Estimating Cholera Burden with Cross-sectional Immunologic Data

用横截面免疫学数据估计霍乱负担

• 批准号: 10388296
• 负责人: Daniel Ted Leung
• 金额: $ 64.72万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-25 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10388296
• 关键词: Acute; Address; Affect; Africa; Antibodies; Antibody Response; Area; Bangladesh; Bangladeshi; Blood; Caring; Cessation of life; Cholera; Cholera Vaccine; Clinical; Collaborations; Computer Models; Computing Methodologies; Country; Data; Decision Making; Demographic Factors; Detection; Development; Devices; Diarrhea; Disease; Disease Outbreaks; Disease Surveillance; Enrollment; Epidemic; Epidemiology; Exposure to; Funding; Future; Generations; Genetic; Haiti; Haitian; Health care facility; Health system; Household; Immune response; Immunologics; Immunology; Incidence; Individual; Infection; Infrastructure; Intervention; Joints; Kinetics; Laboratories; Lateral; Link; Logistics; Measurement; Measures; Methods; Microbiology; Modeling; Nature; Oral; Patients; Persons; Population; Populations at Risk; Predisposition; Reporting; Research Infrastructure; Research Personnel; Resource-limited setting; Risk; Rural; Sanitation; Sensitivity and Specificity; Serology; Serum; Specificity; Spottings; Standardization; Surveillance Methods; System; Time; Translations; Uncertainty; United States National Institutes of Health; Vibrio cholerae; Vibrio cholerae O1; Vibrio cholerae infection; Water; age related; antibody test; base; cohort; diarrheal disease; disorder risk; fighting; high risk; improved; insight; lateral flow assay; machine learning method; novel; pathogen; predictive modeling; serosurveillance; serosurvey; statistical and machine learning; statistics; tool

Project Summary/Abstract Cholera is an acute dehydrating diarrheal disease caused by infection with Vibrio cholerae. It is endemic in over 50 countries, affecting up to 3 million people and causing more than 100,000 deaths annually. A renewed global effort to fight cholera is underway, catalyzed by the large on-going epidemic in Haiti and now aided by new generation oral cholera vaccines. Identifying key populations at high risk of cholera is essential to guide these activities. Current methods to estimate cholera burden are largely based on clinical reporting with infrequent microbiological confirmation. These methods are limited by the sporadic nature of outbreaks, poor surveillance infrastructure, and fundamental uncertainties in the number of asymptomatic or mildly symptomatic cases. Improved methods of detecting cholera exposure and risk are urgently needed. Detection of immune responses in serum (serosurveillance) can provide a new avenue for rapid and accurate estimates of cholera exposure and risk. We currently do not understand what immunological and clinical parameters are most predictive of recent exposure, nor whether immune responses in areas with different levels of endemicity are similar. In preliminary studies, we have used machine learning methods on antibody response data from cholera patients in Bangladesh to classify whether individuals had been exposed in the previous 30-, 90-, or 360-days with high sensitivity and specificity. In this application, we propose to use longitudinal antibody response kinetics, from populations with diverse genetic and epidemiologic profiles, paired with novel statistical and machine learning approaches to provide generalizable tools to estimate the incidence of exposure to Vibrio cholerae from cross sectional serosurveys. In Aim 1, we will develop models to estimate the time since exposure to Vibrio cholerae and exposure incidence from cross-sectional antibody profiles and demographic data using previously collected data from a cohort in Bangladesh. These results will allow us to identify the antibodies and demographic factors that are most useful for prediction of time-since-exposure. In Aim 2, we will collect longitudinal antibody data from a cohort of cholera cases and household contacts in Haiti to develop models for estimating exposure incidence from cross-sectional serosurveillance. This cohort will also enable us to compare the models developed for moderate/severe cases and mild/asymptomatic cases. In Aim 3, we will optimize and validate field-adapted methods to measure cholera-specific antibodies, including the use of dried blood spot and lateral flow assays. We will conduct a proof-of-concept cross-sectional serosurvey using these methods in rural Haiti. Upon the completion of these aims, we will have provided a number of new tools for measure of susceptibility to cholera in a population. These tools will have the potential to transform cholera control efforts from the current reactive strategies to proactive ones, with the potential to contribute to disease elimination.

项目总结/文摘

项目成果

Global diversity of policy, coverage, and demand of COVID-19 vaccines: a descriptive study.

• DOI: 10.1186/s12916-022-02333-0
• 发表时间: 2022-04-04
• 期刊: BMC medicine
• 影响因子: 9.3
• 作者: Chen Z;Zheng W;Wu Q;Chen X;Peng C;Tian Y;Sun R;Dong J;Wang M;Zhou X;Zhao Z;Zhong G;Yan X;Liu N;Hao F;Zhao S;Zhuang T;Yang J;Azman AS;Yu H
• 通讯作者: Yu H

Systemic, Mucosal, and Memory Immune Responses following Cholera.

• DOI: 10.3390/tropicalmed6040192
• 发表时间: 2021-10-27
• 期刊: Tropical medicine and infectious disease
• 影响因子: 2.9
• 作者: Ryan ET;Leung DT;Jensen O;Weil AA;Bhuiyan TR;Khan AI;Chowdhury F;LaRocque RC;Harris JB;Calderwood SB;Qadri F;Charles RC
• 通讯作者: Charles RC

Estimating the proportion of clinically suspected cholera cases that are true Vibrio cholerae infections: A systematic review and meta-analysis.

• DOI: 10.1371/journal.pmed.1004286
• 发表时间: 2023-09
• 期刊: PLoS medicine
• 影响因子: 15.8

A Novel Luminescence-Based Serum Bactericidal Assay for Vibrio cholerae Reduces Assay Variation, Is Time- and Cost-Effective, and Directly Measures Continuous Titer Values.

一种新型的基于发光的霍乱弧菌血清杀菌测定可减少测定变异，具有时间和成本效益，并直接测量连续滴度值。

• DOI: 10.4269/ajtmh.21-0136
• 发表时间: 2021
• 期刊: The American journal of tropical medicine and hygiene
• 作者: Wahlig,TaylorA;Brintz,BenJ;Prettyman,Melanie;Azman,AndrewS;Leung,DanielT
• 通讯作者: Leung,DanielT

Sero-evaluation of Immune Responses to Vibrio cholerae in a Postelimination Setting.

消除后环境中霍乱弧菌免疫反应的血清评估。

• DOI: 10.1093/ofid/ofaa136
• 发表时间: 2020
• 期刊: Open forum infectious diseases
• 影响因子: 4.2
• 作者: Diep,TaiThe;Jensen,Owen;VanThuong,Nguyen;Nhi,NguyenThiNgoc;Thu,NguyenNgocAnh;Quang,VoNgoc;Hieu,TruongCong;Thang,HoangAnh;Thuy,NguyenDieu;Thang,HoVinh;Tuyen,HoTrung;Ngan,LeDang;Ha,NguyenThiThanh;Dung,ThanDuc;Ande
• 通讯作者: Ande