Abstract
BackgroundVaccine failure is an important concern in the tropics with many contributing elements. Among them, it has been suggested that exposure to natural infections might contribute to vaccine failure and recurrent disease outbreaks. We tested this hypothesis by examining the influence of co-infections on maternal and infant measles-specific IgG levels.MethodsWe conducted an observational analysis using samples and data that had been collected during a larger randomised controlled trial, the Entebbe Mother and Baby Study (ISRCTN32849447). For the present study, 711 pregnant women and their offspring were considered. Helminth infections including hookworm, Schistosoma mansoni and Mansonella perstans, along with HIV, malaria, and other potential confounding factors were determined in mothers during pregnancy and in their infants at age one year. Infants received their measles immunisation at age nine months. Levels of total IgG against measles were measured in mothers during pregnancy and at delivery, as well as in cord blood and from infants at age one year.ResultsAmong the 711 pregnant women studied, 66% had at least one helminth infection at enrolment, 41% had hookworm, 20% M. perstans and 19% S. mansoni. Asymptomatic malaria and HIV prevalence was 8% and 10% respectively. At enrolment, 96% of the women had measles-specific IgG levels considered protective (median 4274 mIU/ml (IQR 1784, 7767)). IgG levels in cord blood were positively correlated to maternal measles-specific IgG levels at delivery (r = 0.81, p < 0.0001). Among the infants at one year of age, median measles-specific IgG levels were markedly lower than in maternal and cord blood (median 370 mIU/ml (IQR 198, 656) p < 0.0001). In addition, only 75% of the infants had measles-specific IgG levels considered to be protective. In a multivariate regression analysis, factors associated with reduced measles-specific antibody levels in infancy were maternal malaria infection, infant malaria parasitaemia, infant HIV and infant wasting. There was no association with maternal helminth infection.ConclusionMalaria and HIV infection in mothers during pregnancy, and in their infants, along with infant malnutrition, may result in reduction of the antibody response to measles immunisation in infancy. This re-emphasises the importance of malaria and HIV control, and support for infant nutrition, as these interventions may have benefits for vaccine efficacy in tropical settings.
Highlights
Vaccine failure is an important concern in the tropics with many contributing elements
Within the Entebbe Mother and Baby study (EMaBS), we have shown that anthelminthic treatment during pregnancy had no effect on infant antibody levels following measles immunisation [18]
We considered the possibility that maternal helminths might have other effects on the infant response that are not modified by treatment during pregnancy, or that other chronic immunomodulating infections such as HIV or malaria may influence the infant response to immunisation
Summary
Vaccine failure is an important concern in the tropics with many contributing elements. It has been suggested that exposure to natural infections might contribute to vaccine failure and recurrent disease outbreaks We tested this hypothesis by examining the influence of co-infections on maternal and infant measles-specific IgG levels. It has been hypothesised that in utero exposure of the child to maternal helminth infection may have a long-term effect on the child’s immunological development, including their response to immunisation [16,17]. Contrary to this hypothesis, within the Entebbe Mother and Baby study (EMaBS), we have shown that anthelminthic treatment during pregnancy had no effect on infant antibody levels following measles immunisation [18]. We explored these possibilities in an observational analysis within the EMaBS cohort, which had been established for a trial of anthelminthic treatment during pregnancy in Entebbe, Uganda
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