A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana.

BACKGROUND:Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting. METHODOLOGY:We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1-15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%. FINDINGS:The mean age of participants was 9.5 years (S.D.3.1, range: 1-15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2-100) in the azithromycin group and 96.9% (95% CI: 94.1-99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9-64.9) in the azithromycin group and 49.1% (95% CI: 41.2-56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority. CONCLUSIONS:A single oral dose of azithromycin, at a dosage of 30mg/kg, was non-inferior to a single dose of intramuscular benzathine penicillin for the treatment of early yaws among Ghanaian patients, and provides additional support for the WHO policy for use of oral azithromycin for the eradication of yaws in resource-poor settings. TRIAL REGISTRATION:Pan African Clinical Trials Registry PACTR2013030005181 http://www.pactr.org/

Baseline Characteristics of Intention- to- Treat Population.

<p>Baseline Characteristics of Intention- to- Treat Population.</p

Sub Group Analysis of Primary Outcome (Clinical Cure at 3 Weeks).

<p>Sub Group Analysis of Primary Outcome (Clinical Cure at 3 Weeks).</p

Analysis of Serological Cure by Baseline RPR Titre.

<p>Analysis of Serological Cure by Baseline RPR Titre.</p

Treatment Outcomes (PP).

<p>Treatment Outcomes (PP).</p

Study Districts Ga South, Awutu Senya and West Akim Districts of Ghana.

<p>In 2012 the Awutu Senya district was divided into Awutu Senya and Awutu Senya East districts.</p

Before and After Treatment with Benzathine penicillin Papillomatous ulcer on the neck of patient showing complete healing after 3 weeks of treatment with benzathine penicillin: A. Before Treatment, B. After Treatment.

<p>Before and After Treatment with Benzathine penicillin Papillomatous ulcer on the neck of patient showing complete healing after 3 weeks of treatment with benzathine penicillin: A. Before Treatment, B. After Treatment.</p

Trial Profile: Flow of patients through various stages of trial.

<p>Trial Profile: Flow of patients through various stages of trial.</p