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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 -
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 -
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 -
The Yale Journal of Biology and Medicine Jun 2017Unlike many of the nontyphoidal serovars such as . Typhimurium that cause restricted gastroenteritis, Typhi is unique in that it causes life-threatening typhoid fever... (Review)
Review
Unlike many of the nontyphoidal serovars such as . Typhimurium that cause restricted gastroenteritis, Typhi is unique in that it causes life-threatening typhoid fever in humans. Despite the vast difference in disease outcomes that Typhi and Typhimurium cause in humans, there are few genomic regions that are unique to Typhi. Of these regions, the most notable is the small locus encoding typhoid toxin, an AB toxin that has several distinct characteristics that contribute to . Typhi's pathogenicity. As a result, typhoid toxin and its role in . Typhi virulence have been studied in an effort to gain insight into potential treatment and prevention strategies. Given the rise of multidrug-resistant strains, research in this area has become increasingly important. This article discusses the current understanding of typhoid toxin and potential directions for future research endeavors in order to better understand the contribution of typhoid toxin to Typhi virulence.
Topics: Endotoxins; Host-Pathogen Interactions; Humans; Salmonella typhi; Typhoid Fever; Viral Tropism
PubMed: 28656014
DOI: No ID Found -
Annals of Clinical Microbiology and... May 2016Blood culture is often used in definitive diagnosis of typhoid fever while, bone marrow culture has a greater sensitivity and considered reference standard. The... (Review)
Review
Blood culture is often used in definitive diagnosis of typhoid fever while, bone marrow culture has a greater sensitivity and considered reference standard. The sensitivity of blood culture measured against bone marrow culture results in measurement bias because both tests are not fully sensitive. Here we propose a combination of the two cultures as a reference to define true positive S. Typhi cases. Based on a systematic literature review, we identified ten papers that had performed blood and bone marrow culture for S. Typhi in same subjects. We estimated the weighted mean of proportion of cases detected by culture measured against true S. Typhi positive cases using a random effects model. Of 529 true positive S. Typhi cases, 61 % (95 % CI 52-70 %) and 96 % (95 % CI 93-99 %) were detected by blood and bone marrow cultures respectively. Blood culture sensitivity was 66 % (95 % CI 56-75 %) when compared with bone marrow culture results. The use of blood culture sensitivity as a proxy measure to estimate the proportion of typhoid fever cases detected by blood culture is likely to be an underestimate. As blood culture sensitivity is used as a correction factor in estimating typhoid disease burden, epidemiologists and policy makers should account for the underestimation.
Topics: Blood Culture; Bone Marrow; False Negative Reactions; False Positive Reactions; Humans; Salmonella typhi; Sensitivity and Specificity; Typhoid Fever
PubMed: 27188991
DOI: 10.1186/s12941-016-0147-z -
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 -
PLoS Neglected Tropical Diseases Sep 2021Little is known about the genetic diversity of Salmonella enterica serovar Typhi (S. Typhi) circulating in Latin America. It has been observed that typhoid fever is...
Little is known about the genetic diversity of Salmonella enterica serovar Typhi (S. Typhi) circulating in Latin America. It has been observed that typhoid fever is still endemic in this part of the world; however, a lack of standardized blood culture surveillance across Latin American makes estimating the true disease burden problematic. The Colombian National Health Service established a surveillance system for tracking bacterial pathogens, including S. Typhi, in 2006. Here, we characterized 77 representative Colombian S. Typhi isolates collected between 1997 and 2018 using pulse field gel electrophoresis (PFGE; the accepted genotyping method in Latin America) and whole genome sequencing (WGS). We found that the main S. Typhi clades circulating in Colombia were clades 2.5 and 3.5. Notably, the sequenced S. Typhi isolates from Colombia were closely related in a global phylogeny. Consequently, these data suggest that these are endemic clades circulating in Colombia. We found that AMR in S. Typhi in Colombia was uncommon, with a small subset of organisms exhibiting mutations associated with reduced susceptibility to fluoroquinolones. This is the first time that S. Typhi isolated from Colombia have been characterized by WGS, and after comparing these data with those generated using PFGE, we conclude that PFGE is unsuitable for tracking S. Typhi clones and mapping transmission. The genetic diversity of pathogens such as S. Typhi is limited in Latin America and should be targeted for future surveillance studies incorporating WGS.
Topics: Anti-Bacterial Agents; Colombia; Drug Resistance, Bacterial; Population Surveillance; Salmonella typhi; Typhoid Fever
PubMed: 34529660
DOI: 10.1371/journal.pntd.0009755 -
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