Dengue Virus Infections and Maternal Antibody Decay in a Prospective Birth Cohort Study of Vietnamese Infants

Oxford University Clinical Research Unit, Hong Vuong Hospital, Ho Chi Minh City, Vietnam.
The Journal of Infectious Diseases (Impact Factor: 6). 11/2009; 200(12):1893-900. DOI: 10.1086/648407
Source: PubMed
Dengue hemorrhagic fever can occur in primary dengue virus (DENV) infection of infants. The decay of maternally derived DENV
immunoglobulin (Ig) G and the incidence of DENV infection were determined in a prospectively studied cohort of 1244 Vietnamese
infants. Higher concentrations of total IgG and DENV-reactive IgG were found in cord plasma relative to maternal plasma. Maternally
derived DENV-neutralizing and E protein–reactive IgG titers declined to below measurable levels in >90% of infants by 6 months
of age. In contrast, IgG reactive with whole DENV virions persisted until 12 months of age in 20% of infants. Serological
surveillance identified 10 infants with asymptomatic DENV infection for an incidence of 1.7 cases per 100 person-years. DENV-neutralizing
antibodies remained measurable for ⩾1 year after infection. These results suggest that whereas DENV infection in infants is
frequently subclinical, there is a window between 4 and 12 months of age where virion-binding but nonneutralizing IgG could
facilitate antibody-dependent enhancement

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    • "New-borns are assumed to be immunologically naïve to all serotypes and are born into the class of susceptibles (S). Although the presence of maternal antibodies is shown to affect the risk of infection, the impact on the overall dynamics is believed to be minimal and thus not taken into consideration [43] . Susceptibles become primarily infected by serotype i (I i ) at rate βSI i and α TRANS βSI ji proportional to the number of primarily and secondarily infectious individuals respectively. "
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    • "Epidemiological studies over the last few decades have indeed reported that most of the DHF/DSS cases occur upon secondary infection with a heterologous DENV serotype [5, 6]. Increased risk of DHF/DSS was also reported in infants at 5–9 months of age born to dengue immune mothers when maternally acquired antibodies wane to sub-neutralizing levels [7][8][9][10]. These epidemiological observations were explained by the antibody-dependent enhancement (ADE) of infection hypothesis, whereby actively (during primary infection) or passively (through maternal transfer) acquired anti-DENV antibodies cross react but fail to neutralize a heterologous (or homologous) serotype of DENV [5]. "
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    • "Clinical evidence for a role of antibodies in dengue pathogenesis comes from observations of the increased risk of DHF/DSS in 5– 9 month-old infants, when maternal antibodies against DENV have waned to sub-neutralizing levels (Chau et al., 2009Chau et al., , 2008 Duangchinda et al., 2010; Kliks et al., 1988; Simmons et al., 2007). While infection with a heterologous DENV serotype in young children or adults would trigger anamnestic, cross-reactive responses from both B and T cells (Chau et al., 2008; Duangchinda et al., 2010 ), only maternal antibodies cross the placenta to the infant. "
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