Effectiveness and safety of reactive focal mass drug administration (rfMDA) using dihydroartemisinin-piperaquine to reduce malaria transmission in the very low-endemic setting of Eswatini: A pragmatic cluster randomised controlled trial

Sibonakaliso Vilakati, Nontokozo Mngadi, Jade Benjamin-Chung, Nomcebo Dlamini, Mi Suk Kang Dufour, Brooke Whittemore, Khayelihle Bhangu, Lisa M. Prach, Kimberly Baltzell, Nomcebo Nhlabathi, Calisile Malambe, Bongani Dlamini, Danica Helb, Bryan Greenhouse, Gugu Maphalala, Deepa Pindolia, Muhindo Kalungero, Getahun Tesfa, Roly Gosling, Nyasatu NtshalintshaliSimon Kunene, Michelle S. Hsiang

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction To reduce malaria transmission in very low-endemic settings, screening and treatment near index cases (reactive case detection (RACD)), is widely practised, but the rapid diagnostic tests (RDTs) used miss low-density infections. Reactive focal mass drug administration (rfMDA) may be safe and more effective. Methods We conducted a pragmatic cluster randomised controlled trial in Eswatini, a very low-endemic setting. 77 clusters were randomised to rfMDA using dihydroartemisin-piperaquine (DP) or RACD involving RDTs and artemether-lumefantrine. Interventions were delivered by the local programme. An intention-to-treat analysis was used to compare cluster-level cumulative confirmed malaria incidence among clusters with cases. Secondary outcomes included safety and adherence. Results From September 2015 to August 2017, 222 index cases from 47 clusters triggered 46 RACD events and 64 rfMDA events. RACD and rfMDA were delivered to 1455 and 1776 individuals, respectively. Index case coverage was 69.5% and 62.4% for RACD and rfMDA, respectively. Adherence to DP was 98.7%. No serious adverse events occurred. For rfMDA versus RACD, cumulative incidences (per 1000 person-years) of all malaria were 2.11 (95% CI 1.73 to 2.59) and 1.97 (95% CI 1.57 to 2.47), respectively; and of locally acquired malaria, they were 1.29 (95% CI 1.00 to 1.67) and 0.97 (95% CI 0.71 to 1.34), respectively. Adjusting for imbalance in baseline incidence, incidence rate ratio for rfMDA versus RACD was 0.95 (95% CI 0.55 to 1.65) for all malaria and 0.82 (95% CI 0.40 to 1.71) for locally acquired malaria. Similar results were obtained in a per-protocol analysis that excluded clusters with <80% index case coverage. Conclusion In a very low-endemic, real-world setting, rfMDA using DP was safe, but did not lower incidence compared with RACD, potentially due to insufficient coverage and/or power. To assess impact of interventions in very low-endemic settings, improved coverage, complementary interventions and adaptive ring trial designs may be needed. Trial registration number NCT02315690.

Original languageEnglish (US)
Article numbere005021
JournalBMJ Global Health
Volume6
Issue number6
DOIs
StatePublished - Jun 30 2021

Keywords

  • malaria
  • public health

ASJC Scopus subject areas

  • Health Policy
  • Public Health, Environmental and Occupational Health

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