Biology subjects

Ribeiro, I.

Publications and source records attributed to Ribeiro, I..

4 recordsLinked to original sources

bioRxiv2021

High variation in immune responses and parasite phenotypes in naturally acquired Trypanosoma cruzi infection in a captive non-human primate breeding colony in Texas, USA

Trypanosoma cruzi, the causative agent of human Chagas disease, is endemic to the southern region of the United States where it routinely infects many host species. The indoor/outdoor housing configuration used in many non-human primate research and breeding facilities in the southern U.S. provides the opportunity for infection by T. cruzi and thus provides source material for in-depth investigation of host and parasite dynamics in a natural host species under highly controlled and restricted conditions. For cynomolgus macaques housed at such a facility, we used a combination of serial blood quantitative PCR (qPCR) and hemoculture to confirm infection in >92% of seropositive animals, although each method alone failed to detect infection in >20% of cases. Parasite isolates obtained from 43 of the 64 seropositive macaques were of 2 broad genetic types (discrete typing units, (DTUs) I and IV); both within and between these DTU groupings, isolates displayed a wide variation in growth characteristics and virulence, elicited host immune responses, and susceptibility to drug treatment in a mouse model. Likewise, the macaques displayed a diversity in T cell and antibody response profiles that rarely correlated with parasite DTU type, length of infection, or age of the primate. This study reveals the complexity of infection dynamics, parasite phenotypes, and immune response patterns that can occur in a primate group, despite being housed in a uniform environment at a single location, and the limited time period over which the T. cruzi infections were established. Author SummaryWe evaluated naturally occurring infections of Trypanosoma cruzi, the causative agent of human Chagas disease, in an indoor/outdoor primate colony at a breeding facility in Texas, USA. Using serial quantitative PCR and hemoculture, we confirmed infection in 92% of the 64 seropositive animals, but neither of these two methods confirmed more than 80% of the cases. Parasites by hemoculture fell into two genetic groups (discrete typing units I and IV), and displayed large variation in growth characteristics, elicited cellular and humoral immune responses as well as virulence and drug susceptibility when tested in mice. EKG abnormalities were found in 13 out of 51 qPCR-positive macaques. Our results demonstrate the complexity of these infection parameters in this colony in spite of the uniform and geographically constrained housing conditions of the macaques.

microbiology↗

bioRxiv2018

A pharmacokinetic-pharmacodynamic assessment of the hepatic and bone-marrow toxicities of the new trypanoside fexinidazole

Fexinidazole is a novel oral treatment for Trypanosoma brucei gambiense human African trypanosomiasis: g-HAT. Fexinidazole is also active against other kinetoplastid parasites, notably T. cruzi the causative agent of Chagas disease.During the course of a dose ranging assessment in chronic indeterminate Chagas disease, delayed neutropenia and significant increases in hepatic transaminases were observed and clinical investigations were suspended. We retrospectively analyzed all available pharmacokinetic and pharmacodynamic data on fexinidazole in normal healthy volunteers and in patients with chronic Chagas disease and g-HAT, in order to assess the determinants of toxicity.\n\nA population pharmacokinetic model was fitted to plasma concentration data on the bioactive fexinidazole sulfone metabolite from three phase 1 studies, two g-HAT phase 2/3 field trials and one Chagas phase 2 field trial (462 individuals in total). Bayesian exposure-response models were then fitted to hematological and liver related pharmacodynamic outcomes in chronic Chagas patients.\n\nNeutropenia, reductions in platelet counts, and elevations in liver transaminases were all found to be exposure and thus dose dependent in patients with chronic Chagas disease. Clinically insignificant transient reductions in neutrophil and platelet counts consistent with these exposure-response relationships were observed in the g-HAT trials. In contrast, no evidence of hepatotoxicity was observed in the g-HAT trials.\n\nFexinidazole treatment results in a dose dependent liver toxicity and transient bone marrow suppression in Chagas disease. Regimens of shorter duration should be trialled for Chagas. The currently recommended regimen for sleeping sickness provides exposures within a satisfactory safety margin for bone marrow suppression and does not cause hepatotoxicity.

pharmacology and toxicology↗

bioRxiv2018

Remotely sensed indicators and open-access biodiversity data to assess bird diversity patterns in Mediterranean rural landscapes.

Changes in ecosystem area are often used to assess human impacts on habitats and estimate biodiversity change. However, because species respond to structural changes at fine spatial scales the use of area alone may not capture all relevant changes. Operational costs limit the assessment of biodiversity change at a simultaneously fine spatial resolution and large scales. The development of cost-effective and expedite methods to monitor biodiversity change is therefore required. We use open access satellite imagery and biodiversity data to investigate the importance of variables of habitat extent and structure in explaining species richness and community dissimilarity of forest and open-land birds at the regional scale. Moreover, because Mediterranean landscapes are subject to seasonal dynamics, we explore the indicator value of remotely sensed variables measured in spring and summer. A large-scale dataset of bird occurrence data, including 8042 observations and 78 species, distributed by 40 landscape-sized cells, was assembled from GBIF after controlling for data quality. We found that summer satellite imagery, when the green perennial vegetation is more apparent, is particularly suited to model the diversity patterns of forest species, because distribution of tree cover in the landscape is well captured. Summer data is also useful to monitor the perennial elements that shape landscape structure and the habitat of open-land species. Specifically, mean NDVI and a second-order NDVI texture variable, were found to be good indicators of forest and open-land habitats, respectively. The use of spring imagery appears to be useful to monitor habitat structure within open-land habitat patches. Overall, NDVI texture measures were found to be good predictors of bird diversity patterns at large scales. Also, we were able to successfully conduct a regional scale analysis using open-access data, which illustrates their potential to inform large scale biodiversity monitoring.

ecology↗

bioRxiv2018

Real Time PCR for the Evaluation of Treatment Response in Clinical Trials of Adult Chronic Chagas Disease: Usefulness of Serial Blood Sampling and qPCR Replicates.

This work evaluated a serial blood sampling procedure to enhance the sensitivity of duplex real time PCR (qPCR) for baseline detection and quantification of parasitic loads and post-treatment identification of failure in the context of clinical trials for treatment of chronic Chagas disease, namely DNDi-CH-E1224-001 (NCT01489228) and MSF-DNDi PCR sampling optimization study (NCT01678599). Patients from Cochabamba (N= 294), Tarija (N = 257), and Aiquile (N= 220) were enrolled. Three serial blood samples were collected at each time-point, and qPCR triplicates were tested per sample. The first two samples were collected during the same day and the third one seven days later.\n\nA patient was considered PCR positive if at least one qPCR replicate was detectable. Cumulative results of multiple samples and qPCR replicates enhanced the proportion of pre-treatment sample positivity from 54.8 to 76.2%, 59.5 to 77.8%, and 73.5 to 90.2% in Cochabamba, Tarija, and Aiquile cohorts, respectively and increased cumulative detection of treatment failure from 72.9 to 91.7%, 77.8 to 88.9%, and 42.9 to 69.1% for E1224 low, short, and high dosage regimes, respectively; and from 4.6 to 15.9% and 9.5 to 32.1% for the benznidazole (BZN) arm in the DNDi-CH-E1224-001 and MSF-DNDi studies, respectively. The monitoring of patients treated with placebo in the DNDi-CH-E1224-001 trial revealed fluctuations in parasitic loads and occasional non-detectable results. This serial sampling strategy enhanced PCR sensitivity to detecting treatment failure during follow-up and has the potential for improving recruitment capacity in Chagas disease trials which require an initial positive qPCR result for patient admission.

microbiology↗