The Transmission of Artemisinin Resistant Parasites Before and After Conventional Artemisinin-combination Therapy

The Transmission of Artemisinin Resistant Parasites Before and After Conventional Artemisinin-combination Therapy: a Longitudinal Study

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.

Inclusion Criteria:

• age ≥2 years
• blood smear positive for P. falciparum gametocytes
• mono-infection with P. falciparum confirmed by positive blood smear;
• parasitaemia of >100 P. falciparum asexual forms/µL;
• ability to swallow oral medication;
• ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule;
• informed consent from parent or guardian;
• haemoglobin ≥ 7.0 g/dl for children below 10 years of age or ≥8.0g/dL for older individuals

Exclusion Criteria:

• presence of general danger signs;
• mixed or mono-infection with another Plasmodium species detected by microscopy;
• presence of severe malnutrition defined as a very low weight for height (below -3z scores of the median WHO growth standards), by visible severe wasting, or by the presence of nutritional oedema.
• presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
• history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested