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20 6.1.1 Reducing overall drug pressure

21 6.1.2 Improving the way drugs are used

21 6.1.3 Combination therapy

21 7. Conclusions and recommendations

23 7.1 Priorities

23 8. Bibliography

24 Figure and tables Figure 1. Approximate distribution of malaria

2 Table 1. Comparative descriptions of available malaria diagnostic methods

4 Table 2. Antimalarial drugs for uncomplicated malaria

6 Table 3. Distribution of drug-resistant Plasmodium falciparum malaria

10 DRUG RESISTANCE IN MALARIA WHO/CDS/CSR/DRS/2001.4 iv

1 WHO/CDS/CSR/DRS/2001.4 DRUG RESISTANCE IN MALARIA 1. Introduction of the greatest challenges facing malaria control today. Drug resistance has been implicated in the spread of malaria to new areas and re-emergence of malaria in areas where the disease had been eradi- cated. Drug resistance has also played a significant role in the occurrence and severity of epidemics in some parts of the world. Population movement has introduced resistant parasites to areas previously free of drug resistance. The economics of developing new pharmaceuticals for tropical diseases, includ- ing malaria, are such that there is a great disparity between the public health importance of the disease and the amount of resources invested in developing new cures (1, 2). This disparity comes at a time when malaria parasites have demonstrated some level of resistance to almost every anti- malarial drug currently available, significantly increasing the cost and complexity of achieving parasitological cure. The purpose of this review is to describe the state of knowledge regarding drug- resistant malaria and to outline the current thinking regarding strategies to limit the advent, spread, and intensification of drug-resistant malaria. Malaria remains an important public health concern in countries where transmission occurs regularly, as well as in areas where transmission has been largely controlled or eliminated. Malaria is a complex disease that varies widely in epidemiology and clinical manifestation in different parts of the world. This variability is the result of factors such as the species of malaria parasites that occur in a given area, their susceptibility to commonly used or available antimalarial drugs, the distribution and efficiency of mosquito vectors, climate and other environmental conditions and the behaviour and level of acquired immunity of the exposed human populations. In particular, young children, pregnant women, and non-immune visitors to malarious areas are at greatest risk of severe or fatal illness. Many malaria control strategies exist, but none are appropriate and affordable in all contexts. Malaria control and prevention efforts need to be designed for the specific environment in which they will be used and need to take into account the local epidemiology of malaria and the level of avail- able resources and political will. Antimalarial drug resistance has emerged as one DRUG RESISTANCE IN MALARIA WHO/CDS/CSR/DRS/2001.4

2 2. Diseaseincidenceandtrends (5) and the Medicines for Malaria Venture (6) a history of unpredictable support for malaria-related research and control activities in endemic countries have left many of these countries with little techni- cal capacity for malaria control activities. Each year an estimated

300 to

500 million clini- cal cases of malaria occur, making it one of the most common infectious diseases worldwide. Malaria can be, in certain epidemiological circumstances, a devastating disease with high morbidity and mor- tality, demanding a rapid, comprehensive response. In other settings, it can be a more pernicious pub- lic health threat. In many malarious areas of the world, especially sub-Saharan Africa, malaria is ranked among the most frequent causes of mor- bidity and mortality among children and is often the leading identifiable cause. WHO estimates that more than 90% of the 1.5 to 2.0 million deaths 2.1 Geographical distribution and populations at risk Malaria occurs in over