title: A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana.
abstract: 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.
  
  
  
  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%.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Pan African Clinical Trials Registry PACTR2013030005181 http://www.pactr.org/.
authors.affiliation: Ga West Municipal Health Administrations, Ghana Health Service, Amasaman, Ghana.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kwakye-Maclean
authors.affiliation: National Yaws Eradication Program, Ghana Health Service, Accra, Ghana.
authors.forename: Nsiire
authors.initials: N
authors.lastname: Agana
authors.affiliation: Department of Epidemiology, School of Public Health, University of Ghana, Legon, Ghana.
authors.forename: John
authors.initials: J
authors.lastname: Gyapong
authors.affiliation: Department of Epidemiology, School of Public Health, University of Ghana, Legon, Ghana.
authors.forename: Priscilia
authors.initials: P
authors.lastname: Nortey
authors.affiliation: Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Yaw
authors.initials: Y
authors.lastname: Adu-Sarkodie
authors.affiliation: National Public Health Reference Laboratory, Korle-Bu Teaching Hospital, Accra Ghana.
authors.forename: Esther
authors.initials: E
authors.lastname: Aryee
authors.affiliation: Global Yaws Eradication Programme, Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland.
authors.forename: Kingsley
authors.initials: K
authors.lastname: Asiedu
authors.affiliation: Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Roland
authors.initials: R
authors.lastname: Ballard
authors.affiliation: Department of Epidemiology, School of Public Health, University of Ghana, Legon, Ghana.
authors.forename: Fred
authors.initials: F
authors.lastname: Binka
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017963:Azithromycin / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D005869:Ghana; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D008297:Male; D010401:Penicillin G Benzathine / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014210:Treponema pallidum; D015001:Yaws / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin; D010401:Penicillin G Benzathine