Effect of albendazole treatments on the prevalence of atopy in children living in communities endemic for geohelminth parasites: a cluster-randomised trial

doi:10.1016/S0140-6736(06)68697-2

The Lancet

Volume 367, Issue 9522, 13–19 May 2006, Pages 1598-1603

https://doi.org/10.1016/S0140-6736(06)68697-2 Get rights and content

Summary

Background

Epidemiological studies have shown inverse associations between geohelminth (intestinal helminth) infection and atopy, leading to the suggestion that geohelminths might protect against allergy. Periodic deworming of school children with anthelmintics is a widely implemented intervention and has raised concerns that such programmes could increase allergy. We investigated the effect of repeated anthelmintic treatments with albendazole over 12 months on the prevalence of atopy and clinical indices of allergy.

Methods

We did a cluster-randomised controlled trial in schoolchildren from 68 rural schools. Children were randomly assigned by school to either albendazole (34 schools, 1164 children) every 2 months for 12 months, or to no intervention (34 schools, 1209 children). The intervention schools received a total of seven albendazole treatments. The primary outcome was atopy at 12 months (allergen skin-test reactivity), and analysis was by intention-to-treat for whole-school analyses and per protocol for children. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN61195515.

Findings

Data for analysis were available for all schools and from 67·4% (784 of 1164) and 70·1% (848 of 1209) of children in albendazole and no-treatment groups, respectively. Albendazole treatment caused large reductions in geohelminth prevalence over the study period (adjusted odds ratio 0·13, 95% CI 0·09–0·19, p<0·001), but there was no evidence that treatment was associated with an increase in atopy prevalence (0·97, 0·68–1·39, p=0·862), or clinical allergy (wheeze, 1·07, 0·54–2·11, p=0·848) in the albendazole compared with the no-treatment group.

Interpretation

We saw no increase in the prevalence of atopy or clinical allergy associated with albendazole treatment. Deworming programmes for schoolchildren are unlikely to be accompanied by an increase in allergy.

Introduction

Illness caused by the geohelminth parasites Ascaris lumbricoides, Trichuris trichiura, and hookworm is an important cause of disability in poor regions of the tropics, where such parasites are estimated to infect around 2 billion people.¹ In 2001, the World Health Assembly endorsed a strategy for the control of geohelminth infections and associated morbidity through the regular treatment of high-risk groups, particularly school-age children.² In line with these political developments, national governments and donor organisations such as the World Bank have prioritised anthelmintic treatment programmes for school-age children.³

A causal inverse association has been proposed between geohelminths and allergy because of the low prevalence of allergic disease seen in areas where geohelminth infections are highly prevalent.⁴ Many epidemiological studies have investigated the relation between geohelminths and allergy and have provided conflicting evidence for an association,⁴ with some studies showing a strong inverse relation between geohelminth infections and prevalence of allergy symptoms5, 6 or atopy.7, 8, 9 Small intervention studies have suggested that anthelmintic treatment might increase the prevalence¹⁰ and incidence¹¹ of atopy. Whether programmes of repeated anthelmintic treatments targeted at schools might have the adverse effect of increasing atopic reactivity and allergic disease remains to be established.

We have shown that geohelminth infections are inversely associated with risk of skin-test reactivity to allergens in children attending rural schools in Ecuador.12, 13 We postulated that geohelminth infections were suppressing skin-test reactivity to aeroallergens on the basis of a biological model in which helminth infections might inhibit actively allergic effector responses including immediate hypersensitivity.¹⁴ We therefore did a cluster-randomised trial to establish the effect of anthelmintic treatments every 2 months for 12 months on the frequency of atopy and indices of clinical allergy in schools where the prevalence of geohelminth infections is high.

Section snippets

Study area and participants

The study was done between June 21, 2002, and Aug 24, 2004, in 68 rural schools in adjacent districts of Pichincha Province, Ecuador, where we have reported previously an inverse relation between risk of atopy and geohelminths.12, 13 The study area is a tropical and sub-tropical region at altitudes between 126 and 1730 metres. All rural schools located within the study area, with fewer than 150 children, with road access during the wet season, and where initial meetings to explain the purpose

Results

Figure 1 shows the trial profile. We recorded no adverse events relating to albendazole treatment. 74 schools were approached for inclusion, and six were excluded before baseline assessments because too few parents attended initial community meetings (five schools) and because of recent mass anthelmintic treatment (one). The average cluster size (range) was 35·5 (14–91) children in no-treatment and 34·3 (12–77) in albendazole schools. The design resulted in a similar distribution of baseline

Discussion

Anthelmintic treatments with albendazole every 2 months for a year had no effect on the proportion of children with skin-test reactivity to aeroallergens or on the frequency of allergy symptoms or exercise-induced bronchospasm. This study is the largest published so far to examine the effect of anthelmintic treatment on atopy risk and provides evidence that an increase in allergy is unlikely to accompany deworming programmes.

Several potential limitations exist to the interpretation of the study

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There is considerable research interest in the role of helminth infections in the development of allergic diseases. However, findings from previous studies are mixed. Existing systematic reviews of these studies are outdated. We performed a systematic review of the global literature on the association between helminth infections and development and clinical outcomes of allergic diseases.
We searched Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, PubMed, Global Index Medicus, Scielo, KoreaMed, Google Scholar, and Lilacs for studies published up to January 2020. We included observational epidemiological studies (cohort, case-control, and cross-sectional studies) of children and adults reporting associations between helminth infections and asthma, allergic rhinitis, eczema, and atopy. We performed random-effects meta-analysis to summarize the effect estimates.
We included 80 studies with 99,967 participants. In the meta-analyses, we did not observe an overall association between helminth infections and allergic diseases. There was, however, evidence that Ascaris lumbricoides infections were associated with an increased risk of bronchial hyperreactivity in children (risk ratio, 1.41; 95% CI, 1.17-1.70; I² = 50; P for I² = .09), and were associated with an increased risk of atopy among helminth-infected adults (risk ratio, 1.37; 95% CI, 1.18-1.61; I² = 52; P for I² = .02). We found no study that addressed the association between helminth infection and clinical outcomes of allergic diseases. The overall strength of the underlying evidence was low to moderate.
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Several epidemiology studies have shown inverse associations of chronic parasitic worm infections with allergy and atopy in regions of high prevalence of such infections (van den Biggelaar et al., 2004; Leonardi-Bee et al., 2006; Mpairwe et al., 2008; Rujeni et al., 2012; Webb et al., 2016). Other studies in schoolchildren have produced conflicting results with regard to the effects of deworming on SPT responses (van den Biggelaar et al., 2004; Cooper et al., 2006) A study in Indonesia found that SPT reactivity increased after 1 year of albendazole treatment, in Gabon SPT reactivity was significantly reduced in children infected with S.haematobium and in Ecuador, albendazole treatment had no effect on the prevalence of SPT reactivity (Lynch et al., 1993; van den Biggelaar et al., 2000; Cooper et al., 2006; Staal et al., 2018). In this study, when we examined the effects of S.haematobium infection status and SPT status on NMDS scores our results showed that SPT status had a significant effect on NMDS scores for NMDS3 (IgA) for S.cerevisiae with SPT-negative individuals having significantly higher IgA response compared to SPT-positive individuals.
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The mycobiome formed <1% of the sequenced gut microbiome and 228 fungal genera were identified. The most abundant genera detected were Protomyces, Taphrina, and Aspergillus. S.haematobium infection had a significant effect on fungal genera. Prevalence of SPT sensitisation to ≥1 fungal species was 96%, and individuals were frequently sensitised to Saccharomyces cerevisiae. Antibodies were detected in 100% of the population. There was no relationship between mycobiome abundance and IgE titres or IgE/IgG4 ratios for each fungal species; no significant differences between SPT reactivity and abundance of fungal species except for S. cerevisiae; and fungal seroreactivity did not significantly differ with age. There were some sex (m>f for, Epicoccum nigrum and Penicillium chrysogenum) and SPT reactivity –related differences in seroreactivity.
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ArticlesEffect of albendazole treatments on the prevalence of atopy in children living in communities endemic for geohelminth parasites: a cluster-randomised trial

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Study area and participants

Results

Discussion

Lancet

J Allergy Clin Immunol

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

Trends Immunol

Lancet

World Health Assembly Resolution 54.19. Schistosomiasis and soil-transmitted helminth infections

Soil-transmitted helminthiasis

Nature Rev Microbiol

Wheezing, allergy and parasite infection in children in urban and rural Ethiopia

Am J Resp Crit Care Med

Modulation of the allergic reactivity of slum children by helminthic infection

Parasite Immunol

The prevalence of parasite infestation and house dust mite sensitisation in Gabonese schoolchildren

Int Arch Allergy Immunol

Atopy, intestinal helminth infection and total serum IgE in rural and urban adult Gambian communities

Clin Exp Allergy

Articles
Effect of albendazole treatments on the prevalence of atopy in children living in communities endemic for geohelminth parasites: a cluster-randomised trial