Efficacy of primaquine regimens for primaquine-resistant Plasmodium vivax malaria in Thailand.

Abstract

Abstract. To define the current efficacy of Fansidar (F. Hoffmann-La Roche Ltd., Basel Switzerland) (pyrimethamine and sulfadoxine), primaquine in a high dose, and artesunate for treating acute Plasmodium vivax malaria, we conducted a comparative clinical trial of these 3 drugs in an open-label study. Patients (15-65 years old) were assigned to 1 of 4 treatments regimens in a serial order. Ninety percent of the patients were infected at Thailand-Myanmar border. Patients in group I (n ϭ 23) received Fansidar (3 tablets, 75 mg of pyrimethamine and 1,500 mg of sulfadoxine, a single dose on the first day), group II (n ϭ 23) received Fansidar (3 tablets, 75 mg of pyrimethamine and 1,500 mg of sulfadoxine, a single dose on the first day) and then received primaquine (30 mg a day for 14 days), group III (n ϭ 23) received primaquine (30 mg a day for 14 days), and group IV (n ϭ 23) received artesunate (200 mg once a day for 3 days) and then primaquine (30 mg a day for 14 days). Cure rates on day 28 of follow-up were 40%, 100%, 100%, and 100% in groups I, II, II, and IV, respectively. There were 4 and 5 patients in group I showing post-treatment reappearance of parasitemia at Յ 16 days and between 17 and 28 days, respectively. Patients in the other 3 groups showed negative parasitemias within 7 days after treatment. Artesunate plus primaquine (group IV) cleared parasitemia faster than the other 3 regimens. There is a high proportion of ineffectiveness of Fansidar for treatment of P. vivax malaria and it should be no longer used for treatment of P. vivax malaria acquired at the Thailand-Myanmar border. A high dose of primaquine is safe and effective in the treatment of P. vivax malaria during the 28-day follow-up period.Plasmodium vivax causes a clinically benign illness but relapse is frequent. It is a common cause of malaria in Asia and South America. In a recent study among a population residing on the western border of Thailand, P. vivax was found in 2,573 (54%) of 4,728 persons over a period of 2 years.

Identification of cryptic coinfection with Plasmodium falciparum in patients presenting with vivax malaria.

“…Dipsticks are now available to do this. In malaria-endemic areas of Thailand, although the inoculation rate is low (approximately one infectious bite per person-year) 26 double infections with P. falciparum and P. vivax detected after parasite clearance for one species are common [2][3][4][5][6] ; approximately 1 in 10 patients with vivax malaria developed subsequent P. falciparum malaria, [4][5][6] and ϳ 1 in 3 with falciparum malaria developed subsequent vivax malaria. 2,3 In Thailand, the standard recommended regimen for vivax malaria treatment is chloroquine for 3 days, followed by primaquine for 2 weeks to eradicate exoerythrocytic forms.…”

“…This finding concurs with our earlier observations. [4][5][6] The majority (85%) of these mixed infections were still negative for P. falciparum on microscopy, even when rechecked by an experienced mi-croscopist. This might in part have resulted from the difficulty in differentiating the young ring forms of P. falciparum and P. vivax.…”

“…24,25 However, the late ap- pearance of one species after curative therapy for another (without reexposure) is common. [2][3][4][5][6] Approximately 10% of the patients in this study experienced subsequent P. falciparum parasitemia after P. vivax clearance. This finding concurs with our earlier observations.…”

“…1 Plasmodium vivax relapse after curative treatment for P. falciparum, or subsequent appearance of P. falciparum after P. vivax clearance, occurs in ϳ 30% of cases. [2][3][4][5][6] Mixed infections with P. falciparum and P. vivax are clinically unpredictable. In Thailand, as in many parts of the world, P. falciparum is highly chloroquine resistant 7 and therefore is not suppressed by conventional treatment of vivax malaria.…”

Therapeutic Efficacies of Artesunate-Sulfadoxine-Pyrimethamine and Chloroquine-Sulfadoxine-Pyrimethamine in Vivax Malaria Pilot Studies: Relationship to Plasmodium vivax dhfr Mutations

“…Despite the coexistence of falciparum and vivax malaria in many parts of the world where malaria treatment is usually based on clinical diagnosis, there have been few studies assessing the efficacy of artemisinin derivatives in treating vivax malaria and none in the area of CQ-resistant P. vivax. Studies of artesunate (ART) monotherapy for P. vivax infection have demonstrated rapid clearance of fever and parasites (1,6,33,43). However, with its very short half-life, no ART remains by the time of the first relapse of P. vivax infection, approximately 3 weeks after treatment begins, resulting in a high frequency of 28-day treatment failure with ART monotherapy (33).…”