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Objetivo: Avaliar a influência da localização da enterocolite necrosante neonatal na mortalidade de recém-nascidos (RN) submetidos à laparotomia exploradora. Métodos: Estudo de coorte prospectiva de 141 recém-nascidos com ECN submetidos consecutivamente à laparotomia exploradora no período de novembro de 1991 a dezembro de 2005. Foram avaliados dados epidemiológicos, localização e extensão da doença, crescimento intra-uterino e o número de óbitos no período de 60 dias após a cirurgia. Resultados: Setenta e quatro (52,5%) crianças eram do sexo masculino, com peso médio de nascimento de 1.589 ± 665 gramas, com idade gestacional média de 33,6 ± 2,9 semanas. Prematuridade ocorreu em 84,4% (119/141) dos RN. Cinqüenta e sete (40,4%) eram pequenos para a idade gestacional. Óbito ocorreu em 68 crianças (48,2%). Na análise bivariada, observou-se que o comprometimento do jejuno-íleo foi associado com alta mortalidade (20 óbitos - 76,9%; OR = 20; intervalo de confiança de 95% = 4,6 - 96,3; p < 0,001) e que a doença no jejuno estava associada à maior extensão da ECN. Entretanto, no modelo de regressão logística múltipla com controle individual de cada variável, a doença no jejuno-íleo (OR = 0,61; intervalo de confiança de 95% = 0,06 - 6,14; p = 0,68) e no intestino grosso (OR = 2,91; intervalo de confiança de 95% = 0,81 - 10,50; p = 0,10) não foram consideradas fatores de risco para o óbito. Conclusões: Em análise adequada, com controle isolado de cada variável estudada, a mortalidade foi independente da localização da ECN no intestino delgado ou no intestino grosso. Porém, a localização da doença no jejuno foi um marcador de maior extensão da ECN e, conseqüentemente, de pior prognóstico. Extensão difusa da doença e recém-nascidos PIG foram os mais importantes fatores de risco de ocorrência de óbito nesses recém-nascidos submetidos à cirurgia. / Aim of the study: To evaluate the effect of disease site on the mortality rate of newborns with necrotizing enterocolitis (NEC) undergoing exploratory laparotomy. Methods: Prospective cohort of 141 consecutive newborns with NEC who underwent laparotomy from November 1991 to December 2005. The study variables included epidemiologic data, disease site and extent, intrauterine growth, and number of deaths in the 60 days after operation. The protocol was approved by the institution’s Research Ethics Committee. Main results: Seventy-four (52.5%) infants were male. Mean birth weight was 1,589 ± 665 g, and mean gestational age was 33.6 ± 2.9 weeks. One-hundred and nineteen (84.4%) newborns were premature. Small for gestational age was observed in 57 (40.4%). Sixty-eight (48.2%) infants died. Bivariate analysis revealed that involvement of the jejunum and ileum was associated with high mortality rates (20 deaths, 76.9%; OR = 20; 95% 95% CI = 4.6 – 96.3; p < 0.001), and that involvement of the jejunum was associated with greater disease extent. After controlling for individual variables, logistic regression showed that the mortality associated with jejunum and ileum involvement (OR = 0.61; 95% CI = 0.06 - 6.14; p = 0.68) did not differ from that associated with large bowel involvement (OR = 2.91; 95% CI = 0.81 – 10.50; p = 0.10); however, jejunum involvement remained significantly associated with disease extent. Conclusions: NEC-related mortality in newborns undergoing laparotomy was not influenced by disease site (small or large bowel). However, jejunum involvement was a marker of greater disease extent and therefore of poor prognosis. Diffuse disease extent and small for gestational age were the most important markers of risk of death in NEC newborns submitted to surgery.

Objetivo: Avaliar a influência da localização da enterocolite necrosante neonatal na mortalidade de recém-nascidos (RN) submetidos à laparotomia exploradora. Métodos: Estudo de coorte prospectiva de 141 recém-nascidos com ECN submetidos consecutivamente à laparotomia exploradora no período de novembro de 1991 a dezembro de 2005. Foram avaliados dados epidemiológicos, localização e extensão da doença, crescimento intra-uterino e o número de óbitos no período de 60 dias após a cirurgia. Resultados: Setenta e quatro (52,5%) crianças eram do sexo masculino, com peso médio de nascimento de 1.589 ± 665 gramas, com idade gestacional média de 33,6 ± 2,9 semanas. Prematuridade ocorreu em 84,4% (119/141) dos RN. Cinqüenta e sete (40,4%) eram pequenos para a idade gestacional. Óbito ocorreu em 68 crianças (48,2%). Na análise bivariada, observou-se que o comprometimento do jejuno-íleo foi associado com alta mortalidade (20 óbitos - 76,9%; OR = 20; intervalo de confiança de 95% = 4,6 - 96,3; p < 0,001) e que a doença no jejuno estava associada à maior extensão da ECN. Entretanto, no modelo de regressão logística múltipla com controle individual de cada variável, a doença no jejuno-íleo (OR = 0,61; intervalo de confiança de 95% = 0,06 - 6,14; p = 0,68) e no intestino grosso (OR = 2,91; intervalo de confiança de 95% = 0,81 - 10,50; p = 0,10) não foram consideradas fatores de risco para o óbito. Conclusões: Em análise adequada, com controle isolado de cada variável estudada, a mortalidade foi independente da localização da ECN no intestino delgado ou no intestino grosso. Porém, a localização da doença no jejuno foi um marcador de maior extensão da ECN e, conseqüentemente, de pior prognóstico. Extensão difusa da doença e recém-nascidos PIG foram os mais importantes fatores de risco de ocorrência de óbito nesses recém-nascidos submetidos à cirurgia. / Aim of the study: To evaluate the effect of disease site on the mortality rate of newborns with necrotizing enterocolitis (NEC) undergoing exploratory laparotomy. Methods: Prospective cohort of 141 consecutive newborns with NEC who underwent laparotomy from November 1991 to December 2005. The study variables included epidemiologic data, disease site and extent, intrauterine growth, and number of deaths in the 60 days after operation. The protocol was approved by the institution’s Research Ethics Committee. Main results: Seventy-four (52.5%) infants were male. Mean birth weight was 1,589 ± 665 g, and mean gestational age was 33.6 ± 2.9 weeks. One-hundred and nineteen (84.4%) newborns were premature. Small for gestational age was observed in 57 (40.4%). Sixty-eight (48.2%) infants died. Bivariate analysis revealed that involvement of the jejunum and ileum was associated with high mortality rates (20 deaths, 76.9%; OR = 20; 95% 95% CI = 4.6 – 96.3; p < 0.001), and that involvement of the jejunum was associated with greater disease extent. After controlling for individual variables, logistic regression showed that the mortality associated with jejunum and ileum involvement (OR = 0.61; 95% CI = 0.06 - 6.14; p = 0.68) did not differ from that associated with large bowel involvement (OR = 2.91; 95% CI = 0.81 – 10.50; p = 0.10); however, jejunum involvement remained significantly associated with disease extent. Conclusions: NEC-related mortality in newborns undergoing laparotomy was not influenced by disease site (small or large bowel). However, jejunum involvement was a marker of greater disease extent and therefore of poor prognosis. Diffuse disease extent and small for gestational age were the most important markers of risk of death in NEC newborns submitted to surgery.

Objetivo: Avaliar a influência da localização da enterocolite necrosante neonatal na mortalidade de recém-nascidos (RN) submetidos à laparotomia exploradora. Métodos: Estudo de coorte prospectiva de 141 recém-nascidos com ECN submetidos consecutivamente à laparotomia exploradora no período de novembro de 1991 a dezembro de 2005. Foram avaliados dados epidemiológicos, localização e extensão da doença, crescimento intra-uterino e o número de óbitos no período de 60 dias após a cirurgia. Resultados: Setenta e quatro (52,5%) crianças eram do sexo masculino, com peso médio de nascimento de 1.589 ± 665 gramas, com idade gestacional média de 33,6 ± 2,9 semanas. Prematuridade ocorreu em 84,4% (119/141) dos RN. Cinqüenta e sete (40,4%) eram pequenos para a idade gestacional. Óbito ocorreu em 68 crianças (48,2%). Na análise bivariada, observou-se que o comprometimento do jejuno-íleo foi associado com alta mortalidade (20 óbitos - 76,9%; OR = 20; intervalo de confiança de 95% = 4,6 - 96,3; p < 0,001) e que a doença no jejuno estava associada à maior extensão da ECN. Entretanto, no modelo de regressão logística múltipla com controle individual de cada variável, a doença no jejuno-íleo (OR = 0,61; intervalo de confiança de 95% = 0,06 - 6,14; p = 0,68) e no intestino grosso (OR = 2,91; intervalo de confiança de 95% = 0,81 - 10,50; p = 0,10) não foram consideradas fatores de risco para o óbito. Conclusões: Em análise adequada, com controle isolado de cada variável estudada, a mortalidade foi independente da localização da ECN no intestino delgado ou no intestino grosso. Porém, a localização da doença no jejuno foi um marcador de maior extensão da ECN e, conseqüentemente, de pior prognóstico. Extensão difusa da doença e recém-nascidos PIG foram os mais importantes fatores de risco de ocorrência de óbito nesses recém-nascidos submetidos à cirurgia. / Aim of the study: To evaluate the effect of disease site on the mortality rate of newborns with necrotizing enterocolitis (NEC) undergoing exploratory laparotomy. Methods: Prospective cohort of 141 consecutive newborns with NEC who underwent laparotomy from November 1991 to December 2005. The study variables included epidemiologic data, disease site and extent, intrauterine growth, and number of deaths in the 60 days after operation. The protocol was approved by the institution’s Research Ethics Committee. Main results: Seventy-four (52.5%) infants were male. Mean birth weight was 1,589 ± 665 g, and mean gestational age was 33.6 ± 2.9 weeks. One-hundred and nineteen (84.4%) newborns were premature. Small for gestational age was observed in 57 (40.4%). Sixty-eight (48.2%) infants died. Bivariate analysis revealed that involvement of the jejunum and ileum was associated with high mortality rates (20 deaths, 76.9%; OR = 20; 95% 95% CI = 4.6 – 96.3; p < 0.001), and that involvement of the jejunum was associated with greater disease extent. After controlling for individual variables, logistic regression showed that the mortality associated with jejunum and ileum involvement (OR = 0.61; 95% CI = 0.06 - 6.14; p = 0.68) did not differ from that associated with large bowel involvement (OR = 2.91; 95% CI = 0.81 – 10.50; p = 0.10); however, jejunum involvement remained significantly associated with disease extent. Conclusions: NEC-related mortality in newborns undergoing laparotomy was not influenced by disease site (small or large bowel). However, jejunum involvement was a marker of greater disease extent and therefore of poor prognosis. Diffuse disease extent and small for gestational age were the most important markers of risk of death in NEC newborns submitted to surgery.

Made available in DSpace on 2016-08-18T17:27:37Z (GMT). No. of bitstreams: 1 Dissertacao CAMILA MARIA SANTANA COSTA BUNA.pdf: 1078836 bytes, checksum: 614336d682cc50d8f7758d2f5265a615 (MD5) Previous issue date: 2015-07-06 / The Necrotizing enterocolitis (ECN) is a severe gastrointestinal illness caused by multiple factors and is among the leading causes of neonatal mortality in the Neonatal Intensive Care Unit of the Environment (NICU). The incidence of NEC is inversely proportional to gestational age and birth weight, reaching 12% of children weighing less than 1500g and triggering death in 30% of casos.Tem up to analyze the occurrence of ECN and associated factors its development in newborns (NB) with low weight. It is an epidemiological case-control study, conducted from March 1, 2014 to June 30, 2015, in two NICUs in Sao Luis, MA. The sample size was calculated considering a case to three controls (1:3), establishing confidence level of 95% and power of 80% study, sufficient to detect an OR = 2.5, making 236 newborns (RN) underweight, and 59 infants with NEC diagnoses (case group) and 177 infants without NEC (control group). In analyzing the data maternal variables (gestational period and the type of delivery) and newborn (birth and hospitalization) were organized in six blocks, arranged in a hierarchical structure, and analyzed in STATA 11.0 program. The differences between means were assessed by Student's t-test, whereas the differences between the medians by Man Whitney test. It was considered as the dependent variable, the ECN, and as independent, maternal and neonatal variables. Univariate analysis was performed between independent variables of two groups: case and control, estimated the OR values, with reference category OR = 1, built the confidence intervals of 95% and certain values of p. In the hierarchical analysis was carried out by the group of variables in levels according to influence the outcome. Of the 59 cases of NEC, 61.02% were female, with a median of 45 days hospital stay; and 177 controls without ECN, 54.55% were male, with a median hospital stay of 19.5 days. As for the clinical outcome of cases of NEC, 40.68% progressed to death. At the end of hierarchical analysis remained statistically significant association, the use of antenatal corticosteroids (OR = 2.90; p <0.001), reduced amniotic fluid (OR = 2.03;p<0.001), resuscitation at birth (OR = 1, 35, p = 0.010), birth weight ≤1500g (OR = 3.32, p <0.001), transfusions (OR = 2.11, p = 0.040) and the use of surfactant (OR = 2.41, p = 0.020). It concludes that maternal aspects related to pregnancy and neonatal concerning the birth and hospitalization may be influencing the appearance of NEC. / A Enterocolite Necrosante(ECN) é uma grave enfermidade gastrintestinal, de causa multifatorial e está entre as principais causas de mortalidade neonatal no ambiente da Unidade de Terapia Intensiva Neonatal (UTIN). A incidência da ECN é inversamente proporcional à idade gestacional e o peso de nascimento, atingindo 12% das crianças com peso inferior a 1500g e desencadeando o óbito em 30% dos casos.Tem-se como objetivo analisar a ocorrência de ECN e os fatores associados ao seu desenvolvimento em recém-nascidos (RN)de baixo peso. Trata-se de um estudo epidemiológico tipo caso controle, realizado no período de 01 de março de 2014 a 30 de junho de 2015, em duas UTINs de São Luís-MA. O tamanho da amostra foi calculado considerando um caso para três controles (1:3), estabelecendo nível de confiança de 95% e poder do estudo de 80%,suficiente para detectar um OR=2,5, perfazendo 236 recém-nascidos (RN) de baixo peso, sendo 59 RN com diagnósticos de ECN (grupo caso) e 177 RN sem ECN (grupo controle). Na análise dos dados as variáveis maternas (período gestacional e o tipo de parto) e neonatais (nascimento e hospitalização) foram organizadas em seis blocos e dispostas em uma estrutura hierarquizada, e analisadas no programa STATA 11.0. As diferenças entre as médias foram avaliadas pelo teste T-Student, enquanto que as diferenças entre as medianas pelo teste de Man Whitney. Considerou-se como variável resposta, a ECN, e como independentes, as variáveis maternas e neonatais. Foi realizada análise univariada entre as variáveis independentes dos doisgrupos: caso e controle, estimados os valores das OR, tendo como categoria de referência OR=1, construídos os intervalos de confiança de 95% e determinados os valores de p. Na análise hierarquizada foi realizadoo agrupamento das variáveis em níveis segundo a influência no desfecho. Dos 59 casos de ECN, 61,02% eram do sexo feminino,com mediana do tempo de hospitalização de 45 dias; edos 177 controles sem ECN, 54,55% eram do sexo masculino, com mediana do tempo de hospitalização de 19,5 dias. Quanto ao desfecho clínico dos casos de ECN, 40,68% evoluíram a óbito. Ao final da análise hierarquizada mantiveram associação estatisticamente significante, o uso de corticóide antenatal (OR=2,90; p<0,001), líquido amniótico reduzido (OR=2,03;p<0,001), reanimação ao nascimento (OR=1,35; p=0,010), peso ao nascimento ≤1500g (OR=3,32;p<0,001), transfusão (OR=2,11;p=0,040) e uso de surfactante (OR=2,41;p=0,020). Conclui-se que os aspectos maternos relacionados ao período gestacional e os neonatais referentes ao nascimento e hospitalização podem estarinfluenciando no aparecimento da ECN.

No description available.

Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Introduction: An association between maternal human immunodeficiency virus (HIV) infection and Necrotizing Enterocolitis (NEC) in preterm infants has been reported. The impact of probiotics in an HIV-exposed very low birth weight (VLBW) infant on the occurrence of NEC is uncertain at present; however it is known that probiotics have protective effects against inflammation and prevent NEC. Postnatal growth restriction is a major issue in preterm, especially extremely-low-birth-weight (ELBW) infants and probiotics have been found to improve feeding tolerance in preterm infants. Human milk oligosaccharides (HMO) also known as the prebiotics of human milk, are known to have bifidogenic and anti-adhesive effects. Infants that receive human milk show a reduced incidence of NEC compared to those who receive infant formula. Very little is known about the composition of breast milk in the HIV-infected mother. Objective: The primary objective of the study was to assess the effect of probiotics on the incidence and severity of NEC in high-risk infants born to HIV-positive and HIV-negative women. The secondary objectives were to assess the effect of probiotic administration on feeding tolerance and growth outcomes of HIV-exposed but uninfected preterm infants, to describe the HMO composition of HIV-infected mothers breast milk and lastly to determine if HMO composition affects the incidence of NEC in HIV-exposed preterm very low birth weight infants. Patients and Methods: A randomized, double blind, placebo controlled trial was conducted for the period July 2011 to August 2012. HIV-exposed and HIV-unexposed premature (<34 weeks gestation) infants with a birth weight of ≥500g and ≤1250g were randomized to receive either a probiotic or a placebo. The probiotic consisted of 1x109 CFU, L. rhamnosus GG and B. infantis per day and was administered for 28 days. NEC was graded according to Bell’s criteria. Anthropometrical parameters and daily intakes were monitored. Breats milk samples were analysed for oligosaccharide content. Results: 74 HIV-exposed and 110 HIV-unexposed infants were enrolled and randomized (mean birth-weight, 987g; mean gestational 28.7 weeks). The incidence of death and NEC did not differ significantly between the HIV-exposed and unexposed groups but a significantly higher NEC incidence was found in the control group. There was no difference in the average daily weight gain for treatment groups or HIV exposure. The HIV-exposed group achieved significantly higher z-scores for length and head circumference at day 28 than the unexposed group (p<0.01 and p=0.03, respectively). There were no differences in the incidence of any signs of feeding intolerance and abdominal distension between the groups. Our results show significantly higher absolute concentrations of 2’-fucosyllactose, laco-N-tetraose and lacto-N-fucopentaose 1 and higher relative abundance of 3’-sialyllactose, difucosyl-lacto-N-tetraose and fucosyl-disialyllacto-N-hexaose in HIV-infected compared to -uninfected Secretor women. DSLNT concentrations were significantly lower in the breast milk of mothers whose infants developed NEC compared to infants without NEC. Conclusion: Probiotic supplementation reduced the incidence of NEC in the premature infants; however results failed to show a lower incidence of NEC in HIV-exposed premature infants. Probiotic supplementation did not affect growth outcomes or the incidence of any signs of feeding intolerance in HIV-exposure. The data confirms previous reports that HIV-infected mothers have higher 3’sialyllactose milk concentrations. Most intriguing though, the data also indicates that low levels of DSLNT in the mother’s milk increase the infant’s risk for NEC, which is in accordance with results from previously published animal studies and warrants further investigation. / AFRIKAANSE OPSOMMING: Inleiding: ʼn Verwantskap tussen moederlike menslike immuniteitsgebreksvirus (MIV) en nekrotiserende enterokolitis (NEK) in premature babas is aangemeld. Die impak van probiotika in ʼn MIV-blootgestelde baie lae geboortemassa (BLGM) baba op die voorkoms van NEK is tans nog onseker, maar dit is wel bekend dat probiotika ʼn beskermende effek het teen inflammasie en die voorkoms van NEK. Nageboortelike groei beperkings is ʼn groot probleem in premature, veral ekstreme lae geboortemassa (ELGM) babas. Daar is gevind dat probiotika voeding toleransie in premature babas kan verbeter. Menslike melk oligosakkariede (MMO), ook bekend as die prebiotika van menslike melk, is bekend om bifidogeniese en anti-kleef effekte te hê. Babas wat moedersmelk ontvang toon ʼn verlaagde voorkoms van NEK in vergelyking met diegene wat baba formule melk ontvang. Baie min inligting is bekend oor die samestelling van borsmelk in die MIV-positiewe moeder. Doel: Die primêre doel van die studie was om die effek van probiotika op die voorkoms en die graad van NEK in hoë risiko babas van MIV-positiewe en MIV-negatiewe vroue te bepaal. Die sekondêre doelwitte was om die effek van probiotika op voeding verdraagsaamheid en groei uitkomste van MIV-blootgestelde, maar nie- geinfekteerde premature babas te evalueer sowel as die MMO samestelling van MIV-positiewe moeders se borsmelk te beskryf en laastens om die invloed van die MMO samestelling op die voorkoms van NEK in baie lae geboortegewig MIV-blootgestelde premature babas te beskryf. Pasiënte en Metodes: ʼn Gerandomiseerde, dubbelblinde, plasebo-beheerde studie is vir die tydperk Julie 2011 tot Augustus 2012 onderneem. MIV-blootgestelde en nie-blootgestelde premature (<34 weke) babas met 'n geboorte gewig van ≥500g en ≤1250g was ewekansig verdeel om probiotika of plasebo te ontvang. Die probiotika het bestaan uit 1x109 kolonie vormende eenhede, L. rhamnosus GG en B. infantis per dag en is toegedien vir 28 dae. NEK is gegradeer volgens Bell se kriteria. Antropometriese parameters en daaglikse inname is gemonitor. Borsmelk monsters is geanaliseer vir oligosakkaried inhoud. Resultate: 74 MIV-blootgestelde en 110 MIV-nie-blootgestelde babas is ingesluit en ewekansig ingedeel (gemiddelde geboorte gewig, 987g, gemiddelde gestasie 28,7 weke). Die voorkoms van die sterftes en NEK het nie beduidend verskil tussen die MIV-blootgestelde en nie-blootgestelde groepe nie, maar 'n beduidende verskil is gevind vir NEK voorkoms tussen die studie en die kontrole groep. Daar was geen verskil in die gemiddelde daaglikse gewigstoename tussen die behandelings groepe of MIV-blootstelling nie. Die MIV-blootgestelde groep het beduidend hoër z-tellings vir lengte en kopomtrek op dag 28 getoon teenoor die nie-blootgestelde groep (p <0.01 en p = 0,03, onderskeidelik). Daar was geen verskille in die voorkoms van voeding onverdraagsaamheid en abdominale distensie tussen die twee groepe nie. Ons resultate dui op aansienlik hoër absolute konsentrasies van 2'-fucosyllactose, laco-N-tetraose en lakto-N-fucopentaose 1 en hoër relatiewe voorkoms van 3'-sialyllactose, difucosyl-lakto-N-tetraose en fucosyl-disialyllacto-N-hexaose in MIV-positiewe vroue in vergelyking met-negatiewe Sekretor vroue. DSLNT konsentrasies was aansienlik laer in die melk van moeders wie se babas NEK ontwikkel het in vergelyking met babas sonder NEK. Gevolgtrekking: Probiotika aanvullings verminder die voorkoms van NEK in premature babas, maar die resultate kon nie ʼn laer voorkoms van NEK in MIV-blootgestelde premature babas bewys nie. Probiotiese aanvulling het geen invloed op groei uitkomste of die voorkoms van voeding onverdraagsaamheid in MIV-blootstelling getoon nie. Die data bevestig vorige verslae wat aandui dat MIV-besmette moeders hoër 3'sialyllactose borsmelk konsentrasies het. ʼn Interessante aspek is dat lae vlakke van DSLNT in die moeder se melk beduidend is van ʼn verhoogde risiko vir NEK, wat in ooreenstemming is met die resultate uit voorheen gepubliseerde dier studies en regverdig verdere ondersoeke.

A suinocultura brasileira representa uma importante atividade econômica para o país, o qual ocupa lugar de destaque na produção e exportação de carne suína no mundo. O destaque do país na produção de suínos, deve-se a melhorias na sanidade, manejo, produção integrada e, principalmente, no aprimoramento gerencial dos produtores. O primeiro artigo consistiu em determinar a frequência e a distribuição das doenças infecciosas (DI) diagnosticadas através de exame de necropsia e histopatologia em suínos nas fases de crescimento e terminação ao longo de 12 anos (2005-2016) no sul do Brasil. Foram avaliados 1906 laudos anatomopatológicos de suínos nas fases de crescimento/terminação, dos quais as DI corresponderam a 75,6% (1441 casos) do total. As infecções por circovírus suíno tipo 2 (PCV2) foram as mais frequentes, contabilizando 51,3% (739/1441) dos casos, seguidas por DI que afetam o sistema respiratório (30,1% dos casos). Dentre essas, destacam-se a influenza suína A (15,1%; 218/1441) e pneumonias bacterianas (15%; 216/1441). O diagnóstico de influenza exibiu uma frequência elevada entre os anos de 2010 a 2013, totalizando 43,1% (167/387) dos casos. Após este período, ambas DI respiratórias exibiram caráter endêmico. As DI que afetam o sistema digestório totalizaram 10,5% (151/1441) dos diagnósticos, com as seguintes condições: enterocolite por Salmonella spp. (43,7%; 66/151), enteropatia proliferativa por Lawsonia spp. (41,7%; 63/151) e colite por Brachyspira spp. (14,6%; 22/151). Além dessas, as polisserosites e meningites bacterianas representaram 5,8% (84/1441) e 2,3% (33/1441) dos casos diagnosticados, respectivamente. O segundo artigo descreve três surtos de doença por circovírus suíno tipo-2 (PCVD) com lesões envolvendo musculatura esquelética. Em um curso clínico de 7 a 10 dias, 92 suínos apresentaram apatia, emagrecimento e diarreia. Ainda, cerca de 30 dos suínos afetados, apresentavam dificuldade de locomoção, fraqueza muscular, paresia de membros pélvicos e decúbito permanente. Quatro suínos exibiram palidez em músculos esqueléticos dos membros pélvicos, torácicos e dorso-lombares. As lesões microscópicas observadas consistiam de miosite necrótica granulomatosa, predominantemente, em membros pélvicos e torácicos, e em menor intensidade nos músculos dorso-lombares. No exame imuno-histoquímico para PCV2 observou-se marcação multifocal acentuada, predominantemente, no citoplasma e núcleos de macrófagos, linfócitos e células gigantes multinucleadas, além de marcação discreta no citoplasma no citoplasma de fibras necróticas da musculatura esquelética. As amostras de músculo esquelético foram positivas na reação em cadeia de polimerase para PCV2 e a ampliação exibiu 99% de identidade com sequências pertencentes ao genótipo PCV2b. / Brazilian pig farms represent an important economic activity for the country, which occupies a prominent place in the production and export of pork in the world. The country's prominence in pork production is due to improvements in sanitation, management, integrated production and, mainly, in the managerial improvement of the producers. The first study aimed to determine the frequency and distribution of infectious diseases (ID) diagnosed through necropsy and histopathology examination in growing-finishing swine along 12 years (2005-2016) in Southern Brazil. A total of 1906 anatomopathological exams performed in growing-finishing swine were evaluated, of which ID accounted for 75.6% (1441 cases) of the total. Porcine circovirus type 2 (PCV2) infections were the most frequent, accounting for 51.3% of the cases (739/1441), followed by respiratory system ID (30.1% of the cases). Among these, the main conditions were swine influenza (15.1%; 218/1441) and bacterial pneumonia (15%; 216/1441). Influenza diagnosis had a higher frequency between 2010 and 2013, accounting for 43,1% (167/387) of the cases. After this period, both respiratory ID had an endemic occurrence. Digestive system ID accounted for 10.5% (151/1441) of the diagnosis, with the main conditions diagnosed: Salmonella spp. enterocolitis (43.7%; 66/151), Lawsonia spp. proliferative enteropathy (41.7%; 63/151) and Brachyspira spp. colitis (14.6%; 22/151). Besides these, polyserositis and bacterial meningitis represented, respectively, 5.8% (84/1441) and 2.3% (33/1441) of the cases diagnosed. The second study describes three outbreak of porcine circovirus disease (PCVD) with the involvement of skeletal muscle. In a clinical course of 7 to 10 days, 92 pigs had apathy, weight loss and diarrhea. Approximately 30 of these 92 pigs had stiff gait, muscle weakness, hind limb paresis, and recumbency. 4 pigs necropsied presented pale discoloration from hind and thoracic limbs, as well from dorsal lumbar skeletal muscles. The microscopical lesions consisted of granulomatous necrotizing myositis mainly of hind and thoracic limbs, and mildly from dorsal lumbar muscles. Immunohistochemistry exam for PCV2 revealed marked multifocal intracytoplasmic and intranuclear staining predominantly in macrophages, lymphocytes and multinucleated giant cells, with a lower amount in the cytoplasm of necrotic fibers of the skeletal muscle. Affected muscle samples were polymerase chain reaction– positive for PCV2 and the amplicon exhibited 99% identity with sequences belonging to the PCV2b genotype.

Submitted by Ana Damasceno (ana.damasceno@unipampa.edu.br) on 2017-06-07T18:12:48Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Baixa diversidade e sucessão microbiana anormal estão associadas à enterocolite necrosante em recém-nascidos prematuros.pdf: 1587508 bytes, checksum: c407e4cf94f25b2272a7d25213f72873 (MD5) / Made available in DSpace on 2017-06-07T18:12:48Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Baixa diversidade e sucessão microbiana anormal estão associadas à enterocolite necrosante em recém-nascidos prematuros.pdf: 1587508 bytes, checksum: c407e4cf94f25b2272a7d25213f72873 (MD5) Previous issue date: 2017-04-07 / As múltiplas causas de Enterocolite Necrosante (NEC) e seus indicativos clínicos utilizados para o diagnóstico ainda se mantêm elusivos. Biomarcadores alternativos para o diagnóstico precoce de NEC em recém-nascidos prematuros e um melhor entendimento dos fatores de risco para o desenvolvimento de NEC são desafios emergentes. Em uma tentativa de contribuir para a solução deste problema, neste trabalho nós rastreamos as mudanças no microbioma dos recém-nascidos (diversidade microbiana, abundância e estrutura) com NEC, iniciando com a primeira evacuação (mecônio) e continuando até a liberação, e comparamos essas mudanças com os prematuros sem o diagnóstico de NEC. Um estudo metataxonomico foi conduzido usando 88 amostras fecais, a partir da primeira evacuação até a 5ª semana de vida, obtidas de 25 recém-nascidos prematuros (14 controles e 11 casos de NEC) selecionados de um grupo de 52 prematuros. Nossos dados revelaram que casos de NEC apresentaram baixa diversidade e uma transição anormal da comunidade microbiana até o diagnóstico de NEC. Um microrganismo pertencendo a família Enterobacteriaceae foi consistentemente mais abundante em prematuros com NEC do que nos controles, mesmo nas amostras de mecônio, e foi considerado um constituinte chave da comunidade microbiana correlacionada com a doença. Finalmente, nos também detectamos uma distorção na associação micróbio-micróbio nas amostras de mecônio dos casos de NEC. Portanto, nossos dados sugerem que a detecção precoce de elevada dominância de Enterobacteriaceae, baixa diversidade e associações micróbio-micróbio nos primeiros dias de vida poderiam ser utilizados como indicativo de risco de desenvolvimento de Enterocolite Necrosante nas UTIs neonatais brasileiras. / The multiple causes of Necrotizing Enterocolitis (NEC) as well as the clinical predictors used for diagnosis have remained elusive to date. Alternative biomarkers for early diagnosis of NEC in premature infants and a better understanding of risk factors for NEC development are emergent challenges. In attempt to contribute to solve this problem, in this work we tracked the changes in the newborn’s microbiome (microbial diversity, abundance and structure) with Necrotizing Enterocolitis beginning with the first stool (meconium) continuing until discharge and compare those changes with preterns without NEC diagnosis. A metataxonomy study was conducted using 88 fecal samples from the first stool (meconium) until the 5th week of life obtained from 25 preterm babies (14 controls and 11 NEC cases) selected from a cohort of 52 premature infants. Our data revealed low microbial diversity in NEC cases and an abnormal transition of the microbial community until NEC diagnosis. A microbial phylotype belonging to the Enterobacteriaceae family were consistently more abundant in NEC than in the controls even in meconium samples and was considered a key constituent of the microbial community that correlated with the disease. Finally, we also detected a disruption of microbial-microbial associations in the meconium samples of NEC cases. Thus, our data suggests that early detection of high dominance of Enterobacteriaceae, low diversity and altered microbial-microbial associations at the first days of life could be used as an indicative of risk of preterm development of Necrotizing Enterocolitis in Brazilian NICU’s.

Le microbiote digestif humain joue un rôle essentiel et bénéfique pour son hôte mais il est également impliqué dans un nombre croissant de pathologies. Les connaissances sur la composition de cet écosystème ont récemment été révolutionnées grâce à l’utilisation de techniques moléculaires. Cependant, ces techniques comportent des limites importantes. C’est ainsi que le concept de « culturomique » a été introduit ; il consiste en la multiplication de milieux et conditions de culture et l’identification rapide de colonies bactériennes par spectrométrie de masse (MALDITOF) ou par amplification et séquençage du gène de l’ARN ribosomal 16S. Dans la première partie de ce travail, nous avons mis en évidence une association entre la présence de Clostridium butyricum dans les selles et la survenue d’entérocolite ulcéro-nécrosante que ce soit par méthodes de pyroséquençage et culture ou par PCR quantitative en temps réel spécifique de C. butyricum; identifié après séquençage du génome complet de toutes nos souches de C. butyricum, la présence du gène de la β-hémolysine (toxine). Dans la deuxième partie de ce travail, nous avons montré par cuturomique que les bactéries à Gram-négatif (BGN) étaient fréquemment disséminées au sein du microbiote cutané transitoire des patients hospitalisés en réanimation ; le réservoir serait essentiellement digestif. En conclusion, le microbiote digestif constitue un réservoir sousestimé de bactéries pathogènes. La microbiologie moderne incluant les nouvelles méthodes de culture permet d’étendre de manière considérable les connaissances sur la composition de cet écosystème et son implication en pathologie humaine. / He human gut microbiota plays an important and beneficial role in its host but it is also involved in a growing number of diseases. Knowledge of the composition of this ecosystem have recently been revolutionized by the use of molecular techniques. However, these techniques have significant limitations. Thus, the concept of "culturomics" has been introduced; it consists of the multiplication of culture conditions and the rapid identification of bacterial colonies by mass spectrometry (MALDI-TOF) or by PCR 16S RNA gene sequencing. In the first part of this work, we have demonstrated an association between the presence of Clostridium butyricum in the stool and the occurrence of necrotizing enterocolitis whether by pyrosequencing methods and Culture or by quantitative PCR specific real time C. butyricum; identified after sequencing the complete genome of all our strains of C. butyricum, the presence of the gene of β-hemolysin (toxin). In the second part of this work, we showed by cuturomics that Gram-negative bacteria (BGN) were frequently spread out over the transitional skin microbiota of patients hospitalized in intensive care; the reservoir would essentially digestive. In conclusion, the gut microbiota is an underestimated reservoir of pathogenic bacteria. Modern microbiology including new culture-based methods is currently extending exponentially our knowledge on gut microbiota giving rise to new insights into the pathogenesis or the transmission of infectious diseases.