Dihydroartemisinin-piperaquine for Seasonal Malaria Chemoprophylaxis in Tanzania (SMC-DP)

Effectiveness of Dihydroartemisinin-piperaquine as Seasonal Malaria Chemoprophylaxis in Extended High Transmission Settings of Tanzania: an Open Cluster Randomized Clinical Trial.

Background: Malaria prevalence has declined globally following the scale-up of the interventions, including insecticide-treated bed-net, indoor residual spraying, and prompt diagnosis and treatment with artemisinin-based combination therapy (ACT). Despite the gained success in the control, malaria has remained a major public health problem, particularly affecting children aged < 5 years in sub-Saharan Africa. Most of the malaria transmissions occur during the rainy season, a relatively short period. Intervention using antimalarial chemotherapy in children during the transmission season has been shown to prevent malaria-related morbidity and mortality. The World Health Organization has recommended seasonal malaria chemoprevention (SMC) using Sulphadoxine-pyrimethamine (SP) plus amodiaquine (AQ) in children aged 3-59 months in areas with highly seasonal malaria transmission. However, SP-AQ resistance is widespread in Tanzania. Therefore, this study will assess the effectiveness of Dihydroartemisinin-piperaquine (DHA-PQ) as SMC for the control of malaria among children in Tanzania.

Methods: Afebrile children aged 3-59 months from Nanyumbu and Masasi districts in the Mtwara region will be enrolled in an open cluster randomized clinical trial, administered monthly with a full course of DHA-PQ for three or four consecutive months during the high malaria transmission season of the three consecutive years. Three approaches of DHA-PQ SMC administration will be tested; a door-to-door approach using community health workers (CHWs), outreach visits using local health facilities clinicians/nurses, and village health posts using selected CHWs. Study participants will then be followed-up to evaluate the impact of the intervention on all-course of malaria morbidity and mortality; adverse events associated with the intervention; acceptability, adherence, coverage, and cost-effectiveness of the intervention; treatment-seeking behavior; and the risk of rebound after the withdrawal of the intervention. The primary outcome will be a prevalence of clinical malaria defined as the presence of fever (axillary temperature of 37.5 degrees Celsius) or a history of fever in the past 24 hours and the presence of P. falciparum asexual parasitemia at any density.

Findings: The findings will be disseminated through community meetings, seminars, local and international conferences, and publication in international journals.

Impact: The findings from this study will provide information on the effectiveness of DHA-PQ for seasonal prevention of malaria morbidity and mortality in children aged < 5 years in Tanzania.

Study Overview

• Status: Completed
• Conditions: Malaria; Chemoprophylaxis; Underfive Children
• Intervention / Treatment: Drug: Dihydroartemisinin-piperaquine

• Study Type: Interventional
• Enrollment (Actual): 13800
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Tanzania
  • Dar es Salaam, Tanzania, 65001
    • Muhimbili University of Health and Allied Ssciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• being afebrile,
• willing to participate in the trial, and
• the ability to swallow oral medications.

Exclusion Criteria:

• a presence of an acute febrile illness or severe illness that impairs the ability to take oral medication
• HIV-positive child receiving cotrimoxazole prophylaxis,
• a child who has received a dose of antimalarial drug including dihydroartemisinin-piperaquine during the past month; and
• a history of allergy to DHA-PQ.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dihydroartemisinin-piperaquine; Dihydroartemisinin-piperaquine will be administered to the intervention arm	Drug: Dihydroartemisinin-piperaquine; The drug will be administered once a day for three consecutive days for three months (March, April, and May)
No Intervention: Control; Individuals that will get malaria infection and present at the health facility with clinical signs and symptoms will be treated according to the Tanzania National Malaria Treatment guidelines using artemether-lumefantrine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of clinical malaria	Defined as the presence of any malaria-related signs/symptoms plus P. falciparum asexual parasitemia at any density. For it to be considered a clinical malaria there must be any signs or symptoms related to malaria infection and the presence of asexual P. falciparum parasites confirmed by mRDT or microscopy.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of severe malaria	Defined according to the WHO criteria	12 months
Prevalence of malaria infection	Defined as the presence of asexual parasitemia. Individuals do not show any signs or symptoms related to malaria infection but they have asexual P. falciparum parasites confirmed by mRDT or microscopy.	12 months
Prevalence of anaemia	Prevalence of mild, moderate, or severe anaemia defined as an hemoglobin concentration of 11 g/dL, 8 g/dL, or 5 g/dL, respectively.	12 months
Prevalence of hospital admissions	Prevalence of individuals admitted to the health facility due to malaria infection during the SMC will be assessed. Hospital admission will be defined as a stay of at least 24 hours in hospital for treatment.	12 months
Prevalence of participants with any anthropometric indices.	The prevalence of children with anthropometric indices including wasting, stunting, or underweight as defined by WHO will be assessed before and after the three rounds of SMC and then compared.	12 months
Prevalence of household heads with positive health seeking behavior	Initiatives to seek treatment once feels sick. A questionnainne will be used to gather information from the household heads of the children involved in the study on what initiatives do they take when they or their children become sick.	12 months
Prevalence of molecular markers	Molecular markers of artemisinin and partner drugs resistance.	12 months

Collaborators and Investigators

• Sponsor: Richard Mwaiswelo
• Collaborators: National Institute for Medical Research, Tanzania; Muhimbili University of Health and Allied Sciences; Hubert Kairuki Memorial University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: May 4, 2023
• First Submitted That Met QC Criteria: May 15, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 15, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Piperaquine; Artenimol
• Other Study ID Numbers: MUHAS-REC-10-2019-062

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared with individuals locally and globally following guidelines stipulated in the Data and Material Transfer Agreement.
• IPD Sharing Time Frame: 12 months
• IPD Sharing Access Criteria: Request to the PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No