Helminths – A randomised, double-blind, placebo-controlled trial.

Impact of Anthelminthic Treatment in Pregnancy and Childhood on Immunisations, Infections and Eczema in Childhood: A Randomised Controlled Trial

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050325?imageURI=info:doi/10.1371/journal.pone.0050325.t002

Background

Helminth 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 Findings

A 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.

Conclusions

Routine 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.

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Further Reading

Review Article

Is Autism a Member of a Family of Diseases Resulting from Genetic/Cultural Mismatches? Implications for Treatment and Prevention

http://www.hindawi.com/journals/aurt/2012/910946/

The use of modern medicine, toilets, water treatment facilities, and cleaning agents in our culture has led to a substantial alteration or even loss of living organisms that have coevolved with humans.

Three primary components of the biome which are potentially important have been affected [43]: (a) loss of interactions with soil bacteria, (b) alterations of the microbiome, the normal bacteria that are associated with the human body, and (c) loss of helminths, worms that typically inhabit the gut of mammalian species.

Substantial evidence points toward all three of these factors as being important in stabilization of the human immune system.

Although not widely appreciated, several lines of evidence point very strongly if not conclusively to the idea that helminths in particular are necessary for a stable immune system.

This evidence has been reviewed extensively [1, 43] and can be very briefly summarized as follows.

(i)Helminths are found almost ubiquitously in preindustrial humans [44] and in nondomesticated mammals, including chimpanzees [45].

Even when helminths cannot be found, the immune system shows signs of stimulation by helminths [46].

(ii)Helminths produce and secrete a number of molecules which regulate the host immune system [47].

(iii)Addition of helminths to laboratory animals blocks allergic, inflammatory, and autoimmune diseases [47].

(iv)Addition of helminths to humans cures inflammatory bowel disease [48] and stops the progression of multiple sclerosis [49].

(v)The effects of biome depletion on the immune system are not necessarily instantaneous because long-term effects of immune interactions with the biome can span decades or, through epigenetics, even generations [1]. Nevertheless, the epidemiology of hyperimmune disease reveals an inverse correlation between helminths and disease.

(vi)Humans with helminths and rodents colonized with helminths have profoundly less reactive immune systems than do either without helminths [44, 50, 51].(vii)A long coevolutionary history of helminths and vertebrates, in conjunction with the potent immunoregulatory effects of the former, is consistent with the idea that the human immune system is literally, physically dependent on helminths [1].”

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