A prospective study will be carried out in an area where parasites with reduced sensitivity to malaria drugs (artemisinins) have recently emerged. The study will recruit participants from patients who attend the clinic with uncomplicated malaria and asymptomatically infected individuals. Participants are treated with conventional artemisinin-combination therapies (ACT) as part of standard clinical care. From this population, we will select P. falciparum gametocyte carriers. Before, during and after ACT treatment, the transmission potential of artemisinin resistant and wild type infections will be assessed by microscopy, molecular methods, parasite culture and mosquito feeding assays. Parasite clearance will be determined in the first days (d0-3) after treatment. The study population will consist of passively recruited patients with uncomplicated P. falciparum malaria and asymptomatically infected individuals who are microscopy positive for gametocytes. Participants will be treated with conventional therapies for uncomplicated malaria without randomization: artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA-PPQ). All doses are supervised. Parasite clearance is assessed ex vivo by ring-stage survival assays and by daily slides during the first days of treatment. Gametocyte carriage and gametocyte commitment/production will be determined for resistant and wild type infections before, during and after treatment. In addition, venous blood will be collected at three timepoints to assess transmission to mosquitoes before (d0), during (d2) and after treatment (d7). The total duration of participation will be 7 days, the primary endpoint will be the reduction in mosquito infection rates at d2 (artemether-lumefantrine) or d7 (dihydroartemisinin-piperaquine) compared to pre-treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
120
Participants in the Artemether-Lumefantrine arm will be treated with standard doses of AL (Coartem, Novartis). Tablets containing 20/80 mg artemether and 120/480 mg lumefantrine will be administered per manufacturer guidelines. All doses will be given under direct supervision with fatty food.
Participants in the DHA-PPQ arm will be treated with standard doses of DHA-PPQ. Tablets containing 40 mg dihydroartemisinin/320 mg piperaquine tablets (Eurartesim, Sigma Tau or Duocotecxin, Beijing Holley-Cotect Pharmaceutical Co) will be administered per manufacturer guidelines. All doses will be given under direct supervision on an empty stomach, as per manufacturer instructions.
Dr. Ambrosoli Memorial Hospital
Kalongo, Agago district, Uganda
RECRUITINGPatongo Health Facility IV
Patongo, Agago district, Uganda
RECRUITINGMean within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline.
Mean within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline (day 0, pre-treatment) to day 2 post treatment in the AL and day 7 post-treatment in the DHA-PPQ arm. Infectivity is assessed by mosquito membrane feeding assays; percent reduction is calculated separately for ΔPfK13 vs wild type infections.
Time frame: day 2 vs day 0 (AL arm) and day 7 vs day 0 (DP arm)
Mean within person percent change (presented as percent reduction) in mosquito infection rate from baseline
Mean within person percent change (presented as percent reduction) in mosquito infection rate from baseline to all feeding time-points. Infectivity is assessed by mosquito membrane feeding assays; comparisons are performed within treatment arms for ΔPfK13 vs wild type infections.
Time frame: days 0, 2, 7
Mean oocyst intensity (in all/all infected mosquitoes)
Mean oocyst intensity (in all/all infected mosquitoes) will be assessed at all feeding time-points; comparisons are performed within treatment arms for ΔPfK13 vs wild type infections
Time frame: days 0, 2, 7
Male and female gametocyte sex ratio (proportion male)
Male and female gametocyte sex ratio (proportion male) at all time-points, determined by molecular assays; comparisons are performed within treatment arms for ΔPfK13 vs wild type infections.
Time frame: days 0, 1, 2, 3, 7
Gametocyte circulation time
Gametocyte circulation time (cumulative), determined by microscopy or molecular assays, compared between treatment arms and between ΔPfK13 vs wild type infections
Time frame: days 0, 1, 2, 3, 7
Gametocyte area under the curve
Gametocyte area under the curve (cumulative), determined by microscopy or molecular assays, compared between treatment arms, and between ΔPfK13 vs wild type infections
Time frame: days 0, 1, 2, 3, 7
Asexual parasite prevalence
Asexual parasite prevalence at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms, between arms, and between ΔPfK13 vs wild type infections
Time frame: days 0, 1, 2, 3, 7
Asexual parasite density
Asexual parasite density at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms, between arms, and between ΔPfK13 vs wild type infections
Time frame: days 0, 1, 2, 3, 7
Total parasite prevalence
Total parasite prevalence at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms, between arms, and between ΔPfK13 vs wild type infections
Time frame: days 0, 1, 2, 3, 7
Total parasite density
Total parasite density at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms, between arms, and between ΔPfK13 vs wild type infections
Time frame: days 0, 1, 2, 3, 7
The density of ΔPfK13 vs wild type genotypes
The density of ΔPfK13 vs wild type genotypes in peripheral blood, the asexual parasite fraction and gametocyte fraction before and after initiation of treatment. The relative abundance of ΔPfK13 genotypes will be compared between pre- and post-treatment timepoints
Time frame: days 0, 1, 2, 3, 7
The density of ΔPfK13 vs wild type genotypes in oocysts and sporozoites in mosquitoes that become infected before and after initiation of treatment
The density of ΔPfK13 vs wild type genotypes in oocysts and sporozoites in mosquitoes that become infected before and after initiation of treatment. The relative abundance of ΔPfK13 genotypes will be compared between pre- and post-treatment timepoints
Time frame: days 0, 2, 7
Mean within person percent change (presented as percent reduction) in mosquito infection rate from baseline after gametocyte enrichment
Mean within person percent change (presented as percent reduction) in mosquito infection rate from baseline to all feeding time-points. Infectivity is assessed by mosquito membrane feeding assays after gametocyte enrichment; comparisons are performed within treatment arms for ΔPfK13 vs wild type infections.
Time frame: days 0, 2, 7
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.