Prevalence of mutations in Plasmodium falciparum genes associated with resistance to different antimalarial drugs in Nyando, Kisumu County in Kenya

Musyoka, Kelvin B.; Kiiru, John; Aluvaala, Eva; Omondi, Protus; Chege, William; Judah, Terry; Kiboi, Daniel; Ngángá, Joseph; Kimani, Francis

doi:10.1016/j.meegid.2019.104121

Cited by 9 publications

(8 citation statements)

References 32 publications

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“…The withdrawal of CQ as a therapy for malaria has led to the almost complete re-emergence of CQ-sensitive parasite populations in Malawi [14], Kenya and Tanzania [15,16], and Northern regions of Uganda [5]. In other regions of the world, CQ resistant parasites persist decades after CQ cessation [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern Uganda by high‐resolution melt analysis

Kassaza

Long

McDaniels

et al. 2021

Malar J

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Background Chloroquine (CQ) resistance is conferred by mutations in the Plasmodium falciparum CQ resistance transporter (pfcrt). Following CQ withdrawal for anti-malarial treatment, studies across malaria-endemic countries have shown a range of responses. In some areas, CQ sensitive parasites re-emerge, and in others, mutant haplotypes persist. Active surveillance of resistance mutations in clinical parasites is essential to inform treatment regimens; this effort requires fast, reliable, and cost-effective methods that work on a variety of sample types with reagents accessible in malaria-endemic countries. Methods Quantitative PCR followed by High-Resolution Melt (HRM) analysis was performed in a field setting to assess pfcrt mutations in two groups of clinical samples from Southwestern Uganda. Group 1 samples (119 in total) were collected in 2010 as predominantly Giemsa-stained slides; Group 2 samples (125 in total) were collected in 2015 as blood spots on filter paper. The Rotor-Gene Q instrument was utilized to assess the impact of different PCR-HRM reagent mixes and the detection of mixed haplotypes present in the clinical samples. Finally, the prevalence of the wild type (CVMNK) and resistant pfcrt haplotypes (CVIET and SVMNT) was evaluated in this understudied Southwestern region of Uganda. Results The sample source (i.e. Giemsa-stained slides or blood spots) and type of LCGreen-based reagent mixes did not impact the success of PCR-HRM. The detection limit of 10− 5 ng and the ability to identify mixed haplotypes as low as 10 % was similar to other HRM platforms. The CVIET haplotype predominated in the clinical samples (66 %, 162/244); however, there was a large regional variation between the sample groups (94 % CVIET in Group 1 and 44 % CVIET in Group 2). Conclusions The HRM-based method exhibits the flexibility required to conduct reliable assessment of resistance alleles from various sample types generated during the clinical management of malaria. Large regional variations in CQ resistance haplotypes across Southwestern Uganda emphasizes the need for continued local parasite genotype assessment to inform anti-malarial treatment policies.

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Section: Introductionmentioning

confidence: 99%

Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern Uganda by high‐resolution melt analysis

Kassaza

Long

McDaniels

et al. 2021

Malar J

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“…The causative agents for malaria infections are Plasmodium protozoans (i.e. Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax), although most severe infections are caused by P. falciparum [2][3][4]. Most deaths are recorded among African children below the age of 5 years [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax), although most severe infections are caused by P. falciparum [2][3][4]. Most deaths are recorded among African children below the age of 5 years [1][2][3][4]. This calls for an urgent need for new anti-malarial therapies for any one of the following reasons:…”

Section: Introductionmentioning

confidence: 99%

The potential of anti-malarial compounds derived from African medicinal plants: a review of pharmacological evaluations from 2013 to 2019

Bekono

Ntie‐Kang

Onguéné

et al. 2020

Malar J

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Background African Traditional Medicine (ATM) is used for the healthcare of about 80% of the rural populations of the continent of Africa. The practices of ATM make use of plant-products, which are known to contain plant-based secondary metabolites or natural products (NPs), likely to play key roles in drug discovery, particularly as lead compounds. For various reasons, including resistance of strains of Plasmodium to known anti-malarial drugs, local African populations often resort to plant-based treatments and/or a combination of this and standard anti-malarial regimens. Emphasis has been laid in this review to present the anti-malarial virtue of the most recently published phytochemicals or natural products, which have been tested by in vitro and in vivo assays. Methods The data was based on the current version of the African Compound Libraries, which are constantly being updated based on inputs from journal articles and student theses (M.Sc/Ph.D) from African University libraries. Emphasis was laid on data published after 2012. In order to carry out the original data collection, currently being included in the African Compounds Database, individual journal websites were queried using the country names in Africa as search terms. Over 40,000 articles “hits” were originally retrieved, then reduced to about 9000 articles. The retained articles/theses was further queried with the search terms “malaria”, “malarial”, “plasmodium”, “plasmodial” and a combination of them, resulting in over 500 articles. Those including compounds with anti-malarial activities for which the measured activities fell within the established cut off values numbered 55, which were all cited in the review as relevant references. Results and discussion Pure compounds derived from African medicinal plants with demonstrated anti-malarial/antiplasmodial properties with activities ranging from “very active” to “weakly active” have been discussed. The majority of the 187 natural products were terpenoids (30%), followed by flavonoids (22%), alkaloids (19%) and quinones (15%), with each of the other compound classes being less than 5% of the entire compound collection. It was also observed that most of the plant species from which the compounds were identified were of the families Rubiaceae, Meliaceae and Asphodelaceae. The review is intended to continue laying the groundwork for an African-based anti-malarial drug discovery project.

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“…Hence, the reversion of mutant alleles to the wildtype alleles that are sensitive to CQ treatment [38]. Interestingly, a study has reported that in Anopheles arabiensis vectors, there is a selective picking and infection with wildtype P. falciparum harbouring Pfcrt K76 and Pfmdr1 N86 genes in human population which harbours Pfcrt T76 close to 90% among malaria parasites isolates [39,40]. The host-parasite relationship is essential for the selection of traits which determines the fitness of parasites [41].…”

Section: Discussionmentioning

confidence: 99%

Age-depended Selection of Chloroquine-sensitive Plasmodium Falciparum in Some part of Central Region of Ghana

Asare

Afrifa

Yeboah

2021

Preprint

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Introduction The return of chloroquine-sensitive P. falciparum in sub-Saharan Africa countries offers the opportunity for reintroduction of chloroquine either in combination with other drugs or as a single therapy for the management of malaria. The reintroduction of chloroquine can serve as a stopgap to salvage the impending danger of complete failure of malaria treatment due to artemisinin drug resistance. Further, chloroquine reintroduction requires the understanding of the underlying factors that influence the reemergence of chloroquine-sensitive P. falciparum in the endemic areas. This study assesses the effects of age on the pattern for selection of CQ sensitive P. falciparum markers in the Central Region of Ghana Methodology Genomic DNA was extracted from an archived filter paper blood blot from Cape Coast, Elmina, Assin Foso and Twifo Praso using Chelex DNA extraction method. The age information to each extracted sample was collected. The prevalence of chloroquine-sensitive genotyping of Pfcrt K76 and Pfmdr1 N86 was assessed using nested PCR and RFLP. Results The overall prevalence of CQ sensitive P. falciparum marker (Pfcrt K76) at Central Region of Ghana was 66.36%, whereas the prevalence of Pfcrt K76 at Cape Coast, Assin Foso, Twifo Praso and Elmina were 71.74%, 65.22%, 66.67% and 61.54% respectively. The prevalence of Pfcrt K76 among the age categories showed that 0-5 years category predominantly selects CQ sensitive Pfcrt K76 marker at Cape Coast (34.76%), Assin Foso (37.68%) and Twifo Praso (39.98%). In the case of Pfmdr1 N86, the total prevalence was 84.11% with Cape Coast having 64%, Elmina with 92.26%, Assin Foso with 88.39% and Twifo Praso with 89.91% There was strong correlation of reemergence of chloroquine-sensitive malaria parasites between Cape Coast and Assin Foso, (r=0.8568, p=0.0318) Cape Coast and Twifo Praso (r=0.8671, p=0.0285) and Assin Foso and Twifo Praso, (r=0.9913, p=0.0005). Conclusion The study showed that the selection and expansion of chloroquine-sensitive P. falciparum are influenced by age and geographical area. This finding has a significant implication for the future treatment, management and control of P. falciparum malaria.

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Prevalence of mutations in Plasmodium falciparum genes associated with resistance to different antimalarial drugs in Nyando, Kisumu County in Kenya

Cited by 9 publications

References 32 publications

Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern Uganda by high‐resolution melt analysis

Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern Uganda by high‐resolution melt analysis

The potential of anti-malarial compounds derived from African medicinal plants: a review of pharmacological evaluations from 2013 to 2019

Age-depended Selection of Chloroquine-sensitive Plasmodium Falciparum in Some part of Central Region of Ghana

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Prevalence of mutations in Plasmodium falciparum genes associated with resistance to different antimalarial drugs in Nyando, Kisumu County in Kenya

Cited by 9 publications

References 32 publications

Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern Uganda by high‐resolution melt analysis

Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern Uganda by high‐resolution melt analysis

The potential of anti-malarial compounds derived from African medicinal plants: a review of pharmacological evaluations from 2013 to 2019

Age-depended Selection of Chloroquine-sensitive&nbsp;Plasmodium Falciparum&nbsp;in Some part of Central Region of Ghana

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Age-depended Selection of Chloroquine-sensitive Plasmodium Falciparum in Some part of Central Region of Ghana