TY - JOUR
T1 - Case Series of Primaquine-Induced Haemolytic Events in Controlled Trials with G6PD Screening
AU - Kosasih, Ayleen
AU - James, Robert
AU - Chau, Nguyen Hoang
AU - Karman, Michelle M.
AU - Panggalo, Lydia Visita
AU - Wini, Lyndes
AU - Thanh, Ngo Viet
AU - Obadia, Thomas
AU - Satyagraha, Ari Winasti
AU - Asih, Puji Budi Setia
AU - Syafruddin, Din
AU - Taylor, Walter R.J.
AU - Mueller, Ivo
AU - Sutanto, Inge
AU - Karunajeewa, Harin
AU - Pasaribu, Ayodhia Pitaloka
AU - Baird, J. Kevin
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/9
Y1 - 2023/9
N2 - Primaquine for radical cure of Plasmodium vivax malaria poses a potentially life-threatening risk of haemolysis in G6PD-deficient patients. Herein, we review five events of acute haemolytic anaemia following the administration of primaquine in four malaria trials from Indonesia, the Solomon Islands, and Vietnam. Five males aged 9 to 48 years were improperly classified as G6PD-normal by various screening procedures and included as subjects in trials of anti-relapse therapy with daily primaquine. Routine safety monitoring by physical examination, urine inspection, and blood haemoglobin (Hb) assessment were performed in all those trials. Early signs of acute haemolysis, i.e., dark urine and haemoglobin drop >20%, occurred only after day 3 and as late as day 8 of primaquine dosing. All patients were hospitalized and fully recovered, all but one following blood transfusion rescue. Hb nadir was 4.7 to 7.9 g/dL. Hospitalization was for 1 to 7 days. Hb levels returned to baseline values 3 to 10 days after transfusion. Failed G6PD screening procedures in these trials led G6PD-deficient patients to suffer harmful exposures to primaquine. The safe application of primaquine anti-relapse therapy requires G6PD screening and anticipation of its failure with a means of prompt detection and rescue from the typically abrupt haemolytic crisis.
AB - Primaquine for radical cure of Plasmodium vivax malaria poses a potentially life-threatening risk of haemolysis in G6PD-deficient patients. Herein, we review five events of acute haemolytic anaemia following the administration of primaquine in four malaria trials from Indonesia, the Solomon Islands, and Vietnam. Five males aged 9 to 48 years were improperly classified as G6PD-normal by various screening procedures and included as subjects in trials of anti-relapse therapy with daily primaquine. Routine safety monitoring by physical examination, urine inspection, and blood haemoglobin (Hb) assessment were performed in all those trials. Early signs of acute haemolysis, i.e., dark urine and haemoglobin drop >20%, occurred only after day 3 and as late as day 8 of primaquine dosing. All patients were hospitalized and fully recovered, all but one following blood transfusion rescue. Hb nadir was 4.7 to 7.9 g/dL. Hospitalization was for 1 to 7 days. Hb levels returned to baseline values 3 to 10 days after transfusion. Failed G6PD screening procedures in these trials led G6PD-deficient patients to suffer harmful exposures to primaquine. The safe application of primaquine anti-relapse therapy requires G6PD screening and anticipation of its failure with a means of prompt detection and rescue from the typically abrupt haemolytic crisis.
KW - acute haemolytic anaemia
KW - G6PD deficiency
KW - G6PD screening
KW - primaquine
KW - randomized controlled trials
UR - http://www.scopus.com/inward/record.url?scp=85172871987&partnerID=8YFLogxK
U2 - 10.3390/pathogens12091176
DO - 10.3390/pathogens12091176
M3 - Article
AN - SCOPUS:85172871987
SN - 2076-0817
VL - 12
JO - Pathogens
JF - Pathogens
IS - 9
M1 - 1176
ER -