Monitoring and deterring drug-resistant malaria in the era of combination therapy
ABSTRACT As chloroquine and sulfadoxine-pyrimethamine (SP) are replaced by more effective artemisinin-based combination therapies (ACTs), strategies for monitoring (and, if possible, deterring) drug-resistant malaria must be updated and optimized. In vitro methods for measuring resistance will be critical for confirming and characterizing resistance to ACTs. Molecular markers are useful for tracking the emergence and dissemination of resistance and guiding treatment policy where resistance is low or moderate. Genomic approaches may help identify molecular markers for resistance to artemisinins and their partner drugs. Studies of reported ACT treatment failure should include assessing factors other than resistance that affect efficacy, including pharmacokinetics. Longitudinal clinical trials are particularly useful for comparing the benefits and risks of repeated treatment in high transmission settings. The malaria research and control community should not fail to exploit this opportunity to apply the lessons of the last 50 years to extend the useful therapeutic lives of ACTs.
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- "ACT regimens may be more effective for IPT than SP alone, but this has not been demonstrated. Resistance to SP is rapidly increasing throughout much of Africa (Laufer et al. 2007; Talisuna et al. 2007), which may reduce its effectiveness for use in IPT. Furthermore, there is some evidence that IPT with SP may encourage the development of resistance (Sokhna et al. 2008), although data are conflicting (Greenwood 2007). "
ABSTRACT: To assess the efficacy of intermittent preventive treatment (IPT) against malaria in school-aged children. This was an open randomized controlled trial of seasonal IPT among school children (IPTsc) aged 6-13 years in Kollé, Mali. The study began in September 2007 and completed follow-up in May 2008. Students were randomized to one of three study arms: Sulfadoxine-pyrimethamine plus artesunate (SP/AS), amodiaquine plus artesunate (AQ/AS) or vitamin C. All students received two full treatment doses, given 2 months apart during the season of high transmission from September to December. Groups were compared with respect to incidence of clinical malaria, asymptomatic parasitemia and haemoglobin concentration. A total of 296 students were randomized, and retention in the study was 99.3%. Clinical malaria incidence in the SP/AS and AQ/AS arms was reduced by 66.6% and 46.5%, respectively, vs. vitamin C (P < 0.001). There were fewer clinic visits for any cause among the children receiving SP/AS or AQ/AS (P = 0.024). The prevalence of asymptomatic parasitemia was fivefold higher in the vitamin C arm than either SP/AS or AQ/AS at each post-treatment evaluation (P < 0.001). At the end of the transmission period, children treated with IPT had lower rates of anaemia (SP/AS, 17.7%; AQ/AS, 16.0%; vitamin C, 29.6%; P = 0.039). IPT among school children reduced the rates of clinical malaria, all-cause acute clinic visits, asymptomatic parasitemia and anaemia among school-aged children.Tropical Medicine & International Health 06/2009; 14(7):784-91. DOI:10.1111/j.1365-3156.2009.02294.x · 2.30 Impact Factor
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- "Our goal is to determine the genetic structure and gene flow of malaria parasite populations, and to provide baseline mutation frequencies at the onset of large-scale ACT application for malaria control. The baseline mutation frequency information is useful in tracking the evolution of genes associated with SP-and CQ-resistance when SP and CQ selection pressure on malaria parasites is relaxed, and in the deployment of appropriate antimalarial drugs (Laufer et al., 2007). "
ABSTRACT: Human travel to malaria endemic lowlands from epidemic highlands has been shown to increase the risk of malaria infections in the highlands. In order to gain insight on the impact of human travel, we examined prevalence, genetic variability and population genetic structure of Plasmodium falciparum in asymptomatic children from one highland site and three surrounding malaria endemic lowland sites in Western Kenya, using multilocus microsatellite genotyping. We further analyzed the frequencies of mutations at the genes conferring resistance to chloroquine and sulfadoxine-pyrimethamine. We found a significant decrease in malaria prevalence in the highland site from 2006 to 2007, 1 year after the introduction of the artemisinin-based combination therapy as first-line treatment for uncomplicated malaria and the scale-up of insecticide-treated bed nets. Population genetic diversity, measured by the number of observed and effective microsatellite alleles and Nei's unbiased genetic diversity, was high and comparable for both highland and lowland populations. Analysis of molecular variance did not detect a significant genetic structure across highland and lowland regions. Similarly, mutations at key antimalarial-resistance codons of the pfcrt, pfmdr1, pfdhfr and pfdhps genes were found at comparable high frequencies in all four sites. High level of gene flow and lack of significant genetic structure in malaria parasites between highland and lowland areas suggest the importance of human travel in shaping parasite population structure.Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 05/2009; 9(5):806-12. DOI:10.1016/j.meegid.2009.04.015 · 3.26 Impact Factor
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ABSTRACT: The use of antimicrobial drugs has saved countless lives and reduced the morbidity of infectious diseases. However, the growing threat from resistant microorganisms calls for cost-effective interventions to prevent the emergence of new resistant strains and the spread of existing ones. One approach to reduce the incidence of infections due to antibiotic-resistant organisms is to control the inappropriate use of antibiotics in both the hospital and community settings. In order to achieve this goal, it is necessary to identify the factors involved in physician’s antibiotic prescription patterns and to elaborate educational interventions that can be adapted to different clinical scenarios. Several studies in developed countries have shown the potential benefit of these interventions. However, developing countries pose a special situation as they lack adequate pharmacological surveillance systems, antimicrobial drugs are widely available to the public (even without prescription), and continuous medical education programs for physicians are non-existent. The implementation of educational programs directed to the judicious use of antimicrobial drugs might probe to be the most efficient intervention in developing countries in the worldwide battle against antimicrobial resistance.