Laboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: Antimicrobial resistance and implications for vaccine policy

• Published in: PLoS neglected tropical diseases Vol. 12; no. 4; p. e0006408
• Main Authors: Britto, Carl D, Dyson, Zoe A, Duchene, Sebastian, Carter, Michael J, Gurung, Meeru, Kelly, Dominic F, Murdoch, David R, Ansari, Imran, Thorson, Stephen, Shrestha, Shrijana, Adhikari, Neelam, Dougan, Gordon, Holt, Kathryn E, Pollard, Andrew J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.04.2018; Public Library of Science (PLoS)
• Subjects: Adolescent; Anti-Infective Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial agents; Antimicrobial resistance; Bacterial infections; Biochemistry; Biology and Life Sciences; Biomedical research; Biotechnology; Blood culture; Causes of; Child; Child, Preschool; Children; Chromosomes; Ciprofloxacin; Ciprofloxacin - therapeutic use; Complications and side effects; Computer and Information Sciences; Data; Demographic aspects; Disease control; Drug resistance; Drug Resistance, Bacterial; Dynamics; Female; Fever; Fluoroquinolones; Fluoroquinolones - therapeutic use; Funding; Gene sequencing; Genes; Genomes; Genotype; Genotypes; Health sciences; Hospitals; Humans; Immunization; Imports; Infant; Infections; Male; Medicine and Health Sciences; Microbial drug resistance; Molecular biology; Molecular chains; Multidrug resistance; Mutation; Nepal - epidemiology; People and Places; Physiological aspects; Policies; Population structure; Prevention; Public health; Salmonella; Salmonella enterica; Salmonella typhi; Salmonella typhi - genetics; Salmonella typhi - immunology; Salmonella typhi - isolation & purification; Salmonella typhi - physiology; Strains; Strains (organisms); Supervision; Surveillance; Systematic review; Transmission; Tropical diseases; Typhoid; Typhoid fever; Typhoid Fever - epidemiology; Typhoid Fever - microbiology; Typhoid Fever - prevention & control; Typhoid-Paratyphoid Vaccines; Vaccines; United Kingdom; Victoria Australia; Pakistan; United Kingdom > UK; Australia; Nepal; India
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0006408

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. 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. 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.