Analysis of drug resistance marker genes of Plasmodium falciparum after implementation of artemisinin-based combination therapy in Pune district, India

Ozarkar, Aarti; Kanyal, Abhishek; Dass, Swati; Deshpande, Prakash; Deobagkar, Deepti D.; Karmodiya, Krishanpal

doi:10.1007/s12038-021-00200-3

Cited by 5 publications

(2 citation statements)

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“…The result obtained is similar to the observations made in Malawi, Tanzania, Mozambique, Northern Uganda, Saudi Arabia [23][24][25][26][27], but in contrast to southern Benin [28] and in other parts of India reported recently [29][30][31][32]. The present study, although limited to a small number of samples, indicates not only the presence of three types haplotypes (CVMNK: wild type, CVIET mutant type: believed to be of Southeast Asian origin, CVMNT mutant type: believed to be of African Origin) but also inform the high genetic diversity present in field isolates of P. falciparum for CQ drug-resistant genes in Odisha, India.…”

Section: Discussionsupporting

confidence: 90%

Molecular surveillance of anti-malarial drug resistance genes in Plasmodium falciparum isolates in Odisha, India

Rana

Khan

Sandeepta

et al. 2022

Malar J

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Background Despite significant progress in eliminating malaria from the state of Odisha, India, the disease is still considered endemic. Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been introduced since 2010 as first-line treatment for uncomplicated Plasmodium falciparum malaria. This study aimed to investigate the prevalence of mutations associated with resistance to chloroquine (CQ), sulfadoxine-pyrimethamine (SP), and artesunate (ART) in P. falciparum parasites circulating in the state. Methods A total of 239 isolates of P. falciparum mono infection were collected during July 2018-November 2020 from the four different geographical regions of the state. Genomic DNA was extracted from 200 µL of venous blood and amplified using nested polymerase chain reaction. Mutations on gene associated with CQ (Pfcrt and Pfmdr1) were assessed by PCR amplification and restriction fragment length polymorphism, artemisinin (Pfk13) gene by DNA sequencing and SP (Pfdhfr and Pfdhps) genes by allele-specific polymerase chain reaction (AsPCR). Results The point mutation in Pfcrt (K76T) was detected 2.1%, in Pfmdr1 (N86Y) 3.4%, and no mutations were found in Pfkelch13 propeller domain. Prevalence of Pfdhfr, Pfdhps and Pfhdfr-Pfdhps (two locus) gene mutations were 50.43%, 47.05% and 49.79% respectively. The single, double, triple and quadruple point mutations in Pfdhfr gene was 11.2%, 8.2%, 17.2% and 3.4% while, in Pfdhps gene was 10.9%,19.5%, 9.5% and 2.7% respectively. Of the total 13 haplotypes found in Pfdhfr, 8 were detected for the first time in the state and of the total 26 haplotypes found in Pfdhps, 7 were detected for the fisrt time in the state. The linked quintuple mutation Pfdhfr (N51I-C59R-S108N)-Pfdhps (A437G-K540E) responsible for clinical failure (RIII level of resistance) of SP resistance and A16V-S108T mutation in Pfdhfr responsible for cycloguanil was absent. Conclusion The study has demonstrated a low prevalence of CQ resistance alleles in the study area. Despite the absence of the Pfkelch13 mutations, high prevalence of Pfdhfr and Pfdhps point mutations undermine the efficacy of SP partner drug, thereby threatening the P. falciparum malaria treatment policy. Therefore, continuous molecular and in vivo monitoring of ACT efficacy is warranted in Odisha.

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Section: Discussionsupporting

confidence: 90%

Molecular surveillance of anti-malarial drug resistance genes in Plasmodium falciparum isolates in Odisha, India

Rana

Khan

Sandeepta

et al. 2022

Malar J

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“…Recent studies also showed a similar observation of high frequency of wildtype Pfdhps in various parts of India (Pathak et al, 2020;Jacob et al, 2021;Rana et al, 2022) and wildtype Pfdhfr haplotype in Odisha (Rana et al, 2022). However, double mutant Pfdhfr haplotypes prevail in central (Pathak et al, 2020), western (Ozarkar et al, 2021) and northeastern part of India (Jacob et al, 2021).…”

Section: Discussionmentioning

confidence: 58%

Antimalarial drug resistance profiling of Plasmodium falciparum infections in India using Ion Torrent deep sequencing

Kale,

Uplekar,

Bandyopadhyay

et al. 2024

Front. Malar.

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IntroductionTracking the emergence and spread of antimalarial drug resistance is critical for supporting progress towards the control and eventual elimination of malaria in South Asia, especially India. Plasmodium falciparum has evolved resistance to virtually every antimalarial drug, and significant progress has been made to identify the molecular genetic mechanisms involved in the most common types of resistance.MethodsAn amplicon sequencing protocol was used for molecular surveillance of antimalarial drug resistance in a total of 158 patient isolates collected from December 2012 to September 2015 from three sites in south, west and east India: Tamil Nadu, Gujarat, and Odisha respectively. Five full length Plasmodium falciparum genes whose mutant proteins are implicated in antimalarial drug resistance were investigated: Pfcrt for chloroquine, Pfdhfr for pyrimethamine, Pfdhps for sulfadoxine, Pfk13 for artemisinin and Pfmdr1 for resistance to multiple antimalarial drugs.ResultsWe observed a high proportion of wild-type Pfcrt and Pfdhfr haplotypes from the P. falciparum-dominant site Rourkela, while mutant Pfcrt and Pfdhfr haplotypes were fixed at the P. vivax dominant sites Chennai and Nadiad. The wild-type Pfdhps haplotype was predominant across all study sites. We identified mutations in the propeller domain of Pfk13, although they are not associated with resistance to artemisinin. Finally, using samples taken from the same patient on day 2, day 7, and day 14 after artemisinin combination treatment, we were able to observe changes in allele frequency of drug resistance genes during the course of an infection.DiscussionThis is the first high-throughput deep sequencing study of five full-length P. falciparum genes in clinical isolates from three different study sites in India with varying transmission ecologies. Amplicon sequencing based on ion-torrent has the potential to track changes in the frequency of drug resistant alleles as a patient is undergoing drug therapy, and to identify new resistance mutations as they increase in frequency in the patient. This study showed possibility of whole gene sequencing, leads to in-depth molecular surveillance of multiple antimalarial resistant candidates and furthermore suggests investigations on reversal of resistant genotypes due to usage of artemisinin combination therapy in P. falciparum prevalent areas of the country.

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Characterization of drug resistance genes in Indian Plasmodium falciparum and Plasmodium vivax field isolates

Narang,

Jakhan,

Tamang

et al. 2024

Acta Tropica

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Analysis of drug resistance marker genes of Plasmodium falciparum after implementation of artemisinin-based combination therapy in Pune district, India

Cited by 5 publications

References 24 publications

Molecular surveillance of anti-malarial drug resistance genes in Plasmodium falciparum isolates in Odisha, India

Molecular surveillance of anti-malarial drug resistance genes in Plasmodium falciparum isolates in Odisha, India

Antimalarial drug resistance profiling of Plasmodium falciparum infections in India using Ion Torrent deep sequencing

Characterization of drug resistance genes in Indian Plasmodium falciparum and Plasmodium vivax field isolates

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