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

Abstract

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.

Prospective birth cohort in a hyperendemic dengue area in Northeast Brazil: methods and preliminary results

“…2,17 . This maternal anti-dengue immune profile seems to be different from studies conducted in pregnant women in Asian countries where the majority of pregnant women were immune against two or more DENV serotypes 5,8,9 . In these Asian countries, unlike Brazil 2 , a high proportion of dengue cases in infants progress to severe dengue forms 3,21 .…”

“…Prospective cohort studies have proved important in understanding the epidemiology and immunopathogenesis of dengue fever in pediatric populations 6,8,9,10 . However, few studies to date have involved children aged less than four years and only one published study has included Latin American populations 11 .…”

The pathogenesis of dengue

“…At the age of 3-4 months, maternally-derived virus neutralizing antibodies have generally declined below measurable levels in infants, however non-neutralising antibodies, which represent a much greater fraction of the virion-binding antibody population, remain present. [48][49][50] These virion-binding, non-neutralising antibodies are thought to enhance the risk of clinically apparent and severe dengue through a process of ADE. [51][52][53][54] In support of this hypothesis, neat plasma from 6-month old healthy Vietnamese infants enhances the infectivity of DENV-2 in Fc receptor bearing cells significantly more than plasma collected at the time of birth or at 1-yr of age.…”

Contribution of Dengue Fever to the Burden of Acute Febrile Illnesses in Papua New Guinea: An Age-Specific Prospective Study

“…We omitted IgG status of children below 1 year of age in stratified analysis to avoid possible interference with remaining circulating maternal antibodies. 26,27 RESULTS Baseline characteristics. Five hundred seventy-eight patients presenting at the outpatient clinics of Yagaum rural hospital or Jomba Clinic with temperatures > 38°C or history of fever were enrolled in the study from October 2007 to June 2008; 48% were female, 75% were living in a rural area, and the mean age was 9.0 years (median = 5 years, range = 0-60 years).…”