Combatting antimicrobial resistance in Nepal: the need for precision surveillance programmes and multi-sectoral partnership.
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ABSTRACT:
SUBMITTER: Acharya KP
PROVIDER: S-EPMC8210179 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Antimicrobial resistance (AMR) is a global problem, and Nepal is no exception. Countries are expected to report annually to the World Health Organization on their AMR surveillance progress through a Global Antimicrobial Resistance Surveillance System, in which Nepal enrolled in 2017. We assessed the quality of AMR surveillance data during 2019-2020 at nine surveillance sites in Province 3 of Nepal for completeness, consistency, and timeliness and examined barriers for non-reporting sites. Here, we present the results of this cross-sectional descriptive study of secondary AMR data from five reporting sites and barriers identified through a structured questionnaire completed by representatives at the five reporting and four non-reporting sites. Among the 1584 records from the reporting sites assessed for consistency and completeness, 77-92% were consistent and 88-100% were complete, with inter-site variation. Data from two sites were received by the 15th day of the following month, whereas receipt was delayed by a mean of 175 days at three other sites. All four non-reporting sites lacked dedicated data personnel, and two lacked computers. The AMR surveillance data collection process needs improvement in completeness, consistency, and timeliness. Non-reporting sites need support to meet the specific requirements for data compilation and sharing.
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Project description:Antibiotics are the cornerstone of modern medicine and agriculture, and rising antibiotic resistance is one the biggest threats to global health and food security. Identifying new and different druggable targets for the development of new antibiotics is absolutely crucial to overcome resistance. Adjuvant strategies that either enhance the activity of existing antibiotics or improve clearance by the host immune system provide another mechanism to combat antibiotic resistance. Targeting a combination of essential and non-essential enzymes that play key roles in bacterial metabolism is a promising strategy to develop new antimicrobials and adjuvants, respectively. The enzymatic synthesis of L-cysteine is one such strategy. Cysteine plays a key role in proteins and is crucial for the synthesis of many biomolecules important for defense against the host immune system. Cysteine synthesis is a two-step process, catalyzed by two enzymes. Serine acetyltransferase (CysE) catalyzes the first step to synthesize the pathway intermediate O-acetylserine, and O-acetylserine sulfhydrylase (CysK/CysM) catalyzes the second step using sulfide or thiosulfate to produce cysteine. Disruption of the cysteine biosynthesis pathway results in dysregulated sulfur metabolism, altering the redox state of the cell leading to decreased fitness, enhanced susceptibility to oxidative stress and increased sensitivity to antibiotics. In this review, we summarize the structure and mechanism of characterized CysE and CysK/CysM enzymes from a variety of bacterial pathogens, and the evidence that support targeting these enzymes for the development of new antimicrobials or antibiotic adjuvants. In addition, we explore and compare compounds identified thus far that target these enzymes.
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Project description:Background: Children are substantially affected by enteric fever in most settings with a high burden of the disease, including Nepal. However pathogen population structure and transmission dynamics are poorly delineated in young children, the proposed target group for immunization programs. Here we present whole genome sequencing and antimicrobial susceptibility data on 198 S. Typhi and 66 S. Paratyphi A isolated from children aged 2 months to 15 years of age during blood culture surveillance at Patan Hospital, Nepal, 2008-2016.Principal findings: S. Typhi was the dominant agent and comprised several distinct genotypes, dominated by 4.3.1 (H58). The heterogeneity of genotypes in children under five was reduced compared to data from 2005-2006, attributable to ongoing clonal expansion of H58. Most isolates (86%) were non-susceptible to fluoroquinolones, associated mainly with S. Typhi H58 lineage II and S. Paratyphi A harbouring mutations in the quinolone resistance-determining region (QRDR); non-susceptible strains from these groups accounted for 50% and 25% of all isolates. Multi-drug resistance (MDR) was rare (3.5% of S. Typhi, 0 S. Paratyphi A) and restricted to chromosomal insertions of resistance genes in H58 lineage I strains. Temporal analyses revealed a shift in dominance from H58 Lineage I to H58 Lineage II, with the latter being significantly more common after 2010. Comparison to global data sets showed the local S. Typhi and S. Paratyphi A strains had close genetic relatives in other South Asian countries, indicating regional strain circulation. Multiple imports from India of ciprofloxacin-resistant H58 lineage II strains were identified, but these were rare and showed no evidence of clonal replacement of local S. Typhi.Significance: These data indicate that enteric fever in Nepal continues to be a major public health issue with ongoing inter- and intra-country transmission, and highlights the need for regional coordination of intervention strategies. The absence of a S. Paratyphi A vaccine is cause for concern, given its prevalence as a fluoroquinolone resistant enteric fever agent in this setting.
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