Evaluation of the role of clathrin and bacterial viability in the endocytosis of Lawsonia intracellularis.

Lawsonia intracellularis is an obligate intracellular bacterium and causative agent of proliferative enteropathy. The pathogenesis of L. intracellularis is not completely understood, including the endocytic mechanisms to access the host cell cytoplasm. In this study, we evaluated the mechanisms involved in endocytosis of L. intracellularis in vitro using intestinal porcine epithelial cells (IPEC-J2). Confocal microscopy was used to co-localize L. intracellularis and clathrin. Clathrin gene knockdown was then applied to verify whether L. intracellularis endocytosis is clathrin-dependent. Finally, internalization of viable and non-viable (bacteria were inactivated by heat) L. intracellularis organisms were assessed to study the role of the host cell during bacterial endocytosis. L. intracellularis organisms were observed co-localized with clathrin by confocal microscopy but the amount of L. intracellularis internalized in cells, with and without clathrin knockdown, did not differ statistically. The internalization of non-viable L. intracellularis showed a decrease in the internalization in cells with less clathrin synthesis (P<0.05). The present study is the first to elucidate the involvement of clathrin in the endocytosis of L. intracellularis. Clathrin-mediated endocytosis was shown to be an important, but not required, process for L. intracellularis internalization in porcine intestinal epithelial cells. Independence of bacterial viability for host cell internalization was also confirmed.

Synergic Effect of Brachyspira hyodysenteriae and Lawsonia intracellularis Coinfection: Anatomopathological and Microbiome Evaluation.

Brachyspira hyodysenteriae and Lawsonia intracellularis coinfection has been observed in the diagnostic routine; however, no studies have evaluated their interaction. This study aimed to characterize lesions and possible synergisms in experimentally infected pigs. Four groups of piglets, coinfection (CO), B. hyodysenteriae (BRA), L. intracellularis (LAW), and negative control (NEG), were used. Clinical signals were evaluated, and fecal samples were collected for qPCR. At 21 days post infection (dpi), all animals were euthanized. Gross lesions, bacterial isolation, histopathology, immunohistochemistry, and fecal microbiome analyses were performed. Diarrhea started at 12 dpi, affecting 11/12 pigs in the CO group and 5/11 pigs in the BRA group. Histopathological lesions were significantly more severe in the CO than the other groups. B. hyodysenteriae was isolated from 11/12 pigs in CO and 5/11 BRA groups. Pigs started shedding L. intracellularis at 3 dpi, and all inoculated pigs tested positive on day 21. A total of 10/12 CO and 7/11 BRA animals tested positive for B. hyodysenteriae by qPCR. A relatively low abundance of microbiota was observed in the CO group. Clinical signs and macroscopic and microscopic lesions were significantly more severe in the CO group compared to the other groups. The presence of L. intracellularis in the CO group increased the severity of swine dysentery.

Diversity and potential genetic relationships amongst Brazilian Brachyspira hyodysenteriae isolates from cases of swine dysentery.

The aim of this study was to evaluate genetic diversity, distribution, evolution and population structure of Brazilian Brachyspira hyodysenteriae strains isolated from swine. Multilocus Sequence Typing (MLST) analysis using seven housekeeping genes was applied to 46 isolates obtained from outbreaks of swine dysentery that occurred between 2011 and 2015 in the states of Minas Gerais, São Paulo, Mato Grosso, Rio Grande do Sul and Santa Catarina. Historical isolates from Rio Grande do Sul obtained in 1998 were also included in the study. An independent international profile of the global sequences deposited in the B. hyodysenteriae database was used for comparisons with the Brazilian strains. All isolates from 2011 to 2015 were classified into nine sequence type (STs) and divided into four clonal complexes. These findings indicated genetic relationships among the B. hyodysenteriae from different Brazilian states, among historical strains isolated in 1998 and from recent outbreaks, and relatedness with global isolates. Seven STs were unique and, to date, only reported in Brazil.

Experimental Infection of Pigs with a ST 245 Brachyspira hyodysenteriae Isolated from an Asymptomatic Pig in a Herd with No History of Swine Dysentery.

Swine dysentery (SD) is characterized by a severe mucohemorrhagic colitis caused by infection with Brachyspira species. In infected herds the disease causes considerable financial loss due to mortality, slow growth rates, poor feed conversion, and costs of treatment. B. hyodysenteriae is the most common etiological agent of SD and infection is usually associated with disease. However, isolated reports have described low pathogenic strains of B. hyodysenteriae. The aim of this study was to describe an experimental infection trial using a subclinical B. hyodysenteriae isolated from an animal without clinical signs and from a disease-free herd, to evaluate the pathogenicity and clinical pathological characteristics compared to a highly clinical isolate. Forty-eight 5-week-old pigs were divided into three groups: control, clinical and the subclinical isolates. The first detection/isolation of B. hyodysenteriae in samples of the animals challenged with a known clinical B. hyodysenteriae strain (clinical group) occurred 5th day post inoculation. Considering the whole period of the study, 11/16 animals from this group were qPCR positive in fecal samples, and diarrhea was observed in 10/16 pigs. In the subclinical isolate group, one animal had diarrhea. There were SD large intestine lesions in 3 animals at necropsy and positive B. hyodysenteriae isolation in 7/15 samples of the subclinical group. In the control group, no diarrhea, gross/microscopic lesions, or qPCR positivity were observed. Clinical signs, bacterial isolation, macroscopic and histologic lesions were significantly difference among groups, demonstrating low pathogenicity of the subclinical isolate in susceptible pigs.

Effects of Lawsonia intracellularis infection in the proliferation of different mammalian cell lines.

Lawsonia intracellularis is an obligate intracellular bacterium that causes proliferative enteropathy in various animal species. While cellular proliferation of intestinal cells is recognized as the hallmark of L. intracellularis infection in vivo, it has not been demonstrated in in vitro models. In order to assay the effect of L. intracellularis, various cell lines were infected with pathogenic and non-pathogenic passages of the bacterium. Because of the high proliferative rate of these cell lines, serum deprivation, which is known to reduce proliferation, was applied to each of the cell lines to allow the observation of proliferation induced by L. intracellularis. Using antibodies for Ki-67 and L. intracellularis in dual immunofluorescence staining, we observed that L. intracellularis was more frequently observed in proliferating cells. Based on wound closure assays and on the amount of eukaryotic DNA content measured over time, we found no indication that cell lines infected with L. intracellularis increased proliferation and migration when compared to non-infected cells (p > 0.05). Cell arrest due to decreased serum in the culture media was cell-line dependent. Taken together, our findings provide data to support and expand previous subjective observations of the absence of in vitro proliferation caused by L. intracellularis in cell cultures and confirm that cell lines infected by L. intracellularis fail to serve as adequate models for understanding the cellular changes observed in proliferative enteropathy-affected intestines.

Phenotypic characterization of swine peripheral blood monocyte-derived macrophages and ex vivo infection with Salmonella enterica serovar Typhimurium.

Macrophages are critical mediators of the inflammatory process, playing a relevant role in the pathogenesis of Salmonella Typhimurium. The protocols for isolation, culture, and differentiation of monocytes into macrophages and their interaction with Salmonella are well established in humans and murine models, but little information is available in swine. The aims of this study were to establish an efficient protocol for macrophage culture and to evaluate the interaction of the invA mutant strain and the wild type (WT) Salmonella Typhimurium with porcine macrophages. Peripheral blood monocyte-derived macrophages from pigs were obtained, separated by density-gradient centrifugation, and cultured in Teflon vials for 10 days. After the differentiation period, cultures consisted of 92.4% CD14+ cells. In addition, these cells showed phagocytic ability, demonstrated by the presence of the same amount of WT and invA mutant Salmonella Typhimurium 1 h after interaction with macrophages. The early cytotoxic effect was Salmonella pathogenicity island (SPI)-[1]dependent, in which log-phase WT strains were more efficient (p < 0.01) than the invA mutant strain at inducing the death of macrophages.

Oral fluid for detection of exposure to Lawsonia intracellularis in naturally infected pigs.

To demonstrate the utility of oral fluid (OF) for indirect diagnostic detection of Lawsonia intracellularis (Li), 15 pig farms were studied. Serum and fecal samples were collected from 20 animals from five different age groups on each farm. OF samples were collected from animals in two pens of the same age groups. Serum and OF samples were analyzed in an immunoperoxidase in monolayer assay (IPMA) for the detection of anti-Li immunoglobulin G (IgG) and A (IgA). Compatible results were found between PCR and IgG in OF in four of the five ages evaluated. Simultaneous detection of IgG in serum and OF was mainly observed on farms showing clinical signs suggestive of porcine proliferative enteropathy (PPE). These findings demonstrate the potential usefulness of OF in detecting anti-Li antibodies as a diagnostic tool that can be used to monitor PPE in herds with clinical signs compatible with the disease.

Travel health. Part 1: preparing the tropical traveller.

The health threats of modern day travel change as population, wealth and tourism increase across the world. A series of three articles have been written to describe the spectrum of health issues associated with travel. Pre-travel health advice has become more focused on risk assessment and educating the traveller about infectious disease and the more frequent non-infectious hazards associated with travel, while ensuring they are not unnecessarily exposed to injury from vaccines and drugs. In part one, the role of the health advisor and the needs of the traveller are examined. The importance of risk assessment during a consultation is described and factors that influence recommendations and prescribing are explored. As most travel-associated morbidity and mortality is non-vaccine preventable, the focus of the pre-travel consultation should be on educating the traveller and influencing behaviour change. The second article in this series deals with the highest risk group of travellers--residents who visit friends and relatives. It highlights their specific problems and special needs and how to influence their risk of disease by addressing their health beliefs and their cultural dimension of risk. The third article explores the common, and not so common, clinical problems found in returned travellers. Nurses have to deal with a large range of clinical problems and diagnostic dilemmas when attending to the returned traveller. The review provides a perspective on the frequency and severity of problems and how nurses should manage travel associated disease.

Evaluation of the involvement of mice (Mus musculus) in the epidemiology of porcine proliferative enteropathy.

The aim of this study was to evaluate the fecal-oral transmission of L. intracellularis between mice and pigs. The study was divided into two parts. The first part aimed to determine whether mice could be infected by feces from pigs that are experimentally infected with L. intracellularis. Thirty-four Swiss mice received L. intracellularis PCR-positive feces from experimentally infected pigs (M1) for four consecutive days. Twelve other mice received swine negative feces (M2). Pools of mice feces were collected on alternating days post-exposure (dpe). The second part of the study aimed to test whether pigs could be infected when exposed to L. intracellularis PCR-positive feces from experimentally infected mice. Twelve 5-week-old pigs received feed mixed with L. intracellularis PCR-positive mice feces (P1), while the other two pigs received PCR-negative mice feces (P2) for four consecutive days. In the first study, the amount of L. intracellularis provided to M1 boxes per day was between 106 and 108. Mice shed, an average of 104 bacterial units every collection day. Three mice from M1 were positive for L. intracellularis by immunohistochemistry (IHC) at the end of the study. In the second part of the study, pigs in P1 received an average of 105 bacterial units per day. Ten pigs were infected by L. intracellularis based on positive qPCR and/or immunohistochemistry and serology results. These pigs shed an average of 104L. intracellularis/g of feces. Mice and pigs experimentally infected with L. intracellularis can infect each other, therefore, rodents should be considered players in the epidemiology of this disease in pig farms.

Incidence rate and risk factors for giardiasis and strongyloidiasis in returning UK travellers.

BACKGROUND: Few studies have investigated incidence rate and risk factors for giardiasis and strongyloidiasis in returning UK travellers. The clinical presentations of these two diseases are often similar and difficult to distinguish. This study was conducted to investigate the incidence rate and the risk factors for symptomatic giardiasis and strongyloidiasis in returned tropical travellers. METHODS: We retrospectively analysed 3306 consecutive attendances presenting to the emergency clinic at the Hospital for Tropical Diseases in London, the UK from September 2008 to May 2010. Odds ratios between the diagnoses and patient variables were analysed by logistic regression. RESULTS: Giardiasis was diagnosed in 92/3306 cases (2.8%, proportionate morbidity), and the incidence rate per 1000 person-months was 12.5. Multivariate analysis with logistic regression revealed that Caucasian ethnicity (adjusted odds ratio (aOR): 2.37, 95% confidence interval (CI): 1.12-5.03, P value = 0.025), travel length ≥32 days (aOR: 2.63, 95%CI: 1.43-4.83, P = 0.002), travelling to South or South East Asia (aOR: 4.90, 95%CI: 2.03-11.8, P < 0.001, aOR: 3.36, 95%CI: 1.43-7.93, P = 0.006), afebrile presentation (aOR: 2.14, 95%CI: 1.14-4.03, P = 0.018), and presenting with gastro-intestinal symptoms (aOR: 14.6, 95%CI: 6.08-35.0, P < 0.001) were all associated with giardiasis. In contrast, strongyloidiasis was found only in 0.94% (proportionate morbidity) of the cases (31/3306), and the incidence rate per 1000 person-months was 3.1. Multivariate analysis revealed that male sex (aOR: 3.05, 95%CI: 1.36-6.85, P = 0.007), and non-Caucasian ethnicity (aOR: 2.69, 95%CI: 1.32-5.49, P = 0.007) were associated with strongyloidiasis. CONCLUSIONS: The incidence rate and risk factors for both infectious diseases were identified. The results of this study might guide clinicians to make more accurate and timely diagnoses in returned tropical travellers.

Avaliação do estado nutricional e da dieta de crianças e adolescentes com síndrome de down / Evaluación del estado nutricional y de la dieta de niños y adolescentes con síndrome de down / Evaluation of nutritional status and diet of children and adolescents with down syndrome

RESUMO Introdução: As crianças com síndrome de Down (SD) podem apresentar maior incidência de neofobia e de seletividade alimentar, sobrepeso e obesidade. A alimentação saudável e equilibrada é de suma importância para o crescimento adequado dessas crianças. Objetivo: Avaliar a adequação dos componentes da dieta e o estado nutricional de crianças e adolescentes com síndrome de Down em seguimento no ambulatório de pediatria genética do Hospital das Clínicas de Botucatu. Método: Estudo clínico descritivo transversal, com coleta de dados clínicos e avaliação nutricional, realizadopor meio de dados antropométricos e recordatório alimentar para avaliação da dieta. Análise estatística dos testes de Qui-quadrado e de Tukey. Resultados: Foram incluídos 35 crianças e dois adolescentes. Os diagnósticos nutricionais foram 2,7% de magreza, 81,1% de eutrofia, 8,1% de obesidade e 8,1% em risco ou sobrepeso. Houve excesso de ingestão de lipídeos naqueles com sobrepeso e obesidade, e a dieta deficiente em fibras foi prevalente a partir do primeiro ano de vida, bem como excesso de calorias e adequação de ferro e zinco. Entre os dois adolescentes, predominou a dieta com déficits em macro e micronutrientes, exceto em vitamina C e colesterol. Conclusões: A dieta com excesso de calorias, carboidratos e lipídios, como tambémcom déficit de fibras, aponta uma alimentação pouco balanceada entre crianças e adolescentes com SD, principalmente após o primeiro ano de vida, apesar do seu adequado estado nutricional.

RESUMEN Introducción: los niños consíndrome de Down (SD) pueden presentar mayor incidencia de neofobia yde selectividad alimentaria, sobrepeso y obesidad. La alimentación saludabley equilibradaes de gran importancia para el crecimiento adecuado de estos niños. Objetivo: la adecuación de los componentes de la dieta yel estado nutricional de niños y adolescentes con síndrome de Downasistidosen la clínica médica depediatría genética delHospital das Clínicas de Botucatu. Método: estudio clínico descriptivo transversal, con recolección de datos clínicos yevaluación nutricional, realizado medianteindicadores antropométricos y recordatorio alimentario para la evaluación de la dieta. Análisis estadísticode laspruebas de ji-cuadrado y de Tukey. Resultados: fueron incluidos 35niños ydos adolescentes. Los diagnósticos nutricionales fueron 2,7% de delgadez, 81,1% de eutrofia, 8,1% de obesidady8,1% en riesgo o sobrepeso. Hubo exceso de ingestión delípidosenaquellos con sobrepeso y obesidad, yla dieta deficiente en fibrasfueprevalentea partir del primer año de vida, así como exceso de calorías y adecuación de hierro y zinc. Entre los dos adolescentes, predominóla dieta con déficits en macro y micronutrientes, excepto en vitamina C y colesterol. Conclusiones: la dieta con exceso de calorías, carbohidratosylípidos, como tambiéncondéficit de fibras, señala una alimentación poco balanceada entre niños y adolescentes con SD, principalmente trasel primer año de vida, apesar de su adecuado estado nutricional.

ABSTRACT Introduction: Children with Down syndrome (DS) may have a prevalence of neophobia and food selectivity, overweight, and obesity. A healthy and balanced diet is of utmost importance for the proper growth of these children. Objective: To evaluate the adequacy of diet components and the nutritional status of children and adolescents with Down syndrome followed up at the outpatient care of genetic pediatrics, Hospital das Clínicas de Botucatu. Method: A cross-sectional descriptive clinical study, with a collection of clinical data and nutritional assessment, using anthropometric data and dietary records to evaluate the diet. Statistical analysis of the Chi-square and Tukey tests were performed. Results: A total of 35 children and two adolescents were included. Nutritional diagnoses were 2.7% lean, 81.1% eutrophic, 8.1% obese, and 8.1% at risk or overweight. There was an excess of lipid intake in overweight and obese children, and a fiber-deficient diet was prevalent since the first year of age, as well as extra calories and adequate iron and zinc intake. Among the two adolescents, a diet with deficits in macro and micronutrients, except for vitamin C and cholesterol, stood out. Conclusions: A diet with an excess of calories, carbohydrates, and lipids, as well as a fiber-deficient diet, indicates an unbalanced diet among children and adolescents with DS, especially after one year of age, despite their adequate nutritional status.

Use of oral fluids to detect anti Lawsonia intracellularis antibodies in experimentally infected pigs / Utilização de fluidos orais para detecção de anticorpos anti Lawsonia intracellularis em suínos experimentalmente infectados

Several pathogens and antibodies derived from serum or produced in tissues associated with the oral cavity are present in the oral fluid (OF). Considering the applicability of this alternative sample, recent studies in veterinary medicine have tested OF as a replacement for serum in diagnostic assays. The aim of this study was to standardize the immunoperoxidase monolayer assay (IPMA) to detect anti-Lawsonia intracellularis immunoglobulin A (IgA) and immunoglobulin G (IgG) in OF samples from experimentally infected pigs. Sixty-two pigs were divided into two groups: control (T1, n=30) and inoculated with L. intracellularis (T2, n=32). Blood, OF and fecal samples were collected at 0, 7, 14, 21, 28 and 42 days post-inoculation (dpi). Some adaptations of the standard technique for serum were made to IPMA for the detection of IgA and IgG in OF. The IPMA showed high specificity and sensitivity for serum samples and high specificity and moderate sensitivity for the detection of IgA and IgG in OF. There was high agreement between the results of serum IgG and OF IgA and IgG. Based on our results, oral fluid samples may be used for the evaluation and determination of anti-L. intracellularis antibodies in pigs, but not for individual diagnosis of swine proliferative enteropathy.(AU)

Vários patógenos e anticorpos derivados do soro ou produzidos em tecidos associados a cavidade oral estão presentes no fluido oral (FO). Considerando a aplicabilidade dessa amostra alternativa, estudos recentes em medicina veterinária têm testado o FO como substituto do soro para testes diagnósticos. O objetivo desse estudo foi padronizar a imunoperoxidase em monocamada de célula (IPMC) para a detecção de imunoglobulina A e imunoglobulina G anti-Lawsonia intracellularis em amostras de FO de suínos experimentalmente infectados. Um total de 62 suínos foram divididos em dois grupos: controle (T1, n=30) e inoculados com L. intracellularis (T2, n=32). Sangue, FO e amostras de fezes foram coletados aos 0, 7,14, 21, 28 e 42 dias após a inoculação (dpi). Algumas adaptações da técnica foram realizadas na técnica padrão da IPMC para a detecção de IgA e IgG. A IPMC demostrou alta especificidade e sensibilidade para amostras de soro e alta especificidade de moderada sensibilidade para a detecção de IgA e IgG em FO. Houve alta concordância entre resultados de detecção de IgG em soro com a IgA e IgG em amostras de FO. Baseado em nossos resultados, amostras de fluido oral podem ser usadas em avaliações e detecção de anticorpos anti-L. intracellularis em suínos, porém não de forma individual.(AU)

Surveillance of post-caesarean surgical site infections in a hospital with limited resources, Cambodia.

INTRODUCTION: In Cambodia, we implemented a pilot surveillance of superficial surgical site infections (SSSI) following caesarean deliveries (CD) in a provincial hospital, to estimate their incidence, describe their clinical management, and determine their causative pathogens. METHODOLOGY: Between October 2010 and February 2011, all women admitted for CD were included in the surveillance. Their clinical condition was monitored for a post-operative period of 30 days, including two assessments performed by surgeons. Cases were clinically diagnosed by surgeons, with bacterial cultures performed. RESULTS: Of the 222 patients admitted for CD, 176 (79.3%) were monitored for 30 days. Of these, 11 were diagnosed with a SSSI, giving an incidence rate of 6.25% (95% CI 3.2-10.9). Four of the cases (36.4%) were detected after hospital discharge. Length of hospitalization was significantly longer for the SSSI cases. All 222 patients were prescribed antibiotics. Ampicillin was administered intravenously to 98.6% of them, with subsequent oral amoxicillin given to 82.9%. Three of six pus samples collected were positive on culture: two with Staphylococcus aureus and one with Staphylococcus lugdunensis. One S.aureus was methicillin resistant (MRSA). The other was clindamycin and erythromycin resistant. CONCLUSION: Surveillance of health-care associated infections in a setting with limited resources is challenging but feasible. Effective post-discharge surveillance was essential for the estimation of the incidence rate of SSSI following caesarean deliveries. This surveillance led to a peer-review of medical practices.

Minimum inhibitory concentration of Brazilian Brachyspira hyodysenteriae strains / Concentração inibitória mínima de cepas Brachyspira hyodysenteriae brasileiras

The objectives of this study were to characterize Brachyspira hyodysenteriae isolates and to evaluate the antimicrobial susceptibility patterns of strains obtained from pigs in Brazil based on the minimal inhibitory concentration test (MIC). The MIC was performed for 22 B. hyodysenteriae isolates obtained from 2011 to 2013 using the following antimicrobial drugs: tylosin, tiamulin, valnemulin, doxycycline, lincomycin and tylvalosin. Outbreaks of swine dysentery were diagnosed based on clinical presentation, bacterial isolation, gross and microscopic lesions, duplex PCR for B. hyodysenteriae and B. pilosicoli and nox gene sequencing. All obtained MIC values were consistently higher or equal to the microbiological cut-off described in the literature. The MIC 90 values for the tested drugs were 8µg/ml for doxycycline, >4µg/ml for valnemulin, 8µg/ml for tiamulin, 32µg/ml for tylvalosin, >64µg/ml for lincomycin and >128µg/ml for tylosin. These results largely corroborate those reported in the literature. Tiamulin, doxycycline and tylvalosin showed the lowest MIC results. All of the samples subjected to phylogenetic analysis based on the nox gene sequence exhibited similar results, showing 100% identity to B. hyodysenteriae. This is the first study describing the MIC pattern of B. hyodysenteriae isolated in Brazil.(AU)

Os objetivos deste trabalho foram a caracterização de isolados de Brachyspira hyodysenteriae e avaliar os padrões de sensibilidade antimicrobiana de isolados obtidos a partir de suínos no Brasil com base no teste de concentração inibitória mínima (MIC). A MIC foi realizada em 22 isolados de B. hyodysenteriae obtidos entre 2011 a 2013 usando os seguintes antimicrobianos: tilosina, tiamulina, valnemulina, doxiciclina, lincomicina e tilvalosina. Surtos de disenteria suína foram diagnosticados com base na apresentação clínica, isolamento bacteriano, lesões macroscópicas e microscópicas, PCR duplex para B. hyodysenteriae e B. pilosicoli e sequenciamento do gene nox. Todos os valores de MIC obtidos foram consistentemente mais elevados ou igual ao ponto de corte microbiológica descrito na literatura. Os valores de MIC 90 para os fármacos testados foram de 8 µg / mL para a doxiciclina, > 4 µg/ml de valnemulina, 8 µg / mL para a tiamulina, 32 µg / ml para tilvalosina, > 64 µg / ml para a lincomicina e > 128 µg / ml de tilosina. Estes resultados corroboram em grande parte com os relatados na literatura. Tiamulina, doxiciclina e tilvalosina apresentaram os menores resultados de MIC. Todas as amostras submetidas à análise filogenética com base na sequência do gene nox exibiram resultados semelhantes, indicando 100% de identidade com B. hyodysenteriae. Este é o primeiro estudo que descreve o padrão MIC de B. hyodysenteriae isoladas no Brasil.(AU)

Type B insulin resistance developing during interferon-alpha therapy.

OBJECTIVE: To report a rare case of diabetes caused by type B insulin resistance due to development of insulin receptor autoantibodies during treatment of hepatitis C with interferon-alpha and ribavirin. METHODS: Clinical and laboratory findings in the case are presented. The literature on type B insulin resistance and interferon-induced autoimmunity is reviewed. RESULTS: A 55-year-old African American man with hepatitis C was treated with interferon and ribavirin. Eight months later, he presented with rapid onset of hyperglycemia, profound weakness, and weight loss. Severe hyperglycemia persisted despite insulin infusion rates as high as 125 U/h. The presence of insulin receptor autoantibodies was confirmed by immunoprecipitation of recombinant human insulin receptor with patient serum. Assays for autoantibodies to islet cell antigens and glutamic acid decarboxylase were negative. The interferon and ribavirin were discontinued. His insulin requirement spontaneously declined to low levels over a 6-month period. Two years after discharge of the patient, insulin receptor autoantibodies could no longer be demonstrated in his serum. He remains euglycemic and is no longer taking insulin. CONCLUSION: This case demonstrates that type B insulin resistance can occur as a complication of interferon-alpha therapy. To our knowledge, this is the first reported case in the United States of type B insulin resistance with development of insulin receptor autoantibodies during treatment with interferon-alpha.