Shoichi Shimizu1, Tadashi Kikuchi1, Michiko Koga1, Yasuyuki Kato2, Hiroyuki Matsuoka3, Haruhiko Maruyama4, Mikio Kimura5. 1. Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan. 2. Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan. 3. Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Shimotsuke, Japan. 4. Department of Infectious Diseases, Division of Parasitology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. 5. Department of Internal Medicine, Shin-Yamanote Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan. Electronic address: kimumiki@shinyamanote.jp.
Abstract
BACKGROUND: Recently, a dose of 30 mg (base) primaquine daily for 14 days is increasingly recommended for radical cure of Plasmodium vivax malaria. However, total primaquine doses, or those per body weight, are also recognized as important. In Japan, primaquine is not a licensed medicine, but has been used through the Research Group on Chemotherapy of Tropical Diseases for >3 decades. METHODS: Based on clinical records submitted to the Research Group, patients with P. vivax and Plasmodium ovale malaria treated with primaquine were analyzed to determine the efficacy and safety of the antimalarial drug. RESULTS: Seventy-five P. vivax cases, including 3 in children, and 19 P. ovale cases were enrolled. Five of the P. vivax cases demonstrated at least one relapse despite primaquine therapy. Total primaquine doses per body weight were obtained in 4 of the 5 relapsed patients, presenting 9 malaria episodes totally, and most of the primaquine failures were caused with a total dose ≤ 3.5 mg/kg. Liver function disturbance was reported in 2 cases. CONCLUSION: In order to optimize radical cure of P. vivax, the total primaquine dose per body weight should be considered, at least 3.5 mg/kg or even more if contracted in countries with significant drug resistance. Possibility of primaquine hepatotoxicity in chronic liver disease patients remains to be elucidated.
BACKGROUND: Recently, a dose of 30 mg (base) primaquine daily for 14 days is increasingly recommended for radical cure of Plasmodium vivaxmalaria. However, total primaquine doses, or those per body weight, are also recognized as important. In Japan, primaquine is not a licensed medicine, but has been used through the Research Group on Chemotherapy of Tropical Diseases for >3 decades. METHODS: Based on clinical records submitted to the Research Group, patients with P. vivax and Plasmodium ovale malaria treated with primaquine were analyzed to determine the efficacy and safety of the antimalarial drug. RESULTS: Seventy-five P. vivax cases, including 3 in children, and 19 P. ovale cases were enrolled. Five of the P. vivax cases demonstrated at least one relapse despite primaquine therapy. Total primaquine doses per body weight were obtained in 4 of the 5 relapsed patients, presenting 9 malaria episodes totally, and most of the primaquine failures were caused with a total dose ≤ 3.5 mg/kg. Liver function disturbance was reported in 2 cases. CONCLUSION: In order to optimize radical cure of P. vivax, the total primaquine dose per body weight should be considered, at least 3.5 mg/kg or even more if contracted in countries with significant drug resistance. Possibility of primaquinehepatotoxicity in chronic liver diseasepatients remains to be elucidated.