Trachoma
Conditions
Keywords
Trachoma, Azithromycin, Mass treatment
Brief summary
Trachoma, an ocular infection caused by C. trachomatis, is the second leading infectious cause of blindness worldwide. Years of repeated infection with C. trachomatis cause the eyelid to scar and contract and ultimately to rotate inward such that the eyelashes rub against the eyeball and abrade the cornea (trichiasis). The World Health Organization (WHO) has endorsed a multi-faceted strategy to combat trachoma, which includes the use of antibiotic treatment to reduce the community pool of infection with C. trachomatis. The objective of this study is to conduct a randomized, community-based trial in three countries (Niger, Tanzania and The Gambia), representing different baseline endemicities, of alternative coverages and frequencies of administration of mass antibiotic treatment as well as to determine the cost-effectiveness of these different strategies from a program perspective.
Detailed description
A randomized, 2x2 factorial designed trial will be implemented in each of the three countries. Communities will be randomized to two different coverage targets (80%-89% versus ≥90%) for three years of mass treatment. In The Gambia and Tanzania, communities will be further randomized to yearly mass treatment versus mass treatment at baseline followed by yearly mass treatment only if trachoma prevalence in sentinel children is greater than 5%. The communities will continue to be followed and treatment will resume if trachoma prevalence is found to be 20% or greater at the 12 or 18 month surveys. In Niger, communities will be randomized to the different coverage levels for annual mass azithromycin distribution and further randomized to biannual treatment at the two coverage targets for children ages twelve or younger. Cross-sectional rates of trachoma and infection will be determined by examining sentinel children, age five years or younger, randomly selected from each community based on a community census. The census will be updated each year, and villages will be monitored at baseline, 6, 12, 18, 24, 30, and 36 months for infection and clinical disease. The three-year study is in accord with the WHO guidelines which recommend three years of annual mass treatment followed by a re-survey to determine need for further treatment. The investigators will evaluate the efficacy of guiding further mass treatment according to a laboratory test for Chlamydia or WHO guidelines. Where investigators estimate communities have infection rates less than 5% in sentinel children, or trachomatous inflammation (TF) ( rates less than 5%, the community will be graduated from further mass treatment and followed for up to three years to look for evidence of re-emergent infection and disease. If rates of infection are found to be 20% or more return at the 12 or 18 month survey, mass treatment will be re-initiated.
Interventions
DRUGAzithromycin
Comparison of community coverage rate
Sponsors
Bill and Melinda Gates Foundation
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
The study was a factorial study model to begin with in all 3 countries (Niger,Tanzania and Gambia) but because we never stopped treatment in Tanzania and Niger site.Hence the study design was collapsed to a simple design in Tanzania and Niger.The study model was kept as a factorial design for the Gambia site. Protocol Enrollment refers to the number of communities, not the number of participants enrolled.
Eligibility
Sex/Gender
ALL
Age
No minimum to 5 Years
Healthy volunteers
Yes
Inclusion criteria
for communities: * Communities are located in the target districts and accessible by vehicle * The community leaders consent to have the community enrolled * Rapid assessment and/or available data suggest trachoma rates are higher than 20% in the community. * The community size is \<5,000 persons or \>250 persons. If a community meets the inclusion criteria and community leaders consent to have the community enrolled, then sentinel children will be selected based on the following criteria: * The child is age 5 years or younger * The child must be a resident in an eligible, sample community (defined as either living in the community since birth, or moved in with parents or guardians). * The child must not have an ocular condition that would preclude grading trachoma or taking an ocular specimen. * The child must be willing to have a swab taken as part of being a sentinel child (this is critical for The Gambia and Tanzania, as each swab result counts towards meeting the stopping rule) * The child must have an identifiable guardian capable of providing consent to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | At baseline | Mass drug administration (MDA) with azithromycin or topical tetracycline is recommended by World Health Organization (WHO) for 3 years in districts where the prevalence of trachoma is\>=10 % in children aged 1-9 years. The prevalence of trachoma (TF) was measured using the Simplified WHO Grading System. Both eyelids were everted and tarsal conjunctiva graded for signs of clinical trachoma. Ocular photographs of right eye were taken on random samples of sentinel children to determine the drift in grading over time. To detect CT infection, an ocular swab of the right eye using a Dacron swab was collected from the sentinel kids. The swab was stored dry, and frozen until shipped and processed in the laboratory. Air control swabs were also taken to test for field and laboratory contamination. |
| Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | 3 years | 100 random sentinel children aged 0- 5 years per community were to be examined for prevalence of trachoma & CT infection in Tanzania & Gambia. 50-100 random sentinel children aged 0-5 years per community were to be examined in Niger per community for prevalence of TF and CT infection. Outcomes are reported at the community level because raw data could not be accessed. There is no way to determine how many participants were examined in each arm. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
The study recruited communities with trachoma rates 20 % or higher from 3 countries - Tanzania, Gambia and Niger. Protocol Enrollment refers to the number of communities, not the number of participants enrolled. The final analysis was done at community level.
Participants by arm
| Arm | Count |
|---|---|
| ≥90% Coverage With Azithromycin Target Selected communities will receive mass treatment annually for three years.
Azithromycin: Comparison of community coverage rate | 0 |
| ≥90% Coverage With Azithromycin Target Selected communities will receive mass treatment annually for three years.
Azithromycin: Comparison of community coverage rate | 40 |
| 80%-89% Coverage With Azithromycin Target Selected communities will receive mass treatment annually for three years.
Azithromycin: Comparison of community coverage rate | 0 |
| 80%-89% Coverage With Azithromycin Target Selected communities will receive mass treatment annually for three years.
Azithromycin: Comparison of community coverage rate | 40 |
| ≥90% Coverage With Azithromycin , Treatment Based Treatment to be administered at baseline then continued yearly if trachoma prevalence is greater than 5%
In Niger, treatment will be every 6-months for children ages twelve and under.
Azithromycin: Comparison of coverage levels at baseline treatment followed by annual treatment if prevalence of trachoma is \>5%. In Niger, there will be a comparison of coverage levels in everyone versus in children ages twelve and under who are treated every 6-months. | 0 |
| ≥90% Coverage With Azithromycin , Treatment Based Treatment to be administered at baseline then continued yearly if trachoma prevalence is greater than 5%
In Niger, treatment will be every 6-months for children ages twelve and under.
Azithromycin: Comparison of coverage levels at baseline treatment followed by annual treatment if prevalence of trachoma is \>5%. In Niger, there will be a comparison of coverage levels in everyone versus in children ages twelve and under who are treated every 6-months. | 24 |
| 80%-89% Coverage With Azithromycin : Treatment Based Treatment to be administered at baseline then continued yearly if trachoma prevalence is greater than 5%
In Niger, treatment will be every 6-months for children ages twelve and under.
Azithromycin: Comparison of coverage levels at baseline treatment followed by annual treatment if prevalence of trachoma is \>5%. In Niger, there will be a comparison of coverage levels in everyone versus in children ages twelve and under who are treated every 6-months. | 0 |
| 80%-89% Coverage With Azithromycin : Treatment Based Treatment to be administered at baseline then continued yearly if trachoma prevalence is greater than 5%
In Niger, treatment will be every 6-months for children ages twelve and under.
Azithromycin: Comparison of coverage levels at baseline treatment followed by annual treatment if prevalence of trachoma is \>5%. In Niger, there will be a comparison of coverage levels in everyone versus in children ages twelve and under who are treated every 6-months. | 24 |
| Total | 128 |
Baseline characteristics
| Characteristic | ≥90% Coverage With Azithromycin Target | 80%-89% Coverage With Azithromycin Target | ≥90% Coverage With Azithromycin , Treatment Based | 80%-89% Coverage With Azithromycin : Treatment Based | Total |
|---|---|---|---|---|---|
| Age, Customized Age not analyzed | NA community | NA community | NA community | NA community | NA community |
| Region of Enrollment Gambia | 12 community | 12 community | 12 community | 12 community | 48 community |
| Region of Enrollment Niger | 12 community | 12 community | 12 community | 12 community | 48 community |
| Region of Enrollment Tanzania | 16 community | 16 community | 0 community | 0 community | 32 community |
| Sex/Gender, Customized Sex/Gender not analyzed | NA community | NA community | NA community | NA community | NA community |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 |
Outcome results
Primary
Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months
100 random sentinel children aged 0- 5 years per community were to be examined for prevalence of trachoma & CT infection in Tanzania & Gambia. 50-100 random sentinel children aged 0-5 years per community were to be examined in Niger per community for prevalence of TF and CT infection. Outcomes are reported at the community level because raw data could not be accessed. There is no way to determine how many participants were examined in each arm.
Time frame: 3 years
Population: We analyzed and reported the results of the trial at community level.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | C.trachomatis infection in Tanzania at 3 years | 5.4 community | Standard Deviation 3.7 |
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | C.trachomatis infection in Niger at 3 years | 7.1 community | Standard Deviation 6.8 |
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | Prevalence of trachoma (TF) in Niger at 3 years | 8.9 community | Standard Deviation 8.8 |
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | C.trachomatis infection in Gambia at 3 years | 0.2 community | Standard Deviation 4.1 |
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | Prevalence of trachoma (TF) in Tanzania at 3 years | 9.0 community | Standard Deviation 5.9 |
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | Prevalence of trachoma (TF) in Gambia at 3 years | 3.0 community | Standard Deviation 17.1 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | C.trachomatis infection in Gambia at 3 years | 1.0 community | Standard Deviation 9.5 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | Prevalence of trachoma (TF) in Tanzania at 3 years | 6.1 community | Standard Deviation 4 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | C.trachomatis infection in Tanzania at 3 years | 4.0 community | Standard Deviation 2.7 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | Prevalence of trachoma (TF) in Gambia at 3 years | 2.3 community | Standard Deviation 14.9 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | Prevalence of trachoma (TF) in Niger at 3 years | 7.1 community | Standard Deviation 7.8 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | C.trachomatis infection in Niger at 3 years | 4.6 community | Standard Deviation 7.9 |
| ≥90% Coveage With Azithromycin , Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | C.trachomatis infection in Gambia at 3 years | 0.7 community | Standard Deviation 8.2 |
| ≥90% Coveage With Azithromycin , Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | C.trachomatis infection in Niger at 3 years | 3.3 community | Standard Deviation 3.6 |
| ≥90% Coveage With Azithromycin , Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | Prevalence of trachoma (TF) in Niger at 3 years | 5.4 community | Standard Deviation 3.9 |
| ≥90% Coveage With Azithromycin , Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | Prevalence of trachoma (TF) in Gambia at 3 years | 3.2 community | Standard Deviation 17.6 |
| 80%-89% Coverage With Azithromycin : Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | C.trachomatis infection in Gambia at 3 years | 0.2 community | Standard Deviation 4.2 |
| 80%-89% Coverage With Azithromycin : Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | C.trachomatis infection in Niger at 3 years | 4.4 community | Standard Deviation 6 |
| 80%-89% Coverage With Azithromycin : Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | Prevalence of trachoma (TF) in Gambia at 3 years | 2.5 community | Standard Deviation 15.7 |
| 80%-89% Coverage With Azithromycin : Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | Prevalence of trachoma (TF) in Niger at 3 years | 10.1 community | Standard Deviation 10.5 |
Comparison: This is analysis done in Tanzania:~Only the main effect of coverage was analyzed.We hypothesized that increasing the coverage of MDA to greater than 90 % as monitored in children would result in more rapid decline in infection and trachoma compared to usual coverage.Here we are looking at the prevalence of infection.p-value: 0.2295% CI: [-1, 3.8]Regression, Linear
Comparison: This is the analysis done in Tanzania:~Only the main effect of coverage was analyzed.We hypothesized that increasing the coverage of MDA to greater than 90 % as monitored in children would result in more rapid decline in infection and trachoma compared to usual coverage.~Here we are looking at the prevalence of trachomap-value: 0.7395% CI: [-0.3, 5.3]Ordinary least squares linear regression
Comparison: This is the statistical analysis for Niger:~We hypothesized that increasing the coverage of MDA to greater than 90 % as monitored in children would result in more rapid decline in infection and trachoma compared to usual coverage.Here we are looking at the prevalence of infection.p-value: 0.295% CI: [-11.1, 1.9]Regression, Linear
Comparison: This is the statistical analysis for Niger:~We hypothesized that increasing the coverage of MDA to greater than 90 % as monitored in children would result in more rapid decline in infection and trachoma compared to usual coverage.Here we are looking at the prevalence of trachoma.p-value: 0.695% CI: [-7.7, 12.5]Regression, Linear
Primary
Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline
Mass drug administration (MDA) with azithromycin or topical tetracycline is recommended by World Health Organization (WHO) for 3 years in districts where the prevalence of trachoma is\>=10 % in children aged 1-9 years. The prevalence of trachoma (TF) was measured using the Simplified WHO Grading System. Both eyelids were everted and tarsal conjunctiva graded for signs of clinical trachoma. Ocular photographs of right eye were taken on random samples of sentinel children to determine the drift in grading over time. To detect CT infection, an ocular swab of the right eye using a Dacron swab was collected from the sentinel kids. The swab was stored dry, and frozen until shipped and processed in the laboratory. Air control swabs were also taken to test for field and laboratory contamination.
Time frame: At baseline
Population: At baseline 8 communities were randomized to each arm in Tanzania, 12 communities were randomized to each arm in Gambia and Niger.~Stop rule could not be applied in Tanzania.Communities in stop arm were moved to ≥90% coverage or 80%-89% coverage with azithromycin target arm and only main effect of coverage was analyzed in Tanzania.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | Prevalence of trachoma in Tanzania at baseline | 30.7 community | Standard Deviation 16.3 |
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Tanzania at baseline | 24.6 community | Standard Deviation 12.4 |
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | prevalence of trachoma in Gambia at baseline | 7.4 community | Standard Deviation 26.1 |
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Gambia at baseline | 0.9 community | Standard Deviation 9.9 |
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | prevalence of trachoma in Niger at baseline | 28.4 community | Standard Deviation 13.9 |
| ≥90% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Niger at baseline | 21.9 community | Standard Deviation 16.7 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Niger at baseline | 20.5 community | Standard Deviation 16.8 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Gambia at baseline | 0.7 community | Standard Deviation 8.6 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | Prevalence of trachoma in Tanzania at baseline | 30.3 community | Standard Deviation 13.5 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | prevalence of trachoma in Gambia at baseline | 5.6 community | Standard Deviation 23.1 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Tanzania at baseline | 17.8 community | Standard Deviation 10.3 |
| 80%-89% Coverage With Azithromycin Target | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | prevalence of trachoma in Niger at baseline | 27.0 community | Standard Deviation 17.3 |
| ≥90% Coveage With Azithromycin , Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Tanzania at baseline | 23.0 community | Standard Deviation 11.2 |
| ≥90% Coveage With Azithromycin , Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | prevalence of trachoma in Gambia at baseline | 6.2 community | Standard Deviation 24.1 |
| ≥90% Coveage With Azithromycin , Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Gambia at baseline | 1.2 community | Standard Deviation 10.8 |
| ≥90% Coveage With Azithromycin , Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Niger at baseline | 15.6 community | Standard Deviation 8.8 |
| ≥90% Coveage With Azithromycin , Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | prevalence of trachoma in Niger at baseline | 23.9 community | Standard Deviation 12 |
| ≥90% Coveage With Azithromycin , Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | Prevalence of trachoma in Tanzania at baseline | 31.1 community | Standard Deviation 9.5 |
| 80%-89% Coverage With Azithromycin : Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | prevalence of trachoma in Niger at baseline | 24.7 community | Standard Deviation 13 |
| 80%-89% Coverage With Azithromycin : Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Niger at baseline | 24.9 community | Standard Deviation 14.1 |
| 80%-89% Coverage With Azithromycin : Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Tanzania at baseline | 22.4 community | Standard Deviation 23.3 |
| 80%-89% Coverage With Azithromycin : Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | C.trachomatis infection in Gambia at baseline | 0.2 community | Standard Deviation 2.9 |
| 80%-89% Coverage With Azithromycin : Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | Prevalence of trachoma in Tanzania at baseline | 30.5 community | Standard Deviation 10.4 |
| 80%-89% Coverage With Azithromycin : Treatment Based | Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | prevalence of trachoma in Gambia at baseline | 6.1 community | Standard Deviation 23.8 |