Malaria and artemisinin resistance: a bibliometric analysis

With roughly 50 % of the global population at risk for infection, malaria is one of the most serious public health problems in the world. This infection is caused by single-celled protozoa of the genus Plasmodium. By the turn of the century, the majority of antimalarial drugs were no longer effective against Plasmodium falciparum. However, one year after World Health Organization's final endorsement for the global use of ACTs, an appearance of artemisinin-resistant Plasmodium falciparum was seen in the border regions of Thailand and Cambodia and has since spread to other areas on the globe in subsequent years. The purpose of this work is to summarize the knowledge structure and trend of malaria and artemisinin resistance from 2012 to 2022. The VOS viewer application was used to bibliometrically analyze publications from 2012 to 2022. A total of 169 papers that discussed the keywords were used. VOS viewer application was used to produce maps based on the scientific data between the top authors and top terms in clusters. The research trend of artemisinin resistance and malaria was reported to be on the decline from 2019 to 2022. The bibliographic analysis offered an intellectual framework for the study area by identification of research groups and themes. The years with the most publications were 2015-2017, with 23 articles published each year. The most often used keywords in the research were artemisinin resistance (38 occurrences). The spread of artemisinin-resistant P. falciparum in significant regions of Southeast Asia threatens to destabilize malaria control globally. One of the most pressing global health concerns today is preventing artemisinin resistance from spreading to Africa, where the consequences for childhood mortality might be severe.

Artemisinin drug resistance and monitoring: a narrative review

Artemisinin drug resistance is one of the major reasons for malaria treatment failures in the sub-Saharan African countries where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria. The occurrence of single nucleotide polymorphisms (SNPs) is found to correlate with antimalarial drug resistance. With artemisinin, the SNPs occurs at the Kelch 13-propeller gene locus on chromosome 13. The artemisinin drug resistance surveillance strategy involves continuous monitoring of Kelch 13-propeller biomarker to detect emergence of mutations which could herald drug resistance in the region. In this narrative review paper, we examined existing literature to bridge the knowledge gap and accentuate the importance of routine surveillance for artemisinin resistance in sub-Saharan Africa. We conducted our search on PubMed database and Google Scholar to identify peer-reviewed articles, reports, and abstracts on artemisinin drug resistance using the following keywords; 'artemisinin drug resistance', 'antimalarial drug resistance', 'artemisinin-based combination therapy', 'Kelch 13-propeller', 'K13- propeller gene', and 'K13 molecular marker'. The review provided pertinent information on artemisinin derivatives, artemisinin-based combination therapy, molecular action of artemisinin, definition of artemisinin resistance, genetic basis of artemisinin drug resistance and discovery of Kelch 13, and the importance of artemisinin resistance surveillance. Molecular surveillance can provide healthcare policy makers a forecast of impending threats to malaria treatment. This is more so when drugs are in combination therapy, for instance, molecular surveillance can give a hint that one drug is failing despite the fact that in combination, it is still apparently clinically effective.

Artemisinin drug resistance and monitoring: a narrative review

Artemisinin drug resistance is one of the major reasons for malaria treatment failures in the sub-Saharan African countries where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria. The occurrence of single nucleotide polymorphisms (SNPs) is found to correlate with antimalarial drug resistance. With artemisinin, the SNPs occurs at the Kelch 13-propeller gene locus on chromosome 13. The artemisinin drug resistance surveillance strategy involves continuous monitoring of Kelch 13-propeller biomarker to detect emergence of mutations which could herald drug resistance in the region. In this narrative review paper, we examined existing literature to bridge the knowledge gap and accentuate the importance of routine surveillance for artemisinin resistance in sub-Saharan Africa. We conducted our search on PubMed database and Google Scholar to identify peer-reviewed articles, reports, and abstracts on artemisinin drug resistance using the following keywords; 'artemisinin drug resistance', 'antimalarial drug resistance', 'artemisinin-based combination therapy', 'Kelch 13-propeller', 'K13- propeller gene', and 'K13 molecular marker'. The review provided pertinent information on artemisinin derivatives, artemisinin-based combination therapy, molecular action of artemisinin, definition of artemisinin resistance, genetic basis of artemisinin drug resistance and discovery of Kelch 13, and the importance of artemisinin resistance surveillance. Molecular surveillance can provide healthcare policy makers a forecast of impending threats to malaria treatment. This is more so when drugs are in combination therapy, for instance, molecular surveillance can give a hint that one drug is failing despite the fact that in combination, it is still apparently clinically effective.

La résistance aux médicaments à base d'artémisinine est l'une des principales raisons des échecs du traitement du paludisme dans les pays d'Afrique subsaharienne où la polythérapie à base d'artémisinine (ACT) est le traitement de première intention du paludisme simple. L'apparition de polymorphismes mononucléotidiques (SNP) est corrélée à la résistance aux médicaments antipaludiques. Avec l'artémisinine, les SNP se produisent au locus du gène Kelch 13- propeller sur le chromosome 13. La stratégie de surveillance de la résistance aux médicaments à base d'artémisinine implique une surveillance continue du biomarqueur Kelch 13-propeller pour détecter l'émergence de mutations qui pourraient annoncer une résistance aux médicaments dans la région. Dans cet article de revue narrative, nous avons examiné la littérature existante pour combler le manque de connaissances et accentuer l'importance de la surveillance de routine de la résistance à l'artémisinine en Afrique subsaharienne. Nous avons effectué notre recherche sur la base de données PubMed et Google Scholar pour identifier des articles, des rapports et des résumés évalués par des pairs sur la résistance aux médicaments à base d'artémisinine en utilisant les mots-clés suivants; «résistance aux médicaments à base d'artémisinine¼, «résistance aux médicaments antipaludiques¼, «thérapie combinée à base d'artémisinine¼, «Kelch 13-propeller¼, «gène K13-propeller¼ et «marqueur moléculaire K13¼. L'examen a fourni des informations pertinentes sur les dérivés de l'artémisinine, la polythérapie à base d'artémisinine, l'action moléculaire de l'artémisinine, la définition de la résistance à l'artémisinine, la base génétique de la résistance aux médicaments à base d'artémisinine et la découverte de Kelch 13, ainsi que l'importance de la surveillance de la résistance à l'artémisinine. La surveillance moléculaire peut fournir aux responsables des politiques de santé une prévision des menaces imminentes pour le traitement du paludisme. C'est d'autant plus vrai lorsque les médicaments sont en thérapie combinée, par exemple, la surveillance moléculaire peut donner un indice qu'un médicament échoue malgré le fait qu'en combinaison, il est toujours apparemment cliniquement efficace.

Artemisinin-based antimalarial combination therapy amongst healthcare professionals in a tertiary facility in south-south Nigeria: preferences, tolerability, and cost considerations

Background: Nigeria adopted the Artemisinin-Based Combination Therapy (ACT) as the mainstay of treating uncomplicated malaria in February 2005. However, the individual preferences for the use of these medicines by health care professionals (HCP) as distinct from their observed prescribing practices is largely unknown. This study determined the preferences, tolerability and cost of the ACTs among HCP in Benin-City. Methods: This descriptive cross-sectional study was conducted in the University of Benin Teaching Hospital, Benin-City, Nigeria. Consenting HCPs were recruited consecutively for the study. Semi structured questionnaires were administered to doctors, nurses and pharmacists in the hospital. Information obtained included demographics, treatment of malaria in the previous year, antimalarial medication preferences and tolerability as well as cost of ACT. Results: A total of 556 HCPs, 295 doctors (54.1%), nurses 200 (36.0%), pharmacists 61(11.0%) completed the questionnaire. In the previous year, 224 (75.9%) doctors, 153 (79.1%) nurses, and 48 (70.5%) pharmacists had treatment for malaria and self-medication was highest among doctors (228,77.3%). Artemether-Lumenfantrine was the most preferred antimalarial used, 294 (52.8%); however, 1.6% used chloroquine sulphate and ACTs were perceived to be ineffective by 25.4%. Adverse effects were experienced by 167 (29.1%) resulting in 50 (9.0%) discontinuing their medication. Between 500 and 1500 Naira (~US$1-4) was expended on ACT by 66.3% of the staff, while 21.4% were concerned about the high cost of medications. Conclusion: This study highlights the use and preferences, self-medication practices, perceived lack of effectiveness and high cost of ACTs from a HCP perspective. There is an urgent need to address these concerns in view of adverse consequences as well as the likely possibility of its the impact on prescribing practices.

The current use of the artemisinin-based combination therapies in adult patients at a tertiary hospital, South-South Nigeria

Objective:The antimalarial preferences, tolerability, and cost of the Artemisinin-based combination therapies (ACTs) among adult patients and caregivers are largely understudied despite being the recommendedtreatment for Plasmodium falciparum.We, therefore, evaluated antimalarial preferences, tolerability, and cost of the ACTs among adult patients attending the University of Benin Teaching Hospital, Nigeria. Methods:This was a cross-sectional study conducted among adult patients and their caregivers atthe University of Benin Teaching Hospital, Nigeria,using a semi-structured questionnaire. Their preferred antimalarial medication, previous use of antimalarial monotherapies, current ACT use; cost considerations, and adverse effects profile were sought.Result:Six hundred respondents were recruited with a mean age of 41.4±16.3years and M/F ratio of 1.4. The majority (88.0%), reported that they had between 1-5 episodes of malaria fever in a year. Only 28.2% received doctors' prescriptions while 85.8% purchased their antimalarial medications from a pharmacy. Sixty percent of the respondents used at least one ACT; mainly Artemether-Lumefantrine (AL) 312(52.0%). Only 9.3% reported previous adverse effects with the ACTs with 4.0% of respondents discontinuing their medications. The mean (SD) cost of purchasing ACTs was 1,516.47±760.3 (3.65 USD) Naira.Conclusion: This study showed adult patients' preference for the ACTs, especially Artemether-Lumefantrine despite some inclination towards antimalarial monotherapies and parenteral route. There was also a high rate of use of malaria presumptive treatment, but only a few reported adverse effects. There is a need to make ACTs affordable because the cost is still presently high for most Nigerians.

Assessment of adverse drug reactions in the home management of malaria cases of children under 5 years using artemisinin-based combination therapy in Mfou health district, Center region of Cameroon

health concerns in Cameroon. Its treatment is frequently initiated at home, most often with street drugs. The home management of malaria cases entails the prescription of Artemisinin-based combination (ACTs) as first-line therapy for treatment of uncomplicated malaria after having confirmed the malaria case using rapid diagnostic tests. But induced adverse reactions of this therapy are not well known in Cameroon. Thus, a prospective, observational, cohort study of adverse events associated with ACTs was conducted from January 2013 to November 2013 in the health district of Mfou. Children under 5 years receiving ACTs for malaria treatment at home were enrolled. Suspected ADRs and other clinical events were recorded. Data were managed and analysed using Epi Info version 3.5.3 and Statistical Package for Social Sciences, statistical software version 20. Of the 479 children investigated, 56.8% (n=272/479) were males, the age group 25-59 months (49.5%; n=237/479) was most represented, 27.1% (n=130/479) had experienced one form of ADRs, male children (56.2%; n=73/130) and the age group 25-59 months (50.8%; n=66/130) were most affected. No significant association was found between age, sex and incidence of adverse ACTs reactions. The main experienced ACTs reactions were tiredness (43.1%; n=56/130) followed by lack of appetite (24.6%; n=32/130). The incidence ACTs ARDs was found to be relatively low and tolerable. Home management of malaria cases using ACTs should be encouraged and community members should be trained to improve the recognizing and reporting of adverse effects

Management of malaria in pregnancy by Traditional Birth Attendants in Ogun State, Nigeria

Background: Malaria in pregnancy is a major public health issue in sub-Saharan Africa. Most deliveries in this region are attended by the Traditional Birth Attendants (TBAs).Objective: To assess the knowledge and practice of prevention and treatment of malaria in pregnancy amongst TBAs in Ogun State, south-west Nigeria.Methods: This descriptive, cross-sectional study used systematic random sampling to select 200 registered TBAs within the state. Pre-tested, semi-structured interviewer-based questionnaires were used to obtain relevant data.Results: The mean age of respondents was 37.7 ± 2.2 years. Most of the respondents had secondary school education (82.0%) and were females (89.0%). The majority (68.0%) had good knowledge of malaria during pregnancy; 83.0% used blood test for the diagnosis of malaria while 62.2% of these used Malaria Rapid Diagnostic Test kits. A third of the respondents (33.0%) used Artemisinin-Combination Therapy for treatment while 13.0% used Chloroquine. The majority (85.5%) of the respondents did not practice directly observed therapy in intermittent preventive treatment for malaria using Sulphadoxine-Pyrimethamine (SP). The age of the respondents was significantly associated with their level of knowledge (p = 0.019).Conclusion: The TBAs had high level of knowledge and good practice of the management of malaria in pregnancy. However, some still treated malaria with Chloroquine and were not conversant with the use of SP for the prevention of malaria. It is recommended that capacity building sessions for the TBAs be instituted to improve the quality of care they provide

Evaluation of adverse drug reactions to artemisinin-based combination therapy in a Nigeria University Community

Purpose : The study was carried out to evaluate the incidence of adverse reactions to antimalarial drugs among residents of a Nigeria university community with a focus on arte- misinin-based combination therapy (ACT). Specifically; the profile of use; and the reporting culture of people with respect to experienced reactions were noted. Method : Ques- tionnaires were administered to respondents at the university health centre between November 2006 and January 2007. Information on demographic characteristics; nature of experienced adverse reactions and the most frequently used ACT; among other questions; were collected. Descriptive statistics and Fisher's Exact test were used to evaluate the distribution of respondent's opinion. Result: The study achieved a response rate of 86. The results revealed that 210 (70.0) of respondents said they had used artemisinin-based combination drugs while 134 (44.7) said they used artemisinin derivatives alone as monotherapy for malaria treatment. Artesunate plus amodiaquine 94 (31.3) as a co-packaged product was the most commonly used ACT. Incidence of the experienced adverse reactions to ACT was reported to be generally mild and well tolerated. Conclusion : Efforts to improve the use of ACT in the management of acute uncomplicated P. falciparum malaria is recommended. Furthermore; an effective mechanism to improve reporting of adverse effects of ACT is also recommended

Mieux prescrire les derrives de l'artemisinine

N.A.

Les accusations portees sur les ACT sont-elles fondees ?

N.A.

Traitement du paludisme de l'enfant en Afrique : les ACT en question

Les Artemisinin-based Combination Therapies (ACT) representent la majorite des alternatives aux antipaludiques de reference et sont sur le point d'etre deployees largement en Afrique. Elles sont particulierement attractives pour traiter les enfants. Les vertus annoncees de ces associations sont multiples : puissance accrue; rapidite d'action; stabilisation de la chimioresistance et reduction de la transmission. L'abondante litterature consacree aux ACT depuis quelques annees permet de faire le point sur ces divers aspects; en insistant sur la question du confort des enfants malades

Controle de qualite de trois antipaludiques derives de l'artemisine (Arthemether; artesunate; dihydroartemisinine) laboratoire national de sante

Des etudes relatives aux controles de qualite des medicaments et des aliments sont regulierement menees au Laboratoire National de la Sante. La presente etude s'inscrit dans le cadre de controle de qualite des medicaments. Il s'agit d'une etude prospective qui s'est realisee d'octobre 2003 en novembre 2004. L'objectif general est la contribution a l'amelioration de la qualite des medicaments antipaludiques derives de l'artemisinine. 101 echantillons tous des specialites ont ete analyses parmi lesquels 6 etaient non conformes; soit un taux de 5;90p.100. Les comprimes ont represente la forme galenique la moins conforme avec 8p.100. Toutes les non conformites concernaient l'artesunate qui etait la molecule la plus representee de notre etude. Les echantillons provenant de l'Amerique et de l'Europe etaient tous conformes ; par contre ceux de l'Afrique et de l'Asie avaient respectivement des taux de non conformite de 10p.100 et 15p.100. S'agissant du secteur de prelevement; les echantillons non conformes provenaient tous du secteur prive. Les non conformites rencontrees etaient de deux types : le surdosage et le defaut de desagregation

Use of Artemisinin (Qinghaosu) Derivatives in Treatment of Malaria

Derivatives of the Chinese herbal remedy ginghaosu (artemisinin) are useful in the treatment of multiple-drug resistant malaria. This review covers the discovery; development; clinical pharmacology and toxicology of these compounds; with emphasis on those derivatives currently in use in parts of Africa