Effect of WHO-yaws Elimination Strategy in Lihir Island, Papua New Guinea (YESA-13)

Lihir Medical Centre

Status and phase: Completed; Phase 3

Conditions: Yaws

Treatments: Drug: Azithromycin

Study type: Interventional

Funder types: Other

Identifiers

NCT01955252

YESA-13

Details and patient eligibility

About

The trial that the investigators are proposing is a pilot study to determine the effect of the new WHO-yaws eradication strategy in Lihir Island (population 18,000), Papua New Guinea. New treatment policies were developed by WHO in 2012 to replace those of the 1950s. The recommended practice is to offer an initial MDA with azithromycin to the entire population, followed by resurveys every 6 months to detect and treat remaining cases.We will use serology surveys, clinical surveys and ulcer aetiology studies to measure the effect of mass azithromycin treatment on the community burden of yaws infection.

Full description

Yaws is a re-emerging endemic treponemal infection caused by Treponema pallidum subp pertenue. This bacterium causes a chronic relapsing disease, characterized by highly contagious primary and secondary cutaneous lesions and non-contagious tertiary late destructive lesions. The Pacific Islands are believed to be a major focus of yaws worldwide, though population-based data on prevalence are lacking for many countries.

Azithromycin (30mg/kg) has recently been shown to be effective in the treatment of yaws and is now central to WHO's yaws eradication strategy. Substituting a single dose of an oral antibiotic for a painful penicillin injection is a significant advantage because infection control measures required for injection of penicillin will no longer be required and treatment will be more acceptable to communities who need it.

Previous attempts to eradicate yaws by mass treatment of active cases with injectable drugs yielded unsuccessful results. A major campaign to eradicate yaws in the 1950s and 1960s with longacting, injectable penicillin greatly reduced the number of cases of the disease worldwide but incubating and latent cases that were not treated developed relapses with infectious yaws lesions, thereby becoming a source of reinfection.

While the earlier strategy in the 1950s, targeted just those people who were visibly infected, the new WHO-plan calls for blanket coverage of at least 90% of the population. The ratio of clinically apparent to latent cases with no symptoms is estimated as high as 1:6 and mass drug administration (MDA) of the entire population is the best approach to ensure that incubating and latent infections are adequately dealt with.

The currently recommended treatment for eradication is one dose of oral azithromycin (30 mg/Kg; maximum 2g) to be given to entire populations in areas known to harbor yaws. For the MDA to be effective, it is required to have substantial coverage in the first round. The initial mass treatment should be followed by resurveys every 6 months to detect and treat remaining cases.

Because of the potential bacterial resistance appearance treatment failure needs to be monitored. Macrolide resistance is associated with point mutations at positions A2058 and A2059 of the 23S ribosomal RNA gene and molecular analysis need to be done in clinical specimens from patients who do not respond to treatment.

Enrollment: 16,000 patients

Sex: All

Ages: 2+ months old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Whole resident population for MDA and clinical surveys, and children 5-15 years in sentinel sites for cross-sectional serological surveys.

Exclusion criteria

• Children younger than 2 months and pregnant women;
• Known allergy to macrolide antibiotics;
• Refusal of individual or guardian (for individual inclusion).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16,000 participants in 1 patient group

Azithromycin

Experimental group

Description:

All participants older than 2 months (population 18,000) will be offered a single oral dose of oral azithromycin (tablets) 30 mg per Kg up to a maximum dose of 2g. Women who tell the investigators they are pregnant and people with known allergy to macrolides will be offered benzathine benzylpenicillin. This will be a single arm study. Study participants who met the inclusion criteria and agree to sign the consent form will be managed with proposed drug and systematically observed to measure outcomes of interest.

Treatment:

Drug: Azithromycin