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Non-target effects of ivermectin mass drug administration designed for malaria on human ectoparasitoses in Kenya and Mozambique

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Universitat de Barcelona. Facultat de Medicina i Ciències de la Salut

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[eng] INTRODUCTION: Ectoparasitic diseases such as scabies, tungiasis, headlice and bedbugs are widespread globally, and tend to be more prevalent in resource-poor settings and in vulnerable populations. Limited treatment options are available. Similar populations are affected by malaria. Ivermectin MDA for malaria vector control is currently being evaluated, and given the known effects of ivermectin against ectoparasites, this intervention may have secondary effects on ectoparasitic diseases. Several large-scale observational studies that have already demonstrated the efficacy of ivermectin MDA against scabies. One study has also demonstrated an effect of ivermectin MDA against headlice. Small-scale studies have suggested that ivermectin has effects against tungiasis and bedbugs; however, the impact of ivermectin MDA is less clear. In addition to the potential positive effects of ivermectin MDA for malaria, it is important to consider that the intervention may have negative impacts on non-target ectoparasitic diseases, such as the development of resistance.
OBJECTIVES: The general objective of this thesis was to explore the secondary effects of ivermectin MDA designed for malaria on human ectoparasitic diseases in two sub-Saharan African settings. The specific objectives of the thesis were to assess the specificity and sensitivity of the diagnosis of scabies by non-expert fieldworkers; to assess the effect of ivermectin MDA designed for malaria on scabies, headlice, tungiasis and bed bugs; and to explore potential unintended effects of ivermectin MDA for malaria on ectoparasitic resistance.

METHODS:

In order to validate our scabies outcome assessment method (Objective 1), we conducted a diagnostic accuracy study to determine the specificity and sensitivity of scabies assessments made by minimally trained fieldworkers. We trained field-workers with a minimum of secondary school education in the diagnosis of scabies. After the training, we assessed the diagnostic accuracy of assessments made by nine field-workers compared with the reference standard. 193 participants were assessed for scabies. To assess the efficacy of ivermectin MDA on scabies, headlice and tungiasis (Objective 2)., we conducted two cluster-randomized controlled trials in Mopeia, Mozambique and in Kwale, Kenya. A single dose of ivermectin was given monthly to eligible humans or humans and livestock (humans: 400 µg/kg, livestock: 1% injectable 200 µg/kg) in 3 consecutive months during the rainy season. The control group received 400mg albendazole (humans only). The humans and livestock arm was only present in Mozambique. In Mozambique, 39 clusters (13 per arm) were randomly selected for the nested assessment of headlice and scabies prevalence, and treated participants were followed up at, 1, 2 and 3 months and untreated (ineligible) participants were followed up at 3 and 6 months after baseline. The primary outcome was scabies prevalence at 3 months, determined by clinical history and examination of exposed skin. Headlice and tungiasis diagnoses were determined by examination of the scalp and feet, respectively. The presence of bedbugs was determined by a questionnaire. Data were analysed using a logistic regression model with a GEE (Generalised Estimating Equation) approach. We also conducted a laboratory study in which field-collected bed bugs were exposed to ivermectin-treated blood, and mortality and oviposition rates were recorded. Finally, to explore ectoparasite resistance mechanisms (Objective 3), a search was conducted in relevant databases, using terms related to ivermectin, human and veterinary ectoparasites, and resistance. Abstracts (5893) were screened, and data on the study organism, the type of resistance, the analysis methods, and, where applicable, the gene loci of interest were extracted.

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[cat] INTRODUCCIÓ:

Les malalties ectoparasitàries, com la sarna, la tungiasi, els polls i les xinxes estan ampliament esteses arreu del món i tendeixen a ser més freqüents en entorns amb pocs recursos i en poblacions vulnerables. Les opcions terapèutiques disponibles són limitades. Poblacions similars també es veuen afectades per la malària. Actualment, s'està avaluant l’administració massiva (MDA) de ivermectina per al control del vector de la malària, i atès que la ivermectina té efectes coneguts contra els ectoparàsits, aquesta intervenció pot tenir efectes secundaris sobre les malalties ectoparasitàries. Diversos estudis observacionals a gran escala ja han demostrat l'eficàcia de la MDA d’ivermectina contra la sarna. Un estudi també ha demostrat un efecte de la MDA d’ivermectina contra els polls. Estudis a petita escala han suggerit que la ivermectina té efectes contra la tungiasi i les xinxes; tanmateix, l'impacte de la MDA d’ivermectina sobre aquestes malalties és menys clar. A més dels possibles efectes beneficiosos de laMDA d’ivermectina per a la malària, és important tenir en compte que aquesta intervenció pot tenir impactes negatius en malalties ectoparasitàries no diana, com ara el desenvolupament de resistència.
OBJECTIUS:

L'objectiu general d'aquesta tesi és explorar els efectes secundaris de la MDA d’ivermectina dissenyada per a la malària sobre malalties ectoparasitàries humanes en dos entorns de l'Àfrica subsahariana. Els objectius específics de la tesi són avaluar l'especificitat i la sensibilitat del diagnòstic de la sarna per part de treballadors de camp mínimament formats; avaluar l'efecte de la MDA d’ivermectina dissenyada per a la malària sobre la sarna, els polls, la tungiasi i les xinxes; i explorar els possibles efectes no desitjats de la MDA d’ivermectina per a la malària sobre la resistència als ectoparàsits.

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(c) Furnival-Adams, Joanna Elena Claire, 2025

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Tesis Doctorals - Facultat - Medicina i Ciències de la Salut

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Non-target effects of ivermectin mass drug administration designed for malaria on human ectoparasitoses in Kenya and Mozambique