Reply to Antinori et al

Clinical Infectious Diseases, May 2015

David A. Miller, Mahmoud M. Traina, Sheba K. Meymandi

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Reply to Antinori et al

CID TO THE EDITOR-We appreciate the additional experience and considerations of Antinori et al, including the occurrence of arthritis as an adverse event of benznidazole and Strongyloides coinfection. The prevalence of chronic Chagas disease in the United States is nearly 1 in 1000 [1], placing it outside of the National Institute of Health definition of rare diseases [2]. Yet the chagasic population remains largely undiagnosed, and therapeutic advancement remains hindered by the lagging development of sensitive and Reply to Antinori et al - timely markers for successful palliation or cure. Indices of treatment efficacy worthy of further investigation include novel serum biomarkers as well as localized modalities such as cardiac magnetic resonance imaging and positron emission tomography [3]. Meanwhile, the disease burden in the pauciendemic and nonendemic areas of North America and Europe, respectively, largely affects adults [1], in whom benznidazole and nifurtimox are less well tolerated. Dosing adjustments may conceivably alter the risk of toxicity, changing the threshold for therapy [4, 5], and perhaps enable treatment of patients with renal or hepatic dysfunction. Still, there remains no commercially available level testing for either drug. Although we look forward to publication of pharmacokinetic data from ongoing studies, we believe it will be wise to adopt a standardized method for benznidazole serum level monitoring to employ in routine treatment as a means to protect our patients and garner collective experience. Additionally, combination regimens may widen the therapeutic window [6]. We hope that community outreach, increased physician awareness, and blood bank screening will continue to increase capture of this at-risk population. Note Potential conflicts of interest. All authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 1. Bern C , Montgomery SP . An estimate of the burden of Chagas disease in the United States . Clin Infect Dis 2009 ; 49 : e52 - 4 . 2. National Institutes of Health. National Center for Advancing Translational Sciences. Office of Rare Diseases . Available at: http://raredis Accessed 10 March 2015 . 3. Prado C , Fine E , Kobaet W , et al. Micro-positron emission tomography in the evaluation of Trypanosoma cruzi-induced heart disease: comparison with other modalities . Am J Trop Med Hyg 2009 ; 81 : 900 - 5 . 4. Altcheh J , Moscatelli G , Mastrantonio G , et al. Population pharmacokinetic study of benznidazole in pediatric Chagas disease suggests efficacy despite lower plasma concentrations than in adults . PLoS Negl Trop Dis 2014 ; 8 : e2907 . 5. Pinazo MJ , Guerrero L , Posada E , et al. Benznidazole-related adverse drug reactions and their relationship to serum drug concentrations in patients with chronic Chagas disease . Antimicrob Agents Chemother 2013 ; 57 : 390 - 5 . 6. Bustamante JM , Craft JM , Crowe BD , et al. New, combined, and reduced dosing treatment protocols cure Trypanosoma cruzi infection in mice . J Infect Dis 2014 ; 209 : 150 - 62 . Correspondence: David A. Miller , MD, MPH, Division of Infectious Diseases, Harbor-UCLA Medical Center , 1000 W Carson St , Box 466 , Torrance, CA 90509 (dmiller.harbor@

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David A. Miller, Mahmoud M. Traina, Sheba K. Meymandi. Reply to Antinori et al, Clinical Infectious Diseases, 2015, 1875-1876, DOI: 10.1093/cid/civ232