Short Course Radical Cure of P. Vivax Malaria in Nepal

This study is designed as a multicentre randomized, open label trial to assess the safety and efficacy of a low dose short course PQ treatment (3.5mg/kg total dose given over 7 days) in glucose-6-phosphate dehydrogenase (G6PD) normal patients with P.vivax and P falciparum to reduce the risk of subsequent P.vivax episodes.

Plasmodium vivax is associated with recurrent infections weeks or months following the acute infection due to reactivation of dormant liver stages. Recurrent infections can be associated with a febrile illness, cumulative risk of severe anaemia, direct and indirect mortality, and are the most important source of onward transmission of the parasite. In co-endemic areas, there is a very high risk (up to 50%) of patients representing with P.vivax malaria following treatment of P falciparum. Hence, in co-endemic regions there is a strong rationale for eradicating P.vivax hypnozoites from the liver in patients presenting with uncomplicated P. falciparum infections. The recently completed multicentre IMPROV study compared the efficacy of a 7 day PQ regimen (1.0mg/kg/day for 7 days) with a 14 day regimen (0.5mg/kg/day for 14 days). The 7 day PQ regimen was non-inferior to the 14 day regimen and 5 times more efficacious at reducing P.vivax recurrence than the control. This study is designed as a multicentre randomized, open label trial to assess the safety and efficacy of a low dose short course PQ treatment (3.5mg/kg total dose given over 7 days) in G6PD normal patients with P.vivax and P falciparum to reduce the risk of subsequent P.vivax episodes.

patients with falciparum malaria will receive artemether-lumefantrine (AL) twice daily over three days plus a low dose course of primaquine (PQ) (3.5mg/kg total dose) given 7 days during schizontocidal treatment

patients with vivax malaria will receive chloroquine (CQ) daily for three days plus a low dose course of PQ (3.5mg/kg total dose) given over 7 days during schizontocidal treatment.

patients with falciparum malaria will receive artemether-lumefantrine (AL) twice daily over three days (plus a single dose PQ)

patients with vivax malaria will receive chloroquine (CQ) daily for three days plus a low dose course of PQ (total dose 3.5mg/kg) over 14 days

Jasoprim, Malirid, Neo-Quipenyl, Pimaquin, Pmq, Primachina, Primacin, Primaquina, Primaquine, Primaquine diphosphate, Primaquine Phosphate, and Remaquin

The incidence risk of symptomatic P. vivax malaria at month 6 in patients enrolled with P. vivax and P. falciparum infection.

The incidence risk of symptomatic P. vivax malaria at month 6 in patients enrolled with P. falciparum

The incidence risk of symptomatic P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection

The incidence risk of all (symptomatic and asymptomatic) P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection

The incidence risk of asymptomatic P. vivax malaria at day 28 in patients enrolled with P. falciparum and vivax malaria infection

Inclusion Criteria: P. falciparum and/or vivax infection Fever (axillary temperature ≥37.5⁰C) or history of fever in preceding 48 hours Age >1 years G6PD normal by Rapid Diagnostic Test (RDT) as per national guidelines Written informed consent Able to comply with all study procedures and timelines Exclusion Criteria: General danger signs or symptoms of severe malaria Anaemia, defined as Hb <8g/dl Pregnant women as determined by Urine β-HCG pregnancy test Breast feeding women Known hypersensitivity to any of the drugs given Regular use of drugs with haemolytic potential Blood transfusion within the last 4 months

Study Protocol and Statistical Analysis Plan will be made available to others. Data collected for the study, including individual patient data and the final trial dataset are reserved for the chief investigator and co-investigators of the trial. The trial will be reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Trial results will be published in peer-reviewed open access journals and disseminated to trial stakeholders, including participants, as per ethical guidelines.

The data are available for access via the WorldWide Antimalarial Resistance Network (WWARN.org). Requests for access will be reviewed by a Data Access Committee to ensure that use of data protects the interests of the participants and researchers according to the terms of ethics approval and principles of equitable data sharing. Requests can be submitted by email to malariaDAC@iddo.org via the Data Access Form available at WWARN.org/accessing-data. The WWARN is registered with the Registry of Research Data Repositories (re3data.org).