Sequence Analysis of the <i>K13</i>-Propeller Gene in Artemisinin Challenging <i>Plasmodium falciparum</i> Isolates from Malaria Endemic Areas of Odisha, India: A Molecular Surveillance Study

Rana, Ramakanta; Ranjit, Manoranjan; Bal, Madhusmita; Khuntia, Hemant Kumar; Krishna, Sri; Das, Ashim

doi:10.1155/2020/8475246

Cited by 9 publications

(6 citation statements)

References 26 publications

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“…Routine molecular surveillance of parasites in these areas has also identified changes in the frequency of drug resistant mutations as different antimalarial drugs have been discontinued, such as the reversion to sensitive genotypes due to removal of the drug chloroquine [19]. More recently, sequencing studies have been used to identify if mutations in the P. falciparum kelch13 gene, implicated in resistance to artemisinin, have arisen in multiple parts of Odisha [19,22], but as yet no such mutations have been identified.…”

Section: Introductionmentioning

confidence: 99%

The effectiveness of malaria camps as part of the Durgama Anchalare Malaria Nirakaran (DAMaN) program in Odisha, India: study protocol for a cluster-assigned quasi-experimental study

Ompad

Kessler

Eijk

et al. 2021

Global Health Action

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The Indian state of Odisha has a longstanding battle with forest malaria. Many remote and rural villages have poor access to health care, a problem that is exacerbated during the rainy season when malaria transmission is at its peak. Approximately 62% of the rural population consists of tribal groups who are among the communities most negatively impacted by malaria. To address the persistently high rates of malaria in these remote regions, the Odisha State Malaria Control Program introduced 'malaria camps' in 2017 where teams of health workers visit villages to educate the population, enhance vector control methods, and perform villagewide screening and treatment. Malaria rates declined statewide, particularly in forested areas, following the introduction of the malaria camps, but the impact of the intervention is yet to be externally evaluated. This study protocol describes a cluster-assigned quasi-experimental stepped-wedge study with a pretest-posttest control group design that evaluates if malaria camps reduce the prevalence of malaria, compared to control villages which receive the usual malaria control interventions (e.g. IRS, ITNs), as detected by PCR.

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Section: Introductionmentioning

confidence: 99%

The effectiveness of malaria camps as part of the Durgama Anchalare Malaria Nirakaran (DAMaN) program in Odisha, India: study protocol for a cluster-assigned quasi-experimental study

Ompad

Kessler

Eijk

et al. 2021

Global Health Action

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“…Forward and reverse sequences for each sample were aligned and single nucleotide polymorphism (SNP) mutations identified using the SeqMan Pro assembler (DNASTAR Inc., Madison, WI). The sequences were manually inspected for quality and re-sequenced when SNPs were ambiguous [ 20 – 22 ]. The translated DNA and protein sequences were compared to the wild-type P. falciparum Pf3D7 reference strain sequence (NCBI Reference Sequence: XM_001350122.1).…”

Section: Methodsmentioning

confidence: 99%

Plasmodium falciparum kelch13 polymorphisms identified after treatment failure with artemisinin-based combination therapy in Niger

Arzika

Lobo

Lamine

et al. 2023

Malar J

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Background Artemisinin-based combination therapy (ACT) is the most effective treatment for malaria, and has significantly reduced morbimortality. Polymorphisms associated with the Plasmodium falciparum Kelch gene (Pfkelch13) have been associated with delayed parasite clearance even with ACT treatment. Methods The Pfkelch13 gene was sequenced from P. falciparum infected patients (n = 159) with uncomplicated malaria in Niger. An adequate clinical and parasitological response (ACPR) was reported in 155 patients. Four (n = 4) patients had treatment failure (TF) that were not reinfections—two of which had late parasitological failures (LPF) and two had late clinical failures (LCF). Results Thirteen single nucleotide polymorphisms (SNPs) were identified of which seven were non-synonymous (C469R, T508S, R515T, A578S, I465V, I437V, F506L,), and three were synonymous (P443P, P715P, L514L). Three SNP (C469R, F506L, P715P) were present before ACT treatment, while seven mutations (C469R, T508S, R515T, L514L, P443P, I437V, I465V) were selected by artemether/lumefantrine (AL)—five of which were non-synonymous (C469R, T508S, R515T, I437V, I465V). Artesunate/amodiaquine (ASAQ) has selected any mutation. One sample presented three cumulatively non-synonymous SNPs—C469R, T508S, R515T. Conclusions This study demonstrates intra-host selection of Pfkelch13 gene by AL. The study highlights the importance of LCF and LPF parasites in the selection of resistance to ACT. Further studies using gene editing are required to confirm the potential implication of resistance to ACT with the most common R515T and T508S mutations. It would also be important to elucidate the role of cumulative mutations.

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“…Sanger method, for both the forward and reverse primers as detailed in reference [20], with slight adjustments. Sanger sequencing was conducted using the 3130 ABI Prism DNA sequence Genetic Analyzer from Life Technologies, Carlsbad, CA, USA.…”

Section: Amplification Of K13-propeller Genesmentioning

confidence: 99%

Slow parasite clearance, absent K13 gene polymorphisms and observation of amino-acids silent mutations among malaria non-responsive patients: A case study of Kisii County, Kenya.

BWOGO,

Mong’are,

Masai

et al. 2024

Preprint

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Malaria poses a substantial global health challenge, with the majority of instances concentrated in countries within Sub-Saharan Africa. A variety of antimalarial medications have been created to address the widespread occurrence of Plasmodium falciparum malaria. Since 2004, Artemisinin-based Combination Therapy (ACT) has been the primary treatment for uncomplicated malaria in Kenya. Nevertheless, there is a rising concern attributable to the increasing reports of ACT resistance, particularly in Southeast Asia, and its extension into Africa. In particular, mutations in the Kelch propeller domain on chromosome 13 (Pfk13) have been associated with resistance to ACT. However, our comprehension of mutation prevalence in Africa remains mostly unexplored, especially as slow parasite clearance becomes increasingly prevalent. In this study, we assess polymorphisms in the Plasmodium falciparum Kelch13 propeller gene among malaria non-responsive patients who attended selected hospitals in endemic regions of Kisii County, Kenya. The research found out that all participants experiencing delayed parasite clearance had low parasitemia levels (< 500) after completing the full dose of the ACT drug, as opposed to their parasitemia levels before taking the ACT drugs. The parasite density for all participants in the study who experienced delayed parasite clearance on the first day before taking the ACT drug showed a high mean ± SE of 13951.9 ± 3564.72. In contrast, during the third-day visit, the mean was notably lower at 327.90 ± 41.11, coinciding with their claim of not responding to the drug. Upon sequencing the K13-propeller gene of the isolates and conducting a search for synonymous and non-synonymous mutations in the propeller region of K13, no polymorphism was observed. Surprisingly, upon further investigation into the amino acids of the isolated samples, silent mutations were observed. Continued global surveillance of artemisinin resistance remains crucial, and our findings offer insights into the possible dissemination of resistant parasites in East Africa. These findings suggest that the detection of silent mutations particularly those associated with delayed parasite clearance following ACT, may imply a gradual emergence of ACT-resistant parasites. This warrants additional investigation through in-vitro assays to determine the functional significance of these findings.

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Sequence Analysis of the K13-Propeller Gene in Artemisinin Challenging Plasmodium falciparum Isolates from Malaria Endemic Areas of Odisha, India: A Molecular Surveillance Study

Cited by 9 publications

References 26 publications

The effectiveness of malaria camps as part of the Durgama Anchalare Malaria Nirakaran (DAMaN) program in Odisha, India: study protocol for a cluster-assigned quasi-experimental study

The effectiveness of malaria camps as part of the Durgama Anchalare Malaria Nirakaran (DAMaN) program in Odisha, India: study protocol for a cluster-assigned quasi-experimental study

Plasmodium falciparum kelch13 polymorphisms identified after treatment failure with artemisinin-based combination therapy in Niger

Slow parasite clearance, absent K13 gene polymorphisms and observation of amino-acids silent mutations among malaria non-responsive patients: A case study of Kisii County, Kenya.

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