The Optimal Timing Of Primaquine To Prevent Malaria Transmission After Artemisinin-Combination Therapy

THE OPTIMAL TIMING OF PRIMAQUINE TO PREVENT MALARIA TRANSMISSION AFTER ARTEMISININ-COMBINATION THERAPY

The investigators' Hypothesis is that "The correct timing of gametocytocidal drug in combination with an effective Artemisinin Combination Therapy can limit the infectiousness of malaria-infected individuals to less than one week after initiation of treatment"

Study Overview

• Status: Unknown
• Conditions: Malaria Transmission
• Intervention / Treatment: Drug: Artemether Lumefantrine; Drug: Artemether Lumefantrine 6 dose regimen & single dose of Primaquine on day 0; Drug: Artemether Lumefantrine 6 dose regimen and single dose Primaquine on day 2

Detailed Description

Global malaria elimination is back on the agenda, gametocytocidal drugs such as primaquine are currently advocated for use in the interventions that aim to interrupt malaria transmission and hence elimination. Mature gametocytes are responsible for malaria transmission. Artemisinin based combination therapies (ACTs) has limited effect on the young gametocytes. Primaquine is able to clear mature gametocytes that remain after treatment with ACTs. Complete clearance of mature gametocytes will depend on the ideal time primaquine is given after ACT. It is important therefore that is administered at optimal time in order to have significant impact on clearing gametocytes to interrupt malaria transmission. An additional consideration is operational administration of Primaquine and compliance both of which are likely to be enhanced if the drug is administered on the day of diagnosis.

In this study, the investigators aim to determine optimal timing of primaquine administration in addition to ACT by comparing administration on day 0 with administration on day 2.

The investigators' primary end points are gametocyte prevalence and density by microscopy and Quantitative Nucleic Acid Based Amplification (QT-NASBA) on day 14, which will be compared between the two primaquine treatment arms.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• Tanzania
  • Bagamoyo, Tanzania
    • Recruiting
    • Bagamoyo Research and Training Centre
    • Contact: Seif Shekalaghe, MD, PhD; Phone Number: +255 755 470472; Email: sshekalaghe@ihi.or.tz
    • Sub-Investigator: Chris Drakeley, PhD
    • Sub-Investigator: Teun Bousema, PhD
    • Sub-Investigator: Salim Abdulla, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 3 years - 17 years
• Residents of research area
• Willingness to come for complete scheduled follow-up.
• Uncomplicated malaria with P. falciparum mono-infection
• Axillary temperature > 37.5°C and < 39.5°C, or history of fever in previous 48 hours.
• No history of adverse reactions to study medication
• Understanding of the procedures of the study by parent or guardian and willing to participate by signing written informed consent forms

Exclusion Criteria:

• Haemoglobin below 9g/dl
• Inability to take drugs orally
• Known hypersensitivity to any of the drugs given
• Reported treatment with antimalarial chemotherapy in the past 2 weeks
• Evidence of chronic disease or acute infection other than malaria
• Domicile outside the study area
• Signs of severe malaria( such as respiratory distress, altered consciousness deep breathing, anaemia)
• Participating in other malaria studies conducted in the region
• Mixed malaria parasite species infection
• Positive pregnant test by Urine (UPT) if participant is female aged above 12 years
• G6PD deficient using the fluorescence spot test

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group 1; Active comparator: Artemether Lumefantrine 6 dose regime orally	Drug: Artemether Lumefantrine
EXPERIMENTAL: Group 2; Experimental: Artemether Lumefantrine 6 dose regime Plus single dose Primaquine (0.75/kg) on day 0	Drug: Artemether Lumefantrine 6 dose regimen & single dose of Primaquine on day 0
EXPERIMENTAL: Group 3; Experimental: Artemether Lumefantrine 6 dose regimen plus single dose of Primaquine (0.75/kg) on day 2	Drug: Artemether Lumefantrine 6 dose regimen and single dose Primaquine on day 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gametocyte prevalence and density by microscopy and QT-NASBA	By microscopy and QT-NASBA techniques we will determine and compare gametocyte prevalence and density on day 14 between the Primaquine treatment 2 and 3 arms.	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemoglobin level	We will compare the level of baseline haemoglobin on days 3, 7, 10 and 14 after the start of treatment between the two Primaquine arms	days 3, 7, 10 and 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of infected mosquitoes	We will determine the proportion of infected mosquitoes on day 7 after initiation of treatment and the intensity of infection (oocyst burden)by use of membrane feeding assay technique.	day 7

Collaborators and Investigators

• Sponsor: Kilimanjaro Clinical Research Institute
• Collaborators: London School of Hygiene and Tropical Medicine; Ifakara Health Institute
• Investigators: Principal Investigator: Seif Shekalaghe, MD, PhD, Kilimanjaro Clinical Research Institute and Ifakara Health Institute

Publications and helpful links

General Publications

• Shekalaghe S, Mosha D, Hamad A, Mbaga TA, Mihayo M, Bousema T, Drakeley C, Abdulla S. Optimal timing of primaquine to reduce Plasmodium falciparum gametocyte carriage when co-administered with artemether-lumefantrine. Malar J. 2020 Jan 21;19(1):34. doi: 10.1186/s12936-020-3121-3.

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ANTICIPATED): October 1, 2013
• Study Completion (ANTICIPATED): October 1, 2013

Study Registration Dates

• First Submitted: July 20, 2013
• First Submitted That Met QC Criteria: July 23, 2013
• First Posted (ESTIMATE): July 24, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): July 24, 2013
• Last Update Submitted That Met QC Criteria: July 23, 2013
• Last Verified: July 1, 2013

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; Lumefantrine; Artemether; Primaquine; Artemether, Lumefantrine Drug Combination
• Other Study ID Numbers: PRIMAQUINE STUDY