Article Text

Download PDFPDF

Study protocol for a cluster randomised controlled factorial design trial to assess the effectiveness and feasibility of reactive focal mass drug administration and vector control to reduce malaria transmission in the low endemic setting of Namibia
  1. Oliver F Medzihradsky1,2,
  2. Immo Kleinschmidt3,4,
  3. Davis Mumbengegwi5,
  4. Kathryn W Roberts1,
  5. Patrick McCreesh6,
  6. Mi-Suk Kang Dufour7,
  7. Petrina Uusiku8,
  8. Stark Katokele8,
  9. Adam Bennett1,
  10. Jennifer Smith1,
  11. Hugh Sturrock1,
  12. Lisa M Prach1,
  13. Henry Ntuku1,
  14. Munyaradzi Tambo4,
  15. Bradley Didier9,
  16. Bryan Greenhouse10,
  17. Zaahira Gani11,
  18. Ann Aerts11,
  19. Roly Gosling1,
  20. Michelle S Hsiang1,2,6
  1. 1 Malaria Elimination Initiative, Global Health Group, University of California San Francisco, San Francisco, California, USA
  2. 2 Department of Pediatrics, Benioff Children’s Hospital, University of California San Francisco, San Francisco, California, USA
  3. 3 Department of Infectious Disease Epidemiology, The London School of Hygiene and Tropical Medicine, London, UK
  4. 4 Faculty of Health Sciences, School of Pathology, University of Witwatersrand, Johannesburg, South Africa
  5. 5 Multidisciplinary Research Centre, University of Namibia, Windhoek, Namibia
  6. 6 Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  7. 7 Division of Prevention Science, University of California San Francisco, San Francisco, California, USA
  8. 8 National Vector-borne Diseases Control Programme, Ministry of Health and Social Services, Windhoek, Namibia
  9. 9 Clinton Health Access Initiative, Boston, Massachusetts, USA
  10. 10 Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA
  11. 11 Novartis Foundation, Basel, Switzerland
  1. Correspondence to Dr Michelle S Hsiang; michelle.hsiang{at}


Introduction To interrupt malaria transmission, strategies must target the parasite reservoir in both humans and mosquitos. Testing of community members linked to an index case, termed reactive case detection (RACD), is commonly implemented in low transmission areas, though its impact may be limited by the sensitivity of current diagnostics. Indoor residual spraying (IRS) before malaria season is a cornerstone of vector control efforts. Despite their implementation in Namibia, a country approaching elimination, these methods have been met with recent plateaus in transmission reduction. This study evaluates the effectiveness and feasibility of two new targeted strategies, reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in Namibia.

Methods and analysis This is an open-label cluster randomised controlled trial with 2×2 factorial design. The interventions include: rfMDA (presumptive treatment with artemether-lumefantrine (AL)) versus RACD (rapid diagnostic testing and treatment using AL) and RAVC (IRS with Acellic 300CS) versus no RAVC. Factorial design also enables comparison of the combined rfMDA+RAVC intervention to RACD. Participants living in 56 enumeration areas will be randomised to one of four arms: rfMDA, rfMDA+RAVC, RACD or RACD+RAVC. These interventions, triggered by index cases detected at health facilities, will be targeted to individuals residing within 500 m of an index. The primary outcome is cumulative incidence of locally acquired malaria detected at health facilities over 1 year. Secondary outcomes include seroprevalence, infection prevalence, intervention coverage, safety, acceptability, adherence, cost and cost-effectiveness.

Ethics and dissemination Findings will be reported on, in peer-reviewed publications and through stakeholder meetings with MoHSS and community leaders in Namibia.

Trial registration number NCT02610400; Pre-results.

  • malaria
  • Plasmodium falciparum
  • reactive case detection
  • presumptive treatment
  • mass drug administration
  • artemether-lumefantrine
  • vector control
  • indoor residual spraying
  • pirimiphos-methyl
  • Namibia
  • low transmission
  • elimination
  • cluster randomisation

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See:

View Full Text

Statistics from


  • Contributors MSH, IK and RG conceptualised and developed the study and its design. DM, AB, JS, HS, M-SKD, KWR and OFM contributed to study design. All authors contributed to protocol development. KWR, MSH, M-SKD and OM wrote the protocol. OM, MSH and IK wrote the manuscript. All authors approved the manuscript final draft.

  • Funding This work is financially supported by Novartis Foundation [A122666], the Bill & Melinda Gates Foundation [OPP1138299] and the Horchow Family Fund [5300375400]. Cofunding for drugs, RDTs and other existing infrastructure was also provided by the MoHSS.

  • Competing interests AA and ZG are employed by Novartis Foundation. All other authors declare no competing interests.

  • Patient consent Not required.

  • Ethics approval The protocol has been approved by the Ministry of Health and Social Services of Namibia, University of Namibia Centre for Research and Publications, University of California San Francisco Human Research Protection Program (HRPP; #15-17422) and The London School of Hygiene and Tropical Medicine Observational/Interventions Research Ethics Committee (#10411). This trial is registered at (NCT02610400, Unique Protocol ID: OPP1089413_Namibia_TPE).

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.