The comparative susceptibility of 13 geographic strains of Aedes aegypti to oral infection with dengue viruses was studied by feeding the mosquitoes on a virus-erythrocyte-sugar suspension. Significant variation in susceptibility to four dengue serotypes was observed among the geographic strains tested. Mosquito strains which were more susceptible to one serotype were also more susceptible to the other serotypes, suggesting that the factors controlling susceptibility were the same for all types. The amount of virus required to infect mosquitoes orally varied inversely with the susceptibility of the geographic strain. Thresholds of infection were not the same for dengue types 1, 2, 3 and 4. There was no apparent difference in infectivity between prototype and recently isolated strains of dengue types 1 and 3. Crossing experimentibility as the resistant parent. No difference was observed between resistant and susceptible mosquito strains in the rate or the amount of viral replication after infection by the parenteral route, or in their ability to transmit dengue 2 virus after infection by the oral route.
Abstract. A prospective study on dengue (DEN) viruses was initiated in October 1995 in Gondokusuman kecamatan, Yogyakarta, Indonesia. This report presents data from the first year of the study. The studied cohort included all children 4-9 years of age living in the kecamatan. Blood samples for serology were collected from 1,837 children in October 1995 and again in October 1996. Blood samples for virus isolation and serology were collected from cohort children who were seen in municipal health clinics with febrile syndromes or admitted to hospitals with a provisional diagnosis of dengue hemorrhagic fever. Dengue serotype antibody prevalence and 1995-1996 infection rates were calculated using a single dilution (1:60) 70% plaque reduction endpoint neutralization test. Prevalence of dengue antibody at the beginning of the study was DEN 1 ϭ 12%, DEN 2 ϭ 16%, DEN 3 ϭ 2%, DEN 4 ϭ 4%, and two or more dengue infections ϭ 22%. Total dengue antibody prevalence increased from 38% in 4-year-old children to 69% in 9-year-old children. During the observation period, primary dengue infection rates were DEN 1 ϭ 4.8%, DEN 2 ϭ 7.7%, DEN 3 ϭ 4.2%, and DEN 4 ϭ 3.4%, while two or more dengue infections occurred in 6.7% of the study population. The secondary dengue infection rate was 19.0%. From febrile cases, all four dengue viruses were isolated with DEN 3 predominating. Seven children were hospitalized, including one fatal case with a hospital diagnosis of dengue shock syndrome. Based upon presence of antibody in the initial cohort bleeding and the serologic response both weeks and several months following illness, all had secondary dengue infections. Neutralizing antibody patterns in the initial cohort bleeding and in late convalescent serum samples permitted recognition of dengue infection sequence in five patients: DEN 2-DEN 1 (3), DEN 2-DEN 4 (1), DEN 1-DEN 3 (1), and none in the sequence DEN 1-DEN 2. In the total cohort 6.5% of the observed secondary infections were of the sequence DEN 2-DEN 1, while 4.9% were DEN 1-DEN 2, a highly pathogenic sequence in previous studies. Reduced pathogenic expression of secondary DEN 2 with enhanced pathogenic expression of secondary DEN 1 infections was an unexpected finding. Further studies will be required to understand the respective contributions to pathogenicity of antibody from initial dengue infections versus the biological attributes of the second infecting dengue viruses.The dengue (DEN) viruses (serotypes 1, 2, 3, and 4) are transmitted in nearly all tropical countries with a total population at risk in excess of 2.5 billion people.
A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted in a cohort of adult volunteers from two textile factories located in West Java, Indonesia. Volunteers in the cohort were bled every three months and were actively followed for the occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In areas where no symptomatic cases were detected, the incidence of asymptomatic or mild infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype identified, but all four serotypes were detected among the cohort. Four cases of DHF and one case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of a longitudinal cohort study of naturally acquired DF and DHF in adults.
A two-year study using a cluster investigation method was conducted in West Jakarta, Indonesia to demonstrate the detection of dengue cases prior to onset of clinical illness. The clusters consisted of family members and neighbors of 53 hospitalized dengue index cases. Among 785 adult and child volunteers enrolled, 17 (2.2%) post-enrollment dengue (PED) infections were identified. Eight PED cases were asymptomatic and nine were symptomatic. Symptomatic cases included eight with dengue fever and one with dengue hemorrhagic fever (DHF) (grade II). Among the eight asymptomatic PED cases, viremia was detected in two. Eleven volunteers had acute dengue infections at the time of enrollment. Four of the 11 developed DHF, resulting in a total of five DHF cases detected during the investigation. This study design can serve as a benchmark for future investigations that seek to define early immunologic events following dengue infections that contribute to the development of DHF.
Two years' follow-up investigation of a hepatitis E virus (HEV) outbreak in West Kalimantan, Indonesia in 1991 was carried out to investigate the epidemiology of epidemic HEV transmission and the persistence of the immunoglobulin G (IgG) antibody response. Sixty cases identified as anti-HEV IgG positive during the outbreak in 1991 were matched with 67 controls and examined, together with 318 members of their families. Overall, the prevalence of anti-HEV IgG among the 445 subjects (representing 127 households) was 59%. There was no significant difference in anti-HEV prevalence between cases (72%) and controls (61%). Loss of detectable anti-HEV IgG after 2 years was demonstrated in 17 of 60 subjects (28%) who were originally positive for anti-HEV in 1991. The mean number of anti-HEV positive subjects per household was 2.04. Cross-sectional prevalence of anti-HEV IgG increased significantly with age (P = 0.01). When communities were grouped into areas of low (< 40%), medium (40-59%) and high (> or = 60%) anti-HEV prevalence, use of river water for drinking and cooking (P < 0.001), personal washing (P < 0.0001), and human excreta disposal (P < 0.001) were associated with high prevalence communities. Conversely, boiling drinking water was negatively associated with increased prevalence (P = 0.02). Subnormal rainfall during the month (August) leading up to the 1991 outbreak (19 cm compared to the monthly mean of 209 cm in 1985-1993) may have contributed to favourable epidemic conditions.
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