Retrospective study of the mortality of the Vieira's titi monkey (Plecturocebus vieirai) at the Sorocaba Zoo, Brazil.

BACKGROUND: The Vieira's titi monkey (Plecturocebus vieirai) was recently described and characterized as endemic to Brazil. According to the IUCN red list, this species is classified as critically endangered (CR). At the date of the publication of this manuscript, there are no published data on the health aspects of this species. METHODS: For this study, the necropsy, and histopathological data of the mortality of P. vieirai at Sorocaba Zoo (São Paulo, Brazil) were collected and analyzed. RESULTS: Causes of death diagnosed included disorders of the urinary, gastrointestinal, immune, and circulatory systems. CONCLUSIONS: This study provides information regarding the pathological conditions of P. vieirai and points to urinary and gastrointestinal diseases as the main causes of death in this species at Sorocaba Zoo. These results can help veterinarians who have this species under their care diagnose and deal with it more quickly, increasing the probability of survival.

Molecular detection of Sarcocystis sp. in a kept under human care black capuchin monkey (Sapajus nigritus., Goldfuss 1809) with necrotizing encephalitis.

A senile male black capuchin monkey (Sapajus nigritus) kept under human care in a Zoo was found dead after 2 weeks presenting signals of weight loss and hyporexia. Histopathological revealed a necrotizing encephalitis. Although it was not observed microscopically, Sarcocystis sp infection was detected in brain tissue from molecular assays. These infections have been rarely described in neotropical primates, particularly associated with tissue lesions.

Natural mycobacterium tuberculosis complex infection in a brown howler monkey (Alouatta guariba clamitans) in Brazil.

Neotropical primates rarely exhibit active tuberculosis. A brown howler monkey was found injured in an urban area. Histopathology revealed granulomatous inflammation in the lungs, lymph nodes, and liver. Immunohistochemistry and molecular analysis confirmed the presence of Mycobacterium tuberculosis complex. The findings highlight the importance of TB surveillance in nonhuman primates.

Slc11a1 gene polymorphism influences dextran sulfate sodium (DSS)-induced colitis in a murine model of acute inflammation.

Ulcerative Colitis (UC) is an inflammatory disease characterized by colonic mucosal lesions associated with an increased risk of carcinogenesis. UC pathogenesis involves environmental and genetic factors. Genetic studies have indicated the association of gene variants coding for the divalent metal ion transporter SLC11A1 protein (formerly NRAMP1) with UC susceptibility in several animal species. Two mouse lines were genetically selected for high (AIRmax) or low (AIRmin) acute inflammatory responses (AIR). AIRmax is susceptible, and AIRmin is resistant to DSS-induced colitis and colon carcinogenesis. Furthermore, AIRmin mice present polymorphism of the Slc11a1 gene. Here we investigated the possible modulating effect of the Slc11a1 R and S variants in DSS-induced colitis by using AIRmin mice homozygous for Slc11a1 R (AIRminRR) or S (AIRminSS) alleles. We evaluated UC by the disease activity index (DAI), considering weight loss, diarrhea, blood in the anus or feces, cytokines, histopathology, and cell populations in the distal colon epithelium. AIRminSS mice have become susceptible to DSS effects, with higher DAI, IL6, G-CSF, and MCP-1 production and morphological and colon histopathological alterations than AIRminRR mice. The results point to a role of the Slc11a1 S allele in DSS colitis induction in the genetic background of AIRmin mice.

Naturally Acquired Rabies in White-Eared Opossum, Brazil.

Opossums are considered resistant to rabies. Nonhematophagous bats are reservoirs of rabies in urban areas of South America. We analyzed bats and opossums tested for rabies during 2021 in a highly urbanized city in Brazil to understand spillover in an urban setting. Wildlife surveillance is necessary to prevent rabies in humans and domestic animals.

Disseminated Mucor indicus infection in a marmoset (Callithrix sp.).

Mucormycosis is rarely described in Platyrrhines. Herein, we describe the pathologic and molecular features of a gastric and hepatic infection by Mucor indicus in a marmoset (Callithrix sp.).

Effects of Tezepelumab on Quality of Life of Patients with Moderate-to-Severe, Uncontrolled Asthma: Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: To assess the effects of tezepelumab on quality of life (QoL) in patients with moderate-to-severe, uncontrolled asthma. RECENT FINDINGS: Tezepelumab improves pulmonary function tests (PFTs) and reduces the annualized asthma exacerbation rate (AAER) in patients with moderate-to-severe, uncontrolled asthma. We searched MEDLINE, Embase, and Cochrane Library from inception to September 2022. We included randomized controlled trials comparing tezepelumab versus placebo in patients aged ≥ 12 years with asthma on medium- or high-dose inhaled corticosteroids with ≥ 1 additional controller medication for ≥ 6 months and who had ≥ 1 asthma exacerbation in the 12 months before enrollment. We estimated effects measures with a random-effects model. Of 239 records identified, three studies were included, with a total of 1,484 patients. Tezepelumab significantly decreased biomarkers of T helper 2-driven inflammation, including blood eosinophil count (MD -135.8 [95% CI -164.37, -107.23]) and fractional exhaled nitric oxide (MD -9.64 [95% CI -13.75, -5.53]); improved PFTs, including pre-bronchodilator forced expiratory volume in 1 s (MD 0.18 [95% CI 0.08-0.27]); reduced the AAER (MD 0.47 [95% CI 0.39-0.56]); improved asthma-specific health-related QoL in the Asthma Control Questionnaire-6 (MD -0.33 [95% CI -0.34, -0.32]), Asthma Quality of Life Questionnaire for 12 Years and Older (MD 0.34 [95% CI 0.33, -0.35]), Asthma Symptom Diary (MD -0.11 [95% CI -0.18, -0.04]), and European Quality of Life 5 Dimensions 5 Levels Questionnaire (SMD 3.29 [95% CI 2.03, 4.55]) scores, although not clinically important; and did not change key safety outcomes, including any adverse event (OR 0.78 [95% CI 0.56-1.09]).

Genomic Surveillance of Yellow Fever Virus Epizootic in São Paulo, Brazil, 2016 - 2018.

São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species.

First report on herpesvirus in black-fronted titi (Callicebus nigrifrons) kept under human care.

Keeping Neotropical primates in captivity puts them at great risk of illness because of their susceptibility to human herpesvirus. This is the first report on herpesvirus in Callicebus nigrifrons that developed clinical disease and was confirmed by immunohistochemical and RT-PCR. Diagnosis and prevention are essential for the conservation of species.

Propensity Score Matching to Determine the Impact of Metformin on All-Cause Mortality in Older Veterans with Diabetes Mellitus.

OBJECTIVES: To determine whether metformin is associated with reduced all-cause mortality in older adults with diabetes mellitus as compared with insulin or sulfonylureas, and to evaluate whether the metformin cumulative exposure followed a dose-response relation. METHODS: Retrospective cohort study with propensity score matching in veterans 65 years old and older with diabetes mellitus. Patients who had new prescriptions for metformin were matched for demographic and clinical factors with patients receiving new prescriptions for insulin or sulfonylureas using propensity score matching. All-cause mortality risks were compared between metformin and insulin/sulfonylureas using multivariate Cox regression models. A similar approach was used for tertiles of cumulative metformin doses. RESULTS: A sample of 174 veterans taking metformin was matched with 174 who took insulin/sulfonylureas. Most patients were men (97.4%), White (80.45%), and their mean ± standard deviation age was 69.15 ± 7.65 years. Metformin exposure was associated with reduced risk of all-cause mortality (hazard ratio 0.57, 95% confidence interval 0.39-0.84, P = 0.005). The upper tertile of cumulative metformin exposure was associated with lower all-cause mortality in the fully adjusted model (hazard ratio 0.28, 95% confidence interval 0.10-0.77, P = 0.013). CONCLUSIONS: This propensity matching study shows that metformin exposure is associated with a lower risk of all-cause mortality. Higher metformin cumulative exposure seems to reduce the risk of all-cause mortality in older veterans with diabetes mellitus.

Repurposing topical triclosan for cutaneous leishmaniasis: Preclinical efficacy in a murine Leishmania (L.) amazonensis model.

Leishmaniasis remains an important neglected tropical infection caused by the protozoan Leishmania and affects 12 million people in 98 countries. The treatment is limited with severe adverse effects. In the search for new therapies, the drug repositioning and combination therapy have been successfully applied to neglected diseases. The aim of the present study was to evaluate the in vitro and in vivo anti-Leishmania (Leishmania) amazonensis potential of triclosan, an approved topical antimicrobial agent used for surgical procedures. in vitro phenotypic studies of drug-treated parasites were performed to evaluate the lethal action of triclosan, accompanied by an isobolographic ex-vivo analysis with the association of triclosan and miltefosine. The results showed that triclosan has activity against L. (L.) amazonensis intracellular amastigotes, with a 50% inhibitory concentration of 16 µM. By using fluorescent probes and transmission electron microscopy, a pore-forming activity of triclosan toward the parasite plasma membrane was demonstrated, leading to depolarization of the mitochondrial membrane potential and reduction of the reactive oxygen species levels in the extracellular promastigotes. The in vitro interaction between triclosan and miltefosine in the combination therapy assay was classified as additive against intracellular amastigotes. Leishmania-infected mice were treated with topical triclosan (1% base cream for 14 consecutive days), and showed 89% reduction in the parasite burden. The obtained results contribute to the investigation of new alternatives for the treatment of cutaneous leishmaniasis and suggest that the coadministration of triclosan and miltefosine should be investigated in animal models.

Differential Yellow Fever Susceptibility in New World Nonhuman Primates, Comparison with Humans, and Implications for Surveillance.

A major outbreak of yellow fever (YF) occurred in Brazil during 2016-2018. Epizootics in New World nonhuman primates are sentinel events for YF virus circulation. However, genus-specific susceptibilities and suitability for YF surveillance remain poorly understood. We obtained and compared epidemiologic, histopathologic, immunohistochemical, and molecular results from 93 human and 1,752 primate cases submitted during the recent YF outbreak in Brazil (2017), with the support of the Brazilian National YF Surveillance Program. We detected heterogeneous YF-associated profiles among the various genera of primates we analyzed. Alouatta primates were the most reliable sentinel; Sapajus and Callicebus primates had higher viral loads but lower proportional mortality rates. Callithrix primates were the least sensitive, showing lower viral loads, lower proportional mortality rates, and no demonstrable YF virus antigen or extensive lesions in liver, despite detectable viral RNA. These differences in susceptibility, viral load, and mortality rates should be considered in strategic surveillance of epizootics and control measures for YF.

Concurrent yellow fever and pulmonary aspergillosis due to Aspergillus fumigatus in a free-ranging howler monkey (Alouatta sp).

Herein, we describe a unique case of concomitant angioinvasive pulmonary aspergillosis due to Aspergillus fumigatus and yellow fever in a free-ranging howler monkey (Alouatta sp). Lung samples were negative for influenza viruses A and B.

Yellow Fever as Cause of Death of Titi Monkeys (Callicebus Spp.).

From 2016 to 2018, an epidemic wave of yellow fever (YF) occurred in Brazil, affecting a large number of Platyrrhini monkeys. Titi monkeys (Callicebus spp.) were severely affected yet pathological characterizations are lacking. This study characterized epizootic YF in 43 titi monkeys (Callicebus spp.) with respect to the microscopic lesions in liver, kidney, spleen, heart, brain, and lung, as well as the distribution of immunolabeling for YF virus antigen, and the flaviviral load in the liver. Of 43 titi monkeys examined, 18 (42%) were positive for yellow fever virus (YFV) by immunohistochemistry or reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Affected livers had consistent marked panlobular necrotizing hepatitis, lipidosis, and mild inflammation, with intense immunolabeling for YFV mainly in centrilobular hepatocytes (zone 1; P = .05). In the spleen, consistent findings were variable lymphoid depletion (10/11), lymphoid necrosis (lymphocytolysis; 4/11), and immunolabeling for YFV in histiocytic cells (3/16). The main finding in the kidney was multifocal acute necrosis of tubular epithelium (5/7) that was occasionally associated with intracytoplasmic immunolabeling for YFV (6/15). These data indicate that titi monkeys are susceptible to YFV infection, developing severe hepatic lesions and high viral loads, comparable to humans and Alouatta spp. Thus, Callicebus spp. may be reliable sentinels for YF surveillance.

Hypervirulent Klebsiella pneumoniae as Unexpected Cause of Fatal Outbreak in Captive Marmosets, Brazil.

After the sudden death of captive marmosets in São Paulo, Brazil, we conducted a histologic and microbiologic study. We found hyperacute septicemia caused by hypermucoviscous sequence type 86 K2 Klebsiella pneumoniae. We implemented prophylactic antimicrobial therapy, selected dedicated staff for marmoset interactions, and sanitized the animals' fruit to successfully control this outbreak.

Depression but not frailty contributed to a higher risk for all-cause hospitalizations in male older veterans.

INTRODUCTION: Frailty is a state of vulnerability to stressors resulting in higher morbidity, mortality, and utilization in older adults. Depression and frailty often coexist, suggesting a bidirectional relationship that may increase the effects of each individual condition on clinical outcomes and health-care utilization in older adults. OBJECTIVE: To determine the effects of concurrent frailty and depression on all-cause hospitalizations. METHODS/DESIGN: Prospective cohort study, conducted at a Veterans Affairs (VA) Medical Center. The participants were male, community-dwelling veterans 65 years and older. From 4 January through 30 December 2016, a 46-item frailty index was generated from data obtained from the VA electronic health record. Trained staff conducted in-depth reviews of electronic health records ascertaining depression status. Patients were followed through 31 December 2017 for all-cause hospitalizations following the initial assessment of frailty. After adjusting for covariates, the association of frailty and depression with all-cause hospitalizations was determined with the Andersen-Gill model, accounting for repeated hospitalizations. RESULTS: Five hundred fifty-three male patients were part of the study, mean age 76.3 (SD = 8.2) years. One hundred eighty-one patients (32.7%) had depression diagnoses. During a median follow-up period of 530 days (interquartile range [IQR] = 245), 123 patients (22.2%) had 240 hospitalizations. Frailty status was not associated with future hospitalizations (adjusted hazard ratio [HR] = 1.61; 95% CI, 95-2.74; P > .05). Depression was associated with higher all-cause hospitalizations (adjusted HR = 1.57; 95% CI, 1.09-2.26); P = .0157). CONCLUSIONS: Depression but not frailty was significantly associated with higher rates of all-cause hospitalization. Implementing interventions that target older adults with both frailty and depression may reduce the burden of both conditions and reduce hospitalizations.

Is there an association between ageist attitudes and frailty?

BACKGROUND: Frailty is defined as a state of vulnerability to stressors that is associated with higher morbidity, mortality and healthcare utilization in older adults. Ageism is "a process of systematic stereotyping and discrimination against people because they are old." Explicit biases involve deliberate or conscious controls, while implicit bias involve unconscious processes. Multiple studies show that self-directed ageism is a risk factor for increased morbidity and mortality. The purpose of this study was to determine whether explicit ageist attitudes are associated with frailty in Veterans. METHODS: This is a cross-sectional study of Veterans 50 years and older who completed the Kogan's Attitudes towards Older People Scale (KAOP) scale to assess explicit ageist attitudes and the Implicit Association Test (IAT) to evaluate implicit ageist attitudes from July 2014 through April 2015. We constructed a frailty index (FI) of 44 variables (demographics, comorbidities, number of medications, laboratory tests, and activities of daily living) that was retrospectively applied to the time of completion of the KAOP and IAT. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multinomial logistic regression models with frailty status (robust, prefrail and frail) as the outcome variable, and with KAOP and IAT scores as the independent variables. Age, race, ethnicity, median household income and comorbidities were considered as covariates. RESULTS: Patients were 89.76% male, 48.03% White, 87.93% non-Hispanic and the mean age was 60.51 (SD = 7.16) years. The proportion of robust, pre-frail and frail patients was 11.02% (n = 42), 59.58% (n = 227) and 29.40% (n = 112) respectively. The KAOP was completed by 381 and the IAT by 339 participants. In multinomial logistic regression, neither explicit ageist attitudes (KAOP scale score) nor implicit ageist attitudes (IAT) were associated with frailty in community dwelling Veterans after adjusting for covariates: OR = .98 (95% CI = .95-1.01), p = .221, and OR:=.97 (95% CI = .37-2.53), p = .950 respectively. CONCLUSIONS: This study shows that neither explicit nor implicit ageist attitudes were associated with frailty in community dwelling Veterans. Further longitudinal and larger studies with more diverse samples and measured with other ageism scales should evaluate the independent contribution of ageist attitudes to frailty in older adults.

The association of health literacy, numeracy and graph literacy with frailty.

BACKGROUND: Frailty is a state of vulnerability to stressors which may result in high mortality, morbidity, and health-care utilization in older adults. Whether health literacy, graph literacy and numeracy are associated with frailty is unknown. AIM: To assess the association of health literacy, numeracy and graph literacy with frailty in male veterans. METHODS: This is a retrospective study of 470 cognitively intact, non-depressed veterans who completed evaluations of health literacy, numeracy and graph literacy at Miami VA facility in 2012. A 43-item frailty index was created as a proportion of all potential variables (demographics, comorbidities, number of medications, laboratory tests, and activities of daily life). Odds ratios and 95% confidence intervals were calculated by multinomial logistic regression models with frailty status (robust, prefrail and frail) as the outcome variable, and with health literacy, numeracy, and graph literacy scores as independent variables. Age, race, ethnicity, education, socio-economic status, and comorbidities were considered as covariates. RESULTS: Patients were 100% male, 40% White, 82% non-Hispanic, mean age was 56.8 years. The proportion of robust, pre-frail and frail was 10.0%, 61.3% and 28.7%, respectively. Neither health literacy nor objective nor subjective numeracy was associated with frailty after adjustment for covariates. In contrast, higher graph literacy scores were associated with a lower risk for frailty (p = .015) even after adjusting known risk factors for frailty. DISCUSSION AND CONCLUSION: Neither health literacy nor numeracy is associated with frailty. Higher graph literacy score is associated with a lower risk for frailty even after adjusting for known risk factors for frailty.

Toxoplasmosis and Sarcocystis spp. infection in wild pinnipeds of the Brazilian coast.

The protozoans Toxoplasma gondii and Sarcocystis spp. (Sarcocystidae: Apicomplexa) affect a wide variety of vertebrates. Both have been reported to infect pinnipeds, with impacts on health ranging from inapparent to fulminant disease and death. However, little is known regarding their infections and associated pathology in South American pinnipeds. We used histological techniques to survey for the presence of T. gondii and Sarcocystis spp. in 51 stranded pinnipeds from Brazil. Immunohistochemical and molecular assays were employed in those cases consistent with Sarcocystidae infection. T. gondii cysts were detected in the central nervous system and heart of a South American fur seal Arctocephalus australis, associated with meningoencephalitis, myocarditis and endocarditis, and confirmed by immunohistochemistry. Additionally, this animal presented Sarcocystis sp. cysts in brain and heart tissues. Four additional specimens-2 Subantarctic fur seals A. tropicalis, an Antarctic fur seal A. gazella and another South American fur seal-presented intrasarcoplasmic cysts compatible with Sarcocystis spp. in muscle samples. There was no inflammation associated with the Sarcocystis spp. tissue cysts and all cysts were negative for S. neurona immunohistochemistry. The B1 gene of T. gondii was amplified in the 5 pinnipeds infected by Sarcocystidae protozoans. To our knowledge, this is the first report of toxoplasmosis in wild South American pinnipeds and of Sarcocystis spp. in South American fur seals. Detection of terrestrial parasites in aquatic mammals could be an indicator of their presence in the marine environment.

Outbreak of Yellow Fever among Nonhuman Primates, Espirito Santo, Brazil, 2017.

In January 2017, a yellow fever outbreak occurred in Espirito Santo, Brazil, where human immunization coverage is low. Histologic, immunohistologic, and PCR examinations were performed for 22 deceased nonhuman New World primates; typical yellow fever features were found in 21. Diagnosis in nonhuman primates prompted early public health response.