Variation in Calculating and Reporting Antimalarial Efficacy against Plasmodium falciparum in Sub-Saharan Africa: A Systematic Review of Published Reports

Antimalarials, in particular artemisinin-based combination therapies (ACTs), are critical tools in reducing the global burden of malaria, which is concentrated in sub-Saharan Africa. Performing and reporting antimalarial efficacy studies in a transparent and standardized fashion permit comparison of efficacy outcomes across countries and time periods. This systematic review summarizes study compliance with WHO laboratory and reporting guidance pertaining to antimalarial therapeutic efficacy studies and evaluates how well studies from sub-Saharan Africa adhered to these guidelines. We included all published studies (January 2020 or before) performed in sub-Saharan Africawhere ACT efficacy for treatment of uncomplicated Plasmodium falciparum infectionwas reported. The primary outcomewas a composite indicator for study methodology consistent with WHO guidelines for statistical analysis of corrected efficacy, defined as an article presenting a Kaplan–Meier survival analysis of corrected efficacy or reporting a perprotocol analysis where new infections were excluded from the numerator and denominator. Of 581 articles screened, we identified 279 for the review. Molecular correction was used in 83% (232/279) to distinguish new infections from recrudescences in subjects experiencing recurrent parasitemia. Only 45% (99/221) of articles with therapeutic efficacy as a primary outcome and performing molecular correction reported corrected efficacy outcomes calculated in a way consistent with WHO recommendations. These results indicate a widespread lack of compliance with WHOrecommendedmethods of analysis, whichmay result in biases in how antimalarial effectiveness is being measured and reported from sub-Saharan Africa

Epidemiology of Malaria and Other Diseases of Public Health Importance and Implications for Interventions in High Transmission Settings in Sub-Saharan Africa

Infectious diseases remain a major cause of disability of death in low-resource settings. Malaria alone was responsible for an estimated 405,000 deaths globally in 2018, with the 94% of these deaths occurring in sub-Saharan Africa. In Mozambique and Democratic Republic of the Congo (DRC), communicable diseases, including malaria, lower respiratory infections, and neonatal disorders are among the top causes of disability and death. Understanding malaria and co-endemic diseases in these two countries can aid the planning, evaluation, and targeting of public health interventions. Additionally, studying the efficacy of the drugs used to treat malaria will preserve the ability for malaria cases to be treated successfully. The three studies in this dissertation describe the epidemiology of malaria and co-endemic diseases of public health importance in Mozambique and evaluate the efficacy of medicines used to treat malaria in DRC. The first study will describe the spatial epidemiology of malaria in two high-burden districts in northern Mozambique to explore the utility of exploration of local spatial heterogeneity in high-transmission settings. The second study will investigate patterns in antibody responses to several infectious pathogens of public health importance in Mozambique, providing an opportunity to understand common predictors of infectious diseases endemic in this region. The third study will examine the efficacy of three artemisinin-based combination therapies used to treat uncomplicated malaria and molecular markers of antimalarial resistance in five sites in DRC. Collectively, the three studies in this dissertation describe factors that have implications for intervention planning and disease surveillance in areas with high malaria and other tropical disease burden and limited health resources. Careful consideration of transmission setting can support more efficient and higher quality data collection and may allow for intervention design tailored to the local realities that can target multiple diseases of public health importance

Contributions of the US Centers for Disease Control and Prevention in Implementing the Global Health Security Agenda in 17 Partner Countries

The Global Health Security Agenda (GHSA), a partnership of nations, international organizations, and civil society, was launched in 2014 with a mission to build countries’ capacities to respond to infectious disease threats and to foster global compliance with the International Health Regulations (IHR 2005). The US Centers for Disease Control and Prevention (CDC) assists partner nations to improve IHR 2005 capacities and achieve GHSA targets. To assess progress through these CDC-supported efforts, we analyzed country activity reports dating from April 2015 through March 2017. Our analysis shows that CDC helped 17 Phase I countries achieve 675 major GHSA accomplishments, particularly in the cross-cutting areas of public health surveillance, laboratory systems, workforce development, and emergency response management. CDC’s engagement has been critical to these accomplishments, but sustained support is needed until countries attain IHR 2005 capacities, thereby fostering national and regional health protection and ensuring a world safer and more secure from global health threats

Prescriber practices and patient adherence to artemisinin-based combination therapy for the treatment of uncomplicated malaria in Guinea, 2016

Abstract Background The World Health Organization recommends the use of artemisinin-based combination therapy (ACT) to treat uncomplicated malaria for the control of malaria across the world. There are several types of ACT used across malaria-endemic countries, yet there is little information about preferences and adherence practices regarding different types of ACT. The objective of this study was to evaluate levels of adherence to two types of ACT, artemether–lumefantrine (AL) and artesunate + amodiaquine (ASAQ), for the treatment of uncomplicated malaria among prescribers and patients in Guinea in 2016. Methods The study included a review of records of malaria patients and three health-facility, cross-sectional surveys. Patients diagnosed with uncomplicated malaria and prescribed ACT (n = 1830) were recruited and visited in their home after receiving the medication and administered a questionnaire regarding ACT adherence. Prescribers (n = 115) and drug dispensers (n = 43) were recruited at the same public health facilities and administered questionnaires regarding prescribing practices and opinions regarding the national treatment policies and protocols. Results According to the registry review, 35.8% of all-cause consultations were recorded as malaria. Of these, 26.6% were diagnosed clinically without documentation of laboratory confirmation. The diagnosis of uncomplicated malaria represented 64.1% of malaria cases among children under 5 years and 74.9% of those 5 years of age and older. An ACT was prescribed for 83.5% of cases of uncomplicated malaria. Among participants in the study, ACT adherence was 95.4% (95% CI 94.4, 96.3). Overall, about one in four patients (23.4%; 95% CI 21.5, 25.3) reported experiencing adverse events. While patients prescribed ASAQ were significantly more likely to report experiencing adverse effects than patients on AL (p < 0.001), given the overall high adherence, there was no evidence of a statistically significant difference in adherence between AL and ASAQ. Patients 5 years or older who reported experiencing adverse events were more likely to be non-adherent. Conclusion Although there were more reported adverse events associated with ASAQ when compared with AL, both prescribers and patients were found to be mostly adherent to ACT for the treatment of malaria, regardless of ACT type

Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017–2018

International audienceBackgroundThe World Health Organization recommends regularly assessing the efficacy of artemisinin-based combination therapy (ACT), which is a critical tool in the fight against malaria. This study evaluated the efficacy of two artemisinin-based combinations recommended to treat uncomplicated Plasmodium falciparum malaria in Burkina Faso in three sites: Niangoloko, Nanoro, and Gourcy.MethodsThis was a two-arm randomized control trial of the efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Children aged 6–59 months old were monitored for 42 days. The primary outcomes of the study were uncorrected and PCR-corrected efficacies to day 28 for AL and 42 for DP. Molecular markers of resistance to artemisinin derivatives and partner drugs were also analysed.ResultsOf 720 children enrolled, 672 reached study endpoints at day 28, 333 in the AL arm and 339 in the DP arm. PCR-corrected 28-day per protocol efficacy in the AL arm was 74% (64–83%) in Nanoro, 76% (66–83%) in Gourcy, and 92% (84–96%) in Niangoloko. The PCR-corrected 42-day per protocol efficacy in the DP arm was 84% (75–89%) in Gourcy, 89% (81–94%) in Nanoro, and 97% (92–99%) in Niangoloko.No Pfk13 mutation previously associated with artemisinin-resistance was observed. No statistically significant association was found between treatment outcome and presence of the 86Y mutation in the Pfmdr1 gene. There was also no association observed between treatment outcome and Pfpm2 or Pfmdr1 copy number variation.ConclusionThe results of this study indicate evidence of inadequate efficacy of AL at day 28 and DP at day 42 in the same two sites. A change of first-line ACT may be warranted in Burkina Faso