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Background: Vaccine 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. Methods: We 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. Results: Among 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. Conclusion: Malaria 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. [ABSTRACT FROM AUTHOR]

Background: The 'external validity' of randomized controlled trials is an important measure of quality, but is often not formally assessed. Trials concerning mass drug administration for helminth control are likely to guide public health policy and careful interpretation of their context is needed. We aimed to determine how representative participants in one such trial were of their community. We explore implications for trial interpretation and resulting public health recommendations.Methods: The trial assessed was the Entebbe Mother and Baby Study (EMaBS), a trial of anthelminthic treatment during pregnancy and early childhood. In a novel approach for assessing external validity, we conducted a two-stage cluster sample community survey within the trial catchment area and compared characteristics of potentially-eligible community children with characteristics of children participating in the trial.Results: A total of 173 children aged three to five-years-old were surveyed from 480 households. Of children surveyed, we estimated that mothers of 60% would have been eligible for recruitment, and of these, 31% had actually been enrolled. Children surveyed were compared to 199 trial children in the same age group reviewed at annual trial visits during the same time period. There were significant differences in ethnicity between the trial participants and the community children, and in socioeconomic status, with those in the trial having, on average, more educated parents and higher maternal employment. Trial children were less likely to have barefoot exposure and more likely to use insecticide-treated bed nets. There were no significant differences in numbers of reported illness events over the last year.Conclusions: The trial had not enrolled all eligible participants, and those enrolled were of higher socioeconomic status, and had lower risk of exposure to the parasitic infections targeted by the trial interventions. It is possible the trial may have underestimated the absolute effects of anthelminthic treatment during pregnancy and early childhood, although the fact that there were no differences in reported incidence of common infectious diseases (one of the primary outcomes of EMaBS) between the two groups provides reassurance. Concurrent community surveys may be an effective way to test the external validity of trials.Emabs Trial Registration: ISRCTN32849447, registered 22 July 2005. [ABSTRACT FROM AUTHOR]

Background: Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods) and antibodies against Kaposi's sarcoma herpesvirus (KSHV), measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda., Results: Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01), hookworm (67% vs 56% p = 0.001) and Mansonella perstans (69% vs 59% p = 0.05); seroprevalence increased with increasing intensity of hookworm infection (p < 0.001[trend]). No associations were found for HIV, five other parasites or active syphilis. These effects were not explained by socioeconomic status or education., Conclusions: Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.