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ELife Sep 2023The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse serovar Typhi (Typhi) genomic data to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000).
METHODS
This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch.
RESULTS
Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes.
CONCLUSIONS
The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies.
FUNDING
No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).
Topics: Humans; Salmonella typhi; Typhoid Fever; Anti-Bacterial Agents; Travel; Drug Resistance, Bacterial; Ciprofloxacin
PubMed: 37697804
DOI: 10.7554/eLife.85867 -
Microbiology (Reading, England) Oct 2023The pathogenicity island 2 (SPI-2)-encoded type III secretion system (injectisome) is assembled following uptake of bacteria into vacuoles in mammalian cells. The...
The pathogenicity island 2 (SPI-2)-encoded type III secretion system (injectisome) is assembled following uptake of bacteria into vacuoles in mammalian cells. The injectisome translocates virulence proteins (effectors) into infected cells. Numerous studies have established the requirement for a functional SPI-2 injectisome for growth of Typhimurium in mouse macrophages, but the results of similar studies involving Typhi and human-derived macrophages are not consistent. It is important to clarify the functions of the . Typhi SPI-2 injectisome, not least because an inactivated SPI-2 injectisome forms the basis for live attenuated . Typhi vaccines that have undergone extensive trials in humans. Intracellular expression of injectisome genes and effector delivery take longer in the . Typhi/human macrophage model than for . Typhimurium and we propose that this could explain the conflicting results. Furthermore, strains of both . Typhimurium and . Typhi contain intact genes for several 'core' effectors. In . Typhimurium these cooperate to regulate the vacuole membrane and contribute to intracellular bacterial replication; similar functions are therefore likely in . Typhi.
Topics: Mice; Animals; Humans; Salmonella typhi; Genomic Islands; Bacterial Proteins; Salmonella typhimurium; Macrophages; Mammals
PubMed: 37862087
DOI: 10.1099/mic.0.001405 -
ACS Omega Jul 2023Typhi ( Typhi), the invasive typhoidal serovar of that causes typhoid fever in humans, is a severe threat to global health. It is one of the major causes of high... (Review)
Review
Typhi ( Typhi), the invasive typhoidal serovar of that causes typhoid fever in humans, is a severe threat to global health. It is one of the major causes of high morbidity and mortality in developing countries. According to recent WHO estimates, approximately 11-21 million typhoid fever illnesses occur annually worldwide, accounting for 0.12-0.16 million deaths. infection can spread to healthy individuals by the consumption of contaminated food and water. Typhoid fever in humans sometimes is accompanied by several other critical extraintestinal complications related to the central nervous system, cardiovascular system, pulmonary system, and hepatobiliary system. Pathogenicity Island-1 and Pathogenicity Island-2 are the two genomic segments containing genes encoding virulent factors that regulate its invasion and systemic pathogenesis. This Review aims to shed light on a comparative analysis of the virulence and pathogenesis of the typhoidal and nontyphoidal serovars of
PubMed: 37521659
DOI: 10.1021/acsomega.3c02386 -
MBio Aug 2023We performed whole-genome sequencing of 174 Typhi and 54 Paratyphi A isolates collected through prospective surveillance in the context of a phased typhoid conjugate...
We performed whole-genome sequencing of 174 Typhi and 54 Paratyphi A isolates collected through prospective surveillance in the context of a phased typhoid conjugate vaccine introduction in Navi Mumbai, India. We investigate the temporal and geographical patterns of emergence and spread of antimicrobial resistance. We evaluated the relationship between the spatial distance between households and genetic clustering of isolates. Most isolates were non-susceptible to fluoroquinolones, with nearly 20% containing ≥3 quinolone resistance-determining region mutations. Two H58 isolates carried an IncX3 plasmid containing bla, associated with ceftriaxone resistance, suggesting that the ceftriaxone-resistant isolates from India independently evolved on multiple occasions. Among . Typhi, we identified two main clades circulating (2.2 and 4.3.1 [H58]); 2.2 isolates were closely related following a single introduction around 2007, whereas H58 isolates had been introduced multiple times to the city. Increasing geographic distance between isolates was strongly associated with genetic clustering (odds ratio [OR] = 0.72 per km; 95% credible interval [CrI]: 0.66-0.79). This effect was seen for distances up to 5 km (OR = 0.65 per km; 95% CrI: 0.59-0.73) but not seen for distances beyond 5 km (OR = 1.02 per km; 95% CrI: 0.83-1.26). There was a non-significant reduction in odds of clustering for pairs of isolates in vaccination communities compared with non-vaccination communities or mixed pairs compared with non-vaccination communities. Our findings indicate that . Typhi was repeatedly introduced into Navi Mumbai and then spread locally, with strong evidence of spatial genetic clustering. In addition to vaccination, local interventions to improve water and sanitation will be critical to interrupt transmission. IMPORTANCE Enteric fever remains a major public health concern in many low- and middle-income countries, as antimicrobial resistance (AMR) continues to emerge. Geographical patterns of typhoidal spread, critical to monitoring AMR and planning interventions, are poorly understood. We performed whole-genome sequencing of . Typhi and . Paratyphi A isolates collected in Navi Mumbai, India before and after a typhoid conjugate vaccine introduction. From timed phylogenies, we found two dominant circulating lineages of . Typhi in Navi Mumbai-lineage 2.2, which expanded following a single introduction a decade prior, and 4.3.1 (H58), which had been introduced repeatedly from other parts of India, frequently containing "triple mutations" conferring high-level ciprofloxacin resistance. Using Bayesian hierarchical statistical models, we found that spatial distance between cases was strongly associated with genetic clustering at a fine scale (<5 km). Together, these findings suggest that antimicrobial-resistant . Typhi frequently flows between cities and then spreads highly locally, which may inform surveillance and prevention strategies.
Topics: Humans; Salmonella typhi; Typhoid Fever; Anti-Bacterial Agents; Ceftriaxone; Bayes Theorem; Prospective Studies; Vaccines, Conjugate; Drug Resistance, Bacterial; Genotype; Microbial Sensitivity Tests; India
PubMed: 37504577
DOI: 10.1128/mbio.01179-23 -
Cureus Jul 2023Enteric fever is a systemic infection caused by highly virulent serovars: Typhi and Paratyphi. Diagnosis of enteric fever is challenging due to a wide variety of... (Review)
Review
Enteric fever is a systemic infection caused by highly virulent serovars: Typhi and Paratyphi. Diagnosis of enteric fever is challenging due to a wide variety of clinical features which overlap with other febrile illnesses. The current diagnostic methods are limited because of the suboptimal sensitivity of conventional tests like blood culture in detecting organisms and the invasive nature of bone marrow culture. It emphasizes the need to develop improved and more reliable diagnostic modalities. The rising rates of multidrug-resistant strains call for an accurate understanding of the current management of the disease. Proper public health measures and large-scale immunization programs will help reduce the burden of the disease. A comprehensive surveillance system can help detect the chronic carrier state and is crucial in understanding antibiotic susceptibility patterns. We conducted an all-language literature search on Medline, Cochrane, Embase, and Google Scholar till May 2022. The following search words and medical subject headings (MeSH) were used: "enteric fever," " Typhi," "multidrug-resistant ," chronic carrier state," " detection, "and "typhoid vaccine." We reviewed the literature on clinical features, pathophysiology, new diagnostic tests, and interventions to prevent the disease. This article explores enteric fever and its various clinical features and addresses the emerging threat of multidrug resistance. It focuses on novel methods for diagnosis and prevention strategies, including vaccines and the use of surveillance systems employed across different parts of the world.
PubMed: 37575696
DOI: 10.7759/cureus.41831 -
The Journal of Infectious Diseases Apr 2024Environmental surveillance (ES) for Salmonella Typhi potentially offers a low-cost tool to identify communities with a high burden of typhoid fever.
BACKGROUND
Environmental surveillance (ES) for Salmonella Typhi potentially offers a low-cost tool to identify communities with a high burden of typhoid fever.
METHODS
We developed standardized protocols for typhoid ES, including sampling site selection, validation, characterization; grab or trap sample collection, concentration; and quantitative PCR targeting Salmonella genes (ttr, staG, and tviB) and a marker of human fecal contamination (HF183). ES was implemented over 12 months in a historically high typhoid fever incidence setting (Vellore, India) and a lower incidence setting (Blantyre, Malawi) during 2021-2022.
RESULTS
S. Typhi prevalence in ES samples was higher in Vellore compared with Blantyre; 39/520 (7.5%; 95% confidence interval [CI], 4.4%-12.4%) vs 11/533 (2.1%; 95% CI, 1.1%-4.0%) in grab and 79/517 (15.3%; 95% CI, 9.8%-23.0%) vs 23/594 (3.9%; 95% CI, 1.9%-7.9%) in trap samples. Detection was clustered by ES site and correlated with site catchment population in Vellore but not Blantyre. Incidence of culture-confirmed typhoid in local hospitals was low during the study and zero some months in Vellore despite S. Typhi detection in ES.
CONCLUSIONS
ES describes the prevalence and distribution of S. Typhi even in the absence of typhoid cases and could inform vaccine introduction. Expanded implementation and comparison with clinical and serological surveillance will further establish its public health utility.
Topics: Humans; Typhoid Fever; Salmonella typhi; Malawi; Incidence; India; Typhoid-Paratyphoid Vaccines
PubMed: 37775091
DOI: 10.1093/infdis/jiad427