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Artemisinin-based combination therapy (ACT) and drug resistance molecular markers: A systematic review of clinical studies from two malaria endemic regions - India and sub-Saharan Africa.

ABSTRACT: Artemisinin-based combination therapies (ACT) are currently used as a first-line malaria therapy in endemic countries worldwide. This systematic review aims at presenting the current scenario of drug resistance molecular markers, either selected or involved in treatment failures (TF) during in vivo ACT efficacy studies from sub-Saharan Africa (sSA) and India. Eight electronic databases were comprehensively used to search relevant articles and finally a total of 28 studies were included in the review, 21 from sSA and seven from India. On analysis, Artemether + lumefantrine (AL) and artesunate + sulfadoxine-pyrimethamine (AS + SP) are the main ACT in African and Indian regions with a 28-day efficacy range of 54.3-100% for AL and 63-100% for AS + SP respectively. It was observed that mutations in the Pfcrt (76T), Pfdhfr (51I, 59R, 108N), Pfdhps (437G) and Pfmdr1 (86Y, 184F, 1246Y) genes were involved in TF, which varied with respect to ACTs. Based on studies that have genotyped the Pfk13 gene, the reported TF cases, were mainly linked with mutations in genes associated with resistance to ACT partner drugs; indicating that the protection of the partner drug efficacy is crucial for maintaining the efficacy of ACT. This review reveals that ACT are largely efficacious in India and sSA despite the fact that some clinical efficacy and epidemiological studies have reported some validated mutations (i.e., 476I, 539T and 561H) in circulation in these two regions. Also, the role of PfATPase6 in ART resistance is controversial still, while P. falciparum plasmepsin 2 (Pfpm2) in piperaquine (PPQ) resistance and dihydroartemisinin (DHA) + PPQ failures is well documented in Southeast Asian countries but studied less in sSA. Hence, there is a need for continuous molecular surveillance of Pfk13 mutations for emergence of artemisinin (ART) resistance in these countries.

SUBMITTER: Arya A

PROVIDER: S-EPMC7887327 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Artemisinin-based combination therapy (ACT) and drug resistance molecular markers: A systematic review of clinical studies from two malaria endemic regions - India and sub-Saharan Africa.

Arya Aditi A Kojom Foko Loick P LP Chaudhry Shewta S Sharma Amit A Singh Vineeta V

International journal for parasitology. Drugs and drug resistance 20201213

Artemisinin-based combination therapies (ACT) are currently used as a first-line malaria therapy in endemic countries worldwide. This systematic review aims at presenting the current scenario of drug resistance molecular markers, either selected or involved in treatment failures (TF) during in vivo ACT efficacy studies from sub-Saharan Africa (sSA) and India. Eight electronic databases were comprehensively used to search relevant articles and finally a total of 28 studies were included in the re ...[more]

PMID: 33556786

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Project description:BACKGROUND:Artemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike. METHODS:A PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014. RESULTS:The literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n?=?35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi. CONCLUSION:ACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and safety data on ACT use for non-falciparum species particularly for P. ovale, P. malariae and P. knowlesi should be a research priority. TRIAL REGISTRATION:CRD42014009103.

Project description:BackgroundMalaria still remains a life-threatening disease worldwide causing between 190 and 311 million cases of malaria in 2008. Due to increased resistance to sulphadoxine-pyrimethamine (SP), the Ministry of Health in Malawi, as in many sub-Saharan African countries, changed the malaria treatment policy to use artemisinin-based combination therapy (ACT). In order to optimize the correct use of this drug, and protect against the development of the parasite's resistance, it is important to assess the knowledge and practices of medical practitioners on the use of ACT and its impact on adherence to new treatment policy guidelines.MethodsA cross-sectional survey was conducted to assess the knowledge and perceptions of Malawian medical doctors and pharmacists on the use of ACT and the drivers of treatment choice and clinical treatment decisions. Medical doctors and pharmacists who are involved in managing malaria patients in Malawi were recruited and a self-administered questionnaire was used to obtain information on socio-demographic characteristics of the study participants, knowledge on ACT, source of information on ACT and methods used to decide on the treatment of patients with malaria.ResultsMost of the participants (95.7%) know at least one form of ACT, 67.4% reported that different forms of ACT have different characteristics, 77.3% reported that there are special formulations for children. The most commonly mentioned ACT was artemether-lumefantrine (AL), by 94.6% of the participants and 75.0% of the participants indicated that they prefer to prescribe AL. 73.9% of participants had ever received information on ACT. However, only 31.5% had received training on management of malaria using ACT. There were 71.7% respondents who had heard of ACT causing side effects. Only 25.0% of the participants had received training on how to report SAEs.ConclusionIt was found that most of the participants know about ACT and treatment guidelines for malaria. However, most of the participants have not received any training on how to use ACT and how to report adverse effects arising from the use of ACT. There is need for more training of health care professionals to ensure correct and effective use of ACT.

Dataset Information

Artemisinin-based combination therapy (ACT) and drug resistance molecular markers: A systematic review of clinical studies from two malaria endemic regions - India and sub-Saharan Africa.

Publications

Artemisinin-based combination therapy (ACT) and drug resistance molecular markers: A systematic review of clinical studies from two malaria endemic regions - India and sub-Saharan Africa.

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