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Report Of Four Volunteers With Primary, Secondary And Tertiary Dengue Infections During A Prospective Cohort Study

Report Of Four Volunteers With Primary, Secondary And Tertiary Dengue Infections During A Prospective Cohort Study
Hadi Yusuf, Primal Sudjana dan Bachti Alisjahbanab
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A prospective study of dengue fever (DF) and dengue haemorrhagic fever (DHF) in adults was conducted at two factories in Bandung, Indonesia, between August 2000 and July 2004. A total of 2978 employees were followed for the development of fever and clinical signs of DF/DHF. Among 1431 patients reporting a febrile illness, dengue infections were detected in 177 individuals. Four enrollees with evidence of previous dengue exposure experienced two consecutive episodes of dengue infection. Analysis of preillness sera revealed that one patient had neutralizing antibodies (nAbs) to DENV-1, two had nAbs to DENV-2, and another had nAbs to DENV-2, 3 and 4. The individual with pre-illness neutralizing antibodies to DENV-1 experienced a DENV-3 secondary infection, followed by a third infection with an unknown serotype. One of the two individuals with pre-illness neutralizing antibodies to DENV-2 experienced a DENV-3 and then a DENV-1 infection. The other DENV-2 immune patient experienced sequential infections with DENV-4 and DENV-3 viruses. Finally, the individual with pre-illness neutralizing antibodies against three dengue viruses had a subsequent infection with DENV-4, followed one year later by DENV-3. In this instance, the patient acquired grade II DHF (WHO criteria) from the subsequent DENV-4 infection. These data provide confirmatory evidence that humans can experience three sequential heterologous dengue infections. Importantly, the occurrence of a second and third infection in individuals with pre-illness antibodies against multiple dengue serotypes indicates that neutralizing antibodies are cross-reactive in vitro but not cross-protective in vivo.

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