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( Pukrittayakamee et al., 2010 ) but its use as monotherapy would be neither
optimal nor advisable.
Prevention of recrudescence by total eradication of asexual blood-stage
parasitaemia is critically important for reducing P. vivax transmission. For
a drug to completely sterilise the blood, it needs to be at or above the
minimum inhibitory concentration for as many asexual cycles as it takes
to remove the very last parasite, or at least to reduce parasitaemia to a level
at which the human's immune system can remove the residuum ( White,
1999 ). Parasite multiplication rate, drug potency and drug elimination half-
life govern the total duration of treatment required, which in turn is a key
determinant of drug adherence. Optimal patient adherence can theoretically
be achieved by using a single-dose drug regimen.
Chloroquine has high potency against sensitive P. vivax strains and is
slowly eliminated allowing a practical 3-day treatment regimen. It is cheap
and well tolerated and, therefore, has been the drug of choice for vivax
malaria since the mid-twentieth century. Resistance of P. vivax to this drug is
spreading from a presumed epicentre in New Guinea ( Douglas et al., 2010 ;
Baird, 2009 ). In the worst-affected areas such as in Papua New Guinea,
Eastern Indonesia, the western parts of India and Western Thailand, a sig-
nificant proportion of P. vivax infections will persist, and thus recrudesce,
in the face of high chloroquine concentrations ( Karunajeewa et al., 2008 ;
Baird et al., 1995 , 1997 ; Sumawinata et al., 2003 ; Sutanto et al., 2009 ; Rijken
et al., 2011 ; Singh, 2000 ). In Papua New Guinea and Eastern Indonesia,
over half of the P. vivax infections recrudesce within 28 days of treatment
( Karunajeewa et al., 2008 ; Baird et al., 1995 , 1997 ; Sumawinata et al., 2003 ;
Sutanto et al., 2009 ). Although the degree of chloroquine resistance is less
severe in other vivax-endemic areas, there is clear evidence that the efficacy
of chloroquine is declining in many of these places ( Douglas et al., 2010 ).
Currently, the most effective schizontocidal treatment of P. vivax is a 3-day
course of an artemisinin derivative in combination with a highly active,
but more slowly eliminated, partner drug ( Ratcliff et al., 2007 ; Hasugian
et al., 2007 ; Karunajeewa et al., 2008 ; Awab et al., 2010 ; Poravuth et al.,
2011 ; Phyo et al., 2011 ). The rapidly eliminated artemisinin component
quickly clears the bulk of the parasite biomass and the more slowly elimi-
nated partner drug persists long enough to remove any remaining parasites.
Artemisinin-combination therapies currently recommended by the World
Health Organization for falciparum malaria include artemether plus lume-
fantrine (AM + LUM), artesunate plus amodiaquine (AS + AQ), artesunate
plus mefloquine (AS + MQ), artesunate plus sulfadoxine-pyrimethamine
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