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.
OBJECTIVESRecent reports suggest that Schistosoma infection may increase the risk of acquiring human immunodeficiency virus (HIV). We used data from a large cross-sectional study to investigate whether Schistosoma mansoni infection is associated with increased HIV prevalence.METHODSWe conducted a household survey of residents in island fishing communities in Mukono district, Uganda, between October 2012 and July 2013. HIV status was assessed using rapid test kits. Kato-Katz (KK) stool tests and urine-circulating cathodic antigen (CCA) were used to test for Schistosoma infection. Multivariable logistic regression, allowing for the survey design, was used to investigate the association between S. mansoni infection and HIV infection.RESULTSData from 1412 participants aged 13 years and older were analysed (mean age 30.3 years, 45% female). The prevalence of HIV was 17.3%. Using the stool Kato-Katz technique on a single sample, S. mansoni infection was detected in 57.2% (719/1257) of participants; urine CCA was positive in 73.8% (478/650) of those tested. S. mansoni infection was not associated with HIV infection. [KK (aOR = 1.04; 95% CI: 0.74–1.47, P = 0.81), CCA (aOR = 1.53; 95% CI: 0.78–3.00, P = 0.19)]. The median S. mansoni egg count per gram was lower in the HIV-positive participants (P = 0.005).CONCLUSIONSThese results add to the evidence that S. mansoni has little effect on HIV transmission, but may influence egg excretion.
Background Praziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas. Animal models demonstrate Schistosoma parasite resistance to praziquantel after repeated exposure. Methods We conducted a parasitological survey in 26 fishing communities in Uganda after 4 years of quarterly (13 communities) or annual (13 communities) praziquantel MDA, with Schistosoma infection detected by single-stool-sample Kato-Katz. A test of cure was done in participants who were positive on both urine circulating cathodic antigen test and 3-sample Kato-Katz. We calculated cure rates (CRs) and egg reduction rates (ERRs) based on 3-sample Kato-Katz and infection intensity using worm-specific circulating anodic antigen (CAA) in blood, comparing these between quarterly and annually treated participants. Results Single-sample Kato-Katz Schistosoma mansoni prevalence was 22% in 1,056 quarterly treated participants and 34% in 1,030 annually treated participants (risk ratio, 0.62; 95% confidence interval [CI], 0.40 to 0.94). Among 110 test-of-cure participants, CRs were 65% and 51% in annually and quarterly treated villages, respectively (odds ratio, 0.65; 95% CI, 0.27 to 1.58); ERRs were 94% and 81% (difference, –13%; 95% CI, –48% to 2%). There was no impact of quarterly vs annual praziquantel on S. mansoni by CAA. Conclusions In this schistosomiasis hot spot, there was little evidence of decreased praziquantel efficacy. However, in the absence of alternative therapies, there remains a need for continued vigilance of praziquantel efficacy in the MDA era.
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