2023
DOI: 10.1101/2023.02.01.526739
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Frequency variation and dose modification of benznidazole administration for the treatment ofTrypanosoma cruziinfection in mice, dogs and non-human primates

Abstract: Trypanosoma cruzi naturally infects a broad range of mammalian species and frequently results in the pathology that has been most extensively characterized in human Chagas disease. Currently employed treatment regimens fail to achieve parasitological cure of T. cruzi infection in the majority of cases. In this study, we have extended our previous investigations of more effective, higher dose, intermittent administration protocols using the FDA-approved drug benznidazole (BNZ), in experimentally infected mice a… Show more

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Cited by 7 publications
(18 citation statements)
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“…The objective of using a dosing protocol is to administer benznidazole at a higher dose for a longer duration of time to treat actively replicating and dormant parasites. 10,11,19 In mice, a modified dosing regimen with weekly or twice weekly administration of benznidazole at a dose 2.5 to 5 times the standard daily dose successfully eradicated established T cruzi infection. 19 A similar regimen also cured a proportion of dogs and nonhuman primates.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The objective of using a dosing protocol is to administer benznidazole at a higher dose for a longer duration of time to treat actively replicating and dormant parasites. 10,11,19 In mice, a modified dosing regimen with weekly or twice weekly administration of benznidazole at a dose 2.5 to 5 times the standard daily dose successfully eradicated established T cruzi infection. 19 A similar regimen also cured a proportion of dogs and nonhuman primates.…”
Section: Discussionmentioning
confidence: 99%
“…In mice, a modified dosing regimen with weekly or twice weekly administration of benznidazole at a dose 2.5 to 5 times the standard daily dose successfully eradicated established T cruzi infection 19 . A similar regimen also cured a proportion of dogs and nonhuman primates 10 . Our recent study investigated the prophylactic use of a similar protocol for preventing T cruzi infection in dogs 11 .…”
Section: Discussionmentioning
confidence: 99%
“…Although other serological methods such as IFA and rapid immunoassays have been used extensively in diagnostic and research settings and are considered validated for those purposes based on human literature and correlation with clinical signs, few previous studies have been conducted which quantify their performance in terms of sensitivity and specificity relative to a gold standard. The multiplex MIA has been used in previous studies to test dogs, humans, nonhuman primates, and mice 3,5,12 ; however, this is the first study to estimate its sensitivity/specificity for diagnostic purposes. While this study determined an optimal single cutoff point of 2 positive antigens to balance the inverse relationship between sensitivity and specificity, when implementing this assay in a true diagnostic setting, it may be most useful to utilize a three-tiered approach bracketing cut-off values to maximize both values (i.e., classifying samples as negative below the cut-off which gives 100% sensitivity, positive at the cut-off which gives 100% specificity, and "suspect" in between).…”
Section: Discussionmentioning
confidence: 99%
“…Additional studies with known Leishmania- positive and -negative samples, from areas in which T. cruzi exposure is unlikely, could ultimately provide more definitive answers to this question. Other studies 2,3 have used different sets of T. cruzi proteins in the multiplex assay, and one of the advantages of the multiplex platform is the ability to expand or modify antigens to optimize the test. If implementing our assay in settings in which more definitive discrimination from Leishmania positivity is crucial (e.g., where infection with either pathogen is possible), additional proteins unique to T. cruzi may be added to increase specificity.…”
Section: Discussionmentioning
confidence: 99%
“…Although other serologic methods, such as IFA and rapid ICTs, have been used extensively in diagnostic and research settings and are considered validated for those purposes based on human literature and their correlation with clinical signs, few previous studies have been conducted that quantify their sensitivity and specificity relative to a gold standard. The multiplex MIA has been used in studies to test dogs, humans, non-human primates, and mice 3,5,12 ; however, sensitivity and specificity had not been estimated for diagnostic purposes. Although we determined an optimal single cutoff point of 2 positive antigens to balance the inverse relationship between sensitivity and specificity, when implementing our assay in a true diagnostic setting, it may be most useful to utilize a 3-tiered approach bracketing cutoff values to maximize both values (i.e., classifying samples as negative below the cutoff that gives 100% sensitivity, positive at the cutoff that gives 100% specificity, and “suspect” in between).…”
Section: Discussionmentioning
confidence: 99%