Dataset Information

Phage Revolution Against Multidrug-Resistant Clinical Pathogens in Southeast Asia.

ABSTRACT: Southeast Asia (SEA) can be considered a hotspot of antimicrobial resistance (AMR) worldwide. As recent surveillance efforts in the region reported the emergence of multidrug-resistant (MDR) pathogens, the pursuit of therapeutic alternatives against AMR becomes a matter of utmost importance. Phage therapy, or the use of bacterial viruses called bacteriophages to kill bacterial pathogens, is among the standout therapeutic prospects. This narrative review highlights the current understanding of phages and strategies for a phage revolution in SEA. We define phage revolution as the radical use of phage therapy in infectious disease treatment against MDR infections, considering the scientific and regulatory standpoints of the region. We present a three-phase strategy to encourage a phage revolution in the SEA clinical setting, which involves: (1) enhancing phage discovery and characterization efforts, (2) creating and implementing laboratory protocols and clinical guidelines for the evaluation of phage activity, and (3) adapting regulatory standards for therapeutic phage formulations. We hope that this review will open avenues for scientific and policy-based discussions on phage therapy in SEA and eventually lead the way to its fullest potential in countering the threat of MDR pathogens in the region and worldwide.

SUBMITTER: Carascal MB

PROVIDER: S-EPMC8830912 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Phage Revolution Against Multidrug-Resistant Clinical Pathogens in Southeast Asia.

Carascal Mark B MB Dela Cruz-Papa Donna May DM Remenyi Roland R Cruz Mely Cherrylynne B MCB Destura Raul V RV

Frontiers in microbiology 20220127

Southeast Asia (SEA) can be considered a hotspot of antimicrobial resistance (AMR) worldwide. As recent surveillance efforts in the region reported the emergence of multidrug-resistant (MDR) pathogens, the pursuit of therapeutic alternatives against AMR becomes a matter of utmost importance. Phage therapy, or the use of bacterial viruses called bacteriophages to kill bacterial pathogens, is among the standout therapeutic prospects. This narrative review highlights the current understanding of ph ...[more]

PMID: 35154059

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Project description:BackgroundA multidrug-resistant co-lineage of Plasmodium falciparum malaria, named KEL1/PLA1, spread across Cambodia in 2008-13, causing high rates of treatment failure with the frontline combination therapy dihydroartemisinin-piperaquine. Here, we report on the evolution and spread of KEL1/PLA1 in subsequent years.MethodsFor this genomic epidemiology study, we analysed whole genome sequencing data from P falciparum clinical samples collected from patients with malaria between 2007 and 2018 from Cambodia, Laos, northeastern Thailand, and Vietnam, through the MalariaGEN P falciparum Community Project. Previously unpublished samples were provided by two large-scale multisite projects: the Tracking Artemisinin Resistance Collaboration II (TRAC2) and the Genetic Reconnaissance in the Greater Mekong Subregion (GenRe-Mekong) project. By investigating genome-wide relatedness between parasites, we inferred patterns of shared ancestry in the KEL1/PLA1 population.FindingsWe analysed 1673 whole genome sequences that passed quality filters, and determined KEL1/PLA1 status in 1615. Before 2009, KEL1/PLA1 was only found in western Cambodia; by 2016-17 its prevalence had risen to higher than 50% in all of the surveyed countries except for Laos. In northeastern Thailand and Vietnam, KEL1/PLA1 exceeded 80% of the most recent P falciparum parasites. KEL1/PLA1 parasites maintained high genetic relatedness and low diversity, reflecting a recent common origin. Several subgroups of highly related parasites have recently emerged within this co-lineage, with diverse geographical distributions. The three largest of these subgroups (n=84, n=79, and n=47) mostly emerged since 2016 and were all present in Cambodia, Laos, and Vietnam. These expanding subgroups carried new mutations in the crt gene, which arose on a specific genetic background comprising multiple genomic regions. Four newly emerging crt mutations were rare in the early period and became more prevalent by 2016-17 (Thr93Ser, rising to 19·8%; His97Tyr to 11·2%; Phe145Ile to 5·5%; and Ile218Phe to 11·1%).InterpretationAfter emerging and circulating for several years within Cambodia, the P falciparum KEL1/PLA1 co-lineage diversified into multiple subgroups and acquired new genetic features, including novel crt mutations. These subgroups have rapidly spread into neighbouring countries, suggesting enhanced fitness. These findings highlight the urgent need for elimination of this increasingly drug-resistant parasite co-lineage, and the importance of genetic surveillance in accelerating malaria elimination efforts.FundingWellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.

Dataset Information

Phage Revolution Against Multidrug-Resistant Clinical Pathogens in Southeast Asia.

Publications

Phage Revolution Against Multidrug-Resistant Clinical Pathogens in Southeast Asia.

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