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Uncertainty surrounding projections of the long-term impact of ivermectin treatment on human onchocerciasis.

ABSTRACT: Recent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual) ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci. Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach elimination. A crucial assumption has been that microfilarial production by Onchocerca volvulus is reduced irreversibly by 30-35% with each (annual) ivermectin round. However, other modelling-based analyses suggest that ivermectin may not have such a cumulative effect. Uncertainty in this (biological) and other (programmatic) assumptions would affect projected outcomes of long-term ivermectin treatment.We modify a deterministic age- and sex-structured onchocerciasis transmission model, parameterised for savannah O. volvulus-Simulium damnosum, to explore the impact of assumptions regarding the effect of ivermectin on worm fertility and the patterns of treatment coverage compliance, and frequency on projections of parasitological outcomes due to long-term, mass ivermectin administration in hyperendemic areas. The projected impact of ivermectin distribution on onchocerciasis and the benefits of switching from annual to biannual distribution are strongly dependent on assumptions regarding the drug's effect on worm fertility and on treatment compliance. If ivermectin does not have a cumulative impact on microfilarial production, elimination of onchocerciasis in hyperendemic areas may not be feasible with annual ivermectin distribution.There is substantial (biological and programmatic) uncertainty surrounding modelling projections of onchocerciasis elimination. These uncertainties need to be acknowledged for mathematical models to inform control policy reliably. Further research is needed to elucidate the effect of ivermectin on O. volvulus reproductive biology and quantify the patterns of coverage and compliance in treated communities.

SUBMITTER: Turner HC

PROVIDER: S-EPMC3636241 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Uncertainty surrounding projections of the long-term impact of ivermectin treatment on human onchocerciasis.

Turner Hugo C HC Churcher Thomas S TS Walker Martin M Osei-Atweneboana Mike Y MY Prichard Roger K RK Basáñez María-Gloria MG

PLoS neglected tropical diseases 20130425 4

<h4>Background</h4>Recent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual) ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci. Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach elimination. A crucial assumption has been that microfilarial production by Onchocerca volvulus is reduced irreversibly by 30-35% with each (annual) ivermectin round. However, oth ...[more]

PMID: 23634234

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Project description:Control of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age children living in endemic areas. There is limited data on the effectiveness of long-term periodic anthelmintic treatment on the prevalence of STHs, particularly from operational programmes. The current study investigated the impact of 15 to 17 years of treatment with the broad-spectrum anthelmintic ivermectin, used for the control of onchocerciasis, on STH prevalence and intensity in school-age and pre-school children.A cross-sectional study was conducted in communities that had received annual or twice-annual ivermectin treatments and geographically adjacent communities that had not received treatment in two districts of Esmeraldas Province in Ecuador. Stool samples were collected from school-age children and examined for STH infection using the Kato-Katz and formol-ether concentration methods. Samples were collected also from pre-school children and examined by the formol-ether concentration method. Data on risk factors for STH infection were collected by parental questionnaire. We sampled a total of 3,705 school-age children (6-16 years) from 31 treated and 27 non-treated communities, and 1,701 pre-school children aged 0-5 years from 18 treated and 18 non-treated communities. Among school-age children, ivermectin treatment had significant effects on the prevalence (adjusted OR = 0.06, 95% CI 0.03-0.14) and intensity of Trichuris trichiura infection (adjusted RR = 0.28, 95% CI 0.11-0.70), but appeared to have no impact on Ascaris lumbricoides or hookworm infection. Reduced prevalence and intensities of T. trichiura infection were observed among children not eligible to receive ivermectina, providing some evidence of reduced transmission of T. trichiura infection in communities receiving mass ivermectin treatments.Annual and twice-annual treatments with ivermectin over a period of up to 17 years may have had a significant impact on T. trichiura infection. The present data indicate that the long-term control of onchocerciasis with ivermectin may provide additional health benefits by reducing infections with trichuriasis. The addition of a second anthelmintic drug such as albendazole may be useful for a long-term effect on A. lumbricoides infection.

Project description:BACKGROUND:Currently, the predominant onchocerciasis control strategy in Africa is annual mass drug administration (MDA) with ivermectin. However, there is a consensus among the global health community, supported by mathematical modelling, that onchocerciasis in Africa will not be eliminated within proposed time frameworks in all endemic foci with only annual MDA, and novel and alternative strategies are urgently needed. Furthermore, use of MDA with ivermectin is already compromised in large areas of central Africa co-endemic with Loa loa, and there are areas where suboptimal or atypical responses to ivermectin have been documented. An onchocerciasis vaccine would be highly advantageous in these areas. METHODOLOGY/PRINCIPAL FINDINGS:We used a previously developed onchocerciasis transmission model (EPIONCHO) to investigate the impact of vaccination in areas where loiasis and onchocerciasis are co-endemic and ivermectin is contraindicated. We also explore the potential influence of a vaccination programme on infection resurgence in areas where local elimination has been successfully achieved. Based on the age range included in the Expanded Programme on Immunization (EPI), the vaccine was assumed to target 1 to 5 year olds. Our modelling results indicate that the deployment of an onchocerciasis vaccine would have a beneficial impact in onchocerciasis-loiasis co-endemic areas, markedly reducing microfilarial load in the young (under 20 yr) age groups. CONCLUSIONS/SIGNIFICANCE:An onchocerciasis prophylactic vaccine would reduce the onchocerciasis disease burden in populations where ivermectin cannot be administered safely. Moreover, a vaccine could substantially decrease the chance of re-emergence of Onchocerca volvulus infection in areas where it is deemed that MDA with ivermectin can be stopped. Therefore, a vaccine would protect the substantial investments made by present and past onchocerciasis control programmes, decreasing the chance of disease recrudescence and offering an important additional tool to mitigate the potentially devastating impact of emerging ivermectin resistance.

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Project description:BACKGROUND:Many studies have reported an association between epilepsy, nodding syndrome (NS), and onchocerciasis (river blindness). A high prevalence of epilepsy has been noted particularly in onchocerciasis hyperendemic areas where onchocerciasis is not or insufficiently controlled with mass ivermectin distribution. There is evidence that increasing the coverage of ivermectin reduces the incidence of epilepsy, and anecdotal evidence suggests a reduction in seizure frequency in onchocerciasis-associated epilepsy (OAE) patients who receive ivermectin. Finding an alternative treatment for epilepsy in these patients will have major consequences. OBJECTIVE:The goal of the study is to assess whether ivermectin treatment decreases the frequency of seizures and leads to seizure freedom in OAE patients, including patients with NS. If we are able to demonstrate such an effect, this would strengthen the argument that onchocerciasis is causing epilepsy and therefore we should increase our efforts to eliminate onchocerciasis. METHODS:We will conduct a randomized clinical trial in the Democratic Republic of Congo to compare seizure freedom in onchocerciasis-infested epilepsy patients who receive immediate ivermectin treatment with delayed (after 4 months) ivermectin treatment. All participants will simultaneously receive antiepilepsy drugs (AEDs) according to local guidelines for epilepsy treatment. The primary endpoint is seizure freedom defined as no seizures during the 4 month of follow-up. Secondary endpoint is significant (>50%) seizure reduction compared to baseline seizure frequency. Reduction of seizures will be compared between ivermectin and nonivermectin arms. RESULTS:Start of enrollment is planned for August 2017, and we expect to have enrolled all 110 participants by December 2017. Results are expected in June 2018. CONCLUSIONS:If ivermectin treatment in addition to AEDs is able to lead to seizure freedom or significantly reduces seizure frequency in OAE patients, this will have major consequences for epilepsy treatment in onchocerciasis-endemic regions. Ivermectin is donated for free and in non Loa-Loa-endemic regions has negligible side effects. Reducing the burden of epilepsy will have a major impact on quality of life and socioeconomic status of families with affected members in Africa. TRIAL REGISTRATION:ClinicalTrials.gov NCT03052998; https://clinicaltrials.gov/ct2/show/NCT03052998 (Archived by WebCite at http://www.webcitation.org/6roFVQSG0).

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Uncertainty surrounding projections of the long-term impact of ivermectin treatment on human onchocerciasis.

Publications

Uncertainty surrounding projections of the long-term impact of ivermectin treatment on human onchocerciasis.

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