communities in outbreak areas and those in non-outbreak areas. There is no significant influence attributed to 'boiling water' on acute HEV. No climatic influences (flooding or drought) predisposed this instance of epidemic HEV transmission. This outbreak represents the first documented evidence of epidemic HEV transmission in Java, Indonesia.

Epidemic dengue transmission in southern Sumatra, Indonesia.

An outbreak of dengue fever (DF), dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS) in the city of Palembang, south Sumatra, Indonesia was investigated to (i) validate epidemic occurrence, (ii) confirm dengue virus aetiology and associated serotype(s), (iii) provide a demonstrable measure of community impact, and (iv) identify causative relationship (if any) with climatic El Niño Southern Oscillation (ENSO) influences. Trend analysis based on a 6-year retrospective review of hospital records demonstrates a 3-fold increase in clinical cases for the outbreak period (January-April 1998), relative to historical records. In the 2 hospitals surveyed, the monthly mean number of outbreak-related dengue cases over 4 months was 833 (range 650-995 cases/month); the mean monthly value for the previous 72 months was 107 (range 14-779 cases/month). An apparent trend in epidemic transmission was observed, evolving from a 5-year cyclic phenomenon to an annual occurrence, often indistinguishable from one year to the next. The proportional distribution of clinical outbreak cases into DF, DHF and DSS diagnostic categories was 24%, 66%, and 10%, respectively. The population aged 10-19 years accounted for the largest (35%) proportion of hospitalized DHF cases, followed by children aged 5-9 years (25%) and children aged 4 years (16%). Serum samples obtained during acute illness from 221 hospitalized patients were examined using serology, RT-PCR, and virus isolation in cell culture: 59% of samples had laboratory evidence of a dengue infection. All 4 dengue virus serotypes (DEN 1-4) were identified in epidemic circulation, with DEN 3 predominating (43%). DEN 1 was the principal serotype associated with less severe dengue illness, suggesting that virulence may be, in part, a function of infecting serotype. The climatic influence of ENSO on rainfall and temperature in the months leading up to and during the outbreak was dramatic, and is likely to contribute to favourable outbreak conditions.

The unique riverine ecology of hepatitis E virus transmission in South-East Asia.

The ecology of hepatitis E virus (HEV) transmission in South-East Asia was assessed from a review of 6 published and 3 unpublished NAMRU-2 reports of hepatitis outbreak investigations, cross-sectional prevalence studies, and hospital-based case-control studies. Findings from Indonesia and Viet Nam show epidemic foci centred in jungle, riverine environments. In contrast, few cases of acute, clinical hepatitis from cities in Indonesia, Viet Nam and Laos could be attributed to HEV. When communities in Indonesia were grouped into areas of low (< 40%), medium (40-60%), and high (> 60%) prevalence of anti-HEV antibodies, uses of river water for drinking and cooking, personal washing, and human excreta disposal were all significantly associated with high prevalence of infection. Conversely, boiling of river drinking water was negatively associated with higher prevalence (P < 0.01). The protective value of boiling river water was also shown in sporadic HEV transmission in Indonesia and in epidemic and sporadic spread in Viet Nam. Evidence from Indonesia indicated that the decreased dilution of HEV in river water due to unusually dry weather contributed to risk of epidemic HEV transmission. But river flooding conditions and contamination added to the risk of HEV infection in Viet Nam. These findings attest to a unique combination of ecological and environmental conditions predisposing to epidemic HEV spread in South-East Asia.

Prevalence of enteric hepatitis A and E viruses in the Mekong River delta region of Vietnam.

A study of antibody prevalence for hepatitis A virus (HAV) and hepatitis E virus (HEV) was carried out in southwestern Vietnam in an area adjacent to a known focus of epidemic HEV transmission. The purpose of this investigation was first to provide a prevalence measure of hepatitis infections, and second to determine the outbreak potential of HEV as a function of the susceptible population. Blood specimens collected from 646 persons in randomly selected village hamlets were examined by an ELISA for anti-HEV IgG and anti-HAV IgG. The prevalences of anti-HEV IgG and anti-HAV IgG were 9% and 97%, respectively. There was a significant increase (P < 0.01) in age-specific anti-HEV IgG. A notable increase in anti-HAV IgG prevalence (P < 0.0001) occurred between child populations 0-4 (64%) and 5-9 (95%) years of age. No evidence of familial clustering of anti-HEV IgG-positive individuals was detected, and household crowding was not associated with the spread of HEV. Boiling of water was found to be of protective value against HEV transmission. A relatively low prevalence of anti-HEV indicates considerable HEV outbreak potential, against a background of 1) poor, water-related hygiene/sanitation, 2) dependence on a (likely human/animal waste)-contaminated Mekong riverine system, and 3) periodic river flooding.

Shipboard impact of a probable Norwalk virus outbreak from coastal Japan.

Norwalk virus has been implicated in shipboard diarrheal disease outbreaks throughout Asia. A large outbreak of suspected Norwalk virus was investigated on a U.S. Naval aircraft carrier following the clinical recognition of 450 cases of gastroenteritis over a 2-week period (September 14-28, 1997) during coastal exercises. A random sampling of 44 cases from 450 personnel who sought medical attention was compared with 19 controls. Junior enlisted sailors and marines comprised 97% of all cases. There was no evidence of shipboard geographic clustering of cases. Furthermore, no single food type was associated with illness on the basis of comparative analysis (cases versus controls). Principal case signs and symptoms reported included watery stools (89%), nausea (82%), and vomiting (77%). Anecdotal reports indicated > 50% of the cases received rehydration therapy. An absence of fever was also noted in 32% of the cases and only 5% had blood in their stools. The mean duration of illness was 37 hr, with a range of 3-96 hr. Laboratory findings based on reverse transcription-polymerase chain reaction and Southern hybridization methods showed that 21 (72%) of 29 patients had evidence of the UK2 prototype of the Norwalk virus. A cross-sectional study of 131 crew members from the ships population (n = 4,200) showed an attack rate of 44%. Attack rate is a variant of an incident rate applied to a narrowly defined population observed for a limited period of time, such as during an outbreak. The numerator is people who get sick and the denominator is people (population) at risk. An extrapolation of these findings suggests as many as 1,806 sailors may have been affected during the outbreak, of which only 26% (of the 57 outbreak related cases) where identified from sick call records. There was no difference in the mean ages between outbreak and non-outbreak affected crewmen, or geographic clustering based on berthing or work spaces. Outbreak-related cases reported signs and symptoms of watery-stools (79%), nausea (65%), and vomiting (47%). The mean duration of illness was 28 hr, ranging from 2 to 96 hr. Thirty-one percent of outbreak affected cases reported a sick call visit. Loss of work was reported by 39% of the outbreak affected population. This report documents the epidemic potential of Norwalk virus and the associated impact on fleet operational readiness. Additionally, that this outbreak occurred against a background of 3 other consecutive gastroenteritis outbreaks onboard the same ship (March 1997, February/March 1998, and June 1998), all sharing the same clinical and epidemiologic profiles, suggests possible shipboard persistence of Norwalk virus over time, despite periodic ship-wide disinfection efforts.

Impact of epidemic influenza A-like acute respiratory illness in a remote jungle highland population in Irian Jaya, Indonesia.

A suspected epidemic of unknown etiology was investigated in April/May 1996 in the remote jungle highlands of easternmost Indonesia. Trend analysis demonstrates the area-wide occurrence of a major respiratory infection outbreak in November 1995 through February 1996. The monthly mean rate of respiratory infection episodes for the peak outbreak months (2,477 episodes/100,000 persons) was significantly higher (P < .0001) than for the 34 months leading up to the outbreak (109 episodes/100,000 persons). Notable were the high attack rates, particularly among adults: 202 episodes/1,000 persons aged 20-50 years in one community. Excess morbidity attributed to the outbreak was an estimated 4,338 episodes. The overall case-fatality rate was 15.1% of outbreak cases. Laboratory evidence confirmed the circulation of influenza A/Taiwan/1/86-like viruses in the study population, and high hemagglutination inhibition titer responses were indicative of recent infections. Historical documents from neighboring Papua New Guinea highlight the role of influenza A virus in repeated area outbreaks.

Short report: surveillance of rickettsial infections in Indonesian military personnel during peace keeping operations in Cambodia.

Indonesian peacekeepers in Cambodia provided a unique study population to estimate the threat of rickettsial exposure to Rickettsia typhi (murine typhus), Orientia tsutsugamushi, (scrub typhus), and R. conorii (spotted fever) for the region. Prescreening prevalence measure showed a large proportion (36%) of soldiers with antibodies to R. typhi. Predeployment prevalence for antibodies to O. tsutsugamushi was 8%, with no evidence of background R. conorii infections. Actual seroconversions of R. typhi (3) and O. tsutsugamushi (1), attributed to exposure(s) in Cambodia, translated into annualized incidence rates of 24 and 8 per 1,000 per year, respectively. Surveillance of rickettsial infections and/or disease is particularly warranted in Cambodia with recent recognition of drug-resistant scrub typhus in neighboring Thailand.

Lymphocyte proliferative response and subset profiles during extended periods of chloroquine or primaquine prophylaxis.

Immune suppression and disturbances of normal leukocyte populations are side effects attributed to many antimalarial drugs and were concerns during a recent year-long placebo-controlled trial that compared daily primaquine (0.5 mg of base per kg of body weight per day) with weekly chloroquine (300 mg of base one time per week) for malaria prophylaxis. The study took place in Irian Jaya, Indonesia, from July 1994 to August 1995 and enrolled 129 Javanese men with normal glucose-6-phosphate dehydrogenase function. Tests for lymphocyte function and subset composition were conducted blindly on a cross-section of subjects during weeks 10 (n = 42) and 48 (n = 72) of supervised prophylaxis. Lymphocyte function, measured as the proliferative response of peripheral blood mononuclear cells to a panel of mitogens (pokeweed mitogen, phytohemagglutinin, and concanavalin A) and antigens (purified protein derivative of Mycobacterium tuberculosis and Clostridium tetani toxoid) and expressed as a stimulation index, allowed for statistical comparison between groups and sampling times. The lymphocyte subset composition for each group and time point was based on flow cytometry profiling, and the results were expressed as the mean percentages of CD3 (total T cells), CD19 (total B cells), CD4+ (T-helper and inducer cells), and CD8+ (T suppressor and cytotoxic cells), CD3/CD16+ CD56 (natural killer cells), CD3/anti-HLA-DR (activated T cells) cells and the CD4+/CD8+ ratios. Lymphocyte stimulation indices were statistically comparable among the placebo, primaquine, and chloroquine groups at both time points, although the primaquine group was distinguished by having repeatedly greater proportions of subjects with high ( > 3.0) stimulation indices. The lymphocyte subset profiles of these groups at both time points were also similar and undistorted relative to those of healthy reference populations matched for age, sex, and ethnicity. The results provide quantitative support for the safety of daily primaquine prophylaxis.