Dataset Information

The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial.

ABSTRACT:

Background

Chronic parasitic infections are associated with active immunomodulation which may include by-stander effects on unrelated antigens. It has been suggested that pre-natal exposure to parasitic infections in the mother impacts immunological development in the fetus and hence the offspring's response to vaccines, and that control of parasitic infection among pregnant women will therefore be beneficial.

Methodology/principal findings

We used new data from the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy conducted in Uganda, to further investigate this hypothesis. 2705 mothers were investigated for parasitic infections and then randomised to albendazole (400mg) versus placebo and praziquantel (40mg/kg) during pregnancy in a factorial design. All mothers received sulfadoxine/pyrimethamine for presumptive treatment of malaria. Offspring received Expanded Programme on Immunisation vaccines at birth, six, 10 and 14 weeks. New data on antibody levels to diphtheria toxin, three pertussis antigens, Haemophilus influenzae type B (HiB) and Hepatitis B, measured at one year (April 2004 -May 2007) from 1379 infants were analysed for this report. Additional observational analyses relating maternal infections to infant vaccine responses were also conducted. Helminth infections were highly prevalent amongst mothers (hookworm 43.1%, Mansonella 20.9%, Schistosoma mansoni 17.3%, Strongyloides 11.7%, Trichuris 8.1%) and 9.4% had malaria at enrolment. In the trial analysis we found no overall effect of either anthelminthic intervention on the measured infant vaccine responses. In observational analyses, no species was associated with suppressed responses. Strongyloidiasis was associated with enhanced responses to pertussis toxin, HiB and Hep B vaccine antigens.

Conclusions/significance

Our results do not support the hypothesis that routine anthelminthic treatment during pregnancy has a benefit for the infant's vaccine response, or that maternal helminth infection has a net suppressive effect on the offspring's response to vaccines.

Trial registration

ISRCTN.com ISRCTN32849447.

SUBMITTER: Nash S

PROVIDER: S-EPMC5298230 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial.

Nash Stephen S Mentzer Alexander J AJ Lule Swaib A SA Kizito Dennison D Smits Gaby G van der Klis Fiona R M FR Elliott Alison M AM

PLoS neglected tropical diseases 20170208 2

<h4>Background</h4>Chronic parasitic infections are associated with active immunomodulation which may include by-stander effects on unrelated antigens. It has been suggested that pre-natal exposure to parasitic infections in the mother impacts immunological development in the fetus and hence the offspring's response to vaccines, and that control of parasitic infection among pregnant women will therefore be beneficial.<h4>Methodology/principal findings</h4>We used new data from the Entebbe Mother ...[more]

PMID: 28178298

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Project description:BackgroundHelminth infections may modulate immune responses to unrelated pathogens and allergens; these effects may commence prenatally. We addressed the hypothesis that anthelminthic treatment in pregnancy and early childhood would improve responses to immunisation and modulate disease incidence in early childhood with both beneficial and detrimental effects.Methods and findingsA randomised, double-blind, placebo-controlled trial was conducted in Entebbe, Uganda [ISRCTN32849447]. In three independent randomisations, 2507 pregnant women were allocated to receive single-dose albendazole or placebo, and praziquantel or placebo; 2016 of their offspring were randomised to receive quarterly single-dose albendazole or placebo from age 15 months to 5 years. Primary outcomes were post-immunisation recall responses to BCG and tetanus antigens, and incidence of malaria, diarrhoea, and pneumonia; incidence of eczema was an important secondary outcome. Analysis was by intention-to-treat. Of 2345 live births, 1622 (69%) children remained in follow-up at age 5 years. 68% of mothers at enrolment, and 11% of five-year-olds, had helminth infections. Maternal hookworm and Schistosoma mansoni were effectively treated by albendazole and praziquantel, respectively; and childhood hookworm and Ascaris by quarterly albendazole. Incidence rates of malaria, diarrhoea, pneumonia, and eczema were 34, 65, 10 and 5 per 100 py, respectively. Albendazole during pregnancy caused an increased rate of eczema in the children (HR 1.58 (95% CI 1.15-2.17), p?=?0.005). Quarterly albendazole during childhood was associated with reduced incidence of clinical malaria (HR 0.85 (95% CI 0.73-0.98), p?=?0.03). There were no consistent effects of the interventions on any other outcome.ConclusionsRoutine use of albendazole in pregnancy may not always be beneficial, even in tropical developing countries. By contrast, regular albendazole treatment in preschool children may have an additional benefit for malaria control where helminths and malaria are co-endemic. Given the low helminth prevalence in our children, the effect of albendazole on malaria is likely to be direct.Trial registrationCurrent Controlled Trials ISRCTN32849447.

Project description:Objective To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus.Design Systematic review of randomised controlled trials, cohort studies, and case-control studies.Data sources Embase, PubMed, Cochrane library, and Trip searched between 1947 and January 2014. Publications submitted by a panel of experts in the specialty were also included.Eligibility criteria for selecting studies All human studies reporting non-specific immunological effects after vaccination with standard childhood immunisations. Studies using recombinant vaccines, no vaccine at all, or reporting only vaccine specific outcomes were excluded. The primary aim was to systematically identify, assemble, and review all available studies and data on the possible non-specific or heterologous immunological effects of BCG; measles; mumps, measles, and rubella (MMR); diphtheria; tetanus; and pertussis vaccines.Results The initial search yielded 11 168 references; 77 manuscripts met the inclusion criteria for data analysis. In most included studies (48%) BCG was the vaccine intervention. The final time point of outcome measurement was primarily performed (70%) between one and 12 months after vaccination. There was a high risk of bias in the included studies, with no single study rated low risk across all assessment criteria. A total of 143 different immunological variables were reported, which, in conjunction with differences in measurement units and summary statistics, created a high number of combinations thus precluding any meta-analysis. Studies that compared BCG vaccinated with unvaccinated groups showed a trend towards increased IFN-γ production in vitro in the vaccinated groups. Increases were also observed for IFN-γ measured after BCG vaccination in response to in vitro stimulation with microbial antigens from Candida albicans, tetanus toxoid, Staphylococcus aureas, lipopolysaccharide, and hepatitis B. Cohort studies of measles vaccination showed an increase in lymphoproliferation to microbial antigens from tetanus toxoid and C albicans Increases in immunogenicity to heterologous antigens were noted after diphtheria-tetanus (herpes simplex virus and polio antibody titres) and diphtheria-tetanus-pertussis (pneumococcus serotype 14 and polio neutralising responses) vaccination.Conclusions The papers reporting non-specific immunological effects had heterogeneous study designs and could not be conventionally meta-analysed, providing a low level of evidence quality. Some studies, such as BCG vaccine studies examining in vitro IFN-γ responses and measles vaccine studies examining lymphoproliferation to microbial antigen stimulation, showed a consistent direction of effect suggestive of non-specific immunological effects. The quality of the evidence, however, does not provide confidence in the nature, magnitude, or timing of non-specific immunological effects after vaccination with BCG, diphtheria, pertussis, tetanus, or measles containing vaccines nor the clinical importance of the findings.

Project description:BackgroundExcessive gestational weight gain (GWG) is associated with an increased risk of pregnancy and obstetric complications. The "healthy living in pregnancy" (GeliS) study was performed in a routine care setting with the aim of limiting excessive GWG. The purpose of this secondary analysis is to evaluate the effect of the intervention on physical activity (PA) behaviour and to assess the impact of PA intensities on GWG.MethodsThe cluster-randomised, multicentre GeliS trial was performed in a routine care setting alongside scheduled prenatal visits. Pregnant women with a pre-pregnancy BMI between 18.5 and 40.0 kg/m2 were either assigned to the control group receiving usual care or to the intervention group. Participants in the intervention group attended three antenatal counselling sessions on diet and PA and one additional postpartum session. Data on PA behaviour were collected twice, before the end of the 12th (baseline) and after the 29th week of gestation using the Pregnancy Physical Activity Questionnaire.ResultsPA data were available for 1061 (93%) participants in the intervention and 1040 (93%) in the control group. Women in the intervention group reported significant improvements in the levels of total PA (p < 0.001), total PA of light intensity and above (p < 0.001), moderate-intensity (p = 0.024) and vigorous-intensity activities (p = 0.002) as well as sport activities (p < 0.001) in late pregnancy compared to the control group. The proportion of women meeting the international PA recommendations in late pregnancy was significantly higher in the intervention (64%) versus the control group (49%, p < 0.001). Activities of light-intensity and above (p = 0.006), light-intensity (p = 0.002) and vigorous-intensity (p = 0.014) in late pregnancy were inversely associated with total GWG.ConclusionWe found significant evidence of improvements in the PA pattern of pregnant women receiving lifestyle counselling within the framework of routine care. Most PA intensities were inversely associated with total GWG which indicates that PA across different intensities should be promoted.Trial registrationNCT01958307, ClinicalTrials.gov, retrospectively registered 9 October, 2013.

Dataset Information

The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial.

Background

Methodology/principal findings

Conclusions/significance

Trial registration

Publications

The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial.

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