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Human Direct Skin Feeding versus Membrane Feeding to Assess the Mosquitocidal Efficacy of High-Dose Ivermectin (IVERMAL Trial)

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Smit, Menno ORCID: https://orcid.org/0000-0003-3405-6638, Ochomo, Eric O, Aljayyoussi, Ghaith, Kwambai, Titus, Abong’o, Bernard O, Bousema, Teun, Waterhouse, David, Bayoh, Nabie M, Gimnig, John E, Samuels, Aaron M, Desai, Meghna R, Phillips-Howard, Penelope ORCID: https://orcid.org/0000-0003-1018-116X, Kariuki, Simon K, Wang, Duolao ORCID: https://orcid.org/0000-0003-2788-2464, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 and terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617 (2019) 'Human Direct Skin Feeding versus Membrane Feeding to Assess the Mosquitocidal Efficacy of High-Dose Ivermectin (IVERMAL Trial)'. Clinical Infectious Diseases.

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Abstract

Background
Ivermectin is being considered for mass-drug-administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. In a recent trial, 3-day courses of 300 and 600 mcg/kg/day were shown to kill Anopheles mosquitoes for at least 28 days post-treatment when fed patients’ venous blood using membrane-feeding-assays. Direct-skin-feeding on humans may lead to higher mosquito-mortality as ivermectin capillary-concentrations are higher. We compared mosquito-mortality following direct-skin- and membrane-feeding.
Methods
We conducted a mosquito feeding study nested within a randomized, double-blind, placebo-controlled trial of 141 adults with uncomplicated malaria in Kenya comparing 3-day ivermectin 0 (n=46), 300 (n=48), or 600 mcg/kg/day (n=47), co-administered with dihydroartemisinin-piperaquine. On post-treatment day-7, direct-skin and membrane-feeding assays were conducted using laboratory-reared Anopheles gambiae s.s.. Mosquito survival was assessed daily for 28-days-post-feeding.
Results
Between July-20–2015 and May-7-2016, 69 of 141 patients participated in both direct-skin- and membrane-feeding (placebo n=23, 300mcg/kg/day n=24, 600mcg/kg/day n=22). The 14-day-post-feeding mortality for mosquitoes fed on blood 7-days post-treatment from patients in both ivermectin arms pooled was similar with direct-skin-feeding (n=2,941 mosquitoes) versus membrane-feeding (n=7,380 mosquitoes): cumulative-mortality (RR=0.99, 0.95–1.03, p=0.69) and survival-time (HR=0.96, 0.91–1.02, p=0.19). Results were consistent by sex, body-mass-index, and across the range of ivermectin capillary concentrations studied (0.72–73.9 ng/mL).
Conclusions
Direct-skin-feeding and membrane-feeding on day 7 resulted in similar mosquitocidal-effects of ivermectin across a wide range of drug-concentrations, suggesting that the mosquitocidal-effects seen with membrane-feeding accurately reflect those of natural-biting. Membrane-feeding, which is more patient-friendly and ethically acceptable, can likely reliably be used to assess ivermectin’s mosquitocidal-efficacy.

Item Type: Article
Subjects: QV Pharmacology > QV 38 Drug action.
QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes
QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
QX Parasitology > Insects. Other Parasites > QX 650 Insect vectors
WA Public Health > Preventive Medicine > WA 240 Disinfection. Disinfestation. Pesticides (including diseases caused by)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1093/cid/ciy1063
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 02 Jan 2019 10:50
Last Modified: 24 Apr 2019 08:52
URI: https://archive.lstmed.ac.uk/id/eprint/9916

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