Os desafios na conduta terapêutica em pacientes acometidos com feridas crônicas / Challenges in the therapeutic conduct in patients affected with chronic wounds / Retos en la conducta terapéutica en pacientes afectados de heridas crónicas

Considerado um grave problema em saúde pública, as feridas crônicas são patologias que desafiam o manejo terapêutico e infelizmente acometem milhares de pessoas em todo o mundo. Essa doença apresenta altos índices de morbidade impactando negativamente na qualidade de vida dos seus portadores, além de influenciar negativamente no domínio "bem-estar", principalmente quando associado aos fatores clínicos podendo estar relacionado há anos de tratamento sem cura da ferida. As feridas crônicas são caracterizadas por demora ou dificuldade nos processos de cicatrização e reparação ordenada da integridade anatômica e funcional da pele durante um período de no mínimo três meses. Porém, algumas lesões permanecem por anos e até décadas sem cicatrizar. Objetivo: O escopo dessa revisão é mostrar o limitado arsenal terapêutico bem como a dificuldade no manejo clínico e dessa forma proporcionar uma reflexão sobre sua fisiopatologia e a urgente necessidade de novas opções e condutas terapêuticas que possam auxiliar no tratamento desses pacientes. Metodologia: Trata-se de uma revisão integrativa da literatura sobre feridas crônicas, cujo critérios de inclusão foram artigos publicados no período de janeiro de 2005 a fevereiro de 2023. Conclusão: A problemática acerca dessa patologia é vasta, tratando de uma doença de difícil cura, com uma gama de fatores associados que dificultam a cura da lesão, estendendo essa doença a altos índices de morbidade. Novas condutas terapêuticas e novos fármacos, precisam ser desenvolvidos urgentemente. Destaca-se que o uso de probióticos e o emprego da nanotecnologia tem mostrado um grande potencial inovador no tratamento de pacientes portadores de feridas crônicas.

Considered a serious public health problem, chronic wounds are pathologies that defy therapeutic management and unfortunately affect thousands of people around the world. This disease has high morbidity rates, negatively impacting the quality of life of its patients, in addition to negatively influencing the "well-being" domain, especially when associated with clinical factors, which may be related to years of treatment without healing of the wound. Chronic wounds are characterized by delay or difficulty in healing processes and orderly repair of the anatomical and functional integrity of the skin over a period of at least three months. However, some injuries remain for years and even decades without healing. Objective: The scope of this review is to show the limited therapeutic arsenal as well as the difficulty in clinical management and thus provide a reflection on its pathophysiology and the urgent need for new options and therapeutic approaches that can help in the treatment of these patients. Methodology: This is an integrative review of the literature on chronic wounds, whose inclusion criteria were articles published from January 2005 to February 2023. Conclusion: The problem surrounding this pathology is vast, dealing with a difficult-to-cure disease, with a range of associated factors that make healing of the lesion difficult, extending this disease to high morbidity rates. New therapeutic approaches and new drugs need to be developed urgently. It is noteworthy that the use of probiotics and the use of nanotechnology have shown great innovative potential in the treatment of patients with chronic wounds.

Consideradas un grave problema de salud pública, las heridas crónicas son patologías que desafían el manejo terapéutico y que, lamentablemente, afectan a miles de personas en todo el mundo. Esta enfermedad presenta altas tasas de morbilidad, impactando negativamente en la calidad de vida de sus pacientes, además de influir negativamente en el dominio "bienestar", especialmente cuando se asocia a factores clínicos, que pueden estar relacionados con años de tratamiento sin curación de la herida. Las heridas crónicas se caracterizan por un retraso o dificultad en los procesos de cicatrización y reparación ordenada de la integridad anatómica y funcional de la piel durante un periodo de al menos tres meses. Sin embargo, algunas heridas permanecen durante años e incluso décadas sin cicatrizar. Objetivo: El alcance de esta revisión es mostrar el limitado arsenal terapéutico así como la dificultad en el manejo clínico y así aportar una reflexión sobre su fisiopatología y la urgente necesidad de nuevas opciones y enfoques terapéuticos que puedan ayudar en el tratamiento de estos pacientes. Metodología: Se trata de una revisión integradora de la literatura sobre heridas crónicas, cuyos criterios de inclusión fueron artículos publicados desde enero de 2005 hasta febrero de 2023. Conclusiones: La problemática que rodea a esta patología es amplia, tratándose de una enfermedad de difícil curación, con una serie de factores asociados que dificultan la cicatrización de la lesión, extendiendo esta enfermedad a altas tasas de morbilidad. Es urgente desarrollar nuevos enfoques terapéuticos y nuevos fármacos. Cabe destacar que el uso de probióticos y el empleo de nanotecnología han mostrado un gran potencial innovador en el tratamiento de pacientes con heridas crónicas.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and esophageal rupture by candida infection: A case report and review.

We probably describe the first report of esophageal rupture in a patient with autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy (APECED, OMIM # 240300), who had candida esophagitis as the main feature for decades. Strong evidence shows that this rupture may have been caused directly and indirectly by chronic candidiasis. In this way, we demonstrate how severe and harmful the persistent esophageal candidiasis can cause in the esophagus, especially in immunodeficient patients.

Susceptibility of Candida albicans Strains Isolated from Vaginal Secretion in Front of the Mycocins of Wickerhamomyces anomalus.

Mycocins are substances that have the potential to affect other sensitive yeasts or microorganisms. Wickerhamomyces anomalus is a yeast that produces mycocins that have great biotechnological potential, being highly competitive in many habitats, as it is adaptable to a wide range of environmental conditions. Thus, they are targets for studies in different areas, including the environment, industry, and medical sciences. Yeasts of the genus Candida are of great importance due to the high frequency with which they colonize and infect the human host. Yeast infections are often difficult to treat due to the acquisition of resistance against antifungals, leading to studies focusing in new treatment alternatives. This work aims to verify the inhibition of Candida albicans isolated from vaginal secretion by mycocins produced by Wickerhamomyces anomalus. Tests were carried out in solid medium and microdilution tests, where mycocins proved to be efficient in inhibiting the growth of C. albicans, hemolysis, and irritation in an organotypic model, which showed that the mycocins produced by W. anomalus are safe and non-irritating. Thus, the results of this work can provide scientific evidence for the application of mycocins in the production of new antifungal alternatives.

Relation between CANDIDA species isolated from vaginal mucosa and lesions caused by high-risk human papillomavirus hpv for cervical cancer

This study characterized and related yeasts of the genus Candida isolated from vaginal mucous membranes of women with lesions caused by high-risk HPV for cervical cancer. Forty-two women treated at the Lower Genital Tract Pathology Clinic of the University of São Paulo Medical School Hospital of Clinics were examined, with 30 high-grade (G1) uterine lesions with a mean age of 36.5 years ± 11. 1 and 12 with low grade (G2) uterine lesions with a mean age of 34.7 years ± 15.5. Clinical conditions and laboratory data on HPV were collected from patients' medical records; the socio-demographic data obtained from an appropriate questionnaire. For the study of association between the variables, Odds Ratio analysis was used from the STATA 13.1 program. Patients G1 had a higher prevalence for diabetes and the results indicated 27% prevalence of Candida spp. in vaginal mucosa, in G2 this was 33% in vaginal mucosa. Among the species found in vaginal mucosa of patients, Candida albicans was the most isolated with 88%, followed by C. tropicalis (8%) and C. glabrata (4%). The strains of C. albicans isolated from mucosa presented sensitivity to all antifungal agents tested, unlike the C. tropicalis strain isolated in G2 in vaginal mucosa, which presented a resistance profile to fluconazole. Thus, monitoring and supervision through clinical and laboratory testing of HPV patients is important, reinforcing the need for care, treatment and prevention of HPV-related infections and Candida spp.

Multicenter study of Candida species in oral mucosa of different patients: analysis of 711 strains and literature review

This study aimed to identify Candida spp. collected from oral mucosa and maintained in culture collections, correlating the findings with the medical history of patients and comparing with data from the literature over the past five years. Seven hundred and eleven oral Candida spp. isolates, collected between 2013 and 2017, were selected and identified using traditional and molecular methods. In addition, a literature review was performed with the key words: "Oral", "Candida" and "Yeast". Seven species of the genus Candida: were identified C. albicans(73.3%); C. tropicalis (9.3%); C. parapsilosis (8.2%); C. glabrata (3.9%); C. guilliermondii(2.8%); C. krusei (1.7%) and C. lusitaniae (0.3%). The strains identified as C. albicans were submitted to molecular methods using specific primers and of these, 5.8% were identified as C. dubliniensis strains. The greatest diversity of strains was found in patients presenting no systemic diseases or HIV +, while the highest percentage of strains of Candidanon-albicanswere observed in cancer patients. This study reports a representative distribution of Candidaspecies among individuals exhibiting distinct clinical conditions, in order to contribute to the design of future research on details of aspects involved in the infections caused by these microorganisms. The correct identification of oral Candida strains contributes to a realistic epidemiological approach and future clinical protocols against these pathogens

Apiotrichum veenhuisii isolated from a pediatric patient with acute myeloid leukemia: The first case in humans.

This is the first report of the yeast Apiotrichum veenhuisii (formerly Trichosporon veenhuisii) causing disease in humans; its virulence and in vitro behavior against antifungals were also studied. The sample was isolated from biopsy fragments of disseminated lesions on the skin of a pediatric patient with acute myeloid leukemia. The studied virulence factors evidenced that the strain tested negative for secretion of the enzymes proteinase, phospholipase, and hemolysin. The isolate was characterized as low biofilm producer. Except for amphotericin B and voriconazole, the sample presented high minimum inhibitory concentration values against azole and echinocandins.

Infections Caused by Fusarium Species in Pediatric Cancer Patients and Review of Published Literature.

Fusarium species have emerged as responsible for a broad spectrum of infections, including superficial, locally invasive and disseminated ones, especially in the hospital environment. Since there are few reports of invasive and disseminated fusariosis in children, the aim of this study was to report four cases of nosocomial infection caused by this microorganism in children with cancer hospitalized in a public children's hospital located in Brazil. Two of these patients were female and two were male. All patients presented febrile neutropenia, while three patients had acute lymphocytic leukemia and one patient had Wilms' tumor as underlying disease. In two cases, fungi were isolated from blood and identified as Fusarium oxysporum species complex after phenotypic and genotypic studies, while in two other cases fungi were isolated from skin biopsies and identified as Fusarium solani species complex. One patient died 12 days after the onset of cutaneous lesions. All isolates, after susceptibility testing, presented high levels of minimum inhibitory concentration for itraconazole, voriconazole and amphotericin B. Considering the emergence of filamentous fungi as etiologic agents of nosocomial infections, health professionals should be aware of the problems these infections, especially fungal ones, may cause to debilitated patients.

Antifungal Activity of Chitosan-Coated Poly(lactic-co-glycolic) Acid Nanoparticles Containing Amphotericin B.

Amphotericin B (AmB) is one of the most used drugs for the treatment of systemic fungal infections; however, the treatment causes several toxic manifestations, including nephrotoxicity and hemolytic anemia. Chitosan-coated poly(lactide-co-glycolide) (PLGA) nanoparticles containing AmB were developed with the aim to decrease AmB toxicity and propose the oral route for AmB delivery. In this work, the antifungal efficacy of chitosan-coated PLGA nanoparticles containing AmB was evaluated in 20 strains of fungus isolates from patients with vulvovaginal candidiasis (01 Candida glabrata and 03 Candida albicans), bloodstream infections (04 C. albicans and 01 C. tropicalis) and patients with urinary tract infection (04 Candida albicans, 02 Trichosporon asahii, 01 C. guilhermondii, 03 C. glabrata) and 01 Candida albicans ATCC 90028. Moreover, the cytotoxicity over erythrocytes was evaluated. The single-emulsion solvent evaporation method was suitable for obtaining chitosan-coated PGLA nanoparticles containing AmB. Nanoparticles were spherical in shape, presented mean particle size about 460 nm, positive zeta potential and encapsulation efficiency of 42%. Moreover, nanoparticles prolonged the AmB release. All the strains were susceptible to plain AmB and nanostructured AmB, according to EUCAST breakpoint version 8.1 (resistant > 1 µg/mL), using broth microdilution method. In C. albicans (urine, blood, and vulvovaginal secretion isolates, and 1 ATCC), the MIC value of AmB-loaded nanoparticles varied from 0.25 to 0.5 µg/mL and EUCAST varied from 0.03 to 0.5 µg/mL. In urine and vulvovaginal secretion isolates of C. glabrata, the MIC value of AmB-loaded nanoparticles varied from 0.25 to 0.5 µg/mL and EUCAST varied from 0.03 to 0.015 µg/mL. In urine isolates of C. guilhermondii, the MIC value of AmB-loaded nanoparticles was 0.12 µg/mL and EUCAST was 0.06 µg/mL. In blood isolates of C. tropicalis, the MIC value of AmB-loaded nanoparticles was 0.5 µg/mL and EUCAST was 0.25 µg/mL. Finally, in urine isolates of T asahii, the MIC value of AmB-loaded nanoparticles was 1 µg/mL and EUCAST varied from 0.5 to 1 µg/mL. In the cytotoxicity assay, plain AmB was highly hemolytic (100% in 24 h) while AmB-loaded chitosan/PLGA nanoparticles presented negligible hemolysis.

Saúde itinerante nos centros municipais de educação infantil do município de Guarapuava - PR; os desafios da promoção da saúde em crianças expostas a doenças parasitárias / Travelling health in the municipal kindergartens in the city of Guarapuava - PR; the challenges of health promotion in children exposed to parasitic diseases

A presença de enteroparasitoses em crianças em idade pré-escolar tem sido motivo de preocupação pelos órgãos de saúde principalmente devido ao impacto negativo sobre o crescimento e desenvolvimento intelectual dessas crianças. As infecções por parasitas intestinais podem levar a quadros de desnutrição e formas de gastroenterite crônica. O presente trabalho analisou crianças em idade pré-escolar frequentadoras de 11 unidades CMEIs (Centros Municipais de Educação Infantil) na cidade de Guarapuava-PR em 11 unidades. Foram estudadas 287 crianças e o índice de positividade para enteroparasitoses foi de 13,9%. A idade média das 287 crianças foi de 2,7 anos e a maioria das crianças analisadas foram domicialiadas em zona urbana 84,3% e somente 15,7% em zona rural, com média de filhos por família de 2,08 membros. A prevalência das parasitoses mostrou que G. duodenalis foi o protozoário mais isolado com 70,4%, seguido de Ascaris lumbricoides 6,8% o único helminto encontrado. Com relação à terapêutica empregada 20% das crianças tratadas com o fármaco albendazol continuaram apresentando exames positivos para os mesmos parasitas. Já com o fármaco benzoilmetronidazol todas as crianças apresentaram resultados negativos para presença de parasitas nas fezes. Os fatores de risco para enteroparasitoses indicaram que a presença da variável água tratada foi menor nos casos positivos. Nossos resultados mostraram que G. duodenalis foi o parasita mais isolado em crianças em idade pré-escolar.

The presence of enteroparasitoses in pre-school children has been a concern of health agencies mainly due to the negative impact on the growth and intellectual development of those children. Intestinal parasite infections can lead to malnutrition and chronic forms of gastroenteritis. The present study analyzed pre-school children attending 11 CMEIs (Municipal Kindergarten Schools) in the city of Guarapuava ­ PR. A total of 287 children were studied, resulting in a positive index for enteroparasitoses of 13.9%. The mean age of the 287 children was 2.7 years and most of the children analyzed were domiciled in urban areas (84.3%), with only 15.7% living in rural areas, with a mean number of children per family of 2.08. The parasite prevalence showed that G. duodenalis was the most frequently isolated protozoan, with 70.4%; followed by Ascaris lumbricoides with 6.8%, the only helminth found. Regarding therapy, 20% of the children treated with albendazole continued to present positive tests for the same parasites. When treated with benzoylmetronidazole, all children presented negative results for the presence of parasites in the faeces. The risk factors for enteroparasitoses showed that the variable treated water was lower in the positive cases. The results of this study showed that G. duodenalis was the most frequently parasite isolated in pre-school children.

Perfil das mulheres usuárias do sus com lesões intraepiteliais em um município do oeste do Paraná / Profile of female users of the brazilian unified health system with intraepithelial lesions in a city in western Parana

O câncer cervical é o quarto tipo de tumor mais frequente entre mulheres e quarta causa de mortalidade feminina por câncer no Brasil. Neste trabalho o objetivo foi demostrar o perfil das mulheres atendidas pelo SUS que apresentaram lesões intraepiteliais de baixo grau (LSIL) e alto grau (HSIL) no exame preventivo citopatológico realizado por um laboratório de citopatologia credenciado ao SUS que atende Cascavel-PR e distritos. No período de maio de 2014 a maio de 2015 foram observados 395 exames citopatológicos com LSIL e 160 com HSIL, cuja faixa etária predominante foi dos 25 aos 64 anos (70,64%). Em média observou-se os seguintes resultados: a JEC esteve presente em 90,56% das amostras; o colo cervical apresentou-se normal em 77,31% das mulheres e 43,58% destas mulheres em estudo haviam realizado um exame anterior em até um ano, sendo que o maior motivo para realização do mesmo foi o rastreamento (89,11%). Mais que 90% das mulheres não apresentaram sangramentos, seja após a relação sexual ou menopausa. As lesões também prevaleceram em mulheres atendidas na UBS (61,98%) mesmo elas sendo em menor número se comparadas àquelas atendidas por USF. Esses dados demostram a importância da realização desse exame, pois na maioria das lesões as mulheres não apresentaram sintomas ou alterações clínicas.

Cervical cancer is the fourth most frequent kind of cancer among women and the fourth cause of female mortality due to cancer in Brazil. The purpose of this work was to present the profile of women attended by the Brazilian Unified Health System (SUS) who showed low-grade (LSIL) and high-grade (HSIL) intraepithelial lesions at the cytopathology screening test performed by a SUS-accredited cytopathology laboratory serving the city of Cascavel-PR and its districts. In the period between May 2014 and May 2015, a total of 395 cytopathologic test presenting LSIL and 160 with HSIL were observed. The age group ranged from 25 to 64 years old (70.64%). The following average results were observed: squamocolumnar junction was present in 90.56% of the samples; normal cervix in 77.31% of women and 43.58% of the women in the study had already had an examination within the previous year, with the main reason for the present exam was screening (89.11%). More than 90% of women did not present any bleeding, either after sexual intercourse or menopause. The lesions also prevailed in women attending primary health care (61.98% of lesions) even though they were in lower number when compared to those served by family health programs. Such information demonstrates the importance of carrying out this examination, since most lesions are asymptomatic or do not show any clinical changes.

Dermatophytosis and immunovirological status of HIV-infected and AIDS patients from Sao Paulo city, Brazil.

Over the past decades, more people became infected with human immunodeficiency virus (HIV) and developed acquired immunodeficiency syndrome (AIDS). Because of that the incidence of fungal infections rose dramatically. It happened because this virus can modify the course of fungal diseases, leading to altered clinical pictures. The aim of this study was to evaluate epidemiological and biological aspects of dermatophytosis in HIV-positive and AIDS patients living in the city of São Paulo, Brazil. A total of 84 (44 HIV-positive and 40 AIDS) patients were enrolled in this study. The patients were tested for dermatophyte infections, as well as for the CD4(+) /CD8(+) and HIV viral load counts. Tinea unguium was most frequently observed in AIDS patients, whereas Tinea pedis was mostly observed in HIV-positive patients. The most frequent dermatophyte species was Trichophyton rubrum. CD4(+) counts and CD4(+) /CD8(+) ratios were not associated with a higher risk for dermatophytosis. On the other hand, viral load higher than 100 000 copies/ml was associated with a higher frequency of dermatophytosis. The results suggest to that although dermatophytosis is common in HIV-positive and AIDS patients, the degree of immunosuppression does not seems to correlate with increased risk of this fungal infection. In addition, high viral load as a predictive risk factor for dermatophyte infection should be subject of further evaluations.

Species distribution and antifungal susceptibility of yeasts isolated from vaginal mucosa

Aims: Vulvovaginal candidiasis is one of the most common complaints in the medical clinic. In recent years, due to the increasing frequency of non-albicans species, the number of cases of therapeutic failure has increased considerably, generating the need for research to learn the profile of yeasts isolated in vulvovaginal candidiasis. The aims of this study were to collect samples of vaginal secretion, verify the presence of yeast, identify the species of yeast, and verify their in vitro susceptibility profile against six antifungal agents – amphotericin B, nystatin, fluconazole, itraconazole, ketoconazole and voriconazole. Materials and Methods: Vaginal secretion was collected from 130 patients with symptoms characteristic of vulvovaginal candidiasis (VVC). For amphotericin B, fluconazole, itraconazole, ketoconazole and voriconazole, the in-vitro tests were carried out using the commercial Etest susceptibility testing kit; for nystatin the disk diffusion method was used. Results: The yeasts isolated were: Candida albicans (90 percent), C. glabrata (5 percent), C. parapsilosis (3 percent) and C. tropicalis (2 percent). By the CLSI method, all the isolates were susceptible to fluconazole, ketoconazole, nystatin and voriconazole. Tests showed that 98.8 percent of the isolates were susceptible to amphotericin B and 97.6 percent to itraconazole. Conclusion: Although a high number of resistant strains were not found, these studies may help guide physicians to the most convenient therapeutic orientation, conducting treatment specific to the identified yeast species.

Candidíase vulvovaginal é uma das queixas mais comuns na clínica médica. Nos últimos anos, devido ao aumento da frequência das espécies não albicans, o número de casos em que há falha terapêutica também aumentou, gerando a necessidade de pesquisas para conhecer o perfil das leveduras isoladas nos casos de candidíase vulvovaginal. Os objetivos deste estudo foram coletar amostras de secreção vaginal, verificar a presença de leveduras, identificar as espécies mais frequentes, e verificar o seu perfil in vitro de suscetibilidade frente a seis agentes antifúngicos – anfotericina B, nistatina, fluconazol, itraconazol, cetoconazol e voriconazol. Material e Métodos: A secreção vaginal foi coletada de 130 pacientes com sintomas característicos da candidíase vulvovaginal (CVV). Para anfotericina B, fluconazol, itraconazol, cetoconazol e voriconazol, os testes in vitro foram realizados utilizando o kit de sensibilidade comercial Etest, para nistatina, o método utilizado foi utilizado de difusão em disco. Resultados: As leveduras isoladas foram: C. albicans (90 porcento), C. glabrata (5 porcento), C. parapsilosis (3 porcento) e C. tropicalis (2 porcento). Pelo método CLSI, todas as amostras foram sensíveis ao fluconazol, cetoconazol, nistatina e voriconazol. Os testes mostraram que 98,8 porcento dos isolados foram sensíveis à anfotericina B e 97,6 porcento para itraconazol. Conclusão: Embora, não tenha sido encontrado um grande número de isolados resistentes, este estudo pode auxiliar o médico, na escolha da orientação terapêutica mais conveniente visando à realização de tratamento para as espécies de leveduras identificadas.

Candiduria in a public hospital of São Paulo (1999-2004): characteristics of the yeast isolates.

The study involved 100 yeast isolates, obtained from urine samples provided by a Public Pediatric Hospital of São Paulo, Brazil, from 1999 to 2004. The most frequent species was Candida albicans, followed by C. tropicalis, C. glabrata and C. parapsilosis. In regard to virulence, 97% of the isolates showed index 3 for proteinase and 63% index 2 for phospholipase. The most frequent killer biotypes were 511 and 888.

Candiduria in a public hospital of São Paulo (1999-2004): characteristics of the yeast isolates

The study involved 100 yeast isolates, obtained from urine samples provided by a Public Pediatric Hospital of São Paulo, Brazil, from 1999 to 2004. The most frequent species was Candida albicans, followed by C. tropicalis, C. glabrata and C. parapsilosis. In regard to virulence, 97 percent of the isolates showed index 3 for proteinase and 63 percent index 2 for phospholipase. The most frequent killer biotypes were 511 and 888.

Estudou-se 100 amostras de leveduras, isoladas de urina, provenientes de Hospital Público Infantil de São Paulo Brasil, no período de 1999-2004. A espécie mais freqüente foi Candida albicans, seguida de C. tropicalis, C. glabrata e C. parapsilosis. Em relação à virulência, 97 por cento dos isolados apresentaram índice 3 para proteinase e, 63 por cento índice 2 para fosfolipase. Os biótipos "killer" mais freqüentes foram o 511 e 888.

Virulence profile of strains of Cryptococcus neoformans var. grubii evaluated by experimental infection in BALB/c mice and correlation with exoenzyme activity.

To evaluate the virulence profile of strains of Cryptococcus neoformans var. grubii, 62 strains of this yeast were inoculated into BALB/c mice. It was found that 69 % of the strains were significantly more lethal to the mice and were recovered from a higher percentage (60 %) of the organs compared with the other 31 % of the strains, which were recovered from 35 % of organs tested. Those strains that provoked higher death rates were also recovered from the central nervous system at a higher rate (84 %) than the less lethal strains (32 %). This finding led to an investigation of the factors that enhanced the capacity for neurological infection and death of the animals. The results of this study suggested that environmental strains present different degrees of virulence. The correlation of exoenzyme production before and after inoculation and between the groups of mice indicated that exoenzyme production had no influence on differences in virulence among the strains studied.