Vírus sincicial respiratório : fatores associados à gravidade da doença e impacto da imunização passiva

Orientadora: Profa..Dra.Sonia Mara RaboniTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna e Ciências da Saúde. Defesa : Curitiba, 26/11/2021Inclui referênciasResumo: O Vírus Sincicial Respiratório (VSR) é o mais frequente causador de infecções respiratórias em crianças. Fatores imunológicos e virais podem influenciar na gravidade e predisposição à infecção. A ausência de vacinas e antiviral específico torna a imunoprofilaxia com o palivizumabe (PVZ), a única opção preventiva. Este estudo descreve características clínicas, epidemiológicas, perfil molecular do VSR, fatores genéticos de suscetibilidade e avalia adesão e falhas de proteção à imunoprofilaxia. Estudo de coorte prospectivo em dois grupos de crianças, entre 0 a 2 anos, (i) hospitalizadas no Hospital Pequeno Príncipe com quadro de Infecção Respiratória Aguda e (ii) crianças que receberam PVZ na Unidade de Saúde Mãe Curitibana. A genotipagem viral foi realizada com técnicas moleculares, RT-PCR multiplex. Os polimorfismos de nucleotídeo único (SNPs) (rs12979860 e rs8099917) da interleucina-28B foram caracterizados por RT-PCR. Um total de 758 crianças foram incluídas, 468 coorte-hospitalizadas e 290 coorte-PVZ. Dos 468 pacientes: 202 (43,2%) foram positivas para VSR, sendo 74 genotipadas com maior prevalência VSR BA; 113 (24,1%) para outros vírus respiratórios (ORV) e 153 (32,7%) negativos. Os pacientes com VSR apresentaram significativamente maior gravidade (p=0,03), com maior necessidade de UTI e uso de ventilação mecânica. Nos pacientes sem comorbidades e positivos para VSR, a combinação dos dois genótipos de SNPs: CT / TG e TT / TT para IL28B rs12979860 e IL28B rs8099917, respectivamente, foram significativamente mais frequentes (p<0,001). Não houve óbito no grupo VSR. Entre as 290 crianças com uso de PVZ, houve uma adesão média de 90% entre o esquema total de doses, 93 (32%) apresentaram infecção respiratória e 41(44%) foram investigadas, sendo que em 8 (19,5%) detectado VSR, 20 (48,8%) OVR e 13 (31,7%) negativos. Conclusões: este estudo destacou a maior gravidade da infecção respiratória por VSR, comparado a OVR e reforça a hipótese de associações de SNPs da IL28B com maior suscetibilidade às infecções por VSR. Maior severidade nos quadros de SRAG foram associados a presença de comorbidade, sexo masculino, uso de antimicrobianos e infecções por VSR. Observou-se falhas de proteção pós-PVZ, ainda não relatadas em nosso meio.Abstract: Respiratory Syncytial Virus (RSV) is the most frequent cause of respiratory infections in children. Immune and viral factors can influence the severity and predisposition to infection. The absence of vaccines and specific antivirals makes immunoprophylaxis with palivizumab (PVZ) the only preventive option. This study describes clinical and epidemiological characteristics, molecular profile of the RSV, genetic susceptibility factors and evaluates adherence and protection failures to immunoprophylaxis. Prospective cohort study in two groups of children, aged 0 to 2 years, (i) hospitalized at Hospital Pequeno Príncipe with an Acute Respiratory Infection and (ii) children who received PVZ at the Mãe Curitibana Health Unit. The Viral genotyping diagnosis was performed using molecular techniques, multiplex RTPCR. Single nucleotide polymorphisms (SNPs) (rs12979860 and rs8099917) of interleukin-28B were characterized by RT-PCR. A total of 758 children were included, 468 cohort-hospitalized and 290 cohort-PVZ. Of the 468 patients: 202 (43.2%) were positive for RSV, with 74 genotyped with a higher prevalence of RSV BA9; 113 (24.1%) for other respiratory viruses (ORV) and 153 (32.7%) negative. Patients with RSV were significantly more severe (p = 0.03), with greater need for ICU and use of mechanical ventilation, and no death occurred. In patients without comorbidities and positive for RSV, the combination of the two genotypes of SNPs: CT / TG and TT / TT for IL28B rs12979860 and IL28B rs8099917, respectively, were significant (p<0.001). There were no deaths in the RSV group. Among the 290 children using PVZ, there was an average adherence of 90% between the total dose schedule, 93(32.0%) had respiratory infection and 41(44.0%) were investigated, being 8 (19.5%) detected RSV, 20 (48.8%) OVR and 13 (31.7%) negative. There were no reports of death in the PVZ cohort. Conclusions: This study highlighted the greater severity of respiratory RSV infection compared to OVR and reinforced the hypothesis of associations of IL28B SNPs with greater susceptibility to RSV infections. Greater severity of SARI was associated with the presence of comorbidity, male gender and use of antimicrobials and RSV infections. Breakthrough -infections post-PVZ were observed, not yet reported in our region

Estudo dos fatores de risco para infecçao hospitalar em unidade de terapia intensiva referencia para trauma na cidade de Curitiba nos anos de 2000 e 2001

Orientador: Rogério Andrade MulinariCo-orientadora: Eliane Mara CesarioDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna. Defesa: Curitiba, 2004Inclui bibliografia e anexosResumo: A infecção hospitalar (IH) e um dos principais problemas de saúde publica e um dos eventos adversos mais temidos, em especial nas unidades de terapia intensiva. Progressos no transporte e no primeiro atendimento dos politraumatizados contribuem para que um número crescente de pacientes sobrevivam ao trauma, o que resulta, muitas vezes, em internamentos prolongados em unidades de terapia intensiva. Diversos fatores contribuem para a vulnerabilidade destes pacientes as infecções, manipulação intensa, cirurgias de emergência, múltiplos procedimentos invasivos, perda de barreira protetora mucosa e cutânea e uso de hemoderivados. O objetivo do estudo foi determinar os fatores de risco para infecção hospitalar entre os pacientes de trauma internados em uma unidade de terapia intensiva. O estudo de coorte histórico incluiu 416 (352M, 64F) pacientes, no período de janeiro de 2000 e dezembro de 2001. A taxa de infecção hospitalar foi de 69,5%, o índice de óbito geral foi de 29,3%, sendo 28,7% e 29,8% nos pacientes com IH e sem IH, respectivamente. A analise univariada demonstrou associação de IH e mais de um segmento anatômico atingido pelo trauma (OR= 1,6, ICg5% 1,1 - 2,4), ventilação mecânica por período maior do que três dias (OR= 12,8, ICg5/0 6,87 - 24,02), mais de uma cirurgia (OR=3,13, ICg5% 1,8 - 5,6), neurocirurgia (OR=2,1, ICg5 três dias, numero de procedimentos invasivos e numero de cirurgias.Abstract: Nosocomial Infection (NI) is one of the leading public health problems and one of most dreaded adverse events, especially in the intensive care units. Progress in transport and in initial care of patients with multiple trauma has increased survival but determine prolonged stay at the hospital and in the intensive care units. Several factors contribute for vulnerability to infections in these patients such as, intensive manipulation, emergency surgeries, multiple invasive devices, lost of cutaneous and mucouses barrier and use of blood transfusion. The objective of the study was to identify risks factors for nosocomial infection in trauma patients hospitalized in a intensive care units. The historical cohort study included 416 patients, (352M, 64F) between January 1 2000 and December 31 2001. The overall nosocomial infection rate was 69.7%, mortality of 29.3% and mortality of 28.7% and 29.3% in patients with and without nosocomial infection. Univariate analysis indicated association of infection and trauma in injury of more than one anatomic segment (OR= 1.6, ICg5% 1.1 - 2.4), use of mechanical ventilation for more than three days (OR= 12.8, IC g s% 6.87 - 24.02) more than one surgery (OR=3.13, IC95o/o 1.8 - 5.6) neurosurgery (Of?=2.1, ICg5% 1.3 - 3.3), more than two invasive devices (OR=4.7, IC gs% 3.0 -7.4) injury to head or neck (OR= 1.6 ICg5% 1.0 - 2.4). The most frequent agents isolated were: Coagulase-negative Staphylococcus, Acinetobacter baumanii and meticilin resistant Staphylococcus aureus (MRSA). The most common site of infection were: pneumonia (49.3%), primary bloodstream infection (19%), urinary tract infection (12.4%) and catheter associated infection (11%). The length of stay was 9.3 days, median of 7 days (min 2, max 65). The length of stay for infected trauma patients was 14.7 days, median of 13 days (min 3, max 65) and for noninfected trauma patients was 4.9 days, median of 4 days (min 2, max 20), respectively. The predictors variables for nosocomial infection identified in multivariate analysis were more than three days of mechanical ventilation, number of invasive devices and number of surgeries

Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

Vírus sincicial respiratório : fatores associados à gravidade da doença e impacto da imunização passiva

Orientadora: Profa..Dra.Sonia Mara RaboniTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna e Ciências da Saúde. Defesa : Curitiba, 26/11/2021Inclui referênciasResumo: O Vírus Sincicial Respiratório (VSR) é o mais frequente causador de infecções respiratórias em crianças. Fatores imunológicos e virais podem influenciar na gravidade e predisposição à infecção. A ausência de vacinas e antiviral específico torna a imunoprofilaxia com o palivizumabe (PVZ), a única opção preventiva. Este estudo descreve características clínicas, epidemiológicas, perfil molecular do VSR, fatores genéticos de suscetibilidade e avalia adesão e falhas de proteção à imunoprofilaxia. Estudo de coorte prospectivo em dois grupos de crianças, entre 0 a 2 anos, (i) hospitalizadas no Hospital Pequeno Príncipe com quadro de Infecção Respiratória Aguda e (ii) crianças que receberam PVZ na Unidade de Saúde Mãe Curitibana. A genotipagem viral foi realizada com técnicas moleculares, RT-PCR multiplex. Os polimorfismos de nucleotídeo único (SNPs) (rs12979860 e rs8099917) da interleucina-28B foram caracterizados por RT-PCR. Um total de 758 crianças foram incluídas, 468 coorte-hospitalizadas e 290 coorte-PVZ. Dos 468 pacientes: 202 (43,2%) foram positivas para VSR, sendo 74 genotipadas com maior prevalência VSR BA; 113 (24,1%) para outros vírus respiratórios (ORV) e 153 (32,7%) negativos. Os pacientes com VSR apresentaram significativamente maior gravidade (p=0,03), com maior necessidade de UTI e uso de ventilação mecânica. Nos pacientes sem comorbidades e positivos para VSR, a combinação dos dois genótipos de SNPs: CT / TG e TT / TT para IL28B rs12979860 e IL28B rs8099917, respectivamente, foram significativamente mais frequentes (p<0,001). Não houve óbito no grupo VSR. Entre as 290 crianças com uso de PVZ, houve uma adesão média de 90% entre o esquema total de doses, 93 (32%) apresentaram infecção respiratória e 41(44%) foram investigadas, sendo que em 8 (19,5%) detectado VSR, 20 (48,8%) OVR e 13 (31,7%) negativos. Conclusões: este estudo destacou a maior gravidade da infecção respiratória por VSR, comparado a OVR e reforça a hipótese de associações de SNPs da IL28B com maior suscetibilidade às infecções por VSR. Maior severidade nos quadros de SRAG foram associados a presença de comorbidade, sexo masculino, uso de antimicrobianos e infecções por VSR. Observou-se falhas de proteção pós-PVZ, ainda não relatadas em nosso meio.Abstract: Respiratory Syncytial Virus (RSV) is the most frequent cause of respiratory infections in children. Immune and viral factors can influence the severity and predisposition to infection. The absence of vaccines and specific antivirals makes immunoprophylaxis with palivizumab (PVZ) the only preventive option. This study describes clinical and epidemiological characteristics, molecular profile of the RSV, genetic susceptibility factors and evaluates adherence and protection failures to immunoprophylaxis. Prospective cohort study in two groups of children, aged 0 to 2 years, (i) hospitalized at Hospital Pequeno Príncipe with an Acute Respiratory Infection and (ii) children who received PVZ at the Mãe Curitibana Health Unit. The Viral genotyping diagnosis was performed using molecular techniques, multiplex RTPCR. Single nucleotide polymorphisms (SNPs) (rs12979860 and rs8099917) of interleukin-28B were characterized by RT-PCR. A total of 758 children were included, 468 cohort-hospitalized and 290 cohort-PVZ. Of the 468 patients: 202 (43.2%) were positive for RSV, with 74 genotyped with a higher prevalence of RSV BA9; 113 (24.1%) for other respiratory viruses (ORV) and 153 (32.7%) negative. Patients with RSV were significantly more severe (p = 0.03), with greater need for ICU and use of mechanical ventilation, and no death occurred. In patients without comorbidities and positive for RSV, the combination of the two genotypes of SNPs: CT / TG and TT / TT for IL28B rs12979860 and IL28B rs8099917, respectively, were significant (p<0.001). There were no deaths in the RSV group. Among the 290 children using PVZ, there was an average adherence of 90% between the total dose schedule, 93(32.0%) had respiratory infection and 41(44.0%) were investigated, being 8 (19.5%) detected RSV, 20 (48.8%) OVR and 13 (31.7%) negative. There were no reports of death in the PVZ cohort. Conclusions: This study highlighted the greater severity of respiratory RSV infection compared to OVR and reinforced the hypothesis of associations of IL28B SNPs with greater susceptibility to RSV infections. Greater severity of SARI was associated with the presence of comorbidity, male gender and use of antimicrobials and RSV infections. Breakthrough -infections post-PVZ were observed, not yet reported in our region

Estudo dos fatores de risco para infecçao hospitalar em unidade de terapia intensiva referencia para trauma na cidade de Curitiba nos anos de 2000 e 2001

Orientador: Rogério Andrade MulinariCo-orientadora: Eliane Mara CesarioDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna. Defesa: Curitiba, 2004Inclui bibliografia e anexosResumo: A infecção hospitalar (IH) e um dos principais problemas de saúde publica e um dos eventos adversos mais temidos, em especial nas unidades de terapia intensiva. Progressos no transporte e no primeiro atendimento dos politraumatizados contribuem para que um número crescente de pacientes sobrevivam ao trauma, o que resulta, muitas vezes, em internamentos prolongados em unidades de terapia intensiva. Diversos fatores contribuem para a vulnerabilidade destes pacientes as infecções, manipulação intensa, cirurgias de emergência, múltiplos procedimentos invasivos, perda de barreira protetora mucosa e cutânea e uso de hemoderivados. O objetivo do estudo foi determinar os fatores de risco para infecção hospitalar entre os pacientes de trauma internados em uma unidade de terapia intensiva. O estudo de coorte histórico incluiu 416 (352M, 64F) pacientes, no período de janeiro de 2000 e dezembro de 2001. A taxa de infecção hospitalar foi de 69,5%, o índice de óbito geral foi de 29,3%, sendo 28,7% e 29,8% nos pacientes com IH e sem IH, respectivamente. A analise univariada demonstrou associação de IH e mais de um segmento anatômico atingido pelo trauma (OR= 1,6, ICg5% 1,1 - 2,4), ventilação mecânica por período maior do que três dias (OR= 12,8, ICg5/0 6,87 - 24,02), mais de uma cirurgia (OR=3,13, ICg5% 1,8 - 5,6), neurocirurgia (OR=2,1, ICg5 três dias, numero de procedimentos invasivos e numero de cirurgias.Abstract: Nosocomial Infection (NI) is one of the leading public health problems and one of most dreaded adverse events, especially in the intensive care units. Progress in transport and in initial care of patients with multiple trauma has increased survival but determine prolonged stay at the hospital and in the intensive care units. Several factors contribute for vulnerability to infections in these patients such as, intensive manipulation, emergency surgeries, multiple invasive devices, lost of cutaneous and mucouses barrier and use of blood transfusion. The objective of the study was to identify risks factors for nosocomial infection in trauma patients hospitalized in a intensive care units. The historical cohort study included 416 patients, (352M, 64F) between January 1 2000 and December 31 2001. The overall nosocomial infection rate was 69.7%, mortality of 29.3% and mortality of 28.7% and 29.3% in patients with and without nosocomial infection. Univariate analysis indicated association of infection and trauma in injury of more than one anatomic segment (OR= 1.6, ICg5% 1.1 - 2.4), use of mechanical ventilation for more than three days (OR= 12.8, IC g s% 6.87 - 24.02) more than one surgery (OR=3.13, IC95o/o 1.8 - 5.6) neurosurgery (Of?=2.1, ICg5% 1.3 - 3.3), more than two invasive devices (OR=4.7, IC gs% 3.0 -7.4) injury to head or neck (OR= 1.6 ICg5% 1.0 - 2.4). The most frequent agents isolated were: Coagulase-negative Staphylococcus, Acinetobacter baumanii and meticilin resistant Staphylococcus aureus (MRSA). The most common site of infection were: pneumonia (49.3%), primary bloodstream infection (19%), urinary tract infection (12.4%) and catheter associated infection (11%). The length of stay was 9.3 days, median of 7 days (min 2, max 65). The length of stay for infected trauma patients was 14.7 days, median of 13 days (min 3, max 65) and for noninfected trauma patients was 4.9 days, median of 4 days (min 2, max 20), respectively. The predictors variables for nosocomial infection identified in multivariate analysis were more than three days of mechanical ventilation, number of invasive devices and number of surgeries

Risk factors for nosocomial infection in trauma patients

Several factors are implicated in the increased vulnerability of multiple trauma victims to infection, especially in intensive care-units (ICU). This cohort study was designed to report the incidence, the topography, the etiology and to identify the risk factors for infection in trauma patients admitted in an ICU. From January 2000 to December 2001, 416 trauma patients were admitted to the ICU for more than 24 hours, the mean length of stay was 9.3 days (range 2-65) and 188 (45%) patients developed a total of 290 NI. The most prevailing infections were pneumonia (49%), bloodstream (19%) and urinary tract infections (12%). The variables studied were: the demographic data, diagnosis on admission, site and mechanism of injury, type and number of surgeries, use of invasive devices, days under mechanical ventilation (MV) and site and number of NI. These variables were analyzed with a univariable and multivariable regression analysis. The NI was associated with injury in more than 1 anatomic segment (OR=1.6; CI95%1.06-2.40); mechanical ventilation for more than 3 days (OR=12; CI95% 6.87-24.02); more than 1 surgery (OR=3.13;CI95%1.75-5.65) and more than 2 invasive devices (OR=4.7; CI95%2.99-7.37). Deaths over the first 5 days had high association (RR=3.18) with NI. Three significant variables were identified in the logistic regression, which are: more than 3 days under MV, number of invasive devices and number of surgeries