Acute Uncomplicated Malaria With P.Vivax Infection Clinical Trial
Official title:
An Open Label Randomized Comparison of Two Antimalarial Drugs Regimens in Patient With Plasmodium Vivax Malaria in Thailand
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.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment