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.

Identifying and characterizing high-risk populations in pilot malaria elimination districts in Madagascar: a mixed-methods study.

BACKGROUND: In Madagascar, the districts of Antsirabe II, Faratsiho and Antsiranana I have relatively low malaria incidence rates and have been selected by the National Malaria Control Programme for pilot elimination strategies. The districts have residual transmission despite increasing coverage and quality of malaria services. This study sought to identify priority subpopulations at highest risk for malaria and collect information on intervention preferences and methods that will inform subnational tailoring of malaria service delivery. METHODS: This mixed methods study employed (i) a quantitative malaria risk factor assessment in Antsirabe II and Faratsiho comprising a test-negative frequency matched case-control study and a qualitative risk factor assessment in Antsiranana I; and (ii) a qualitative formative assessment in all three districts. For the case-control study, a mixed effects logistic regression was used with age, sex and district included as fixed effects and health facility included as a random effect. The qualitative risk factor assessment used semi-structured interview guides and key informant interviews. For the qualitative formative assessment in the three districts, a summary report was generated following semi-structured interviews and focus group discussions with high-risk populations (HRPs) and stakeholders. RESULTS: In Antsirabe II and Faratsiho districts, rice agriculture workers, outdoor/manual workers, particularly miners, and those with jobs that required travel or overnight stays, especially itinerant vendors, had higher odds of malaria infection compared to other (non-rice) agricultural workers. In Antsiranana I, respondents identified non-rice farmers, mobile vendors, and students as HRPs. Risk factors among these groups included overnight stays and travel patterns combined with a lack of malaria prevention tools. HRPs reported treatment cost and distance to the health facility as barriers to care and expressed interest in presumptive treatment and involvement of gatekeepers or people who have influence over intervention access or participation. CONCLUSIONS: The study results illustrate the value of in-depth assessments of risk behaviours, access to services and prevention tools, surveillance and prevention strategies, and the involvement of gatekeepers in shaping subnational tailoring to reach previously unreached populations and address residual transmission in elimination settings.

Experiences in Improving the Quality of Community-Based Fever Management from Three Malaria-Endemic African Countries.

The WHO affirms that trained, supervised, and supported community health workers (CHWs) can deliver high-quality health services effectively and has called for documentation of enabling factors, needs, and implementation strategies of successful CHW programs. In response, the U.S. President's Malaria Initiative Impact Malaria Project conducted a study to document implementation approaches, best practices, and lessons learned for quality improvement (QI) of community-based fever management in Madagascar, Malawi, and Mali. The team conducted 10 key informant interviews (KIIs) with individuals at national, regional, and district levels using an open-ended interview guide tailored to each level, and a desk review of documents and materials related to community-based QI. Each country's community health landscape and QI approaches were summarized into four categories identified during the KIIs (training, supervision, coaching/mentoring, and review meetings) and compared. Results found that Madagascar, Malawi, and Mali all had well-defined community health strategies that include QI, but countries could not extend their full package of community-based QI approaches to all CHWs as a result of limited human and financial resources. Vertical funding for health programs limits the scope and coverage of QI approaches, especially at the community level. Recommendations from key informants for strengthening community-based QI included integrating QI approaches to improve cost efficiency, to define roles and responsibilities more clearly, to engage communities and all health system levels in implementation, and to digitize QI tools. Increased financial and skilled human resources are needed for community-based QI activities to achieve their intended effect.

Clinical Outreach Training and Supportive Supervision Quality-of-Care Analysis: Impact of Readiness Factors on Health Worker Competencies in Malaria Case Management in Cameroon, Mali, and Niger.

Improving the quality of malaria clinical case management in health facilities is key to improving health outcomes in patients. The U.S. President's Malaria Initiative Impact Malaria Project has supported implementation of the Outreach Training and Supportive Supervision (OTSS) approach in 11 African countries to improve the quality of malaria care in health facilities through the collection and analysis of observation-based data on health facility readiness and health provider competency in malaria case management. We conducted a secondary analysis of longitudinal data collected during routine supervision in Cameroon (April 2021-March 2022), Mali (October 2020-December 2021), and Niger (November 2020-September 2021) using digitized checklists to assess how service readiness affects health worker competencies in managing patients with fever correctly and providing those with confirmed uncomplicated malaria cases with appropriate treatment and referral. Linear or logistic regression analyses were conducted to assess the effect of facility readiness and its components on observed health worker competencies. All countries demonstrated significant associations between health facility readiness and malaria case management competencies. Data from three rounds of OTSS visits in Cameroon, Mali, and Niger showed a statistically significant positive association between greater facility readiness scores (including the availability of commodities, materials, and trained staff) and health worker competency in case management. These findings provide evidence that health worker performance is likely affected by the tools and training available to them. These results reinforce the need for necessary tools and properly trained staff if high-quality malaria case management services are to be delivered at health facilities.