Clinical trial NCT01906788: The Optimal Timing Of Primaquine To Prevent Malaria Transmission After Artemisinin-Combination Therapy
Official title: THE OPTIMAL TIMING OF PRIMAQUINE TO PREVENT MALARIA TRANSMISSION AFTER ARTEMISININ-COMBINATION THERAPY
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Malaria Transmission
Lead sponsor: Kilimanjaro Clinical Research Institute
Sponsor class: OTHER
Collaborators: name: London School of Hygiene and Tropical Medicine
name: Ifakara Health Institute
First posted: 2013-07-24
Enrollment: 250
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Gametocyte prevalence and density by microscopy and QT-NASBA
timeFrame: Day 14
Secondary outcomes:
measure: Haemoglobin level
timeFrame: days 3, 7, 10 and 14
Other outcomes:
measure: Proportion of infected mosquitoes
timeFrame: day 7
Locations:
city: Bagamoyo
country: Tanzania
facility: Bagamoyo Research and Training Centre
Study officials:
affiliation: Kilimanjaro Clinical Research Institute and Ifakara Health Institute
name: Seif Shekalaghe, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.