Thèses sur le sujet « Bronchopneumonie »

Les bronchopneumonies infectieuses (BPI) sont les maladies les plus fréquentes des jeunes bovins à l’engrais (JB). Les connaissances actuelles sont insuffisantes pour, lors d’épisodes de BPI survenant dans des lots de JB, choisir entre le traitement des seuls malades détectés par inspection visuelle ou de l’ensemble du lot. L’objectif était (i) d’évaluer la sous-détection des malades par inspection visuelle et d’en estimer l’impact sur la performance de croissance et (ii) d’étudier la transmission horizontale de Mannheimia haemolytica et Mycoplasma bovis au sein de lots de JB. Le suivi en continu de la température corporelle a révélé de nombreux retards et défauts de détection associés à une diminution des performances de croissance des JB. Le typage par électrophorèse sur champs pulsés a montré une forte variabilité génétique intra-lot des isolats de M. Haemolytica, ce qui est faveur d’une transmission peu fréquente, et un clone unique de M. Bovis par épisode, ce qui est en faveur d’une transmission fréquente. Nos résultats quant à la sous-détection indiquent que le traitement des seuls malades détectés ne suffit pas pour assurer les meilleures performances de croissance à l’échelle du lot. Nos résultats quant à la transmission indiquent que le traitement collectif pour protéger les bovins sains et réceptifs apparait justifié en cas d’implication de M. Bovis et plus discutable en cas d’implication de M. Haemolytica. Au final, à l’avenir, des systèmes d’alerte permettant une détection sensible des bovins malades ainsi que des méthodes adaptées pour identifier la présence d’une bactérie pathogène hautement transmissible au sein de lots de JB devraient être mis en œuvre.

L’étiologie des bronchopneumonies infectieuses (BPI) des jeunes bovins est multifactorielle, mettant en cause des agents infectieux comme des bactéries, virus ou parasites, et également des facteurs de risques liés à la conduite d’élevage et à l’environnement. Dans cette thèse nous nous sommes intéressés aux virus respiratoires bovins. Nous avons étudié le virome de l’appareil respiratoire superficiel et profond des jeunes veaux atteints de BPI par des approches de séquençage à haut débit pour mieux caractériser les co-infections virales et identifier de nouveaux virus. Par ailleurs nous nous sommes intéressés au contexte dans lequel les virus opèrent en analysant la structure, la diversité, et le dynamisme du bactériote respiratoire chez des veaux sains et atteints de BPI. Les résultats suggèrent que de nombreux virus agissent en interactions et montrent une prédominance du coronavirus bovin (BCoV) dans les cavités nasopharyngées et également dans les poumons des veaux atteints de BPI. L’étude phylogénétique des BCoV isolés indique une ségrégation entre souches européennes d’une part et américaines et asiatiques d’autre part qui semble résulter d’un phénomène de recombinaison dans les années 1960-70. Par ailleurs un astrovirus bovin a été clairement détecté pour la première fois principalement dans les poumons de veaux atteints de BPI. L’analyse du microbiote indique, elle, une disparité écologique entre cavités superficielles et profondes et des interactions possibles entre agents pathogènes connus et différentes communautés bactériennes de la flore résidente. Enfin une partie des travaux a concerné le virus influenza D (IDV), un nouveau virus respiratoire bovin émergent récemment identifié en France. Lors d’une infection expérimentale chez des veaux nous avons démontré que IDV possède un pouvoir pathogène respiratoire modéré et qu’il module la réponse immunitaire innée du veau. Nous avons aussi confirmé le caractère ubiquiste d’IDV en démontrant sa circulation sur le continent africain. En conclusion, grâce à des méthodes de séquençages à haut débit ce travail a permis une meilleure description et caractérisation des virus respiratoires bovins et de leur environnement immédiat. Il ouvre des perspectives pour mieux comprendre le rôle des interactions virales dans la genèse des signes cliniques respiratoires
Bovine infectious bronchopneumonia (BIP) is a complex syndrome that affects young bovines, with a multifactorial etiology often involving one or several viruses and bacteria favored by altered host immunity and disturbed environmental factors. First, using viral metagenomics sequencing tools, we explored the upper (URT) and lower (LRT) respiratory tract viromes of calves with BPI and identified unexpected viruses. In addition, in the same calves, we characterized the structure, diversities and dynamism of the bacterial communities. Results showed different patterns of interactions between the different components of the microbiomes. Among the many detected viruses, the bovine coronavirus (BCoV), showed the highest prevalence in both nasal and pulmonary cavities. Evolutionary and phylogenic analysis of the isolated BCoV strains indicated a clear segregation between European and American/Asian strains, which seems to have resulted from a recombination event during the 1960-70’s. Furthermore, a bovine astrovirus was detected for the first time in the lungs of BIP affected calves. A disparity was noticed in the bacterial community structures between the upper and lower respiratory cavities. Also, there were associations between the presences of certain bacterial taxa and known respiratory pathogens. Finally, a part of the work focused on the emerging influenza D virus (IDV) recently identified in France. Carrying an experimental infection, we showed that IDV has a moderate respiratory pathogenicity and can modulate the innate immune response of the calf. We also showed that IDV circulates in Africa thus confirming its global distribution. In conclusion, thanks to high throughput sequencing methods, this piece of work allowed for a detailed characterization of the bovine respiratory virome and its interacting environment, and further opened new perspectives for a better understanding of viral interactions in bovine BIP

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Estudou-se a broncopneumonia de ocorrência natural em bezerros mantidos em bezerreiro coletivo, e a influência da administração intramuscular de acetato de DL-a-tocoferol na profilaxia e tratamento desta enfermidade. Foram avaliados 60 bezerros machos, com idade máxima de 10 dias, sorteados para comporem os grupos experimentais: GSV (grupo sem vitamina) e GCV (grupo com vitamina). A suplementação foi precedida por exame físico, colheita de sangue para hemograma, determinação de proteínas séricas e GGT, e lavado traqueobrônquico para exame citológico (D0). Os animais de ambos os grupos foram conduzidos ao bezerreiro coletivo, onde permaneceram até o 21º dia (D0 ao D21). Foram distribuídos aleatoriamente, 2 a 2, em baias individuais de 1,20m de largura por 2 m de comprimento. Independentemente do grupo experimental, os animais foram avaliados por exame físico diário e, na presença de sinais clínicos indicativos de broncopneumonia (DX), foram retirados do bezerreiro, avaliados por hemograma e citologia do lavado traqueobrônquico, e tratados com enrofloxacina. Durante o tratamento, o exame físico foi realizado diariamente, e os exames complementares, hemograma e citologia do lavado traqueobrônquico, repetidos uma semana após seu término (DY). Nos animais sadios, além do exame físico diário e dos exames complementares já realizados no D0, foram repetidos hemograma e citologia do lavado traqueobrônquico no último dia (D21) do experimento. Comparou-se a ocorrência de broncopneumonia e a evolução do tratamento nos dois grupos estudados. A suplementação com vitamina E não teve influência na profilaxia e no tratamento de broncopneumonia de bezerros.
Bronchopneumonia of natural occurrence in calf housed calves was studied, and the influence of intramuscular administration of DL-a-tocoferol acetate on prophylaxis and treatment of this disease. Sixty male calves, with maximum age of 10 days, were evaluated, draftees to compose the experimental groups: GSV (animals without supplementation) and GCV (animals with supplementation). Supplementation was preceded by physical examination, collection of blood samples for hemogram, total protein determination and GGT, and tracheobronchial wash for cytological examination (D0). The animals were taken to the calf housing, where they remained until 21º day (D0 to D21). They were distributed, 2 - 2, in individual pens of 1,20m of width for 2 m of length. Independently of the group, all animals were evaluated by physical examination daily and, in presence of indicative clinical signs of bronchopneumonia (DX), they were removed out of the calf housing, evaluated for hemogram and cytology of tracheobronchial wash, and treated with enrofloxacin. During the treatment, physical examination was carried through daily and the complementary examinations, hemogram and cytology of the tracheobronchial wash were repeated one week after its ending (DY). In healthy animals, beyond the daily physical examination and complementary examinations already done on D0, hemogram and cytology of tracheobronchial wash were repeated in the last day of the experiment (D21). Occurrence of bronchopneumonia and evolution of the treatment in both studied groups were compared. The supplementation with vitamin E did not have influence on bronchopneumonia prophylaxis or treatment. Key words: calves, bronchopneumonia, vitamin E, tracheobronchial wash, prophylaxis.

Orientador: Roberto Calderon Gonçalves
Banca: Simone Biagio Chiacchio
Banca: Laurenil Gaste
Resumo: Estudou-se a broncopneumonia de ocorrência natural em bezerros mantidos em bezerreiro coletivo, e a influência da administração intramuscular de acetato de DL-a-tocoferol na profilaxia e tratamento desta enfermidade. Foram avaliados 60 bezerros machos, com idade máxima de 10 dias, sorteados para comporem os grupos experimentais: GSV (grupo sem vitamina) e GCV (grupo com vitamina). A suplementação foi precedida por exame físico, colheita de sangue para hemograma, determinação de proteínas séricas e GGT, e lavado traqueobrônquico para exame citológico (D0). Os animais de ambos os grupos foram conduzidos ao bezerreiro coletivo, onde permaneceram até o 21º dia (D0 ao D21). Foram distribuídos aleatoriamente, 2 a 2, em baias individuais de 1,20m de largura por 2 m de comprimento. Independentemente do grupo experimental, os animais foram avaliados por exame físico diário e, na presença de sinais clínicos indicativos de broncopneumonia (DX), foram retirados do bezerreiro, avaliados por hemograma e citologia do lavado traqueobrônquico, e tratados com enrofloxacina. Durante o tratamento, o exame físico foi realizado diariamente, e os exames complementares, hemograma e citologia do lavado traqueobrônquico, repetidos uma semana após seu término (DY). Nos animais sadios, além do exame físico diário e dos exames complementares já realizados no D0, foram repetidos hemograma e citologia do lavado traqueobrônquico no último dia (D21) do experimento. Comparou-se a ocorrência de broncopneumonia e a evolução do tratamento nos dois grupos estudados. A suplementação com vitamina E não teve influência na profilaxia e no tratamento de broncopneumonia de bezerros.
Abstract: Bronchopneumonia of natural occurrence in calf housed calves was studied, and the influence of intramuscular administration of DL-a-tocoferol acetate on prophylaxis and treatment of this disease. Sixty male calves, with maximum age of 10 days, were evaluated, draftees to compose the experimental groups: GSV (animals without supplementation) and GCV (animals with supplementation). Supplementation was preceded by physical examination, collection of blood samples for hemogram, total protein determination and GGT, and tracheobronchial wash for cytological examination (D0). The animals were taken to the calf housing, where they remained until 21º day (D0 to D21). They were distributed, 2 - 2, in individual pens of 1,20m of width for 2 m of length. Independently of the group, all animals were evaluated by physical examination daily and, in presence of indicative clinical signs of bronchopneumonia (DX), they were removed out of the calf housing, evaluated for hemogram and cytology of tracheobronchial wash, and treated with enrofloxacin. During the treatment, physical examination was carried through daily and the complementary examinations, hemogram and cytology of the tracheobronchial wash were repeated one week after its ending (DY). In healthy animals, beyond the daily physical examination and complementary examinations already done on D0, hemogram and cytology of tracheobronchial wash were repeated in the last day of the experiment (D21). Occurrence of bronchopneumonia and evolution of the treatment in both studied groups were compared. The supplementation with vitamin E did not have influence on bronchopneumonia prophylaxis or treatment. Key words: calves, bronchopneumonia, vitamin E, tracheobronchial wash, prophylaxis.
Mestre

O objetivo deste estudo foi avaliar os aspectos clínicos, a eficiência produtiva, reprodutiva, a resposta imune inata e humoral em fêmeas da raça Holandesa persistentemente infectadas (PI) com BVDV. Para tanto, foram selecionadas 25 PI´s por meio do ELISA antígeno, das quais oito eram bezerras ≤ 12 meses; seis novilhas entre 13 e 24 meses; e onze animais de 25 a 36 meses de idade. O grupo não infectado (NI) foi composto por fêmeas negativas com faixas etárias pareadas às PIs. Em geral, as fêmeas PIs apresentaram maior frequência de diarreia (P=0,012) e Doença Respiratória Bovina (DRB) (P=0,004), especialmente àquelas entre 25 a 36 meses de idade. As PIs apresentaram maior concentração sérica de haptoglobina (P=0,017). As vacas NI´s produziram mais leite (8-12 litros) do que as PIs (P≤0.011). A contagem de células somáticas (CCS) foi maior para as vacas PI´s em relação NI´s durante a lactação (P≤0,066). A média de CCS observada foi de 0,2-0,5 x 105 (células/mL) e 2,0-10,5 x 105 (células/mL) nos grupos PI e NI, respectivamente. A idade na primeira inseminação (P=0,001) e o número de inseminação necessário para a primeira prenhez foi maior para PI do que nas novilhas NI´s (P=0,051). Na avaliação hematológica, as PI´s apresentaram menores valores de hemoglobina (P=0,098), hematócrito (P=0,084), hemoglobina corpuscular média (P=0,092), plaquetas (P=0,040), plaquetócrito (P=0,059) e linfócitos (número absoluto P=0,075; relativo P=0,092) em relação às NI´s. Em contraste, a porcentagem de monócitos foi maior em PI do que animais NI (P=0,014). Em geral, a proporção (%) e a intensidade da fagocitose (MFI) para Staphylococcus aureus e Escherichia coli foram maiores nas PIs do que animais NI (P<0,079). A porcentagem de células que produziram espécies reativas de oxigênio (EROs) endógeno foi menor em PI do que animais de NI (P=0,005). Padrão semelhante foi observado na porcentagem de células que produziram EROs após estímulo com Staphylococcus aureus (P=0,000) ou Escherichia coli (P=0,000). Em contraste, a intensidade da produção de EROS basal foi maior nas PI´s do que nas NI´s (P=0,011). Um padrão semelhante foi observado para a intensidade da produção de EROs quando as células foram estimuladas com Staphylococcus aureus (P=0,011) ou Escherichia coli (P= 0,013). Por meio da soroneutralização, observou-se que os títulos médios dos anticorpos neutralizantes para as BVDV, BRSV e BoHV foram menor no grupo PI (P=0,000). No entanto, os títulos de anticorpos para BPIV-3 foram semelhantes entre os grupos (P=0,146). A proteína sérica total (PT) foi menor nas PI em relação as NI´s (P=0,021). As fêmeas PIs apresentaram maior frequência de diarreia e DRB, além da menor produção leiteira, diminuição da qualidade do leite e menor fertilidade. O leucograma demonstrou diminuição dos tipos celulares, exceto monócitos. No geral, houve resposta imune inata foi exacerbada nas fêmeas PIs, provavelmente pela menor eficiência na produção de EROs. Em relação ao sistema imune específico observou-se linfopenia e títulos nulos ou baixos de anticorpos neutralizantes contra as viroses respiratórias.
The aim of this study was to evaluate the clinical problems, the efficiency of production, reproduction, the innate and humoral immune response of Holstein heifers and cows persistently infected (PI) with BVDV. Therefore, 25 PI animals were selected using ELISA antigen of which, eight were heifers ≤ 12 months; six were heifers between 13 to 24 months; and eleven were animals from 25 to 36 months old. An uninfected group (NI) composed by negative females with same age of PI´s. We observed that PI´s presented more frequency of diarrhea (P=0.012) and Bovine Respiratory Disease (BRD) score (P=0.004), especially the animals from 25 to 36 months old. The PI´s showed higher concentration of haptoglobin (P=0.017). During the lactations the milk production from NI cows was higher (8 to 18,2 litters) than PI (P≤0.011). Somatic cells count (SCC) were higher for PI than NI cows across milk production (P≤0.066). The mean of SCC observed was 0,2-0,5 x105 (cells/mL) in NI group and 2,0-10,5 x105 (cells/mL) for PI cows. The age at first insemination (P=0.001) and number of insemination required for the first pregnancy was higher for PI than NI heifers (P=0.051). For hematological evaluation, PI´s showed lower hemoglobin (P=0,098), hematocrit (P=0,084), mean corpuscular hemoglobin (P=0,092), platelet (P=0,040), plateletcrit (P=0,059) and lymphocytes (absolute number P=0.092; relative P=0,075) than NI. In contrast, the percentage of monocytes was higher in PI than NI animals (P=0.014). In aggregate, the percent of phagocytic cells and the average phagocytic avidity (expressed as mean fluorescence intensity, MFI) for Staphylococcus aureus and Escherichia coli were higher in PI than NI animals (P≤ 0.079). The percentage of cells producing endogenous reactive oxygen species (ROS) activity was lower in PI than NI animals (P=0.005). A similar pattern was observed in the percentage of cells producing ROS after exposure to Staphylococcus aureus (P= 0.000) or Escherichia coli (P=0.000). In contrast, the value for endogenous ROS per cell activity (MFI) was higher in PI than NI animals (P=0.011). A similar pattern was observed for ROS MFI after stimulating with Staphylococcus aureus (P=0.011) or Escherichia coli stimulation (P=0.013). The median conventional SN titers for specific antibody recognizing BVDV, BRSV and BoHV-1 in serum were lower in PI than NI animals (P=0.000). The antibody titers for BPIV3 were similar between the groups animals (P=0,146). In aggregate, the total serum protein (TP) was lower in PI than NI cattle (P=0.021). In summary, PI heifers had more diarrhea, BRD, produced less milk, worst milk quality and poorer reproductive performance than NI cattle. Leukogram showed decreased cell types except monocytes. Overall, there was a higher endogenous level innate cell reactivity in PI heifers and cows than NI animals, probably because of the lower efficiency in ROS production. In relation to the specific immune system it appear that the PI animals were less efficient in clearance of antigens due to lower numbers of lymphocytes and related lower titers of specific antibody against respiratory viruses.

As doenças respiratórias são consideradas um sério problema de sanidade, causando grandes perdas econômicas devido aos altos índices de morbidade e mortalidade, sendo responsáveis por 10 a 40% das mortes em animais adultos e por 17% das mortes durante o período perinatal. O objetivo deste trabalho foi determinar a ocorrência de agentes e buscar associações entre agentes e a broncopneumonia e a associação de sinais clínicos com os agentes presentes. Foram avaliados clinicamente e os dados coletados em ficha própria 96 animais de dois rebanhos da região de Bragança Paulista e Mococa ambas no Estado de São Paulo. Sangue total e lavado traqueobrônquico instilado em haste flexível e o restante da alíquota criopreservada, foram colhidos em animais jovens e adultos, com e sem raça definida e a ocorrência dos principais agentes etiológicos virais (BVDV, VSRB e BoHV) e bacterianos (Mannheimia haemolytica, Pasteurella multocida e micoplasma sp.) causadores de broncopneumonia em bovinos foram pesquisadas. Dos cultivos bacterianos específicos, as aliquotas criopreservada apresentaram 12/96 amostras positivas para mollicutes enquanto os cutivos utilizando as hastes foram 11/96 amostras positivas para P. multocida. No cultivo da P. multocida também foram encontradas Bacillus sp., Staphylococcus sp., Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa e Klebsiella pneumoniae sem que houvesse a ocorrência de M. haemolytica. PCR foi utilizada para detectar a classe mollicutes (68/96) e as espécies M. bovis (2/68), M. dispar (26/68) e M. mycoides subsp. mycoides (0/68). A técnica de vírus neutralização mostrou os seguintes resultados: 31/56 animais soreagentes para BVDV, 35/57 com BoVH e 54/58 com VSRB. Para análise estatística foi utilizado o teste do qui-quadrado em blocos ao acaso. Houve associação entre a presença de broncopneumonia em animais com BVDV (P=0,080) e com P. multocida (P=0,076). Animais da raça holandesa foram associados a presença de broncopneumonia (p= 0,095). Jovens com menos de 12 meses foram associados a presença de mollicutes (P=0,0177). A presença de som submaciço a percussão do gradil toráxico foi associado a ausência de mollicutes (P=0,025). A ausência de M. dispar foi associado a presença de sibilo (P=0,076) e de estertor úmido (P=0,046) na ausculta pulmonar. Houve uma chance maior de 5,5 vezes de apresentar tosse na presença de P. multocida enquanto na sua ausência hà uma maior chance dos animais apresentarem secreção mucosa (7,3) e mucopurulento (5,8), som submaciço (9,6), crepitação fina (13) e estertor úmido (5). Houve associação entre a ausência de M. bovis e a presença de som claro a percussão do gradil toráxico dos bovinos examinados.
Respiratory diseases are considered a serious problem of sanity, causing huge economic losses due to high rates of morbidity and mortality, accounting for 10-40% of deaths in adults and 17% of deaths during the perinatal period. The objective of this study was to determine the occurrence of agents and seek associations between agents and bronchopneumonia and the association of clinical signs with these agents. They were evaluated clinically and data collected in own record 96 animals of two herds of Bragança Paulista region and Mococa both in São Paulo. Whole blood and washed tracheobronchial were harvested in young and adult animals, Holstein and undefined breed and the occurrence of major viral etiologic agents (BVDV, BRSV and BoHV) and bacterial (Mannheimia haemolytica, Pasteurella multocida and Mycoplasma sp.) causing bronchopneumonia in cattle were surveyed. The specific bacterial cultures showed positive samples Mollicutes 12/96 and 11/96 samples positive for P. multocida. In the cultivation of P. multocida were also found Bacillus sp., Staphylococcus sp., Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa and there was no occurrence of M. haemolytica. PCR was used to detect the class Mollicutes (68/96) and the species M. bovis (2/68), M. dispar (26/68) and M. mycoides subsp. mycoides (0/68). The virus neutralization technique showed the following results: 31/56 animals BVDV positive, 35/57 and 54/58 with BoVH with BRSV. Statistical analysis was performed using the chi-square test in blocks. There is an association between bronchopneumonia in animals and the presence of BVDV (p = 0.080) and P. multocida (P = 0.076). Holstein animals were associated with the presence of bronchopneumonia (p = 0.095). Calves under 12 months were associated with the presence of Mollicutes (P = 0.0177). The sound submassive present during percussion of the thoracic cage was associated with the absence of Mollicutes (P = 0.025). The absence of M. dispar was associated with presence of wheezing (P = 0.076) and wet rattle (P = 0.046) in lung auscultation. There was a greater chance of 5.5 times to present cough in the presence of P. multocida as in its absence there is a greater chance of the animals show mucous secretion (7.3) and mucopurulent (5.8), submassive sound (9.6 ), thin crackling (13) and wet rattle (5). There was an association between the absence of M. bovis and the presence of clear sound of chest cage percussion of the examined cattle.

Le genre Pneumocystis regroupe des microchampignons atypiques qui colonisent par voie respiratoire les alvéoles pulmonaires de nombreux mammifères. C’est un pathogène opportuniste qui s’avère particulièrement dangereux lorsque le système immunitaire de l’hôte est déficient (VIH, greffés) et dans ce cas il provoque une pneumonie, la pneumocytsose, fatale en absence de traitement. Du fait que les Pneumocystis spp restent des microchampignons non cultivables, il est alors impossible de manipuler directement ses gènes et la seule solution pour étudier leurs fonctions et leurs localisations, demeure leur expression en système hétérologue. Situé dans l'espace alvéolaire, Pneumocystis spp. sont exposés au stress oxydatif générés par les macrophages alvéolaires, les granulocytes neutrophiles ainsi que par les espèces réactives de l'oxygène (EROs) produits par le métabolisme respiratoire. Pour se protéger, ces micro-organismes ont développé un système spécifique de détoxification des EROs incluant les SuperOxyde Dismutases (SOD). Dans notre étude, la carence en MnSOD d'une souche de Saccharomyces cerevisiae (EG110) dépourvue du gène Scsod2 a été complétée par l'introduction d'un plasmide portant une version inductible du gène Sod2 de P. carinii (Pcsod2). Une fois exprimée la PcMnSOD était capable de complémenter le défaut de croissance de la souche EG110 qui a été exposés à la ménadione. En bref, notre étude a montré une bonne complémentation du gène Sod2 de P. carinii chez une levure déficiente en MnSOD à savoir (i) la reprise de la culture en conditions de stress oxydant, (ii) la mise en évidence de la protéine traduite (Western Blot) et (iii) l’adressage mitochondriale de la protéine hétérologue. Selon le degré d’altération du système immunitaire, les infections à P. jirovecii peuvent présenter des tableaux cliniques variés allant de la colonisation à la pneumocystose. Ces infections semblent être en grande partie liées à des déficits majeurs de l’immunité cellulaire se traduisant plus précisément par une diminution du nombre des lymphocytes TCD4 (LTCD4). Notre deuxième objectif était de parvenir à une appréciation quantitative du risque de contamination par P. carinii en fonction du degré d’immunodépression (ID) des rats exposés. Nous avons ainsi développé un modèle animal de transmission naturelle de P. carinii où des rats nude développant une pneumocystose (« rats donneurs ») sont mis en contact direct avec des rats Sprague Dawley Pneumocystis-free (« rats receveurs ») présentant différents niveaux d’ID (dexamethasone). Après 2 semaines de contact, le niveau de colonisation des rats graduellement ID est déterminé soit par comptage après coloration au Bleu de Toluidine O, soit par qPCR. Cette étude a permis tout d’abord de valider notre modèle d’ID graduelle chez le rat ; mais surtout, et pour la première fois dans un modèle expérimentale chez le rat, nous avons montré une relation inverse entre le niveau de colonisation par P. carinii et le taux de LTCD4 ou LTCD8 circulants. Enfin, nous avons réalisé la première étude épidémiologique portant sur Pneumocystis au Liban. Ce projet franco-libanais a été mis en place au vue de l’importance majeure de la colonisation par Pneumocystis chez les patients immunocompétents, en particulier chez les patients atteints de pathologies pulmonaires chroniques obstructives tels que la BPCO où la colonisation par Pneumocystis est considérée comme un facteur aggravant de la maladie. Nos résultats montrent une faible prévalence de colonisation (5.2%) et une prédominance du génotype mtLSU2 chez les patients atteints de pathologies respiratoires au Liban. De plus, dans notre cohorte de patient présentant des pathologies respiratoires variées, la BPCO semble être la seule maladie respiratoire associée à un facteur de risque de colonisation par P. jirovecii
Pneumocystis is an opportunistic pulmonary fungal pathogen that causes Pneumocystis pneumonia (PcP) in immunocompromised individuals such as patients with HIV infection as well as those without HIV infection who are undergoing immunosuppression as a consequence of chemotherapy or organ transplantation. Pneumocystis colonization in immunocompetent individuals has recently been described by the detection of fungal DNA without signs or symptoms of pneumonia, and accumulating evidences underline its clinical importance. Pneumocystis organisms are airborne transmitted and represent a large group of species of atypical fungi that cannot be continuously grown in culture. Consequently, it is impossible to directly manipulate genes in Pneumocystis species. Located in the alveolar space, Pneumocystis organisms are exposed to oxidative burst from phagocytic alveolar macrophages and neutrophils as well as to reactive oxygen species (ROS) produced by the mitochondrial oxygen metabolism. To counteract this, microorganisms have developed a ROS detoxifying system. This includes superoxide dismutases (SOD). In the present study, the MnSOD deficiency of a Saccharomyces cerevisiae mutant strain was complemented by introducing a plasmid carrying an inducible version of the P. carinii Sod2 gene (Pcsod2). Expression of Pcsod2 revealed that the corresponding MnSOD recombinant protein could complement the growth defect in the mutant yeast strain when cells were exposed to menadione. The mitochondrial localization was confirmed by immuno-colocalization of the P. carinii recombinant MnSOD with the yeast mitochondrial Cox4 protein. These results suggest that Pcsod2 encodes an active MnSOD that is targeted to the mitochondrion. This work increases our understanding of the antioxidant defense mechanisms deployed by the Pneumocystis organisms.The adaptive host response to Pneumocystis infection involves humoral and cellular immune responses working in concert to promote the clearance of infection. Depending on the degree of alteration of the immune system, Pneumocystis infections may have various clinical presentations going from colonization to the most severe form (PcP).These infections appear to be largely related to major deficits in cellular immunity and are more closely reflecting a decrease in the number of CD4 T lymphocytes (LTCD4). Our objective was to achieve a quantitative assessment of the risk of contamination by Pneumocystis depending on the degree of immunosuppression (ID) of the exposed host. Thus, we developed an animal model of natural transmission of P. carinii where rats undergoing gradual ID (dexamethasone) named receivers, are cohoused with nude rats developing PcP, named donors. Following contact between receiver and donor rats, the level of colonization by Pneumocystis of receiver rats is determined by toluidine blue O staining or by qPCR. This study allowed us to validate our gradual ID rat model, in the sense that we were able to maintain the level of circulating LTCD4 and LTCD8 stable. Finally, and for the first time in an experimental rat model, we observed an inverse relationship between the level of colonization by P. carinii and the level of circulating LTCD4 and LTCD8.Finally, we aimed to acquire the first data concerning the prevalence of P. jirovecii in the Lebanese population. This Franco-Lebanese project was set up because the colonization by Pneumocystis is probably of major importance in the public health, especially in susceptible patients such as patients with chronic obstructive pulmonary diseases (COPD) where Pneumocystis is considered as a worsening prognosis factor. Our results show a low prevalence of P. jirovecii colonization (5.2%) and the predominance of mtLSU genotype 2 in patients with respiratory diseases in Lebanon. Moreover, in our cohort of patients with various respiratory diseases, COPD was the only respiratory disease associated with a significant increased risk of P. jirovecii colonization

Zielstellung: Ziel dieser kumulativen Dissertationsarbeit war die vergleichende Untersuchung der Wirtsantwort in verschiedenen Mauslinien nach Infektion mit Streptobacillus (S.) moniliformis und Rodentibacter (R.) pneumotropicus mit Anzeigeparametern für die Klinik, die Pathologie und die Immunantwort. Es sollten neue erregerspezifische enzyme-linked immunosorbent assays (ELISA) evaluiert und durch die Bestimmung der Immunglobulin G (IgG)-Subklassen mausstammspezifische Unterschiede in der Immunantwort aufgezeigt werden. Darüber hinaus waren Sentinelsysteme zu bewerten. Material und Methoden: Es wurden BALB/c und C57BL/6-Mäuse intranasal mit S. moniliformis- oder R. pneumotropicus infiziert und mit Kontaktsentinels vergesellschaftet. Zusätzlich wurde benutzte Einstreu der Infektionskäfige auf Käfige mit nichtinfizierten CD1-Mäusen (Einstreu-Sentinels) übertragen. Die Infektionsgruppen wurden über 4 Wochen, die Sentinels mindestens 7 Wochen alle 12 Stunden klinisch untersucht und die Verläufe dokumentiert. Am Ende der Experimente bzw. bei Erreichen spezifischer Abbruchkriterien wurden die Mäuse tierschutzgerecht euthanasiert und definierte Organproben für pathohistologische und bakteriologische Untersuchungen gewonnen. Die Erreger wurden dabei massenspektrometrisch sowie mittels polymerase chain reaction (PCR) differenziert und in Proben des Respirationstraktes quantitativ erfasst. Erregerspezifische Antikörper wurden in tracheonasaler Spülflüssigkeit und im Serum in eigens etablierten ELISA‘s auf Basis von Ganzzellextrakten bestimmt. Weiterhin erfolgte die Messung des Verhältnisses der IgG-Subtypen IgG1 und IgG2 im ELISA. Ergebnisse: Der Infektionsversuch mit S. moniliformis bestätigte mit einer Mortalität von 75% die bekannte hohe Infektionsanfälligkeit der C57BL/6-Mäuse im Gegensatz zu BALB/c, die keine Krankheitsanzeichen entwickelten. Die wichtigsten pathologischen Manifestationen waren eitrig-nekrotisierende Lymphadenitiden und Pneumonien in Verbindung mit der Reisolation des Infektionsstammes. Mithilfe des etablierten ELISA‘s gelang der Nachweis erregerspezifischer IgG-Antikörper im Serum der Tiere beider Linien. Bei den Kontaktsentinels konnte, bis auf eine Ausnahme, weder kulturell, noch serologisch eine Infektion nachgewiesen werden. Gleiches gilt für alle Einstreu-Sentinels. Molekularbiologisch wurde aber Erreger-DNA in den Lungen der Sentinels festgestellt. Die Infektion mit einem R. pneumotropicus Stamm, welcher genotypisch positiv für alle drei bekannten RTX-Toxine dieses Erregers war, führte zu einer unerwartet hohen Morbidität und Mortalität in beiden Mauslinien. In frühzeitig euthanasierten Tieren beider Linien konnten katarrhalisch-eitrige bis nekrotisierende Bronchopneumonien sowie eine Dissemination des Belastungsstammes in zahlreiche innere Organe nachgewiesen werden. In überlebenden Tieren beider Linien wurde eine deutliche Kolonisation respiratorischer Schleimhäute mit dem Belastungsstamm trotz z.T. hoher mukosaler IgA-Spiegel und Serokonversion im Blut nachgewiesen. Überlebende C57BL/6 Mäuse zeigten eine signifikant niedrigere Bakterienlast in inneren Organen als BALB/c Mäuse. In allen Kontaktsentinels, aber nicht in einem einzigen Einstreu-Sentinel, konnte kulturell und indirekt serologisch eine Infektion mit R. pneumotropicus nachgewiesen werden. Die Bestimmung der IgG-Subklassen in den Seren der C57BL/6-Mäuse beider Infektionsstudien ergab eine Verschiebung des Verhältnisses IgG2/IgG1 von unter 0,8 vor zu über 1,6 nach Infektion. Dies weist auf eine T-Helferzell (Th) 1-dominierte Immunantwort hin. BALB/c-Mäuse behielten dagegen ein Verhältnis unter 0,8 auch nach der Infektion bei, sodass auf eine Th2- Antwort zu schließen war. Schlussfolgerungen: Sowohl für S. moniliformis als auch für R. pneumotropicus konnten Tiermodelle mit diversen Anzeigeparametern etabliert werden, welche für Folgestudien zur Pathogenese oder Immunprophylaxe genutzt werden können. Für beide Erreger wurden neue sensitive und spezifische ELISA-Protokolle in die Diagnostik eingeführt. Kontaktsentinels, aber nicht Einstreu-Sentinels, sind gut geeignet, um R. pneumotropicus-Infektionen nachzuweisen. Die beobachtete stammspezifische Klinik, Pathologie und Immunantwort der C57BL/6-Mäuse nach experimenteller S. moniliformis-Infektion sprach für eine pathologische Th1-Immunantwort. Im Gegensatz dazu war im R. pneumotropicus – Infektionsversuch die Th1-Immunantwort der C57BL/6-Mäuse mit einer effektiveren Reduktion des Erregers in inneren Organen assoziiert. Die unerwartet hohe Morbidität und Mortalität im R. pneumotropicus –Infektionsversuch weist auf eine besonders hohe Virulenz des eingesetzten Stammes hin, sodass in dieser Arbeit erstmalig ein septikämischer Verlauf in Wildtyp-Mäusen nach intranasaler R. pneumotropicus-Infektion nachgewiesen werden konnte.:Inhaltsverzeichnis (I) Abkürzungsverzeichnis (III) 1 Einleitung (1) 2 Literatur (3) 2.1 Streptobacillus moniliformis (3) 2.1.1 Allgemeine Charakteristika (3) 2.1.2 Differenzierung von Streptobacillus spp.(4) 2.1.3 Serologische Methoden zum indirekten Nachweis einer Streptobacillus moniliformis - Infektion (5) 2.1.4 Epidemiologie der durch Streptobacillus moniliformis hervorgerufenen Zoonose (6) 2.1.5 Klinik und Pathologie der Streptobacillus moniliformis-Infektion bei Nagetieren (8) 2.1.6 Klinik und Pathologie der Streptobacillus moniliformis-Infektion in Menschen und anderen Nebenwirten (9) 2.1.7 Pathogenese und Virulenzfaktoren (10) 2.1.8 Prävalenz in Nagern (11) 2.1.9 Sanierung Streptobacillus moniliformis infizierter Nagetierbestände und Prävention (12) 2.2 Rodentibacter (R.) pneumotropicus und heylii (Pasteurella (P.) pneumotropica Biotyp Jawetz und Heyl) (14) 2.2.1 Allgemeine Charakteristika (14) 2.2.2 Ursprüngliche Einteilung in Biotypen und Reklassifikation zu Rodentibacter spp. (14) 2.2.3 Differenzierung von Rodentibacter spp. (15) 2.2.4 Serologische Methoden zum indirekten Nachweis einer Rodentibacter- Infektion (15) 2.2.5 Übertragung (15) 2.2.6 Klinik und Pathologien der Rodentibacter-Infektion in Nagern (16) 2.2.7 Pathogenese und Virulenzfaktoren (18) 2.2.8 Prävalenz (19) 2.2.9 Sanierung Rodentibacter pneumotropicus infizierter Nagetierbestände und Prävention (20) 2.3 Mäuse als Versuchstiere (22) 2.3.1 Inzucht-Stämme (22) 2.3.1.1 Merkmale, Verwendung und Historie der BALB/c-Wildtypmäuse (22) 2.3.1.2 Merkmale, Verwendung und Historie der C57BL/6-Wildtypmäuse (23) 2.3.1.3 Unterschiede der Immunreaktionen in C57BL/6- und der BALB/c- Mäusen (23) 2.3.2 Auszucht-Stämme (24) 2.3.2.1 Merkmale, Verwendung und Historie der CD1-Wildtypmäuse (24) 2.4 Gesundheitsmonitoring in Labortierhaltungen (25) 2.4.1 Empfehlungen der Federation of Laboratory Animal Science Associations (FELASA) (25) 2.4.2 Sentinelsysteme für das Gesundheitsmonitoring in Labormausbeständen (26) 3 Publikationen (28) 3.1 Fornefett J, Krause J, Klose K, Fingas F, Hassert R, Eisenberg T, Grunwald T, Müller U, Schrödl W, Baums CG. Comparative analysis of clinics, pathologies and immune responses in BALB/c and C57BL/6J mice infected with Streptobacillus moniliformis. Microbes and Infection. 2018;20(2):101-110 (28) 3.2 Fornefett J, Krause J, Klose K, Fingas F, Hassert R, Benga L, Grunwald T, Müller U, Schrödl W, Baums CG. Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain. BMC Microbiology. 2018;18(1):45 (39) 4 Übergreifende Diskussion (51) 5 Zusammenfassung (59) 6 Summary (61) 7 Literaturverzeichnis (63) 7.1 Fachliteratur (63) 7.2 Internet (76) 7.3 Gesetzestexte (78) Anhang (79) i Ergänzende Abbildungen (79) ii Ergänzendes Material zu 3.1 “Comparative analysis of clinics, pathologies and immune responses in BALB/c and C57BL/6J mice infected with Streptobacillus moniliformis” (81) iii Ergänzendes Material zu 3.2 “Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain” (83) Liste mit weiteren Veröffentlichungen Danksagung
Objective: Aim of this cumulative doctoral thesis was the comparative analysis of the host response in different mice strains infected with Streptobacillus (S.) moniliformis and Rodentibacter (R.) pneumotropicus with readout parameters for clinics, pathology and immune response. New pathogen specific enzyme linked immunosorbent assay’s (ELISA) were evaluated. Differentiation of immunoglobulin (Ig) G subclasses was conducted to reveal differences in the immune response between the two mice strains. Furthermore, sentinel systems were assessed. Materials and methods: BALB/c and C57BL/6 mice were infected intranasally with S. moniliformis or R. pneumotropicus and housed together with contact sentinels. Soiled bedding from infection cages was transmitted to cages with uninfected CD1 mice (bedding sentinels). Infection groups were observed for 4 weeks, sentinels for at least 7 weeks and the clinical course was documented. At the end of the experiments or when predefined termination criteria were reached, animals were humanely killed. Predefined organ samples were collected for pathohistological and bacteriological screenings. Pathogens were differentiated via mass spectrometry and via polymerase chain reaction (PCR). The specific bacterial load was quantified in samples of the respiratory tract. Pathogen-specific antibodies were detected in tracheonasal lavages and sera using newly established ELISAs based on whole cell extracts. Determination of the ratios of the IgG subtypes (IgG1 to IgG2) was conducted using ELISAs. Results: The S. moniliformis experiment confirmed the known high susceptibility of C57BL/6 mice with a mortality of 75%. This was in contrast to BALB/c, which developed no signs of illness. The major pathologies were purulent-necrotizing inflammations of the lymph nodes and the lung associated with detection of the challenge strain. Specific IgG-antibodies were detected in sera of both mice strains by the newly established ELISAs. In contact and bedding sentinels the infection was not detected by culture or indirectly by serology, except for one contact sentinel. However, pathogen DNA was detectable in the lungs of these animals via PCR. The infection with the R. pneumotropicus strain, which is genotypically positive for all 3 known RTX toxins of this pathogen, leaded to an unexpected high morbidity and mortality in both mice strains. In early losses a catharal-purulent to necrotizing bronchopneumonia as well as dissemination of the challenge strain in various inner organs was recorded. Efficient colonization of the respiratory mucosa through the challenge strain was detected in survivors of both lines despite high mucosal IgA levels and seroconversion in the blood. Surviving C57BL/6 mice showed a significant lower bacterial burden in inner organs than BALB/c. All contact sentinels were culturally and serologically positive for R. pneumotropicus infection in contrast to all bedding sentinels. Differentiation of IgG subclasses in sera of C57BL/6 mice of both experiments revealed a shift of the IgG2/IgG1 ratio from 0.8 prior to infection to 1.6 post infection suggesting a T helper (Th) 1-prone immune response. BALB/c mice remained under 0.8 after infection indicating a Th2-prone immune response. Conclusions: New animal models with various readout parameters were established for both S. moniliformis and R. pneumotropicus. These models can be used in future studies on pathogenesis and immunoprophylaxis. Sensitive und specific ELISA-protocols were established for both pathogens. Contact sentinels but not bedding sentinels are appropriate for detection of R. pneumotropicus-infections. The observed distinct clinic, pathology and immune response of C57BL/6 mice experimentally infected with S. moniliformis indicated on the one hand a pathological Th1 immune response. On the other hand, the Th1 response of C57BL/6 mice to R. pneumotropicus infection was associated with a more efficient clearance of the challenge strain in internal organs. The unprecedented high morbidity and mortality in the R. pneumotropicus experiment indicates high virulence of this strain. Accordingly, this work revealed for the first time septicaemia in wildtype mice after intranasal R. pneumotropicus-infection.:Inhaltsverzeichnis (I) Abkürzungsverzeichnis (III) 1 Einleitung (1) 2 Literatur (3) 2.1 Streptobacillus moniliformis (3) 2.1.1 Allgemeine Charakteristika (3) 2.1.2 Differenzierung von Streptobacillus spp.(4) 2.1.3 Serologische Methoden zum indirekten Nachweis einer Streptobacillus moniliformis - Infektion (5) 2.1.4 Epidemiologie der durch Streptobacillus moniliformis hervorgerufenen Zoonose (6) 2.1.5 Klinik und Pathologie der Streptobacillus moniliformis-Infektion bei Nagetieren (8) 2.1.6 Klinik und Pathologie der Streptobacillus moniliformis-Infektion in Menschen und anderen Nebenwirten (9) 2.1.7 Pathogenese und Virulenzfaktoren (10) 2.1.8 Prävalenz in Nagern (11) 2.1.9 Sanierung Streptobacillus moniliformis infizierter Nagetierbestände und Prävention (12) 2.2 Rodentibacter (R.) pneumotropicus und heylii (Pasteurella (P.) pneumotropica Biotyp Jawetz und Heyl) (14) 2.2.1 Allgemeine Charakteristika (14) 2.2.2 Ursprüngliche Einteilung in Biotypen und Reklassifikation zu Rodentibacter spp. (14) 2.2.3 Differenzierung von Rodentibacter spp. (15) 2.2.4 Serologische Methoden zum indirekten Nachweis einer Rodentibacter- Infektion (15) 2.2.5 Übertragung (15) 2.2.6 Klinik und Pathologien der Rodentibacter-Infektion in Nagern (16) 2.2.7 Pathogenese und Virulenzfaktoren (18) 2.2.8 Prävalenz (19) 2.2.9 Sanierung Rodentibacter pneumotropicus infizierter Nagetierbestände und Prävention (20) 2.3 Mäuse als Versuchstiere (22) 2.3.1 Inzucht-Stämme (22) 2.3.1.1 Merkmale, Verwendung und Historie der BALB/c-Wildtypmäuse (22) 2.3.1.2 Merkmale, Verwendung und Historie der C57BL/6-Wildtypmäuse (23) 2.3.1.3 Unterschiede der Immunreaktionen in C57BL/6- und der BALB/c- Mäusen (23) 2.3.2 Auszucht-Stämme (24) 2.3.2.1 Merkmale, Verwendung und Historie der CD1-Wildtypmäuse (24) 2.4 Gesundheitsmonitoring in Labortierhaltungen (25) 2.4.1 Empfehlungen der Federation of Laboratory Animal Science Associations (FELASA) (25) 2.4.2 Sentinelsysteme für das Gesundheitsmonitoring in Labormausbeständen (26) 3 Publikationen (28) 3.1 Fornefett J, Krause J, Klose K, Fingas F, Hassert R, Eisenberg T, Grunwald T, Müller U, Schrödl W, Baums CG. Comparative analysis of clinics, pathologies and immune responses in BALB/c and C57BL/6J mice infected with Streptobacillus moniliformis. Microbes and Infection. 2018;20(2):101-110 (28) 3.2 Fornefett J, Krause J, Klose K, Fingas F, Hassert R, Benga L, Grunwald T, Müller U, Schrödl W, Baums CG. Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain. BMC Microbiology. 2018;18(1):45 (39) 4 Übergreifende Diskussion (51) 5 Zusammenfassung (59) 6 Summary (61) 7 Literaturverzeichnis (63) 7.1 Fachliteratur (63) 7.2 Internet (76) 7.3 Gesetzestexte (78) Anhang (79) i Ergänzende Abbildungen (79) ii Ergänzendes Material zu 3.1 “Comparative analysis of clinics, pathologies and immune responses in BALB/c and C57BL/6J mice infected with Streptobacillus moniliformis” (81) iii Ergänzendes Material zu 3.2 “Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain” (83) Liste mit weiteren Veröffentlichungen Danksagung

碩士
大葉大學
健康產業管理碩士在職學位學程
106
This study investigates the behavioral response and caregiver burden among children who are hospitalized with bronchopneumonia .The purpose for this study is to observe the correlation between the behavioral response of children receiving spray therapy and the burden of primary caregivers, to provide reference for future clinical practice and individualized care needs,thus restore the health of the children and reduce the burden of caregiver.This study was designed to explore the correlation between the behavioral response of children receiving spray therapy and the burden of primary caregivers in a pediatric hospital in Changhua, Taiwan. A structured questionnaire was used to collect the data and 100 samples were recruited in the study. The questionnaire included“ The basic information sheet for children and primary caregiver contains symptoms of the disease”, “ Child Behavioral Response Scale ”,“Primary Caregivers' Burden Scale”,and“Major Caregivers' Cognitive Scale for Bronchopneumonia Disease”,and used SPSS 22.0 for data analysis.The results of this study: Caregivers alternate among demographic variables of primary caregivers with statistically significant correlations with the relationship of the sick children and average day care. However, the behavioral response to spray therapy in children hospitalized with bronchial pneumonia and the cognition of the primary caregiver on bronchopneumonia disease were not statistically related to the burden of caregivers. In addition bronchial pneumonia hospitalized children with clinical symptoms of dyspnea and caregiver load was significantly correlated.Based on the results of the study, specific data and suggestions are put forward to provide reference for later clinical practice and health education, as well as guidance on nursing care.

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
Introdução: As infeções do trato respiratório continuam a ser um problema frequente na prática clínica, com impacto significativo na morbilidade e mortalidade em todo o mundo. Em Portugal, de acordo com o Instituto Nacional de Estatística, a pneumonia foi a terceira causa de morte em 2018, registando um acréscimo de 2,5% face ao ano anterior. Perante estes dados, o objetivo do presente estudo foi determinar a ocorrência de pneumonia e broncopneumonia numa série postmortem e caracterizar o seu contexto circunstancial. Métodos: Realizou-se um estudo retrospetivo das autópsias efetuadas na Delegação do Centro do Instituto Nacional de Medicina Legal e Ciências Forenses, I.P. entre 2011 e 2017, cujo estudo anatomopatológico revelou a presença de pneumonia lobar aguda ou broncopneumonia aguda neutrofílica. Os dados circunstanciais e clínicos constantes na requisição do exame anatomopatológico foram analisados. Resultados: Numa série de 737 indivíduos autopsiados, 521 (70,7%) eram do sexo masculino e 675 (91,6%) apresentavam comorbilidades. A média de idades foi 63,87 ± 19,8 anos. A maioria das infeções pulmonares foi adquirida na comunidade (65,1%), sendo a morte natural (65,5%) a etiologia médico-legal mais frequente. Quanto à forma de óbito, a maioria dos casos (48,0%) ocorreu como morte súbita, seguida de acidente (29,2%). Observou-se uma associação estatisticamente significativa entre a etiologia médico-legal e o local da infeção, com maior prevalência de óbito natural (91,0%) na pneumonia/broncopneumonia adquirida na comunidade versus maior prevalência de óbito violento na pneumonia/broncopneumonia adquirida a nível hospitalar (82,1%) (p <0,001). Conclusão: A compreensão das circunstâncias subjacentes à morte por infeção pulmonar que ocorreram na comunidade e no hospital nos casos médico-legais analisados forneceu dados-base para estabelecer medidas de prevenção mais fortes e modificar o comportamento da população e dos profissionais de saúde.
Introduction: Respiratory tract infections remain a common problem in clinical practice with a significant impact on morbidity and mortality worldwide. In Portugal, according to the National Statistical Institute, pneumonia was the third leading cause of death in 2018, registering an increase of 2.5% compared to the previous year. Given these data, the aim of the present study was to determine the occurrence of pneumonia and bronchopneumonia in a postmortem series and to characterize its circumstantial context. Materials and Methods: A retrospective study on autopsy samples was performed at the Central Branch of the Portuguese National Institute of Legal Medicine and Forensic Sciences, between 2011 and 2017. Based on the anatomopathological study, we determined the presence of acute pneumonia or bronchopneumonia. The circumstantial and clinical data provided in the request for the anatomopathological examination was analyzed. Results: In a series of 737 patients who underwent autopsy, 521 (70.7%) were male and 675 (91.6%) presented comorbidities. The mean age was 63.87 ± 19.8 years. The most common site of acquisition was community (65.1%), appearing in the form of natural death (65.5%) as such most frequent medicolegal etiology. Concerning the manner of death, most of the cases (48.0%) occurred as sudden deaths, followed by accidents (29.2%) A statistically significant association was observed between the medicolegal etiology and the place where the pulmonary infection was acquired, with higher prevalence of natural obitus (91.0%) correlated with community-acquired pneumonia/bronchopneumonia versus higher prevalence of violent obitus in hospital-acquired pneumonia/bronchopneumonia (82.1%) (p <0.001). Conclusions: Understanding the circumstances underlying pulmonary infection’s death in community and hospital medicolegal dependent cases provided baseline data to establish stronger preventive measures and change populational and healthcare behavior.