Investigation of polymorphisms in the<i>P. falciparum</i>artemisinin resistance marker<i>kelch13</i>in asymptomatic infections in a rural area of Cameroon

Safeukui, Innocent; Fru-Cho, Jerome; Mbengue, Alassane; Suresh, Niraja; Njimoh, Dieudonné Lemuh; Bumah, Violet V.; Nkuo‐Akenji, Theresa; Titanji, Vincent P. K.; Haldar, Kasturi

doi:10.1101/148999

Cited by 6 publications

(7 citation statements)

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“…This is consistent with previous reports conducted in Cameroon. To date, seven epidemiological-molecular studies had been conducted in Cameroon which showed a heterogeneity of mutations in the parasite population 10 years after the implementation of ACTs in the Centre and South West regions of the country [29,32–34,41,42,51]. These studies indicated that less than 4% of all samples showed a mutation in the K13 gene and none were among those associated with artemisinin clearance delay in Southeast Asia.…”

Section: Discussionmentioning

confidence: 99%

“…In Central, West and East Africa, the allelic frequencies reported were generally rare less than 6% [24,27,34,36,49,52,53]. However, one study in Cameroon revealed a high rate, 15.1% of isolates presented at least one non-synonymous SNP in K13 gene [42].…”

Section: Discussionmentioning

confidence: 99%

“…Whereas SNPs were not observed in the three studies conducted among 251, 11 and 22 samples collected in 2015 in another health facility in Yaoundé, Central region of Cameroon, in 2013–2014 in Buea, West region of Cameroon in 2013–2014, and between 2012–2015 among migrant workers who returned to Henan Province from Africa, respectively [29, 32, 51]. In the other studies, high level of diversity was found, such as K189T mutation which was high prevalent among samples from local residents in two studies conducted in rural and semi-urban areas of the South West Region (24.3%-58/239 and et 42.4%-14/33) [41,42]. Some non-synonymous SNPs (K189T, K189N and N217K) found in samples from this part of Cameroun had previously been described [11,24,25,30].…”

Section: Discussionmentioning

confidence: 99%

“…Since 2014, Cameroon has adopted ACTs artesunate-amodiaquine (ASAQ) and artemether–lumefantrine (AL) as first-line treatment of uncomplicated malaria [40]. A few past studies on K13 polymorphism in Cameroon reported no evidence of K13 mutations associated with artemisinin resistance [29, 32–34, 41, 42]. However, this previous studies were limited to the Centre and South West Regions of Cameroon with distinct epidemiological profiles when compared to most other regions of the country and, described eight non-synonymous mutations with great diversity [29, 32–34, 41, 42].…”

Section: Introductionmentioning

confidence: 99%

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K-13 propeller gene polymorphisms isolated between 2014 and 2017 from Cameroonian Plasmodium falciparum malaria patients

et al. 2019

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The emergence of artemisinin-resistant parasites since the late 2000s at the border of Cambodia and Thailand poses serious threats to malaria control globally, particularly in Africa which bears the highest malaria transmission burden. This study aimed to obtain reliable data on the current state of the kelch13 molecular marker for artemisinin resistance in Plasmodium falciparum in Cameroon. DNA was extracted from the dried blood spots collected from epidemiologically distinct endemic areas in the Center, Littoral and North regions of Cameroon. Nested PCR products from the Kelch13-propeller gene were sequenced and analyzed on an ABI 3730XL automatic sequencer. Of 219 dried blood spots, 175 were sequenced successfully. We identified six K13 mutations in 2.9% (5/175) of samples, including 2 non-synonymous, the V589I allele had been reported in Africa already and one new allele E612K had not been reported yet. These two non-synonymous mutations were uniquely found in parasites from the Littoral region. One sample showed two synonymous mutations within the kelch13 gene. We also observed two infected samples with mixed K13 mutant and K13 wild-type infection. Taken together, our data suggested the circulation of the non-synonymous K13 mutations in Cameroon. Albeit no mutations known to be associated with parasite clearance delays in the study population, there is need for continuous surveillance for earlier detection of resistance as long as ACTs are used and scaled up in the community.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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K-13 propeller gene polymorphisms isolated between 2014 and 2017 from Cameroonian Plasmodium falciparum malaria patients

et al. 2019

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“…There are 11 candidate gene polymorphisms associated with delayed parasite clearance [17,19,20]. A number of mutations have also been reported outside the K13 propeller region notably, K189T and E252Q [19,[21][22][23]. In Africa, the highest geographical distribution is A578S [18,19,24] and the presence of R561H mutation has recently been reported in Tanzania [25] and Rwanda [26].…”

Section: Introductionmentioning

confidence: 99%

Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis protocol

Niba

Nji

Evehe

et al. 2020

Preprint

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Background: Cameroon remains a country faced with high malaria burden despite enormous efforts made in the control of the disease. The rapid development and dispersal of mutations associated with anti-malarial drug resistance influenced policy changes from the use of chloroquine, amodiaquine and sulphadoxine-pyrimethamine to the adoption of artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria. Different studies have identified the frequency of key markers in Plasmodium falciparum associated with drug resistance without a clear picture on the localisation of potential hotspots that may drive the emergence of resistance to the currently used ACTs. This systematic review and meta-analysis aims to determine the prevalence and distribution of P. falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from 1990 to present. Methods: The PRISMA, PRISMA-P and STREGA statements will be adopted in the quality assessments of studies to be included in this review. The electronic databases of Medline via Pubmed, EMBASE, Google Scholar and Science Direct will be searched by two independent researchers using different MeSH terms and Boolean operators (AND, OR). More so, unpublished data that will be sourced from academic libraries will also be extracted. Quantitative syntheses will be done using the “metaphor” and “meta” commands in the R statistical software package version 3.5.2. Heterogeneity will be assessed using the Cochrane Q and I2 statistics. The random effects model will be used as benchmark in the determination of heterogeneity between studies. Discussion: The primary outcome of this review is to identify and describe molecular markers conferring drug resistance in Plasmodium falciparum parasites that have been circulating for a period of over 30 years in Cameroon. This review will be able to pool data from previously published and unpublished studies on anti-malarial drug resistance gene mutations. This will provide evidence to support the continuous use of ACTs in the treatment of uncomplicated P. falciparum malaria. Moreover, it is also hoped that potential hotspots driving the emergence and spread of anti-malarial resistance markers will be identified. Systematic review registration: PROSPERO CRD42020162620

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Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)

Niba

Nji

Evehe

et al. 2021

Malar J

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Background Malaria remains highly endemic in Cameroon. The rapid emergence and spread of drug resistance was responsible for the change from monotherapies to artemisinin-based combinations. This systematic review and meta-analysis aimed to determine the prevalence and distribution of Plasmodium falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from January 1998 to August 2020. Methods The PRISMA-P and PRISMA statements were adopted in the inclusion of studies on single nucleotide polymorphisms (SNPs) of P. falciparum anti-malarial drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfatp6, Pfcytb and Pfk13). The heterogeneity of the included studies was evaluated using the Cochran’s Q and I2 statistics. The random effects model was used as standard in the determination of heterogeneity between studies. Results Out of the 902 records screened, 48 studies were included in this aggregated meta-analysis of molecular data. A total of 18,706 SNPs of the anti-malarial drug resistance genes were genotyped from 47,382 samples which yielded a pooled prevalence of 35.4% (95% CI 29.1–42.3%). Between 1998 and 2020, there was significant decline (P < 0.0001 for all) in key mutants including Pfcrt 76 T (79.9%-43.0%), Pfmdr1 86Y (82.7%-30.5%), Pfdhfr 51I (72.2%-66.9%), Pfdhfr 59R (76.5%-67.8%), Pfdhfr 108 N (80.8%-67.6%). The only exception was Pfdhps 437G which increased over time (30.4%-46.9%, P < 0.0001) and Pfdhps 540E that remained largely unchanged (0.0%-0.4%, P = 0.201). Exploring mutant haplotypes, the study observed a significant increase in the prevalence of Pfcrt CVIET mixed quintuple haplotype from 57.1% in 1998 to 57.9% in 2020 (P < 0.0001). In addition, within the same study period, there was no significant change in the triple Pfdhfr IRN mutant haplotype (66.2% to 67.3%, P = 0.427). The Pfk13 amino acid polymorphisms associated with artemisinin resistance were not detected. Conclusions This review reported an overall decline in the prevalence of P. falciparum gene mutations conferring resistance to 4-aminoquinolines and amino alcohols for a period over two decades. Resistance to artemisinins measured by the presence of SNPs in the Pfk13 gene does not seem to be a problem in Cameroon. Systematic review registration PROSPERO CRD42020162620

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Investigation of polymorphisms in theP. falciparumartemisinin resistance markerkelch13in asymptomatic infections in a rural area of Cameroon

Abstract: Background. The genetic variability of the artemisinin resistance (AR) molecular marker

Cited by 6 publications

References 28 publications

K-13 propeller gene polymorphisms isolated between 2014 and 2017 from Cameroonian Plasmodium falciparum malaria patients

K-13 propeller gene polymorphisms isolated between 2014 and 2017 from Cameroonian Plasmodium falciparum malaria patients

Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis protocol

Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)

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