Oriol Mitjà1, Camila González-Beiras2, Charmie Godornes3, Reman Kolmau4, Wendy Houinei5, Haina Abel4, August Kapa4, Raymond Paru4, Sibauk V Bieb5, James Wangi6, Sergi Sanz7, Kingsley Asiedu8, Sheila A Lukehart9, Quique Bassat10. 1. Barcelona Institute for Global Health, Hospital Clinic-University of Barcelona, Barcelona, Spain; Division of Public Health, School of Medicine and Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea; Lihir Medical Centre, International SOS-Newcrest Mining, Lihir Island, Papua New Guinea. Electronic address: oriol.mitja@isglobal.org. 2. Barcelona Institute for Global Health, Hospital Clinic-University of Barcelona, Barcelona, Spain; Lisbon Institute of Hygiene and Tropical Medicine, Lisbon, Portugal. 3. Department of Medicine, University of Washington, Seattle, WA, USA. 4. Lihir Medical Centre, International SOS-Newcrest Mining, Lihir Island, Papua New Guinea. 5. Disease Control Branch, National Department of Health, Port Moresby, Papua New Guinea. 6. Office of the WHO Representative for Papua New Guinea, WHO, Port Moresby, Papua New Guinea. 7. Barcelona Institute for Global Health, Hospital Clinic-University of Barcelona, Barcelona, Spain; Biostatistics Unit, Department of Public Health, Faculty of Medicine, University of Barcelona, Spain. 8. Department of Control of Neglected Tropical Diseases, WHO, Geneva, Switzerland. 9. Department of Medicine, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA. 10. Barcelona Institute for Global Health, Hospital Clinic-University of Barcelona, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain; Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique; Paediatric Infectious Diseases Unit, Paediatric Department, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain.
Abstract
BACKGROUND: Treatment of latent yaws is a crucial component of the WHO yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent yaws. METHODS: This population-based cohort study included children (age <20 years) living on Lihir Island, Papua New Guinea, with high-titre (rapid plasma reagin titre ≥1:8) latent or active yaws, between April, 2013, and May, 2015. Latent yaws was defined as lack of suspicious skin lesions or presence of ulcers negative for Treponema pallidum subsp pertenue on PCR, and active yaws was defined as ulcers positive for T pertenue on PCR. All children received one oral dose of 30 mg/kg azithromycin. The primary endpoint was serological cure, defined as a two-dilution decrease in rapid plasma reagin titre by 24 months after treatment. Treatment of latent yaws was taken to be non-inferior to that of active yaws if the lower limit of the two-sided 95% CI for the difference in rates was higher than or equal to -10%. This study is registered with ClinicalTrials.gov, number NCT01955252. FINDINGS: Of 311 participants enrolled, 273 (88%; 165 with latent yaws and 108 with active yaws) completed follow-up. The primary endpoint was achieved in 151 (92%) participants with latent yaws and 101 (94%) with active yaws (risk difference -2·0%, 95% CI -8·3 to 4·3), meeting the prespecified criteria for non-inferiority. INTERPRETATION: On the basis of decline in serological titre, oral single-dose azithromycin was effective in participants with latent yaws. This finding supports the WHO strategy for the eradication of yaws based on mass administration of the entire endemic community irrespective of clinical status. FUNDING: Newcrest Mining Limited and ISDIN laboratories.
BACKGROUND: Treatment of latent yaws is a crucial component of the WHO yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent yaws. METHODS: This population-based cohort study included children (age <20 years) living on Lihir Island, Papua New Guinea, with high-titre (rapid plasma reagin titre ≥1:8) latent or active yaws, between April, 2013, and May, 2015. Latent yaws was defined as lack of suspicious skin lesions or presence of ulcers negative for Treponema pallidum subsp pertenue on PCR, and active yaws was defined as ulcers positive for T pertenue on PCR. All children received one oral dose of 30 mg/kg azithromycin. The primary endpoint was serological cure, defined as a two-dilution decrease in rapid plasma reagin titre by 24 months after treatment. Treatment of latent yaws was taken to be non-inferior to that of active yaws if the lower limit of the two-sided 95% CI for the difference in rates was higher than or equal to -10%. This study is registered with ClinicalTrials.gov, number NCT01955252. FINDINGS: Of 311 participants enrolled, 273 (88%; 165 with latent yaws and 108 with active yaws) completed follow-up. The primary endpoint was achieved in 151 (92%) participants with latent yaws and 101 (94%) with active yaws (risk difference -2·0%, 95% CI -8·3 to 4·3), meeting the prespecified criteria for non-inferiority. INTERPRETATION: On the basis of decline in serological titre, oral single-dose azithromycin was effective in participants with latent yaws. This finding supports the WHO strategy for the eradication of yaws based on mass administration of the entire endemic community irrespective of clinical status. FUNDING: Newcrest Mining Limited and ISDIN laboratories.
Authors: Michael Marks; Oriol Mitjà; Christian Bottomley; Cynthia Kwakye; Wendy Houinei; Mathias Bauri; Paul Adwere; Abdul A Abdulai; Fredrick Dua; Laud Boateng; James Wangi; Sally-Ann Ohene; Regina Wangnapi; Shirley V Simpson; Helen Miag; Kennedy K Addo; Laud A Basing; Damien Danavall; Kai H Chi; Allan Pillay; Ronald Ballard; Anthony W Solomon; Cheng Y Chen; Sibauk V Bieb; Yaw Adu-Sarkodie; David C W Mabey; Kingsley Asiedu Journal: Lancet Glob Health Date: 2018-02-16 Impact factor: 26.763