Human parainfluenza 3 (HPIV3) is a member of the Paramyxoviridae, a single strain negative-sense non-segmented RNA virus in the order Mononegavirales. It is a respiratory pathogen with a broad spectrum of presentations for which there is currently neither a vaccine nor licensed treatment for HPIV3. To date most research on HPIV3 has been conducted using significantly culture adapted reference strains. Therefore, minimally adapted clinical strains were grown in two cell culture systems: immortalised and primary. Plaque phenotype, growth kinetics and inflammatory response triggered were evaluated and it was found that there is a range of phenotypes exhibited by clinical strains with potential implications in vivo. To examine the genetic diversity of circulating strains of HPIV3 in the UK, a new amplicon based sequencing pipeline for whole genome sequencing of HPIV3 was developed and validated. A short hypervariable region in the HPIV3 genome was identified and evaluated as a potential candidate for subsequent phylogenetic analysis compared to whole genome data. This method was then applied to tracking an HPIV3 outbreak that took place on a paediatric oncology ward. It was found to be a point-source outbreak and the clinical impact in this setting, as well as the infection control procedures involved were evaluated. Finally a robust in vitro model for the evaluation of potential therapeutic candidates for HPIV3, based on a panel of minimally passaged clinical strains as well as a culture-adapted reference strain, was set up. This model was applied to three potential inhibitors of HPIV3: ribavirin, favipiravir and zanamivir. The results showed that clinical strains were at least as susceptible to ribavirin and favipiravir as the laboratory reference strain and significantly more susceptible to zanamivir. This indicates that further work on minimally adapted clinical strains is essential to further the understanding of this important virus.

FÉ, Mariana Mota Moura. Perfil clínico-epidemiológico das infecções respiratórias agudas causadas por vírus parainfluenza em crianças atendidas em um hospital de referência da cidade de Fortaleza-CE. 2007. 139 f. Dissertação (Mestrado em Microbiologia Médica) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2007. / Submitted by denise santos (denise.santos@ufc.br) on 2012-01-05T13:51:47Z No. of bitstreams: 1 2007_dis_mmmfe.pdf: 1257125 bytes, checksum: f99c4398d4f75d5e46570bfa14f1756e (MD5) / Approved for entry into archive by Eliene Nascimento(elienegvn@hotmail.com) on 2012-02-02T16:30:16Z (GMT) No. of bitstreams: 1 2007_dis_mmmfe.pdf: 1257125 bytes, checksum: f99c4398d4f75d5e46570bfa14f1756e (MD5) / Made available in DSpace on 2012-02-02T16:30:16Z (GMT). No. of bitstreams: 1 2007_dis_mmmfe.pdf: 1257125 bytes, checksum: f99c4398d4f75d5e46570bfa14f1756e (MD5) Previous issue date: 2007 / Acute respiratory infections (ARI) are an important public health problem throughout the world and parainfluenza viruses are among the major etiologic agents. The objectives of this study were: a) to determine the frequency of parainfluenza infections among children attending Hospital Infantil Albert Sabin, a major pediatric hospital in Fortaleza - CE, from January 2001 to December 2006; b) to describe the seasonal pattern and the clinical and epidemiological characteristics of these infections; and c) to compare clinical and epidemiological characteristics of parainfluenza infections and infections caused by other respiratory viruses. Nasopharyngeal aspirates from children with acute respiratory symptoms were collected and submitted to indirect immunofluorescence assays to detect human parainfluenza virus 1, 2 and 3 (HPIV-1, 2 and 3), respiratory syncytial virus (RSV), influenza A and B and adenovirus. During the six-year study period, samples were collected from 3,070 generally healthy children and respiratory viruses were demonstrated in 933 cases (30.39%), of which 117 were positive for parainfluenza virus (3.81%). HPIV-3 was the most frequently detected type of parainfluenza virus accounting for 83.76% of cases, followed by HPIV-1 (11.96%) and HPIV-2 (4.27%). HPIV-3 infections were seasonal with most cases observed from September to November. Although the total number of ARIs was directly associated with the time of the rainy season, HPIV-3 infections were inversely related with rainfall indices. Most HPIV-3 infections were seen in outpatients. The mean age of patients infected by HPIV-3 was 20 months, which is significantly younger than for influenza A (mean age: 34 months) and significantly older than for RSV (mean age: 15 months). HPIV-3 patients presented significantly lower indices of dyspnea, cough, crackles, chest retractions and radiologic abnormalities than RSV patients. Upper airway infection was the most frequent clinical syndrome among HPIV-3 patients. HPIV-3 patients needed less oxygen, salbutamol, antibiotics, corticosteroids and nebulization than RSV patients. In contrast with earlier observations for Northeastern Brazil, our results demonstrate a seasonal pattern for the occurrence of HPIV-3 infections with most cases observed during the dry season. The results also suggest that infections caused by HPIV-3 are milder than infections caused by RSV in previously healthy children. / As infecções respiratórias agudas (IRAs) são um importante problema de saúde pública em todo o mundo, e os vírus parainfluenza estão entre os seus agentes mais freqüentes. Este estudo teve como objetivos: determinar a freqüência de IRAs pelo vírus parainfluenza entre crianças atendidas no Hospital Infantil Albert Sabin, hospital pediátrico de referência da cidade de Fortaleza – CE, de janeiro de 2001 a dezembro de 2006; descrever o padrão de sazonalidade e as características clínico-epidemiológicas destas infecções; e comparar as características clínico-epidemiológicas das infecções por parainfluenza com as das IRAs causadas por outros vírus. Foram coletados aspirados de nasofaringe de crianças com sintomas de IRAs, e foi utilizada a imunofluorescência indireta para a detecção dos vírus: parainfluenza humano 1, 2 e 3 (VPIH-1, 2 e 3), vírus sincicial respiratório (VSR), influenza A e B e adenovírus. Nos seis anos de estudo, foram colhidas amostras de 3070 crianças, a maioria delas previamente sadias, com a detecção de vírus respiratórios em 933 (30,39%), e dos vírus parainfluenza em 117 casos (3,81% do total). Dentre os casos de parainfluenza, o VPIH-3 foi o tipo mais freqüente (83,76% dos casos), com menor detecção do VPIH-1 (11,96%) e do VPIH-2 (4,27%). A infecção pelo VPIH-3 apresentou comportamento sazonal, com maior detecção nos meses de setembro a novembro. Embora o total de casos de IRAs tenha apresentado relação direta com os índices pluviométricos, o número de casos de VPIH-3 apresentou relação inversa com a pluviometria, sendo maior nos meses secos. A maioria dos pacientes positivos para parainfluenza foi atendida na emergência ou nos ambulatórios. A média de idades das crianças com infecção pelo VPIH-3 foi de 20 meses, sendo significativamente menor que a das crianças infectadas pelo vírus influenza A (34 meses), e maior que a das infectadas pelo VSR (15 meses). Os pacientes positivos para o VPIH-3 apresentaram significativamente menos dispnéia, tosse, estertores, tiragem intercostal e alterações radiológicas que os positivos para VSR. As infecções de vias aéreas superiores constituíram a síndrome clínica mais freqüente entre os casos de VPIH-3. Os pacientes positivos para VPIH-3 necessitaram menos de terapia com antibióticos, corticóides, oxigênio, nebulização e/ou salbutamol que os positivos para VSR. Os resultados demonstraram um comportamento sazonal do VPIH-3, relacionado aos meses secos, o que não tinha sido relatado previamente no Nordeste brasileiro, além de apontarem para uma menor gravidade das infecções causadas pelo VPIH-3, na comparação com o VSR, em crianças previamente sadias.

No description available.

Master of Veterinary Biomedical Sciences / Department of Clinical Sciences / Bradley White / Objective- To compare serologic response and viral replication following intranasal administration of a modified-live bovine rhinotracheitis (IBR) parainfluenza-3 (PI-3) vaccine in high (32°C) and moderate (21°C) ambient temperatures. Animals- 28 heifers (mean body weight, 206.8 kg) Procedures- Heifers randomly allocated to treatment groups: High Ambient Temperature (HAT, n=10): received vaccine, housed outdoors, Moderate Ambient Temperature (MAT, n=10): received vaccine, housed indoors, High Ambient Control (HAC, n=4): no vaccine, housed outdoors, Moderate Ambient Control (MAC, n=4): no vaccine, housed indoors. Rectal and nasal mucosal temperatures were recorded every 2 hours from 8am to 8pm on trial days 0 and 1. Nasal swabs were collected on trial days 0 through 7 for virus isolation. Serum samples were collected for serology on trial days 0, 7, 14, and 28. Results- Rectal temperatures did not differ among treatment groups over the study period, but nasal temperatures were higher in the HAT calves compared to MAT group at study hours: 6, 24, 30, 32, and 38. Two weeks post-vaccination, IBR titers were significantly greater in vaccinates (HAT,MAT) relative to non-vaccinates (HAC, LAC), but no differences were identified among HAT and MAT. Viable IBR virus was recovered via virus isolation from all vaccinated calves (HAT,MAT) on trial days 1 through 6. Conclusions and Clinical Relevance- The ability to isolate IBR and stimulate the calf immune response following administration of a modified-live IBR-PI3 intranasal vaccine did not differ in calves housed in temperature-controlled and high ambient temperature environments.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / As infecÃÃes respiratÃrias agudas (IRAs) sÃo um importante problema de saÃde pÃblica em todo o mundo, e os vÃrus parainfluenza estÃo entre os seus agentes mais freqÃentes. Este estudo teve como objetivos: determinar a freqÃÃncia de IRAs pelo vÃrus parainfluenza entre crianÃas atendidas no Hospital Infantil Albert Sabin, hospital pediÃtrico de referÃncia da cidade de Fortaleza â CE, de janeiro de 2001 a dezembro de 2006; descrever o padrÃo de sazonalidade e as caracterÃsticas clÃnico-epidemiolÃgicas destas infecÃÃes; e comparar as caracterÃsticas clÃnico-epidemiolÃgicas das infecÃÃes por parainfluenza com as das IRAs causadas por outros vÃrus. Foram coletados aspirados de nasofaringe de crianÃas com sintomas de IRAs, e foi utilizada a imunofluorescÃncia indireta para a detecÃÃo dos vÃrus: parainfluenza humano 1, 2 e 3 (VPIH-1, 2 e 3), vÃrus sincicial respiratÃrio (VSR), influenza A e B e adenovÃrus. Nos seis anos de estudo, foram colhidas amostras de 3070 crianÃas, a maioria delas previamente sadias, com a detecÃÃo de vÃrus respiratÃrios em 933 (30,39%), e dos vÃrus parainfluenza em 117 casos (3,81% do total). Dentre os casos de parainfluenza, o VPIH-3 foi o tipo mais freqÃente (83,76% dos casos), com menor detecÃÃo do VPIH-1 (11,96%) e do VPIH-2 (4,27%). A infecÃÃo pelo VPIH-3 apresentou comportamento sazonal, com maior detecÃÃo nos meses de setembro a novembro. Embora o total de casos de IRAs tenha apresentado relaÃÃo direta com os Ãndices pluviomÃtricos, o nÃmero de casos de VPIH-3 apresentou relaÃÃo inversa com a pluviometria, sendo maior nos meses secos. A maioria dos pacientes positivos para parainfluenza foi atendida na emergÃncia ou nos ambulatÃrios. A mÃdia de idades das crianÃas com infecÃÃo pelo VPIH-3 foi de 20 meses, sendo significativamente menor que a das crianÃas infectadas pelo vÃrus influenza A (34 meses), e maior que a das infectadas pelo VSR (15 meses). Os pacientes positivos para o VPIH-3 apresentaram significativamente menos dispnÃia, tosse, estertores, tiragem intercostal e alteraÃÃes radiolÃgicas que os positivos para VSR. As infecÃÃes de vias aÃreas superiores constituÃram a sÃndrome clÃnica mais freqÃente entre os casos de VPIH-3. Os pacientes positivos para VPIH-3 necessitaram menos de terapia com antibiÃticos, corticÃides, oxigÃnio, nebulizaÃÃo e/ou salbutamol que os positivos para VSR. Os resultados demonstraram um comportamento sazonal do VPIH-3, relacionado aos meses secos, o que nÃo tinha sido relatado previamente no Nordeste brasileiro, alÃm de apontarem para uma menor gravidade das infecÃÃes causadas pelo VPIH-3, na comparaÃÃo com o VSR, em crianÃas previamente sadias / Acute respiratory infections (ARI) are an important public health problem throughout the world and parainfluenza viruses are among the major etiologic agents. The objectives of this study were: a) to determine the frequency of parainfluenza infections among children attending Hospital Infantil Albert Sabin, a major pediatric hospital in Fortaleza - CE, from January 2001 to December 2006; b) to describe the seasonal pattern and the clinical and epidemiological characteristics of these infections; and c) to compare clinical and epidemiological characteristics of parainfluenza infections and infections caused by other respiratory viruses. Nasopharyngeal aspirates from children with acute respiratory symptoms were collected and submitted to indirect immunofluorescence assays to detect human parainfluenza virus 1, 2 and 3 (HPIV-1, 2 and 3), respiratory syncytial virus (RSV), influenza A and B and adenovirus. During the six-year study period, samples were collected from 3,070 generally healthy children and respiratory viruses were demonstrated in 933 cases (30.39%), of which 117 were positive for parainfluenza virus (3.81%). HPIV-3 was the most frequently detected type of parainfluenza virus accounting for 83.76% of cases, followed by HPIV-1 (11.96%) and HPIV-2 (4.27%). HPIV-3 infections were seasonal with most cases observed from September to November. Although the total number of ARIs was directly associated with the time of the rainy season, HPIV-3 infections were inversely related with rainfall indices. Most HPIV-3 infections were seen in outpatients. The mean age of patients infected by HPIV-3 was 20 months, which is significantly younger than for influenza A (mean age: 34 months) and significantly older than for RSV (mean age: 15 months). HPIV-3 patients presented significantly lower indices of dyspnea, cough, crackles, chest retractions and radiologic abnormalities than RSV patients. Upper airway infection was the most frequent clinical syndrome among HPIV-3 patients. HPIV-3 patients needed less oxygen, salbutamol, antibiotics, corticosteroids and nebulization than RSV patients. In contrast with earlier observations for Northeastern Brazil, our results demonstrate a seasonal pattern for the occurrence of HPIV-3 infections with most cases observed during the dry season. The results also suggest that infections caused by HPIV-3 are milder than infections caused by RSV in previously healthy children