Abstract
Background Typhoid fever results from systemic infection with Salmonella enterica serovar Typhi (Typhi) and causes 10 million illnesses annually. Disease control relies on prevention (water, sanitation, and hygiene interventions or vaccination) and effective antimicrobial treatment. Antimicrobial resistant (AMR) Typhi lineages have emerged and become established in many parts of the world. Knowledge of local pathogen populations informed by genomic surveillance, including of lineages (defined by the GenoTyphi scheme) and AMR determinants, is increasingly used to inform local treatment guidelines and to inform vaccination strategy. Current tools for genotyping Typhi require multiple read alignment or assembly steps and have not been validated for analysis of data generated with Oxford Nanopore Technologies (ONT) long-read sequencing devices. Here, we introduce Typhi Mykrobe, a command line software tool for rapid genotyping of Typhi lineages, AMR determinants, and plasmid replicons direct from sequencing reads.
Competing Interest Statement
MML was a co-developer of a Trivalent Salmonella (Enteritidis/Typhimurium/Typhi Vi) conjugate vaccine with Bharat Biotech International and the Wellcome Trust. MML has also received payments from Pfizer for consultancy work. MML holds US patents for Compositions and Methods for Producing Bacterial Conjugate Vaccines. MML was a member of a NIH DSMB that oversaw US government funded efficacy trials of COVID-19 vaccines. DSMB was disbanded after several vaccines were given Emergency Use Authorization. MML was a member of the Vaccines and Related Biological Products Advisory Committee of the FDA. IIB was a consultant for the Weapons Threat Reduction Program, Global Affairs Canada. AJP has been involved an Oxford University partnership with AZ for development of COVI19 vaccines. AJP has received payments for consultancy work from Shionogi. AJP is chair of DHSCs Joint Committee on Vaccination and Immunisation, is a chair of WHOs Salmonella TAG, and was a member of WHOs SAGE. AJP received support from MRNA Moderna. KLC has received payments from Pfizer for presentations and travel support from BD. INO has received payments from the Wellcome Trust for consultancy work and receives royalties for books or book chapters published via Springer, Cornell University Press, and Oxford University Press. INO has received travel support from BMGF, ESCMID, and the American ASM and has held leadership or advisory roles for Wellcome SEDRIC, the BMGF surveillance advisory group, the Thomas Bassir Biomedical Foundation, and International Centre for Antimicrobial Resistance Solutions (ICARS) Technical Advisory Forum. ZI has received travel support from ETH Zurich.
List of abbreviations
- AMR
- antimicrobial resistance
- AST
- antimicrobial susceptibility testing
- CARD
- Comprehensive Antibiotic Resistance Database
- CLSI
- Clinical & Laboratory Standards Institute
- EUCAST
- The European Committee on Antimicrobial Susceptibility Testing
- FDA
- United States of America Food and Drug Administration
- MDR
- multidrug resistance
- MIC
- minimum inhibitory concentration
- ONT
- Oxford Nanopore Technologies
- QRDR
- quinolone resistance-determining regions
- SEAP
- Surveillance for Enteric Fever in Asia Project
- SNV
- single nucleotide variants
- UKHSA
- United Kingdom Health Security Agency
- US CDC
- United States of America Centres for Disease Control and Prevention
- WGS
- whole genome sequencing
- XDR
- extensively drug resistant
