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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Malaria Transmission

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Active comparator: Artemether Lumefantrine 6 dose regime orally | Drug: Artemether Lumefantrine<br> <br> |
| Experimental: Group 2<br>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<br> <br> |
| Experimental: Group 3<br>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<br> <br> |

What is the study measuring?
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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 |