Dataset Information

Epidemiology of Shigella infections and diarrhea in the first two years of life using culture-independent diagnostics in 8 low-resource settings.

ABSTRACT: Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (<10 years, RR: 1.14, 95% CI: 1.03, 1.26), initiating complementary foods before 3 months (RR: 1.10, 95% CI: 1.01, 1.20), and malnutrition (RR: 0.91, 95% CI: 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uniformly increased through the second year of life and was associated with intestinal inflammation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.

SUBMITTER: Rogawski McQuade ET

PROVIDER: S-EPMC7451981 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Epidemiology of Shigella infections and diarrhea in the first two years of life using culture-independent diagnostics in 8 low-resource settings.

Rogawski McQuade Elizabeth T ET Shaheen Fariha F Kabir Furqan F Rizvi Arjumand A Platts-Mills James A JA Aziz Fatima F Kalam Adil A Qureshi Shahida S Elwood Sarah S Liu Jie J Lima Aldo A M AAM Kang Gagandeep G Bessong Pascal P Samie Amidou A Haque Rashidul R Mduma Estomih R ER Kosek Margaret N MN Shrestha Sanjaya S Leite Jose Paulo JP Bodhidatta Ladaporn L Page Nicola N Kiwelu Ireen I Shakoor Sadia S Turab Ali A Soofi Sajid Bashir SB Ahmed Tahmeed T Houpt Eric R ER Bhutta Zulfiqar Z Iqbal Najeeha Talat NT

PLoS neglected tropical diseases 20200817 8

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we ...[more]

PMID: 32804926

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Project description:BackgroundShigella is a leading cause of diarrhea and dysentery in children in low-resource settings, which is frequently treated with antibiotics. The primary goal of a Shigella vaccine would be to reduce mortality and morbidity associated with Shigella diarrhea. However, ancillary benefits could include reducing antibiotic use and antibiotic exposures for bystander pathogens carried at the time of treatment, specifically for fluoroquinolones and macrolides (F/M), which are the recommended drug classes to treat dysentery. The aim of the study was to quantify the reduction in Shigella attributable diarrhea, all diarrhea, and antibiotic use in the first 2 years of life that could be prevented by a Shigella vaccine.Methods and findingsWe used data from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, a birth cohort study that followed 1,715 children with twice weekly surveillance for enteric infections, illnesses, and antibiotic use for the first 2 years of life from November 2009 to February 2014 at 8 sites. We estimated the impact of 2 one-dose (6 or 9 months) and 3 two-dose (6 and 9 months, 9 and 12 months, and 12 and 15 months) Shigella vaccines on diarrheal episodes, overall antibiotic use, and F/M use. Further, we considered additional protection through indirect and boosting effects. We used Monte Carlo simulations to estimate the absolute and relative reductions in the incidence of diarrhea and antibiotic use comparing each vaccination scenario to no vaccination. We analyzed 9,392 diarrhea episodes and 15,697 antibiotic courses among 1,715 children in the MAL-ED birth cohort study. There were 273.8 diarrhea episodes, 30.6 shigellosis episodes, and 457.6 antibiotic courses per 100 child-years. A Shigella vaccine with a mean vaccine efficacy of 60% against severe disease given at 9 and 12 months prevented 10.6 (95% CI [9.5, 11.5]) Shigella diarrhea episodes of any severity per 100 child-years (relative 34.5% reduction), 3.0 (95% CI [2.5, 3.5]) F/M courses for Shigella treatment per 100 child-years (relative 35.8% reduction), and 5.6 (95% CI [5.0, 6.3]) antibiotic courses of any drug class for Shigella treatment per 100 child-years (relative 34.5% reduction). This translated to a relative 3.8% reduction in all diarrhea, a relative 2.8% reduction in all F/M courses, a relative 3.1% reduction in F/M exposures to bystander pathogens, and a relative 0.9% reduction in all antibiotic courses. These results reflect Shigella incidence and antibiotic use patterns at the 8 MAL-ED sites and may not be generalizable to all low-resource settings.ConclusionsOur simulation results suggest that a Shigella vaccine meeting WHO targets for efficacy could prevent about a third of Shigella diarrhea episodes, antibiotic use to treat shigellosis, and bystander exposures due to shigellosis treatment. However, the reductions in overall diarrhea episodes and antibiotic use are expected to be modest (<5%).

Project description:IntroductionSexually transmitted infections (STIs) remain prevalent and are increasing in several populations. Appropriate STI diagnosis is crucial to prevent the transmission and sequelae of untreated infection. We reviewed the diagnostic accuracy of syndromic case management and existing point-of-care tests (POCTs), including those in the pipeline, to diagnose STIs in resource-constrained settings.MethodsWe prioritized updating the systematic review and meta-analysis of the diagnostic accuracy of vaginal discharge from 2001 to 2015 to include studies until 2018. We calculated the absolute effects of different vaginal flowcharts and the diagnostic performance of POCTs on important outcomes. We searched the peer-reviewed literature for previously conducted systematic reviews and articles from 1990 to 2018 on the diagnostic accuracy of syndromic management of vaginal and urethral discharge, genital ulcer and anorectal infections. We conducted literature reviews from 2000 to 2018 on the existing POCTs and those in the pipeline.Results and discussionsThe diagnostic accuracy of urethral discharge and genital ulcer disease syndromes is relatively adequate. Asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections limit the use of vaginal discharge and anorectal syndromes. The pooled diagnostic accuracy of vaginal syndromic case management for CT/NG is low, resulting in high numbers of overtreatment and missed treatment. The absolute effect of POCTs was reduced overtreatment and missed treatment. Findings of the reviews on syndromic case management underscored the need for low-cost and accurate POCTs for the identification, first, of CT/NG, and, second, of Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) and NG and MG resistance/susceptibility testing. Near-patient POCT molecular assays for CT/NG/TV are commercially available. The prices of these POCTs remain the barrier for uptake in resource-constrained settings. This is driving the development of lower cost solutions.ConclusionsThe WHO syndromic case management guidelines should be updated to raise the quality of STI management through the integration of laboratory tests. STI screening strategies are needed to address asymptomatic STIs. POCTs that are accurate, rapid, simple and affordable are urgently needed in resource-constrained settings to support the uptake of aetiological diagnosis and treatment.

Project description:Vasectomy is a highly effective and safe contraceptive method for couples who want to stop childbearing, but only 2.4% of men around the world use this method. We conducted an extensive review of the vasectomy research literature and programmatic reports, published between April 2005 and April 2015, to synthesize barriers and facilitators to vasectomy adoption. Of the more than 230 documents initially retrieved in our search, we ultimately included 75 documents in our review and synthesized the findings according to the Supply-Enabling Environment-Demand (SEED) Programming Model. Regarding promoting demand for vasectomy services, we found there was a general lack of awareness about the method among both men and women, which often fueled erroneous assumptions about how vasectomy affects men. Several types of programmatic activities directly addressed knowledge gaps and negative misperceptions, including community-based and mass media communications, employer-based promotion, and group counseling. For supply of services, the lack of or inaccurate knowledge about vasectomy was also prevalent among providers, particularly among community-based health workers. Programmatic activities to improve service delivery included the use of evidence-based vasectomy techniques such as no-scalpel vasectomy, whole-site trainings, task shifting, cascade training, and mobile outreach. Finally, programmatic approaches to building a more enabling environment included engagement of governments and other community and religious leaders as well as campaigns with gender transformative messaging that countered common myths and encouraged men's positive engagement in family planning and reproductive health. In summary, a successful vasectomy program is comprised of the mutually reinforcing components of continual demand for services and access to and supply of well-trained providers. In addition, there is an underlying need for enabling policies within the cultural and gender environments that extend beyond vasectomy and include men not just as default partners of female family planning clients but as equal beneficiaries of family planning and reproductive health programs in their own right. Accelerating progress toward meaningful integration of vasectomy into a comprehensive contraceptive method mix is only possible when political and financial will are aligned and support the logistical and promotional activities of a male reproductive health agenda.

Dataset Information

Epidemiology of Shigella infections and diarrhea in the first two years of life using culture-independent diagnostics in 8 low-resource settings.

Publications

Epidemiology of Shigella infections and diarrhea in the first two years of life using culture-independent diagnostics in 8 low-resource settings.

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