Background Chagas disease is a zoonotic disease caused by the protozoan parasite Trypanosoma cruzi . The role of dogs as sentinels has been proposed in multiple regions, as they are a domestic reservoir for T. cruzi. Our objective was to determine the prevalence of T. cruzi infection in shelter dogs from southern Louisiana, and assess its magnitude and distribution. Results A total of 540 dogs were enrolled, from 20 animal shelters, and tested for T. cruzi infection by serological tests (rapid test, ELISA and western blot) and PCR. We documented a high prevalence of T. cruzi infection with at least 6.9% (95% CI: 5.0–9.3%) seropositive and 15.7% (95% CI: 12.9–19.1%) PCR-positive dogs. Serological tests showed limited agreement, and concordance between serology and PCR was higher when considering reactivity to single serological tests. Trypanosoma cruzi infection was distributed evenly among shelters. Infection was significantly correlated with age ( R 2 = 0.99), indicating an incidence of new cases of 2.27 ± 0.25% per year. Conclusion Trypanosoma cruzi infection is a significant and widespread veterinary problem in shelter dogs in the region, although it is mostly unnoticed by health professionals. This highlights the need for greater awareness of T. cruzi infection among the veterinary community and dog owners. Electronic supplementary material The online version of this article (10.1186/s13071-019-3572-y) contains supplementary material, which is available to authorized users.

Object Glioblastoma multiforme (GBM) is an aggressive brain cancer with median survival of less than two years with current treatment. GBM exhibits extensive intra-tumor and inter-patient heterogeneity, suggesting that successful therapies should exert broad anti-cancer activities. Therefore, the natural non-toxic pleiotropic agent, resveratrol, was studied for anti-tumorigenic effects against GBM. Methods Resveratrol’s effects on cell proliferation, sphere-forming ability, and invasion were tested using multiple patient-derived GBM stem-like cell (GSC) lines and established U87 glioma cells, and changes in oncogenic AKT and tumor suppressive p53 were analyzed. Resveratrol was also tested in vivo against U87 glioma flank xenografts using multiple delivery methods, including direct tumor injection. Finally, resveratrol was delivered directly to brain tissue to determine toxicity and achievable drug concentrations in the brain parenchyma. Results Resveratrol significantly inhibited proliferation in U87 glioma and multiple patient-derived GSC lines, demonstrating similar inhibitory concentrations across these phenotypically heterogeneous lines. Resveratrol also inhibited the sphere-forming ability of GSCs, suggesting anti-stem cell effects. Additionally, resveratrol blocked U87 glioma and GSC invasion in an in vitro Matrigel transwell assay at doses similar to those mediating anti-proliferative effects. In U87 glioma cells and GSCs, resveratrol reduced AKT phosphorylation and induced p53 expression and activation that led to transcription of downstream p53 target genes. Resveratrol administration via oral gavage or ad libitum in the water supply significantly suppressed GBM xenograft growth; intra-tumor or peri-tumor resveratrol injection further suppressed growth and approximating tumor regression. Intracranial resveratrol injection resulted in 100-fold higher local drug concentration compared to intravenous delivery, and with no apparent toxicity. Conclusions Resveratrol potently inhibited GBM and GBM stem-like cell growth and infiltration, acting partially via AKT deactivation and p53 induction, and suppressed glioblastoma growth in vivo. The ability of resveratrol to modulate AKT and p53, as well as reportedly many other anti-tumorigenic pathways, is attractive for therapy against a genetically heterogeneous tumor such as GBM. Although resveratrol exhibits low bioavailability when administered orally or intravenously, novel delivery methods such as direct injection (i.e. convection enhanced delivery) could potentially be used to achieve and maintain therapeutic doses in brain. Resveratrol’s non-toxic nature and broad anti-GBM effects make it a compelling candidate to supplement current GBM therapies.

Background Chagas disease is a neglected zoonosis of growing concern in the southern US, caused by the parasite Trypanosoma cruzi. We genotyped parasites in a large cohort of PCR positive dogs to shed light on parasite transmission cycles and assess potential relationships between parasite diversity and serological test performance. Methodology/principal findings We used a metabarcoding approach based on deep sequencing of T. cruzi mini-exon marker to assess parasite diversity. Phylogenetic analysis of 178 sequences from 40 dogs confirmed the presence of T. cruzi discrete typing unit (DTU) TcI and TcIV, as well as TcII, TcV and TcVI for the first time in US dogs. Infections with multiple DTUs occurred in 38% of the dogs. These data indicate a greater genetic diversity of T. cruzi than previously detected in the US. Comparison of T. cruzi sequence diversity indicated that highly similar T. cruzi strains from these DTUs circulate in hosts and vectors in Louisiana, indicating that they are involved in a shared T. cruzi parasite transmission cycle. However, TcIV and TcV were sampled more frequently in vectors, while TcII and TcVI were sampled more frequently in dogs. Conclusions/significance These observations point to ecological host-fitting being a dominant mechanism involved in the diversification of T. cruzi-host associations. Dogs with negative, discordant or confirmed positive T. cruzi serology harbored TcI parasites with different mini-exon sequences, which strongly supports the hypothesis that parasite genetic diversity is a key factor affecting serological test performance. Thus, the identification of conserved parasite antigens should be a high priority for the improvement of current serological tests.

Background Trypanosoma cruzi - the causative agent of Chagas disease - is known to circulate in commensal pests, but its occurrence in urban environments is not well understood. We addressed this deficit by determining the distribution and prevalence of T. cruzi infection in urban populations of commensal and wild rodents across New Orleans (Louisiana, USA). We assessed whether T. cruzi prevalence varies according to host species identity and species co-occurrences, and whether T. cruzi prevalence varies across mosaics of abandonment that shape urban rodent demography and assemblage structure in the city. Methods Leveraging city-wide population and assemblage surveys, we tested 1428 rodents comprising 5 species (cotton rats, house mice, Norway rats, rice rats and roof rats) captured at 98 trapping sites in 11 study areas across New Orleans including nine residential neighborhoods and a natural area in Orleans Parish and a neighborhood in St. Bernard Parish. We also assayed Norway rats at one site in Baton Rouge (Louisiana, USA). We used chi-square tests to determine whether infection prevalence differed among host species, among study areas, and among trapping sites according to the number of host species present. We used generalized linear mixed models to identify predictors of T. cruzi infection for all rodents and each host species, respectively. Results We detected T. cruzi in all host species in all study areas in New Orleans, but not in Baton Rouge. Though overall infection prevalence was 11%, it varied by study area and trapping site. There was no difference in prevalence by species, but roof rats exhibited the broadest geographical distribution of infection across the city. Infected rodents were trapped in densely populated neighborhoods like the French Quarter. Infection prevalence seasonally varied with abandonment, increasing with greater abandonment during the summer and declining with greater abandonment during the winter. Conclusions Our findings illustrate that T. cruzi can be widespread in urban landscapes, suggesting that transmission and disease risk is greater than is currently recognized. Our findings also suggest that there is disproportionate risk of transmission in historically underserved communities, which could reinforce long-standing socioecological disparities in New Orleans and elsewhere.