Ex vivo responses of Plasmodium falciparum clinical isolates to conventional and new antimalarial drugs in Niger.

Little is known about resistance of Plasmodium falciparum to antimalarials in Sahelian countries. Here we investigated the drug susceptibilities of fresh isolates collected in Niger post-deployment of artemisinin-based combination therapies (ACTs). We found that the parasites remained highly susceptible to new (dihydroartemisinin, lumefantrine, pyronaridine, and piperaquine) and conventional (amodiaquine and chloroquine) antimalarial drugs. The introduction of ACTs in 2005 and their further deployment nationwide have therefore not resulted in a decrease in P. falciparum susceptibilities to these antimalarials.

Contextual determinants of mass drug administration performance: Modelling fourteen years of lymphatic filariasis treatments in West Africa.

BACKGROUND: Effective mass drug administration (MDA) is the cornerstone in the elimination of lymphatic filariasis (LF) and a critical component in combatting all neglected tropical diseases for which preventative chemotherapy is recommended (PC-NTDs). Despite its importance, MDA coverage, however defined, is rarely investigated systematically across time and geography. Most commonly, investigations into coverage react to unsatisfactory outcomes and tend to focus on a single year and health district. Such investigations omit more macro-level influences including sociological, environmental, and programmatic factors. The USAID NTD database contains measures of performance from thousands of district-level LF MDA campaigns across 14 years and 10 West African countries. Specifically, performance was measured as an MDA's epidemiological coverage, calculated as persons treated divided by persons at risk. This analysis aims to explain MDA coverage across time and geography in West Africa using sociological, environmental, and programmatic factors. METHODOLOGY: The analysis links epidemiological coverage data from 3,880 LF MDAs with contextual, non-NTD data via location (each MDA was specific to a health district) and time (MDA month, year). Contextual data included rainfall, temperature, violence or social unrest, COVID-19, the 2014 Ebola outbreak, road access/isolation, population density, observance of Ramadan, and the number of previously completed MDAs. PRINCIPAL FINDINGS: We fit a hierarchical linear regression model with coverage as the dependent variable and performed sensitivity analyses to confirm the selection of the explanatory factors. Above average rainfall, COVID-19, Ebola, violence and social unrest were all significantly associated with lower coverage. Years of prior experience in a district and above average temperature were significantly associated with higher coverage. CONCLUSIONS/SIGNIFICANCE: These generalized and context-focused findings supplement current literature on coverage dynamics and MDA performance. Findings may be used to quantify typically anecdotal considerations in MDA planning. The model and methodology are offered as a tool for further investigation.

The development and roll-out of a new hydrocoele surgery facility assessment tool for the elimination of lymphatic filariasis.

A hydrocoele surgery facility assessment tool (HSFAT) was developed to assess the readiness of hydrocoele surgery services in health facilities prior to implementation of hydrocoele surgical campaigns for the elimination of lymphatic filariasis (LF). A first version of the tool was piloted in Bangladesh, Malawi and Nepal in 2019, then, following feedback from country programme managers, a second version of the tool was rolled out across countries implementing hydrocoele surgery in the Accelerating the Control of Neglected Tropical Diseases (Ascend) West and Central Africa Programme, including Benin, Burkina Faso, Ghana, Guinea, Niger and Nigeria. The HSFAT assessed facilities across 10 domains: background information, essential amenities, emergency patient transfer, laboratory capacity, surgical procedures and trained staff, infection prevention, non-disposable basic equipment, disposable basic equipment, essential medicines and current hydrocoele practices. The HSFAT results highlight key areas for improvement in different countries and can be used to develop a quality improvement plan, which may include actions with agreed deadlines to improve the readiness and quality of hydrocoele surgery services provided by the health facility, prior to implementation of surgical campaigns and assist country programmes to achieve the dossier requirements set out by the World Health Organization for the elimination of LF.

Risk factors associated with failing pre-transmission assessment surveys (pre-TAS) in lymphatic filariasis elimination programs: Results of a multi-country analysis.

Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five effective rounds of mass drug administration (MDA) and demonstrating low prevalence in subsequent assessments. The first assessments recommended by the World Health Organization (WHO) are sentinel and spot-check sites-referred to as pre-transmission assessment surveys (pre-TAS)-in each implementation unit after MDA. If pre-TAS shows that prevalence in each site has been lowered to less than 1% microfilaremia or less than 2% antigenemia, the implementation unit conducts a TAS to determine whether MDA can be stopped. Failure to pass pre-TAS means that further rounds of MDA are required. This study aims to understand factors influencing pre-TAS results using existing programmatic data from 554 implementation units, of which 74 (13%) failed, in 13 countries. Secondary data analysis was completed using existing data from Bangladesh, Benin, Burkina Faso, Cameroon, Ghana, Haiti, Indonesia, Mali, Nepal, Niger, Sierra Leone, Tanzania, and Uganda. Additional covariate data were obtained from spatial raster data sets. Bivariate analysis and multilinear regression were performed to establish potential relationships between variables and the pre-TAS result. Higher baseline prevalence and lower elevation were significant in the regression model. Variables statistically significantly associated with failure (p-value ≤0.05) in the bivariate analyses included baseline prevalence at or above 5% or 10%, use of Filariasis Test Strips (FTS), primary vector of Culex, treatment with diethylcarbamazine-albendazole, higher elevation, higher population density, higher enhanced vegetation index (EVI), higher annual rainfall, and 6 or more rounds of MDA. This paper reports for the first time factors associated with pre-TAS results from a multi-country analysis. This information can help countries more effectively forecast program activities, such as the potential need for more rounds of MDA, and prioritize resources to ensure adequate coverage of all persons in areas at highest risk of failing pre-TAS.

Low Prevalence of Pfcrt Resistance Alleles among Patients with Uncomplicated Falciparum Malaria in Niger Six Years after Chloroquine Withdrawal.

Chloroquine (CQ) resistance is widespread in Africa, but few data are available for Niger. Pfcrt haplotypes (aa 56-118) and ex vivo responses to CQ and amodiaquine were characterized for 26 isolates collected in South Niger from children under 15 years of age suffering from uncomplicated falciparum malaria, six years after the introduction of artemisinin-based combinations and the withdrawal of CQ. The wild-type Pfcrt haplotype CVMNK was found in 22 of the 26 isolates, with CVIET sequences observed in only three of the samples. We also describe for the first time a new CVINT haplotype. The ex vivo responses were better for CVMNK than for CVIET parasites. Pfcrt sequence data were compared with those obtained for 26 additional parasitized blood samples collected in Gabon, from an area of CQ resistance used as a control. Our findings suggest that there has been a significant decline in CQ-resistant genotypes since the previous estimates for Niger were obtained. No such decline in molecular resistance to CQ was observed in the subset of samples collected in similar conditions from Gabon. These results have important implications for public health and support the policy implemented in Niger since 2005, which aims to increase the efficacy and availability of antimalarial drugs whilst controlling the spread of resistance.