-
Clinical Infectious Diseases : An... Aug 2018Enteric fever is a febrile illness, occurring mostly in Asia and Africa, which can present as a severe and possibly fatal disease. Currently, a case fatality rate (CFR)... (Meta-Analysis)
Meta-Analysis
Enteric fever is a febrile illness, occurring mostly in Asia and Africa, which can present as a severe and possibly fatal disease. Currently, a case fatality rate (CFR) of 1% is assumed when evaluating the global burden of enteric fever. Until now, no meta-analysis has been conducted to summarize mortality from enteric fever. Therefore, we conducted a systematic review and meta-analysis to aggregate all available evidence. We estimated an overall CFR of 2.49% (95% confidence interval, 1.65%-3.75%; n = 44), and a CFR in hospitalized patients of 4.45% (2.85%-6.88%; n = 21 of 44). There was considerably heterogeneity in estimates of the CFR from individual studies. Neither age nor antimicrobial resistance were significant prognostic factors, but limited data were available for these analyses. The combined estimate of the CFR for enteric fever is higher than previously estimated, and the evaluation of prognostic factors, including antimicrobial resistance, urgently requires more data.
Topics: Africa; Anti-Bacterial Agents; Asia; Endemic Diseases; Humans; Paratyphoid Fever; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever
PubMed: 29522159
DOI: 10.1093/cid/ciy190 -
The Cochrane Database of Systematic... May 2018Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are widely available, Ty21a (oral) and Vi polysaccharide (parenteral). Newer typhoid conjugate vaccines are at varying stages of development and use. The World Health Organization has recently recommended a Vi tetanus toxoid (Vi-TT) conjugate vaccine, Typbar-TCV, as the preferred vaccine for all ages.
OBJECTIVES
To assess the effects of vaccines for preventing typhoid fever.
SEARCH METHODS
In February 2018, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and mRCT. We also searched the reference lists of all included trials.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease) in adults and children. Human challenge studies were not eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied inclusion criteria and extracted data, and assessed the certainty of the evidence using the GRADE approach. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella enterica serovar Typhi in blood. We calculated risk ratios (RRs) and efficacy (1 - RR as a percentage) with 95% confidence intervals (CIs).
MAIN RESULTS
In total, 18 RCTs contributed to the quantitative analysis in this review: 13 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 6 trials; Vi-rEPA: 1 trial; Vi-TT: 1 trial), and 9 reported on adverse events. All trials but one took place in typhoid-endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers. Only one trial included data on children under two years of age.Ty21a vaccine (oral vaccine, three doses)A three-dose schedule of Ty21a vaccine probably prevents around half of typhoid cases during the first three years after vaccination (cumulative efficacy 2.5 to 3 years: 50%, 95% CI 35% to 61%, 4 trials, 235,239 participants, moderate-certainty evidence). These data include patients aged 3 to 44 years.Compared with placebo, this vaccine probably does not cause more vomiting, diarrhoea, nausea or abdominal pain (2 trials, 2066 participants; moderate-certainty evidence), headache, or rash (1 trial, 1190 participants; moderate-certainty evidence); however, fever (2 trials, 2066 participants; moderate-certainty evidence) is probably more common following vaccination.Vi polysaccharide vaccine (injection, one dose)A single dose of Vi polysaccharide vaccine prevents around two-thirds of typhoid cases in the first year after vaccination (year 1: 69%, 95% CI 63% to 74%; 3 trials, 99,979 participants; high-certainty evidence). In year 2, trial results were more variable, with the vaccine probably preventing between 45% and 69% of typhoid cases (year 2: 59%, 95% CI 45% to 69%; 4 trials, 194,969 participants; moderate-certainty evidence). These data included participants aged 2 to 55 years of age.The three-year cumulative efficacy of the vaccine may be around 55% (95% CI 30% to 70%; 11,384 participants, 1 trial; low-certainty evidence). These data came from a single trial conducted in South Africa in the 1980s in participants aged 5 to 15 years.Compared with placebo, this vaccine probably did not increase the incidence of fever (3 trials, 132,261 participants; moderate-certainty evidence) or erythema (3 trials, 132,261 participants; low-certainty evidence); however, swelling (3 trials, 1767 participants; moderate-certainty evidence) and pain at the injection site (1 trial, 667 participants; moderate-certainty evidence) were more common in the vaccine group.Vi-rEPA vaccine (two doses)Administration of two doses of the Vi-rEPA vaccine probably prevents between 50% and 96% of typhoid cases during the first two years after vaccination (year 1: 94%, 95% CI 75% to 99%; year 2: 87%, 95% CI 56% to 96%, 1 trial, 12,008 participants; moderate-certainty evidence). These data came from a single trial with children two to five years of age conducted in Vietnam.Compared with placebo, both the first and the second dose of this vaccine increased the risk of fever (1 trial, 12,008 and 11,091 participants, low-certainty evidence) and the second dose increase the incidence of swelling at the injection site (one trial, 11,091 participants, moderate-certainty evidence).Vi-TT vaccine (two doses)We are uncertain of the efficacy of administration of two doses of Vi-TT (PedaTyph) in typhoid cases in children during the first year after vaccination (year 1: 94%, 95% CI -1% to 100%, 1 trial, 1625 participants; very low-certainty evidence). These data come from a single cluster-randomized trial in children aged six months to 12 years and conducted in India. For single dose Vi-TT (Typbar-TCV), we found no efficacy trials evaluating the vaccine with natural exposure.There were no reported serious adverse effects in RCTs of any of the vaccines studied.
AUTHORS' CONCLUSIONS
The licensed Ty21a and Vi polysaccharide vaccines are efficacious in adults and children older than two years in endemic countries. The Vi-rEPA vaccine is just as efficacious, although data is only available for children. The new Vi-TT vaccine (PedaTyph) requires further evaluation to determine if it provides protection against typhoid fever. At the time of writing, there were only efficacy data from a human challenge setting in adults on the Vi-TT vaccine (Tybar), which clearly justify the ongoing field trials to evaluate vaccine efficacy.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Incidence; Randomized Controlled Trials as Topic; Salmonella typhi; Time Factors; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Attenuated
PubMed: 29851031
DOI: 10.1002/14651858.CD001261.pub4 -
The Cochrane Database of Systematic... Jan 2014Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new, modified, conjugated Vi vaccine called Vi-rEPA, are in development.
OBJECTIVES
To evaluate the efficacy and adverse effects of vaccines used to prevent typhoid fever.
SEARCH METHODS
In June 2013, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2013 and scanned the reference lists of all included trials.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease).
DATA COLLECTION AND ANALYSIS
Two review authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella typhi in blood. We calculated risk ratios (RRs) and efficacy (1-RR as a percentage) with 95% confidence intervals (CIs).
MAIN RESULTS
In total, 18 RCTs were included in this review; 12 evaluated efficacy (Ty21a: five trials; Vi polysaccharide: six trials; Vi-rEPA: one trial), and 11 reported on adverse events. Ty21a vaccine (oral vaccine, three doses) A three-dose schedule of Ty21a vaccine prevents around one-third to one-half of typhoid cases in the first two years after vaccination (Year 1: 35%, 95% CI 8% to 54%; Year 2: 58%, 95% CI 40% to 71%; one trial, 20,543 participants; moderate quality evidence; data taken from a single trial conducted in Indonesia in the 1980s). No benefit was detected in the third year after vaccination. Four additional cluster-RCTs have been conducted, but the study authors did not adjust for clustering.Compared with placebo, this vaccine was not associated with more participants with vomiting, diarrhoea, nausea or abdominal pain (four trials, 2066 participants; moderate quality evidence) headache, or rash (two trials, 1190 participants; moderate quality evidence); however, fever (four trials, 2066 participants; moderate quality evidence) was more common in the vaccine group. Vi polysaccharide vaccine (injection, one dose) A single dose of Vi polysaccharide vaccine prevents around two-thirds of typhoid cases in the first year after vaccination (Year 1: 69%, 95% CI 63% to 74%; three trials, 99,979 participants; high quality evidence). In Year 2, the trial results were more variable, with the vaccine preventing between 45% and 69% of typhoid cases (Year 2: 59%, 95% CI 45% to 69%; four trials, 194,969 participants; moderate quality evidence). The three-year cumulative efficacy of the vaccine is around 55% (95% CI 30% to 70%; 11,384 participants, one trial; moderate quality evidence). These data are taken from a single trial in South Africa in the 1980s.Compared with placebo, this vaccine was not associated with more participants with fever (four trials, 133,038 participants; moderate quality evidence) or erythema (three trials, 132,261 participants; low quality evidence); however, swelling (three trials, 1767 participants; moderate quality evidence) and pain at the injection site (one trial, 667 participants; moderate quality evidence) were more common in the vaccine group. Vi-rEPA vaccine (two doses) Administration of two doses of the Vi-rEPA vaccine prevents between 50% and 96% of typhoid cases during the first two years after vaccination (Year 1: 94%, 95% CI 75% to 99%; Year 2: 87%, 95% CI 56% to 96%; one trial, 12,008 participants; moderate quality evidence). These data are taken from a single trial with children 2 to 5 years of age conducted in Vietnam.Compared with placebo, the first and second doses of this vaccine were not associated with increased risk of adverse events. The first dose of this vaccine was not associated with fever (2 studies, 12,209 participants; low quality evidence), erythema (two trials, 12,209 participants; moderate quality evidence) or swelling at the injection site (two trials, 12,209 participants; moderate quality evidence). The second dose of this vaccine was not associated with fever (two trials, 11,286 participants; low quality evidence), erythema (two trials, 11,286 participants; moderate quality evidence) and swelling at the injection site (two trials, 11,286 participants; moderate quality evidence).
AUTHORS' CONCLUSIONS
The licensed Ty21a and Vi polysaccharide vaccines are efficacious. The new and unlicensed Vi-rEPA vaccine is as efficacious and may confer longer immunity.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Randomized Controlled Trials as Topic; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Attenuated
PubMed: 24385413
DOI: 10.1002/14651858.CD001261.pub3 -
The Cochrane Database of Systematic... 2000Antibiotic treatment of salmonella infections aims to shorten illness and prevent serious complications. There are also concerns about increasing antibiotic drug... (Review)
Review
BACKGROUND
Antibiotic treatment of salmonella infections aims to shorten illness and prevent serious complications. There are also concerns about increasing antibiotic drug resistance.
OBJECTIVES
The objective of this review was to assess the effects of antibiotics in adults and children with diarrhoea who have salmonella.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Science Citation Index, African Index Medicus, Lilacs, Extra Med and reference lists of relevant articles. We also contacted experts in the field.
SELECTION CRITERIA
Randomised and quasi-randomised trials comparing antibiotic therapy with placebo or no antibiotic therapy for salmonella infections in symptomatic or asymptomatic adults or children. Typhoid and paratyphoid salmonella infections were excluded.
DATA COLLECTION AND ANALYSIS
Trial quality assessment and data were extracted independently by two reviewers.
MAIN RESULTS
Twelve trials involving 778 participants (with at least 258 infants and children) were included. There were no significant differences in length of illness, diarrhoea or fever between any antibiotic regimen and placebo. The weighted mean difference for length of illness was -0.07 days, 95% confidence interval -0.55 to 0.40; diarrhoea -0.03 days, 95% confidence interval -0.53 to 0.48; fever -0.45 days, 95% confidence interval -0. 98 to 0.08. Antibiotic regimens resulted in more negative cultures during the first week of treatment. Relapses were more frequent in those receiving antibiotics, and there were more cases with positive cultures in the antibiotic groups after three weeks. Adverse drug reactions were more common in the antibiotic groups (odds ratio 1.67, 95% confidence interval 1.05 to 2.67).
REVIEWER'S CONCLUSIONS
There appears to be no evidence of a clinical benefit of antibiotic therapy in otherwise healthy children and adults with non-severe salmonella diarrhoea. Antibiotics appear to increase adverse effects and they also tend to prolong salmonella detection in stools.
Topics: Adult; Anti-Bacterial Agents; Child; Child, Preschool; Diarrhea; Gastroenteritis; Gastrointestinal Diseases; Humans; Infant; Salmonella Infections; Salmonella paratyphi A; Salmonella typhi
PubMed: 10796610
DOI: 10.1002/14651858.CD001167 -
The American Journal of Tropical... Sep 2018Typhoid and paratyphoid fever continue to significantly contribute to global morbidity and mortality. Disease burden is higher in low-and middle-income settings where...
Typhoid and paratyphoid fever continue to significantly contribute to global morbidity and mortality. Disease burden is higher in low-and middle-income settings where surveillance programs are rare and little systematic information exists at population level. This review evaluates national, regional, and global trends in the incidence of typhoid fever and of related morbidity and mortality. A literature search in Medline, Embase, and Web of Science was conducted in June 2016, followed by screening and data extraction in duplicate. Studies reporting blood culture estimates of typhoid or paratyphoid morbidity and mortality were included in the analysis. Our search yielded 5,563 unique records, of which 1978 were assessed for relevance with 219 records meeting the eligibility criteria. serotype Typhi was the most commonly reported organism (91%), with the occurrence of typhoidal (either incidence or prevalence) being the most commonly reported outcome (78%), followed by typhoid fever mortality, ileal perforation morbidity, and perforation mortality, respectively. Fewer than 50% of studies stratified outcomes by age or urban/rural locality. Surveillance data were available from 29 countries and patient-focused studies were available from 32 countries. Our review presents a mixed picture with declines reported in many regions and settings but with large gaps in surveillance and published data. Regional trends show generally high incidence rates in South Asia, sub-Saharan Africa, and East Asia and Pacific where the disease is endemic in many countries. Significant increases have been reported in certain countries but should be explored in the context of long-term trends and underlying at-risk populations.
Topics: Global Health; Humans; Paratyphoid Fever; Public Health; Typhoid Fever; Water Microbiology
PubMed: 30047364
DOI: 10.4269/ajtmh.18-0034 -
The Cochrane Database of Systematic... 2000Whole cell vaccines, consisting of relatively crude preparations of Salmonella typhi administered parenterally, are effective but have a high incidence of adverse... (Review)
Review
BACKGROUND
Whole cell vaccines, consisting of relatively crude preparations of Salmonella typhi administered parenterally, are effective but have a high incidence of adverse effects. Two vaccines have been developed more recently. Ty21a (an attenuated strain of S. typhi administered orally) and Vi (the purified bacterial capsule, given parenterally), have appeared less toxic than the older whole cell vaccines and are thought to be equally effective.
OBJECTIVES
The objective of this review was to assess the effects of typhoid fever vaccines.
SEARCH STRATEGY
We searched the Cochrane Library, Medline, Index Medicus, Embase and reference lists of articles.
SELECTION CRITERIA
Randomised trials comparing typhoid vaccines to other types of vaccine or placebo.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial quality and extracted data.
MAIN RESULTS
Seventeen studies, involving nearly two million people, were included. For the whole cell vaccines single dose regimens provided significant protection for the first two years. Two dose regimens provided significant protection for five years. For the Ty21a vaccine, both two and three dose regimens provided statistically significant protection for two years. The three dose regimen provided protection in the third and fourth years, but protection was not statistically significant in the fifth year. The Vi vaccine provided protection for two years, but the protection in the third year was not significant. The three year cumulative efficacy of two doses of whole cell vaccines was 73% (95% confidence interval 65-80), three doses of Ty21a was 51%, (95% confidence interval 35 to 63) and one dose of Vi was 55% (95% confidence interval 30 to 71). Data on adverse effects were limited, but indicate that whole cell vaccines are more toxic than the newer Ty21a and Vi vaccines.
REVIEWER'S CONCLUSIONS
The whole cell vaccines provided more prolonged protection than either the Ty21a vaccine or the Vi vaccine. However whole cell vaccines are associated with higher toxicity.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Attenuated
PubMed: 10796623
DOI: 10.1002/14651858.CD001261 -
The Cochrane Database of Systematic... Jul 2007Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new modified,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new modified, conjugated Vi vaccine called Vi-rEPA, are in development.
OBJECTIVES
To evaluate vaccines for preventing typhoid fever.
SEARCH STRATEGY
In December 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2004 and scanned the reference lists of all included trials.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or an inactive agent (placebo or vaccine for a different disease).
DATA COLLECTION AND ANALYSIS
Two authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow up and cumulative three-year efficacy, stratifying for vaccine type and dose. We calculated relative risks (RR) and efficacy (1-RR as a percentage) with 95% confidence intervals (CI).
MAIN RESULTS
Of the 17 included RCTs, 10 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 4 trials, Vi-rEPA: 1 trial), and 11 reported on adverse events.Ty21a vaccine (3 doses). According to one trial (20,543 participants), this vaccine provided statistically significant protection in each of the first three years (one: 35%, 95% CI 8% to 54%; two: 58%, 95% CI 40% to 71%; three: 46%, 95% CI -6% to 72%), and the cumulative efficacy for 2.5 to 3 years was 48% (95% CI 34% to 58%). Four cluster-RCTs that did not adjust for clustering were not included in the meta-analyses. Compared with placebo, this vaccine was not associated with an increased rate of fever, vomiting, diarrhoea, nausea or abdominal pain, headache, or rash.Vi polysaccharide vaccine (1 dose). This vaccine provided protection in year one (68%, 95% CI 50% to 80%; 99,979 participants, 3 trials) and year two (60%, 95% CI 31% to 76%; 142,555 participants, 2 trials), but not in year three (11,384 participants, 1 trial). The three-year cumulative efficacy was 55% (95% CI 30% to 70%; 11,384 participants, 1 trial). Compared with placebo, there was no statistically significant difference in the incidence of fever or erythema, but local swelling was more common with the vaccine.Vi-rEPA vaccine (2 doses). In one trial of 12,008 participants, this vaccine provided protection in year one (94%, 95% CI 75% to 99%) and year two (87%, 95% CI 56% to 96%). Cumulative efficacy at 46 months (3.8 years) was 89% (95% CI 76% to 97%). No swelling or erythema occurred in the vaccine or placebo group; fever was more frequent in the vaccine group.
AUTHORS' CONCLUSIONS
The licensed Ty21a and Vi polysaccharide vaccines are efficacious. The new and unlicensed Vi-rEPA vaccine is as efficacious and may confer longer immunity.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Randomized Controlled Trials as Topic; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Attenuated
PubMed: 17636661
DOI: 10.1002/14651858.CD001261.pub2 -
The Lancet. Infectious Diseases Feb 2019Oral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance is uncertain.
METHODS
We did a systematic review and meta-analysis of interventions designed to increase oral vaccine efficacy or immunogenicity. We searched Ovid-MEDLINE and Embase for trials published until Oct 23, 2017. Inclusion criteria for meta-analysis were two or more studies per intervention category and available seroconversion data. We did random-effects meta-analyses to produce summary relative risk (RR) estimates. This study is registered with PROSPERO (CRD42017060608).
FINDINGS
Of 2843 studies identified, 87 were eligible for qualitative synthesis and 66 for meta-analysis. 22 different interventions were assessed for oral poliovirus vaccine (OPV), oral rotavirus vaccine (RVV), oral cholera vaccine (OCV), and oral typhoid vaccines. There was generally high heterogeneity. Seroconversion to RVV was significantly increased by delaying the first RVV dose by 4 weeks (RR 1·37, 95% CI 1·16-1·62) and OPV seroconversion was increased with monovalent or bivalent OPV compared with trivalent OPV (RR 1·51, 95% CI 1·20-1·91). There was some evidence that separating RVV and OPV increased RVV seroconversion (RR 1·21, 95% CI 1·00-1·47) and that higher vaccine inoculum improved OCV seroconversion (RR 1·12, 95% CI 1·00-1·26). There was no evidence of effect for anthelmintics, antibiotics, probiotics, zinc, vitamin A, withholding breastfeeding, extra doses, or vaccine buffering.
INTERPRETATION
Most strategies did not improve oral vaccine performance. Delaying RVV and reducing OPV valence should be considered within immunisation programmes to reduce global enteric disease. New strategies to address the gap in oral vaccine efficacy are urgently required.
FUNDING
Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and WHO Polio Research Committee.
Topics: Administration, Oral; Adolescent; Adult; Child; Child, Preschool; Cholera; Cholera Vaccines; Female; Humans; Immunogenicity, Vaccine; Infant; Infant, Newborn; Male; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Salmonella typhi; Seroconversion; Treatment Outcome; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccination; Vibrio cholerae; Young Adult
PubMed: 30712836
DOI: 10.1016/S1473-3099(18)30602-9 -
PLoS Neglected Tropical Diseases May 2019Typhoid fevers are infections caused by the bacteria Salmonella enterica serovar Typhi (Salmonella Typhi) and Paratyphi A, B and C (Salmonella Paratyphi). Approximately... (Comparative Study)
Comparative Study
BACKGROUND
Typhoid fevers are infections caused by the bacteria Salmonella enterica serovar Typhi (Salmonella Typhi) and Paratyphi A, B and C (Salmonella Paratyphi). Approximately 17.8 million incident cases of typhoid fever occur annually, and incidence is highest in children. The accuracy of current diagnostic tests of typhoid fever is poorly understood. We aimed to determine the comparative accuracy of available tests for the pediatric population.
METHODS
We first conducted a systematic literature review to identify studies that compared diagnostic tests for typhoid fever in children (aged ≤15 years) to blood culture results. We applied a Bayesian latent-class extension to a network meta-analysis model. We modelled known diagnostic properties of bone marrow culture and the relationship between bone marrow and blood culture as informative priors in a Bayesian framework. We tested sensitivities for the proportion of negative blood samples that were false as well as bone marrow sensitivity and specificity.
RESULTS
We found 510 comparisons from 196 studies and 57 specific to the pediatric population. IgM-based tests outperformed their IgG-based counterparts for ELISA and Typhidot tests. The lateral flow IgG test performed comparatively well with 92% sensitivity (72% to 98% across scenario analyses) and 94% specificity. The most sensitive test of those investigated for the South Asian pediatric population was the Reverse Passive Hemagglutination Assay with 99% sensitivity (98% - 100% across scenario analyses). Adding a Widal slide test to other typhoid diagnostics did not substantially improve diagnostic performance beyond the single test alone, however, a lateral flow-based IgG rapid test combined with the typhoid/paratyphoid (TPT) assay yielded improvements in sensitivity without substantial declines in specificity and was the best performing combination test in this setting.
CONCLUSION
In the pediatric population, lateral-flow IgG, TPT and Reverse Passive Hemagglutination tests had high diagnostic accuracy compared to other diagnostics. Combinations of tests may provide a feasible option to increase diagnostic sensitivity. South Asia has the most informed set of data on typhoid diagnostic testing accuracy, and the evidence base in other important regions needs to be expanded.
Topics: Adolescent; Antibodies, Bacterial; Bayes Theorem; Child; Child, Preschool; Diagnostic Tests, Routine; Female; Humans; Male; Reagent Kits, Diagnostic; Salmonella typhi; Sensitivity and Specificity; Typhoid Fever; Young Adult
PubMed: 31067228
DOI: 10.1371/journal.pntd.0007303 -
The Lancet. Global Health Apr 2024Typhoid is a serious public health threat in many low-income and middle-income countries. Several vaccines for typhoid have been recommended by WHO for typhoid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Typhoid is a serious public health threat in many low-income and middle-income countries. Several vaccines for typhoid have been recommended by WHO for typhoid prevention in endemic countries. This study aimed to review the efficacy of typhoid vaccines against culture-confirmed Salmonella enterica serovar Typhi.
METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for studies published in English between Jan 1, 1986 and Nov 2, 2023. We included randomised controlled trials (RCTs) comparing typhoid vaccines with a placebo or another vaccine. This meta-analysis evaluated the efficacy and safety of several typhoid vaccines, including live attenuated oral Ty21a vaccine, Vi capsular polysaccharide (Vi-PS), Vi polysaccharide conjugated to recombinant Pseudomonas aeruginosa exotoxin A vaccine (Vi-rEPA), and Vi-tetanus toxoid conjugate vaccine (TCV). The certainty of evidence for key outcomes was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. The outcome of interest was typhoid fever confirmed by the isolation of Salmonella enterica serovar Typhi in blood and adverse events following immunisation. This study is registered with PROSPERO (CRD42021241043).
FINDINGS
We included 14 RCTs assessing four different vaccines (Ty21a: four trials; Vi-PS: five trials; Vi-rEPA: one trial; TCV: four trials) involving 585 253 participants. All trials were conducted in typhoid endemic countries and the age of participants ranged from 6 months to 50 years. The pooled efficacy against typhoid fever was 45% (95% CI 33-55%; four trials; 247 649 participants; I 59%; moderate certainty) for Ty21a and 58% (44-69%; five trials; 214 456 participants; I 34%; moderate certainty) for polysaccharide Vi-PS. The cumulative efficacy of two doses of Vi-rEPA vaccine at 2 years was 91% (88-96%; one trial; 12 008 participants; moderate certainty). The pooled efficacy of a single shot of TCV at 2 years post-immunisation was 83% (77-87%; four trials; 111 130 participants; I 0%; moderate certainty). All vaccines were safe, with no serious adverse effects reported in the trials.
INTERPRETATION
The existing data from included trials provide promising results regarding the efficacy and safety of the four recommended typhoid vaccines. TCV and Vi-rEPA were found to have the highest efficacy at 2 years post-immunisation. However, follow-up data for Vi-rEPA are scarce and only TCV is pre-qualified by WHO. Therefore, roll-out of TCV into routine immunisation programmes in typhoid endemic settings is highly recommended.
FUNDING
There was no funding source for this study.
Topics: Humans; Infant; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Pseudomonas aeruginosa Exotoxin A; Vaccines, Attenuated; Vaccines, Conjugate; Tetanus Toxoid; Polysaccharides
PubMed: 38485426
DOI: 10.1016/S2214-109X(23)00606-X