Sanitation, Water, and Instruction in Face-washing for Trachoma I/II
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 47,605
- 试验地点
- 1
- 主要终点
- Village-specific ocular chlamydia among 0-5 children over time (first trial: WUHA)
研究概览
简要总结
SWIFT I is a series of 3 cluster-randomized trials designed to assess several alternative strategies for trachoma control in communities that have been treated with many years of mass azithromycin distributions. The first trial (named WUHA) compares communities that receive a comprehensive Water, Sanitation, and Hygiene (WASH) package to those that receive no intervention. The second trial (named TAITU-A) compares communities randomized to targeted antibiotic treatment versus those randomized to mass antibiotics for trachoma, and the third trial (TAITU-B) compares communities randomized to targeted antibiotics versus those randomized to delayed antibiotics.
SWIFT II is a continuation of the first trial (WUHA I). WUHA I is an ongoing cluster-randomized trial in rural Ethiopia designed to determine the effectiveness of water, sanitation, and hygiene (WASH) for trachoma. 40 communities were randomized in a 1:1 ratio either to a comprehensive WASH package or to no intervention. The primary outcome is ocular chlamydia, monitored annually for 3 years.
In WUHA II we will treat all 40 WUHA communities with a single mass azithromycin distribution after the month 36 visit, and then continue the WASH intervention only in the 20 communities originally randomized to the WASH arm. We perform annual monitoring visits at months 48, 60, 72, and 84 for the primary outcome of ocular chlamydia among 0-5 year old children. A second aim of WUHA II is to perform a diagnostic test accuracy study of the tests already being conducted as well as several novel tests for trachoma surveillance. The novel tests include inexpensive, point-of-care nucleic acid amplification tests performed on conjunctival swabs, a lateral flow assay for chlamydia seropositivity tested on dried blood spots, and an automated algorithm to detect clinical signs of trachoma from conjunctival photographs. The primary objective of the second aim is to test the sensitivity and specificity of each of these trachoma surveillance tests.
By comparing the combined azithromycin-WASH communities to communities receiving mass azithromycin alone, we investigate the benefit of combining the "A", "F", and "E" components of the SAFE strategy as opposed to focusing on antibiotics alone. This is an important question given the expense of WASH interventions and the limited resources of trachoma programs.
详细描述
Trachoma is a blinding disease caused by ocular strains of Chlamydia trachomatis. The Carter Center and Proctor Foundation have been jointly conducting trachoma research in the Amhara region of Ethiopia for the past 10 years, through a series of clinical trials. We have found that repeated mass administration of oral azithromycin can greatly reduce the prevalence of trachoma, but mass antibiotics have been unable thus far to eliminate infection.
The World Health Organization recommends not only antibiotics for control of trachoma, but an entire SAFE strategy (Surgery for in-turned eyelids, Antibiotics, Facial hygiene promotion, and Environmental improvements such as latrines and water points). The rationale for the SAFE strategy is based on many years of observational studies on trachoma. Cross-sectional studies have found that clinically active trachoma and ocular chlamydial infection are associated with several indicators of poor hygiene, including dirty faces, face-seeking flies, long distance to water supply, and lack of household latrine. There are few randomized trials testing the impact of WASH improvements on trachoma.
In the past, the WHO has recommended targeted antibiotic treatments to those individuals with active disease, so this could be an alternative treatment strategy that would limit antibiotic use in the community and perhaps be cost-saving. However, little research has assessed targeted treatments as a strategy for trachoma elimination following repeated mass azithromycin distributions.
Our long term goal is to eliminate trachoma even in the most hyperendemic communities. This cluster-randomized clinical trial will determine the role of a comprehensive package of sanitation measures for the elimination of trachoma. We will monitor clinical disease with photography, and monitor infection with a newer chlamydial polymerase chain reaction (PCR) test (Abbott m2000) that is more sensitive than earlier generation tests, and provides quantification. We will monitor other potential health benefits of a WASH intervention and test its overall cost effectiveness. We will also assess a competing strategy for minimizing antibiotic use: that of targeted azithromycin treatments to children testing positive for ocular chlamydia. We will model the long-term cost-effectiveness of these competing strategies for trachoma control after completion of several rounds of mass azithromycin distributions.
Our monitoring has revealed a high uptake of the SWIFT I/WUHA I intervention as well as evidence of subsequent hygiene behavior changes. However, communities started out with a high burden of ocular chlamydia and preliminary data suggests that elimination will be unlikely. We therefore were granted an continuation grant (SWIFT II) to determine the long-term benefit of WASH for trachoma when combined with antibiotics, and second, to explore possibilities for low-cost, highly accurate point-of-care test for chlamydia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 至 120 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Community Level
- •Inclusion Criteria
- •Community in a school district that is within the study area of WagHimra
- •Area within each school district with a site identified for water point construction
- •At least 5 rounds of mass azithromycin distributions had been performed within community
排除标准
- •School districts that are too difficult to reach (more than a 1-day of travel to access)
- •School districts in the 2 urban regions of the study area, since urban communities have better access to water and sanitation and have less trachoma
- •Refusal of village chief
- •Individual Level
- •Inclusion Criteria:
- •All residents residing within a 1.5km radius from the most promising potential water point the water point sites within the school district that were identified for the study
- •Exclusion criteria
- •Refusal of participant [or parent/guardian]
研究组 & 干预措施
Mass antibiotics arm (TAITU)
Mass antibiotic treatment: Communities will receive mass azithromycin treatment of all individuals aged 6 months and up (20mg/kg for children; 1 g for adults); those younger than 6 months, pregnant, or allergic to macrolide antibiotics will be offered a 2-week course of tetracycline.
干预措施: Tetracycline (Drug)
Delayed mass antibiotics arm (TAITU)
Delayed mass antibiotic treatment: Communities will receive no mass azithromycin treatment during the study period. Communities in this treatment group have previously received at least 8 rounds of mass azithromycin treatment. These clusters will be enrolled in an antibiotics treatment program (azithromycin or tetracycline) after the completion of the study.
干预措施: Control (Other)
Standard of care WASH arm (WUHA)
WUHA I: Standard of care WASH intervention: Communities will continue to receive the standard of care WASH programming offered by the Ethiopian government.
WUHA II: Standard of care WASH intervention and treatment: Communities will continue to receive the standard of care WASH programming offered by the Ethiopian government.
A single mass azithromycin distribution will be given in all 40 WUHA I communities (both intervention and control) after the final study visit (i.e., month 36). Children 6 months and up will be offered azithromycin 20mg/kg; those under 6 months will be offered tetracycline.
These communities will receive a WASH package at the conclusion of the SWIFT II study, including water point construction, hygiene and sanitation promotion, and educational materials.
干预措施: Azithromycin (Drug)
WASH arm (WUHA)
WUHA I, Behavioral: Water, sanitation, and hygiene (WASH) intervention: Communities will receive the water, sanitation, and hygiene (WASH) intervention including community water point construction, hygiene and sanitation education and promotion, community-based hygiene promotion workers, household wash stations, household WASH education books, household soap distribution, and a hygiene curriculum for primary schools.
WUHA II, Behavioral and Treatment: WASH intervention communities will continue to receive the water, sanitation, and hygiene (WASH) intervention.
A single mass azithromycin distribution will be given in all 40 WUHA I communities (both intervention and control) after the final study visit (i.e., month 36). Children 6 months and up will be offered azithromycin 20mg/kg; those under 6 months will be offered tetracycline.
干预措施: Water, sanitation, and hygiene (WASH) intervention (Behavioral)
Standard of care WASH arm (WUHA)
WUHA I: Standard of care WASH intervention: Communities will continue to receive the standard of care WASH programming offered by the Ethiopian government.
WUHA II: Standard of care WASH intervention and treatment: Communities will continue to receive the standard of care WASH programming offered by the Ethiopian government.
A single mass azithromycin distribution will be given in all 40 WUHA I communities (both intervention and control) after the final study visit (i.e., month 36). Children 6 months and up will be offered azithromycin 20mg/kg; those under 6 months will be offered tetracycline.
These communities will receive a WASH package at the conclusion of the SWIFT II study, including water point construction, hygiene and sanitation promotion, and educational materials.
干预措施: Standard of care WASH intervention (Behavioral)
Targeted antibiotics arm (TAITU)
Targeted antibiotic treatment: Communities will receive targeted antibiotic treatments for children testing positive for ocular chlamydia at 3, 6, 9, and 12 months after baseline testing. After testing for ocular chlamydia at 12 months, any children testing positive at this time point will receive antibiotic treatments at 15, 18, 21, and 24 months. Children 6 months and up will be offered azithromycin 20mg/kg; those under 6 months will be offered tetracycline.
干预措施: Azithromycin (Drug)
Standard of care WASH arm (WUHA)
WUHA I: Standard of care WASH intervention: Communities will continue to receive the standard of care WASH programming offered by the Ethiopian government.
WUHA II: Standard of care WASH intervention and treatment: Communities will continue to receive the standard of care WASH programming offered by the Ethiopian government.
A single mass azithromycin distribution will be given in all 40 WUHA I communities (both intervention and control) after the final study visit (i.e., month 36). Children 6 months and up will be offered azithromycin 20mg/kg; those under 6 months will be offered tetracycline.
These communities will receive a WASH package at the conclusion of the SWIFT II study, including water point construction, hygiene and sanitation promotion, and educational materials.
干预措施: Tetracycline (Drug)
WASH arm (WUHA)
WUHA I, Behavioral: Water, sanitation, and hygiene (WASH) intervention: Communities will receive the water, sanitation, and hygiene (WASH) intervention including community water point construction, hygiene and sanitation education and promotion, community-based hygiene promotion workers, household wash stations, household WASH education books, household soap distribution, and a hygiene curriculum for primary schools.
WUHA II, Behavioral and Treatment: WASH intervention communities will continue to receive the water, sanitation, and hygiene (WASH) intervention.
A single mass azithromycin distribution will be given in all 40 WUHA I communities (both intervention and control) after the final study visit (i.e., month 36). Children 6 months and up will be offered azithromycin 20mg/kg; those under 6 months will be offered tetracycline.
干预措施: Azithromycin (Drug)
WASH arm (WUHA)
WUHA I, Behavioral: Water, sanitation, and hygiene (WASH) intervention: Communities will receive the water, sanitation, and hygiene (WASH) intervention including community water point construction, hygiene and sanitation education and promotion, community-based hygiene promotion workers, household wash stations, household WASH education books, household soap distribution, and a hygiene curriculum for primary schools.
WUHA II, Behavioral and Treatment: WASH intervention communities will continue to receive the water, sanitation, and hygiene (WASH) intervention.
A single mass azithromycin distribution will be given in all 40 WUHA I communities (both intervention and control) after the final study visit (i.e., month 36). Children 6 months and up will be offered azithromycin 20mg/kg; those under 6 months will be offered tetracycline.
干预措施: Tetracycline (Drug)
Targeted antibiotics arm (TAITU)
Targeted antibiotic treatment: Communities will receive targeted antibiotic treatments for children testing positive for ocular chlamydia at 3, 6, 9, and 12 months after baseline testing. After testing for ocular chlamydia at 12 months, any children testing positive at this time point will receive antibiotic treatments at 15, 18, 21, and 24 months. Children 6 months and up will be offered azithromycin 20mg/kg; those under 6 months will be offered tetracycline.
干预措施: Tetracycline (Drug)
Mass antibiotics arm (TAITU)
Mass antibiotic treatment: Communities will receive mass azithromycin treatment of all individuals aged 6 months and up (20mg/kg for children; 1 g for adults); those younger than 6 months, pregnant, or allergic to macrolide antibiotics will be offered a 2-week course of tetracycline.
干预措施: Azithromycin (Drug)
结局指标
主要结局
Village-specific ocular chlamydia among 0-5 children over time (first trial: WUHA)
时间窗: 12, 24, 36, 48, 60, 84, 96 months
Multiple time points will be used in a mixed effects regression model of the village-specific ocular chlamydia prevalences over time in 0-5 year olds as assessed by PCR.
Ocular chlamydia among 8-12 year olds (second trial: TAITU-A)
时间窗: 24 months
Cluster-specific prevalence of ocular chlamydia among individuals aged 8-12 years, compared between the targeted azithromycin arm and the mass azithromycin arm.
Incident ocular chlamydia in 0-5 year-olds (third trial: TAITU-B)
时间窗: 24 months
Incidence of new ocular chlamydia infection in 0-5 year-olds, compared between the targeted azithromycin arm and the delayed mass azithromycin arm.
Trial-based cost-effectiveness of intervention (intervention costs per percent of chlamydia reduction)
时间窗: 24 months for TAITU, 36 months for WUHA
The short term analysis is designed to provide insight into whether each intervention (WASH or targeted antibiotics) is effective for our primary trial outcome of reducing ocular chlamydial infection in children. The time horizon of these analyses will be the duration of each trial.
次要结局
- Quantitative PCR chlamydia load(12, 24, 36, 48, 60, 84, 96 months)
- Follicular trachoma scores; age-stratified (0-5, 6-9, 10 and up for WUHA; 0-5, 8-12 for TAITU)(12, 24, 36, 48, 60, 84, 96 months)
- Inflammatory trachoma scores; age-stratified (0-5, 6-9, 10 and up for WUHA; 0-5, 8-12 for TAITU)(12, 24, 36, 48, 60, 84, 96 months)
- Clinical trachoma improvement as measured in photography(12, 24, 36, 48, 60, 84, 96 months)
- Chlamydial load, individual level analysis(12, 24, 36, 48, 60, 84, 96 months)
- Ocular chlamydia; age-stratified (6-9, 10 and up for WUHA; 8-12 for TAITU)(12, 24, 36, 48, 60, 84, 96 months)
- Nasopharyngeal pneumococcal macrolide resistance(12, 24, 36, 96 months)
- Proportion of the population with clean faces at the village level(12, 24, 36, 48, 60, 84, 96 months)
- Childhood growth (height)(12, 24, 36 months)
- Childhood growth (weight)(12, 24, 36 months)
- Soil-transmitted helminth prevalence(12, 24, 36 months)
- Soil-transmitted helminth density(12, 24, 36 months)
- Prevalence of chlamydia and other antigen positivity from serological tests(12, 24, 36, 48, 60, 84, 96 months)
- Prevalence of stool-based antigen (diarrheal pathogens, soil transmitted helminths) positivity from serological tests(12, 24, 36, 48, 60, 84, 96 months)
- Intestinal microbiome from rectal sample(24 months)
- Sensitivity and specificity of detecting STH using rectal swabs(24 months)