Blood stage infection with Plasmodium vivax can usually be treated successfully with chloroquine, though resistance is spreading in some areas (notably the Pacific Islands, Papua New Guinea, parts of south-east Asia and especially Indonesia, and Peru). P. vivax is also sensitive to artemisinin-based combination therapies (ACTs) and as no resistance to artemisinin has been reported, these are widely recommended (though combinations which include sulfadoxine-pyrimethamine should be avoided as many strains of P. vivax appear to be resistant to pyrimethamine).

Liver stage (i.e. relapsing) P. vivax can only be treated with one drug: primaquine. Instances of liver stage treatment failure are relatively commonplace, and may be strain or dosage dependent. Primaquine is not recommended for people with G6DP deficiency, so potential patients, and particularly those from locations or ethnic groups known to have high levels of G6DP deficiency, should be tested prior to treatment.

For more plz read at following link.

Regards

http://www.malaria.com/questions/treatment-of-chronic-vivax-malaria

Thanks, Ali. Actually, these matters are covered in the background document (website link given in the original question, but the article is not "open access"), as well as a theoretical temporary blood stage dormancy point that is unrelated to what was asked. The question is very specific pharmacologically. It is concerned with something outside the realms of current general understanding of the treatment of malaria and the conventional view of the life cycle of Plasmodium vivax (see the background publication).

Hello Markus,

As we are aware of the fact that  P.vivax malaria recurrence after drug treatment may have 1 of 3 origins: recrudescence originating fromasexual blood-stage parasites that survived drug treatment, reinfection resulting from a new mosquito inoculation, or relapse arising from the dormant liver stages (hypnozoites). 

One study conducted in the fields of India, Thailand, and Myanmar latter published in the Journal of Infectious Diseases in 2007, found that,  majority of episodes of recurrent vivax malaria presumably arose from hypnozoites that became reactivated after treatment of the initial acute infection. There are 2 generic explanations for this: either (1) there was simultaneous inoculation of different genotypes by a single mosquito or by different mosquitoes within a short period (i.e., 1 or 2 days); or (2) multiple inoculations occurred over a longer period, and the acute infection activated dormant hypnozoites originating from an earlier inoculation. If the first explanation is correct, then either the primary infection with the relapse genotype is at a density below the PCR-genotyping detection level or there is no primary infection and these later emerging parasites have a longer incubation period. The hypnozoites of different parasite strains may have different fixed periods of dormancy, as in the P. vivaxstrains from temperate and tropical zones. However, how activation of the hypnozoites of heterologous genotype occurs is unknown. Previously acquired genotype-specific immunity might preferentially suppress one genotype but would be inconsistent with the appearance of the suppressed genotype some 3 weeks later. A more likely explanation is that genotype-specific immunity develops only against the predominant blood-stage parasites in the mixed-genotype primary infection and that it preferentially suppresses this genotype when it later emerges at relapse. This would imply a threshold parasitemia for the induction of protective antibody responses. More information on the P. vivax genotypes carried by mosquitoes would help to resolve the question of inoculation times. More-sensitive genotype-specific detection methods would resolve the question of whether initial infections contain more genotypes. Irrespective of the timing of inoculation, these data indicated that the hypnozoites activated after treatment usually arise from a subset of sporozoites different from that which caused the initial infection. This implies an unexpected and remarkable regulation of within-host phenotypic behavior among different strains.

Therefore, genotyping analysis of vivax malaria indicates a high rate of mixed-genotype infections even in settings where transmission is low, and it suggests a hitherto unsuspected phenomenon of heterologous activation of hypnozoite populations.

Thanks, Ranjita. Since I coined the term "hypnozoite" in the 1970s and the hypnozoite theory of relapse in malaria was formulated soon thereafter, a "new" matter has arisen. You mentioned 3 origins of recurrent P. vivax malaria. This question is related to a 4th possible origin only (see via the DOI link given in the original question, if you are able to access the article). It was suggested in 2011. Also, leaving aside my own ideas as to the answer, this is a specialized pharmacological question rather than a malarial question per se.

i agree with Ranjita Santra 

i agree with Ranjita Santra 

The question was on a different subject.

Dr Markus,

I have no answer for your question. But I have found it very interesting.

Have you had any development?

Best regards.

Thanks for the comment and enquiry, C. There is nothing further on this, but if something happens, I'll let you know! Kind regards, Miles 

Primaquine itself is not active, but must be metabolized to generate metabolites which are active. It is possible that something interfered with primaquine metabolism so that these active metabolites were not generated.

Many thanks, Michael. This is exactly what I had been (partly) thinking.

P.S.: Also, I wondered whether the metabolites won't necessarily work equally well in all parts of the body where there are parasites - bearing in mind that apart from presumed anti-hypnozoite activity, primaquine also has merozoitocidal and gametocytocidal effects (to whatever extent).