Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum

Abstract

Background The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapy (ACT). However, the emergence of artemisinin (ART) partial resistance in Southeast Asia and emerging reports of delayed parasite sensitivity to ACT in African parasites signal a gradual trend towards treatment failure. Monitoring the prevalence of mutations associated with artemisinin resistance in African populations is necessary to stop resistance in its tracks. Mutations in Plasmodium falciparum genes pfk13, pfcoronin and pfatpase6 have been linked with ART partial resistance. Methods Findings from published research articles on the prevalence of pfk13, pfcoronin and pfatpase6 polymorphisms in Africa were collated. PubMed, Embase and Google Scholar were searched for relevant articles reporting polymorphisms in these genes across Africa from 2014 to August 2021, for pfk13 and pfcoronin. For pfatpase6, relevant articles between 2003 and August 2021 were retrieved. Results Eighty-seven studies passed the inclusion criteria for this analysis and reported 742 single nucleotide polymorphisms in 37,864 P. falciparum isolates from 29 African countries. Five validated-pfk13 partial resistance markers were identified in Africa: R561H in Rwanda and Tanzania, M476I in Tanzania, F446I in Mali, C580Y in Ghana, and P553L in an Angolan isolate. In Tanzania, three (L263E, E431K, S769N) of the four mutations (L263E, E431K, A623E, S769N) in pfatpase6 gene associated with high in vitro IC50 were reported. pfcoronin polymorphisms were reported in Senegal, Gabon, Ghana, Kenya, and Congo, with P76S being the most prevalent mutation. Conclusions This meta-analysis provides an overview of the prevalence and widespread distribution of pfk13, pfcoronin and pfatpase6 mutations in Africa. Understanding the phenotypic consequences of these mutations can provide information on the efficacy status of artemisinin-based treatment of malaria across the continent. Graphical Abstract

Molecular analysis of Bio-makers of Chloroquine resistance in Plasmodium falciparum Isolate from Gombe Local Government Area, Gombe State, Nigeria

“…Therefore, the chances of getting different makers for chloroquine resistance could be higher in Malaysia. In addition, the prevalence of 80.7% in the K76T variant recorded in this study is by far higher than 12.4% in north-western Nigeria [1]. In this present study only two variants (K76T and C72S) of the PCRT gene were reported, this is contrary to the findings in previous research [43] which also reported five different variants(C72S, M74I, N75E/D K76T and A220S) of PCRT gene from India.…”

“…Malaria is regarded as a serious global public health problem, which is partly due to it is cosmopolitan distribution and high rate of mortality traced to the disease, especially in sub-Saharan African countries that bear many consequences of the disease [1]. The disease is caused by four parasite specie in the genus Plasmodium (P. falciparum, P. vivax, P. ovale and P. malariae), recently human infections with the monkey malaria parasite, P. knowlesi, have also been reported from the forested regions of South-East [2].…”

Transmission-Blocking Strategies Against Malaria Parasites During Their Mosquito Stages

“…As a warning, it was reported that resistance to frontline artemisinin-based drugs was spreading in the Greater Mekong Subregion of Southeast Asia. Recent studies have shown that similar artemisinin-resistant strains have appeared in Africa, which may be a dangerous signal for global malaria control ( Lubell et al, 2014 ; Slater et al, 2016 ; Stokes et al, 2021 ; L’Episcopia et al, 2021 ; Owoloye et al, 2021 ). Therefore, to prevent the resurgence of malaria in well-controlled regions and ensure the progressive decline of malaria infection in high-incidence areas, it is necessary to find more effective and safer malaria control strategies.…”

The Antiplasmodial Potential of Medicinal Plants Used in the Cameroonian Pharmacopoeia: An Updated Systematic Review and Meta-Analysis

“…At the end of the last century, introduction of the artemisinin combination therapies (ACTs) provided a much needed, highly efficacious antimalarial treatment, which became the first-line treatment for uncomplicated falciparum malaria in all endemic countries [ 8 ]. The extremely rapid development of resistance to many antimalarials, and even the most recent, such as ACTs in five countries of the Greater Mekong subregion [ 9 , 10 ] and in Africa [ 11 , 12 ], justifies continued research on the factors causing this resistance. Like antibiotic resistance, antimalarial drug resistance is caused by the massive and uncontrolled use of certain molecules that could lead to a selection of resistant strains of Plasmodium over time.…”