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BMC Public Health 2013Diarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development. Despite advances in the... (Review)
Review
BACKGROUND
Diarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development. Despite advances in the understanding of diarrheal disorders and management strategies, globally nearly 750,000 children die annually as a consequence of diarrhea.
METHODS
We conducted a systematic review of the efficacy and effectiveness studies. We used a standardized abstraction and grading format and performed meta-analyses for all outcomes. The estimated effect of cholera, shigella, Enterotoxigenic Escherichia coli (ETEC) and rotavirus vaccines was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules.
RESULTS
A total of 24 papers were selected and analyzed for all the four vaccines. Based on the evidence, we propose a 74% mortality reduction in rotavirus specific mortality, 52% reduction in cholera incidence due to their respective vaccines. We did not find sufficient evidence and a suitable outcome to project mortality reductions for cholera, ETEC and shigella in children under 5 years.
CONCLUSION
Vaccines for rotavirus and cholera have the potential to reduce diarrhea morbidity and mortality burden. But there is no substantial evidence of efficacy for ETEC and shigella vaccines, although several promising vaccine concepts are moving from the development and testing pipeline towards efficacy and Phase 3 trials.
Topics: Bacterial Vaccines; Child; Child, Preschool; Cholera; Cholera Vaccines; Comorbidity; Diarrhea; Dysentery; Dysentery, Bacillary; Escherichia coli Infections; Humans; Immunization Schedule; Infant; Male; Rotavirus Infections; Shigella Vaccines; Viral Vaccines
PubMed: 24564510
DOI: 10.1186/1471-2458-13-S3-S11 -
Travel Medicine and Infectious Disease 2023Southeast Asia is attractive for tourism. Unfortunately, travelers to this region are at risk of becoming infected with Shigella. We conducted a meta-analysis to provide... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Southeast Asia is attractive for tourism. Unfortunately, travelers to this region are at risk of becoming infected with Shigella. We conducted a meta-analysis to provide updates on Shigella prevalence in Southeast Asia, along with their serogroups and serotypes.
METHODS
We conducted a systematic search using PubMed, EMBASE, and Web of Science for peer-reviewed studies from 2000 to November 2022. We selected studies that detected Shigella in stools by culture or polymerase chain reaction (PCR). Two reviewers extracted the data using a standardized form and performed quality assessments using the Joanna Briggs Institute checklist. The random effects model was used to estimate the pooled prevalence of Shigella.
RESULTS
During our search, we identified 4376 studies. 29 studies (from six Southeast Asian countries) were included in the systematic review, 21 each in the meta-analysis of the prevalence of Shigella (Sample size: 109545) and the prevalence of Shigella serogroups. The pooled prevalence of Shigella was 4% (95% CI: 4-5%) among diarrhea cases. Shigella sonnei was the most abundant serogroup in Thailand (74%) and Vietnam (57%), whereas Shigella flexneri was dominant in Indonesia (72%) and Cambodia (71%). Shigella dysenteriae and Shigella boydii were uncommon (pooled prevalence of 1% each). The pooled prevalence of Shigella was 5% (95% CI: 4-6%) in children aged <5 years. The pooled prevalence showed a decreasing trend comparing data collected between 2000-2013 (5%; 95% CI: 4-6%) and between 2014-2022 (3%; 95% CI: 2-4%). Shigella prevalence was 6% in studies that included participants with mixed pathogens versus 3% in those without. Shigella flexneri serotype 2a was the most frequently isolated (33%), followed by 3a (21%), 1b (10%), 2b (3%), and 6 (3%).
CONCLUSIONS
This study provides compelling evidence for the development of effective Shigella vaccines for residents of endemic regions and travellers to these areas.
Topics: Child; Humans; Dysentery, Bacillary; Shigella; Shigella dysenteriae; Shigella flexneri; Indonesia
PubMed: 36792021
DOI: 10.1016/j.tmaid.2023.102554 -
Epidemiology and Infection Feb 2013Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives... (Review)
Review
Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.
Topics: Diarrhea; Dysentery, Bacillary; Epidemiologic Research Design; Human Experimentation; Humans; Incidence; Shigella; Shigella Vaccines; Shigella dysenteriae; Shigella flexneri; Shigella sonnei
PubMed: 22906296
DOI: 10.1017/S0950268812001677 -
Vaccine Dec 2021Diarrhoeal infections are one of the leading causes of child's mortality and morbidity. Vaccines against Shigella, enterotoxigenic E. coli (ETEC), norovirus and invasive...
BACKGROUND
Diarrhoeal infections are one of the leading causes of child's mortality and morbidity. Vaccines against Shigella, enterotoxigenic E. coli (ETEC), norovirus and invasive non-typhoidal Salmonella are in clinical development, however, their full value in terms of short and long-term health and socio-economic burden needs to be evaluated and communicated, to rationalise investment in vaccine development, and deployment. While estimates of mortality of enteric infections exist, the long-term morbidity estimates are scarce and have not been systematically collected.
METHODS
The World Health Organization (WHO) has convened a Burden of Enteric Diseases Morbidity Working Group (BoED MWG) who identified key workstreams needed to characterise the morbidity burden of enteric infections. The group also identified four criteria for the prioritisation of pathogens of which impact on long-term morbidity needs to be assessed.
RESULTS
The BoED MWG suggested to identify and analyse the individual level data from historical datasets to estimate the impact of enteric infections and confounders on long-term morbidity, including growth faltering and cognitive impairment in children (workstream 1); to conduct a systematic review of evidence on the association of aetiology specific diarrhoea with short- and long- term impact on growth, including stunting, and possibly cognitive impairment in children, while accounting for potential confounders (workstream 2); and to conduct a systematic review of evidence on the association of aetiology specific diarrhoea with short- and long- term impact on health outcomes in adults. The experts prioritised four pathogens for this work: Campylobacter jejuni, ETEC (LT or ST), norovirus (G1 or G2), and Shigella (dysenteriae, flexneri, sonnei).
CONCLUSIONS
The proposed work will contribute to improving the understanding of the impact of enteric pathogens on long-term morbidity. The timing of this work is critical as all four pathogens have vaccine candidates in the clinical pipeline and decisions about investments in development, manufacturing or vaccine procurement and use are expected to be made soon.
Topics: Adult; Child; Diarrhea; Enterotoxigenic Escherichia coli; Humans; Morbidity; Shigella; Vaccine Development; World Health Organization
PubMed: 34838322
DOI: 10.1016/j.vaccine.2021.11.033 -
PLoS Neglected Tropical Diseases Feb 2014While Shigellae and strains of enterotoxigenic Escherichia coli (ETEC) are important causes of diarrhea-associated morbidity and mortality among infants and young... (Review)
Review
Estimating diarrheal illness and deaths attributable to Shigellae and enterotoxigenic Escherichia coli among older children, adolescents, and adults in South Asia and Africa.
INTRODUCTION
While Shigellae and strains of enterotoxigenic Escherichia coli (ETEC) are important causes of diarrhea-associated morbidity and mortality among infants and young children (<5 years of age), their health impact in older age groups is unclear. We sought to quantify the overall burden of shigellosis and ETEC diarrhea among older children, adolescents, and adults in Africa and South Asia, the two regions with the highest levels of diarrhea-related morbidity and mortality worldwide.
METHODS
We employed two distinct methodological approaches to estimate the burden of diarrhea due to Shigellae and ETEC among persons ≥ 5 years of age in the WHO regions of South Asia (SEAR) and Africa (AFR). Under method 1, we conducted a systematic review to identify the median proportion of total deaths due to diarrhea and then applied this figure to the number of all-cause deaths that occurred in 2010 among this age group. To estimate the total number of diarrhea deaths attributable to Shigellae and ETEC, we subsequently applied previously published estimates of the median percentage of diarrhea hospitalizations due to Shigellae and ETEC to the estimated number of diarrhea deaths. For method 2, we applied previously published incidence rates to 2010 population figures and estimated the total number of episodes due to Shigellae and ETEC using published estimates of the average proportion of pathogen-positive outpatients from studies of >4 pathogens. We then estimated the number of pathogen-specific deaths by determining the number of hospitalized patients and applying the case-fatality rate.
RESULTS
By method 1, there were 19,451 deaths due to Shigellae and 42,973 due to ETEC in AFR, and 20,691 due to Shigellae and 45,713 due to ETEC in SEAR in 2010. By method 2, there were 15.0 million ETEC episodes and 30.4 million episodes due to Shigellae in AFR, and 28.7 million episodes due to ETEC and 58.1 million episodes due to Shigellae in SEAR in 2010. We were unable to identify published case-fatality rates for ETEC and thus could only estimate Shigellae-related deaths using method 2, by which there were 5,308 and 10,158 Shigellae-related deaths in AFR and SEAR in 2010, respectively.
DISCUSSION
Methods 1 and 2 underscore the importance of Shigellae and ETEC as major causes of morbidity and mortality among older children, adolescents, and adults in AFR and SEAR. Understanding the epidemiology of these pathogens is imperative for the development and use of future vaccines and other preventative interventions.
Topics: Adolescent; Adult; Africa; Asia; Child; Child, Preschool; Dysentery, Bacillary; Enterotoxigenic Escherichia coli; Escherichia coli Infections; Humans; Middle Aged; Shigella; Young Adult
PubMed: 24551265
DOI: 10.1371/journal.pntd.0002705 -
PloS One 2016In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported.... (Review)
Review
BACKGROUND
In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance.
METHODOLOGY
We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context.
PRINCIPAL FINDINGS
Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations.
CONCLUSIONS
It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287.
Topics: Databases, Factual; Dysentery, Bacillary; Hematologic Tests; Humans; Neutropenia; Randomized Controlled Trials as Topic; Severity of Illness Index; Shigella Vaccines; Shigella sonnei; Vaccines
PubMed: 27490698
DOI: 10.1371/journal.pone.0157385 -
Vaccine Mar 2023Immunization is an essential component of national health plans. However, the growing number of new vaccine introductions, vaccination campaigns and increasing... (Review)
Review
Immunization is an essential component of national health plans. However, the growing number of new vaccine introductions, vaccination campaigns and increasing administrative costs create logistic and financial challenges, especially in resource-limited settings. Sub-national geographic targeting of vaccination programs is a potential strategy for governments to reduce the impact of infectious disease outbreaks while optimizing resource allocation and reducing costs, promoting sustainability of critically important national immunization plans. We conducted a systematic review of peer-reviewed literature to identify studies that investigated the cost-effectiveness of geographically targeted sub-national vaccination programs, either through routine immunization or supplementary immunization activities. A total of 16 studies were included in our review, covering nine diseases of interest: cholera, dengue, enterotoxigenic Escherichia coli (ETEC), hepatitis A, Japanese encephalitis, measles, rotavirus, Shigella and typhoid fever. All studies modelled cost-effectiveness of geographically targeted vaccination. Despite the variation in study design, disease focus and country context, studies generally found that in countries where a heterogenous burden of disease exists, sub-national geographic targeting of vaccination programs in areas of high disease burden was more cost-effective than a non-targeted strategy. Sensitivity analysis revealed that cost-effectiveness was most sensitive to variations in vaccine price, vaccine efficacy, mortality rate, administrative and operational costs, discount rate, and treatment costs. This systematic review identified several key characteristics related to geographic targeting of vaccination, including the vaccination strategy used, variations in modelling parameters and their impact on cost-effectiveness. Additional research and guidance is needed to support the appropriateness and feasibility of geographically targeted vaccination and to determine what country context would make this a viable complement to routine immunization programs.
Topics: Cost-Benefit Analysis; Vaccination; Immunization Programs; Immunization; Vaccines
PubMed: 36781333
DOI: 10.1016/j.vaccine.2023.02.006