The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi: a genomic epidemiology study.

BACKGROUND: The emergence of increasingly antimicrobial-resistant Salmonella enterica serovar Typhi (S Typhi) threatens to undermine effective treatment and control. Understanding where antimicrobial resistance in S Typhi is emerging and spreading is crucial towards formulating effective control strategies. METHODS: In this genomic epidemiology study, we sequenced the genomes of 3489 S Typhi strains isolated from prospective enteric fever surveillance studies in Nepal, Bangladesh, Pakistan, and India (between 2014 and 2019), and combined these with a global collection of 4169 S Typhi genome sequences isolated between 1905 and 2018 to investigate the temporal and geographical patterns of emergence and spread of antimicrobial-resistant S Typhi. We performed non-parametric phylodynamic analyses to characterise changes in the effective population size of fluoroquinolone-resistant, extensively drug-resistant (XDR), and azithromycin-resistant S Typhi over time. We inferred timed phylogenies for the major S Typhi sublineages and used ancestral state reconstruction methods to estimate the frequency and timing of international and intercontinental transfers. FINDINGS: Our analysis revealed a declining trend of multidrug resistant typhoid in south Asia, except for Pakistan, where XDR S Typhi emerged in 2016 and rapidly replaced less-resistant strains. Mutations in the quinolone-resistance determining region (QRDR) of S Typhi have independently arisen and propagated on at least 94 occasions, nearly all occurring in south Asia. Strains with multiple QRDR mutations, including triple mutants with high-level fluoroquinolone resistance, have been increasing in frequency and displacing strains with fewer mutations. Strains containing acrB mutations, conferring azithromycin resistance, emerged in Bangladesh around 2013 and effective population size of these strains has been steadily increasing. We found evidence of frequent international (n=138) and intercontinental transfers (n=59) of antimicrobial-resistant S Typhi, followed by local expansion and replacement of drug-susceptible clades. INTERPRETATION: Independent acquisition of plasmids and homoplastic mutations conferring antimicrobial resistance have occurred repeatedly in multiple lineages of S Typhi, predominantly arising in south Asia before spreading to other regions. FUNDING: Bill & Melinda Gates Foundation.

Rapid assessment of injection practices in Mongolia.

BACKGROUND: Anecdotal reports suggest that unsafe injections may transmit blood-borne pathogens in Mongolia. METHODS: The Ministry of Health of Mongolia collected information on injection practices, their determinants, and their consequences through interviews and observations of a small convenience sample of prescribers, injection providers, and members of the general population. RESULTS: The 65 members of the general population reported receiving an average of 13 injections per year. New, single-use injection devices were used in the 20 health care facilities visited. There were breaks in infection control practices while administering injections, including observations of 500-mL intravenous infusion bottles used as multiple-dose diluent vials and 8 of the 28 providers (28%) reporting reuse of device on the same patient. Injection providers reported 2.6 needle-stick injuries per year. Contaminated sharps were burned in a drum. Among persons interviewed, 19 of the 21 prescribers (90%) and 49% of the population were aware of the potential risk of HIV transmission through unsafe injections. CONCLUSIONS: A multidisciplinary initiative is necessary to achieve safe and appropriate use of injections in Mongolia through (1) behavior change, (2) increasing availability of injection devices and sharps boxes, and (3) appropriate sharps waste management.