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Submitted by Patrícia Correia (patriciacorreia@ua.pt) on 2019-03-15T14:55:11Z No. of bitstreams: 1 Jackson et al. - 2011 - Protein translation in Plasmodium parasites.pdf: 684505 bytes, checksum: 38edf99c4713c8361d6b05fa3378c49e (MD5) Approved for entry into archive by Patrícia Correia (patriciacorreia@ua.pt) on 2019-03-15T14:55:27Z (GMT) No. of bitstreams: 1 Jackson et al. - 2011 - Protein translation in Plasmodium parasites.pdf: 684505 bytes, checksum: 38edf99c4713c8361d6b05fa3378c49e (MD5) Made available in DSpace on 2019-03-15T14:55:27Z (GMT). No. of bitstreams: 1 Jackson et al. - 2011 - Protein translation in Plasmodium parasites.pdf: 684505 bytes, checksum: 38edf99c4713c8361d6b05fa3378c49e (MD5) Previous issue date: 2011 The authors are funded by an European Union FP7 Collaborative Project Grant HEALTH-F3-2009-223024 – Mephitis. S.A.R. is funded by Australian Research Council Future fellowship FT0990350. The authors acknowledge and apologize to the authors of many important studies in this field whose findings had to be omitted or referred to only via review papers owing to space constraints. published

The emergence of artemisinin resistance could adversely impact the current strategy for malaria treatment; thus, new drugs are urgently needed. A possible approach to developing new antimalarials is to find new uses for old drugs. Some anticancer agents such as methotrexate and trimetrexate are active against malaria. However, they are commonly perceived to be toxic and thus not suitable for malaria treatment. In this opinion article, we examine how the toxicity of anticancer agents is just a matter of dose or ‘only dose makes the poison’, as coined in Paracelsus’ law. Thus, the opportunity exists to discover new antimalarials using the anticancer pharmacopoeia.

Because of inadequacies in national health information systems, the volumes of drugs required to support an effective policy transition toward artesunate-based combination therapy (ACT) are unknown for most African countries. A series of national surveys and population projections have been used to estimate the age-structured fever burden among 41 malaria endemic countries in Africa. Under present fever-management guidelines, commodity costs and internationally agreed coverage targets, the financial resources to meet the needs of ACT in most African countries are huge. Between US$1.6 billion and US$3.4 billion per annum must be found to give Africa the chance to consider a drug policy based on ACT. Substantial reductions in these costs would be achieved through more effective targeting of resources--only 20% of drugs would be required to manage fevers among the most at-risk pediatric patient populations. Better diagnostics would also be an important consideration for a new ACT policy in Africa.

Antimalarial drug efficacy in uncomplicated malaria should be assessed parasitologically in large, community-based trials, enrolling the age groups most affected by clinical disease. For rapidly eliminated drugs, a 28-day follow-up is needed, but, for slowly eliminated drugs, up to nine weeks could be required to document all recrudescences, and, when possible, the drug levels should also be measured. The WHO 14-day assessments are neither sensitive nor specific. In tropical Plasmodium vivax and Plasmodium ovale infections treated with chloroquine, the first relapse is usually suppressed by residual drug levels. A relapse cannot be distinguished confidently from a recrudescence. Host immunity is a major contributor to the therapeutic response, and can make failing drugs appear effective.