Data Management in Multicountry Consortium Studies: The Enterics For Global Health (EFGH) Shigella Surveillance Study Example.

Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study-a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella--associated diarrhea in children 6 to 35 months old. Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study. Results: This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis. Conclusions: Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data.

Projected impact and cost-effectiveness of community-based versus targeted azithromycin administration strategies for reducing child mortality in sub-Saharan Africa.

BACKGROUND: Trials of mass drug administration (MDA) of azithromycin (AZM) report reductions in child mortality in sub-Saharan Africa (SSA). AZM targeted to high-risk children may preserve benefit while minimizing antibiotic exposure. We modeled the cost-effectiveness of MDA to children 1-59 months of age, MDA to children 1-5 months of age, AZM administered at hospital discharge, and the combination of MDA and post-discharge AZM. METHODS AND FINDINGS: Models employed a payer perspective with a 1-year time horizon. Cost-effectiveness was presented as cost per DALY averted and death averted, with probabilistic sensitivity analyses. The model included parameters for macrolide resistance, adverse events, hospitalization, and mortality sourced from published data. Assuming a base-case 1.64% mortality risk among children 1-59 months old, 3.1% among children 1-5 months old, 4.4% mortality risk post-discharge, and 13.5% mortality reduction per trial data, post-discharge AZM would avert ~45,000 deaths, at a cost of $2.84/DALY (95% uncertainty interval [UI]: 1.71-5.57) averted. MDA to only children 1-5 months old would avert ~186,000 deaths at a cost of $4.89/DALY averted (95% UI: 2.88-11.42), MDA to all under-5 children would avert ~267,000 deaths a cost of $14.26/DALY averted (95% UI: 8.72-27.08). Cost-effectiveness decreased with presumed diminished efficacy due to macrolide resistance. CONCLUSIONS: Targeting AZM to children at highest risk of death may be an antibiotic-sparing and cost-effective, or even cost-saving, strategy to reduce child mortality. However, targeted AZM averts fewer absolute deaths and may not reach all children who would benefit. Any AZM administration decision must consider implications for antibiotic resistance.

Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990-2016.

BACKGROUND: Shigella and enterotoxigenic Escherichia coli (ETEC) are bacterial pathogens that are frequently associated with diarrhoeal disease, and are a significant cause of mortality and morbidity worldwide. The Global Burden of Diseases, Injuries, and Risk Factors study 2016 (GBD 2016) is a systematic, scientific effort to quantify the morbidity and mortality due to over 300 causes of death and disability. We aimed to analyse the global burden of shigella and ETEC diarrhoea according to age, sex, geography, and year from 1990 to 2016. METHODS: We modelled shigella and ETEC-related mortality using a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We used a compartmental meta-regression tool to model the incidence of shigella and ETEC, which enforces an association between incidence, prevalence, and remission on the basis of scientific literature, population representative surveys, and health-care data. We calculated 95% uncertainty intervals (UIs) for the point estimates. FINDINGS: Shigella was the second leading cause of diarrhoeal mortality in 2016 among all ages, accounting for 212 438 deaths (95% UI 136 979-326 913) and about 13·2% (9·2-17·4) of all diarrhoea deaths. Shigella was responsible for 63 713 deaths (41 191-93 611) among children younger than 5 years and was frequently associated with diarrhoea across all adult age groups, increasing in elderly people, with broad geographical distribution. ETEC was the eighth leading cause of diarrhoea mortality in 2016 among all age groups, accounting for 51 186 deaths (26 757-83 064) and about 3·2% (1·8-4·7) of diarrhoea deaths. ETEC was responsible for about 4·2% (2·2-6·8) of diarrhoea deaths in children younger than 5 years. INTERPRETATION: The health burden of bacterial diarrhoeal pathogens is difficult to estimate. Despite existing prevention and treatment options, they remain a major cause of morbidity and mortality globally. Additional emphasis by public health officials is needed on a reduction in disease due to shigella and ETEC to reduce disease burden. FUNDING: Bill & Melinda Gates Foundation.

HIV shedding in the oral cavity: an assessment of HIV type, immunovirologic, demographic and oral factors.

OBJECTIVE: To quantify the prevalence and burden of HIV type 2 (HIV-2) and HIV-1 RNA in the oral cavity of antiretroviral therapy-naive HIV-infected Senegalese individuals and to identify correlates of oral HIV viral loads. DESIGN: A cross-sectional study of 163 HIV-1 and 27 HIV-2-infected antiretroviral therapy-naive Senegalese adults. METHODS: Participants received clinical and oral exams and provided blood and oral wash samples for viral load and plasma CD4 count ascertainment. Logistic and interval regression models were used to identify univariate and multivariable associations between presence and level of oral HIV RNA and various immunovirologic, local and demographic factors. RESULTS: Presence of detectable oral HIV RNA was less common in HIV-2-infected compared with HIV-1-infected study participants (33% vs 67%, OR 0.25, 95% CI 0.11 to 0.59). HIV type was no longer associated with oral shedding of HIV when plasma viral load was considered. Detection of oral HIV RNA was associated with increased plasma viral load in both HIV-1-infected and HIV-2-infected individuals (HIV-1, OR 1.89, 95% CI 1.24 to 2.61; HIV-2, OR 1.93, 95% CI 1.1 to 3.39). Oral HIV-1 detection was also associated with periodontal disease (OR 3.02, 95% CI 1.16 to 7.87). CONCLUSIONS: Oral shedding of HIV-2 RNA is less common than HIV-1 RNA, a likely consequence of lower overall viral burden. Both systemic and local factors may contribute to shedding of HIV in the oral cavity.