Molecular surveillance of chloroquine-resistant Plasmodium falciparum in sub-Saharan African countries after withdrawal of chloroquine for treatment of uncomplicated malaria: A systematic review

Njiro, Belinda J.; Mutagonda, Ritah; Chamani, Amisa Tindamanyile; Mwakyandile, Tosi; Sabas, Deodatus; Bwire, George M.

doi:10.1016/j.jiph.2022.03.015

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…With respect to resistance to quinolone-containing antimalarial drugs, surveillance activities were dominated by monitoring PfCRT K76T mutations that confer resistance to chloroquine but possibly contribute to reduced susceptibility to other drugs such as amodiaquine and LU [34]. Consistently with outcomes from other Sub-Saharan regions [55], we found that the overall proportion of parasites carrying this mutation has decreased overtime in the DRC. This suggests a gradual recovery of chloroquine susceptibility among malaria parasites following the lifting of the drug selective pressure after its withdrawal from clinical use since 2002 [13].…”

Section: Discussionsupporting

confidence: 72%

Malaria drug resistance landscape in the Democratic Republic of the Congo: a spatial mapping systematic review of molecular surveillance surveys

Kalenda

Tshibangu‐Kabamba²,

Kido³

et al. 2023

Preprint

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Context: The Democratic Republic of Congo (DRC), one of the most malaria-affected countries worldwide, is a potential hub for global drug-resistant malaria. This study aimed at summarizing and mapping surveillance surveys of malaria parasites carrying molecular markers of drug-resistance across the country. Methods: A systematic mapping review was carried out before July 2023 by searching for relevant articles through seven databases (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline and Web of Science). Results: We identified 1541 primary studies of which 29 fulfilled inclusion criteria and provided information related to 6385 Plasmodium falciparumclinical isolates (collected from 2000 to 2020). We noted the PfCRT K76T mutation encoding for chloroquine-resistance in median 32.1% [interquartile interval, IQR: 45.2] of analyzed malaria parasites. The proportion of parasites carrying this mutation decreased overtime but wide geographic variations persisted. A single isolate had encoded the PfK13 R561H substitution that is invoked in artemisinin-resistance emergence in the Great Lakes region of Africa. Parasites carrying various mutations linked to resistance to the sulfadoxine-pyrimethamine combination were widespread and reflected a moderate resistance profile (PfDHPS A437G: 99.5% [IQR: 3.9]; PfDHPS K540E: 38.9% [IQR: 47.7]) with median 13.1% [IQR: 10.3] of them being quintuple IRN-GE mutants (i.e., parasites carrying the PfDHFR N51I-C59R-S108Nand PfDHPS A437G-K540E mutations). These quintuple mutants tended to prevail in eastern regions of the country. Among circulating parasites, we did not record any parasites harboring mutations related to mefloquine-resistance, but we could suspect those with decreased susceptibility to quinine, amodiaquine, and lumefantrine based on corresponding molecular surrogates. Conclusion: Drug resistance poses a serious threat to existing malaria therapies and chemoprevention options in the DRC. This review provides a baseline for monitoring public health efforts as well as evidences for decision-making in support of national malaria policies and for implementing regionally tailored control measures across the country.

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Section: Discussionsupporting

confidence: 72%

Malaria drug resistance landscape in the Democratic Republic of the Congo: a spatial mapping systematic review of molecular surveillance surveys

Kalenda

Tshibangu‐Kabamba²,

Kido³

et al. 2023

Preprint

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“…Many studies have described widespread return of chloroquine sensitive alleles of Plasmodium falciparum parasites in parts of Africa after at least a 10-year cessation of chloroquine use in treatment of uncomplicated malaria [28,41,46,47]. The data from the studies support calls for consideration of chloroquine as an addition to ACTs, especially in areas where chloroquine-susceptible Plasmodium falciparum predominates [48,49].…”

Section: Discussionmentioning

confidence: 92%

Declining Frequency of Chloroquine-resistant Haplotype of <em>Plasmodium falciparum</em> (CVIET) in an Endemic Area of Southwest Nigeria 17 Years After Withdrawal of Chloroquine

Amusan¹,

Akinola²,

Akano³

et al. 2023

Preprint

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The replacement of chloroquine with artemisinin-based combination therapies (ACTs) for over a decade has had varying impacts on the ability of malaria parasite to sustain its chloroquine resistance prowess in different malaria-endemic regions. We evaluated the frequency of Plasmodium falciparum chloroquine resistance transporter (PfCRT) mutations in an endemic area of southwest Nigeria 17 years after replacement of chloroquine with ACTs for malaria treatment. Genomic DNA was isolated from dried blood spot samples obtained from 129 patients (aged 1-35 years) with microscopically confirmed P. falciparum infection. PfCRT fragments covering codons 72-76, CVMNK (wildtype) and A220 were amplified and sequenced. Two mutant PfCRT haplotypes on residues 72-76 (CVIET and CVINT) were identified with a prevalence of 18.6% and 2.3%, respectively. Interestingly, the CVINT haplotype was identified for the first time in this region. A220S changes were found in 16.3% of samples occurring concurrently with the CVIET haplotype, while a Q271E mutation occurred in a wildtype isolate. The reduced prevalence of the PfCRT mutant alleles in this study may suggest a gradual disappearance of chloroquine-resistant malaria parasites following reduced drug pressure. It may also be an indicator of the ability of malaria parasites to develop resistance gradually against the current first-line regimen.

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“…We found that frequencies of molecular markers conferring CQ resistance have persisted in the 2019-2020 Malian isolates at similar frequencies compared to a decade ago, despite its removal from any P. falciparum treatment guidelines since 2006 and a report of a decreasing trend in 2017 in Mali 16 . This is unlike other areas in the world where a return in CQ sensitivity has been observed [11][12][13][14]28 and could indicate a low fitness cost associated with maintaining pfcrt resistance polymorphisms in the population or a continued over the counter use of CQ [29][30][31] , thereby highlighting the need to investigate and reduce the availability of this drug in Mali and neighbouring countries.…”

Section: Discussionmentioning

confidence: 93%

Genome-wide genetic variation and molecular surveillance of drug resistance in Plasmodium falciparum isolates from asymptomatic individuals in Ouélessébougou, Mali

Vanheer¹,

Mahamar²,

Mańko³

et al. 2023

Sci Rep

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Sequence analysis of Plasmodium falciparum parasites is informative in ensuring sustained success of malaria control programmes. Whole-genome sequencing technologies provide insights into the epidemiology and genome-wide variation of P. falciparum populations and can characterise geographical as well as temporal changes. This is particularly important to monitor the emergence and spread of drug resistant P. falciparum parasites which is threatening malaria control programmes world-wide. Here, we provide a detailed characterisation of genome-wide genetic variation and drug resistance profiles in asymptomatic individuals in South-Western Mali, where malaria transmission is intense and seasonal, and case numbers have recently increased. Samples collected from Ouélessébougou, Mali (2019–2020; n = 87) were sequenced and placed in the context of older Malian (2007–2017; n = 876) and African-wide (n = 711) P. falciparum isolates. Our analysis revealed high multiclonality and low relatedness between isolates, in addition to increased frequencies of molecular markers for sulfadoxine-pyrimethamine and lumefantrine resistance, compared to older Malian isolates. Furthermore, 21 genes under selective pressure were identified, including a transmission-blocking vaccine candidate (pfCelTOS) and an erythrocyte invasion locus (pfdblmsp2). Overall, our work provides the most recent assessment of P. falciparum genetic diversity in Mali, a country with the second highest burden of malaria in West Africa, thereby informing malaria control activities.

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Molecular surveillance of chloroquine-resistant Plasmodium falciparum in sub-Saharan African countries after withdrawal of chloroquine for treatment of uncomplicated malaria: A systematic review

Cited by 9 publications

References 44 publications

Malaria drug resistance landscape in the Democratic Republic of the Congo: a spatial mapping systematic review of molecular surveillance surveys

Malaria drug resistance landscape in the Democratic Republic of the Congo: a spatial mapping systematic review of molecular surveillance surveys

Declining Frequency of Chloroquine-resistant Haplotype of <em>Plasmodium falciparum</em> (CVIET) in an Endemic Area of Southwest Nigeria 17 Years After Withdrawal of Chloroquine

Genome-wide genetic variation and molecular surveillance of drug resistance in Plasmodium falciparum isolates from asymptomatic individuals in Ouélessébougou, Mali

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