Lower levels of CXCL-8 and IL-2 on admission as predictors of early adverse reactions to Bothrops antivenom in the Brazilian Amazon.

Snakebite envenomings are considered a global health problem. The specific therapy for these envenomings consists of administering animal-derived antivenoms aiming to neutralize the venom toxins. Antivenoms have been used effectively to treat snakebites for more than a century; however, their administration may result in early and/or late adverse reactions. The present study presents the prevalence of early adverse reactions (EARs) towards Bothrops antivenom therapy in a health tertiary unit in the Brazilian Amazon and explores if specific plasma cytokines and chemokines from envenomed patients could be used as predictors of EARs. A cohort of patients bitten by Bothrops atrox was followed-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), from 2014 to 2016. Patients were treated with the Brazilian Bothrops antivenom and CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-y, IL-4, and IL-17A were evaluated in patients' plasma samples before and after antivenom administration. From the total of patients (n = 186), mostly were male (82.3%), inhabiting rural areas (87.1%), with an average age of 35 years. Most of the patients (83.8%) were admitted to the hospital within 6 h after the accident, 26 (14%) reported having suffered a previous snakebite, and 97 (52.1%) received between 7 and 9 antivenom vials. The frequency of antivenom-induced EARs was 11.8% (22), resulting mostly of mild reactions. Urticaria was the major EAR manifestation (46.4%). Interestingly, CXCL-8 and IL-2 showed significantly lower levels in patients who progressed to EARs, although IL-2 levels might not represent biological relevance due the small magnitude difference between groups. This study reveals that CXCL-8 and IL-2 could play a role in the onset of EARs in pit viper envenomings.

Observation of Bothrops atrox Snake Envenoming Blister Formation from Five Patients: Pathophysiological Insights.

In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds.

Observation of Bothrops atrox snake envenoming blister formation from five patients: pathophysiological insights

In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds.

Bothrops atrox Snakebite: How a Bad Decision May Lead to a Chronic Disability: A Case Report.

Snakebites are a neglected and underestimated global health hazard. In the Brazilian Amazon, Bothrops snakebites are the most prevalent and may lead to severe complications. Here we describe a severe case of Bothrops atrox snakebite that, owing to delayed medical assistance, presented with renal and respiratory failure, compartment syndrome, and tissue necrosis. After several fasciotomy surgeries, the patient survived; however, he showed significant functional disability. Prompt management of snake envenomation would aid in the early diagnosis of local and systemic complications and, consequently, would result in a better functional outcome with improved quality of life.

Effects of a single trace mineral injection at beginning of fixed-time AI treatment regimen on reproductive function and antioxidant response of grazing Nellore cows.

Two experiments evaluated the effects of injectable trace minerals (ITM) administered 11 d before artificial insemination (AI) on body weight (BW), body condition score (BCS), ovarian structures, pregnancy rate, and antioxidant response of Nellore cows. In Experiment 1, 20 multiparous cows were assigned to one of two treatments: subcutaneous injection (6 mL/cow; 11 d before AI) of saline solution or ITM (60, 10, 5, and 15 mg/mL of Zn, Mn, Se and Cu, respectively) and BW, BCS, ovarian structures and blood were evaluated. In Experiment 2, 1,144 multiparous cows were assigned to same treatments described in Experiment 1 and pregnancy rate on d 30 was evaluated. In Experiment 1, ITM did not affect (P ≥  0.23) BW, dominant follicle size, ovulation rate, and plasma concentrations of haptoglobin, ceruloplasmin and progesterone (P4). The ITM treatment tended to increase (P =  0.06) cow BCS and reduce (P ≤  0.06) corpus luteum (CL) diameter and volume. Furthermore, ITM treatment tended to increase (P =  0.06) plasma concentrations of SOD and increased (P =  0.007) GSH-Px compared with saline injection. In Experiment 2, ITM treatment tended (P =  0.06) to increase pregnancy rate of cows with BCS ≤ 5.0 but not cows with BCS > 5.0 (P =  0.99). The ITM treatment did not alter BW, plasma P4, and acute phase response, but enhanced plasma concentrations of antioxidant enzymes, and tended to enhance BCS and pregnancy rates to AI of cows with BCS ≤ 5.0, even though there was a smaller corpus luteum size.

Sudden spleen rupture in a Plasmodium vivax-infected patient undergoing malaria treatment.

BACKGROUND: Splenomegaly is one of the most common features of malaria. However, spontaneous splenic rupture, although unusual, represents a severe complication often leading to death. It is mostly seen in acute infection and primary attack, and it is most commonly associated with Plasmodium vivax. Here, a case of spontaneous splenic rupture diagnosed with a portable ultrasound apparatus shortly after starting treatment and with recurrent parasitaemia after splenectomy, is reported. CASE DESCRIPTION: In November 2015, a 45-year-old Brazilian man presented to the hospital in Manaus with fever, headache and myalgia. He was diagnosed with P. vivax malaria and, after a normal G6PD test, he started treatment with chloroquine and primaquine and was discharged. Two days later, he went back to the hospital with abdominal pain, dyspnea, dry cough, pallor, oliguria and fever. Using a portable ultrasound, he was diagnosed of rupture of the spleen, which was removed by emergency surgery. After this episode, he suffered two more malaria episodes with high parasitaemia at approximately 2-month intervals. DNA from different portions of the spleen was extracted and a qualitative PCR was performed to detect P. vivax. CONCLUSIONS: The splenic rupture suffered by this patient occurred 2 days after starting the treatment. Having a portable ultrasound apparatus may have saved the patient's life, as it revealed a haemorrhage needing an urgent surgery. Parasites were detected by PCR in the extracted spleen. This patient suffered two more vivax malaria diagnosed episodes in spite of receiving and completing treatment with chloroquine and primaquine for each clinical attack. Splenic rupture during acute malaria is uncommon, but it is likely underdiagnosed and underreported, because the lack of means and equipment hinders diagnostic confirmation, especially in endemic areas.

Impact of vaccination on the reproductive performance of multiparous Nellore cows / Impacto da vacinação sobre o desempenho reprodutivo de vacas Nelore multíparas

Two experiments were conducted to evaluate the impact of two vaccines on the reproductive performance of multiparous beef cows in Mato Grosso do Sul, Midwest Brazil. In Experiment 1,765 calved multiparous Nellore cows were subjected to the same fixed-time artificial insemination (FTAI) protocol and rebred. Ultrasound pregnancy diagnosis was performed 30 and 90 days post-FTAI (DPI). Rates of pregnancy and pregnancy loss were determined for three periods: from 30 to 90 DPI, from 30 DPI to calving, and from 90 DPI to calving. The cows were assigned to three groups with different vaccination protocols - namely, Group VACMULT (n=250): vaccine against bovine herpesvirus 1 (BoHV-1), bovine viral diarrhea virus (BVDV), and leptospirosis; Group VACL (n=245): vaccine against leptospirosis alone; Group NOVAC (n=270): no vaccination. Serum antibody titers for BoHV-1, BVDV, and leptospirosis, measured in 57 cows from each group indicated active infection, suggesting circulation of these pathogens in the herd. No differences in pregnancy rates were observed across groups. Pregnancy loss rates did not differ significantly across groups within any of the periods investigated (30 to 90 DPI, 30 DPI to calving, or 90 DPI to calving). In Experiment 2, two vaccination protocols for each vaccine were investigated. Group VACGEST was vaccinated on day zero of FTAI (D0) and again 30 days post-FTAI (30 DPI). Group VACPREV was vaccinated on D0 and again on the day of insemination (D11). No significant difference was observed between groups, or significant gestational loss in the group that received the second vaccine on the day of insemination. The results revealed that neither vaccine interfered with the reproductive performance of multiparous cows. No differences were observed between vaccination carried out on both D0 and D11 and that performed on both D0 and D30. The performance of the IBR/BVDV/Leptospirosis vaccine on the day of the artificial insemination did not cause adverse effects on the reproductive parameters.(AU)

Foram delineados dois experimentos para avaliar o impacto de duas vacinas no desempenho reprodutivo de vacas multíparas de bovinos de corte em Mato Grosso do Sul, Centro-Oeste do Brasil. No Experimento 1 foram utilizadas 765 vacas multíparas paridas da raça Nelore submetidas ao mesmo protocolo de inseminação artificial em tempo fixo (IATF) e repassadas por touros. O diagnóstico de gestação por ultrassonografia foi realizado aos 30 e 90 dias pós IATF. A prenhez e a taxa de perda de gestação foram determinadas para três períodos: de 30 a 90 DPI, de 30 DPI até para o parto e de 90 DPI até o parto. As vacas foram distribuídas em três grupos: grupo VACMULT (n=250), vacinado com vacina contra herpesvírus bovino tipo 1 (BoHV-1), vírus da diarreia viral bovina (BVDV) e leptospirose; grupo VACL (n=245), vacinado somente contra leptospirose; e grupo NOVAC (n=270), não vacinado. Títulos de anticorpos no soro de 57 vacas de cada grupo evidenciaram infecção por BoHV-1, BVDV e leptospirose, sugerindo circulação desses patógenos no rebanho. No diagnóstico por ultrassonografia, a prenhez não diferiu em nenhum dos três grupos. A taxa de perda de gestação não diferiu significantemente entre os grupos e dentro de qualquer um dos períodos investigados (30 a 90 DPI, 30 DPI até o parto ou 90 DPI até o parto). No Experimento 2 foram testados dois protocolos de vacinação usando as vacinas contra IBR/BVDV/leptospirose e somente contra leptospirose em ambos. No grupo VACGEST as vacas foram vacinas no dia zero (D0) do protocolo da IATF e 30 dias pós- IATF (30 DPI). No grupo VACPREV a primeira dose foi administrada no D0 e a segunda no mesmo dia da IATF (D11). Não houve diferença significativa entre os grupos, nem perda gestacional significativa no grupo que recebeu a segunda vacina no dia da inseminação (VACPREV). Os resultados mostram que as vacinas contra IBR/BVDV/leptospirose e somente contra leptospirose não interferiram no desempenho reprodutivo de vacas multíparas. Não houve diferença significativa entre o protocolo de vacinação empregado em D0 e D11 e aquele utilizado em D0 e 30 DPI. A realização da vacina contra IBR/BVD/leptospirose no dia da inseminação artificial não provocou efeitos adversos nos parâmetros reprodutivos.(AU)

Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from Bothrops snakebites in the Brazilian Amazon: A randomized controlled clinical trial.

BACKGROUND: Secondary bacterial infections from snakebites contribute to the high complication rates that can lead to permanent function loss and disabilities. Although common in endemic areas, routine empirical prophylactic use of antibiotics aiming to prevent secondary infection lacks a clearly defined policy. The aim of this work was to estimate the efficacy of amoxicillin clavulanate for reducing the secondary infection incidence in patients bitten by Bothrops snakes, and, secondarily, identify risk factors for secondary infections from snakebites in the Western Brazilian Amazon. METHODS AND FINDINGS: This was an open-label, two-arm individually randomized superiority trial to prevent secondary infection from Bothrops snakebites. The antibiotic chosen for this clinical trial was oral amoxicillin clavulanate per seven days compared to no intervention. A total of 345 patients were assessed for eligibility in the study period. From this total, 187 accomplished the inclusion criteria and were randomized, 93 in the interventional group and 94 in the untreated control group. All randomized participants completed the 7 days follow-up period. Enzyme immunoassay confirmed Bothrops envenoming diagnosis in all participants. Primary outcome was defined as secondary infection (abscess and/or cellulitis) until day 7 after admission. Secondary infection incidence until 7 days after admission was 35.5% in the intervention group and 44.1% in the control group [RR = 0.80 (95%CI = 0.56 to 1.15; p = 0.235)]. Survival analysis demonstrated that the time from patient admission to the onset of secondary infection was not different between amoxicillin clavulanate treated and control group (Log-rank = 2.23; p = 0.789).Secondary infections incidence in 7 days of follow-up was independently associated to fibrinogen >400 mg/dL [AOR = 4.78 (95%CI = 2.17 to 10.55; p<0.001)], alanine transaminase >44 IU/L [AOR = 2.52 (95%CI = 1.06 to 5.98; p = 0.037)], C-reactive protein >6.5 mg/L [AOR = 2.98 (95%CI = 1.40 to 6.35; p = 0.005)], moderate pain [AOR = 24.30 (95%CI = 4.69 to 125.84; p<0.001)] and moderate snakebites [AOR = 2.43 (95%CI = 1.07 to 5.50; p = 0.034)]. CONCLUSIONS/SIGNIFICANCE: Preemptive amoxicillin clavulanate was not effective for preventing secondary infections from Bothrops snakebites. Laboratorial markers, such as high fibrinogen, alanine transaminase and C-reactive protein levels, and severity clinical grading of snakebites, may help to accurately diagnose secondary infections. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (ReBec): RBR-3h33wy; UTN Number: U1111-1169-1005.

Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from Bothrops snakebites in the Brazilian Amazon: a randomized controlled clinical trial

Background Secondary bacterial infections from snakebites contribute to the high complication rates that can lead to permanent function loss and disabilities. Although common in endemic areas, routine empirical prophylactic use of antibiotics aiming to prevent secondary infection lacks a clearly defined policy. The aim of this work was to estimate the efficacy of amoxicillin clavulanate for reducing the secondary infection incidence in patients bitten by Bothrops snakes, and, secondarily, identify risk factors for secondary infections from snakebites in the Western Brazilian Amazon. Methods and findings This was an open-label, two-arm individually randomized superiority trial to prevent secondary infection from Bothrops snakebites. The antibiotic chosen for this clinical trial was oral amoxicillin clavulanate per seven days compared to no intervention. A total of 345 patients were assessed for eligibility in the study period. From this total, 187 accomplished the inclusion criteria and were randomized, 93 in the interventional group and 94 in the untreated control group. All randomized participants completed the 7 days follow-up period. Enzyme immunoassay confirmed Bothrops envenoming diagnosis in all participants. Primary outcome was defined as secondary infection (abscess and/or cellulitis) until day 7 after admission. Secondary infection incidence until 7 days after admission was 35.5% in the intervention group and 44.1% in the control group [RR = 0.80 (95% CI = 0.56 to 1.15; p = 0.235)]. Survival analysis demonstrated that the time from patient admission to the onset of secondary infection was not different between amoxicillin clavulanate treated and control group (Log-rank = 2.23; p = 0.789). Secondary infections incidence in 7 days of follow-up was independently associated to fibrinogen >400 mg/dL [AOR = 4.78 (95% CI = 2.17 to 10.55; p<0.001)], alanine transaminase >44 IU/L [AOR = 2.52 (95% CI = 1.06 to 5.98; p = 0.037)], C-reactive protein >6.5 mg/L [AOR = 2.98 (95% CI = 1.40 to 6.35; p = 0.005)], moderate pain [AOR = 24.30 (95% CI = 4.69 to 125.84; p<0.001)] and moderate snakebites [AOR = 2.43 (95% CI = 1.07 to 5.50; p = 0.034)]. Conclusions/Significance Preemptive amoxicillin clavulanate was not effective for preventing secondary infections from Bothrops snakebites. Laboratorial markers, such as high fibrinogen, alanine transaminase and C-reactive protein levels, and severity clinical grading of snakebites, may help to accurately diagnose secondary infections.

CD11c+CD123Low dendritic cell subset and the triad TNF-α/IL-17A/IFN-γ integrate mucosal and peripheral cellular responses in HIV patients with high-grade anal intraepithelial neoplasia: a systems biology approach.

BACKGROUND: The incidence of anal cancer has increased over the past 25 years, and HIV/HPV coinfection is the most important risk factor for anal squamous cell carcinoma. In this study, we demonstrated that the evaluation of systemic and compartmentalized anal mucosa immune response is relevant to differentiating HIV(+) patients at risk of anal intraepithelial neoplasia (AIN). METHODS: A systems biology approach was used to integrate different immunological parameters from anal mucosal tissue and peripheral blood assessed by phenotypic and intracytoplasmic analysis of lymphocytes and dendritic cell subsets. RESULTS: Our data demonstrated that anal mucosal mononuclear cells from AIN(+)HIV(+) patients showed a robust capacity in producing proinflammatory/regulatory cytokines, mainly mTNF-α > IL-4 > IL-10 > IL-6 = IL-17A. Mucosal TNF-α/IFN-γ/IL-17A are selective high-grade squamous intraepithelial lesion (HSIL)-related biomarkers. Higher levels of circulating CD11cCD123cells and CD1a cells along with elevated levels of IFN-γCD4 T cells are major features associated with HSIL in AIN(+)HIV(+) patients. Regardless of the presence of AIN, HIV(+) patients presented a complex biomarker network, rich in negative connections. Among those patients, however, HSIL+ patients displayed stronger positive links between peripheral blood and anal mucosa environments, exemplified by the subnet of IL-17A/TNF-α/CD4IFN-γ/CD11cCD123 cells. CONCLUSIONS: The significant association between HSIL and the levels of TNF-α/IL-17A/IFN-γ along with the different subsets of DCs present in the anal mucosa milieu should be studied in more detail as a way to identify and categorize HIV(+) patients vis à vis the high risk of anal cancer outcome.

Prevalence of and risk factors for penile infection by high-risk human papillomavirus among men infected with HIV.

This study aimed to determine the prevalence of and risk factors for high-risk human papillomavirus (HPV) genital infection and precursor lesions of penile cancer among patients infected with human immunodeficiency virus (HIV). In total, 276 men with a mean age of 34.6 years were included. All participants were subjected to peniscopic examination under magnification, collection of genital exfoliated cells for detecting HPV types using Hybrid Capture, and biopsy surgery of clinically observable lesions and aceto-white areas for histopathological studies. The prevalence of high-risk HPV types was 43%. Peniscopicy showed clinically visible lesions or aceto-white areas in 75/276 participants (27%), of which genital warts were the most common (22/75; 29%). HIV-positive (HIV(+) ) men with CD4(+) T-cell counts <200 cells/mm(3) showed a higher prevalence of penile lesions. Multivariate logistic regression was applied to identify independent risk factors for high-risk HPV types. The results showed that high-risk HPV was associated with lower education level (OR = 1.89, 95% CI: 1.15-3.13), illicit drug use (OR = 1.80, 95% CI: 1.03-3.14), mulatto ethnicity (OR = 2.51, 95% CI: 1.38-4.54), heterosexual orientation (OR = 2.12, 95% CI: 1.30-3.47) symptomatic AIDS (OR = 2.80, 95% CI: 1.65-4.77), AIDS-associated opportunistic infections (OR = 2.92, 95% CI: 1.78-4.78), on HAART (OR = 2.91, 95% CI: 1.78-4.77), and CD4(+) T-cell count <200 cells/mm(3) (OR = 3.31, 95% CI: 1.84-5.96). Immunocompromised men were more susceptible to developing penile lesions associated with high-risk HPV types.

Postmortem characterization of patients with clinical diagnosis of Plasmodium vivax malaria: to what extent does this parasite kill?

BACKGROUND: Severe disease attributable to Plasmodium vivax infection is already well described worldwide; however, autopsies in these patients are scarce. METHODS: From 1996 to 2010, 19 patient deaths with a clinical diagnosis of P. vivax infection occurred in a tertiary care center in the Brazilian Amazon. Seventeen of these 19 deaths were fully autopsied. Clinical charts, macroscopic autopsy reports, and stored paraffinized tissue blocks were retrieved. Nested polymerase chain reaction was performed in paraffinized samples of spleen and lung to confirm P. vivax monoinfection. Immunohistofluorescence was used to detect P. vivax parasitized red blood cells (RBCs). RESULTS: Of 17 autopsies, 13 revealed that death could be attributed to P. vivax infection; in the remaining 4, acute diseases other than malaria were found to be the cause of death. The primary complication in patients in which malaria contributed to death was acute respiratory distress syndrome (ARDS) and pulmonary edema associated with the accumulation of neutrophils in the interalveolar space (6 cases). Spleen rupture (3 cases) and multiorgan dysfunction syndrome (3 cases) were the second most common complications. One child evolving with coma was also characterized, but no parasite was detected in the brain tissue. In one patient who developed ARDS and presented negative peripheral parasitemia by the time of death, scattered parasitized red blood cells were seen inside pulmonary capillaries, suggesting some sequestration in the lung. CONCLUSIONS: In 13 of 17 deceased patients, P. vivax infection was the plausible cause of death. However, more studies are needed to understand pathogenesis related to severe disease.

Clinical and laboratorial study of HPV infection in men infected with HIV.

OBJECTIVES: To determine the prevalence of precursor lesions of penile cancer, to establish the concordance of diagnostic techniques (PCR, Hybrid Capture (HC) and peniscopy with acetic acid 5%) in the diagnosis of Human Papilloma Virus (HPV) of the penis of men infected with HIV and to evaluate the influence of the immune status. PATIENTS, METHODS AND RESULTS: 276 men were studied, with a median age of 34.6 years. Prevalence of High Risk HPV, Low Risk HPV and infection with both, according to HC, was 43%, 32% and 22%, respectively. PCR showed 50% of positivity for HPV DNA. Peniscopy was positive in 27% of individuals. Peniscopy showed good specificity and low sensitivity for the detection of penile HPV, and low concordance with PCR. Men with white lesions had a 3.6 higher relative risk of positivity for HPV. The most common clinical lesion observed was vegetation, identified in 29% of patients. PCR and HC techniques showed high sensitivity for HPV DNA and there was an excellent correlation between them. Immunosuppressed individuals with CD4 < 200 cells/mm(3) had the highest prevalence of premalignant lesions that were observed in 10% of the studied individuals. CONCLUSIONS: Peniscopy was important for identification and treatment of subclinical lesions. PCR and HC techniques were sensitive methods for the detection of HPV DNA with high concordance. Severely immunosuppressed individuals showed a higher prevalence of pre-malignant lesions of the penis.

Clinical and laboratorial study of HPV infection in men infected with HIV

OBJECTIVES: To determine the prevalence of precursor lesions of penile cancer, to establish the concordance of diagnostic techniques (PCR, Hybrid Capture (HC) and peniscopy with acetic acid 5%) in the diagnosis of Human Papilloma Virus (HPV) of the penis of men infected with HIV and to evaluate the influence of the immune status. PATIENTS, METHODS AND RESULTS: 276 men were studied, with a median age of 34.6 years. Prevalence of High Risk HPV, Low Risk HPV and infection with both, according to HC, was 43%, 32% and 22%, respectively. PCR showed 50% of positivity for HPV DNA. Peniscopy was positive in 27% of individuals. Peniscopy showed good specificity and low sensitivity for the detection of penile HPV, and low concordance with PCR. Men with white lesions had a 3.6 higher relative risk of positivity for HPV. The most common clinical lesion observed was vegetation, identified in 29% of patients. PCR and HC techniques showed high sensitivity for HPV DNA and there was an excellent correlation between them. Immunosuppressed individuals with CD4< 200 cells/mm3 had the highest prevalence of pre-malignant lesions that were observed in 10% of the studied individuals. CONCLUSIONS: Peniscopy was important for identification and treatment of subclinical lesions. PCR and HC techniques were sensitive methods for the detection of HPV DNA with high concordance. Severely immunosuppressed individuals showed a higher prevalence of pre-malignant lesions of the penis.

Presence of Borrelia burgdorferi "Sensu Lato" in patients with morphea from the Amazonic region in Brazil.

BACKGROUND: In the present study, Borrelia spirochetes were found in four (26.6%) out of 15 patients with Atrophoderma of Pasini and Pierini (IAPP) and lichen sclerosis et atrophicans (LSA) from the Brazilian Amazon Region. MATERIAL AND METHODS: Borreliosis was investigated by immunohistochemistry and focus floating microscopy for Borrelia burgdorferi in skin biopsy samples from 15 patients with both clinical and histopathology evidences compatible with Morphea, LSA, and IAPP. RESULTS: Spirochetes were detected by specific immunohistochemistry and focus floating microscopy for B. burgdorferi in samples from three patients. A limitation of our study was the fact that we were not able to isolate and culture these organisms. CONCLUSION: Our data confirm the presence of borreliosis cases in the Amazon.

Doença das mucosas associada à dermatite generalizada em bovinos, Mato Grosso do Sul / Mucosal disease associated with generalized dermatitis in cattle, Mato Grosso do Sul, Brazil

São descritos os aspectos epidemiológicos, clínicos, patológicos e diagnósticos de uma forma de dermatite associada à doença das mucosas (DM) em bovinos. Também são abordadas metodologias para a identificação de animais persistentemente infectados (PI) e o impacto nos índices zootécnicos no rebanho afetado. Os casos de dermatite associados com DM ocorreram em dois bovinos Nelore, de 12 e 24 meses de idade, pertencentes a uma fazenda de ciclo completo de bovinos de corte no estado de Mato Grosso do Sul. Os sinais clínicos nesses animais consistiam de emagrecimento lento e progressivo, formação de crostas difusas na pele de todo o corpo, pele ressecada, múltiplas ulcerações nas gengivas e face dorsal da língua, que evoluíram para fendas longitudinais, formação de projeções cornificadas e desprendimento dos cascos. Em um caso, também ocorreu diarréia no estágio final da doença. Na necropsia observaram-se ainda erosões longitudinais no esôfago. O exame histológico revelou focos de necrose de coagulação na mucosa do esôfago e língua, com infiltrado de neutrófilos e linfócitos. As lesões da pele consistiam de necrose de coagulação da epiderme associada com infiltrado de neutrófilos e hiperqueratose. Nos dois casos, a suspeita clínica foi confirmada pelo isolamento viral e identificação dos biótipos citopático e não-citopático do vírus da diarréia viral bovina (BVDV), além da detecção de antígenos virais em tecidos por imunoistoquímica. De um lote de 300 bovinos que tiveram contato com animais afetados, 38 foram testados e apresentaram altos títulos de anticorpos para o BVDV. Amostras de sangue coletadas de 1.025 animais jovens e 40 touros da propriedade foram submetidas a pesquisa de vírus para se identificarem possíveis animais persistentemente infectados (PI). O vírus foi isolado do sangue de três bezerros no teste inicial e, 12 meses depois, em dois deles que permaneceram na propriedade. Imunoistoquímica realizada em biópsia de orelhas identificou...

This paper reports epidemiological, clinical, pathological and laboratory diagnostic aspects of a form of dermatitis associated with mucosal disease (MD) in cattle. It also focuses on the methods used for identifying persistently infected (PI) animals and on the impact of the disease on fertility and weaning rates in the affected herd. Cases of dermatitis associated with MD were diagnosed in two 12 and 24-month-old Nelore calves belonging to a beef cattle farm that operates the full cycle of production (calving, rearing, finishing) in Mato Grosso do Sul, Midwest Brazil. The clinical signs exhibited by affected cattle 0included slow, progressive weight loss; formation of diffuse skin crusts in multiple body areas; skin dryness; multiple ulcerations on the gums and dorsal surface of the tongue which evolved to longitudinal fissures; formation of keratinized projections; and detachment of hoof horn. In addition, diarrhea affected one animal in the late stage of the disease. Necropsies also revealed longitudinal erosions in the esophagus. Histological examination showed coagulation necrosis foci in esophageal and lingual mucosae, with neutrophil and lymphocyte infiltration. Skin lesions consisted of epidermal coagulation necrosis associated with neutrophil infiltration and hyperkeratosis. In both cases, clinical diagnosis was confirmed by the isolation and identification of cytopathic and noncytopathic biotypes of the bovine viral diarrhea virus (BVDV) and immunohistochemical detection of viral antigens in formalin fixed tissues. Out of 300 cattle that had contact with the affected animals, 38 were found to be seropositive - in high neutralizing titers - to BVDV. Blood samples from 1,025 young animals and 40 bulls from the farm were examined for the presence of BVDV to identify potential PI animals. The virus was isolated from blood of three calves in the initial test and, 12 months later, from two of them which had remained...