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              Guidelines for the treatment of malaria – 2  edition


            and P. ovale are generally less prevalent, but they are distributed worldwide, especially in
            the tropical areas of Africa. Further information on treatment is provided in Annex 9.

            Among the four species of Plasmodium that affect humans, only P. vivax and P. ovale
            form hypnozoites, parasite stages in the liver, which can result in multiple relapses of
            infection weeks to months after the primary infection. Thus, a single infection causes
            repeated bouts of illness. The objective of treating malaria caused by P. vivax and P. ovale
            is to cure (radical cure) both the blood stage and the liver stage infections, and, thereby,
            prevent both recrudescence and relapse, respectively. Infection with P. vivax during
            pregnancy, as with P. falciparum, reduces birth weight. In primigravidae, the reduction
            is approximately two thirds of that associated with P. falciparum (110 g compared with
            170 g), but this adverse effect does not decline with successive pregnancies, unlike with
            P. falciparum infections.


            9.1  diagnosis

            The clinical features of uncomplicated malaria are too non-specific for a clinical diagnosis
            of the species of malaria infection to be made. Diagnosis of P. vivax malaria is based on
            microscopy. Although rapid diagnostic tests based on immunochromatographic methods
            are available for the detection of non-falciparum malaria, their sensitivities below parasite
            densities of 500/µl are low. Their relatively high cost is a further impediment to their
            wide use in endemic areas. Molecular markers for genotyping P. vivax parasites have
            been developed to assist epidemiological and treatment studies, but these are still under
            evaluation.


            9.2  susceptibility of P. vivax, P. ovale and P. malariae to antimalarials

            There are very few recent data on the in vivo susceptibility of P. ovale and P. malariae
            to antimalarials. Both species are regarded as very sensitive to chloroquine, although
            there is a single recent report of chloroquine resistance in P. malariae. Experience
            indicates that P. ovale and P. malariae are also susceptible to amodiaquine, mefloquine
            and the artemisinin derivatives. Their susceptibility to antifolate antimalarials, such as
            sulfadoxine-pyrimethamine, is less certain.
            P. vivax susceptibility has been studied extensively and, now that short-term culture
            methodologies have been standardized, clinical studies have been supported by in vitro
            observations. P. vivax is generally still sensitive to chloroquine, although resistance is
            prevalent and increasing in some areas (notably Indonesia, Peru and Oceania). Resistance
            to pyrimethamine has increased rapidly in some areas, and sulfadoxine-pyrimethamine
            is, consequently, ineffective. There are insufficient data on current susceptibility to
            proguanil and chlorproguanil, although resistance to proguanil was selected rapidly
            when it was first used in P. vivax endemic areas.
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