mated reporting of primaquine dose efficacy, tolerability and safety for Plasmodium vivax malaria using a systematic review and individual patient data meta-analysis
Edler P., Rajasekhar M., Price DJ., Adam I., Awab GR., Barber BE., Brasil LW., Chamma-Siqueira NN., Chu CS., Cui L., Daher A., Gomes MDSM., Gonzalez-Ceron L., Grigg MJ., Karunajeewa H., Lacerda MVG., Ladeia-Andrade S., Leslie T., Ley B., Lidia K., Llanos-Cuentas A., Longley RJ., Manning L., Mekonnen DA., Monteiro WM., Moore BR., Nosten F., Pasaribu AP., Pereira DB., Poespoprodjo JR., Pukrittayakamee S., Rijal KR., Saravu K., Siqueira AM., Sutanto I., Taylor WRJ., Thanh PV., Thriemer K., Vieira JLF., White NJ., Yeshiwondim AK., Zuluaga-Idarraga LM., Guerin PJ., Simpson JA., Price RN., Commons RJ., Abreha T., Adhikari B., Alam MS., Anstey NM., Assefa A., Baird JK., Boyd SC., Chau NH., Day NPJ., Degaga TS., Dondorp AM., Erhart A., Ferreira MU., Gadisa E., Ghanchi N., Ghimire P., Green JA., Hassanzai MA., Hwang J., Khan WA., Koh GCKW., Kumar R., Mekuria AH., Mueller I., Naadim MN., Negreiros SC., Nelwan EJ., de Pina-Costa A., Rowland M., Sattabongkot J., Suarez-Kurtz G., Tadesse FG., Viana GMR., von Seidlein L., William T., Woodrow CJ., Woon S-A., Woyessa A.
Abstract Background The antirelapse efficacy of primaquine is related to the total dose administered, whereas the risks of haemolysis and gastrointestinal intolerance are associated with the daily dose administered. National Malaria Control Programmes require local information on efficacy, tolerability and safety to optimize antimalarial treatment policies for Plasmodium vivax malaria control and elimination efforts. Methods A living systematic review identified efficacy studies of uncomplicated P. vivax malaria including patients treated with daily primaquine regimens, published since January 1, 2000. Available data were pooled and an R Shiny app was developed to integrate statistical analyses performed using R and Stata that assessed the impact of primaquine mg/kg dose on efficacy, hematological safety and gastrointestinal tolerability. Results As of January 16, 2025, a total of 9,270 individual patient data records from 41 studies have been collated into the standardized repository. Open-access automated reports were generated for user-selected countries or regions to investigate location specific effects of primaquine dose on efficacy, safety and tolerability. The reports include visual and tabular displays of the outcomes. Conclusions These automated reports leverage a large database to provide accessible data for national and regional policy makers and researchers to assess the clinical consequences of different primaquine regimens in different endemic settings. The reports will inform local and regional policy decisions and research priorities in vivax-endemic areas.