Ethiopia Antimalarial in Vivo Efficacy Study 2012

Following the rapid development of significant drug resistance of Plasmodium falciparum (Pf) to chloroquine and then sulfadoxine-pyrimethamine, artemether- lumefantrine (Coartem or AL) was adopted as first line therapy in Ethiopia in 2004. According to the current national malaria diagnosis and treatment guidelines updated in 2012, first-line treatment for uncomplicated P. falciparum infection is AL. First-line treatment for Plasmodium vivax (Pv) is chloroquine (CQ) alone in malarious areas and with primaquine in non-malarious areas at health center and hospital level. WHO recommends treatment of Pv with CQ or an artemisinin-based combination therapy (ACT) in combination with primaquine. For all clinical infection without laboratory confirmation, AL is the first-line treatment since AL is effective against both Pf and Pv. Thus, in Ethiopia, where treatment for malaria without laboratory confirmation occurs frequently, Pv is often treated with AL as the standard of care. Similarly, the recommended drug for mixed infection with Pf and Pv is AL. Now with wide-spread use of AL and CQ and with evidence that malaria laboratory testing is occurring in about half of those suspected with clinical evidence of malaria infection, the investigators propose to conduct an antimalarial efficacy study to monitor the effectiveness of these therapies in Ethiopia and to determine how efficacious these drugs remain for Pv. In addition, with high rates of relapse with P. vivax infection, the efficacy and safety of co-administering primaquine will be assessed. This information will inform future policy changes with respect to appropriate antimalarial strategies.

Inclusion criteria

• Slide-confirmed infection with P. vivax
• Age > 1 year
• Lives within 20 km of the enrolling health facility
• Weight ≥ 5.0 kg
• Axillary temperature ≥ 37.5º C or history of fever during the previous 48 hours
• Patient or caregiver agrees to all finger pricks and return visits.

Exclusion criteria

• General danger signs or symptoms of severe malaria (see Annex II)
• Signs or symptoms of severe malnutrition, defined as weight-for-age ≤ 3 standard deviations below the mean (NCHS/WHO normalized reference values)
• Slide confirmed infection with any other Plasmodium species. besides P. vivax mono-infection
• Acute anemia, defined as Hg < 8 g/dl
• Known hypersensitivity to any of the drugs being evaluated
• Presence of febrile conditions caused by diseases other than malaria
• Serious or chronic medical condition by history (cardiac, renal, hepatic diseases, sickle cell disease, HIV/AIDS)
• Pregnant or breastfeeding women.
• History or hemolysis or severe anemia
• Regular medication, which may interfere with antimalarial pharmacokinetics