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The New England Journal of Medicine Nov 2002
Review
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Bacterial; Drug Resistance, Multiple; Endemic Diseases; Escherichia coli; Fluoroquinolones; Genome, Bacterial; Humans; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines
PubMed: 12456854
DOI: 10.1056/NEJMra020201 -
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 -
International Journal of Infectious... Aug 2020Enteric fever remains an important diagnostic and treatment challenge in febrile children living in the tropics. In the context of a national Salmonella enterica serovar...
OBJECTIVES
Enteric fever remains an important diagnostic and treatment challenge in febrile children living in the tropics. In the context of a national Salmonella enterica serovar Paratyphi A outbreak, the objective of this retrospective study was to compare features of S. Typhi and S. Paratyphi A infections in Cambodian children.
METHODS
Clinical and laboratory features were reviewed for 192 blood culture-confirmed children with S. Typhi and S. Paratyphi A infections presenting to a paediatric referral hospital in Siem Reap, 2012-2016.
RESULTS
Children with S. Typhi infections were younger, were more likely to have chills and/or diarrhoea, and were more frequently hospitalized than those with S. Paratyphi A infections. Over three quarters (88.3%) of S. Typhi isolates were multidrug-resistant, compared to none of the S. Paratyphi A.
CONCLUSIONS
In this small study of Cambodian children, S. Typhi infections were more severe than S. Paratyphi A infections. Antibiotic resistance limits treatment options for enteric fever in this population.
Topics: Adolescent; Anti-Bacterial Agents; Cambodia; Child; Child, Preschool; Female; Hospitals, Pediatric; Humans; Infant; Male; Paratyphoid Fever; Retrospective Studies; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever
PubMed: 32569838
DOI: 10.1016/j.ijid.2020.06.054 -
Microbial Genomics Aug 2021The emergence of antimicrobial resistance (AMR) to first- and second-line treatment regimens of enteric fever is a global public-health problem, and routine genomic...
The emergence of antimicrobial resistance (AMR) to first- and second-line treatment regimens of enteric fever is a global public-health problem, and routine genomic surveillance to inform clinical and public-health management guidance is essential. Here, we present the prospective analysis of genomic data to monitor trends in incidence, AMR and travel, and assess hierarchical clustering (HierCC) methodology of 1742 isolates of typhoidal salmonellae. Trend analysis of Typhi and . Paratyphi A cases per year increased 48 and 17.3%, respectively, between 2016 and 2019 in England, mainly associated with travel to South Asia. . Paratyphi B cases have remained stable and are mainly associated with travel to the Middle East and South America. There has been an increase in the number of . Typhi exhibiting a multidrug-resistant (MDR) profile and the emergence of extensively drug resistant (XDR) profiles. HierCC was a robust method to categorize clonal groups into clades and clusters associated with travel and AMR profiles. The majority of cases that had XDR . Typhi reported recent travel to Pakistan (94 %) and belonged to a subpopulation of the 4.3.1 (H58) clone (HC5_1452). The phenotypic and genotypic AMR results showed high concordance for . Typhi and . Paratyphi A, B and C, with 99.99 % concordance and only three (0.01 %) discordant results out of a possible 23 178 isolate/antibiotic combinations. Genomic surveillance of enteric fever has shown the recent emergence and increase of MDR and XDR . Typhi strains, resulting in a review of clinical guidelines to improve management of imported infections.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Drug Resistance, Bacterial; England; Female; Genotype; Humans; Infant; Infant, Newborn; Male; Middle Aged; Middle East; Pakistan; Phylogeny; Salmonella typhi; Typhoid Fever; Young Adult
PubMed: 34370659
DOI: 10.1099/mgen.0.000633 -
Microbiological Research Apr 2012Salmonella enterica serovar Typhi (S. Typhi), the aetiologic agent of typhoid fever, is a human restricted pathogen. The molecular mechanism of Salmonella pathogenicity... (Review)
Review
Salmonella enterica serovar Typhi (S. Typhi), the aetiologic agent of typhoid fever, is a human restricted pathogen. The molecular mechanism of Salmonella pathogenicity is complex. The investigations of the molecular mechanisms of Salmonella virulence factors have shown that pathogenic Salmonella spp. are distinguished from their non-pathogenic relatives by the presence of specific pathogenicity genes, often organized in so-called pathogenicity islands (PIs). The type III secretion system (T3SS) proteins encoded by two Salmonella PIs (SPIs) are associated with the pathogenicity at molecular level. The identification of T3SS has provided new insight into the molecular factors and mechanisms underlying bacterial pathogenesis. The T3SS encoded by SPI-1 contains invasion genes; while SPI-2 is responsible for intracellular pathogenesis and has a crucial role for systemic S. enterica infections. These studies reveal a complex set of pathogenic interferences between intracellular Salmonella and its host cells. The understanding of the mechanisms by which Salmonella evade the host defense system and establish pathogenesis will be important for proper disease management.
Topics: Antigens, Bacterial; Bacterial Secretion Systems; Genes, Bacterial; Genomic Islands; Humans; Salmonella typhi; Virulence Factors
PubMed: 21945101
DOI: 10.1016/j.micres.2011.08.001 -
MBio Nov 2018Typhoid fever, caused by serovar Typhi, is a global public health concern due to increasing antimicrobial resistance (AMR). Characterization of Typhi genomes for AMR...
Typhoid fever, caused by serovar Typhi, is a global public health concern due to increasing antimicrobial resistance (AMR). Characterization of Typhi genomes for AMR and the evolution of different lineages, especially in countries where typhoid fever is endemic such as Bangladesh, will help public health professionals to better design and implement appropriate preventive measures. We studied whole-genome sequences (WGS) of 536 Typhi isolates collected in Bangladesh during 1999 to 2013 and compared those sequences with data from a recent outbreak in Pakistan reported previously by E. J. Klemm, S. Shakoor, A. J. Page, F. N. Qamar, et al. (mBio 9:e00105-18, 2018, https://doi.org/10.1128/mBio.00105-18), and a laboratory surveillance in Nepal reported previously by C. D. Britto, Z. A. Dyson, S. Duchene, M. J. Carter, et al. [PLoS Negl. Trop. Dis. 12(4):e0006408, 2018, https://doi.org/10.1371/journal.pntd.0006408]. WGS had high sensitivity and specificity for prediction of ampicillin, chloramphenicol, co-trimoxazole, and ceftriaxone AMR phenotypes but needs further improvement for prediction of ciprofloxacin resistance. We detected a new local lineage of genotype 4.3.1 (named lineage Bd) which recently diverged into a sublineage (named Bdq) containing genes associated with high-level ciprofloxacin resistance. We found a ceftriaxone-resistant isolate with the gene and a genotype distinct from the genotypes of extensively drug-resistant (XDR) isolates from Pakistan. This result suggests a different source and geographical origin of AMR. Genotype 4.3.1 was dominant in all three countries but formed country-specific clusters in the maximum likelihood phylogenetic tree. Thus, multiple independent genetic events leading to ciprofloxacin and ceftriaxone resistance took place in these neighboring regions of Pakistan, Nepal, and Bangladesh. These independent mutational events may enhance the risk of global spread of these highly resistant clones. A short-term global intervention plan is urgently needed. Typhoid fever, caused by serovar Typhi, is responsible for an estimated burden of approximately 17 million new episodes per year worldwide. Adequate and timely antimicrobial treatment invariably cures typhoid fever. The increasing antimicrobial resistance (AMR) of Typhi severely limits the treatment options. We studied whole-genome sequences (WGS) of 536 Typhi isolates collected in Bangladesh between 1999 and 2013 and compared those sequences with data from a recent outbreak in Pakistan and a laboratory surveillance in Nepal. The analysis suggests that multiple ancestral origins of resistance against ciprofloxacin and ceftriaxone are present in three countries. Such independent genetic events and subsequent dissemination could enhance the risk of a rapid global spread of these highly resistant clones. Given the current treatment challenges, vaccination seems to be the most appropriate short-term intervention to reduce the disease burden of typhoid fever at a time of increasing AMR.
Topics: Adolescent; Adult; Ampicillin; Anti-Bacterial Agents; Bangladesh; Child; Child, Preschool; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Female; Genetic Variation; Genome, Bacterial; Genomics; Genotype; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Phylogeny; Salmonella typhi; Typhoid Fever; Whole Genome Sequencing; Young Adult
PubMed: 30425150
DOI: 10.1128/mBio.02112-18 -
Tropical Medicine & International... Aug 2017Next-generation whole-genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding... (Review)
Review
Next-generation whole-genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding have transformed the field of molecular microbiology, epidemiology, infection treatments and vaccine developments. We review the key findings of the publicly accessible genomes of Salmonella enterica serovar Typhi since the first complete genome to the most recent release of thousands of Salmonella Typhi genomes, which remarkably shape the genomic research of S. Typhi and other pathogens. Important new insights acquired from the genome sequencing of S. Typhi, pertaining to genomic variations, evolution, population structure, antibiotic resistance, virulence, pathogenesis, disease surveillance/investigation and disease control are discussed. As the numbers of sequenced genomes are increasing at an unprecedented rate, fine variations in the gene pool of S. Typhi are captured in high resolution, allowing deeper understanding of the pathogen's evolutionary trends and its pathogenesis, paving the way to bringing us closer to eradication of typhoid through effective vaccine/treatment development.
Topics: Biological Evolution; Drug Resistance, Microbial; Genome, Bacterial; Humans; Phylogeny; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines
PubMed: 28544285
DOI: 10.1111/tmi.12899 -
PloS One 2023Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever and, in some cases, chronic carriage after resolution of acute disease. This study examined sequential...
Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever and, in some cases, chronic carriage after resolution of acute disease. This study examined sequential isolates of S. Typhi from a single host with persistent asymptomatic infection. These isolates, along with another S. Typhi isolate recovered from a household contact with typhoid fever, were subjected to whole genome sequencing and analysis. In addition, direct sequencing of the bile fluid from the host with persistent infection was also performed. Comparative analysis of isolates revealed three sub-populations of S. Typhi with distinct genetic patterns. Metagenomic sequencing recognised only two of the three sub-populations within the bile fluid. The detection and investigation of insertion sequences IS10R and associated deletions complemented analysis of single nucleotide polymorphisms. These findings improve our understanding of within-host dynamics of S. Typhi in cases of persistent infection and inform epidemiological investigations of transmission events associated with chronic carriers.
Topics: Humans; Salmonella typhi; Typhoid Fever; Metagenomics; Persistent Infection; Whole Genome Sequencing
PubMed: 37611017
DOI: 10.1371/journal.pone.0289070 -
Proceedings of the National Academy of... Jun 2016Salmonella Typhi is the cause of typhoid fever, a disease that has challenged humans throughout history and continues to be a major public health concern. Unlike... (Review)
Review
Salmonella Typhi is the cause of typhoid fever, a disease that has challenged humans throughout history and continues to be a major public health concern. Unlike infections with most other Salmonellae, which result in self-limiting gastroenteritis, typhoid fever is a life-threatening systemic disease. Furthermore, in contrast to most Salmonellae, which can infect a broad range of hosts, S. Typhi is a strict human pathogen. The unique features of S. Typhi pathogenesis and its stringent host specificity have been a long-standing puzzle. The discovery of typhoid toxin not only has provided major insight into these questions but also has offered unique opportunities to develop novel therapeutic and prevention strategies to combat typhoid fever.
Topics: Animals; Bacterial Proteins; Bacterial Toxins; Host Specificity; Humans; Salmonella typhi; Typhoid Fever
PubMed: 27222578
DOI: 10.1073/pnas.1606335113 -
PLoS Neglected Tropical Diseases Feb 2020Multi-drug resistant typhoid fever remains an enormous public health threat in low and middle-income countries. However, we still lack a detailed understanding of the...
BACKGROUND
Multi-drug resistant typhoid fever remains an enormous public health threat in low and middle-income countries. However, we still lack a detailed understanding of the epidemiology and genomics of S. Typhi in many regions. Here we have undertaken a detailed genomic analysis of typhoid in urban Dhaka, Bangladesh to unravel the population structure and antimicrobial resistance patterns in S. Typhi isolated between 2004-2016.
PRINCIPAL FINDINGS
Whole genome sequencing of 202 S. Typhi isolates obtained from three study locations in urban Dhaka revealed a diverse range of S. Typhi genotypes and AMR profiles. The bacterial population within Dhaka were relatively homogenous with little stratification between different healthcare facilities or age groups. We also observed evidence of exchange of Bangladeshi genotypes with neighboring South Asian countries (India, Pakistan and Nepal) suggesting these are circulating throughout the region. This analysis revealed a decline in H58 (genotype 4.3.1) isolates from 2011 onwards, coinciding with a rise in a diverse range of non-H58 genotypes and a simultaneous rise in isolates with reduced susceptibility to fluoroquinolones, potentially reflecting a change in treatment practices. We identified a novel S. Typhi genotype, subclade 3.3.2 (previously defined only to clade level, 3.3), which formed two localized clusters (3.3.2.Bd1 and 3.3.2.Bd2) associated with different mutations in the Quinolone Resistance Determining Region (QRDR) of gene gyrA.
SIGNIFICANCE
Our analysis of S. Typhi isolates from urban Dhaka, Bangladesh isolated over a twelve year period identified a diverse range of AMR profiles and genotypes. The observed increase in non-H58 genotypes associated with reduced fluoroquinolone susceptibility may reflect a change in treatment practice in this region and highlights the importance of continued molecular surveillance to monitor the ongoing evolution of AMR in Dhaka. We have defined new genotypes and lineages of Bangladeshi S. Typhi which will facilitate the identification of these emerging AMR clones in future surveillance efforts.
Topics: Anti-Bacterial Agents; Bangladesh; DNA, Bacterial; Drug Resistance, Bacterial; Genome, Bacterial; Genotype; Humans; Internationality; Polymorphism, Single Nucleotide; Retrospective Studies; Salmonella Infections; Salmonella typhi; Time Factors; Travel; Urban Population
PubMed: 32106221
DOI: 10.1371/journal.pntd.0008036