Dataset Information

A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital.

ABSTRACT: Background: Salmonella serovars Typhi (S. Typhi) and Paratyphi A (S. Paratyphi A), the causative agents of enteric fever, have been routinely isolated organisms from the blood of febrile patients in the Kathmandu Valley since the early 1990s. Susceptibility against commonly used antimicrobials for treating enteric fever has gradually changed throughout South Asia since this time, posing serious treatment challenges. Here, we aimed to longitudinally describe trends in the isolation of Salmonella enterica and assess changes in their antimicrobial susceptibility in Kathmandu over a 23-year period.

Methods: We conducted a retrospective analysis of standardised microbiological data from April 1992 to December 2014 at a single healthcare facility in Kathmandu, examining time trends of Salmonella-associated bacteraemia and the corresponding antimicrobial susceptibility profiles of the isolated organisms.

Results: Over 23 years there were 30,353 positive blood cultures. Salmonella enterica accounted for 65.4% (19,857/30,353) of all the bacteria positive blood cultures. S. Typhi and S. Paratyphi A were the dominant serovars, constituting 68.5% (13,592/19,857) and 30.5% (6,057/19,857) of all isolated Salmonellae. We observed (i) a peak in the number of Salmonella-positive cultures in 2002, a year of heavy rainfall and flooding in the Kathmandu Valley, followed by a decline toward pre-flood baseline by 2014, (ii) an increase in the proportion of S. Paratyphi in all Salmonella-positive cultures between 1992 and 2014, (iii) a decrease in the prevalence of MDR for both S. Typhi and S. Paratyphi, and (iv) a recent increase in fluoroquinolone non-susceptibility in both S. Typhi and S. Paratyphi isolates.

Conclusions: Our work describes significant changes in the epidemiology of Salmonella enterica in the Kathmandu Valley during the last quarter of a century. We highlight the need to examine current treatment protocols for enteric fever and suggest a change from fluoroquinolone monotherapy to combination therapies of macrolides or cephalosporins along with older first-line antimicrobials that have regained their efficacy.

SUBMITTER: Zellweger RM

PROVIDER: S-EPMC5720835 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital.

Zellweger Raphaël M RM Basnyat Buddha B Shrestha Poojan P Prajapati Krishna G KG Dongol Sabina S Sharma Paban K PK Koirala Samir S Darton Thomas C TC Dolecek Christiane C Thompson Corinne N CN Thwaites Guy E GE Baker Stephen G SG Karkey Abhilasha A

PLoS neglected tropical diseases 20171127 11

<h4>Background</h4>Salmonella serovars Typhi (S. Typhi) and Paratyphi A (S. Paratyphi A), the causative agents of enteric fever, have been routinely isolated organisms from the blood of febrile patients in the Kathmandu Valley since the early 1990s. Susceptibility against commonly used antimicrobials for treating enteric fever has gradually changed throughout South Asia since this time, posing serious treatment challenges. Here, we aimed to longitudinally describe trends in the isolation of Salm ...[more]

PMID: 29176850

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Project description:PurposeThe morbidity and mortality due to typhoid fever can be significantly reduced with the use of effective antibiotics. At present, fluoroquinolones, third generation cephalosporins, and azithromycin are widely used to treat typhoid fever. However, changing antibiotic susceptibility among Salmonella Typhi and Salmonella Paratyphi poses a particular challenge to the therapeutic management of enteric fever. The objective of this study was to assess the antibiotic susceptibility pattern of Salmonella Typhi isolates.Patients and methodsA total of 706 blood specimens were collected from febrile patients attending the outpatient department of Kathmandu Model Hospital during June to September, 2018. The antibiotic susceptibility testing for 11 different antibiotics (nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin, cefixime, ceftriaxone, cefotaxime, azithromycin, cotrimoxazole, chloramphenicol, and amoxicillin) was performed by disk diffusion method. Furthermore, minimum inhibitory concentration (MIC) values of ciprofloxacin, ofloxacin, and azithromycin were determined by agar dilution method. Mutation at gyrA ser83 associated with reduced susceptibility to fluoroquinolones was determined by PCR-RFLP.ResultsOut of 706 blood samples, 6.94% (n = 49) were culture positive for Salmonella enterica (S. Typhi, n = 46). It was revealed that 97.8% S. Typhi isolates were susceptible to conventional first-line antibiotics (ampicillin, chloramphenicol, and cotrimoxazole), 97.3% to cephalosporins and 95.7% to azithromycin. S. Typhi were either resistant or intermediately susceptible to fluoroquinolones: 97.8% to ciprofloxacin, 91.3% to ofloxacin, and 89.1% to levofloxacin. The MIC of ciprofloxacin, ofloxacin, and azithromycin for S. Typhi ranged from 0.008 to 32, 0.03 to 16, and 2 to 8 μg/mL, respectively. Out of 46 S. Typhi isolates, 44 (95.65%) had gyrA ser83 mutation.ConclusionFluoroquinolones have poor activity against Salmonella Typhi. The trends of increasing azithromycin MIC value among S. Typhi might limit its use for the treatment of typhoid fever. Effectiveness of conventional first-line antibiotics in vitro suggests considering their clinical use after large-scale studies.

Project description:BackgroundSalmonella enterica serotype Typhi can colonize and persist in the biliary tract of infected individuals, resulting in a state of asymptomatic chronic carriage. Chronic carriers may act as persistent reservoirs of infection within a community and may introduce infection to susceptible individuals and new communities. Little is known about the interaction between the host and pathogen in the biliary tract of chronic carriers, and there is currently no reliable diagnostic assay to identify asymptomatic S. Typhi carriage.Methodology/principal findingsTo study host-pathogen interactions in the biliary tract during S. Typhi carriage, we applied an immunoscreening technique called in vivo-induced antigen technology (IVIAT), to identify potential biomarkers unique to carriers. IVIAT identifies humorally immunogenic bacterial antigens expressed uniquely in the in vivo environment, and we hypothesized that S. Typhi surviving in the biliary tract of humans may express a distinct antigenic profile. Thirteen S. Typhi antigens that were immunoreactive in carriers, but not in healthy individuals from a typhoid endemic area, were identified. The identified antigens included a number of putative membrane proteins, lipoproteins, and hemolysin-related proteins. YncE (STY1479), an uncharacterized protein with an ATP-binding motif, gave prominent responses in our screen. The response to YncE in patients whose biliary tract contained S. Typhi was compared to responses in patients whose biliary tract did not contain S. Typhi, patients with acute typhoid fever, and healthy controls residing in a typhoid endemic area. Seven of 10 (70%) chronic carriers, 0 of 8 bile culture-negative controls (0%), 0 of 8 healthy Bangladeshis (0%), and 1 of 8 (12.5%) Bangladeshis with acute typhoid fever had detectable anti-YncE IgG in blood. IgA responses were also present.Conclusions/significanceFurther evaluation of YncE and other antigens identified by IVIAT could lead to the development of improved diagnostic assays to identify asymptomatic S. Typhi carriers.

Project description:BackgroundOf the > 2000 serovars of Salmonella enterica subspecies I, most cause self-limiting gastrointestinal disease in a wide range of mammalian hosts. However, S. enterica serovars Typhi and Paratyphi A are restricted to the human host and cause the similar systemic diseases typhoid and paratyphoid fever. Genome sequence similarity between Paratyphi A and Typhi has been attributed to convergent evolution via relatively recent recombination of a quarter of their genomes. The accumulation of pseudogenes is a key feature of these and other host-adapted pathogens, and overlapping pseudogene complements are evident in Paratyphi A and Typhi.ResultsWe report the 4.5 Mbp genome of a clinical isolate of Paratyphi A, strain AKU_12601, completely sequenced using capillary techniques and subsequently checked using Illumina/Solexa resequencing. Comparison with the published genome of Paratyphi A ATCC9150 revealed the two are collinear and highly similar, with 188 single nucleotide polymorphisms and 39 insertions/deletions. A comparative analysis of pseudogene complements of these and two finished Typhi genomes (CT18, Ty2) identified several pseudogenes that had been overlooked in prior genome annotations of one or both serovars, and identified 66 pseudogenes shared between serovars. By determining whether each shared and serovar-specific pseudogene had been recombined between Paratyphi A and Typhi, we found evidence that most pseudogenes have accumulated after the recombination between serovars. We also divided pseudogenes into relative-time groups: ancestral pseudogenes inherited from a common ancestor, pseudogenes recombined between serovars which likely arose between initial divergence and later recombination, serovar-specific pseudogenes arising after recombination but prior to the last evolutionary bottlenecks in each population, and more recent strain-specific pseudogenes.ConclusionRecombination and pseudogene-formation have been important mechanisms of genetic convergence between Paratyphi A and Typhi, with most pseudogenes arising independently after extensive recombination between the serovars. The recombination events, along with divergence of and within each serovar, provide a relative time scale for pseudogene-forming mutations, affording rare insights into the progression of functional gene loss associated with host adaptation in Salmonella.

Dataset Information

A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital.

Publications

A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital.

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