One versus two doses of ivermectin-based mass drug administration for the control of scabies: A cluster randomised non-inferiority trial

Susanna J Lake; Daniel Engelman; Julie Zinihite; Oliver Sokana; Dickson Boara; Titus Nasi; Christina Gorae; Millicent H Osti; Sophie Phelan; Matthew Parnaby; Anneke C Grobler; Tibor Schuster; Ross Andrews; Margot J Whitfeld; Michael Marks; Lucia Romani; Andrew C Steer; John M Kaldor

doi:10.1371/journal.pntd.0011207

One versus two doses of ivermectin-based mass drug administration for the control of scabies: A cluster randomised non-inferiority trial

PLoS Negl Trop Dis. 2023 Mar 17;17(3):e0011207. doi: 10.1371/journal.pntd.0011207. eCollection 2023 Mar.

Authors

Susanna J Lake^{1

2

3}, Daniel Engelman^{1

2

3}, Julie Zinihite¹, Oliver Sokana⁴, Dickson Boara⁴, Titus Nasi⁴, Christina Gorae⁴, Millicent H Osti^{1

2}, Sophie Phelan⁵, Matthew Parnaby¹, Anneke C Grobler⁶, Tibor Schuster⁷, Ross Andrews⁸, Margot J Whitfeld⁹, Michael Marks^{10

11

12}, Lucia Romani^{1

5}, Andrew C Steer^{1

2

3}, John M Kaldor⁵

Affiliations

¹ Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, Australia.
² Department of Paediatrics, University of Melbourne, Melbourne, Australia.
³ Melbourne Children's Global Health, Melbourne, Australia.
⁴ Ministry of Health and Medical Services, Solomon Islands.
⁵ Kirby Institute, University of New South Wales, Sydney, Australia.
⁶ Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, Australia.
⁷ Department of Family Medicine, McGill University, Montreal, Canada.
⁸ Australian National University, Canberra, Australia.
⁹ Department of Dermatology, St Vincent's Hospital, Sydney, Australia.
¹⁰ Clinic Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
¹¹ Hospital for Tropical Diseases, University College London Hospital, London, United Kingdom.
¹² Division of Infection and Immunity, University College London, London, United Kingdom.

Abstract

Background: Mass drug administration (MDA) based on two doses of ivermectin, one week apart, substantially reduces prevalence of both scabies and impetigo. The Regimens of Ivermectin for Scabies Elimination (RISE) trial assessed whether one-dose ivermectin-based MDA would be as effective.

Methods: RISE was a cluster-randomised trial in Solomon Islands. We assigned 20 villages in a 1:1 ratio to one- or two-dose ivermectin-based MDA. We planned to test whether the impact of one dose on scabies prevalence at 12 and 24 months was non-inferior to two, at a 5% non-inferiority margin.

Results: We deferred endpoint assessment to 21 months due to COVID-19. We enrolled 5239 participants in 20 villages at baseline and 3369 at 21 months from an estimated population of 5500. At baseline scabies prevalence was similar in the two arms (one-dose 17·2%; two-dose 13·2%). At 21 months, there was no reduction in scabies prevalence (one-dose 18·7%; two-dose 13·4%), and the confidence interval around the difference included values substantially greater than 5%. There was however a reduction in prevalence among those who had been present at the baseline assessment (one-dose 15·9%; two-dose 10·8%). Additionally, we found a reduction in both scabies severity and impetigo prevalence in both arms, to a similar degree.

Conclusions: There was no indication of an overall decline in scabies prevalence in either arm. The reduction in scabies prevalence in those present at baseline suggests that the unexpectedly high influx of people into the trial villages, likely related to the COVID-19 pandemic, may have compromised the effectiveness of the MDA. Despite the lack of effect there are important lessons to be learnt from this trial about conducting MDA for scabies in high prevalence settings.

Trial registration: Registered with Australian New Zealand Clinical Trials Registry ACTRN12618001086257.

Copyright: © 2023 Lake et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Randomized Controlled Trial
Equivalence Trial
Research Support, Non-U.S. Gov't

MeSH terms

Australia
COVID-19* / epidemiology
Humans
Impetigo* / drug therapy
Impetigo* / epidemiology
Impetigo* / prevention & control
Ivermectin / therapeutic use
Mass Drug Administration
Pandemics
Scabies* / drug therapy
Scabies* / epidemiology
Scabies* / prevention & control

Substances

Ivermectin

Associated data

ANZCTR/ACTRN12618001086257

Grants and funding

The RISE trial is funded by the National Health and Medical Research Council of Australia GNT1127297. DE, LR, JMK and ACS are supported by fellowships from the National Health and Medical Research Council of Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.