Clinical trial NCT01955252: Effect of WHO-yaws Elimination Strategy in Lihir Island, Papua New Guinea
Official title: Effect of WHO-yaws Elimination Strategy in Lihir Island, Papua New Guinea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Yaws
Keywords: Endemic treponematoses
Azithromycin
Mass drug administration
Eradication
Lead sponsor: Lihir Medical Centre
Sponsor class: OTHER
Collaborators: name: Barcelona Institute for Global Health
name: National Department of Health of Papua New Guinea
name: World Health Organization
name: University of Washington
First posted: 2013-10-07
Enrollment: 16000
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Prevalence of yaws latent infection
timeFrame: 42 months
Secondary outcomes:
measure: Prevalence of active yaws disease
timeFrame: 42 months
measure: Macrolide resistance
timeFrame: 42 months
measure: Ulcer aetiology surveys
timeFrame: 42 months
Other outcomes:
Locations:
city: Londolovit
country: Papua New Guinea
facility: Lihir Medical Centre
state: New ireland province
Study officials:
affiliation: Barcelona Institute for Global Health
name: Oriol Mitja, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mitja O, Godornes C, Houinei W, Kapa A, Paru R, Abel H, Gonzalez-Beiras C, Bieb SV, Wangi J, Barry AE, Sanz S, Bassat Q, Lukehart SA. Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study. Lancet. 2018 Apr 21;391(10130):1599-1607. doi: 10.1016/S0140-6736(18)30204-6. Epub 2018 Feb 7.
citation: Mitja O, Gonzalez-Beiras C, Godornes C, Kolmau R, Houinei W, Abel H, Kapa A, Paru R, Bieb SV, Wangi J, Sanz S, Asiedu K, Lukehart SA, Bassat Q. Effectiveness of single-dose azithromycin to treat latent yaws: a longitudinal comparative cohort study. Lancet Glob Health. 2017 Dec;5(12):e1268-e1274. doi: 10.1016/S2214-109X(17)30388-1. Epub 2017 Oct 26.
citation: Mitja O, Houinei W, Moses P, Kapa A, Paru R, Hays R, Lukehart S, Godornes C, Bieb SV, Grice T, Siba P, Mabey D, Sanz S, Alonso PL, Asiedu K, Bassat Q. Mass treatment with single-dose azithromycin for yaws. N Engl J Med. 2015 Feb 19;372(8):703-10. doi: 10.1056/NEJMoa1408586.