Modifying national malaria treatment policies in Peru.

Between 1998 and 2001, the Peruvian Ministry of Health made sweeping changes in its malaria treatment policies in response to a resurgence of disease and the spread and intensification of antimalarial drug resistance. On the Pacific Coast, the first-line treatment for uncomplicated Plasmodium falciparum malaria was changed to combination therapy with sulfadoxine-pyrimethamine plus artesunate; in the Amazon region, mefloquine-artesunate combination therapy was introduced. With these changes in treatment policy, Peru became the first country in the Americas to use combination therapy with an artemisinin drug as its first-line treatment for falciparum malaria and the first country in the world to use two different drug combination therapy regimens based on an artemisinin drug in different regions of the country. This paper describes the process involved in assessing the geographic distribution and intensity of antimalarial drug resistance throughout the country and the use of that information to guide decisions related to national malaria treatment policy.

Evaluation of a simple operational approach for monitoring resistance to antimalarial drugs in Peru.

Since 1994, the Peruvian Malaria Control Program has used a simplified operational approach for monitoring antimalarial drug efficacy, in which blood smears are taken 7 and 14 days after treatment from all patients diagnosed with malaria at Ministry of Health facilities. The proportion of patients with parasitaemia on one of their return visits provides an indication of the efficacy of the drug being administered. We compared this approach for antimalarial drug resistance monitoring to the more labour-intensive and expensive World Health Organization (WHO) 14-day in vivo efficacy trial at six sites in the Amazon Basin and the north coast of Peru. Although the proportion of treatment failures at 7 and 14 days identified by the operational monitoring system was considerably lower than the results of the WHO in vivo efficacy test, the operational approach did accurately reflect the overall efficacy or lack of efficacy of the drugs being evaluated. Differences in the results of the two methods were greatest in the Peruvian Amazon region, where fully supervised treatment and patient follow-up is very difficult due to the widely dispersed population. While the operational approach cannot be considered an alternative to WHO in vivo testing for evaluating the efficacy of antimalarial drugs or for recommending changes in malaria treatment policy, if treatment is supervised and follow-up blood smears taken as scheduled, this method could serve as a simple, inexpensive and sustainable early warning system for reduced drug efficacy.

Practical aspects of in vivo antimalarial drug efficacy testing in the Americas.

The World Health Organization (WHO) has developed guidelines for in vivo antimalarial drug efficacy testing for Plasmodium falciparum and Plasmodium vivax in areas with low-to-moderate transmission, such as the Americas. These guidelines are used widely by ministries of health and national malaria control programs to assess the efficacy of their first-line and second-line drugs for the treatment of malaria and to provide the information necessary to update national malaria treatment policies. Following the WHO guidelines, we have conducted in vivo efficacy trials with a variety of drugs and drug combinations against P. falciparum and P. vivax at 13 sites in Peru, Bolivia, and Ecuador. Based on these experiences, we have identified several modifications that we believe should be made in the WHO recommendations to make them more suitable to the relatively low levels of P. falciparum transmission in the Americas and to the logistic challenges of carrying out such studies in sparsely populated areas, such as the Amazon Basin. These include changes in inclusion and exclusion criteria, in enrollment and follow-up procedures, and in the measurement of study outcomes.