Evaluation of Reactive Focal Mass Drug Administration for Malaria Elimination in Swaziland

NCT02315690 | Completed Phase 3 DMC

• 1 other identifier: Swaziland fMDA
• Study Type: interventional
• Target: 4,000
• Locations: 1 country
• Sites: 1

Brief Summary

This is a cluster randomised controlled trial comparing the impact of two community based malaria interventions: reactive case detection (RACD) vs reactive targeted presumptive treatment (focal mass drug administration, fMDA) on the incidence of malaria in Swaziland.

Conditions

Malaria

Keywords

malaria, Swaziland, reactive case detection, focal mass drug administration

Outcome Measures

Primary Outcomes (1)

• Incidence of malaria cases

  Cumulative incidence of malaria cases by locality

  2 years

Secondary Outcomes (7)

• Seroprevalence

  during end line survey after intervention data collection completed

• Prevalence

  during end line survey after intervention data collection completed

• Coverage

  2 years

• Adherence

  2 years

• Safety related to DHAp

  2 years

Study Arms (2)

Reactive case detection (RACD)

ACTIVE COMPARATOR

Individuals in RACD Target Areas will be tested by RDT (rapid diagnostic test) and if positive, taken to the nearest health facility for treatment with artemether-lumefantrine per national policy.

Procedure: reactive case detection

Reactive focal mass drug administration (fMDA)

EXPERIMENTAL

In the fMDA arm, all individuals in the Target Area will receive dihydroartemisinin-piperaquine (DHAp) once daily for 3 days with the first dose taken no later than 5 weeks from the index case presentation (goal within one week).

Drug: dihydroartemisinin-piperaquine (DHAp)

Interventions

dihydroartemisinin-piperaquine (DHAp) DRUG

In the fMDA arm, all individuals in the target area will receive dihydroartemisinin-piperaquine (DHAp) once daily for 3 days with the first dose taken no later than 5 weeks from the index case presentation (goal within one week).

Also known as: Eurartesim

Reactive focal mass drug administration (fMDA)

reactive case detection PROCEDURE

Individuals in RACD target areas will be tested by RDT and if positive will be taken to the nearest health facility for treatment as per program operating procedures.

Also known as: screen and treat; test and treat

Reactive case detection (RACD)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Index case resides in study locality
• All non-index cases that reside or spent at least one night in the Target Area in the past 5 weeks
• Non-index case resides within 200 meters of index case unless study team was not able to recruit 30 individuals by 3rd visit, in which case non-index case individuals may reside up to 500 meters from index case
• Provide informed consent

You may not qualify if:

• Refusal to participate
• Target Area overlaps with prior RACD Target Area from within the past 5 weeks
• Index case resides in study locality
• All non-index cases that reside or have spent at least one night in the Target Area in the past 5 weeks
• Non-index case resides within 200 meters of index case unless study team was not able to recruit 30 individuals by 3rd visit, in which case non-index case individuals may reside up to 500 meters from index case
• Provide informed consent
• Refusal to participate
• Temperature \> 38.0⁰C, report of fever in the past 48 hours, or other illness (will be referred to the nearest health facility for further evaluation)
• fMDA Target Area overlaps with prior Target Area within the past 8 weeks
• For fMDA specifically (though still eligible for follow-up blood survey):
• Pregnancy, breastfeeding, and women who have had menarche but no menses in the past 4 weeks
• Children less than 6 months of age or \<5 kg
• Known allergy or history of adverse reaction to DP (still eligible for f/u blood surveys)
• Already taken 2 courses of DP in the past year or taken 1 course within the past 2 months
• Moderate or severe renal or hepatic insufficiency

Sponsors & Collaborators

• University of California, San Francisco: lead
• Ministry of Health, Swaziland: collaborator
• Clinton Health Access Initiative, Eswatini: collaborator
• University of Texas: collaborator

Study Sites (1)

Swaziland Ministry of Health

Mbabane, Eswatini

Location

Related Publications (7)

• Hsiang MS, Hwang J, Kunene S, Drakeley C, Kandula D, Novotny J, Parizo J, Jensen T, Tong M, Kemere J, Dlamini S, Moonen B, Angov E, Dutta S, Ockenhouse C, Dorsey G, Greenhouse B. Surveillance for malaria elimination in Swaziland: a national cross-sectional study using pooled PCR and serology. PLoS One. 2012;7(1):e29550. doi: 10.1371/journal.pone.0029550. Epub 2012 Jan 6.

  PMID: 22238621 BACKGROUND

• Sturrock HJ, Novotny JM, Kunene S, Dlamini S, Zulu Z, Cohen JM, Hsiang MS, Greenhouse B, Gosling RD. Reactive case detection for malaria elimination: real-life experience from an ongoing program in Swaziland. PLoS One. 2013 May 20;8(5):e63830. doi: 10.1371/journal.pone.0063830. Print 2013.

  PMID: 23700437 BACKGROUND

• Zani B, Gathu M, Donegan S, Olliaro PL, Sinclair D. Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria. Cochrane Database Syst Rev. 2014 Jan 20;2014(1):CD010927. doi: 10.1002/14651858.CD010927.

  PMID: 24443033 BACKGROUND

• Lwin KM, Phyo AP, Tarning J, Hanpithakpong W, Ashley EA, Lee SJ, Cheah P, Singhasivanon P, White NJ, Lindegardh N, Nosten F. Randomized, double-blind, placebo-controlled trial of monthly versus bimonthly dihydroartemisinin-piperaquine chemoprevention in adults at high risk of malaria. Antimicrob Agents Chemother. 2012 Mar;56(3):1571-7. doi: 10.1128/AAC.05877-11. Epub 2012 Jan 17.

  PMID: 22252804 BACKGROUND

• Nankabirwa JI, Wandera B, Amuge P, Kiwanuka N, Dorsey G, Rosenthal PJ, Brooker SJ, Staedke SG, Kamya MR. Impact of intermittent preventive treatment with dihydroartemisinin-piperaquine on malaria in Ugandan schoolchildren: a randomized, placebo-controlled trial. Clin Infect Dis. 2014 May;58(10):1404-12. doi: 10.1093/cid/ciu150. Epub 2014 Mar 12.

  PMID: 24621953 BACKGROUND

• Hsiang MS, Hwang J, Tao AR, Liu Y, Bennett A, Shanks GD, Cao J, Kachur SP, Feachem RG, Gosling RD, Gao Q. Mass drug administration for the control and elimination of Plasmodium vivax malaria: an ecological study from Jiangsu province, China. Malar J. 2013 Nov 1;12:383. doi: 10.1186/1475-2875-12-383.

  PMID: 24175930 BACKGROUND

• Vilakati S, Mngadi N, Benjamin-Chung J, Dlamini N, Dufour MK, Whittemore B, Bhangu K, Prach LM, Baltzell K, Nhlabathi N, Malambe C, Dlamini B, Helb D, Greenhouse B, Maphalala G, Pindolia D, Kalungero M, Tesfa G, Gosling R, Ntshalintshali N, Kunene S, Hsiang MS. 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. BMJ Glob Health. 2021 Jun;6(6):e005021. doi: 10.1136/bmjgh-2021-005021.

  PMID: 34193475 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Mass Screening; Coal Tar

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and Procedures; Diagnosis; Health Surveys; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Investigative Techniques; Diagnostic Services; Preventive Health Services; Health Services; Health Care Facilities Workforce and Services; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Public Health Practice; Tars; Complex Mixtures

Study Officials

• Michelle S Hsiang, MD

  UTSW, UCSF

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2014
• First Posted: December 12, 2014
• Study Start: September 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: September 5, 2021

Record last verified: 2021-08

Locations

ES (1)