Countrywide insecticide resistance monitoring and first report of the presence of the L1014S knock down resistance in Niger, West Africa.

BACKGROUND: Mass distribution of insecticide-treated nets (ITNs) is the principal malaria vector control strategy adopted by Niger. To better inform on the most appropriate ITN to distribute, the National Malaria Control Programme (NMCP) of Niger and its partners, conducted insecticide resistance monitoring in selected sites across the country. METHODS: The susceptibility of Anopheles gambiae sensu lato (s.l.) to chlorfenapyr and pyrethroid insecticides was investigated in a total of sixteen sites in 2019 and 2020, using 2-5-day-old adults reared from wild collected larvae per site. The susceptibility status, pyrethroid resistance intensity at 5 and 10 times the diagnostic concentrations, and piperonyl butoxide (PBO) synergism with diagnostic concentrations of deltamethrin, permethrin and alpha-cypermethrin were assessed using WHO bioassays. Two doses (100 and 200 µg/bottle) of chlorfenapyr were tested using the CDC bottle assay method. Species composition and allele frequencies for knock-down resistance (kdr-L1014F and L1014S) and acetylcholinesterase (ace-1 G119S) mutations were further characterized using polymerase chain reaction (PCR). RESULTS: High resistance intensity to all pyrethroids tested was observed in all sites except for alpha-cypermethrin in Gaya and Tessaoua and permethrin in Gaya in 2019 recording moderate resistance intensity. Similarly, Balleyara, Keita and Tillabery yielded moderate resistance intensity for alpha-cypermethrin and deltamethrin, and Niamey V low resistance intensity against deltamethrin and permethrin in 2020. Pre-exposure to PBO substantially increased susceptibility with average increases in mortality between 0 and 70% for tested pyrethroids. Susceptibility to chlorfenapyr (100 µg/bottle) was recorded in all sites except in Tessaoua and Magaria where susceptibility was recorded at the dose of 200 µg/bottle. Anopheles coluzzii was the predominant malaria vector species in most of the sites followed by An. gambiae sensu stricto (s.s.) and Anopheles arabiensis. The kdr-L1014S allele, investigated for the first time, was detected in the country. Both kdr-L1014F (frequencies [0.46-0.81]) and L1014S (frequencies [0.41-0.87]) were present in all sites while the ace-1 G119S was between 0.08 and 0.20. CONCLUSION: The data collected will guide the NMCP in making evidence-based decisions to better adapt vector control strategies and insecticide resistance management in Niger, starting with mass distribution of new generation ITNs such as interceptor G2 and PBO ITNs.

[Comparison of the therapeutic efficiency and of the tolerance of the artemether-lumefantrine and artesunate-amodiaquine combination in Niger]. / Comparaison de l'efficacite therapeutique et de la tolerance des combinaisons artemether-lumefantrine et artesunate-amodiaquine au Niger.

Malaria is a major public health problem in Niger. The Global Fund to fight AIDS, Tuberculosis, and Malaria launched, in 2011, an initiative entitled "Affordable Medicines Facility - Malaria" or AMFm which aims to make artemisinin-based combination therapies (ACT) more available, more accessible and to eliminate the development of artemisinin resistance. It is in this context that we have conducted a randomized comparative double open-arm study of the efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (AM) in Gaya.The objective of the study is to evaluate and then to compare the efficiency and tolerance to these two combinations. The study was modeled with the WHO 2003, 28 days protocol.370 febrile patients were examined. 159 patients were included, where 79 (49.4%) were put in the AL arm and 81 (50.6%) were placed in the AM arm. The adequate clinical and parasitological response was 94.8% and 97.1% respectively for AL and AM. There was no statistical significant difference in efficiency between the two therapies (P=0.4). This difference in adverse effects was not statistically significant (P=0.18). Artemether-lumefantrine and artesunate-amodiaquine are two combinations with comparable efficacies and safety.

Le paludisme est un problème majeur de santé publique au Niger. Le Fonds Mondial de la lutte contre le sida, la tuberculose et le paludisme a lancé en 2011 une initiative appelée « Affordable Medecines Facility - Malaria" ou AMFm qui vise à rendre les combinaisons thérapeutiques à base d'artémisinine (CTA) plus disponibles, plus accessibles et de lutter contre la résistance à l'artémisinine. C'est dans ce contexte que nous avons mené une étude comparative, randomisée, à deux bras ouverts de l'efficacité thérapeutique des associations artémether-luméfantrine (AL) et artésunate-amodiaquine (AM) au niveau du site sentinelle de Gaya.L'objectif de l'étude est d'évaluer puis de comparer l'efficacité et la tolérance de ces deux CTA. La méthode utilisée est le protocole OMS/2003 avec le suivi de 28 jours.370 patients fébriles ont été examinés. 159 patients ont été inclus dont 79 (49.4%) pour le bras AL et 80 (50.3%) pour le bras AM. La réponse clinique et parasitologique adéquate est respectivement de 94.8% pour AL et 97.1% AM. Il n'y a pas de différence statistiquement significative d'efficacité entre les deux molécules (P=0.4). Il n'y a pas aussi de différence statistiquement significative d'effet secondaire entre les deux molécules (P=0.18). AL et AM sont d'efficacité et de tolérance comparables.