Reply to Antinori et al
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 , placing it outside of the National Institute of Health definition of rare diseases . 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
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
. Meanwhile, the disease burden in the
pauciendemic and nonendemic areas of
North America and Europe, respectively,
largely affects adults , 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 .
We hope that community outreach,
increased physician awareness, and blood
bank screening will continue to increase
capture of this at-risk population.
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 eases.info.nih.gov/resources/2/rare-diseasesresources. 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@ gmail.com).