Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer.

Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma1-4. Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial5 (programmed death ligand-1 (PD-L1) combined positive score ≥5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries6. Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively7-11. Treatment combining 1 mg kg-1 nivolumab with 3 mg kg-1 ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer12. Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive score ≥5 (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score ≥ 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.

Distribution, seroprevalence and risk factors for bovine brucellosis in Brazil: Official data, systematic review and meta-analysis.

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.

Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study.

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.

Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study.

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.

Detection of Leptospira spp. in genitourinary tract of female goats managed in the brazilian semiarid.

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.

Development of a core outcome set for basal cell carcinoma.

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.

High frequency of seropositive and carriers of Leptospira spp. in pigs in the semiarid region of northeastern Brazil.

Carrier animals are considered key in the transmission cycle of leptospirosis. Although investigations have been carried out on several species, the role of pigs in the epidemiology of the disease is still poorly studied in the semi-arid region. Thus, the objective of this study was to determine the presence of Leptospira spp. in the genitourinary tract of pigs intended for slaughter. Fifty pigs were used: adults and unvaccinated. Samples of the kidney, urine, and vaginal fluid were collected for the molecular detection of Leptospira spp. and blood samples for the serological test. The molecular test was performed using the polymerase chain reaction (PCR), and the serological test was performed with the microscopic agglutination test (MAT). Samples with DNA amplification were submitted to genetic sequencing. Twenty (40%) animals were found with anti-Leptospira spp. antibodies, and the majority of the reactions (50%) occurred for the serogroup Tarassovi. Leptospiral DNA was found in the tissue of 11 (22%) pigs. The gene from a urine sample was sequenced and showed similarity to L. borgpetersenii. The results evidenced a high rate of porcine carriers; therefore, they appear to be important sources of agent infection, being potential transmitters of the disease to other animal species and man.

Seroepidemiological study of Caseous lymphadenitis in sheep from the Northeast region of Brazil using an indirect ELISA.

The objective of this study was to determine the frequency of seropositivity Corynebacterium pseudotuberculosis in sheep in five states of northeastern Brazil, using an indirect enzyme-linked immunosorbent assay (i-ELISA). Young and adult sheep of both sexes were used. Blood samples were collected from 2638 sheep from 223 herds across all states. For the i-ELISA, antigens produced from the strain of C. pseudotuberculosis BRM 029971, a bacterial isolate from the Northeast region of Brazil, were used. Sensitivity and specificity indexes were calculated for the validation of the test, using as reference 49 and 134 serum samples from sheep known to be positive and negative, respectively. The i-ELISA presented four false-negative and four false-positive results, showing a specificity of 97.01%, a sensitivity of 91.84%, and an accuracy of 95.63%. These results were calculated based on an optical density (OD) cutoff point = 0.138. Of the 2638 sheep tested, 996 (37.76%, 95% CI = 35.93-39.62%) were seropositive, and of the 223 evaluated herds, 210 (94.17%, 95% CI = 90.28-96.56%) seropositive. The i-ELISA showed adequate sensitivity and specificity, proving to be a useful tool in the diagnosis of caseous lymphadenitis (CLA) in sheep. Infection by C. pseudotuberculosis, determined by serology, is disseminated in the sheep herds in the states of Northeast Brazil. Thus, there is a need to implement effective control measures that prevent the spread of infectious agents.

Seroepidemiological characterization and risk factors associated with seroconversion to Corynebacterium pseudotuberculosis in goats from Northeastern Brazil.

Goat breeding in the Northeast region of Brazil plays an important socioeconomic role. However, there are significant losses caused by sanitary deficits and infectious diseases, particularly caseous lymphadenitis (CL). Although CL is considered endemic in Northeastern Brazil, a comprehensive and up-to-date study of this disease in goat herds in this region is necessary. The objective of this study was to determine the farm-level and animal-level seroprevalences for the disease and to identify the possible risk factors that characterize CL in the caprine species of five Northeastern's states (Ceará, Piauí, Rio Grande do Norte, Paraíba, and Sergipe). A total of 2744 goat serum samples from 230 farms were collected between 2010 and 2012. The diagnosis of Corynebacterium pseudotuberculosis infection was performed using the indirect ELISA technique. Farm-level and animal-level seroprevalences were 87.8% and 30.3%, respectively, suggesting that C. pseudotuberculosis is widespread in goat herds of the Northeast region. The risk factors were as follows: absence of forage silage (odds ratio = 5.39), not separating animals by sex (odds ratio = 4.16) or by age (odds ratio = 6.30), not replacing old goat breeders (odds ratio = 7.80), and non-treatment of CL lumps prior to spontaneous rupture (odds ratio = 10.34). This study supports the idea that caseous lymphadenitis is widely disseminated in goats from Northeastern Brazil and based on the risk factor analysis attention should be given to the need to establish adequate control measures, such as incision and early drainage of superficial abscesses, quarantine and elimination of affected animals, periodic inspection of the herd, non-introduction of infected animals, and early disposal of animals with recurrent CL.

Strategies of the control of an outbreak of leptospiral infection in dairy cattle in Northeastern Brazil.

The aim of the present study was to describe the strategies of the control of an outbreak of leptospiral infection in dairy cattle in Maranhão State, Northeastern Brazil. In the period from January to July 2015, 18 (17%) out of 106 cows presented abortion, six (5.7%) stillbirth, and 12 (11.3%) repeated estrus, totaling 24 animals with reproductive problems. The diagnosis of leptospirosis was based on serology (microscopic agglutination test-MAT), bacteriological culture, and polymerase chain reaction (PCR). Antibiotic therapy, vaccination protocols, and changes in management practices were suggested as control measures. Of all animals on the farm (n = 280), 136 (48.6%) were seropositive for at least one serovar of Leptospira sp. No pure leptospiral culture was obtained. Eight of the animals with reproductive problems yielded positive PCR results (vaginal fluid of seven animals and urine and vaginal fluid of one animal). Genetic sequencing of a vaginal fluid/urine PCR-positive sample revealed Leptospira borgpetersenii. One year after the adoption of control measures, no reproductive problems were observed. Thus, leptospirosis probably caused the reproductive failures in the herd, and the control and prevention measures implemented were efficient in controlling the disease.

Susceptibility among breeds of sheep experimentally infected with Leptospira interrogans Pomona serogroup.

Leptospirosis is a disease that negatively affects the productive and reproductive indices of ruminants. Sheep are considered highly resistant to infection, although susceptibility may vary among breeds. Thus, the aim of the present study was to analyze the susceptibility between sheep breeds to the experimental infection by leptospires of the Pomona serogroup. Pomona serogroup, Kennewicki serovar strain (1 × 107 bacteria) was inoculated via the conjunctival route in 12 sheep divided into two groups, one comprising Santa Inês ewes and the other comprising crossbred sheep. In each group, five ewes were challenged with the bacterial strain and one was used as control. All sheep were monitored for 60 days, during which blood samples were collected for serological diagnosis and urine and vaginal fluid samples for molecular and microbiological analyses. Finally, as ewes were submitted to euthanasia and necropsy, some tissues of interest were collected for microbiological, molecular, and histopathological diagnoses. The groups were compared regarding the number of positive reactions according to diagnostic tests. All sheep in each group presented antibodies to Leptospira in all serological analyses, except animals of the control group. However the Santa Inês sheep presented higher concentration and duration of the titers, and their positive reactions were detected earlier than those in crossbred sheep. The antibody titers in group A (median 200, geometric mean 317.48) were significantly different from the group B (median 800, geometric mean 918.96) at D60 post-infection (P = 0,032). The Santa Inês sheep presented a higher number of positive reactions than did the crossbred sheep in the molecular diagnostic tests. According to the molecular diagnosis, the Santa Inês sheep presented more reactions (urine and vaginal fluid) compared to crossbred ewes, but there was no predominance in the detection of leptospiral DNA when comparing urine and vaginal fluid results, nor even between the number of positive kidneys and uterus. The Santa Inês sheep presented a higher number of positive bacteriological cultures. No sheep in either group presented alterations in anatomopathological and histopathological findings. Pure-bred sheep may be more susceptible than crossbred sheep to infection by Leptospira sp. Our findings emphasize the importance of the genital tract as a site of extraurinary infection and indicate the possibility of venereal transmission in the species.

Spatial analysis for bovine viral diarrhea virus and bovine herpesvirus type 1 infections in the state of Paraíba, northeastern Brazil.

BACKGROUND: Bovine Viral Diarrhea Virus (BVDV) and Bovine Herpesvirus type 1 (BoHV-1) cause reproductive problems in cattle and restrictions on international trade in animals worldwide. Both infections were detected in cattle herds in the Paraíba state, Northeastern Brazil, however, the spatial distribution and geographic identification of positive herds for these viruses has never been examined. Therefore, the aim of this study was to describe the spatial pattern of apparent prevalence estimate and to identify spatial clustering of positive herds of BVDV and BoHV-1 infections in cattle herds from the state of Paraíba, Northeastern Brazil. RESULTS: The herd-level prevalence for BVDV and BoHV-1 infections in Paraíba were, respectively, 65.5% (95% CI: 61.1-69.7) and 87.8% (95% CI: 84.5-90.5). The average apparent within-herd prevalence of BVDV was 31.8% and of BoHV-1 was 62.4%. The predicted prevalence was highest (0.42-0.75) for BVDV in the west, north and eastern part of Sertão and in the central and eastern part of Agreste/Zona da Mata. For BoHV-1, the highest predicted prevalence (0.74-0.97) was in some local areas across Sertão and throughout the eastern part of Agreste/Zona da Mata. Six significant clusters were detected for BVDV, a primary cluster covering the eastern Sertão region, with 11 herds, radius of 24.10 km and risk relative (RR) of 2.21 (P <  0.001) and five smaller significant clusters, involving one or two herds in Agreste/Zona da Mata region with a high RR. A significant clustering of BoHV-1 positive herds (P <  0.001) was detected in Agreste/Zona da Mata region with a radius of 77.17 km and a RR of 1.27, with 103 cases. Consistency was found between kriging and SatScan results for identification of risk areas for BVDV and BoHV-1 infections. CONCLUSIONS: The clusters detected contemplated different areas of the state, with BVDV cluster located in the Sertão and BoHV-1 in Agreste/Zona da Mata stratum. Through the risk mapping, it was possible to identify the areas in which the risk is significantly elevated, coincided with areas where there are borders with other states and in which there is a high movement of animals.

First study on seroepidemiology and isolation of Toxoplasma gondii in free-range chickens in the semi-arid region of Paraíba state, Brazil.

The aim of this study was to investigate the seroprevalence and isolation of Toxoplasma gondii in free-range chickens in the state of Paraíba, northeastern Brazil. For this, blood samples were collected from 483 chickens in five municipalities in the state of Paraíba. The indirect immunofluorescence assay for anti-T. gondii antibodies was performed. The seropositive birds were slaughtered, and their brains and hearts were collected in order to perform a bioassay in mice. An epidemiological questionnaire was applied on the smallholdings visited, and univariable and multivariable logistic regressions were used to evaluate risk factors. The prevalence of chickens seropositive for T. gondii was found to be 31.5 % (152/483), and 86.1 % (56/65) of the smallholdings were positive. Among the 71 chickens subjected to bioassaying in mice, isolates of T. gondii were obtained from 33 (46.5 %). The isolates were named TgCkBrPB1 to 33. It was observed that the higher the chickens' antibody titer was, the greater the chance of isolating the parasite also was. Sixteen of the 33 isolates (48.5 %) were lethal for all the mice inoculated until 30 days post-inoculation. The risk factors for infection with T. gondii among these free-range chickens were extensive and semi-extensive rearing systems, smallholdings located in urban areas, and presence of cats. The results indicate that the prevalence of T. gondii among chickens in the state of Paraíba is high. Many parasites remained viable in the tissues of the birds studied, and presence of the protozoan was directly related to the management of these birds.

Herd-level prevalence and risk factors for bovine viral diarrhea virus infection in cattle in the State of Paraíba, Northeastern Brazil.

Serological surveys based on a planned sampling on bovine viral diarrhea virus (BVDV) infection in Brazilian cattle herds are scarce. A cross-sectional study was carried out to determine herd- and animal-level seroprevalences and to identify risk factors associated with herd-level seroprevalence for BVDV infection in the State of Paraíba, Northeastern Brazil, from September 2012 to January 2013. The state was divided into three sampling strata, and for each stratum, the prevalence of herds infected with BVDV and the prevalence of seropositive animals was estimated by a two-stage sampling survey. In total, 2443 animals were sampled from 478 herds. A virus-neutralization test was used for BVDV antibody detection. A herd was considered positive when at least one seropositive animal was detected. The herd- and animal-level prevalences in the State of Paraíba were 65.5% (95% confidence interval (CI) = 61.1-69.7%) and 39.1% (95% CI = 33.1-45.6%), respectively. The frequency of seropositive animals per herd ranged from 10 to 100% (median of 50%). The risk factors identified were as follows: more than six calves aged ≤12 months (odds ratio (OR) = 3.72; 95% CI = 2.08-6.66), animal purchasing (OR = 1.66; 95% CI = 1.08-2.55), pasture rental (OR = 2.15; 95% CI = 1.35-3.55), and presence of veterinary assistance (OR = 2.04; 95% CI = 1.10-3.79). Our findings suggest that the implementation of control and prevention measures among farmers, with the aim of preventing dissemination of the agent in the herds, is necessary. Special attention should be given to addressing the identified risk factors, such as sanitary control prior to animal purchasing and to discourage the pasture rental, as well as to encourage the vaccination in the herds.

Global seroprevalence and factors associated with seropositivity for feline immunodeficiency virus (FIV) in cats: A systematic review and meta-analysis.

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.

Molecular e serological detection of Leishmania infantum (Trypanosomatida: Trypanosomatidae) in domestic dogs in Manaus city, Amazonas, Brazil.

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.

Multidrug-resistant Escherichia coli isolated from free-range chickens in the Caatinga biome.

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.

Antimicrobial resistance, enterotoxin and biofilm production genes in Staphylococcus spp. isolated from facilities and fomites in veterinary hospital in the Caatinga biome.

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.

The Role of Transplacental Infection in Leptospira spp. Epidemiology in Cattle in Caatinga Biome, Brazil.

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.

Epidemiological and clinicopathological findings of feline immunodeficiency virus and feline leukemia virus infections in domestic cats from the Brazilian semiarid region.

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.