Efficacy of mass drug administration with ivermectin for control of scabies and impetigo, with coadministration of azithromycin: a single-arm community intervention trial.
Adolescent
Adult
Anti-Infective Agents
/ administration & dosage
Azithromycin
/ administration & dosage
Child
Community Health Services
Female
Humans
Impetigo
/ drug therapy
Ivermectin
/ administration & dosage
Male
Mass Drug Administration
Melanesia
/ epidemiology
Neglected Diseases
Prevalence
Program Evaluation
Scabies
/ drug therapy
Treatment Outcome
Young Adult
Journal
The Lancet. Infectious diseases
ISSN: 1474-4457
Titre abrégé: Lancet Infect Dis
Pays: United States
ID NLM: 101130150
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
14
07
2018
revised:
08
11
2018
accepted:
10
12
2018
pubmed:
9
4
2019
medline:
12
6
2020
entrez:
9
4
2019
Statut:
ppublish
Résumé
In small community-based trials, mass drug administration of ivermectin has been shown to substantially decrease the prevalence of both scabies and secondary impetigo; however, their effect at large scale is untested. Additionally, combined mass administration of drugs for two or more neglected diseases has potential practical advantages, but efficacy of potential combinations should be confirmed. The azithromycin ivermectin mass drug administration (AIM) trial was a prospective, single-arm, before-and-after, community intervention study to assess the efficacy of mass drug administration of ivermectin for scabies and impetigo, with coadministration of azithromycin for trachoma. Mass drug administration was offered to the entire population of Choiseul Province, Solomon Islands, and of this population we randomly selected two sets of ten sentinel villages for monitoring, one at baseline and the other at 12 months. Participants were offered a single dose of 20 mg/kg azithromycin, using weight-based bands. Children weighing less than 12·5 kg received azithromycin oral suspension (20 mg/kg), and infants younger than 6 months received topical 1% tetracycline ointment. For ivermectin, participants were offered two doses of oral ivermectin 200 μg/kg 7-14 days apart using weight-based bands, or 5% permethrin cream 7-14 days apart if ivermectin was contraindicated. Our study had the primary outcomes of safety and feasibility of large-scale mass coadministration of oral ivermectin and azithromycin, which have been previously reported. We report here the prevalence of scabies and impetigo in residents of the ten baseline villages compared with those in the ten 12-month villages, as measured by examination of the skin, which was a secondary outcome of the trial. Further outcomes were comparison of the number of all-cause outpatient attendances at government clinics in Choiseul Province at various timepoints before and after mass drug administration. The trial was registered with the Australian and New Zealand Trials Registry (ACTRN12615001199505). During September, 2015, over 4 weeks, 26 188 people (99·3% of the estimated population of Choiseul [n=26 372] as determined at the 2009 census) were treated. At baseline, 1399 (84·2%) of 1662 people living in the first ten villages had their skin examined, of whom 261 (18·7%) had scabies and 347 (24·8%) had impetigo. At 12 months after mass drug administration, 1261 (77·6%) of 1625 people in the second set of ten villages had their skin examined, of whom 29 (2·3%) had scabies (relative reduction 88%, 95% CI 76·5-99·3) and 81 (6·4%) had impetigo (relative reduction 74%, 63·4-84·7). In the 3 months after mass drug administration, 10 614 attended outpatient clinics for any reason compared with 16 602 in the 3 months before administration (decrease of 36·1%, 95% CI 34·7-37·6), and during this period attendance for skin sores, boils, and abscesses decreased by 50·9% (95% CI 48·6-53·1). Ivermectin-based mass drug administration can be scaled to a population of over 25 000 with high efficacy and this level of efficacy can be achieved when mass drug administration for scabies is integrated with mass drug administration of azithromycin for trachoma. These findings will contribute to development of population-level control strategies. Further research is needed to assess durability and scalability of mass drug administration in larger, non-island populations, and to assess its effect on the severe bacterial complications of scabies. International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, and the Wellcome Trust.
Sections du résumé
BACKGROUND
In small community-based trials, mass drug administration of ivermectin has been shown to substantially decrease the prevalence of both scabies and secondary impetigo; however, their effect at large scale is untested. Additionally, combined mass administration of drugs for two or more neglected diseases has potential practical advantages, but efficacy of potential combinations should be confirmed.
METHODS
The azithromycin ivermectin mass drug administration (AIM) trial was a prospective, single-arm, before-and-after, community intervention study to assess the efficacy of mass drug administration of ivermectin for scabies and impetigo, with coadministration of azithromycin for trachoma. Mass drug administration was offered to the entire population of Choiseul Province, Solomon Islands, and of this population we randomly selected two sets of ten sentinel villages for monitoring, one at baseline and the other at 12 months. Participants were offered a single dose of 20 mg/kg azithromycin, using weight-based bands. Children weighing less than 12·5 kg received azithromycin oral suspension (20 mg/kg), and infants younger than 6 months received topical 1% tetracycline ointment. For ivermectin, participants were offered two doses of oral ivermectin 200 μg/kg 7-14 days apart using weight-based bands, or 5% permethrin cream 7-14 days apart if ivermectin was contraindicated. Our study had the primary outcomes of safety and feasibility of large-scale mass coadministration of oral ivermectin and azithromycin, which have been previously reported. We report here the prevalence of scabies and impetigo in residents of the ten baseline villages compared with those in the ten 12-month villages, as measured by examination of the skin, which was a secondary outcome of the trial. Further outcomes were comparison of the number of all-cause outpatient attendances at government clinics in Choiseul Province at various timepoints before and after mass drug administration. The trial was registered with the Australian and New Zealand Trials Registry (ACTRN12615001199505).
FINDINGS
During September, 2015, over 4 weeks, 26 188 people (99·3% of the estimated population of Choiseul [n=26 372] as determined at the 2009 census) were treated. At baseline, 1399 (84·2%) of 1662 people living in the first ten villages had their skin examined, of whom 261 (18·7%) had scabies and 347 (24·8%) had impetigo. At 12 months after mass drug administration, 1261 (77·6%) of 1625 people in the second set of ten villages had their skin examined, of whom 29 (2·3%) had scabies (relative reduction 88%, 95% CI 76·5-99·3) and 81 (6·4%) had impetigo (relative reduction 74%, 63·4-84·7). In the 3 months after mass drug administration, 10 614 attended outpatient clinics for any reason compared with 16 602 in the 3 months before administration (decrease of 36·1%, 95% CI 34·7-37·6), and during this period attendance for skin sores, boils, and abscesses decreased by 50·9% (95% CI 48·6-53·1).
INTERPRETATION
Ivermectin-based mass drug administration can be scaled to a population of over 25 000 with high efficacy and this level of efficacy can be achieved when mass drug administration for scabies is integrated with mass drug administration of azithromycin for trachoma. These findings will contribute to development of population-level control strategies. Further research is needed to assess durability and scalability of mass drug administration in larger, non-island populations, and to assess its effect on the severe bacterial complications of scabies.
FUNDING
International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, and the Wellcome Trust.
Identifiants
pubmed: 30956111
pii: S1473-3099(18)30790-4
doi: 10.1016/S1473-3099(18)30790-4
pmc: PMC6483975
pii:
doi:
Substances chimiques
Anti-Infective Agents
0
Ivermectin
70288-86-7
Azithromycin
83905-01-5
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
510-518Subventions
Organisme : Wellcome Trust
ID : 102807
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
Références
Clin Infect Dis. 2002 Aug 15;35(4):395-402
pubmed: 12145722
Pediatr Infect Dis J. 2002 May;21(5):375-80
pubmed: 12150171
Lancet. 2006 May 27;367(9524):1767-74
pubmed: 16731272
Lancet. 1991 Apr 27;337(8748):1016-8
pubmed: 1673175
Bull World Health Organ. 2009 Mar;87(3):173-9
pubmed: 19377712
PLoS Negl Trop Dis. 2009 May 26;3(5):e444
pubmed: 19478832
JAMA. 2009 Sep 2;302(9):962-8
pubmed: 19724043
Pediatr Infect Dis J. 2012 Apr;31(4):341-6
pubmed: 22173140
Curr Opin Infect Dis. 2012 Apr;25(2):145-53
pubmed: 22327467
Parasit Vectors. 2012 Dec 21;5:299
pubmed: 23259465
Curr Opin Infect Dis. 2013 Apr;26(2):127-32
pubmed: 23343887
Curr Opin Infect Dis. 2013 Apr;26(2):133-9
pubmed: 23438966
PLoS Negl Trop Dis. 2013 Sep 12;7(9):e2387
pubmed: 24069468
PLoS Negl Trop Dis. 2014 Sep 18;8(9):e3113
pubmed: 25233351
PLoS Negl Trop Dis. 2015 Mar 04;9(3):e0003452
pubmed: 25738499
PLoS Negl Trop Dis. 2015 Oct 30;9(10):e0004151
pubmed: 26516764
N Engl J Med. 2015 Dec 10;373(24):2305-13
pubmed: 26650152
PLoS Negl Trop Dis. 2016 Jun 27;10(6):e0004803
pubmed: 27348119
Ophthalmic Epidemiol. 2016;23(sup1):15-21
pubmed: 27937043
PLoS Negl Trop Dis. 2017 Jan 5;11(1):e0005163
pubmed: 28056015
Lancet Infect Dis. 2017 Dec;17(12):1247-1254
pubmed: 28941561
N Engl J Med. 2018 Apr 26;378(17):1583-1592
pubmed: 29694816
Clin Infect Dis. 2019 Mar 5;68(6):927-933
pubmed: 29985978
Am J Trop Med Hyg. 2018 Oct;99(4):937-939
pubmed: 30062986
Lancet Glob Health. 2018 Oct;6(10):e1132-e1138
pubmed: 30223985
Lancet Infect Dis. 2019 Jan;19(1):e14-e25
pubmed: 30292480
J Antimicrob Chemother. 1993 Jun;31 Suppl E:129-35
pubmed: 8396084