Comparison of Two Antimalarial Drugs Regimens in Patient With Plasmodium Vivax Malaria in Thailand

Overview

In Thailand, the proportion of P.vivax infection has now been increasing and is equal to Plasmodium falciparum since 1998. The incidence of P.vivax has recently been reported as 20 per 1000 population per year. Unlike Plasmodium falciparum, P.vivax infection rarely develops into complicated malaria and death is unusual. However, P.vivax has a dormant stage (the hypnozoite) that persists in the human liver and may cause relapse weeks, months, or even years later. Therefore, P.vivax infection is considered to have greater impact on morbidity than mortality, resulting in significant social and economic burden. Moreover, it is very difficult to control P.vivax transmission, because gametocytes appear almost simultaneously with schizonts. Radical treatment of the infection, therefore, normally consists of a blood schizontocidal course of chloroquine and a course primaquine for the elimination of the hypnozoites as anti-relapse therapy. In Thailand, chloroquine and primaquine have remained the mainstay chemotherapeutics for the treatment of P.vivax for more than 60 years and resistance has not yet been reported . The relapse rates at day 28 are about 50% without primaquine therapy and about 20% with standard primaquine therapy. Relapse has not been observed among patients receiving high dose primaquine therapy (30 mg daily for 14 days). Since January 2007, the evidence of reduced susceptibility of Plasmodium falciparum to artemisinins in Western Cambodia at Thai-Cambodia border was first presented and confirmed in a subsequent detailed pharmacokinetic-pharmacodynamic study. Nevertheless, a trend of gradual decline of in vitro sensitivity to chloroquine has been documented in some areas of the country, particularly Thai-Myanmar border. There has been no clinical-parasitological evidence of chloroquine resistant P.vivax in Thai-Cambodia border, Thailand. The objectives of the present study are to assess in vivo efficacy of first line regimen of chloroquine given with primaquine, and in vitro susceptibility of P.vivax isolates in areas along Thai-Cambodia border, Thailand.

Plasmodium vivax affects 70-80 million cases of malaria worldwide annually, is the major cause of human malaria in parts of Pacific region and South America. In Thailand, the proportion of P.vivax infection has increased and it is now equal to Plasmodium falciparum since 1998. The incidence of P.vivax has recently been reported as 20 per 1000 population per year. Unlike Plasmodium falciparum, P.vivax infection rarely develops into complicated malaria and death is unusual. However, P.vivax has a dormant stage (the hypnozoite) that persists in the human liver and may cause relapse weeks, months, or even years later. Therefore, P.vivax infection is considered to have greater impact on morbidity than mortality, resulting in significant social and economic burden. Moreover, it is very difficult to control P.vivax transmission, because gametocytes appear almost simultaneously with schizonts. Radical treatment of the infection, therefore, normally consists of a blood schizontocidal course of chloroquine and a course primaquine for the elimination of the hypnozoites as antirelapse therapy. However, chloroquine-resistant P.vivax (CRPv) has been emer-ging in different parts of the world. The first report of chloroquine resistant Plasmodium vivax was in 2 Australian soldiers returning from Papua New Guinea in Indonesia and is now spreading over Asia and the Pacific region. In Thailand, chloroquine and primaquine have remained the mainstay chemotherapeutics for the treatment of P.vivax for more than 60 years and resistance has not yet been reported. Occasional failure of the standard primaquine therapy (15 mg daily for 14 days) to prevent relapse has been observed. However, primaquine resistance has not been confirmed. In Thailand, the relapse rates at day 28 are about 50% without primaquine therapy, and about 20% with standard primaquine therapy. Relapse has not been observed among patients receiving high dose primaquine therapy (30 mg daily for 14 days). A number of factors are reportedly associated with relapse, or the reappearance of P.vivax, including inadequate primaquine dosage, high parasitaemia at diagnosis, and short duration of symptoms prior to diagnosis, presence of gametocytes on admission, age, and gender. Because the radical cure of P.vivax hypnozoites requires 14 days of primaquine therapy, adherence to the drug regimen may greatly affect the prevention of relapse. Unfortunately, the effect of patient adherence on 14 day primaquine treatment, and its relation to preventing parasite reappearance, is not well-document. Since January 2007, the evidence of reduced susceptibility of Plasmodium falciparum to artemisinins in Western Cambodia at Thai\_Cambodia border was first presented and confirmed in a subsequent detailed pharmacokinetic-pharmacodynamic study. Nevertheless, a trend of gradual decline of in vitro sensitivity to chloroquine has been documented in some areas of the country, particularly Thai-Myanmar border. There has been no clinical-parasitological evidence of chloroquine resistant P.vivax in Thai-Cambodia border, Thailand. The objectives of the present study are to assess in vivo efficacy of first line regimen of chloroquine given with primaquine, and in vitro susceptibility of P.vivax isolates in areas along Thai-Cambodia border, Thailand.