To optimize the benefit of deploying ACTs, and to have an impact on malaria, it will be necessary to deploy them as widely as possible - this means at most peripheral health clinics and health centres, and in the community. Deployment through the formal public health delivery system alone will not reach many of those who need treatment. In several countries, they must also be available through the private sector. Ultimately, effective treatment needs to be available at community or household level in such a way that there is no financial or physical barrier to access. The strategy to secure full access must be based on an analysis of the national and local health systems, and will often require adjustment based on programme monitoring and operational research. The dissemination of clear national treatment guidelines, use of appropriate information, education and communication materials, monitoring both of the deployment process, access and coverage and provision of adequately packaged and presented antimalarials are needed to optimize the benefits of providing these new effective treatments widely.
7.7.1 Health education
At all levels, from the hospital to the community, education is vital to optimizing antimalarial treatment. Clear guidelines in the language understood by the local users, posters, wall charts, educational videos and other teaching materials, public awareness campaigns, education of and provision of information materials to shopkeepers and other dispensers can all improve the understanding of malaria and the likelihood of improved prescribing and adherence, appropriate referral, and minimizing the unnecessary use of antimalarials.
7.7.2 Adherence to treatment
To achieve the desired therapeutic effectiveness, a drug must be intrinsically efficacious and must be taken in the correct doses at the proper intervals. Patient adherence is a major determinant of the response to antimalarials, as most treatments are taken at home without medical supervision. There have been few studies of adherence. These suggest that 3-day regimens of medicines such as ACTs are adhered to reasonably well, provided that patients or carers are given an adequate explanation at the time of prescribing. Prescribers, shopkeepers or vendors should therefore give a clear and comprehensible explanation of how to use the medicines. Co-formulation is probably a very important contributor to adherence. User-friendly packaging, such as blister packs, also encourage completion of the treatment course and correct dosing.
7.7.3 Quality assurance of antimalarial medicines
Many of the antimalarials available in malaria endemic areas are substandard in that the manufacturing processes have been unsatisfactory, or their pharmaceutical properties do not meet the required pharmacopoeial specifications. Counterfeit tablets and ampoules containing no antimalarials are a major problem in some areas. These may result in fatal delays in appropriate treatment, and may also give rise to a mistaken impression of resistance. WHO, in collaboration with other United Nations agencies, has established an international mechanism to pre-qualify manufacturers of artemisinin compounds and ACTs on the basis of compliance with internationally-recommended standards of manufacturing and quality. It is the responsibility of national ministries of Health and regulatory authorities to ensure the quality of antimalarials provided through both the public and private sectors, through regulation, inspection and law enforcement.
Rare but serious adverse effects are often not detected in clinical trials and can only be detected through pharmacovigilance systems operating in situations of wide population use. There are few data from prospective Phase IV post-marketing studies on rare but potentially serious adverse effects of antimalarials. Chloroquine has the best-documented adverse effect profile. The safety profiles of the artemisinin derivatives, mefloquine and sulfadoxine-pyrimethamine are supported by a reasonable evidence base, but mainly from large clinical trials.
The neurotoxicity observed in animals treated with artemisinin derivatives has prompted large prospective assessments in humans, but no evidence of neurotoxicity has been found. Concerns over the risk of severe liver or skin reactions to sulfadoxine-pyrimethamine treatment have receded with increasing numbers of negative reports. More data are needed on the newer drugs and on amodiaquine as well. There is also an urgent need to obtain more information on the safety of antimalarials, in particular the ACTs, in pregnancy. It is recommended that countries or regions should consider establishing pharmacovigi-lance systems if they have not already done so.