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The Lancet. Infectious Diseases Apr 2024160 years after the discovery of its waterborne transmission and 120 years after the development of the first-generation of vaccines, typhoid fever remains a major... (Review)
Review
160 years after the discovery of its waterborne transmission and 120 years after the development of the first-generation of vaccines, typhoid fever remains a major health threat globally. In this Historical Review, we use WHO's Institutional Repository for Information Sharing to examine changes in typhoid control policy from January, 1940, to December, 2019. We used a mixed-methods approach in the analysis of infection control priorities, combining semi-inductive thematic coding with historical analysis to show major thematic shifts in typhoid control policy, away from water, sanitation, and hygiene (WASH)-based control towards vaccine-based interventions concurrent with declining attention to the disease. Documentary analysis shows that, although international planners never officially disavowed WASH and low-income countries persistently lobbied for WASH, vaccines emerged as a permanent stopgap while meaningful support of sustained WASH strengthening lost momentum-with serious, long-term ramifications for typhoid control.
Topics: Humans; Typhoid Fever; Vaccine-Preventable Diseases; Sanitation; Hygiene; Water Supply; Typhoid-Paratyphoid Vaccines
PubMed: 37995738
DOI: 10.1016/S1473-3099(23)00500-5 -
The Lancet. Microbe Dec 2023The continued emergence of Salmonella enterica serovar Typhi, with ever increasing antimicrobial resistance, necessitates the use of vaccines in endemic countries. A...
BACKGROUND
The continued emergence of Salmonella enterica serovar Typhi, with ever increasing antimicrobial resistance, necessitates the use of vaccines in endemic countries. A typhoid fever outbreak in Harare, Zimbabwe, in 2018 from a multidrug resistant S Typhi with additional resistance to ciprofloxacin was the catalyst for the introduction of a typhoid conjugate vaccine programme. We aimed to investigate the emergence and evolution of antimicrobial resistance of endemic S Typhi in Zimbabwe and to determine the population structure, gene flux, and sequence polymorphisms of strains isolated before a typhoid conjugate vaccine programme to provide a baseline for future evaluation of the effect of the vaccination programme.
METHODS
In this genomic epidemiology study, we used short-read whole-genome sequencing of S Typhi isolated from clinical cases of typhoid fever in Harare, Zimbabwe, between Jan 1, 2012, and Feb 9, 2019, to determine the S Typhi population structure, gene flux, and sequence polymorphisms and reconstructed the evolution of antimicrobial resistance. Maximum likelihood time-scaled phylogenetic trees of Zimbabwe isolates in the context of global isolates obtained from the National Center for Biotechnology Information were constructed to infer spread and emergence of antimicrobial resistance.
FINDINGS
The population structure of S Typhi in Harare, Zimbabwe, from 2012 to 2019 was dominated by multidrug resistant genotype 4.3.1.1.EA1 (H58) that spread to Zimbabwe from neighbouring countries in around 2009 (95% credible interval 2008·5-2010·0). Acquisition of an IncN plasmid carrying antimicrobial resistance genes including a qnrS gene and a mutation in the quinolone resistance determining region of gyrA gene contributed to non-susceptibility and resistance to quinolone antibiotics. A minority population of antimicrobial susceptible S Typhi genotype 3.3.1 strains were present throughout.
INTERPRETATION
The currently dominant S Typhi population is genotype 4.3.1.1 that spread to Zimbabwe and acquired additional antimicrobial resistance though acquisition of a plasmid and mutation in the gyrA gene. This study provides a baseline population structure for future evaluation of the effect of the typhoid conjugate vaccine programme in Harare.
FUNDING
Bill & Melinda Gates Foundation and the Biotechnology and Biological Sciences Research Council Institute Strategic Programme.
Topics: Humans; Typhoid Fever; Vaccines, Conjugate; Salmonella enterica; Typhoid-Paratyphoid Vaccines; Zimbabwe; Phylogeny; Salmonella typhi; Anti-Bacterial Agents; Quinolones; Genomics
PubMed: 37952554
DOI: 10.1016/S2666-5247(23)00214-8 -
Vaccine Nov 2023In Asia, there are an estimated 12 million annual cases of enteric fever, a potentially fatal systemic bacterial infection caused by Salmonella enterica serovars Typhi...
In Asia, there are an estimated 12 million annual cases of enteric fever, a potentially fatal systemic bacterial infection caused by Salmonella enterica serovars Typhi (STy) and Paratyphi A (SPA). The recent availability of typhoid conjugate vaccines (TCV), an increasing incidence of disease caused by SPA and growing antimicrobial resistance (AMR) across the genus Salmonella makes a bivalent STy/SPA vaccine a useful public health proposition. The uptake of a stand-alone paratyphoid vaccine is likely low thus, there is a pipeline of bivalent STy/SPA candidate vaccines. Several candidates are close to entering clinical trials, which if successful should facilitate a more comprehensive approach for enteric fever control. Additionally, the World Health Organization (WHO) has made advancing the development of vaccines that protect young children and working aged adults against both agents of enteric fever a priority objective. This "Vaccine Value Profile" (VVP) addresses information related predominantly to invasive disease caused by SPA prevalent in Asia. Information is included on stand-alone SPA candidate vaccines and candidate vaccines targeting SPA combined with STy. Out of scope for the first version of this VVP is a wider discussion on the development of a universal Salmonella combination candidate vaccine, addressing both enteric fever and invasive non-typhoidal Salmonella disease, for use globally. This VVP is a detailed, high-level assessment of existing, publicly available information to inform and contextualize the public health, economic, and societal potential of pipeline vaccines and vaccine-like products for SPA. Future versions of this VVP will be updated to reflect ongoing activities such as vaccine development strategies and "Full Vaccine Value Assessment" that will inform the value proposition of an SPA vaccine. This VVP was developed by an expert working group from academia, non-profit organizations, public-private partnerships, and multi-lateral organizations as well as in collaboration with stakeholders from the WHO South-East Asian Region. All contributors have extensive expertise on various elements of the VVP for SPA and collectively aimed to identify current research and knowledge gaps.
Topics: Adult; Child; Humans; Child, Preschool; Middle Aged; Typhoid Fever; Salmonella paratyphi A; Paratyphoid Fever; Salmonella typhi; Typhoid-Paratyphoid Vaccines; Salmonella Vaccines
PubMed: 37951691
DOI: 10.1016/j.vaccine.2023.01.054 -
Trends in antimicrobial resistance amongst Salmonella Paratyphi A isolates in Bangladesh: 1999-2021.PLoS Neglected Tropical Diseases Nov 2023Typhoid and paratyphoid remain common bloodstream infections in areas with suboptimal water and sanitation infrastructure. Paratyphoid, caused by Salmonella Paratyphi A,...
BACKGROUND
Typhoid and paratyphoid remain common bloodstream infections in areas with suboptimal water and sanitation infrastructure. Paratyphoid, caused by Salmonella Paratyphi A, is less prevalent than typhoid and its antimicrobial resistance (AMR) trends are less documented. Empirical treatment for paratyphoid is commonly based on the knowledge of susceptibility of Salmonella Typhi, which causes typhoid. Hence, with rising drug resistance in Salmonella Typhi, last-line antibiotics like ceftriaxone and azithromycin are prescribed for both typhoid and paratyphoid. However, unlike for typhoid, there is no vaccine to prevent paratyphoid. Here, we report 23-year AMR trends of Salmonella Paratyphi A in Bangladesh.
METHODS
From 1999 to 2021, we conducted enteric fever surveillance in two major pediatric hospitals and three clinics in Dhaka, Bangladesh. Blood cultures were performed at the discretion of the treating physicians; cases were confirmed by culture, serological and biochemical tests. Antimicrobial susceptibility was determined following CLSI guidelines.
RESULTS
Over 23 years, we identified 2,725 blood culture-confirmed paratyphoid cases. Over 97% of the isolates were susceptible to ampicillin, chloramphenicol, and cotrimoxazole, and no isolate was resistant to all three. No resistance to ceftriaxone was recorded, and >99% of the isolates were sensitive to azithromycin. A slight increase in minimum inhibitory concentration (MIC) is noticed for ceftriaxone but the current average MIC is 32-fold lower than the resistance cut-off. Over 99% of the isolates exhibited decreased susceptibility to ciprofloxacin.
CONCLUSIONS
Salmonella Paratyphi A has remained susceptible to most antibiotics, unlike Salmonella Typhi, despite widespread usage of many antibiotics in Bangladesh. The data can guide evidence-based policy decisions for empirical treatment of paratyphoid fever, especially in the post typhoid vaccine era, and with the availability of new paratyphoid diagnostics.
Topics: Child; Humans; Anti-Bacterial Agents; Typhoid Fever; Salmonella paratyphi A; Azithromycin; Ceftriaxone; Bangladesh; Drug Resistance, Bacterial; Salmonella typhi; Paratyphoid Fever; Microbial Sensitivity Tests
PubMed: 37939101
DOI: 10.1371/journal.pntd.0011723 -
Life Sciences Dec 2023Present study has explored the protective response of dual immunization using two different antigenic entities (i.e. flagellin epitope and cytolethal distending toxin...
AIMS
Present study has explored the protective response of dual immunization using two different antigenic entities (i.e. flagellin epitope and cytolethal distending toxin subunit B (CdtB) protein) against lethal challenge of typhoidal serovars in a murine model.
MAIN METHODS
In-vitro immunogenicity of flagellin epitope-BSA conjugate and CdtB protein was confirmed using Indirect ELISA of typhoid positive patients' sera. Further, both entities were administered intraperitoneally in mice individually or in combination, followed by lethal challenge of typhoidal Salmonellae. Various parameters were analysed such as bacterial burden, mice survival, histopathological analysis, cytokine analysis and immunophenotyping. Serum samples obtained from the immunized mice were used for passive immunization studies, wherein mice survival and mechanism of action of the generated antibodies was studied.
KEY FINDINGS
Active immunization studies using the combination of both entities demonstrated improved mice survival after lethal challenge with typhoidal Salmonellae, reduced bacterial burden in organs, expression of immunophenotypic markers in splenocytes and restored tissue histoarchitecture. When used in combination, the effective doses of both the candidates reduced which may be attributed to multiprong approach used by the immune system to recognize Salmonella. Passive immunization studies further determined the protective efficacy of generated antibodies by different mechanisms such as complement mediated bactericidal action, swarming inhibition and increased phagocytic uptake.
SIGNIFICANCE
Present study is the first phase of the proof-of-concept which may prove to be beneficial in developing an effective bi-functional vaccine candidate to render protection against both Vi-positive as well as Vi-negative Salmonella strains.
Topics: Humans; Animals; Mice; Typhoid Fever; Flagellin; Epitopes; Immunization; Vaccination; Salmonella; Typhoid-Paratyphoid Vaccines
PubMed: 37918629
DOI: 10.1016/j.lfs.2023.122216 -
Study on association factors of intestinal infectious diseases based-Bayesian spatio-temporal model.BMC Infectious Diseases Oct 2023Intestinal infectious diseases (IIDs) are a significant public health issue in China, and the incidence and distribution of IIDs vary greatly by region and are affected...
BACKGROUND
Intestinal infectious diseases (IIDs) are a significant public health issue in China, and the incidence and distribution of IIDs vary greatly by region and are affected by various factors. This study aims to describe the spatio-temporal trends of IIDs in the Chinese mainland and investigate the association between socioeconomic and meteorological factors with IIDs.
METHODS
In this study, IIDs in mainland China from 2006 to 2017 was analyzed using data obtained from the China Center for Disease Control and Prevention. Spatio-temporal mapping techniques was employed to visualize the spatial and temporal distribution of IIDs. Additionally, mean center and standard deviational ellipse analyses were utilized to examine the spatial trends of IIDs. To investigate the potential associations between IIDs and meteorological and socioeconomic variables, spatiotemporal zero-inflated Poisson and negative binomial models was employed within a Bayesian framework.
RESULTS
During the study period, the occurrence of most IIDs has dramatically reduced, with uneven reductions in different diseases. Significant regional differences were found among IIDs and influential factors. Overall, the access rate to harmless sanitary toilets (ARHST) was positively associated with the risk of cholera (RR: 1.73, 95%CI: 1.08-2.83), bacillary dysentery (RR: 1.32, 95%CI: 1.06-1.63), and other intestinal infectious diseases (RR: 1.88, 95%CI: 1.52-2.36), and negatively associated with typhoid fever (RR: 0.66, 95%CI: 0.51-0.92), paratyphoid fever (RR: 0.71, 95%CI: 0.55-0.92). Urbanization is only associated with hepatitis E (RR: 2.48, 95%CI: 1.12-5.72). And GDP was negatively correlated with paratyphoid fever (RR: 0.82, 95%CI: 0.70-0.97), and bacillary dysentery (RR: 0.77, 95%CI: 0.68-0.88), and hepatitis A (RR: 0.84, 95%CI: 0.73-0.97). Humidity showed positive correlation with some IIDs except for amoebic dysentery (RR: 1.64, 95%CI: 1.23-2.17), while wind speed showed a negative correlation with most IIDs. High precipitation was associated with an increased risk of typhoid fever (RR: 1.52, 95%CI: 1.09-2.13), and high temperature was associated with an increased risk of typhoid fever (RR: 2.82, 95%CI: 2.06-3.89), paratyphoid fever (RR: 2.79, 95%CI: 2.02-3.90), and HMFD (RR: 1.34, 95%CI: 1.01-1.77).
CONCLUSIONS
This research systematically and quantitatively studied the effect of socioeconomic and meteorological factors on IIDs, which provided causal clues for future studies and guided government planning.
Topics: Humans; Dysentery, Bacillary; Typhoid Fever; Paratyphoid Fever; Bayes Theorem; Spatio-Temporal Analysis; Intraabdominal Infections; China; Intestinal Diseases; Incidence; Communicable Diseases
PubMed: 37875791
DOI: 10.1186/s12879-023-08665-3 -
The Pediatric Infectious Disease Journal Jan 2024
Topics: Humans; Typhoid Fever; Salmonella typhi; Paratyphoid Fever
PubMed: 37820204
DOI: 10.1097/INF.0000000000004137 -
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 -
BMC Public Health Sep 2023Recently, attention has focused on the impact of global climate change on infectious diseases. Storm flooding is an extreme weather phenomenon that not only impacts the...
BACKGROUND
Recently, attention has focused on the impact of global climate change on infectious diseases. Storm flooding is an extreme weather phenomenon that not only impacts the health of the environment but also worsens the spread of pathogens. This poses a significant challenge to public health security. However, there is still a lack of research on how different levels of storm flooding affect susceptible enteric infectious diseases over time.
METHODS
Data on enteric infectious diseases, storm flooding events, and meteorology were collected for Changsha, Hunan Province, between 2016 and 2020. The Wilcoxon Rank Sum Test was used to identify the enteric infectious diseases that are susceptible to storm flooding. Then, the lagged effects of different levels of storm flooding on susceptible enteric infectious diseases were analyzed using a distributed lag nonlinear model.
RESULTS
There were eleven storm flooding events in Changsha from 2016 to 2020, concentrated in June and July. 37,882 cases of enteric infectious diseases were reported. During non-flooding days, the daily incidence rates of typhoid/paratyphoid and bacillary dysentery were 0.3/100,000 and 0.1/100,000, respectively. During flooding days, the corresponding rates increased to 2.0/100,000 and 0.8/100,000, respectively. The incidence rates of both diseases showed statistically significant differences between non-flooding and flooding days. Correlation analysis shows that the best lags for typhoid/paratyphoid and bacillary dysentery relative to storm flooding events may be 1 and 3 days. The results of the distributed lag nonlinear model showed that typhoid/paratyphoid had the highest cumulative RR values of 2.86 (95% CI: 1.71-4.76) and 8.16 (95% CI: 2.93-22.67) after 4 days of general flooding and heavy flooding, respectively; and bacillary dysentery had the highest cumulative RR values of 1.82 (95% CI: 1.40-2.35) and 3.31 (95% CI: 1.97-5.55) after 5 days of general flooding and heavy flooding, respectively.
CONCLUSIONS
Typhoid/paratyphoid and bacillary dysentery are sensitive enteric infectious diseases related to storm flooding in Changsha. There is a lagging effect of storm flooding on the onset of typhoid/paratyphoid and bacillary dysentery, with the best lagging periods being days 1 and 3, respectively. The cumulative risk of typhoid/paratyphoid and bacillary dysentery was highest at 4/5 days lag, respectively. The higher of storm flooding, the higher the risk of disease, which suggests that the authorities should take appropriate preventive and control measures before and after storm flooding.
Topics: Humans; Dysentery, Bacillary; Urbanization; Typhoid Fever; Communicable Diseases; China
PubMed: 37759167
DOI: 10.1186/s12889-023-16754-w -
Infection and Immunity Oct 2023Enteric fever, caused by oral infection with typhoidal serovars, presents as a non-specific febrile illness preceded by an incubation period of 5 days or more. The...
Enteric fever, caused by oral infection with typhoidal serovars, presents as a non-specific febrile illness preceded by an incubation period of 5 days or more. The enteric fever human challenge model provides a unique opportunity to investigate the innate immune response during this incubation period, and how this response is altered by vaccination with the Vi polysaccharide or conjugate vaccine. We find that on the same day as ingestion of typhoidal , there is already evidence of an immune response, with 199 genes upregulated in the peripheral blood transcriptome 12 hours post-challenge (false discovery rate <0.05). Gene sets relating to neutrophils, monocytes, and innate immunity were over-represented (false discovery rate <0.05). Estimating cell proportions from gene expression data suggested a possible increase in activated monocytes 12 hours post-challenge ( = 0.036, paired Wilcoxon signed-rank test). Furthermore, plasma TNF-α rose following exposure ( = 0.011, paired Wilcoxon signed-rank test). There were no significant differences in gene expression (false discovery rate <0.05) in the 12 hours response between those who did and did not subsequently develop clinical or blood culture confirmed enteric fever or between vaccination groups. Together, these results demonstrate early perturbation of the peripheral blood transcriptome after enteric fever challenge and provide initial insight into early mechanisms of protection.
Topics: Humans; Typhoid Fever; Salmonella typhi; Typhoid-Paratyphoid Vaccines; Vaccines, Attenuated; Vaccination
PubMed: 37725060
DOI: 10.1128/iai.00108-23