The Entebbe Mother and Baby Study is the first randomised, double-blind, placebo-controlled trial of praziquantel treatment during pregnancy. It is also the first trial to examine the effects of praziquantel or of benzimidazole treatment during pregnancy on the broad range of maternal and infant outcomes that might be influenced by pre-natal exposure to helminths. Some of the long-term effects of anthelminthic treatment during pregnancy, including effects on the offspring's own susceptibility to infection and morbidity when exposed to the same species, have yet to be examined. However, the results to date, taken together with the findings of other recent studies, suggest that the risks and benefits of anthelminthic treatment during pregnancy, and policy regarding routine provision of anthelminthics during antenatal care, may need to be reviewed.
In Entebbe, where good, general antenatal care was provided, there was a possible benefit of albendazole for anaemia in mothers with moderate to heavy hookworm infection, but otherwise none of the expected benefits of anthelminthic treatment on anaemia, birth weight, perinatal mortality, infant mortality or infant response to immunisation were realised. These findings were in keeping with results from the two other benzimidazole trials (Torlesse and Hodges, 2001
; Larocque et al. 2006
). Mothers with possible symptomatic helminth infection were excluded from our trial, but such women were unusual in our setting: of 11,783 screened for the study only 17 were excluded for haemoglobin below 8 g/dl, 15 for diarrhoea with blood in stools and none for clinically apparent severe liver disease (Webb et al
). It other settings, or with other helminth species (for example S. japonicum
), the balance of benefits to mother and infant may differ. However, the minimal effects associated with helminths and anthelminthic treatment in our setting are put further into perspective by the strong adverse effects of malaria and HIV infection observed; the prevalence of malaria was 13% and of HIV 12% at baseline, during pregnancy, in our study. We found that maternal malaria and HIV infection were strongly associated with maternal anaemia (Muhangi et al. 2007
), and were also associated with reduced birth weight and increased perinatal mortality (unpublished data). Maternal and infant HIV infection, and infant malaria, were associated with deleterious effects on the infant response to immunisation (Elliott et al. 2010
The three trials have been conducted to date in areas with high hookworm prevalence but low intensity, and this is the common pattern of helminth infection. However, a trial in a setting with heavy hookworm infection might have a different result, especially if background levels of nutrition and iron status are poor. Trial results might also be expected to differ according to helminth species: Necator americanus
and Ancylostoma duodenale
may differ in their pathogencity for anaemia (Albonico et al. 1998
) – and we have not yet determined the prevalent species in Entebbe; schistosome species clearly differ in the immunopathology that they induce (Burke et al. 2009
). The three reported studies demonstrate that placebo-controlled trials can be conducted safely, and additional trials are still needed in different settings.
The observed adverse effect on infantile eczema is a concern, and contributes to the current equipoise in evidence regarding the potential risks and benefits of anthelminthic therapy during pregnancy. Whether this finding can be generalised to other environments is uncertain: Entebbe is unusual among lake-shore communities in Uganda in being relatively urbanised and traversed by a major highway, and hosting the international airport. Pollutants may contribute to the induction of allergy (Venn et al. 2001
), and the results of anthelminthic therapy in such a setting may differ from the results in a purely rural context.
A key question is whether effects on infantile eczema will this translate into an impact on asthma in later life? Studies in affluent countries suggest that while infantile eczema per se
may not predict later asthma, early development of atopy, and eczema associated with atopy and wheeze in early childhood, may be associated with atopic asthma at school-age (Illi et al. 2004
; Williams and Flohr, 2006
). Asthma mortality depends not just on prevalence, but also on quality of care; already 80% of asthma deaths occur in low- and middle-income countries (WHO, 2010
). It is possible that, as low-income countries develop, anthelminthic treatment programmes will contribute to an epidemic increase in allergic disease similar to that experienced in affluent countries during the 20th century (Bach, 2002
). Further research is needed to determine whether this is likely to be the case; if so, measures to equip such countries to manage such an epidemic need to be planned.
Conversely, studies of the underlying mechanisms of helminth-allergy interactions in endemic countries have the potential to provide insights for the development of new tools for the prevention and management of allergic disease, with global health benefits.