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 still generally very sensitive to chloroquine, although resistance is prevalent and increasing in some areas, notably Oceania, Indonesia and Peru (see Annex A.6.4). 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. In general, P. vivax is sensitive to all the other antimalarial drugs; it is more sensitive than P. falciparum to the artemisinin derivatives, and slightly less sensitive to mefloquine (although mefloquine is still effective). In contrast to P. falciparum, asexual stages of P. vivax are susceptible to primaquine. Thus chloroquine + primaquine can be considered as a combination treatment. The only drugs with significant activity against the hypnozoites are the 8-amino-quinolines (bulaquine, primaquine, tafenoquine). There is no standardized in vitro method of drug assessment for hypnozoiticidal activity. In vivo assessment suggests that tolerance of P. vivax to primaquine in East Asia and Oceania is greater than elsewhere.