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Resisting change? Tackling drug-resistant malaria

Malaria affects 300 - 500 million people worldwide each year and causes 1.5 - 2.7 million deaths, mostly among African children. This total would be even higher without the widespread availability of cheap and reasonably effective antimalarial drugs. But drug resistance is increasing. How can we stop the death toll rising? A research programme established by a WHO/TDR task force is tackling this question.

Chloroquine (CQ) has been central to antimalarial treatment for the past 50 years. But CQ resistance is widespread and malaria mortality has risen. Resistance to a second drug, sulphadoxine/pyrimethamine (SP), is well established in south-east Asia and parts of Latin America, and is growing in Africa. Multi-drug resistant malaria has emerged in areas of south-east Asia. Alternative drugs include mefloquine (MQ), halofantrine, quinine combined with doxycycline, amodiaquine or an oral artemisinin (AS) drug. But many of these are unaffordable in most malaria-endemic countries.

There are two ways to tackle the problem of resistance:

develop drugs with different or novel modes of action
use combinations of current drugs that work in different ways, in particular AS-based combinations.

Extensive use of AS combined with MQ on the Thai-Myanmar border has been highly effective over the past seven years. Would this combination be equally beneficial in sub-Saharan Africa, where malaria epidemiology is very different? The study aims to:

compile efficacy and safety profiles of AS combinations to identify those which can be used to treat malaria in the field
validate clinical and laboratory markers of antimalarial drug resistance to predict resistance early and assess the effect of these new interventions
develop and facilitate a policy framework for addressing antimalarial drug resistance
strengthen the drug supply chain from the initial raw material to patient use in order to provide good quality, setting-specific, affordable drugs.

The research represents the largest ever series of antimalarial drug trials, with patients enrolled in 11 sites in Africa. Results show that:

Amodiaquine is effective in west and central Africa, but efficacy is declining in east Africa.
The addition of AS increases efficacy. So a combination of amodiaquine and AS could be used in Africa.
SP efficacy is high in west Africa, but considerably lower in east Africa. While adding AS improves efficacy, it is questionable whether AS and SP should be used in east Africa.
Because of the high failure rates of chloroquine, there are no plans to develop CQ-AS combinations, even though this significantly improves activity.

Researchers and policy-makers must also address implementation issues. Some of these are operational and include evaluating feasibility and sustainability, and assessing whether and how combinations can prevent or delay the emergence of resistance and reduce malaria transmission. Other issues are structural and affect the sustainability of these new interventions:

developing policy instruments
addressing financial factors
producing and supplying high quality affordable drugs
transferring the relevant drug production technologies to developing countries.

Source(s):
'Controlling malaria: challenges and solutions', Tropical Medicine and International Health 6 (11): 922-927, by P. Olliaro, W. Taylor and J. Rigal, 2001
HINARI subscribers can access the full-text article here. Full document.

Funded by: Italian government; Portuguese government; French Ministry of Foreign Affairs; USAID; World Health Organisation; the Wellcome Trust; MSF/Epicentre

id21 Research Highlight: 21 March 2002

Further Information:
Piero Olliaro
UNDP/World Bank/WHO Special Program for Research and Training in Tropical
Diseases (TDR)
1211 Geneva 27
Switzerland

Fax: +41 22 791 4774/4854
Contact the contributor: olliarop@who.int

World Health Organisation

Special Programme for Research and Training in Tropical Diseases (TDR)

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