Made available in DSpace on 2015-03-26T13:46:47Z (GMT). No. of bitstreams: 1 texto completo.pdf: 86037 bytes, checksum: e4f697c00d41650b873d456f7d47cced (MD5) Previous issue date: 2005-04-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In the veterinarian medicine daily routine the caesarian is a highly used technique. Despite the anesthetic protocol chosen, the drug will act direct or indirectly on the fetus, causing neonates vital function depression and contributing to a hazard in their adaptation to the extra-uterine life. Trying to revert in neonates the depressor effects of the anesthesia used on mothers, the application of doxapram chloridate and/or aminofiline is recommended. This work aimed to study the doxapram chloridate and aminofiline, associated or not, efficiency, as well as to compare the sub-lingual and subcutaneous administration of these drugs. A total of 64 puppies were evaluated, distributed in eight groups of eight animals each. Four of these groups received the drugs via subcutaneous (sC) and the other four via sub-lingual (sL). Two groups (G1sC and G1sL) received only placebo; another two (G2sC and G2sL) received aminofiline; in other two groups (G3sC and G3sL) doxapram was administered and the last two (G4sC and G4sL) received aminofiline associated to doxapram. According to the results obtained in the present experiment it was possible to conclude that the aminofiline was more effective than the doxapram and, that the via sub-lingual was more efficient than the subcutaneous in the neonates reanimation. / No cotidiano da medicina veterinária a cesariana é uma técnica cirúrgica bastante empregada. Qualquer que seja o protocolo anestésico escolhido, a droga atuará direta ou indiretamente sobre os fetos, causando depressão das funções vitais do neonato e contribuindo para dificultar sua adaptação à vida extra-uterina. Na tentativa de reverter no neonato os efeitos depressores da anestesia usada na mãe, recomenda-se a aplicação do cloridrato de doxapram e/ou aminofilina. Este trabalho objetivou estudar a eficácia do cloridrato de doxapram e da aminofilina associados ou não, na reanimação de neonatos caninos após cesariana eletiva, bem como comparar a via sublingual com a subcutânea para a administração dessas drogas. Foram avaliados um total de 64 filhotes, distribuídos em oito grupos de oito animais cada. Quatro destes grupos receberam as drogas por via subcutânea (sC) e os outros quatro via sublingual (sL). Dois grupos (G1sC e G1sL) receberam apenas placebo; outros dois (G2sC e G2sL) receberam aminofilina; em outros dois (G3sC e G3sL) administrou-se doxapram e os dois últimos (G4sC e G4sL) receberam aminofilina associada ao doxapram. De acordo com os resultados obtidos no presente experimento foi possível concluir que a aminofilina foi mais eficaz que o doxapram e a via sublingual mais eficiente que a subcutânea na reanimação dos neonatos.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A síndrome da imunodeficiência adquirida (AIDS), causada pelo vírus da imunodeficiência humana (HIV), é uma das mais destrutivas epidemias do mundo, e a infecção pelo HIV em mulheres jovens vem aumentando rapidamente nos dias atuais. Esse fato tem um impacto importante na transmissão vertical do vírus. Apesar da grande maioria dos casos de aids pediátrica em todo mundo resultar da transmissão vertical, aproximadamente dois terços das crianças expostas ao HIV durante a vida fetal não são infectadas pelo vírus. Muitos trabalhos sugerem que durante a gestação doenças infecciosas maternas podem ter consequências complexas para o desenvolvimento do feto, e poucos trabalhos têm explorado o impacto da exposição ao HIV sobre a responsividade imunológica de crianças não infectadas a diferentes estímulos, particularmente na era das drogas antirretrovirais. Portanto, esse trabalho teve como objetivo avaliar eventos imunes em neonatos não-infectados expostos ao HIV-1 nascidos de gestantes que controlam (G1) ou não (G2) a carga viral plasmática, usando neonatos não expostos como controle. Para tanto, sangue do cordão umbilical de cada neonato foi coletado, plasma e células mononucleares foram separados e a linfoproliferação e o perfil de citocinas foram avaliados. Os resultados demonstraram que a linfoproliferação in vitro induzido por ativadores policlonais foi maior nos neonatos do G2. Entretanto, nenhuma cultura de célula respondeu a um conjunto de peptídeos sintéticos do envelope do HIV-1. A dosagem de citocinas no plasma e nos sobrenadantes das culturas ativadas policlonalmente demonstrou que, enquanto a IL-4 e IL-10 foram as citocinas dominantes produzidas nos grupos G1 e controle, a secreção de IFN-γ, IL-1, Il-6, IL-17 e TNF-α foi significativamente superior nos neonatos G2. Níveis sistêmicos de IL-10 observados dentre os neonatos G1 foram maiores naqueles nascidos de mães tratadas com drogas inibidoras da transcriptase reversa do vírus. Por outro lado, níveis superiores de citocinas inflamatórias foram observados dentre estes nascidos de gestantes tratadas com terapia antirretroviral de alta eficácia. Em resumo, nossos resultados indicam uma responsividade imune alterada em neonatos expostos in utero ao HIV-1 e reforça o papel do tratamento materno anti-viral com drogas menos potentes em atenuar tais distúrbios. / The acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), is one the most destructive epidemic in the world, and the HIV-infection in young women has been increasing fast in the recent times. This fact has an important impact on vertical virus transmission. Although the great majority of the pediatric AIDS cases all over the world results from vertical transmission, approximately two thirds of the children exposed to the HIV during the fetal life are not infected by the virus. Many works suggest that during pregnancy, maternal infectious diseases could have complex consequences to the fetus development, and few works have explored the impact of HIV exposition on immunological responsiveness of uninfected children to different stimuli, particularly in the era of the anti-retroviral drugs. Therefore, this work aimed to evaluate immune events in HIV-1-exposed uninfected neonates born from pregnant women who controlled (G1) or not (G2) the plasma viral load, using unexposed neonates as control. Cord blood from each neonate was collected, plasma and mononuclear cells were separated and the lymphoproliferation and cytokine pattern were evaluated. The results demonstrated that the in vitro lymphoproliferation induced by polyclonal activators was higher in the G2 neonates. Nevertheless, no cell culture responded to poll synthetic HIV-1 envelope peptides. The cytokine dosage in the plasma and supernatants of polyclonally-activated cultures demonstrated that, while IL-4 and IL-10 were the dominant cytokines produced in G1 and control groups, the secretion of IFN-γ, IL-1, Il-6, IL-17 and TNF-α was significantly higher in G2 neonates. Systemic levels of IL-10 observed among the G1 neonates were higher in those born from mothers treated with viral transcriptase reverse inhibitors drugs. On the other hand, higher levels of inflammatory cytokines were observed among them born from pregnant women treated with highly active anti-retroviral therapy. In summary, our results indicate an altered immune responsiveness in neonates exposed in utero to HIV and support the role of maternal anti-viral treatment with less potent drugs to attenuate it.

Staphylococcus coagulase-negativo (SCN) estão frequentemente envolvidos em infecções nosocomiais associadas com o uso de cateteres e outros procedimentos médicos invasivos. A habilidade de aderir às superfícies abióticas e de produzir biofilme tem sido reconhecida entre os principais fatores de virulência dos SCN, especialmente de S. epidermidis, a principal espécie responsável por infecções relacionadas à assistência a saúde - IRASs. Dentre as demais espécies de SCN capazes de produzir biofilme, S. haemolyticus tem sido relacionado com quadros de infecções em recém-nascidos (RNs). O presente estudo teve como objetivo principal investigar aspectos microbiológicos e epidemiológicos dos processos infecciosos invasivos relacionados com SCN em neonatos internados em unidade de terapia intensiva neonatal (UTIN) de um hospital universitário do município do Rio de Janeiro (2008-2010). A técnica de PCR multiplex-mPCR foi empregada na determinação das espécies de 40 amostras de SCN isoladas de hemoculturas de RNs fazendo uso de cateteres intravenosos e submetidos à terapia antimicrobiana empírica com vancomicina e/ou gentamicina. A fenotipagem foi realizada por três métodos distintos: Simplificado em microplaca, Vitek 2 e API-Staph. Os perfis de resistência aos antimicrobianos foram verificados através do teste de disco-difusão, determinação de CIM (Oxacilina) e presença do gene mecA. A capacidade de produção de biofilme foi investigada pelos testes do Ágar Vermelho do Congo e ensaios de aderência em superfícies abióticas (poliestireno e vidro) além da PCR para os genes icaAB, atlE e aap. O perfil genômico dos micro-organismos foi determinado pela técnica de PFGE. Os resultados demonstraram o isolamento de S. haemolyticus (77%), S. epidermidis (15%), S. captis (5%) e S. warneri (3%). A análise comparativa dos resultados obtidos pelo m-PCR com métodos fenotípicos demonstrou uma concordância de 97,5% com o esquema simplificado e de ~40% Vitek 2 e o API Staph. A maioria (82,5%) das amostras apresentou perfis variados de multiresistência aos 16 antimicrobianos testados e resistência a oxacilina, apesar de 25% destas não apresentarem o gene mecA. Apesar da maioria das amostras de SCN ter apresentado capacidade de produzir slime e/ou biofilme não foi observada total correlação com a presença dos genes mecA, icaAB, aap, atlE, enfatizando a natureza multifatorial da produção de biofilme de SCN. Diferente do observado para as demais espécies, algumas amostras de S. haemolyticus foram incapazes de aderir ao vidro e ao poliestireno e/ou apresentaram os genes aap (38,7%), atlE (42%) além de icaAB (71%). Na UTIN foi detectada a presença de seis diferentes tipos clonais da espécie prevalente, indicando a disseminação de S. haemolyticusnesta unidade hospitalar e a endemicidade em nossa comunidade. / Coagulase-negative staphylococci (CNS) are often involved in nosocomial infections associated with catheters and other invasive medical procedures. The ability to adhere to abiotic surfaces and produce biofilms has been recognized among the major virulence factors of the SCN, especially Staphylococcus epidermidis, the main species responsible for infections related to health care - IRASs.Among the other species capable of producing biofilm, Staphylococcus haemolyticus has been associated with cases of infections in neonates.Here in, we investigated the microbiological and epidemiological aspects of invasive infections related to CNS in the neonatal intensive care unit (NICU) of a university hospital located at Rio de Janeiro metropolitan area (2008-2010).PCR multiplex-mPCR was used in the determination of the species of 40 CNS strains isolated from blood cultures of neonates making use of intravenous catheters and subjected to empirical antimicrobial therapy with vancomycin and / or gentamicin.Phenotyping was performed by three different methods: Simplified scheme in microplates, Vitek 2 and API-Staph. Antimicrobial resistance profiles were verified by the disk diffusion test, oxacillin MIC determinationand PCR for mecA gene. Evaluation of biofilm production was performed by PCR for genes icaAB, atlE and aap and the tests on Congo Red Agar plates and abiotic surfaces (polystyrene and glass).Clonality was determined by PFGE technique. Data revealed the isolation of S. haemolyticus (77%), S. epidermidis (15%), S. captis (5%) and S. warneri (3%).The comparative analysis of the results obtained by mPCR and phenotypic methods showed 97.5% concordance with the simplified scheme and ~40% with the Vitek 2 and API Staph systems. Different multidrug resistance profiles to 16 antimicrobials, including resistance to oxacillin was observed for 82.5% of the CNS isolates, although the mecA gene was not detected in 25% of these strains.Although most of the CNS isolates showed the ability to produce slime and/or biofilm, a complete correlation with the presence of mecA, icaAB, aap, atlE genes was not observed, emphasizing the multifactorial nature of biofilm production of SCN.Different from other CNS species, some strains of S. haemolyticus were unable to adhere to glass and polystyrene surfaces and/or to exhibit aap (38.7%), atlE (42%), icaAB (71%) genes. PFGE analysis revealed the presence of six different clonal types of the prevalent species, indicating the dissemination in this hospital and endemicity in our community of S. haemolyticus.

As afecções dos componentes umbilicais merecem destaque no período neonatal, pois são comumente encontradas nos bezerros, podendo levar a graves complicações. O diagnóstico das doenças umbilicais muitas vezes não é totalmente esclarecido pela palpação abdominal bimanual, uma vez que, em parcela dos casos, esse método semiológico não é sensível para determinar o grau de acometimento das estruturas umbilicais intra-abdominais. Assim, a ultrassonografia apresenta-se como um valioso exame complementar para o estabelecimento de um diagnóstico preciso sobre a localização e extensão das onfalopatias intra-abdominais. Diante dessas limitações e da raridade de pesquisas com estabelecimento de padrões da ultrassonografia do umbigo, a proposta desse estudo foi avaliar o processo de involução fisiológica dos componentes umbilicais de bezerros sadios, considerando o uso de antisséptico clássico, a tintura de iodo, em concentrações de 2% e 5%, usado na cura do umbigo nos primeiros dias após o nascimento. A avaliação foi realizada por meio do exame ultrassonográfico dos componentes umbilicais, em diferentes posições, caracterizando as modificações ocorridas durante o processo de involução, em relação ao aspecto das imagens, com medidas de diâmetro e espessura dos componentes vasculares e úraco, assim como às peculiaridades decorrentes dos dois tipos de desinfecção da região. Foram avaliados 23 bezerros da raça Holandesa, machos, oriundos de propriedade leiteira localizada no Estado de São Paulo, desde o nascimento até os 30 dias de vida. Os resultados obtidos, evidenciaram que a veia e as artérias umbilicais perdem as suas características de vasos, assumindo aspecto de ligamento devido à proliferação de tecido fibroso. Esse processo caracterizou-se e seguiu um padrão, no qual o tecido fibroso inicialmente estava presente na região interna da parede do vaso, seguindo, com a involução, em direção ao centro da luz vascular. Esse processo de involução é mais precoce em porções dos vasos mais distantes do umbigo externo, não havendo distinção de comportamento determinada por uso das diferentes concentrações do antisséptico. Além das imagens, foram também padronizadas as medidas do diâmetro dos componentes umbilicais e da espessura de suas paredes, ao longo do processo de involução fisiológica, durante os primeiros 30 dias de vida dos bezerros, comprovando-se a precisão do exame ultrassonográfico para essa avaliação e estabelecendo-se referências ultrassonográficas para fundamentar o diagnóstico e escolha do tratamento das onfalopatias / Diseases of the umbilical components are very important in the neonatal period. Commonly found in calves, they can lead to serious complications. Diagnosis of umbilical diseases is often not fully enlightened by bimanual abdominal palpation, since this semiotic method is not sensitive enough to determine the extent of involvement of the umbilical intra-abdominal structures in part of the cases. Thus, ultrasonography is a valuable complementary test for establishing an accurate diagnosis on the location and extent of intra-abdominal omphalitis. Because of these limitations and the scarce research on the establishment of the standards of navel ultrasound, the purpose of this study was to evaluate the physiological involution process of umbilical components of healthy calves, considering the use of classic antiseptic, iodine tincture in concentrations 2% and 5%, used in navel treatment during the first days after birth. Evaluation was performed by ultrasonography of umbilical components in different positions and the changes were characterized during the process of involution regarding the appearance of the images, the measures of the diameter and thickness of vascular and urachus components, as well as the peculiarities from the two types of disinfecting. Twenty-three Holstein male calves, reared in dairy property located in the State of São Paulo, were evaluated from birth to 30 days old. Results obtained showed that the vein and umbilical arteries lose their blood vessels characteristics, assuming a ligament aspect due to fibrous tissue proliferation. This process was characteristic and followed a pattern, in which the fibrous tissue was initially present in the inner part of the vessel wall, following with involution, toward the center of the vessel lumen. This process of involution was earlier in the parts of the blood vessels that were farthest from the external navel, with no particular behavior distinct by the use of different antiseptic concentrations. Besides the images, the measurements of the diameter of the umbilical components and the thickness of their walls were also standardized along the physiological involution process during the first 30 days of life the calf, confirming the accuracy of ultrasonography for such assessment and establishing references to improve the diagnosis and the choice of treatment of umbilical diseases

Since 2006, Uganda has experienced a nonchanging neonatal mortality rate of 27 out of 1,000 live births, which is higher than the global average of 19 deaths for every 1,000 live births. The purpose of this retrospective cross-sectional study was to determine factors affecting access to health services and their impact on newborn deaths in Uganda. Mosley and Chen's model for child survival in developing nations provided the framework for the study. Secondary data from the 2016 demographic and health survey (UDHS) collected by the Uganda Bureau of Statistics (UBOs) was used. A total of 7,538 cases were used and analyzed using binary logistic regression and one-way analysis of covariance (ANCOVA). The results showed attending less than 4 antenatal care (ANC) visits during pregnancy increased the odds of neonatal deaths 1.57 times, while not taking antimalarial drugs during pregnancy increased the odds of neonatal deaths 1.67 times. However, receiving 4 or more tetanus toxoid (TT) vaccine doses before pregnancy was not statistically associated with an increased risk of neonatal death (p = .597). Also, there was no significant relationship between neonatal mortality and whether distance to health facilities was a challenge (p = .276) or receiving medical assistance during childbirth (p = .420). While there were significant differences in deaths of newborns in geographic regions while controlling for the number of ANC visits (p = .023), there were no differences while controlling for all three covariates, F(4, 117) = 2.00, p = .098. Findings may be used to inform government policies on ANC and malaria prevention during pregnancy, which may reduce neonatal mortality rates in Uganda.

Nosokomiale Infektionen bei Früh- und Neugeborenen stellen aufgrund ihrer hohen Inzidenz und Mortalität eine große Herausforderung für die moderne Versorgung dar. Außerdem sind sie Indikatoren für die Pflegequalität, wie auch Verletzungen und Gefäßschädigungen. In dieser retrospektiven Querschnittsstudie wurden die epidemiologische Situation nosokomialer Infektionen auf den neonatologischen Stationen der Universitätskinderklinik Leipzig für das Jahr 2006 beleuchtet, die Abhängigkeit der genannten Komplikationen von Plegepersonalqualifikation und –quantität untersucht, sowie die Stationsauslastung und Personalbesetzung mit deutschen Empfehlungen verglichen. Die Inzidenz systemischer Infektionen lag sowohl auf der neonatologischen Intensiv- als auch auf der Nachsorgestation unter dem deutschlandweiten Durchschnitt. Dagegen traten Lokalinfekte wie Windel-/ Mundsoor und Konjunktivitiden häufig auf. Das beobachtete Keimspektrum zeigte das aus der Literatur bekannte Bild, multiresistente Keime traten nicht auf. Bei der Untersuchung der Abhängigkeiten zeigte sich für die Intensivstation eine signifikante Häufung von Candidainfektionen bei geringerer Stationsauslastung und höherer Personalbesetzung, unabhängig von der Qualifikation des Personals. Auf der Nachsorgestation wurde eine vermehrte Zahl systemischer Infektionen bei höherem Anteil von Schwestern am Gesamtpersonal festgestellt. Beide Stationen waren gegenüber den Empfehlungen fast das ganze Jahr überbelegt und unterbesetzt. Gründe für die gefundenen Abhängigkeiten wurden vermutet in Informationsverlust und Trittbrettfahrerproblemen in größeren Kollektiven und verstärkter minimal-handling-Pflege und verstärkter Hygiene-Compliance in Stresssituationen. Die geringe Inzidenz systemischer Infektionen spricht für eine sichere Pflege und ist demnach sehr positiv zu bewerten, trotzdem sollten die Hintergründe für das Auftreten der Lokalinfekte, auch wenn sie meist einen milden Verlauf zeigten, überprüft werden. Eine Gesamtbeurteilung der Pflege ist anhand der gemachten Untersuchungen nicht möglich, da aufgrund der Retrospektive keinerlei Faktoren wie Belastungseinschätzung der Schwestern, Lerneinschätzung der Schüler oder Betreuungseinschätzung der Eltern einfließen konnten.

Le Virus Respiratoire Syncytial (VRS) est responsable de 70 % des cas de bronchiolite chez les enfants de moins de cinq ans. La survenue de bronchiolites sévères chez le nourrisson est un facteur de risque de développement d’asthme en grandissant. Aucun vaccin contre le VRS n’est disponible chez l’Homme. Le système immunitaire inné est la première ligne de défense de l’organisme contre les infections. De plus, en interaction avec la flore bactérienne commensale des poumons, l’immunité innée participe à la maturation de la réponse immunitaire adaptative qui confère à l’individu une protection sur le long terme vis-à-vis des pathogènes. Afin d’expliquer la susceptibilité néonatale au VRS, nous avons caractérisé un nouveau mécanisme de contrôle de la réponse innée antivirale lors de l’infection de souriceaux. Nous avons également testé une nouvelle approche de modulation de la réponse immunitaire au VRS par le microbiote pulmonaire. Ainsi, mieux comprendre les mécanismes immunologiques et virologiques responsables de bronchiolites sévères en période néonatale permettra de développer des moyens de lutte sûrs et efficaces contre l’infection par le VRS. / Respiratory Syncytial Virus (RSV) is responsible for 70 % of bronchiolitis in children under five years old. Severe bronchiolitis in infants is a risk factor for asthma development. No vaccine against RSV is available in humans. The innate immune system is the first line of defense against infections. Moreover, in interaction with lung microbiota, innate immunity shapes adaptive immune response responsible for long-term protection against pathogens. To explain the susceptibility of young children to RSV, we characterized a novel regulatory mechanism of the innate antiviral response during neonatal RSV infection in the murine model. We also tested a new approach for modulating immune responses to RSV by the pulmonary microbiota. Thus, a better understanding of immunological and virological mechanisms responsible for severe bronchiolitis during the neonatal period will allow the development of safe and effective therapeutic strategies against RSV infection.

L’émergence et la dissémination des bactéries résistantes aux antibiotiques sont préoccupantes. L’infection causée par les bactéries multi-résistantes (BMR) aggrave le pronostic des malades infectés et augmente les dépenses liées à leur prise en charge. Parmi les BMR, les bactéries à Gram négatif (BGN), plus particulièrement les entérobactéries productrices de béta-lactamase à spectre étendu (E-BLSE) sont les plus fréquemment isolées. La résistance aux antibiotiques pourrait avoir un impact sur la morbidité et la mortalité dans les pays à revenu faible ou intermédiaire (PRFI) en raison du potentiel d’émergence et de diffusion de bactéries résistantes aux antibiotiques, et du fardeau des infections bactériennes dans ces pays. Cependant, les données sur la résistance bactérienne sont rares et très majoritairement hospitalières dans les PRFI. De plus, dans ces pays, les infections bactériennes néonatales sévères (septicémies, pneumonies et méningites) représentent encore les principales causes de décès chez les nouveau-nés. Les entérobactéries sont majoritairement responsables de ces infections néonatales. Ainsi, investiguer la transmission d'E-BLSE chez le nouveau-né permettrait de proposer des stratégies de prévention. Ce travail de recherche s’est appuyé sur le programme BIRDY (Bacterial Infections and antibiotic Resistant Diseases among Young children in low-income countries). Le premier objectif était d’estimer la prévalence de la colonisation par des E-BLSE chez les femmes enceintes à Madagascar ainsi que les facteurs favorisant cette colonisation. Les résultats ont montré une prévalence globale de colonisation de 18.5% [IC à 95% 14.5-22.6]. Des facteurs reflétant un niveau socioéconomique plus élevé comme l’accès privatif à l’eau de boisson et avoir une maison individuelle sont associés à la colonisation. Le second objectif de ce travail était d'étudier l'incidence de la première colonisation par des E-BLSE chez les nouveau-nés en milieu communautaire et d'identifier les facteurs de risque d'acquisition. Les résultats révèlent une incidence globale d'acquisitions d'E-BLSE de 10.4 pour 1000 nouveau-nés-jours [IC à 95% : 8.0; 13.4]. Par ailleurs, nous avons mis en évidence que le faible poids à la naissance HR ajusté 2.7 [IC à 95% 1.2 ; 5.9], l'accouchement par césarienne HR ajusté 3.4 [IC à 95% 1.7 ; 7.1], la prise maternelle d'antibiotique à l'accouchement HR ajusté 2.2 [IC à 95% 1.1 ; 4.5] étaient des facteurs de risque d'acquisition d'E-BLSE. Le troisième objectif était de documenter les infections néonatales. Nous avons trouvé une incidence d'infections néonatales de 30.6 cas pour 1000 naissances vivantes [IC à 95%: 23.4 ; 40.1].Nos résultats montrent que les mesures de santé publique devraient axer sur l’amélioration de la prise en charge de la grossesse et sur le diagnostic précoce des infections néonatales. / The emergence and spread of antibiotic-resistant bacteria is a concern. Infection caused by multidrug-resistant bacteria (MDR) worsens the prognosis of infected patients and increases the costs associated with their management. Among the MDRs, Gram-negative bacteria (GNB), especially extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) are the most frequently isolated. Antibiotic resistance may have an impact on morbidity and mortality in low- and middle-income countries (LMICs) because of the potential for emergence and spread of antibiotic-resistant bacteria, and the burden of bacterial infections in these countries. However, data on bacterial resistance are scarce or came from the hospital, for the great majority, in LMICs. In these settings, severe neonatal bacterial infections (sepsis, pneumoniae and meningitis) still represent the leading causes of death in newborns. Enterobacteriaceaeare responsible for a great part of these neonatal infections. Thus, investigating the transmission of ESBL-PE in newborns would make it possible to propose prevention strategies. This work was based on the BIRDY program (Bacterial Infections and Antibiotic Resistant Diseases among Young Children in Low-Income Countries). The first objective was to estimate the prevalence of colonization by ESBL-PE in pregnant women in Madagascar as well as the risk factors of this colonization. The results showed an overall colonization prevalence of 18.5% [95% CI 14.5-22.6]. Factors reflecting a higher socioeconomic level such as private access to drinking water and having a house are associated with colonization. The second objective of this work was to study the incidence of ESBL-PE colonization in community-based infants and to identify acquisition risk factors. The results reveal an overall incidence of ESBL-PE acquisition of 10.4 per 1000 newborn-days [95% CI: 8.0; 13.4]. In addition, we found that low birth weight adjusted HR 2.7 [95% CI 1.2; 5.9], cesarean section delivery adjusted HR 3.4 [95% CI 1.7; 7.1], maternal intake of antibiotic at delivery adjusted HR 2.2 [95% CI 1.1; 4.5] were risk factors for the acquisition of ESBL-PE. The third objective was to document neonatal infections. We found an incidence of neonatal infections of 30.6 cases per 1000 live births [95% CI: 23.4; 40.1]. Our results suggest that public health measures should focus on the improvement of pregnancy follow-up and early diagnosis of neonatal infections.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease and one of the most severe complications that develop in premature infants following mechanical ventilation, exposure to supplemental oxygen, and inflammation. The hallmarks of the lung pathology are arrested lung development, including fewer and larger alveoli with less septation, thickening of alveolar septa, and impaired development of the capillary network. BPD is associated with increased mortality, respiratory morbidity, neurodevelopmental impairment, and increased healthcare costs. Significant advancements in neonatology in the last several decades, including antenatal steroids and exogenous surfactant replacement therapy, more gentle ventilation methods, and judicious oxygen use, have allowed for the survival of more preterm infants. However, the incidence of BPD still remains high and currently, there is no cure for the disease. Novel effective interventions at this stage of life are of exceptional value. Considering their great potential in promoting tissue regeneration and modulating inflammation, mesenchymal stromal cells (MSCs) represent a promising avenue for treating several disorders, including BPD. Umbilical cord-derived MSCs (UC-MSCs) offer biological advantages over other MSC sources (easily available, high proliferative capacity, and better repair efficacy). Pioneering work in our lab showed that MSCs prevent injury to the developing lung in a rat model mimicking BPD. However, there are still considerable challenges that must be overcome before MSCs can be effectively implemented in clinical trials. As such, UC-MSC heterogeneity is poorly understood, with concerns regarding variations from donors and batches. Thus, to improve the reproducibility of basic research and clinical applications, and to identify the optimal therapeutic cell product, better molecular characterization of UC-MSCs and the development of standardized BPD models will be essential in the clinical translation of MSC therapy for BPD. Moreover, considering that BPD is a disease of prematurity, the therapeutic potential of UC-MSCs isolated from preterm birth is of major interest. In the study presented here, using single-cell RNA sequencing (scRNA-seq), we characterized MSCs isolated from the UC of term and preterm pregnancies at delivery (term and preterm donors), as well as non-progenitor control cell line, human neonatal dermal fibroblasts (HNDFs). Moreover, we associated UC-MSC transcriptomic profiles with their therapeutic potential in hyperoxia-induced lung injury in neonatal rats. Finally, we developed and characterized a novel two-hit (2HIT) BPD model in neonatal mice, assessed UC-MSCs' optimal route of injection, timing, and dose, and evaluated their therapeutic effects in that model. We showed that UC-MSCs isolated from the majority of term and preterm donors, including preterm donors with pregnancy-related complications, have limited heterogeneity and possessed a transcriptome enriched in genes related to cell cycle and cell proliferation activity (termed "progenitor-like" cells). In contrast, UC-MSCs isolated from one term and two preterm donors with preeclampsia displayed a unique transcriptome comprised of many genes related to fibroblast activity, including extracellular matrix (ECM) organization (termed "fibroblast-like" cells). In addition, treatment with progenitor-like UC-MSCs, but not with fibroblast-like cells nor HNDFs, significantly improved lung structure, function, and pulmonary hypertension (PH) in hyperoxia-induced lung injury in neonatal rats. We identified marker genes for the therapeutic UC-MSCs (progenitor-like cells) and non-therapeutic cells (fibroblast-like cells and HNDFs). Among them, the high expression of major histocompatibility complex class I (MHCI) is associated with a reduced therapeutic effect. Furthermore, we developed a novel 2HIT BPD mice model with in-depth characterization of the innate immune response and lung injury. 2HIT injury caused a transient type 1 proinflammatory cytokine response and a significant decrease in type 2 anti-inflammatory cytokine lung expression and number of anti-inflammatory M2 type alveolar macrophages. Moreover, 2HIT mice showed impaired lung compliance and growth. Repeated intravenous (i.v.) injections of UC-MSCs at a dose of 20×10⁶ cells/kg body weight (BW) on postnatal day (PD) one and two improved survival, BW, lung compliance, and growth of 2HIT animals. In conclusion, scRNA-seq experimentation provided evidence that UC-MSCs isolated from different donors harbor different transcriptomes with progenitor-like or fibroblast-like characteristics. Only progenitor-like cells provided a therapeutic effect in hyperoxia-induced lung injury in neonatal rats. The development of a novel murine 2HIT BPD model allowed us to characterize the innate immune response and lung pathology and confirm the optimal dose of UCMSCs to provide therapeutic potential in that model. These results will enable better therapeutic selection of UC-MSCs and help improve treatment regimen prior to ultimate clinical translation.

The purpose of this study was to conduct an integrated review of the literature examining the use of non-pharmacologic pain management strategies in premature neonates and to explore the relationship between health outcomes and time to discharge from the neonatal intensive care unit (NICU). Non-pharmacologic pain management strategies include human touch, facilitated tucking, non-nutritive sucking, and kangaroo care. A systematic review of the literature was conducted from multiple online databases. Peer reviewed, English-language articles containing the keywords ‘pain management’, ‘neonatal intensive care unit’, and ‘non-pharmacologic’ were included for synthesis. Exclusion criteria included articles with a focus on infants not admitted to the NICU and infants with a gestational age greater than 37 weeks. Results revealed positive outcomes when alternative pain-relieving methods, rather than drug therapy, were used in the NICU. A majority of articles suggest facilitated tucking is very successful in lowering a preterm infant’s pain. However, facilitated tucking alone was significantly less effective in relieving procedural pain compared to facilitated tucking in combination with oral sucrose administration. Kangaroo care and gentle human touch also proved to reduce physiologic and behavioral signs of pain in neonates. The literature reveled an overall positive outcome when non-pharmacologic pain interventions are used in the NICU, with some behavioral interventions showing better efficacy than others at relieving neonatal pain. None of the reviewed articles explored the relationship between reduced length of stay and parameters assessing health outcomes based on pain control in neonates. The literature indicated nurses play a significant role in the use of pain-relieving methods in neonatal populations. Implications for future research that focuses on successful behavioral based pain management strategies that assists in refining neonatal pain relief would be of great benefit to improving health outcomes related to infant survival after discharge from the NICU.