Background Helminth infection may influence cardiometabolic risk through effects on inflammation and metabolism. We hypothesised that helminths are protective and their treatment detrimental to metabolic outcomes. Methods We conducted a cluster-randomised trial in 26 fishing communities, Lake Victoria, Uganda. We investigated effects of community-wide intensive (quarterly single-dose praziquantel, triple dose albendazole) versus standard (annual single-dose praziquantel, six-monthly single-dose albendazole) anthelminthic treatment on metabolic outcomes, and observational associations between helminth infection and metabolic outcomes. The primary outcome, homeostatic model assessment of insulin resistance (HOMA-IR) and secondary outcomes (including blood pressure, fasting blood glucose and lipids) were assessed in a survey conducted after four years of intervention among individuals ≥10 years. Results We analysed 1898 participants. The intervention had no effect on HOMA-IR (adjusted geometric mean ratio [95%CI] 0.96 [0.86,1.07] p=0.42) but resulted in higher mean LDL-cholesterol in the intensive arm (2.86 vs 2.60 mmol/L, adjusted mean difference [95%CI] 0.26 [-0.03,0.56] p=0.08). Lower LDL-cholesterol levels were observed in S. mansoni (2.37 vs 2.80 mmol/L, -0.25 [-0.49,-0.02] p=0.04) and Strongyloides infected (2.34 vs 2.69mmol/L, -0.32 [-0.53,-0.12] p=0.003) participants compared with uninfected. S. mansoni infection was associated with lower total cholesterol levels (4.24 vs 4.64 mmol/L, -0.25 [-0.44,-0.07] p=0.01). Participants with moderate to heavy S. mansoni infection had lower triglycerides, LDL-cholesterol and diastolic blood pressure levels. Conclusions Helminth infections improve lipid profiles and may lower blood pressure. Further studies to confirm causality and investigate mechanisms will contribute to understanding the epidemiological transition and may suggest new approaches to prevent cardiometabolic disease. Clinical trials registration ISRCTN47196031

BackgroundThe Hygiene Hypothesis proposes that infection exposure protects against inflammatory conditions. Helminths possess allergen-like molecules and may specifically modulate allergy-related immunological pathways to inhibit responses which protect against them. Mass drug administration is recommended for helminth-endemic communities to control helminth-induced pathology, but may also result in increased rates of inflammation-mediated diseases in resource-poor settings. Immunological studies integrated with implementation of helminth control measures may elucidate how helminth elimination contributes to ongoing epidemics of inflammatory diseases. We present the design of the Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA), a cluster-randomised trial evaluating the risks and benefits of intensive versus standard anthelminthic treatment for allergy-related diseases and other health outcomes.Methods/DesignThe setting is comprised of island fishing communities in Mukono district, Uganda. Twenty-six communities have been randomised in a 1:1 ratio to receive standard or intensive anthelminthic intervention for a three-year period. Baseline characteristics were collected immediately prior to intervention rollout, commenced in February 2013. Primary outcomes are reported wheeze in the past 12 months and atopy (skin prick test response and allergen-specific immunoglobulin (asIg) E concentration). Secondary outcomes are visible flexural dermatitis, helminth infections, haemoglobin, growth parameters, hepatosplenomegaly, and responses to vaccine antigens. The trial provides a platform for in-depth analysis of clinical and immunological consequences of the contrasting interventions.DiscussionThe baseline survey has been completed successfully in a challenging environment. Baseline characteristics were balanced between trial arms. Prevalence of Schistosoma mansoni, hookworm, Strongyloides stercoralis and Trichuris trichiura was 52%, 23%, 13%, and 12%, respectively; 31% of Schistosoma mansoni infections were heavy (>400 eggs/gram). The prevalence of reported wheeze and positive skin prick test to any allergen was 5% and 20%, respectively. Respectively, 77% and 87% of participants had Dermatophagoides- and German cockroach-specific IgE above 0.35 kUA/L. These characteristics suggest that the LaVIISWA study will provide an excellent framework for investigating beneficial and detrimental effects of worms and their treatment, and the mechanisms of such effects.Trial registrationThis trial was registered with Current Controlled Trials (identifier: ISRCTN47196031) on 7 September 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0702-5) contains supplementary material, which is available to authorized users.

BackgroundParasitic helminths are potent immunomodulators and chronic infections may protect against allergy‐related disease and atopy. We conducted a cross‐sectional survey to test the hypothesis that in heavily helminth‐exposed fishing villages on Lake Victoria, Uganda, helminth infections would be inversely associated with allergy‐related conditions.MethodsA household survey was conducted as baseline to an anthelminthic intervention trial. Outcomes were reported wheeze in last year, atopy assessed both by skin prick test (SPT) and by the measurement of allergen‐specific IgE to dust mites and cockroach in plasma. Helminth infections were ascertained by stool, urine and haemoparasitology. Associations were examined using multivariable regression.ResultsTwo thousand three hundred and sixteen individuals were surveyed. Prevalence of reported wheeze was 2% in under‐fives and 5% in participants ≥5 years; 19% had a positive SPT; median Dermatophagoides‐specific IgE and cockroach‐specific IgE were 1440 and 220 ng/ml, respectively. S. mansoni, N. americanus, S. stercoralis, T. trichiura, M. perstans and A. lumbricoides prevalence was estimated as 51%, 22%, 12%, 10%, 2% and 1%, respectively. S. mansoni was positively associated with Dermatophagoides‐specific IgE [adjusted geometric mean ratio (aGMR) (95% confidence interval) 1.64 (1.23, 2.18)]; T. trichiura with SPT [adjusted odds ratio (aOR) 2.08 (1.38, 3.15)]; M. perstans with cockroach‐specific IgE [aGMR 2.37 (1.39, 4.06)], A. lumbricoides with wheeze in participants ≥5 years [aOR 6.36 (1.10, 36.63)] and with Dermatophagoides‐specific IgE [aGMR 2.34 (1.11, 4.95)]. No inverse associations were observed.ConclusionsContrary to our hypothesis, we found little evidence of an inverse relationship between helminths and allergy‐related outcomes, but strong evidence that individuals with certain helminths were more prone to atopy in this setting.

Despite reductions in S. mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy, allergy-related disease or helminth-related pathology. This could be due to sustained low-intensity infections, thus a causal link between helminths and allergy outcomes cannot be discounted. Intensive community-based MDA has limited impact in high-schistosomiasis-transmission fishing communities, in the absence of other interventions.

Background Nucleic acid amplification tests (NAATs) are increasingly being used as diagnostic tools for soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Ancylostoma duodenale and A. ceylanicum), Strongyloides stercoralis and Schistosoma in human stool. Currently, there is a large diversity of NAATs being applied, but an external quality assessment scheme (EQAS) for these diagnostics is lacking. An EQAS involves a blinded process where test results reported by a laboratory are compared to those reported by reference or expert laboratories, allowing for an objective assessment of the diagnostic performance of a laboratory. In the current study, we piloted an international EQAS for these helminths (i) to investigate the feasibility of designing and delivering an PLOS NEGLECTED TROPICAL DISEASES