RESUMEN

Leishmaniasis are zoonosis widely spread in Brazil, caused by the protozoan of the genus Leishmania, which includes several species. The disease manifests itself in the visceral or tegumentary form, and the main reservoir is the dogs. Manaus is the largest city in the Brazilian Amazon region, and despite the importance of the municipality, practically nothing is known about leishmaniosis in humans and animals. The objective of this study was to evaluate the occurrence and risk factors associated with the presence of Leishmania infantum in domiciliated dogs from Manaus. Molecular (polymerase chain reaction) and serological (immunofluorescent antibody test) methods were used as an indication of the circulation of the parasite. Blood samples for 154 domiciled dogs were obtained, and prevalence ratio and analysis of the variables were performed. Serum antibodies anti-Leishmania spp. were detected in 20.8% (95% CI: 14.4%-27.2%). Access to the street and zone of residence (P < 0.01) were associated with higher seropositivity. Molecular diagnosis for L. infantum detected positivity in 60 (39%) of the 154 (95% CI: 31.3%-46.7%) animals, and the variables street access, contact with dogs, and zone of residence were associated with higher frequencies of positivity (P < 0.05). Both serology and molecular diagnosis detected positive dogs in the municipality. This is the first description of the circulation of L. infantum infecting dogs in Manaus. As the municipality is classified as nonendemic, studies of isolation and characterization of the isolate must be done urgently.

RESUMEN

Antimicrobial-resistant Escherichia coli is a global health challenge from a One Health perspective. However, data on its emergence in the Caatinga biome are limited. This biome is exclusive to the Brazilian Northeast and offers unique epidemiological conditions that can influence the occurrence of infectious diseases and antimicrobial resistance. In this study, the carriage proportion, antimicrobial susceptibility, and population structure of cephalosporin-resistant E. coli were assessed in 300 cloacal swab samples of free-range chickens from three Brazilian states covered by the Caatinga biome. The results showed that 44 (14.7%) samples were positive for cephalosporin-resistant E. coli, and Paraíba state had the highest frequency of isolates (68.2%). Genes encoding cephotaximase-Munich or ampicillin class C (AmpC) enzymes were identified in 30 (68.2%) and 8 (18.2%) isolates, respectively, comprising 31 E. coli isolates. Overall, molecular typing by genome restriction using XbaI endonuclease followed by pulsed-field gel electrophoresis revealed four clusters from two properties of Paraíba state composed by extended-spectrum ß-lactamase-producing and AmpC-producing E. coli carrying blaCTX-M-1-like and blaMIR-1/ACT-1 genes and belonging to different phylogenetic groups. There is a need to control antimicrobial resistance while taking into account the genetic diversity of the strains and their implications for animal and public health, especially in free-range chickens reared in the Brazilian Caatinga biome.

RESUMEN

The feline immunodeficiency virus (FIV) is a retrovirus of the Lentivirus genus, distributed worldwide, that causes persistent infection with a significant impact on the cats' health. Due to the importance of this infection in feline medicine, this pioneering study aimed to obtain an integrated estimate of the global seroprevalence of FIV in cats and to characterize the factors associated with this infection. Four electronic databases were screened for observational studies with FIV seroprevalence in cats published globally for this systematic review and meta-analysis. The initial search method returned 873 studies, of which 113 met all predefined criteria and were therefore included in this review. Meta-analysis with general data was performed, and a combined global seropositivity of 9.43 % (95 % CI: 8.24 % - 10.78 %) was found. Seropositivity was 14.34 % (95 % CI = 10.92 % - 18.61 %) in Asia, 11.90 % (95 % CI = 9.82 % - 14.34 %) in Oceania, 10.90 % (95 % CI = 5.71 % - 19.82 %) in Central America, 9.43 % (95 % CI = 6.95 % - 12.66 %) in South America, 9 % (95 % CI = 0 - 80 %) in Africa, 8.98 % (95 % CI = 7.31 % - 10.98 %) in Europe, and 5.93 % (95 % CI = 4.33 % - 8.07 %) in North America. Meta-analysis of factors associated with seropositivity demonstrated that FIV seroprevalence was higher in male (Prevalence ratio [PR] = 2.53, 95 % CI = 2.16 - 2.95), adult (PR = 2.83, 95 % CI = 2.24 - 3.56), unowned status (PR = 1.47, 95 % CI = 1.07 - 2.03), sick status (PR = 2.46, 95 % CI = 1.97 - 3.06), and cats with outdoor access (PR = 4.38, 95 % CI = 2.26 - 8.47). The results demonstrated that FIV is globally distributed and has a high seroprevalence in some geographical areas. Information compiled from this research is relevant to understanding the worldwide epidemiology of FIV. It presents the potential to contribute to the planning of strategies focused on controlling and reducing cases in cat populations.

Asunto(s)

RESUMEN

Leptospirosis is an infectious disease that affects domestic animals, wild animals, and humans. It represents a public health problem and has an important economic impact on livestock. This study aims to investigate the importance of genital and transplacental infection in the epidemiology of leptospirosis in cows maintained in Caatinga biome conditions, Northeastern Brazil, as well as reporting organs colonized by Leptospira spp. in embryos and fetuses. Blood, urinary tract (urine, bladder, and kidney), and reproductive tract (vaginal fluid, uterus, uterine tube, ovary, and placenta) samples were collected from 15 slaughtered pregnant cows. Two embryos and 13 fetuses were sampled. Central nervous system and choroid ovoid samples were collected from embryos. Blood, central nervous system, lung, peritoneal liquid, abomasal content, liver, spleen, urine, bladder, kidney, and reproductive system samples were collected from fetuses. Diagnostic methods included the microscopic agglutination test (MAT) using a collection of 24 serovars belonging to 17 different pathogenic serogroups of five species as antigens, as well as polymerase chain reaction (PCR). Anti-Leptospira spp. antibodies were found in 9 cows (60%), while 13 cows (86.67%) had at least one organ or urine with leptospiral DNA. No fetus was seroreactive. Among the embryos and fetuses, 13 (86.67%) presented leptospiral DNA, proving a high frequency of transplacental infection (100%). For cows, the most frequent biological materials regarding Leptospira spp. DNA detection were placenta (13 out of 15 samples; 86.7%), uterus (10 out of 15 samples; 66.7%), and vaginal fluid (5 out of 15 samples; 33.3%), while, for fetuses/embryos, the most frequent PCR-positive samples were choroid ovoid (1/2; 50%), spleen (6/13; 46.2%), kidney (5/13; 38.5%), and central nervous system (5/15; 33.3%). Sequenced samples based on the LipL32 gene presented 99% similarity with L. borgpetersenii. The results indicate that transplacental infection is an efficient way of spreading Leptospira spp. in cows maintained in Caatinga biome conditions. Therefore, prevention and control strategies must include actions that interrupt transmission through this alternative route.

RESUMEN

The Caatinga biome occurs only in Brazil and offers epidemiological conditions that should be assessed differently from other regions of Brazil and the world. Thus, the aim of this survey was to identify antimicrobial resistance, enterotoxin and biofilm production genes in Staphylococcus spp. isolated from facilities and fomites in a veterinary hospital in Caatinga biome. Samples were collected from surfaces of small animal clinical care tables (n =8), cages in the dog and cat hospitalisation sector and animals with infectious diseases (n = 21), small animal surgical centre (n =8), sterilisation sector (n =7) and stethoscopes (n = 32) by using sterile swabs. Bacterial isolation and identification, antimicrobial resistance phenotypic test and molecular detection of antimicrobial resistance, biofilm formation and enterotoxin genes were carried out. Ninety-five bacterial isolates were obtained, and 29 (30.5%) were identified as Staphylococcus spp. Overall, 13 isolates (44.8%) of six species of Staphylococcus spp. showed antimicrobial resistance profile, as well as S. haemolyticus expressed phenotypic profile of multidrug resistance. The antimicrobials with the highest resistance rates were penicillin and tetracycline. The most frequent resistance genes were blaZ and tetM, both detected in 10 (76.9%) isolates. The mecA, tetL and tetK genes had frequencies of 38.5% (5/13), 23.1% (3/13) and 15.4% (2/13), respectively. The biofilm production marker, icaD gene, was detected in one S. sciuri strain. SEE gene, which encodes enterotoxins, was detected in 15.4% (2/13) of the strains (S. pseudintermedius and S. intermedius). The occurrence of Staphylococcus spp. carrying resistance genes to diferent classes of antimicrobials, presenting MDR phenotypic pattern and carrying enterotoxins and biofim encoding genes recovered from veterinary hospital facilities and fomites in the Caatinga biome reinforce the need to implement prevention cares in veterinary practices to avoid One Health-concerning conditions.

Asunto(s)

RESUMEN

Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses of great importance for domestic cats with a worldwide distribution. A retrospective study was conducted to determine the epidemiological and clinicopathological aspects of the infection by FIV and FeLV in cats from the Brazilian semiarid region. Cats treated between 2011 and 2021 at the teaching veterinary hospital of the Federal Rural University of the Semi-Arid Region that were submitted to a point-of-care (POC) test to detect anti-FIV IgG antibodies and FeLV antigen were enrolled in the study. Overall, 454 cats were selected, of which 30.2% [95% CI = 26.0% - 34.3%] were FIV-positive, 1.1% [95% CI = 0.9% - 1.2%] were FeLV-positive, and 0.7% [95% CI = 0.1% - 1.3%] were coinfected by both retroviruses. No statistical association was found between the studied retroviruses (P = 0.144). Multivariable analysis detected significant associations between FIV infection and male sex [OR = 5.7, 95% CI = 3.0-10.7, P < 0.0001), age between 19 and 78 months [OR = 5.2, 95% CI = 2.2-12.1, P < 0.0001], age greater than 78 months [OR = 12.8, 95% CI = 5.1-31.9, P < 0.0001], crossbreed [OR = 4.1, 95% CI = 1.2-13.4, P = 0.021], the presence of oral disease [OR = 2.1, 95% CI = 1.3-3.4, P = 0.004], reduced red blood cell (RBC) count [OR = 3.7, 95% CI = 1.9-7.2, P < 0.0001], and an albumin:globulin (A:G) ratio lower than 0.6 [OR = 3.4, 95% CI = 1.6-7.1, P = 0.001]. No statistical analyses were performed for FeLV infection due to the low number of positive animals. In the quantitative analyses of hematological parameters, FIV-positive cats presented lower values for RBC, hemoglobin, hematocrit, lymphocytes, and platelets compared to the negative animals. In the biochemical profile, cats infected with FIV showed higher creatinine, urea, total protein, and globulin values, while lower values for albumin and A:G ratio were observed (P < 0.05). The findings of this study characterized the prevalence, clinicopathological findings, and risk factors associated with FIV and FeLV in cats from the Brazilian semiarid region. They may help support veterinary practitioners in diagnosing feline retroviruses. The FIV prevalence observed is among the highest reported in Brazil, demonstrating the need for prevention and control strategies for this retrovirus.

Asunto(s)

RESUMEN

Bovine brucellosis is an endemic disease in Brazil, and evidence-based assessments of the available literature on its seroprevalence and risk factors are limited. The aim of this study was to systematically review and summarize studies related to seroprevalence and risk factors of bovine brucellosis in the entire Brazil, in addition to comparing published data with the most recent official reports. Articles available in scientific databases and published between October 2006 and October 2021 were evaluated. Forty-five publications were included in the meta-analysis on the seroprevalence of brucellosis and 29 publications in the review on risk factors. The largest number of publications was found for the State of Mato Grosso do Sul (n=4), and the highest and lowest seroprevalences were observed in Acre (11%; 95% CI: 8.0-14.0%) and in the Federal District (0.4%; 95% CI: 0.2-0.7%). The main risk factors were the purchase of animals for breeding, vaccination, the number of heifers (female ≥2 years), the presence of calving paddocks and the occurrence of abortions. The need for new official studies has been suggested to determine the true prevalence of bovine brucellosis in Brazil, supported by the National Program for the Control and Eradication of Animal Brucellosis and Tuberculosis.

Asunto(s)

RESUMEN

BACKGROUND: Targeted therapy and immunotherapy have shown intracranial activity in melanoma with CNS metastases, but there remains an unmet need, particularly for patients with symptomatic CNS metastases. We aimed to evaluate atezolizumab in combination with cobimetinib or vemurafenib plus cobimetinib in patients with melanoma with CNS metastases. METHODS: TRICOTEL was a multicentre, open-label, single-arm, phase 2 study done in two cohorts: a BRAFV600 wild-type cohort and a BRAFV600 mutation-positive cohort, recruited at 21 hospitals and oncology centres in Brazil, France, Germany, Hungary, Italy, Spain, and Switzerland. Eligible patients were aged 18 years or older with previously untreated metastatic melanoma, brain metastases of 5 mm or larger in at least one dimension, and an Eastern Cooperative Oncology Group performance status of 2 or less. Patients in the BRAFV600 wild-type cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral cobimetinib (60 mg once daily, days 1-21). Patients in the BRAFV600 mutation-positive cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral vemurafenib (720 mg twice daily) plus oral cobimetinib (60 mg once daily, days 1-21); atezolizumab was withheld in cycle 1. Treatment was continued until progression, toxicity, or death. The primary outcome was intracranial objective response rate confirmed by assessments at least 4 weeks apart, as assessed by independent review committee (IRC) using modified Response Evaluation Criteria in Solid Tumours version 1.1. Because of early closure of the BRAFV600 wild-type cohort, the primary endpoint of intracranial objective response rate by IRC assessment was not done in this cohort; intracranial objective response rate by investigator assessment was reported instead. Efficacy and safety were analysed in all patients who received at least one dose of study medication. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT03625141. FINDINGS: Between Dec 13, 2018, and Dec 7, 2020, 65 patients were enrolled in the BRAFV600 mutation-positive cohort; the BRAFV600 wild-type cohort was closed early after enrolment of 15 patients. Median follow-up was 9·7 months (IQR 6·3-15·0) for the BRAFV600 mutation-positive cohort and 6·2 months (3·5-23·0) for the BRAFV600 wild-type cohort. Intracranial objective response rate was 42% (95% CI 29-54) by IRC assessment in the BRAFV600 mutation-positive cohort and 27% (95% CI 8-55) by investigator assessment in the BRAFV600 wild-type cohort. Treatment-related grade 3 or worse adverse events occurred in 41 (68%) of 60 patients who received atezolizumab plus vemurafenib plus cobimetinib in the BRAFV600 mutation-positive cohort, the most common of which were lipase increased (15 [25%] of 60 patients) and blood creatine phosphokinase increased (11 [18%]). Eight (53%) of 15 patients treated with atezolizumab plus cobimetinib in the BRAFV600 wild-type cohort had treatment-related grade 3 or worse adverse events, most commonly anaemia (two [13%]) and dermatitis acneiform (two [13%]). Treatment-related serious adverse events occurred in 14 (23%) of 60 patients who received triplet therapy in the BRAFV600 mutation-positive cohort and two (13%) of 15 in the BRAFV600 wild-type cohort. No treatment-related deaths occurred. INTERPRETATION: Atezolizumab plus vemurafenib and cobimetinib provided intracranial activity in patients with BRAFV600-mutated melanoma with CNS metastases. FUNDING: F Hoffmann-La Roche.

RESUMEN

Donkeys (Equus asinus) are historically known for their close relationship to humanity, which raises the need to study zoonotic diseases that affect them. In this perspective, leptospirosis stands out as a disease with an economic and public health impact, and its occurrence is facilitated in times of higher rainfall indexes, especially in large urban centers. In view of the scarcity of information about leptospirosis in donkeys, the objective of this study was to detect the presence of Leptospira spp. and anti-leptospiral antibodies in donkeys rescued by a zoonosis center located in the Caatiga biome, Brazilian semiarid region. Overall, 30 donkeys of both sexes, aged between 4 months and 15 years, were used, from which 64 serum samples were collected and submitted to the microscopic agglutination test (MAT). In addition, 64 samples of urine, vaginal and preputial fluid, in duplicates, were subjected to the polymerase chain reaction (PCR) and microbiological. Sixteen (53.3%) animals tested positive in at least one diagnostic test, 12 (40%) of which were positive at MAT and seven (23.3%) in the molecular and bacteriological detection (urine, vaginal, and preputial fluid samples). This is the first report identifying donkeys infected with Leptospira spp. by molecular and bacteriological diagnosis in Brazil, and the first in the world to detect this agent in their genital fluids. The study also shows that donkeys are commonly exposed to leptospires in the Caatinga biome, and this constitutes a One Health-based concern, demonstrating the importance of broad studies where large numbers of humans and animals coexist when investigating zoonotic infections and when planning and implementing control measures for donkeys-associated leptospirosis.

RESUMEN

Bovine neosporosis is a globally important disease, causing abortions and significant economic losses. In Brazil, studies on neosporosis in cattle are few and based on limited samples and/or from limited areas. We aimed to determine the herd and animal levels seroprevalence and associated factors for Neospora caninum infections in cattle from the state of Paraíba, Northeastern Brazil, using a planned sampling. Herds (n = 434) and cows aged ≥24 months (n = 1891) were randomly selected, and serum samples were tested with the immunofluorescence antibody test (IFAT) using as cut-off point the antibody titer 200. Herd-level and animal-level seroprevalences were 17.8% (95% CI = 14.3%-21.8%) and 18.1% (95% CI = 14.7%-22.1%), respectively. The factors associated with N. caninum infection were farm located in the Sertão mesoregion (Prevalence ratio [PR] = 2.37), mixed production (PR = 1.64), herd size of 34-111 animals (PR = 3.50) and herd size >111 animals (PR = 6.14). The results indicate high N. caninum circulation in the bovine population of the state of Paraíba, semiarid of Brazil, mainly in the Sertão mesoregion, where the highest apparent herd and animal-level prevalences of positive herds were identified. Control strategies should be adopted to mitigate the impact of disease on cattle production, as well as it's suggested the encouragement of conducting surveys in wildlife from Caatinga biome, mainly canids, to provide information on the importance of these animals on the epidemiology of bovine neosporosis.

Asunto(s)

RESUMEN

Importance: There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Objective: To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN. Design, Setting, and Participants: The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock). Interventions: Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal. Main Outcomes and Measures: The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety. Results: Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n = 159; nivolumab, n = 82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n = 123; nivolumab, n = 61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P = .29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease. Conclusions and Relevance: The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02823574.

Asunto(s)

RESUMEN

The objective of this study was to report the occurrence of Mycobacterium avium subspecies paratuberculosis (MAP) in dairy goats, via description of their clinical presentation, histopathological findings, and molecular identification of the infectious agent. Screening was performed using IS900 real-time PCR (qPCR) in milk samples from 179 properties in the semiarid of Northeast region of Brazil. Pooled milk samples from all lactating goats from processing plants were submitted to molecular diagnosis. One property had a positive result at qPCR. The production unit which had the positive sample for MAP was located, and an on-site visit to this property was performed to collect individual milk samples, seven of which tested MAP positive by IS900 qPCR. With permission from the owner, two goats (Animal 1 was positive and Animal 2 was negative on first qPCR for MAP) were acquired and euthanized. Animals 1 and 2 had milk and portions of the duodenum, ileum, colon, and mesenteric lymph nodes positive at qPCR for MAP. Animal 1 also had MAP DNA detected in part of the jejunum and cecum. In animal 2, the ileocecal valve tested positive. MAP was not detected in the blood or feces of either animal; however; it was confirmed for the association of clinical findings, histopathology, and qPCR. The gene IS900 from the positive samples were sequenced and showed a 99% similarity with MAP. The MAP was identified for the first time in the goat milk and tissues in the semiarid region of Northeast Brazil.

Asunto(s)

RESUMEN

Serum samples (n = 1532) were collected between May 2011 to April 2012 from goats from 76 herds (49 from dairy farms and 27 herds for genetic improvement) from three geographical regions from the state of Pernambuco, Brazil: Zona da Mata, Agreste, and Sertão. Samples were processed using agar gel immunodiffusion test, with p28 CAEV antigen. The objective was to determine the risk factors for small ruminant lentivirus (SRLV) in dairy goats and goats with high genetic value. Overall, seroprevalence was 13.7% (210/1532) [95% CI: 12-15.4%] in animals and 67.1% (51/76) [95% CI: 56.5%- 77.7%] in herds. In dairy farms the seroprevalence was 73.5% (36/49) [95% CI: 61.1%- 85.8%], and in properties with animals of high genetic value it was 55.6% (15/27) [95% CI: 36.8%- 74.3%]. Robust Poisson regression analysis adjusted by the random effect of the herd showed that risk factors were: importing bucks from another Brazilian state (prevalence ratio [PR] = 4.73 [95% CI: 2.05; 10.88]), not isolating sick animals (PR = 3.27 [95% CI: 2.24; 4.76]), and participating in fairs/animal crowding (PR = 1.52 [95% CI: 1.09; 2.11]). Prevalence results show that SRLV is present in caprine herds in the state of Pernambuco and identified risk factors are strongly related to animal transit. Considering the epidemiological situation, the first step for mitigating the consequences of this disease would be controlling animal transit.

Asunto(s)

RESUMEN

In recent decades, the scientific community has been faced with an increased risk of emerging or re-emerging zoonotic diseases, such as leptospirosis, mainly originating from anthropic actions [...].

RESUMEN

Studies related to the prevalence of leptospirosis in the semiarid region showed that even during long periods of drought, the disease has a remarkable frequency in herds in the region. It is a neglected disease and the extent of its effects in the Brazilian semiarid region is not known. The dynamics of this agent is well studied in the urinary tract, however, there are not many studies regarding the genital tract in female goats. Observing this scenario, the present work aimed to diagnose Leptospira spp. in female goats kept in the Brazilian semiarid region by means of serological, molecular and isolation techniques. Blood samples, vaginal fluid, urine and fragments of organs from the genitourinary tract were collected from 40 goats destined for slaughter. Microscopic agglutination test (MAT) was used as a serological technique, with a battery of 24 serovars. The Polymerase Chain Reaction (PCR) of the vaginal fluid, urine and organ fragments was performed, as well as the bacterial growth of these same products in a selective medium. Isolation positive samples were subjected to PCR. It was observed that two (5%) animals were serologically positive for the Pyrogenes serogroup. A total of 29 (72.5%) animals were PCR positive, with DNA present in 51/160 (31.8%) samples from the genital tract and 34/120 (28.3%) from the urinary tract, with no statistical difference. For bacterial growth, 22/40 (55%) animals were positive for growth, with morphology being observed in 19/160 (11.8%) for the genital tract and 16/120 (13.3%) for the urinary tract, with no statistical difference. Two uterus samples showed 99% similarity with L. interrogans after sequencing. Thus, female goats kept under semiarid conditions were positive for Leptospira spp, with positive samples from both the urinary and genital tracts, which possible is an alternative way of adapting and maintaining the agent for severe and adverse conditions.

Asunto(s)

RESUMEN

The Adenoviridae family is composed by a high diversity of viruses that are extremely resistant in environment and are frequently excreted in animal reservoir feces for long periods. The knowledge of adenovirus (AdV) diversity among wild species may be important for the understanding of the epidemiology of putative emerging diseases. Cavia aperea aperea, commonly known as wild guinea pigs, wild cavies, or preas, are small herbivorous rodents widely distributed throughout South America and classified in Caviidae family, as well as domestic guinea pigs and capybaras. In order to investigate their potential role as reservoir of zoonotic agents, the present study aimed to verify the presence of AdV in fecal samples of 14 preas from Northeast Brazil. When submitted to nested PCR, two out of 14 samples (14.28%) were positive for AdV and classified as human Mastadenovirus C (HAdV-C) using DNA sequencing and phylogenetic analysis. Wild guinea pigs are synanthropic rodents that live in close contact with humans. The investigation of viral agents in rodents is important due to their potential role as reservoirs of human and animal pathogens. Moreover, the present work presents the first known evidence of HAdV in wild guinea pig stool samples, which may represent both the impact of anthropogenic pollution to wild animals and an important knowledge in terms of human health.

Asunto(s)

RESUMEN

BACKGROUND: Targeted therapy and immunotherapy have shown intracranial activity in melanoma with CNS metastases, but there remains an unmet need, particularly for patients with symptomatic CNS metastases. We aimed to evaluate atezolizumab in combination with cobimetinib or vemurafenib plus cobimetinib in patients with melanoma with CNS metastases. METHODS: TRICOTEL was a multicentre, open-label, single-arm, phase 2 study done in two cohorts: a BRAFV600 wild-type cohort and a BRAFV600 mutation-positive cohort, recruited at 21 hospitals and oncology centres in Brazil, France, Germany, Hungary, Italy, Spain, and Switzerland. Eligible patients were aged 18 years or older with previously untreated metastatic melanoma, CNS metastases of 5 mm or larger in at least one dimension, and an Eastern Cooperative Oncology Group performance status of 2 or less. Patients in the BRAFV600 wild-type cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral cobimetinib (60 mg once daily, days 1-21). Patients in the BRAFV600 mutation-positive cohort received intravenous atezolizumab (840 mg, days 1 and 15 of each 28-day cycle) plus oral vemurafenib (720 mg twice daily) plus oral cobimetinib (60 mg once daily, days 1-21); atezolizumab was withheld in cycle 1. Treatment was continued until progression, toxicity, or death. The primary outcome was intracranial objective response rate confirmed by assessments at least 4 weeks apart, as assessed by independent review committee (IRC) using modified Response Evaluation Criteria in Solid Tumours version 1.1. Because of early closure of the BRAFV600 wild-type cohort, the primary endpoint of intracranial objective response rate by IRC assessment was not done in this cohort; intracranial objective response rate by investigator assessment was reported instead. Efficacy and safety were analysed in all patients who received at least one dose of study medication. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT03625141. FINDINGS: Between Dec 13, 2018, and Dec 7, 2020, 65 patients were enrolled in the BRAFV600 mutation-positive cohort; the BRAFV600 wild-type cohort was closed early after enrolment of 15 patients. Median follow-up was 9·7 months (IQR 6·3-15·0) for the BRAFV600 mutation-positive cohort and 6·2 months (3·5-23·0) for the BRAFV600 wild-type cohort. Intracranial objective response rate was 42% (95% CI 29-54) by IRC assessment in the BRAFV600 mutation-positive cohort and 27% (95% CI 8-55) by investigator assessment in the BRAFV600 wild-type cohort. Treatment-related grade 3 or worse adverse events occurred in 41 (68%) of 60 patients who received atezolizumab plus vemurafenib plus cobimetinib in the BRAFV600 mutation-positive cohort, the most common of which were lipase increased (15 [25%] of 60 patients) and blood creatine phosphokinase increased (ten [17%]). Eight (53%) of 15 patients treated with atezolizumab plus cobimetinib in the BRAFV600 wild-type cohort had treatment-related grade 3 or worse adverse events, most commonly anaemia (two [13%]) and dermatitis acneiform (two [13%]). Treatment-related serious adverse events occurred in 14 (23%) of 60 patients in the BRAFV600 mutation-positive cohort and two (13%) of 15 in the BRAFV600 wild-type cohort. One death in the BRAFV600 mutation-positive cohort (limbic encephalitis) was considered to be related to atezolizumab treatment. INTERPRETATION: Adding atezolizumab to vemurafenib plus cobimetinib provided promising intracranial activity in patients with BRAFV600-mutated melanoma with CNS metastases. FUNDING: F Hoffmann-La Roche.

Asunto(s)

RESUMEN

Leptospirosis is poorly studied in small ruminants raised in field semiarid conditions. In this study we compared serological, bacteriological and molecular diagnostic methods in ewes maintained in field Brazilian semiarid conditions. Blood, vaginal fluid and urine samples were collected from 60 Morada Nova ewes raised in a semi-intensive system in the Brazilian semiarid. Diagnostic tests performed were microscopic agglutination test (MAT), polymerase chain reaction (PCR) and bacterial isolation. Anti-Leptospira sp. antibodies were found in eight (13.33%) animals analyzed by MAT at reciprocal titer 25 (cut-off 25), while Leptospira sp. DNA was detected in urine or vaginal fluid of 56 animals (93.33%). There was growth of leptospires in 10 urine cultures and in 11 vaginal fluid cultures, however, two of urine (2/60-3.33%) and eight cultures of vaginal fluid (8/60-13.33%) were confirmed by PCR. Two samples of vaginal fluid (one of each animal) were submitted to sequencing demonstrating 99% similarity with L. santarosai and L. interrogans. The highest MAT sensitivities were obtained with reciprocal titer 25 (cut-off 25) compared to 50 and 100. The performance of different diagnostic techniques for leptospirosis in ewes raised in field semiarid conditions allowed a better evaluation of the herd, as well as made it possible to identify carrier animals. Genital route may be important for efficient transmission and without dependence on environmental factors in ewes from semiarid, as well as it's highlighted that titer 1:25 in serology was more efficient, indicating its use in ewes in field semiarid conditions.

Asunto(s)

RESUMEN

BACKGROUND: There is variation in the outcomes reported in clinical studies of basal cell carcinoma. This can prevent effective meta-analyses from answering important clinical questions. OBJECTIVE: To identify a recommended minimum set of core outcomes for basal cell carcinoma clinical trials. METHODS: Patient and professional Delphi process to cull a long list, culminating in a consensus meeting. To be provisionally accepted, outcomes needed to be deemed important (score, 7-9, with 9 being the maximum) by 70% of each stakeholder group. RESULTS: Two hundred thirty-five candidate outcomes identified via a systematic literature review and survey of key stakeholders were reduced to 74 that were rated by 100 health care professionals and patients in 2 Delphi rounds. Twenty-seven outcomes were provisionally accepted. The final core set of 5 agreed-upon outcomes after the consensus meeting included complete response; persistent or serious adverse events; recurrence-free survival; quality of life; and patient satisfaction, including cosmetic outcome. LIMITATIONS: English-speaking patients and professionals rated outcomes extracted from English language studies. CONCLUSION: A core outcome set for basal cell carcinoma has been developed. The use of relevant measures may improve the utility of clinical research and the quality of therapeutic guidance available to clinicians.

Asunto(s)

RESUMEN

Equine hepacivirus (EqHV) belongs to the Flaviviridae family, genus Hepacivirus and has the greatest genomic identity with the hepatitis C virus (HCV), one of the main causes of chronic liver disease in humans. Due to the limited applicability of studies of HCV in animal hosts, the interest in studies of characterization of viral homologues has been growing. For this reason, we performed a systematic review of the literature with meta-analysis of the prevalence of EqHV and genetic sequencing studies. Twenty-three studies from four different continents were analyzed. The OR meta-analysis (0.98; 95% CI = 0.69-1.39) showed no influence of sex (female or male) on the risk of infection. Variables associated with EqHV infection were indirectly related to animal management such as transport, reproductive practices, among others. The combined prevalence of positive animals was 7.88% (95% CI = 5.23-11.69%), with the highest proportions in Asia (16.13%; 95% CI = 7.79-30.43%), followed by South America (12.03%; 95% CI = 9.58-15.01%), Africa (8.69%; 95% CI = 6.71-11.20%), and Europe (3.63%; 95% CI = 2.10-6.22%). However, these results represent the regional stratification of the epidemiological studies for EqHV published to date and, therefore, cannot extrapolate to determine the continental prevalence of EqHV. It is therefore important to update the systematic review as further research becomes available.

Asunto(s)