Typhoid and paratyphoid fever cause 14.3 million illnesses and 135,000 deaths each year globally. It remains a major public health problem in low-and-middle-income countries (LMICs), particularly in Asian and sub-Saharan African regions.
At CHRF, we have been conducting typhoid and paratyphoid surveillance since the 1990s.
We have sequenced ~1,500 Salmonella Typhi.
List of CHRF’s publications and research findings on typhoid and paratyphoid genomics:
Genomic Surveillance of Salmonella Paratyphi A: Neglected No More?
Published in: Open Forum Infectious Diseases
Publication year: 2023
Summary:
Salmonella enterica serovar Paratyphi A, the causative agent of paratyphoid fever, is a neglected tropical disease with a high burden and mortality in low- and middle-income countries. Limited information is available regarding its genomic diversity, especially from South Asian countries that are collectively responsible for >80% of all paratyphoid cases. At the 2021 International Conference on Typhoid and Other Salmonelloses, researchers from around the globe presented their work on Salmonella Paratyphi A genomics. Presentations described recent genomic data from South Asia and the development of Paratype, an open-access single-nucleotide polymorphism-based genotyping scheme, to segregate Salmonella Paratyphi A genomes in a systematic and sustainable manner. In this review, we attempt to summarize the progress made thus far on Salmonella Paratyphi A genomics and discuss the questions that remain to better understand the pathogen and develop interventions to fight it.
Published in: Lancet Microbe
Publication year: 2022
Summary:
This study focused on the genomic epidemiology of Salmonella enterica serovar Typhi (S Typhi) and its antimicrobial resistance patterns. The researchers sequenced the genomes of S.typhi strains from multiple countries and analyzed their temporal and geographical distribution. The findings showed a decline in multidrug-resistant typhoid in South Asia, except for Pakistan, where extensively drug-resistant (XDR) S Typhi emerged and rapidly replaced less-resistant strains. Mutations associated with antimicrobial resistance were observed predominantly in South Asia, with multiple instances of international and intercontinental transfers of resistant strains. The study highlights the importance of understanding the emergence and spread of antimicrobial-resistant S Typhi for effective control strategies.
Paratype: A genotyping tool for Salmonella Paratyphi A reveals its global genomic diversity
Published in: Nature Communications
Publication year: 2022
Summary:
Salmonella Paratyphi A, the primary etiology of paratyphoid, is estimated to cause 3.4 million infections annually, worldwide. With rising antimicrobial resistance and no licensed vaccines, genomic surveillance is key to track and monitor transmission, but there is currently no reliable genotyping framework for this pathogen. Here, we sequence 817 isolates from South Asia and add 562 publicly available genomes to build a global database representing 37 countries, covering 1917–2019. We develop a single nucleotide polymorphism-based genotyping scheme, Paratype, that segregates the Salmonella Paratyphi A population into three primary and nine secondary clades, and 18 genotypes. Each genotype is assigned a unique allele definition located on an essential gene. Using Paratype, we identify spatiotemporal genomic variation and antimicrobial resistance markers. We release Paratype as an open-access tool that can use raw read files from both Illumina and Nanopore platforms and thus can assist surveillance studies tracking Salmonella Paratyphi A across the globe
Salmonella enterica Serovar Typhi on an Island: No H58, No Multidrug Resistance, but for How Long?
Published in: mBio
Publication year: 2022
Summary:
Little genomic data is available for typhoid fever from island nations, though the disease has a moderately high burden there. Sikorski et al. (M. J. Sikorski, T. H. Hazen, S. N. Desai, S. Nimarota-Brown, et al., mBio 13:e01920-22, 2022, https://doi.org/10.1128/mbio.01920-22) studied 306 Salmonella enterica serovar Typhi genomes from the Samoan Islands collected during 1983 to 2020 and reported dominance of a rare genotype, 2.5.4, and no H58 (genotype 4.3.1). They found pansusceptibility of all isolates to three first lines of antimicrobial agents (ampicillin, chloramphenicol, and cotrimoxazole). This commentary evaluates the importance of these findings for the Samoan Islands and how they can help the global typhoid community. The microbial community in the environment and human gut could have played a role in the lack of antimicrobial resistance (AMR). However, drug-resistant strains may arrive soon at the island, as their international spread is common. Further investigation would help the global typhoid community to better understand the evolution of an isolated pathogen community and the effect of vaccination there.
Tracking the Emergence of Azithromycin Resistance in Multiple Genotypes of Typhoidal Salmonella
Published in: mBio
Publication year: 2021
Summary:
The increasing prevalence of antimicrobial resistance in Salmonella serovars Typhi and Paratyphi A, which cause typhoid and paratyphoid, is a major concern due to the emergence of resistance against azithromycin, the last remaining oral drug for extensively drug-resistant (XDR) typhoid. This study reports additional cases of azithromycin-resistant Salmonella Typhi and Paratyphi A in Bangladesh between 2016 and 2018. Genomic analysis confirms that the resistance is due to a single-point mutation in the AcrB efflux pump. The study also introduces a rapid and low-cost PCR tool for the detection of this mutation, which is crucial for early intervention and surveillance of pan-oral drug resistance. The findings highlight the urgent need to address antimicrobial resistance in these bacterial strains.
Published in: BMC Genomics
Publication year: 2019
Summary:
This study aimed to investigate the genomic changes associated with antimicrobial resistance (AMR) in S. Typhi. The researchers analyzed 73 S. Typhi isolates and identified five variants of the Salmonella genomic island (SGI) 11, which carries AMR genes. They also discovered new plasmids, including two that carried AMR genes. The presence of specific plasmids and SGI11 variants was associated with certain S. Typhi lineages. The findings highlight the importance of understanding the spread of AMR elements and the potential role of vaccination programs in mitigating their impact.
Ceftriaxone-resistant Salmonella Typhi carries an IncI1-ST31 plasmid encoding CTX-M-15
Published in: Journal of Medical Microbiology
Publication year: 2018
Summary:
The emergence of ceftriaxone-resistant Salmonella Typhi has raised concerns about the treatment of typhoid fever. This study used whole genome sequencing to investigate an isolate of ceftriaxone-resistant S. Typhi obtained from a child in 2000. The analysis revealed that the closest relative of the isolate was from the Democratic Republic of the Congo in 2015, but there was no evidence of an outbreak. The study identified a plasmid belonging to the incompatibility group I1 (IncI1-ST31) carrying the gene blaCTX-M-15, which confers ceftriaxone resistance. The plasmid showed high similarity to those found in S. Enteritidis and E. coli, indicating that S. Typhi can acquire ceftriaxone resistance through the acquisition of common plasmids. The findings highlight the potential transmission of resistance from E. coli to S. Typhi and the need for alternative treatment options.
Published in: mBio
Publication year: 2018
Summary:
Typhoid fever, caused by Salmonella enterica serovar Typhi, is a global public health concern due to increasing antimicrobial resistance (AMR). A study analyzed the whole-genome sequences of 536 S. Typhi isolates collected in Bangladesh from 1999 to 2013. The findings revealed a new local lineage (lineage Bd) with high-level ciprofloxacin resistance and a distinct genotype for ceftriaxone resistance. Multiple independent genetic events leading to resistance were observed in Bangladesh, Pakistan, and Nepal, increasing the risk of global spread. Given the challenges of treating AMR, vaccination is urgently recommended as a short-term intervention to reduce the burden of typhoid fever and mitigate the spread of highly resistant clones.