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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 -
BMC Public Health Aug 2023Despite significant progress in sanitation status and public health awareness, intestinal infectious diseases (IID) have caused a serious disease burden in China. Little...
BACKGROUND
Despite significant progress in sanitation status and public health awareness, intestinal infectious diseases (IID) have caused a serious disease burden in China. Little was known about the spatio-temporal pattern of IID at the county level in Zhejiang. Therefore, a spatio-temporal modelling study to identify high-risk regions of IID incidence and potential risk factors was conducted.
METHODS
Reported cases of notifiable IID from 2008 to 2021 were obtained from the China Information System for Disease Control and Prevention. Moran's I index and the local indicators of spatial association (LISA) were calculated using Geoda software to identify the spatial autocorrelation and high-risk areas of IID incidence. Bayesian hierarchical model was used to explore socioeconomic and climate factors affecting IID incidence inequities from spatial and temporal perspectives.
RESULTS
From 2008 to 2021, a total of 101 cholera, 55,298 bacterial dysentery, 131 amoebic dysentery, 5297 typhoid, 2102 paratyphoid, 27,947 HEV, 1,695,925 hand, foot and mouth disease (HFMD), and 1,505,797 other infectious diarrhea (OID) cases were reported in Zhejiang Province. The hot spots for bacterial dysentery, OID, and HEV incidence were found mainly in Hangzhou, while high-high cluster regions for incidence of enteric fever and HFMD were mainly located in Ningbo. The Bayesian model showed that Areas with a high proportion of males had a lower risk of BD and enteric fever. People under the age of 18 may have a higher risk of IID. High urbanization rate was a protective factor against HFMD (RR = 0.91, 95% CI: 0.88, 0.94), but was a risk factor for HEV (RR = 1.06, 95% CI: 1.01-1.10). BD risk (RR = 1.14, 95% CI: 1.10-1.18) and enteric fever risk (RR = 1.18, 95% CI:1.10-1.27) seemed higher in areas with high GDP per capita. The greater the population density, the higher the risk of BD (RR = 1.29, 95% CI: 1.23-1.36), enteric fever (RR = 1.12, 95% CI: 1.00-1.25), and HEV (RR = 1.15, 95% CI: 1.09-1.21). Among climate variables, higher temperature was associated with a higher risk of BD (RR = 1.32, 95% CI: 1.23-1.41), enteric fever (RR = 1.41, 95% CI: 1.33-1.50), and HFMD (RR = 1.22, 95% CI: 1.08-1.38), and with lower risk of HEV (RR = 0.83, 95% CI: 0.78-0.89). Precipitation was positively correlated with enteric fever (RR = 1.04, 95% CI: 1.00-1.08), HFMD (RR = 1.03, 95% CI: 1.00-1.06), and HEV (RR = 1.05, 95% CI: 1.03-1.08). Higher HFMD risk was also associated with increasing relative humidity (RR = 1.20, 95% CI: 1.16-1.24) and lower wind velocity (RR = 0.88, 95% CI: 0.84-0.92).
CONCLUSIONS
There was significant spatial clustering of IID incidence in Zhejiang Province from 2008 to 2021. Spatio-temporal patterns of IID risk could be largely explained by socioeconomic and meteorological factors. Preventive measures and enhanced monitoring should be taken in some high-risk counties in Hangzhou city and Ningbo city.
Topics: Male; Humans; Typhoid Fever; Bayes Theorem; Dysentery; China; Communicable Diseases
PubMed: 37644452
DOI: 10.1186/s12889-023-16552-4 -
The Lancet. Global Health Sep 2023Vaccines prevent infections and could subsequently reduce antimicrobial use. A 1-week mass vaccination campaign was done with Typbar-TCV (Bharat Biotech, Hyderabad,...
BACKGROUND
Vaccines prevent infections and could subsequently reduce antimicrobial use. A 1-week mass vaccination campaign was done with Typbar-TCV (Bharat Biotech, Hyderabad, India) between Feb 25 and March 4, 2019. We investigated whether this typhoid conjugate vaccine campaign could affect antimicrobial prescribing in children presenting to primary care in Harare, Zimbabwe.
METHODS
In this mixed methods study, data for acute paediatric outpatient consultations between Jan 1, 2018, and March 31, 2020, were collected from five clinics in Harare. Interrupted time series analysis was done to compare prescription data before and after the campaign. To contextualise findings, qualitative data were collected between April 20, 2021, and July 20, 2022, comprising ethnographic research (ie, workshops, surveys, observations, and interviews) in 14 clinics. Ethnographic data were used for thematic analysis. The primary outcome was monthly antimicrobial prescriptions in children aged 6 months to 15 years, normalised by the number of trauma events in all age groups.
FINDINGS
In the data collection period, 27 107 paediatric consultations were recorded. 17 951 (66·2%) of 27 107 children were prescribed antimicrobials. Despite the perceived reduction in typhoid cases and a decreasing trend in the prescription of antimicrobials commonly used to treat typhoid (ie, ciprofloxacin and azithromycin), mass vaccination with Typbar-TCV did not affect the total rate of antimicrobials (adjusted rate ratio, 1·20, 95% CI 0·70-2·05, p=0·51) or the rate of typhoid antimicrobials prescribed (0·93, 0·44-1·96, p=0·85). Unsafe water sources and insufficient diagnostic services were reported to contribute to the continued disease burden and antimicrobial prescription.
INTERPRETATION
Non-specific febrile illness caused by confirmed or suspected typhoid is a common cause of antimicrobial use in endemic areas. Although effective in preventing typhoid fever, we were unable to identify any effect of Typbar-TCV on antimicrobial prescribing. Ethnographic research showed the effect of contextual factors on antimicrobial prescribing, including concerns regarding safe water access, appropriate sewage disposal, health-care and diagnostic availability. To realise effects beyond disease burden reduction, holistic approaches addressing these concerns are needed so that the value of vaccines mitigating the effects of antimicrobial use as a driver of antimicrobial resistance is fully achieved.
FUNDING
Wellcome Trust.
TRANSLATION
For the Shona translation of the abstract see Supplementary Materials section.
Topics: Child; Humans; Typhoid-Paratyphoid Vaccines; Vaccines, Conjugate; Typhoid Fever; Zimbabwe; Anti-Infective Agents; Mass Vaccination
PubMed: 37591588
DOI: 10.1016/S2214-109X(23)00319-4 -
The Lancet. Global Health Sep 2023
Topics: Humans; Typhoid-Paratyphoid Vaccines; Vaccines, Conjugate; Typhoid Fever; Vaccination
PubMed: 37591573
DOI: 10.1016/S2214-109X(23)00365-0 -
Journal of the Pediatric Infectious... Sep 2023We assessed anti-Vi IgG/IgA responses to typhoid conjugate vaccine (TCV) in children enrolled in a double-blind randomized controlled, phase 2 trial in Burkina Faso.... (Randomized Controlled Trial)
Randomized Controlled Trial
We assessed anti-Vi IgG/IgA responses to typhoid conjugate vaccine (TCV) in children enrolled in a double-blind randomized controlled, phase 2 trial in Burkina Faso. Anti-Vi IgG seroconversion and anti-Vi IgA titers were higher in TCV than control recipients at 30-35 months post-vaccination. TCV induces durable immunity in Burkinabe children vaccinated at 15 months.
Topics: Humans; Child; Infant; Typhoid Fever; Vaccines, Conjugate; Typhoid-Paratyphoid Vaccines; Burkina Faso; Antibody Formation; Immunoglobulin A; Immunoglobulin G; Antibodies, Bacterial
PubMed: 37589596
DOI: 10.1093/jpids/piad058 -
The American Journal of Tropical... Sep 2023India has one of the highest estimated burdens of enteric fever globally. Prior to the implementation of Typbar-TCV typhoid conjugate vaccine (TCV) in a public sector... (Review)
Review
India has one of the highest estimated burdens of enteric fever globally. Prior to the implementation of Typbar-TCV typhoid conjugate vaccine (TCV) in a public sector pediatric immunization campaign in Navi Mumbai, India, we conducted a retrospective review of blood culture-confirmed cases of typhoid and paratyphoid fevers to estimate the local burden of disease. This review included all blood cultures processed at a central microbiology laboratory, serving multiple hospitals, in Navi Mumbai (January 2014-May 2018) that tested positive for either Salmonella Typhi or Salmonella Paratyphi A. Of 40,670 blood cultures analyzed, 1,309 (3.2%) were positive for S. Typhi (1,201 [92%]) or S. Paratyphi A (108 [8%]). Culture positivity was highest in the last months of the dry season (April-June). Our findings indicate a substantial burden of enteric fever in Navi Mumbai and support the importance of TCV immunization campaigns and improved water, sanitation, and hygiene.
Topics: Child; Humans; Typhoid Fever; Retrospective Studies; Blood Culture; Salmonella typhi; Paratyphoid Fever; Salmonella paratyphi A; India; Typhoid-Paratyphoid Vaccines
PubMed: 37549903
DOI: 10.4269/ajtmh.23-0102 -
PloS One 2023To estimate the coverage rate of typhoid conjugate vaccine (TCV) among children aged 6 months to 15 years in Lyari Town Karachi, Pakistan.
OBJECTIVE
To estimate the coverage rate of typhoid conjugate vaccine (TCV) among children aged 6 months to 15 years in Lyari Town Karachi, Pakistan.
METHODS
A cross-sectional survey was conducted to estimate the vaccine coverage of Typbar TCV in Lyari Town Karachi utilizing the World Health Organization (WHO) recommended rapid vaccine coverage assessment technique (30 clusters × 7 households). Sampling was powered at town level and multistage cluster sampling was used. Four union councils were randomly selected from a total of 11 and the survey was conducted in those union councils. After consent was obtained, parents of age-eligible children living in the selected union councils were invited to participate in the survey and information was collected on Typbar TCV vaccination status of children aged 6 months to 15 years.
RESULTS
Overall, 2325 children were included in the survey. The mean age of the participants was 7.60 ± 3.84 years. The ratio of males to females was equal in the survey sample; 1163 (50.02%) were male. In the total target population, 82% children were found to be vaccinated; however, the vaccination status could be verified for 80%. The vaccine coverage of TCV was comparable among the four union councils and the overall coverage of TCV vaccine in Lyari Town was found to be 80%. The coverage was significantly lower in younger children, 5% and 17% among children aged 6 months to < 2 years and 2 years to < 5 years respectively and 78% among children aged 5 years to 15 years.
CONCLUSION
The overall immunization coverage rate with TCV was found to be satisfactory. Immunization coverage was comparable among both sexes and the selected union councils but it was relatively low among children in younger age groups.
Topics: Female; Humans; Male; Child; Infant; Child, Preschool; Typhoid Fever; Vaccines, Conjugate; Typhoid-Paratyphoid Vaccines; Pakistan; Cross-Sectional Studies; Poverty Areas
PubMed: 37549155
DOI: 10.1371/journal.pone.0289582 -
Trials Aug 2023Typhoid fever causes nearly 110,000 deaths among 9.24 million cases globally and disproportionately affects developing countries. As a control measure in such regions,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Typhoid fever causes nearly 110,000 deaths among 9.24 million cases globally and disproportionately affects developing countries. As a control measure in such regions, typhoid conjugate vaccines (TCVs) are recommended by the World Health Organization (WHO). We present here the protocol of a cluster randomised vaccine trial to assess the impact of introducing TyphiBEV® vaccine to those between 1 and 30 years of age in a high-burden setting.
METHODS
The primary objective is to determine the relative and absolute rate reduction of symptomatic, blood-culture-confirmed S. Typhi infection among participants vaccinated with TyphiBEV® in vaccine clusters compared with the unvaccinated participants in non-vaccine clusters. The study population is residents of 30 wards of Vellore (a South Indian city) with participants between the ages of 1 and 30 years who provide informed consent. The wards will be divided into 60 contiguous clusters and 30 will be randomly selected for its participants to receive TyphiBEV® at the start of the study. No placebo/control is planned for the non-intervention clusters, which will receive the vaccine at the end of the trial. Participants will not be blinded to their intervention. Episodes of typhoid fever among participants will be captured via stimulated, passive fever surveillance in the area for 2 years after vaccination, which will include the most utilised healthcare facilities. Observers blinded to the participants' intervention statuses will record illness details. Relative and absolute rate reductions will be calculated at the end of this surveillance and used to estimate vaccine effectiveness.
DISCUSSION
The results from our trial will allow countries to make better-informed decisions regarding the TCV that they will roll-out and may improve the global supplies and affordability of the vaccines.
TRIAL REGISTRATION
Clinical Trials Registry of India (CTRI) CTRI/2022/03/041314. Prospectively registered on 23 March 2022 ( https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62548&EncHid=&userName=vellore%20typhoid ). CTRI collects the full WHO Trial Registration Data Set.
Topics: Humans; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Typhoid Fever; Vaccines, Conjugate; Typhoid-Paratyphoid Vaccines; Vaccination; India
PubMed: 37537677
DOI: 10.1186/s13063-023-07555-y -
Journal of Clinical Laboratory Analysis Jul 2023Acute febrile illness (AFI) is a prevalent disease in developing countries that is difficult to diagnose due to the diversity of infectious organisms and the poor...
BACKGROUND
Acute febrile illness (AFI) is a prevalent disease in developing countries that is difficult to diagnose due to the diversity of infectious organisms and the poor quality of clinical diagnosis. TaqMan array card (TAC) can detect up to 35 AFI-associated organisms in 1.5 h, addressing diagnostic demands. In this study, we aimed to evaluate the role of TAC in determining the causative organisms in hospitalized AFI patients.
METHODS
The study had a cross-sectional design and enrolled 120 admitted patients with persistent fever for three or more days from the medicine ward of Chittagong Medical College Hospital (CMCH) and Bangladesh Institute of Tropical and Infectious Diseases Hospital (BITID). Blood samples were collected and then subjected to automated BacT/Alert blood culture, microbial culture, TAC assay, and typhoid/paratyphoid test.
RESULTS
The total number of study participants was 120, among them 48 (40%) samples showed a positive result in TAC card, 29 (24.16%) were TP positive and nine (7.51%) were culture positive. The number of organisms detected by the TAC card was 13 bacteria, three viruses, one protozoan, and one fungus. The sensitivity and specificity of the TAC assay for different bacterial pathogen compared to blood culture was 44.44%, and 90.99%, respectively. In contrast, the TP test had a sensitivity and specificity of 100% and 80%, respectively, compared to the blood culture test.
CONCLUSION
TAC can be a handful tool for detecting multiple organisms in AFI with high specificity which can facilitate early diagnosis of different pathogens contributing to AFI.
Topics: Humans; Cross-Sectional Studies; Bangladesh; Bacteria; Fever; Typhoid Fever
PubMed: 37496432
DOI: 10.1002/jcla.24948 -
Vaccine Aug 2023This study aimed to evaluate the parental acceptance of Typhoid Conjugate Vaccine (TCV) and to determine the predictors of TCV vaccination status among children in an...
BACKGROUND
This study aimed to evaluate the parental acceptance of Typhoid Conjugate Vaccine (TCV) and to determine the predictors of TCV vaccination status among children in an outbreak setting of extensively drug resistant (XDR) typhoid fever in Karachi, Pakistan.
METHODS
A cross-sectional survey using the WHO recommended rapid vaccine coverage assessment technique was conducted. Out of 11, four union councils (UCs) in Lyari Town were randomly selected. A parent or primary caretaker from the eligible household was interviewed. Data were collected using a locally validated vaccine attitudes scale (VAS). Sum of scores was calculated for VAS. A higher score denoted negative attitudes and perceptions regarding TCV and vice versa. Multivariable logistic regression was performed to determine the predictors of TCV vaccination status.
RESULTS
Based on the 14-item parental VAS, 78.0 % of the parents had a score between 0 to <40 and 22 % had a score ≥40. VAS score of <40 was significantly associated with higher odds of receiving TCV during the campaign setting (adjusted Odds Ratio (aOR): 1.30; 95 % Confidence Interval (CI): 1.02, 1.66). The odds of receiving TCV vaccination were higher among children whose parents were aware of the ongoing vaccination campaign in the area (aOR: 4.57; 95 % CI: 2.93, 7.12) and expressed willingness to get their child vaccinated against typhoid fever (aOR: 2.54; 95 % CI: 1.82, 3.55).
CONCLUSION
Parental awareness of the ongoing vaccination campaign, positive perception and attitudes towards vaccine were found to be significantly associated with TCV vaccination among children. Appropriately structured pre-vaccination awareness campaigns focused on childhood vaccination targeted towards parents are necessary to improve parental awareness, attitude and behavior towards vaccination.
Topics: Humans; Child; Typhoid Fever; Vaccines, Conjugate; Typhoid-Paratyphoid Vaccines; Pakistan; Cross-Sectional Studies; Vaccination; Parents; Disease Outbreaks
PubMed: 37463829
DOI: 10.1016/j.vaccine.2023.07.003