Background

Global malaria control is being threatened on an unprecedented scale by a rapidly growing resistance of Plasmodium falciparum to current monotherapies such as chloroquine, sulfadoxine-pyrimethamine (SP) and amodiaquine. Multi-drug resistant falciparum malaria is widely prevalent in South-East Asia and South America. Now Africa, the continent with the highest burden of malaria is also being seriously affected by drug resistance.

WHO recommendations

As a response to the antimalarial drug resistance situation, WHO recommends that treatment policies for falciparum malaria in all countries experiencing resistance to monotherapies should be combination therapies, preferably those containing an artemisinin derivative (ACT - artemisinin-based combination therapy).

The therapeutic options currently recommended by WHO are listed below:

1. artemether/lumenfantrine

2. artesunate plus amodiaquine

3. artesunate plus SP (in areas where SP efficacy remains high)

4. amodiaquine plus SP, in areas where efficacy of both amodiaquine and SP remains high (mainly limited to West Africa).

5. artesunate plus megloquine, an additional recommended combination treatment which is reserved for areas of low transmission.

The current WHO policy on antimalarial treatment is based on the recommendations and conclusions of two consultations of international experts on malaria chemotherapy, held in November 2000 and April 2001.

Over the last three years 20 countries (7 in Africa) have updated their treatment policies to include ACTs as either first-or second-line treatment of malaria. This was based on WHO advice, and was made possible with the participation of RBM partners and increased mobilization of international funding.

In 2002 the Global Fund to fight AIDS, Tuberculosis and Malaria was established, and it has become one of the main international funding mechanisms to support the implementation of highly effective interventions for the control of these three diseases in endemic developing countries. The Global Fund is now the largest financial supporter of ACTs in countries. It has committed a total of US$ 30 million over the 5-year life of the Global Fund Board-approved proposals from African countries for the purchase of ACTs in three proposal rounds. Moreover, as a result of flexibility in the use of funds committed to these programs, even more funds may be allocated to purchase ACTs as countries continuously evaluate their drug policies and how to best utilize grants from the Global Fund. Indeed a number of recipient countries in Africa, which originally requested funding for chloroquine, are already in the process of re-evaluating their drug policies towards the use of ACTs, examples being Senegal, Ghana, Benin, Mali, Chad, and Gambia. In addition to the Global Fund, national Governments and RBM partners, such as UN Organizations, Bilateral Agencies and NGOs (MSF in particular) have contributed to the sourcing and financing of ACTs in Africa.

The single non artemisinin-based combination therapy (amodiaquine plus SP) listed among WHO recommended options is reserved for countries which are unable to move into ACTs. However, the following limitations of this option should be noted:

1. The number of countries, where efficacy of both amodiaquine and SPis high, is limited and restricted mainly to West Africa.

2. As both amodiaquine and SP are currently used widely as mono-therapies it is unlikely that the adoption of this combination therapy will significantly delay the spread of resistance to either drug. Therefore, the adoption of CT with amodiaquine plus SP is likely to be a short-term solution.

3. Even in areas where the efficacy of both amodiaquine and SP remain high, their combined use will compromise the useful therapeutic life of both, and thus endanger their potential use as partner drugs for artesunate in ACTs.

4. There is currently no replacement for SP as a drug for Intermittent Preventive Treatment (IPT) in pregnancy. Rather than compromise its therapeutic life by using it as a component of a CT, SP should be reserved for IPT.

5. As the process of drug policy change and implementation is resource - and time-intensive (experience shows it to take from one to three years), all efforts for improving access to treatment should be directed towards implementing the most effective and durable treatment policy.

One of the principal reasons for countries wishing to adopt non artemisinin-based combinations (CTs) is their lower price. However, multiple financial mechanisms are now available in countries, and international support is being mobilized to help countries adopt ACTs, and an increasing number of countries are now replacing ineffective mono-therapies with ACTs rather than CTs.

To facilitate access to ACTs, WHO has, in collaboration with UNICEF, established a system for pre-qualification of manufacturers of artemisinin derivatives, negotiated price agreements with manufacturers, engaged in international procurement, and set up systems of pharmacovigilance in early use countries. A service for malaria medicines and supplies is now being established by WHO and RBM partners to facilitate access to ACTs. This will be a component of a larger facility for improving access to medicines and supplies for HIV/AIDS, TB and Malaria.

Conclusions

Consistent with WHO recommendations, malaria endemic countries which are experiencing resistance to currently used monotherapy antimalarial medicines (chloroquine, SP or amodiaquine) should change treatment policies to the more effective ACTs.