Clinical trial NCT02721186: Effectiveness of Mass Drug Administration for Reducing Seasonal Malaria Transmission in Zanzibar
Official title: Effectiveness of Mass Drug Administration (MDA) for Reducing Seasonal Malaria Transmission Towards Its Elimination in Hotspot Areas in Zanzibar - a Cluster-randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Plasmodium Infections
Keywords: Malaria
Plasmodium
Mass drug administration
Malaria elimination
Zanzibar
Dihydroartemisinin-Piperaquine
Single low dose Primaquine
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Mahidol Oxford Tropical Medicine Research Unit
name: RTI International
name: The President's Malaria Initiative
name: University of California, San Francisco
name: Uppsala University
name: Zanzibar Malaria Elimination Programme
First posted: 2016-03-29
Enrollment: 22500
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The overall aim of this study is to determine the effectiveness of two rounds of mass drug administration (MDA) with dihydroartemisinin-piperaquine (DHAp) + single low dose (SLD) primaquine for reducing seasonal malaria transmission in Shehias considered hotspots on Unguja Island, Zanzibar.

Detailed description: Study design: This is a cluster-randomised controlled study with two arms: an intervention arm with two rounds of MDA with dihydroartemisinin-piperaquine (DHAp) + single low dose (SLD) primaquine, and a control arm with no MDA.

Study site and study population: The study will be conducted in 16 hotspot Shehias (8 Shehias randomly allocated to each arm), in three districts (West, Central and South districts) in Unguja Island, Zanzibar. Hotspot Shehias \[Shehia being the smallest administrative structure in Zanzibar\] are defined as Shehias with an annual malaria incidence of \>0.8%, calculated as the number of confirmed malaria infections notified at health facilities and during active case detection in 2015 / Shehia projected population for 2015. The study population will include all consenting residents of the selected Shehias, reaching approximately 24000 people.

Study implementation: Two rounds of MDA with DHAp (D-ARTEPP, Guilin Pharmaceutical (Shanghai) Co., Ltd., China) and SLD (0.25mg/kg) primaquine (Primaquine, Remedica Ltd.,Cyprus ) will be conducted approximately four weeks apart in the intervention Shehias, at the anticipated lowest point of malaria transmission prior to the onset of malaria transmission associated with the main rains in April-June 2016. The first drug dose including DHAp and SLD primaquine will be given under supervision whenever possible; the other two doses of the standard once daily DHAp regimen will be taken unsupervised at home. Labelled packets containing all three doses will be left with the head of household with clear instructions for individuals not present at the time of the household visit.

Study objectives: The primary objective of the study is to determine the effectiveness of two rounds of MDA with DHAp + SLD primaquine for reducing seasonal malaria transmission in Shehias considered hotspots on Unguja Island, Zanzibar. The secondary objectives of the study include determining MDA coverage, compliance, and safety after one and two rounds of DHAp + SLD primaquine.

Eligibility criteria: Inclusion Criteria:

* Permanent or temporary resident of study Shehias (i.e., persons who stayed in the selected household the night before the interview)
* Provision of informed consent (refusal must be recorded)
* Age \>6 months

Exclusion Criteria:

* Women pregnant in first trimester (assessed by a specific set of questions designed to exclude pregnancy)
* Severe disease that requires immediate referral to health facility or hospital
* Concurrent antimalarial treatment at time of MDA or during the last 14 days
* Inability to take oral medication

Additional exclusion criteria for treatment with SLD Primaquine:

* Pregnancy (all trimesters, assessed by a specific set of questions designed to exclude pregnancy)
* Women breast feeding infants aged \< 6months

Primary outcomes:
measure: Cumulative notified malaria incidence in the MDA and control Shehias
timeFrame: 6 months after second round of MDA
Secondary outcomes:
measure: PCR determined community prevalence of Plasmodium infections in the MDA and control Shehias
timeFrame: Baseline and 3 months after second round of MDA
Other outcomes:
measure: Population coverage of the MDA intervention at each round
timeFrame: Through completion of first and second round of MDA, i.e. 15 days and 48 days after initiation of MDA, respectively.
measure: Proportion of population receiving two rounds of MDA
timeFrame: Through completion of the second round of MDA, i.e. 48 days after initiation of MDA.
measure: Population compliance to the MDA intervention at each round
timeFrame: 7 days after both first and second round of MDA
measure: Occurence of adverse events after MDA with DHAp and SLD primaquine
timeFrame: 14 days after both first and second round of MDA
measure: Cumulative notified malaria incidence in the MDA and control Shehias during the following high transmission season.
timeFrame: 15 months after second round of MDA
Locations:
city: Mwanakwerekwe
country: Tanzania
facility: Zanzibar Malaria Elimination Programme
state: Urban District, Zanzibar
Study officials:
affiliation: Karolinska Institutet
name: Anders Björkman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Zanzibar Malaria Elimination Programme
name: Abdullah S Ali, Programme Manager
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shah MP, Hwang J, Choi L, Lindblade KA, Kachur SP, Desai M. Mass drug administration for malaria. Cochrane Database Syst Rev. 2021 Sep 29;9(9):CD008846. doi: 10.1002/14651858.CD008846.pub3.
citation: Morris U, Msellem MI, Mkali H, Islam A, Aydin-Schmidt B, Jovel I, Shija SJ, Khamis M, Ali SM, Hodzic L, Magnusson E, Poirot E, Bennett A, Sachs MC, Tarning J, Martensson A, Ali AS, Bjorkman A. A cluster randomised controlled trial of two rounds of mass drug administration in Zanzibar, a malaria pre-elimination setting-high coverage and safety, but no significant impact on transmission. BMC Med. 2018 Dec 10;16(1):215. doi: 10.1186/s12916-018-1202-8.