Malaria
Conditions
Interventions
AP and PQ arm for P. vivax
AP and PQ arm for Pf
CQ and PQ arm for Pv
AL and PQ arm for Pf
AP and delayed PQ for Pv
CQ and delayed PQ
Sponsors
ICAP at Columbia University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Those living within 20 km of the catchment of the health facility with a traceable address or phone contact number • Volunteer to give their address or phone number and willing to not travel for the duration of the study • Volunteer to comply with the study protocol, visit schedule, or get traced in case defaulted • Age = 18 years • Slide-confirmed infection with Pf, with parasitemia of 500-100,000 asexual forms/µl or slide confirmed infection with Pv with > 250 asexual forms/µl • For the gametocyte clearance and mosquito feeding endpoints, patients with microscopy-detected gametocytes prior to treatment will be eligible to be enrolled • Axillary temperature = 37.5º C or history of fever during the previous 24 or 48 hours for Pf and Pv infection, respectively • Ability to swallow oral medication
Exclusion criteria
Exclusion criteria: • General danger signs or symptoms of severe malaria • Mixed Plasmodium infection • Severe anemia, defined as hemoglobin (Hb) < 7 g/dl • Presence of febrile conditions caused by diseases other than malaria (e.g. measles, acute lower respiratory tract infection, COVID-19, severe diarrhea with dehydration) • Serious or chronic medical condition (e.g. cardiac, renal, hepatic diseases, sickle cell disease, HIV/AIDS) • Positive pregnancy test or breastfeeding • Refusal to take a pregnancy test for women of child-bearing age (defined as 18–49 years old or menstruating) • History of hypersensitivity to study or rescue medication in this study • Taking regular medication which may interfere with antimalarial pharmacokinetics or efficacy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Day 28 rate of adequate clinical and parasitological response (ACPR) of AL-PQ for Pf and CQ-PQ for PV. The absence of parasitemia by day 28 without previously meeting any of the criteria for Early Treatment Failure, Late Clinical Failure, and Late Parasitological Failure. The PCR-adjusted and unadjusted proportion of treatment failures will be determined together with the frequency of severe malaria, anemia, and hospitalizations by the treatment arm. ;Day 28 rate of ACPR of AP-PQ for Pf and for PV. The absence of parasitemia by day 28 without previously meeting any of the criteria for Early Treatment Failure, Late Clinical Failure, and Late Parasitological Failure. The PCR-adjusted and unadjusted proportion of treatment failures will be determined together with the frequency of severe malaria, anemia, and hospitalizations by the treatment arm.;Day 42 rate of ACPR of AP-PQ for PV. The absence of parasitemia by day 42 without previously meeting any of the criteria for Early Treatment Failure, Late Clinical Failure, and Late Parasitological Failure. The PCR-adjusted and unadjusted proportion of treatment failures will be determined together with the frequency of severe malaria, anemia, and hospitalizations by the treatment arm. ;Safety and tolerability of combination treatment;Day 42 rate of ACPR of AP-PQ for Pf. The absence of parasitemia by day 42 without previously meeting any of the criteria for Early Treatment Failure, Late Clinical Failure, and Late Parasitological Failure. The PCR-adjusted and unadjusted proportion of treatment failures will be determined together with the frequency of severe malaria, anemia, and hospitalizations by the treatment arm. | — |
Secondary
| Measure | Time frame |
|---|---|
| Document genetic polymorphisms implicated in antimalarial drug resistance. We will deploy length polymorphism genotyping techniques and/or targeted amplicon sequencing to monitor known/novel drug resistance markers. Molecular studies including polymorphisms and copy number variations of pfcrt, pfmdr1, PfK13, pvcrt-o, pvmdr1, pvdhfr, pvdhps and plasmepsin associated with altered drug sensitivity (including those not currently known or characterized) will be performed for surveillance purposes and will have no impact on the clinical management of study patients. ;To assess gametocytocidal effect of single dose PQ for Pf in the 2 Pf arms. Gametocyte carriage/clearance rates are determined as the proportion of patients with gametocytes on days 0, 1, 2, 3, 7, and 14. Gametocyte concentration will be quantified by microscopy and stage specific reverse transcriptase qPCR (RT-qPCR) will be performed from the RNAprotect samples. Blood samples in RNAprotect buffer will be used for the extraction of RNA. RNA-based stage-specific assays include gametocyte sex specific and asexual stage specific markers. ;Within-person change in infectivity to mosquitoes, comparing infectivity pre-treatment with infectivity post-initiation of treatment. Infectivity is assessed as a percentage of infected mosquitoes and the infection burden in these mosquitoes. The proportion of infectious individuals will be determined as the proportion of patients who infect at least one mosquito on days 0, 1, 2, and 3. The proportion of infected mosquitoes is determined as the proportion of infected mosquitoes (as the proportion of total dissected mosquitoes) on days 0, 1, 2, and 3 expressed as an absolute proportion on each of these days and as percentage reduction on days 1, 2, and 3 compared to pre-treatment (day 0). Infection burden in mosquitoes is determined as the density of oocysts in mosquitoes on days 0, 1, 2, and 3 expressed as absolute density on each of these days and as percentage reduction on | — |
Countries
Ethiopia
Contacts
Public ContactBereket Alemayehu
ICAP at Columbia University
Outcome results
None listed