Biology subjects

Saunders, A. B.

Publications and source records attributed to Saunders, A. B..

3 recordsLinked to original sources

bioRxiv2023

Validation of a multiplex microsphere immunoassay for detection of Trypanosoma cruzi antibodies in dogs

The vector-borne protozoan parasite Trypanosoma cruzi causes Chagas disease in humans, dogs, and many other mammalian hosts. Canine Chagas disease is increasingly diagnosed in dogs of the southern US where triatomine insect vectors occur, and there are limited veterinary diagnostic options; currently, only the indirect fluorescent antibody (IFA) test is offered at a single accredited diagnostic laboratory. This study evaluated a multiplex microsphere immunoassay (MIA) for detecting antibodies against T. cruzi in dogs and compared with existing serological methods to establish cut-off values and relative sensitivity/specificity. Dog sera (n=135) which were previously characterized using the IFA and off-label use of two commercial rapid assays were tested on the multiplex MIA against 12 different antigens: nine T. cruzi antigens, a negative control recombinant protein (green fluorescent protein), a Leishmania antigen, and a canine parvovirus antigen (used as an antibody control given near-ubiquitous parvovirus vaccination). For each sample, the ratio of median fluorescence intensity (MFI) for each T. cruzi antigen to that of GFP was calculated. Samples with an antigen/GFP ratio greater than 4 standard deviations above the mean of 25 known negative sera were considered positive on that antigen. Samples testing positive on 2 or more antigens were considered positive for T. cruzi antibodies. Compared to the IFA, the multiplex MIA demonstrated a relative sensitivity of 100% and specificity of 96.97%. Given its precision, high-throughput format, potential for automation, and lack of subjective interpretation, the multiplex MIA should be considered a valid and improved assay for T. cruzi antibodies in dogs.

microbiology↗

bioRxiv2023

Frequency variation and dose modification of benznidazole administration for the treatment of Trypanosoma cruzi infection in mice, dogs and non-human primates

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 and in naturally infected dogs and non-human primates (NHP). Collectively these studies demonstrate that twice-weekly administration of BNZ for more than 4 months at doses that are [~]2.5-fold that of previously used daily dosing protocols, provided the best chance to obtain parasitological cure. Dosing less frequently or for shorter time periods was less dependable in all species. Prior treatment using an ineffective dosing regimen in NHPs did not prevent the attainment of parasitological cure with an intensified BNZ dosing protocol. Furthermore, parasites isolated after a failed BNZ treatment showed nearly identical susceptibility to BNZ as those obtained prior to treatment, confirming the low risk of induction of drug resistance with BNZ and the ability to adjust the treatment protocol when an initial regimen fails. These results provide guidance for the use of BNZ as an effective treatment for T. cruzi infection and encourage its wider use, minimally in high value dogs and at-risk NHP, but also potentially in humans, until better options are available.

microbiology↗

bioRxiv2021

Unprecedented incidence of Trypanosoma cruzi infections in a cohort of dogs directly detected through longitudinal tracking at multi-dog kennels, Texas, USA

Canine Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is increasingly recognized as a health concern for dogs in the USA, and infected dogs may signal geographic regions of risk for human disease. Dogs living in multi-dog kennel environments where triatomine vectors are endemic may be at high risk for infection. We monitored a cohort of 64 T. cruzi-infected and uninfected dogs from across 10 kennels in Texas, USA, to characterize changes in infection status over time. We used robust diagnostic criteria in which reactivity on multiple independent platforms was required to be considered positive. Among the 30 dogs enrolled as serologically- and/or PCR-positive, all but one dog showed sustained positive T. cruzi diagnostic results over time. Among the 34 dogs enrolled as serologically- and PCR-negative, 10 new T. cruzi infections were recorded over a 12-month period. The resulting incidence rate was 30.7 T. cruzi infections per 100 dogs per year. This study highlights the risk of T. cruzi infection to dogs in kennel environments, despite multiple vector control methods employed by kennel owners. To protect both dog and human health, there is an urgent need to develop more integrated vector control methods as well as prophylactic and curative antiparasitic treatment options for T. cruzi infection in dogs.

zoology↗