Artemisinin Resistance–Associated K13 Polymorphisms of Plasmodium falciparum in Southern Rwanda, 2010–2015

Tacoli, Costanza; Gai, Prabhanjan P.; Bayingana, Claude; Sifft, Kevin C.; Geus, Dominik; Ndoli, Jules; Sendegeya, Augustin; Gahutu, Jean Bosco; Mockenhaupt, Frank P.

doi:10.4269/ajtmh.16-0483

Cited by 77 publications

(86 citation statements)

References 19 publications

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“…The decreased artemisinin effectiveness is correlated with Kelch13 molecular markers [12]; in addition; there is resistance against partner drugs, such as mefloquine and piperaquine [13, 14]. It is not clear how long it will take for these resistant strains to have clinical impact in Africa [15] but this is a matter of great concern. The spread may be slowed by the successful deployment of triple combinations of artemisinin plus two partner drugs, and this is being actively explored.…”

Section: Introductionmentioning

confidence: 99%

New developments in anti-malarial target candidate and product profiles

Burrows

Duparc

Gutteridge

et al. 2017

Malar J

389

472

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A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.

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Section: Introductionmentioning

confidence: 99%

New developments in anti-malarial target candidate and product profiles

Burrows

Duparc

Gutteridge

et al. 2017

Malar J

389

472

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“…This observation was also made among children under 5 years of age in the study area [18] and may stem from recurring parasitaemia following treatment. Drug resistance markers associated with reappearing parasitaemia following artemether-lumefantrine treatment are established in the study area [33, 34], but reports on actual treatment failure are absent. No information on the completeness of treatment was collected, i.e., on adherence to the 3-days regimen, but incomplete drug intake, e.g., in the community or after the first dose in a health facility, may have contributed to reappearing parasitaemia.…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic only at first sight: malaria infection among schoolchildren in highland Rwanda

Sifft

Geus

Mukampunga

et al. 2016

Malar J

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Background Plasmodium infection and malaria in school children are increasingly recognized as a relevant public health problem, but data on actual prevalence and health consequences are insufficient. The present study from highland southern Rwanda aimed at estimating infection prevalence among children attending school, at identifying associated factors and at assessing the clinical consequences of these infections.MethodsIn a survey including 12 schools in the Huye district of Rwanda, 1089 children aged 6–10 years were clinically and anthropometrically examined, malaria parasites were diagnosed by microscopy and PCR, haemoglobin concentrations were measured, and socio-economic and behavioural parameters as well as medical histories were obtained.ResultsUpon examination, the vast majority of children was asymptomatic (fever 2.7%). Plasmodium infection was detected in 22.4% (Plasmodium falciparum, 18.8%); 41% of these were submicroscopic. Independent predictors of infection included low altitude, higher age, preceding antimalarial treatment, and absence of electricity or a bicycle in the household. Plasmodium infection was associated with anaemia (mean haemoglobin difference of −1.2 g/dL; 95% CI, −0.8 to −1.5 g/dL), fever, underweight, clinically assessed malnutrition and histories of fever, tiredness, weakness, poor appetite, abdominal pain, and vomiting. With the exception of underweight, these conditions were also increased at submicroscopic infection.ConclusionMalaria infection is frequent among children attending school in southern highland Rwanda. Although seemingly asymptomatic in the vast majority of cases, infection is associated with a number of non-specific symptoms in the children´s histories, in addition to the impact on anaemia. This argues for improved malaria surveillance and control activities among school children.

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“…In northwestern Thailand, A675V was unique to Mae Hong Son in 2011 to 2012, while R561H was unique to both Mae Hong Son and Tak (90 km south of Mae Sot) during the period from 2011 to 2014. The A675V mutation has been reported in neighboring Myanmar, China, India, and more recently in Rwanda (26)(27)(28)(29). The R561H mutation appears to be unique to Myanmar, China, and northwestern Thailand, suggesting that the introduction of these mutant lineages occurred with cross-border movements of people (28).…”

Section: Kobasa Et Almentioning

confidence: 97%

Emergence and Spread of kelch13 Mutations Associated with Artemisinin Resistance in Plasmodium falciparum Parasites in 12 Thai Provinces from 2007 to 2016

Kobasa

Talundzic

Sugaram

et al. 2018

Antimicrob Agents Chemother

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Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS) and manifests as slow parasite clearance in patients and reduced ring stage susceptibility to artemisinins in survival assays. The gene mutations associated with artemisinin-resistant parasites are now widespread in the GMS. We genotyped 277 samples collected during an observational study from 2012 to 2016 from eight provinces in Thailand to identify mutations. The results were combined with previously reported genotyping results from Thailand to construct a map illustrating the evolution of mutations from 2007 to 2016 in that country. Different mutant alleles were found in strains with different geographical origins. The artemisinin resistance-conferring Y493H and R539T mutations were detected mainly in eastern Thailand (bordering Cambodia), while P574L was found only in western Thailand and R561H only in northwestern Thailand. The C580Y mutation was found across the entire country and was nearing fixation along the Thai-Cambodia border. Overall, the prevalence of artemisinin resistance mutations increased over the last 10 years across Thailand, especially along the Thai-Cambodia border. Molecular surveillance and therapeutic efficacy monitoring should be intensified in the region to further assess the extent and spread of artemisinin resistance.

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Artemisinin Resistance–Associated K13 Polymorphisms of Plasmodium falciparum in Southern Rwanda, 2010–2015

Cited by 77 publications

References 19 publications

New developments in anti-malarial target candidate and product profiles

New developments in anti-malarial target candidate and product profiles

Asymptomatic only at first sight: malaria infection among schoolchildren in highland Rwanda

Emergence and Spread of kelch13 Mutations Associated with Artemisinin Resistance in Plasmodium falciparum Parasites in 12 Thai Provinces from 2007 to 2016

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