Therapeutic efficacy and tolerability of artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Niger, 2020.

BACKGROUND: Monitoring therapeutic efficacy is important to ensure the efficacy of artemisinin-based combination therapy (ACT) for malaria. The current first-line treatment for uncomplicated malaria recommended by the National Malaria Control Program in Niger is artemether-lumefantrine (AL). In 2020, an in vivo study was carried out to evaluate clinical and parasitological responses to AL as well as the molecular resistance to the drug in three sentinel sites: Agadez, Tessaoua and Gaya, in Niger. METHODS: A multi-center, single-arm trial was conducted according to the 28-day World Health Organization (WHO) 2009 therapeutic efficacy study protocol. Children between 6 months and 15 years with confirmed uncomplicated Plasmodium falciparum infection and 1000-200,000 asexual parasites/µL of blood were enrolled and followed up for 28 days. Uncorrected and PCR-corrected efficacy results at day 28 were calculated, and molecular correction was performed by genotyping the msp1, msp2, and glurp genes. The pfk13, pfdhfr, pfdhps, pfcrt and pfmdr genes were analyzed by PCR and Sanger sequencing. The Kaplan-Meier curve assessed parasite clearance. RESULTS: A total of 255 patients were enrolled in the study. The adequate clinical and parasitological response after PCR correction was 98.9% (95% CI 96.4-101.0%), 92.2% (85.0-98.5%) and 97.1% (93.1-101.0%) in Gaya, Tessaoua and Agadez, respectively. No adverse events were observed. Ten mutations (SNP) were found, including 7 synonyms (K248K, G690G, E691E, E612E, C469C, G496G, P718P) and 3 non-synonyms (N594K, R255K, V714S). Two mutations emerged: N594K and V714S. The R255K mutation detected in Southeast Asia was also detected. The pfdhpsK540E and pfdhfrI164L mutations associated with high levels of resistance are absent. There is a reversal of chloroquine resistance. CONCLUSION: The study findings indicate that AL is effective and well tolerated for the treatment of uncomplicated malaria in three sites in Niger. The emergence of a pfk13 mutation requires additional testing such as the Ring Stage Assay and CRISPR/Cas9 to confirm the role of these emerging mutations. Trial registration NCT05070520, October 7, 2021.

Analysis of attitudes and practices influencing adherence to seasonal malaria chemoprevention in children under 5 years of age in the Dosso Region of Niger.

BACKGROUND: Seasonal malaria chemoprevention (SMC) consists of the intermittent administration of a 3 day course of anti-malarial medications during the months of highest malaria risk in the Sahel region, where malaria transmission is highly seasonal. SMC is an effective intervention to reduce episodes of uncomplicated and severe malaria in children. However, morbidity cannot be lowered without adherence to medications. The objective of this study was to examine SMC medication adherence and to identify the attitudes and practices of caregivers during the 2020 SMC campaign in the Dosso region. METHODS: This study was conducted based on data from independent monitoring using random cluster sampling. Adherence levels and the attitudes and practices of caregivers were evaluated using data from caregivers' self-reports and analysed according to Bernard Vrijens' taxonomy. RESULTS: At the initiation of treatment phase, 99% of children (N = 2296) received their first administration of medication, with 90% of caregivers (N = 1436) knowing that the medications help prevent malaria. However, only 56% of caregivers (N = 1856) reported that treatment initiation took place under direct observation by the distributor. At the implementation of treatment phase, 90% of children (N = 2132) took their medication on the second day and 84% (N = 1068) took it the third day. "Forgetting," "not having time," and "the mother's absence" were the main reasons caregivers gave to explain discontinuation of the 3 day course of medication. CONCLUSION: This simple, low-cost survey demonstrated that coverage of SMC and adherence by caregivers to completing the full 3 day medication course was high. The survey also showed that knowledge, attitudes, and practices of some caregivers regarding adherence to medications during the SMC campaign could be improved. Expanding distributors' training, developing and providing them with tools for interpersonal communication, and strengthening supervision could lead to even higher adherence.

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.

The use of video job-aids to improve the quality of seasonal malaria chemoprevention delivery.

Mobile phones are increasingly used in community health programmes, but the use of video job-aids that can be displayed on smart phones has not been widely exploited. We investigated the use of video job-aids to support the delivery of seasonal malaria chemoprevention (SMC) in countries in West and Central Africa. The study was prompted by the need for training tools that could be used in a socially distanced manner during the COVID-19 pandemic. Animated videos were developed in English, French, Portuguese, Fula and Hausa, illustrating key steps for administering SMC safely, including wearing masks, washing hands, and social distancing. Through a consultative process with the national malaria programmes of countries using SMC, successive versions of the script and videos were reviewed to ensure accurate and relevant content. Online workshops were held with programme managers to plan how to use the videos in SMC staff training and supervision, and the use of the videos was evaluated in Guinea through focus groups and in-depth interviews with drug distributors and other staff involved in SMC delivery and through direct observations of SMC administration. Programme managers found the videos useful as they reinforce messages, can be viewed at any time and repeatedly, and when used during training sessions, provide a focus of discussion and support for trainers and help retain messages. Managers requested that local specificities of SMC delivery in their setting be included in tailored versions of the video for their country, and videos were required to be narrated in a variety of local languages. In Guinea, SMC drug distributors found the video covered the all the essential steps and found the video easy to understand. However, not all key messages were followed as some of the safety measures, social distancing and wearing masks, were perceived by some as creating mistrust amongst communities. Video job-aids can potentially provide an efficient means of reaching large numbers of drug distributors with guidance for safe and effective distribution of SMC. Not all distributors use android phones, but SMC programmes are increasingly providing drug distributors with android devices to track delivery, and personal ownership of smartphones in sub-Saharan Africa is growing. The use of video job-aids for community health workers to improve the quality delivery of SMC, or of other primary health care interventions, should be more widely evaluated.

[Organization of a free mass distribution campaign of long-lasting insecticidal mosquito nets in the context of COVID-19 in Niger]. / Organisation d´une campagne de masse et gratuite de distribution des moustiquaires imprégnées d´insecticides à longue durée d´action dans le contexte de la COVID-19 au Niger.

Long-lasting insecticidal mosquito nets (LLIMNs) are needed for malaria vector control. However, their distribution is not yet optimal in sub-Saharan regions. According to projections, COVID-19 pandemic will further delay the distribution of LLIMNs. In Niger, a distribution campaign of LLIMNs with a multi-sectoral approach (state-partner-civil society) was organized in compliance with barrier measures for preventing transmission of COVID-19. A door-to-door strategy was chosen to implement this campaign, in order to avoid entry into confined spaces and to engage community. A total of 13,994,681 people received LLIMNs (reflecting a success rate of 101%) in six targeted regions. A collective effort is needed to sustain the fight against malaria in the COVID-19 era.