Effect of WHO-yaws Elimination Strategy in Lihir Island, Papua New Guinea

Yaws Clinical Trial

— YESA-13  

Official title:

Effect of WHO-yaws Elimination Strategy in Lihir Island, Papua New Guinea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01955252
• Other study ID #: YESA-13
• Status: Completed
• Phase: Phase 3
• First received: September 24, 2013
• Last updated: August 25, 2017
• Start date: March 2013
• Est. completion date: May 2017

Study information

• Verified date: January 2017
• Source: Lihir Medical Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16000
• Est. completion date: May 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months and older

Eligibility

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).

Related Conditions & MeSH terms

• Yaws

Intervention

Drug:
• Azithromycin
Investigators will do a baseline survey of every children from 5 to 15 years in the village. To detect yaws infection, investigators will collect a blood specimen for serology (qualitative and quantitative RPR testing and TPHA assay). Investigators will identify yaws-like ulcers by means of dermatological examination. Investigators will swab papilloma and ulcers and specimens will be flown to University of Washington (Seattle). PCR methods will consist of primary screening for the presence or absence of T. p. pertenue DNA, Haemophilus ducreyi DNA and detection of the A2058G and A2059G mutations associated with azithromycin resistance. Investigators will begin treatment with antibiotics immediately after completion of the baseline survey. Everyone in the villages will be offered azithromycin, subsequently a field team will treat all active clinical cases and their contacts 6 monthly. For all subjects, follow-up examination will be performed at 6,12,18,24,30,36,40,and 42 months

Locations

Country	Name	City	State
Papua New Guinea	Lihir Medical Centre	Londolovit	New ireland province

Sponsors (5)

Lead Sponsor	Collaborator
Lihir Medical Centre	Barcelona Institute for Global Health, National Department of Health of Papua New Guinea, University of Washington, World Health Organization

Country where clinical trial is conducted

Papua New Guinea, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of yaws latent infection	Prevalence of yaws infection is determined by the combination of a positive TPHA and RPR titer of 1:4 or above (which can be considered as the marker for true disease) in 1200 children 5-15 years in 6 randomly selected villages.	42 months
Secondary	Prevalence of active yaws disease	Determined by means of dermatological examination (WHO definitions) with laboratory confirmation using serology and PCR methods.	42 months
Secondary	Macrolide resistance	Estimate the prevalence of molecular markers of macrolide resistance in T. pallidum subsp. pertenue in patients with active yaws both before and after the mass drug administration.	42 months
Secondary	Ulcer aetiology surveys	PCR-surveillance of yaws-like ulcers in randomly selected villages every survey. This will allow to compare the relative proportion of T. pallidum pertenue ulcers vs other aetiological agents	42 months