The main conclusions and recommendations agreed at the Informal Consultation are set out below.

5.1 General

1. There are regional differences in patterns of antimalarial drug resistance in countries and policy options should reflect these differences.
2. Previous documentation has suggested that a therapeutic failure rate of
3. 25% is a useful indicator for change in antimalarial treatment policy. However, it is acknowledged that the decision to change will depend on country circumstances. Because of the time required to implement a change in policy (usually 2-3 years), the evaluation of potential alternatives should begin as soon as failure of the specific drug starts to emerge.
4. It is broadly acknowledged that the options available to countries for improved antimalarial treatment policies are limited, especially in regions of highest resource constraints such as sub-Saharan Africa. In many instances, the lack of resources has resulted in countries continuing the use of drugs whose effectiveness is limited by drug resistance.
5. The potential value of drug combinations, notably those including an artemisinin derivative, to improve efficacy, delay development and selection of drug-resistant parasites and thus prolong the useful therapeutic life of existing antimalarial drugs is widely accepted. Combinations that do not contain an artemisinin derivative could be a preferred option for reasons of cost and accessibility in some countries.
6. Combination therapy could be a viable option for countries that already have widespread resistance of P. falciparum to chloroquine, amodiaquine and sulfadoxine- pyrimethamine, provided issues of cost and complexity of implementation can be addressed.
7. Amodiaquine, not recommended for chemoprophylaxis by WHO due to bone marrow and hepatic toxicity following prophylactic use, deserves re-evaluation as a potential therapeutic replacement for chloroquine. It may have particular value as a low-cost component in combination therapy. Results from further clinical trials on safety and efficacy are awaited.
8. Amodiaquine should be given at a therapeutic dose of 30 mg/kg over 3 days (10 mg/kg daily for 3 days) for simplicity of administration in place of the previously recommended 25- 35 mg/kg.
9. The role of intramuscular artemether/arteether as an alternative to intravenous quinine because of simplicity of administration and less frequent dosing schedule in the management of severe malaria in complex emergency situations is re-emphasized.
10. The lack of validated, safe and effective preventive therapies for use in pregnancy in epidemic situations, especially in areas with multidrug-resistant P. falciparum was noted and needs to be addressed urgently.
11. Choice of specific options for antimalarial combination therapy for different epidemiological settings, particularly in Africa, was not on the agenda of this meeting. Given the agreed potential of such options, a further technical meeting to review available evidence and make recommendations on antimalarial combination therapy should be convened.
12. Effective antimalarial treatment policies will rely on access to drugs that are significantly more expensive than chloroquine, amodiaquine and sulfadoxine-pyrimethamine. Appropriate political and institutional actions and improved financing are prerequisites to successful advances in this area. These issues deserve immediate serious attention, especially for Africa.

5.2 Future research and other activities

1. There is an urgent need for field research, linked to appropriate pharmaceutical product development, to assess the effectiveness of potential combination therapies that include artemisinin and its derivatives in different epidemiological and health system settings in Africa.
2. The effectiveness of other combinations (not including an artemisinin derivative) with cheaper and already available antimalarial drugs such as 4-aminoquinoline and sulfa drugs for use in Africa should also be explored. This should also be linked to appropriate pharmaceutical product development.
3. Amodiaquine toxicity and its potential cross-resistance with chloroquine require further evaluation as these characteristics may limit the useful therapeutic life of this antimalarial drug.
4. Studies should be conducted to determine whether the continued use of certain drugs as monotherapy will compromise their usefulness as a component of combination therapies.
5. There is an urgent need for more information on and improved options for preventive intermittent treatment in pregnancy and for treatment in complex emergency situations.
6. Studies should be conducted to evaluate the potential of pre-referral use of a single application of rectal artesunate capsules in endemic countries in Africa.
7. Further data are required on factors affecting access to treatment, including health-seeking behaviours, in endemic countries.
8. There is a need for a continuing monitoring system for antimalarial sensitivity patterns, especially in Africa where stronger information bases and inter-country exchanges are required. Efforts should be made to intensify support for resistance monitoring and to develop improved easy-to-use tools, kits and methodologies to facilitate this activity.
9. Sustainable drug discovery and development activities are required to ensure future improvements in malaria chemotherapy.
10. Greater engagement between researchers and decision-makers is essential to ensure that research informs policy and that policy and control needs inform research.
11. Substantial strengthening of health systems is needed to enable them to deliver and promote rationale use and wider access to antimalarial chemotherapy.

A meeting planned for 2001 will address strategy development, resource mobilization and public-private partnerships for improving access to antimalarial drugs.