Studies on Adding Artesunate to Existing Antimalarial Therapies With Chloroquine, Amodiaquine & Sulphadoxine-pyrimethamine in Pakistan

The incidence of falciparum malaria in Pakistan has risen 6-fold over the last 15 years and chloroquine resistance is prevalent in every malarious area examined. Chloroquine's position as first line treatment must be reconsidered. Resistance to the favoured second-line treatment, sulphadoxine-pyrimethamine SP, is 10% and rising fast. It is critical to preserve the effective life of SP by using it in combination with a non-related fast-acting antimalarial such as artesunate (AS). It is conceivable that use of AS in combination with chloroquine itself might even recover the latter's effectiveness and restrain the selection of stronger levels of chloroquine resistance. To determine the tolerability and efficacy of AS combination therapy in the subcontinent, randomized controlled trials will be conducted by HealthNet International and government staff, with technical support from LSHTM, in Afghan refugee camps in Pakistan against the current therapies of chloroquine, amodiaquine and SP. Current policy is to use primaquine(PQ) as the gametocytocidal drug with CQ or SP. It is not clear whether this has any value in the face of high levels of CQ resistance. The efficacy of PQ in combination with CQ or SP will be examined in individual randomised trial in comparison with CQ or SP alone.

In the past, treatment of falciparum and vivax malaria was with chloroquine. With development of drug resistance treatment of the two species is diverging and this places higher priority on accurate differential diagnosis which cannot always be met at peripheral health posts. There may be advantage in harmonising treatment of the two species with ACT. Thus the current treatment for vivax, chloroquine, shall be compared with that of ACT with artesunate and SP, the likely ACT to be adopted for falciparum malaria.

Protocol design:

Randomised, single-blind, controlled trials comparing for falciparum malaria (1) artesunate (AS) and chloroquine (CQ), vs CQ alone, vs CQ and primaquine (PQ); (2) AS and sulphadoxine-pyrimethamine (SP), vs SP alone, vs SP and PQ; (3) AS and amodiaquine (AQ), vs AQ alone.

Randomised, single-blind, controlled trial comparing for vivax malaria: AS and sulphadoxine-pyrimethamine (SP), vs CQ alone.