Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar

Study Overview
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Brief Summary
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This is a cluster randomized trial on effectiveness of different modalities of Single Double Dose of Rifampicin Post-Exposure Prophylaxis (SDDR-PEP) for leprosy in the Comoros (Anjouan and Mohéli) and Madagascar. The study aims to identify which approach to the selection of contacts for post exposure prophylaxis is most effective to reduce incident leprosy, and to Interrupt ongoing transmission from asymptomatic persons in the process of developing multibacillary leprosy.

Detailed Description
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For the purpose of the study, villages on the Comoros and Madagascar that will be randomly assigned to one of the study arms, will be screened on a yearly basis for 4 consecutive years. Depending on which of the 4 arms a village is assigned to, people in the surroundings of a leprosy patient will or will not be offered Post-Exposure Prophylaxis (PEP) using rifampicin at 20mg/kg single dose: No Post-Exposure Prophylaxis (PEP) is given to anyone PEP is given to all household contacts of incident leprosy cases PEP is given to all people who live in a 100m radius of incident leprosy cases PEP is given to all household contacts of incident leprosy cases as well as to all others who live within a 100m radius of an incident leprosy case and test positive in the UCP-LFA detecting anti-M. leprae PGL-I IgM antibodies (Ab) in fingerstick blood (anti-PGL-1)

Official Title
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Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar

Conditions
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Leprosy

Intervention / Treatment
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* Drug: Rifampicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Living in one of the study villages Aged 2 years and above Able and willing to provide informed consent Exclusion Criteria: Signs of active leprosy (*) Signs of active pulmonary tuberculosis (cough ≥2 weeks duration) (*) Having received Rifampicin within the last 24 months (*) (*) These people may still be included for yearly leprosy screening, but will be excluded to receive PEP

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A cluster randomized trial in which villages are assigned to one of four intervention groups
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: No PEP<br>No PEP will be distributed | |
| Other: Household PEP<br>PEP will be given to all household contacts of an incident leprosy patient | Drug: Rifampicin<br>* Rifampicin will be given in the same way to arms 2, 3 and 4 (weight dependent). Only the strategy of whom to offer PEP differs between the arms.<br>|
| Experimental: PEP 100m<br>PEP will be given to all household contacts of leprosy patients and to all other people living within a 100m radius of an incident leprosy patient. | Drug: Rifampicin<br>* Rifampicin will be given in the same way to arms 2, 3 and 4 (weight dependent). Only the strategy of whom to offer PEP differs between the arms.<br>|
| Other: PEP 100m + positive for anti-PGL-I IgM Ab<br>PEP will be given to all household contacts of leprosy patients and to all other people living within a 100m radius of an incident leprosy patient who test positive in the UCP-LFA detecting anti-M. leprae PGL-I IgM Ab in fingerstick blood (anti-PGL-I) | Drug: Rifampicin<br>* Rifampicin will be given in the same way to arms 2, 3 and 4 (weight dependent). Only the strategy of whom to offer PEP differs between the arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare effectiveness in curbing transmission of leprosy of three different approaches of post exposure prophylaxis | Three incidence rate ratios between the comparator arm (arm 1) and each of the three intervention arms. These ratios will be based on incidence rates measured between the first and fourth household survey in each of the intervention arms, always divided by that of the comparator arm. | 45 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess cost and feasibility of SDDR-PEP under program conditions | Costs will be calculated per person screened, per person treated with SDDR-PEP and per leprosy case averted. | 45 months | 
| Identify patterns of clustering in transmission of leprosy, allowing better targeting of control measures | We will quantify the degree of clustering as the average proportion of leprosy cases belonging to a same phylogenetic cluster by village. Geographic clustering will also be assessed by calculating risk ratios for being diagnosed with leprosy as a function of geographic distance from incident cases diagnosed earlier in each of the four arms | 45 months | 
| Monitor rifampicin resistance among leprosy patients | We will quantify prevalence of Rifampicin resistant strains of M. leprae on each of the study islands making use of molecular markers | 45 months | 
| Estimate incidence and prevalence of smear positive pulmonary tuberculosis in the study villages | During door-to-door surveys for leprosy we will enquire about chronic cough and screen for pulmonary tuberculosis if indicated. Prevalence of pulmonary tuberculosis will be calculated per island based on the results of the baseline survey, using as denominator the total population screened on the island. After each survey round annual incidence rates will be calculated based on the results of the follow-up surveys | 45 months |