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.

How Outreach Training and Supportive Supervision (OTSS) Affect Health Facility Readiness and Health-Care Worker Competency to Prevent and Treat Malaria in Niger: A Secondary Analysis of OTSS Data.

The quality of health services is key to the goal of averting morbidity and mortality from malaria. From July 2020 to August 2021, PMI Impact Malaria supported the implementation of four rounds of Outreach Training and Supportive Supervision (OTSS) in 12 health districts in the two regions of Niger: Dosso and Tahoua. Through OTSS, trained supervisors conducted onsite visits to observe an average of 174 healthcare workers (HCWs) per round in 96 public primary health facilities, managing persons with fever or conducting antenatal care (ANC) consultations, and then provided instant and individualized feedback and onsite training. Data from health facility readiness, case management, and malaria in pregnancy (MiP) checklists across the four rounds were analyzed using Wilcoxon's and the χ2 tests. These analyses highlighted improved facility readiness, including an increased likelihood that HCWs had received classroom training, and facilities had increased availability of guidelines and algorithms by round 4 compared with round 1. Median HCW performance scores showed an improvement in the correct performance and interpretation of malaria rapid diagnostic tests, in classification of malaria as uncomplicated or severe, and in the management of uncomplicated malaria across the four rounds. For MiP services, malaria prevention and the management of pregnant women with malaria also improved from round 1 to round 4. These findings provide further evidence that OTSS can achieve rapid improvements in health facility readiness and HCW competency in managing outpatients and ANC clients.

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.

Evaluating the impact of biannual school-based and community-wide treatment on urogenital schistosomiasis in Niger.

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinated a five-year study implemented in several countries, including Niger, to provide an evidence-base for programmatic decisions regarding cost-effective approaches to preventive chemotherapy for schistosomiasis control. METHODS: This was a cluster-randomised trial investigating six possible combinations of annual or biannual community-wide treatment (CWT), school-based treatment (SBT), and holidays from mass treatment over four years. The most intense arm involved two years of annual CWT followed by 2 years of biannual CWT, while the least intensive arm involved one year of annual SBT followed by a year without treatment and two more years of annual SBT. The primary outcome of interest was prevalence and intensity of Schistosoma haematobium among 100 children aged 9-12 years sampled each year. In addition, 100 children aged 5-8 years in their first year of school and 50 adults (aged 20-55 years) were tested in the first and final fifth year of the study. RESULTS: In total, data were collected from 167,500 individuals across 225 villages in nine districts within the Niger River valley, Western Niger. Overall, the prevalence of S. haematobium decreased from baseline to Year 5 across all study arms. The relative reduction of prevalence was greater in biannual compared with annual treatment across all arms; however, the only significant difference was seen in areas with a high starting prevalence. Although adults were not targeted for treatment in SBT arms, a statistically significant decrease in prevalence among adults was seen in moderate prevalence areas receiving biannual (10.7% to 4.8%) SBT (P < 0.001). Adults tested in the annual SBT group also showed a decrease in prevalence between Year 1 and Year 5 (12.2% to 11.0%), but this difference was not significant. CONCLUSIONS: These findings are an important consideration for schistosomiasis control programmes that are considering elimination and support the idea that scaling up the frequency of treatment rounds, particularly in areas of low prevalence, will not eliminate schistosomiasis. Interestingly, the finding that prevalence decreased among adults in SBT arms suggests that transmission in the community can be reduced, even where only school children are being treated, which could have logistical and cost-saving implications for the national control programmes.

Assessing the Health Impact of the following Measures in Schools in Maradi (Niger): Construction of Latrines, Clean Water Supply, Establishment of Hand Washing Stations, and Health Education.

Objective. To assess the effect on health of the following measures in schools in Maradi (Niger): clean water supply, construction of latrines, establishment of hand washing stations, and health education. Methodology. It was a "before and after" intervention study on a sample of school children aged 7 to 12 years in the Maradi region. The interventions included building of latrines, supplying clean water, setting up hand washing stations, and teaching health education lessons. An individual questionnaire, analysis of stool samples, and a group questionnaire were administered to children and teachers, respectively. The threshold for significance was set at P < 0.05. Results. A statistically significant reduction in cases of diarrhoea and abdominal pains was noted after the project. Overall, carriage of at least one parasite increased from 7.5% before the project to 10.2% after it (P = 0.04). In the programme group schools, there was a statistically significant increase in the prevalence of Hymenolepis nana, from 0 to 1.9 (P = 0.02). Pinworm prevalence remained stable in this group but increased significantly in the control group. Conclusions. Putting health infrastructure in place in schools obviously had an impact on hygiene-related habits in the beneficiary schools and communities.

Significant sequelae after bacterial meningitis in Niger: a cohort study.

BACKGROUND: Beside high mortality, acute bacterial meningitis may lead to a high frequency of neuropsychological sequelae. The Sahelian countries belonging to the meningitis belt experience approximately 50% of the meningitis cases occurring in the world. Studies in Africa have shown that N. meningitidis could cause hearing loss in up to 30% of the cases, exceeding sometimes measles. The situation is similar in Niger which experiences yearly meningitis epidemics and where rehabilitation wards are rare and hearing aids remain unaffordable. The aim of this study was to estimate the frequency of neuropsychological sequelae after acute bacterial meningitis in four of the eight regions of Niger. METHODS: Subjects exposed to acute bacterial meningitis were enrolled into a cohort with non exposed subjects matched on age and gender. Consenting subjects were interviewed during inclusion and at a control visit two months later. If clinical symptoms or psychological troubles persisted at both visits among the exposed subjects with a frequency significantly greater than that observed among the non exposed subjects, a sequelae was retained. The comparison of the frequency of sequelae between non exposed and exposed subjects to bacterial meningitis was also calculated using the Fisher exact test. RESULTS: Three persisting functional symptoms were registered: headaches, asthenia, and vertigo among 31.3, 36.9, and 22.4% respectively of the exposed subjects. A significant motor impairment was retrieved among 12.3% of the exposed versus 1.6% of the non exposed subjects. Hearing loss significantly disabled 31.3% of the exposed subjects and 10.4% exhibited a serious deafness. CONCLUSIONS: This study carried out in Niger confirms two serious neurological sequelae occurring at high frequencies after bacterial meningitis: severe and profound hearing loss and motor impairment. Cochlear implantation and hearing aids are too expensive for populations living in developing countries. Neurological sequelae occurring after meningitis should sensitize African public health authorities on the development of rehabilitation centers. All these challenges can be met through existing strategies and guidelines.

Controlling schistosomiasis: significant decrease of anaemia prevalence one year after a single dose of praziquantel in Nigerian schoolchildren.

BACKGROUND: In the framework of the monitoring and evaluation of the Nigerian schistosomiasis and soil-transmitted helminth control programme, a follow-up of children took place in eight sentinel sites. The objective of the study was to assess the evolution of Schistosoma haematobium infection and anaemia in schoolchildren after a single administration of praziquantel (PZQ) and albendazole. METHODS/PRINCIPAL FINDINGS: Pre-treatment examination and follow-up at one year post-treatment of schoolchildren aged 7, 8, and 11 years, including interview, urine examination, ultrasound examination of the urinary tract, and measurement of haemoglobin. Before treatment, the overall prevalence of S. heamatobium infection was 75.4% of the 1,642 enrolled children, and 21.8% of children excreted more than 50 eggs/10 ml urine. Prevalence increased with age. The overall prevalence of anaemia (haemoglobin <11.5 g/dl) was 61.6%, decreasing significantly with increasing age. The mean haemoglobinemia was 11 g/dl. In bivariate analysis, anaemia was significantly more frequent in children infected with S. haematobium, although it was not correlated to the intensity of infection. Anaemia was also associated with micro-haematuria and to kidney distensions. In a sub-sample of 636 children tested for P. falciparum infection, anaemia was significantly more frequent in malaria-infected children. In multivariate analysis, significant predictors of anaemia were P. falciparum infection, kidney distension, and the village. One year after a single-dose praziquantel treatment (administered using the WHO PZQ dose pole) co-administered with albendazole (400 mg single dose) for de-worming, the prevalence of S. haematobium infection was 38%, while the prevalence of anaemia fell to 50.4%. The mean haemoglobinemia showed a statistically significant increase of 0.39 g/dl to reach 11.4 g/dl. Anaemia was no longer associated with S. haematobium or to P. falciparum infections, or to haematuria or ultrasound abnormalities of the urinary tract. CONCLUSIONS: The high prevalence of anaemia in Nigerian children is clearly a result of many factors and not of schistosomiasis alone. Nevertheless, treatment of schistosomiasis and de-worming were followed by a partial, but significant, reduction of anaemia in schoolchildren, not explainable by any other obvious intervention.

Emergence of Schistosoma mansoni in the Niger River valley, Niger.

Urinary and intestinal schistosomiasis are both endemic in Niger with a dominance of Schistosoma haematobium. This study pointed out the appearance of the infection to S. mansoni in the Niger River valley, where it was until then unknown in Niger. In one year the prevalence increased from 5.9 to 19.5%.