Evidence of Artemisinin-Resistant <i>Plasmodium falciparum</i> Malaria in Eastern India

Das, Sabyasachi; Saha, Bhaskar; Hati, Amiya Kumar; Roy, Somenath

doi:10.1056/nejmc1713777

Cited by 107 publications

(106 citation statements)

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“…The situation has become perilous with the increasing resistance of Plasmodium against common antimalarial drugs . In fact, resistance against artemisinin has also been reported from various parts of Asia and Africa . In addition, most known therapeutic drugs against Plasmodium restrict or kill parasites during its blood stage.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 In fact, resistance against artemisinin has also been reported from various parts of Asia and Africa. 4,5 In addition, most known therapeutic drugs against Plasmodium restrict or kill parasites during its blood stage. The need for an effective vaccine against malaria that targets both blood as well as liver stage has become indispensable for the control and eradication of malaria.…”

Section: Introductionmentioning

confidence: 99%

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Identification and characterization of protective CD8⁺ T‐epitopes in a malaria vaccine candidate SLTRiP

Quadiri

Kalia

Kashif

et al. 2020

Immunity Inflam & Disease

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Introduction Efforts are required at developing an effective vaccine that can inhibit malaria prevalence and transmission. Identifying the critical immunogenic antigens and understanding their interactions with host proteins forms a major focus of subunit vaccine development. Previously, our laboratory showed that SLTRiP conferred protection to the liver stage of Plasmodium growth in rodents. In the follow‐up of earlier research, we demonstrate that SLTRiP‐mediated protection is majorly concentrated in specific regions of protein. Method To identify particular protective regions of protein, we synthesized multiple nonoverlapping fragments from SLTRiP protein. From this, we designed a panel of 8‐20mer synthetic peptides, which were predicted using T‐epitope‐based prediction algorithm. We utilized the IFN‐γ enzyme‐linked immunosorbent spot assay to identify immunodominant peptides. The latter were used to immunize mice, and these mice were challenged to assess protection. Results The protective polypeptide fragment SLTRiP C3 and SLTRiP C4 were identified, by expressing and testing multiple fragments of PbSLTRiP protein. The immune responses generated by these fragments were compared to identify the immunodominant fragment. The T‐epitopes were predicted from SLTRiP protein using computer‐based algorithms. The in vitro immune responses generated by these peptides were compared with each other to identify the immunodominant T‐epitope. Immunization using these peptides showed significant reduction in parasite numbers during liver stage. Conclusion Our findings show that the protective efficacy shown by SLTRiP is localized in particular protein fragments. The peptides designed from such regions showed protective efficacy equivalent to whole protein. The sequence conservation analysis with human Plasmodium species also showed that these peptides were conserved. In conclusion, these peptides or their equivalent from other Plasmodium species could impart protection against malaria in their respective hosts too. Our studies provide a basis for the inclusion of these peptides in clinical vaccine constructs against malaria.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification and characterization of protective CD8⁺ T‐epitopes in a malaria vaccine candidate SLTRiP

Quadiri

Kalia

Kashif

et al. 2020

Immunity Inflam & Disease

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“…On one hand, in the year 2010, the Government of India launched the National Malaria Control Policy for the complete eradication of malaria infection starting from the rural level by providing LLINs and ACT kits to the village-level health workers ASHA; and the other hand, recent detection of the low frequency, candidate gene mutations of Kelch13 G625R, R539T in certain regions of North Eastern India has put in danger the eradication program. The recent researchers from India could not highlight completely whether these mutant alleles are able to repress the protein expression or causing direct clinical Artemisinin failure [9,24,25] remains a research question to be evaluated through molecular genotyping of K13 polymorphism.…”

Section: Introductionmentioning

confidence: 99%

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

Rana

Ranjit

Bal

et al. 2020

BioMed Research International

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Estimation of the spread and advancement of Plasmodium falciparum artemisinin-resistant parasites can be done by probing polymorphisms in the kelch (Pfk13) domain (a validated molecular marker). This study aimed to provide baseline information for future artemisinin surveillance by analyzing the k13-propeller domain in P. falciparum field isolates collected from 24 study areas in 14 malaria hot spots of Odisha (previously Orissa) during July 2018-January 2019. A total of 178 P. falciparum mono infections were assessed. An 849-base pair fragment encoding the Pfk13 propeller was amplified by nested polymerase chain reaction and sequenced in both directions (PCR). After DNA alignment with the 3D7 reference sequence, all samples were found to be wild type. It can be anticipated that malaria public health is not under direct threat in Odisha relating to ART resistance.

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“…Artemisinin (ART) resistance in malaria parasites is rapidly spreading through Southeast Asia, and recent reports indicate that resistance has reached Southern Asia (1–3). As artemisinin combination therapies (ACTs) are the recommended course of treatment for uncomplicated malaria by the World Health Organization (WHO), the rapid rise and spread of ART resistance raises concerns for the future of malaria treatment (4).…”

Section: Introductionmentioning

confidence: 99%

The extended recovery ring stage survival assay provides superior prediction of patient clearance half life and increases throughput

Davis

Singh

Vendrely

et al. 2019

Preprint

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1 5 Building, University of Oxford Old Road Campus, Oxford, UK 1 6 1 7 *Corresponding author: Michael T. Ferdig (ferdig.1@nd.edu) 1 8 § These authors contributed equally to this work 1 9 3 1the erythrocytic cycle. Cultures were left to reinvade to early ring-stage and parasitemia was 3 2 quantified using flow cytometry. Cultures were diluted to 2% hematocrit and 0.5% parasitemia 3 3 in a 96-well plate to start the assay, allowing for increased throughput and decreased variability 3 4 between biological replicates. Parasites were treated with 700nM of dihydroartemisinin or an 3 5 equivalent amount of dimethyl sulfoxide (DMSO) for 6 h, washed three times in drug-free media, 3 6 and incubated for 66 or 114 h, when samples were collected and frozen for PCR amplification. A 3 7 SYBR Green-based quantitative PCR method was used to quantify the fold-change between 3 8 treated and untreated samples.

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Evidence of Artemisinin-Resistant Plasmodium falciparum Malaria in Eastern India

Cited by 107 publications

References 3 publications

Identification and characterization of protective CD8⁺ T‐epitopes in a malaria vaccine candidate SLTRiP

Identification and characterization of protective CD8⁺ T‐epitopes in a malaria vaccine candidate SLTRiP

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

The extended recovery ring stage survival assay provides superior prediction of patient clearance half life and increases throughput

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Evidence of Artemisinin-Resistant Plasmodium falciparum Malaria in Eastern India

Cited by 107 publications

References 3 publications

Identification and characterization of protective CD8+ T‐epitopes in a malaria vaccine candidate SLTRiP

Identification and characterization of protective CD8+ T‐epitopes in a malaria vaccine candidate SLTRiP

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

The extended recovery ring stage survival assay provides superior prediction of patient clearance half life and increases throughput

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Identification and characterization of protective CD8⁺ T‐epitopes in a malaria vaccine candidate SLTRiP

Identification and characterization of protective CD8⁺ T‐epitopes in a malaria vaccine candidate SLTRiP