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1.
An Acad Bras Cienc ; 92(1): e20180584, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32236294

RESUMO

Despite numerous studies evaluating influenza and Respiratory Syncytial Virus (RSV), there is still a lack of knowledge about them, especially in tropical countries. We compared the relative importance of respiratory viruses by examining their spatiotemporal patterns, age-specific hospitalization data and mortality data for 2007-2012 obtained from official sources. The data were aggregated into "respiratory infection seasonal zones" formed combining states that had similar seasonal patterns of pneumonia and influenza (P&I). Equatorial-North where P&I peaks in the middle of the year, Equatorial-South where P&I peaks in the first semester and coincides with the rainy-season, Subtropical where P&I peaks are clearly concentrated in the winter season, and Tropical Midwest and South-East where P&I peaks are a transition between the South-Equatorial and the Sub-tropical. Our analyses indicate that RSV has higher impact than influenza in equatorial region of Brazil, which was particularly evident during the circulation of the 2009pdm strain, and suggests that seasonal influenza may have a lower impact in Equatorial Brazil (and perhaps in other tropical regions of the world) than previously considered. Accordingly, we suggest that the broad assumption that influenza is the main cause of viral respiratory hospitalizations and death in equatorial regions be questioned with greater emphasis in future studies.


Assuntos
Mortalidade Hospitalar , Influenza Humana/mortalidade , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/classificação , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Notificação de Doenças , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pandemias , Estações do Ano , Adulto Jovem
2.
BMC Res Notes ; 12(1): 581, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521197

RESUMO

OBJECTIVES: We have assessed the risk factors for the occurrence of hospital-acquired (HA) and community-acquired (CA) viral acute respiratory tract infections (ARTIs) in children. Children (1-60 months) who were having ARTI on admission (CA) and develops ARTI following 48 h after admission or 3 days of discharge (HA) were included. Indirect immunofluorescence assay (IFA) was performed and multivariable analyses were done to determine the risk factors for the development of viral CA and HA-ARTI. RESULTS: Total of 818 with ARTIs, 226 (27.6%) RSV cases were detected. Out of 226, 86 (38.0%) HA-RSV cases were detected. CA-viral-ARTI was significantly high (p < 0.05). Compared to CA-RSV-ARTI immunodeficiency, seizures, trisomy-21 and congenital heart disease (CHD) were having 2.3, 3.2, 1.8- and 2.2-times risk for acquiring HA-RSV respectively. The number of deaths was significantly high following HA-RSV. The associated burden was significant following HA-RSV and it was 429.77 disability-adjusted life years. Children who are having immunodeficiency, CHD, seizure episodes and trisomy 21 would lead to the acquisition of nosocomial RSV infections in great. Adherence to meticulous infection control practices will be helpful to minimize the HA-viral ARTIs in great.


Assuntos
Infecção Hospitalar/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Doença Aguda , Pré-Escolar , Imunodeficiência de Variável Comum/complicações , Infecção Hospitalar/virologia , Estudos Transversais , Síndrome de Down/complicações , Feminino , Cardiopatias Congênitas/complicações , Hospitalização , Humanos , Lactente , Masculino , Infecções por Vírus Respiratório Sincicial/mortalidade , Vírus Sincicial Respiratório Humano , Infecções Respiratórias/mortalidade , Fatores de Risco , Convulsões/complicações , Sri Lanka
3.
Transpl Infect Dis ; 21(4): e13105, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31081570

RESUMO

BACKGROUND: Immunocompromised hematologic malignancy (HM) patients experience high mortality after respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI). We measured radiologic severity to determine whether it could improve the performance of 60-day mortality models based only upon immunodeficiency severity. METHODS: We studied 155 HM patients, including 84 hematopoietic cell transplant recipients, who developed RSV LRTI from 2001 to 2013. We measured immunodeficiency using lymphopenia (lymphocyte count <200 cells/mm3 ), Immunodeficiency Severity Index (ISI), and Severe Immunodeficiency (SID) criteria. Radiologic severity was measured by the Radiologic Severity Index (RSI, range 0-72) at time of LRTI (baseline-RSI) and peak severity (peak-RSI). Delta-RSI was defined as the difference between baseline-RSI and peak-RSI. We used logistic regression models to measure the association of immunodeficiency and RSI with 60-day all-cause mortality, and measured model discrimination using areas under the receiver-operating characteristics curves, calibration using Brier scores, and explained variance using pseudo-R2 values. RESULTS: Forty-one patients died within 60 days of RSV LRTI. Severe immunodeficiency was associated with higher mortality. Peak-RSI (odds ratio [OR] 1.06/point, 95% confidence interval [CI] 1.04-1.08), and delta-RSI (OR 1.07/point, 95% CI 1.05-1.10) were associated with 60-day mortality after RSV LRTI, but not baseline-RSI. Addition of peak-RSI or delta-RSI to baseline immunodeficiency improved the discrimination, calibration, and explained variance (P < 0.001) of 60-day mortality models. CONCLUSIONS: Although baseline immunodeficiency in HM patients helps predict 60-day mortality after RSV LRTI, mortality risk estimates can be further refined by also measuring LRTI progression using RSI. RSI is well-suited as a marker of LRTI severity in RSV infection.


Assuntos
Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/virologia , Infecções por Vírus Respiratório Sincicial/mortalidade , Índice de Gravidade de Doença , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Neoplasias Hematológicas/complicações , Humanos , Hospedeiro Imunocomprometido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções Respiratórias/virologia , Estudos Retrospectivos , Fatores de Risco
4.
Influenza Other Respir Viruses ; 13(4): 331-338, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30977284

RESUMO

OBJECTIVES: Respiratory syncytial virus (RSV) is an important cause of morbidity and mortality in adults. Existing studies are limited by the number of seasons studied and most have focused on the immunocompromised. METHODS: A retrospective cohort study was conducted on all adults (≥18 years) with a positive RSV molecular test admitted from 2009 to 2015 to one hospital in Chicago, IL. Epidemiologic and outcomes data were collected after IRB approval. RESULTS: Of the 489 eligible patients, 227 had RSV A and 262 had RSV B. Patients had a median age of 61 years and comorbidity (eg, chronic lung disease [40.6%], obesity [37.8%], and cardiac disease [34.3%]). On presentation, most had cough (86.5%), fever (42.4%), and shortness of breath (38.2%). Severe disease was present in 27.6% of patients. Antibiotic was used in 76.3% inpatients and 45.8% at discharged despite few patients (4.7%) having documented bacterial infections. Supplemental oxygen and mechanical ventilation were utilized in 44.6% and 12.3%, respectively, while ICU level care was required in 26.9%. Most patients were discharged home (82.7%). Most deaths (68.4%, 13/19) were attributed to pneumonia or hypoxemia likely from RSV. Most fatal cases were seen in those with recent cancer treatment and older adults. CONCLUSIONS: Respiratory syncytial virus in hospitalized adults is associated with significant morbidity and mortality with 26.9% requiring ICU level care. Antibiotics are commonly prescribed to patients with documented RSV, and antibiotics are frequently continued after diagnosis. Novel antiviral therapies are needed for RSV to improve outcomes and potentially improve antibiotic stewardship in patients without a bacterial infection.


Assuntos
Hospitalização/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/mortalidade , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Humanos , Hospedeiro Imunocomprometido , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sincicial Respiratório Humano/genética , Estudos Retrospectivos , Ribavirina/uso terapêutico , Adulto Jovem
5.
Infection ; 47(3): 425-433, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30649684

RESUMO

PURPOSE: We studied the incidence, morbidity and mortality of all patients presenting in our teaching hospital with proven influenza virus and/or respiratory syncytial virus (RSV) infection during the influenza epidemic season 2018 which was characterized by a predominant incidence of influenza virus B type B of the Yamagata line. METHODS: In the fall of 2017, specific precaution measures in addition to standard measures were implemented, including standardized testing for influenza virus A,B and RSV by multiplex PCR of pharyngeal swabsData from all consecutive patients were analyzed retrospectively. RESULTS: Overall 651 patients were examined for the presence of influenza virus and RSV; 214 patients had influenza virus A (n = 36), B (n = 152), and/or RSV (n = 30), including four patients with dual infection. 86% of cases had influenza virus (80% B), and 14% RSV infection. N = 23 cases were treated as outpatients. The rate of acute viral respiratory infections (influenza virus and RSV) was 191 of 2776 (6.9%) admissions to medical wards. Of n = 191 hospitalized cases, n = 44 cases (20.6%) had nosocomial infection. Viral infections were associated with a high morbidity (pneumonia 28.5%, mortality 4.7%). Independent predictors of prolonged hospitalization were the presence of pneumonia, NIV and renal complications, and independent predictors of pneumonia were age ≥ 65 years, bedridden status and CRP ≥ 2.9 mg/dL. CONCLUSIONS: The rate of nosocomial cases was high despite established precaution measures. RSV was associated with morbidity and mortality comparable to influenza. Pneumonia remains the main complication of acute viral respiratory infections, and antimicrobial treatment should include both antiviral as well as antibacterial agents.


Assuntos
Coinfecção/epidemiologia , Epidemias , Influenza Humana/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Doença Aguda/epidemiologia , Doença Aguda/mortalidade , Adulto , Idoso , Coinfecção/mortalidade , Coinfecção/virologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/mortalidade , Infecção Hospitalar/virologia , Feminino , Alemanha/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Vírus da Influenza A/fisiologia , Vírus da Influenza B/fisiologia , Influenza Humana/mortalidade , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Morbidade , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/fisiologia , Estudos Retrospectivos , Adulto Jovem
6.
Pediatr Infect Dis J ; 38(6): 589-594, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30672892

RESUMO

BACKGROUND: Respiratory syncytial virus is the leading cause of acute lower respiratory infection in children. We aimed to describe the clinical-epidemiologic pattern and risk factors for mortality associated with RSV infection. METHODS: This is a prospective, cross-sectional study of acute lower respiratory infection in children admitted to the Children's Hospital during 2000 to 2017. Viral diagnosis was made by fluorescent antibody techniques or real-time-polymerase chain reaction. We compared clinical-epidemiologic characteristics of RSV infection in nonfatal versus fatal cases. Multiple logistic regression was used to identify independent predictors of mortality. RESULTS: Of 15,451 patients with acute lower respiratory infection, 13,033 were tested for respiratory viruses and 5831 (45%) were positive: RSV 81.3% (4738), influenza 7.6% (440), parainfluenza 6.9% (402) and adenovirus 4.3% (251). RSV had a seasonal epidemic pattern coinciding with months of lowest average temperature. RSV cases show a case fatality rate of 1.7% (82/4687). Fatal cases had a higher proportion of prematurity (P < 0.01), perinatal respiratory history (P < 0.01), malnourishment (P < 0.01), congenital heart disease (P < 0.01), chronic neurologic disease (P < 0.01) and pneumonia at clinical presentation (P = 0.014). No significant difference between genders was observed. Most deaths occurred among children who had complications: respiratory distress (80.5%), nosocomial infections (45.7%), sepsis (31.7%) and atelectasis (13.4%). Independent predictors of RSV mortality were moderate-to-severe malnourishment, odds ratio (OR): 3.69 [95% confidence interval (CI): 1.98-6.87; P < 0.0001]; chronic neurologic disease, OR: 4.14 (95% CI: 2.12-8.08; P < 0.0001); congenital heart disease, OR: 4.18 (95% CI: 2.39-7.32; P< 0.0001); and the age less than 6 months, OR: 1.99 (95% CI: 1.24-3.18; P = 0.004). CONCLUSIONS: RSV showed an epidemic pattern affecting mostly young children. Malnourishment, chronic neurologic disease, congenital heart disease and the age less than 6 months were the independent risk factors for RSV mortality.


Assuntos
Efeitos Psicossociais da Doença , Monitoramento Epidemiológico , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções Respiratórias/mortalidade , Doença Aguda/epidemiologia , Fatores Etários , Argentina/epidemiologia , Estudos Transversais , Feminino , Hospitalização , Humanos , Lactente , Modelos Logísticos , Masculino , Mortalidade , Razão de Chances , Estudos Prospectivos , Vírus Sincicial Respiratório Humano/imunologia , Infecções Respiratórias/virologia , Fatores de Risco
7.
Clin Infect Dis ; 68(1): 113-119, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29788036

RESUMO

Background: Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in children. Mortality rates in previously healthy children hospitalized with RSV are <0.5%, but up to 37% in patients with underlying medical conditions. The objective of this study was to characterize factors associated with deaths among children hospitalized with RSV infection in Canadian pediatric centers. Methods: A retrospective case series of children aged ≤18 years with RSV-associated deaths at centers affiliated with the Pediatric Investigators Collaborative Network on Infections in Canada from 2003­2013, inclusive, was performed [corrected]. Cases were identified using RSV-specific International Classification of Diseases codes to capture deaths where a diagnosis of RSV infection was present. Results: Eleven centers reported 79 RSV-associated deaths. RSV was regarded as primarily responsible for death in 32 cases (40.5%). Median age at death was 11 months (range, <1 month to 16 years). Thirty-nine patients (49.4%) were male. Fourteen patients (17.7%) had no known risk factors for severe RSV infection. Healthcare-associated RSV infections (HAIs) accounted for 29 deaths (36.7%), with RSV judged to be the primary cause of death in 9 of these cases. Conclusions: RSV-associated deaths were predominantly associated with chronic medical conditions and immunocompromised states among infants; however, 1 in 5 deaths occurred among patients with no known risk factors for severe RSV. Mortality associated with HAI accounted for over a third of cases. These findings highlight patient groups that should be targeted for RSV prevention strategies such as infection control practices, immunoprophylaxis, and future vaccination programs.


Assuntos
Infecções por Vírus Respiratório Sincicial/mortalidade , Adolescente , Bronquiolite/mortalidade , Canadá/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pneumonia Viral/mortalidade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
8.
Antiviral Res ; 161: 125-133, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30503888

RESUMO

Human respiratory syncytial virus (HRSV) infection is a significant cause of morbidity and mortality, particularly among the children and the elderly. Despite extensive efforts, there is currently no formally approved vaccine and effective antiviral options against HRSV infection are limited. The development of vaccines and antiviral strategies for HRSV was partly hampered by the lack of an efficient lethal mouse model to evaluate the efficacy of the candidate vaccines or antivirals. In this study, we established a lethal HRSV mouse model by consecutively passaging a clinical HRSV isolate, GZ08-0. GZ08-18 was isolated from mouse bronchioalveolar lavage fluids at the 50th passage of GZ08-0. Importantly, all GZ08-18-inoculated mice succumbed to the infection by day 7 post infection, whereas all GZ08-0-inoculated mice recovered from the infection. Subsequent investigations demonstrated that GZ08-18 replicated to a higher titer in mouse lungs, induced more prominent lung pathology, and resulted in higher expression levels of a number of key pro-inflammatory cytokines including IFN-γ, MIP-1α, and TNF-α in comparison to that of GZ08-0. The cyclophosphamide pretreatment rendered the mice more susceptible to a lethal outcome with less rounds of virus inoculation. Full genome sequencing revealed 17 mutations in GZ08-18, some of which might account for the dramatically increased pathogenicity over GZ08-0. In addition, by using ribavirin as a positive control, we demonstrated the potential application of this lethal mouse model as a tool in HRSV investigations. Overall, we have successfully established a practical lethal mouse model for HRSV with a mouse-adapted virus, which may facilitate future in vivo studies on the evaluation of candidate vaccines and drugs against HRSV.


Assuntos
Envelhecimento , Modelos Animais de Doenças , Infecções por Vírus Respiratório Sincicial/mortalidade , Vírus Sincicial Respiratório Humano/patogenicidade , Animais , Antivirais/uso terapêutico , Linhagem Celular , Ciclofosfamida/farmacologia , Genoma Viral , Humanos , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sincicial Respiratório Humano/fisiologia , Ribavirina/uso terapêutico , Replicação Viral
9.
Am J Respir Crit Care Med ; 199(4): 518-528, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30230909

RESUMO

RATIONALE: Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients. OBJECTIVES: To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients. METHODS: This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified. MEASUREMENTS AND MAIN RESULTS: Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22-3.50). CONCLUSIONS: Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.


Assuntos
Doenças Hematológicas/virologia , Hospedeiro Imunocomprometido , Infecções Respiratórias/virologia , Idoso , Estado Terminal , Feminino , Doenças Hematológicas/complicações , Doenças Hematológicas/mortalidade , Mortalidade Hospitalar , Humanos , Influenza Humana/complicações , Influenza Humana/diagnóstico , Influenza Humana/mortalidade , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Infecções por Paramyxoviridae/complicações , Infecções por Paramyxoviridae/diagnóstico , Infecções por Paramyxoviridae/mortalidade , Infecções por Picornaviridae/complicações , Infecções por Picornaviridae/diagnóstico , Infecções por Picornaviridae/mortalidade , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/mortalidade
10.
J Infect Dis ; 219(3): 358-364, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30165655

RESUMO

Background: Numerous deaths in children aged <5 years in the developing world occur at home. Acute respiratory infections (ARIs) are thought to play an important role in these deaths. Risk factors and pathogens linked to fatal episodes remain unclear. Methods: A case-control study among low-income children aged <5 years was performed in Buenos Aires, Argentina, to define risk factors and viral pathogens among those who died of ARI at home. Results: A total of 278 families of children aged <5 years (of whom 104 died and 174 were healthy controls) participated in the study. A total of 87.5% of ARI-associated deaths occurred among infants aged <12 months. The estimated mortality rate due to ARI among infants was 5.02 deaths/1000 live births. Dying at home from ARI was associated with living in a crowded home (odds ratio [OR], 3.73; 95% confidence interval [CI], 1.41-9.88), having an adolescent mother (OR, 4.89; 95% CI, 1.37-17.38), lacking running water in the home (OR, 4.39; 95% CI, 1.11-17.38), incomplete vaccinations for age (OR, 3.39; 95% CI, 1.20-9.62), admission to a neonatal intensive care unit (OR, 7.17; 95% CI, 2.21-23.27), and no emergency department visit during the ARI episode (OR, 72.32; 95% CI, 4.82-1085.6). The at-home death rate due to respiratory syncytial virus infection among infants was 0.26 deaths/100 live births and that due to influenza was 0.07 deaths/1000 live births. Conclusions: Social vulnerabilities underlie at-home mortality due to ARI. Mortality rates due to RSV and influenza virus infection are high among infants at home and are similar to those reported for hospitalized children.


Assuntos
Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções Respiratórias/mortalidade , Argentina/epidemiologia , Estudos de Casos e Controles , Assistência à Saúde , Hospitalização , Humanos , Lactente , Recém-Nascido , Influenza Humana/mortalidade , Unidades de Terapia Intensiva , Análise Multivariada , Razão de Chances , Orthomyxoviridae , Pobreza , Características de Residência , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios , Infecções Respiratórias/virologia , Fatores de Risco , Fatores Socioeconômicos
11.
Transpl Infect Dis ; 20(6): e12994, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30195271

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with high mortality in patients with hematologic malignancies (HM). We sought to determine whether allogeneic hematopoietic cell transplant (allo-HCT) recipients would be at higher risk for 60-day mortality. METHODS: We examined a retrospective cohort of adults with HM with or without HCT treated for RSV LRTI (n = 154) at our institution from 1996-2013. We defined possible RSV LRTI as RSV detected only in the upper respiratory tract with new radiologic infiltrates and proven RSV LRTI as RSV detected in BAL fluid with new radiologic infiltrates. Immunodeficiency Scoring Index (ISI) and Severe Immunodeficiency (SID) criteria were calculated for HCT recipients. Multivariable logistic regression analyses were performed to identify independent risk factors associated with 60-day all-cause mortality. RESULTS: Mortality was high in HM patients (25%), but there was no difference between those without HCT, autologous or allo-HCT recipients in logistic regression models. Separate multivariate models showed that at RSV diagnosis, neutropenia (OR 8.3, 95% CI 2.8-24.2, P = 0.005) and lymphopenia (OR 3.7, 95% CI 1.7-8.2, P = 0.001) were associated with 60-day mortality. Proven LRTI was associated with higher 60-day mortality (neutropenia model: OR 4.7, 95%CI 1.7-13.5; lymphopenia model: OR 3.3, 95% CI 1.2-8.8), and higher ICU admission. In HCT recipients, high ISI and very severe immunodeficiency by SID criteria were associated with higher 60-day all-cause mortality. CONCLUSIONS: Mortality is similarly high among HM patients without HCT and HCT recipients. High-grade immunodeficiency and detection of RSV from BAL fluid are associated with higher 60-day mortality.


Assuntos
Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Vírus Respiratório Sincicial/mortalidade , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/mortalidade , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/virologia , Broncoscopia , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Linfopenia/sangue , Linfopenia/imunologia , Linfopenia/mortalidade , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Neutropenia/sangue , Neutropenia/imunologia , Neutropenia/mortalidade , Neutropenia/virologia , Infecções por Vírus Respiratório Sincicial/sangue , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Infecções Respiratórias/sangue , Infecções Respiratórias/imunologia , Infecções Respiratórias/virologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo/efeitos adversos , Adulto Jovem
12.
J Antimicrob Chemother ; 73(11): 3162-3169, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30113677

RESUMO

Objectives: Respiratory syncytial virus (RSV) infection causes morbidity and mortality in cancer patients. However, studies describing this infection in patients with haematological malignancies are scarce. We sought to evaluate the clinical impact of RSV infection on this patient population. Methods: We reviewed the records of patients with haematological malignancies and RSV infections cared for at our institution between January 2000 and March 2013. Results: Of the 181 patients, 71 (39%) had AML, ALL or myelodysplastic syndrome, 12 (7%) had CML or CLL, 4 (2%) had Hodgkin lymphoma, 35 (19%) had non-Hodgkin lymphoma and 59 (33%) had multiple myeloma. Most patients [117 (65%)] presented with an upper respiratory tract infection (URTI) and 15 (13%) had a subsequent lower respiratory tract infection (LRTI). The overall LRTI rate was 44% and the 90 day mortality rate was 15%. Multivariable regression analysis showed that having both neutropenia and lymphocytopenia (adjusted OR = 7.17, 95% CI = 1.94-26.53, P < 0.01) and not receiving ribavirin-based therapy during RSV URTI (adjusted OR = 0.03; 95% CI = 0.01-0.11, P < 0.001) were independent risk factors for LRTI. Having both neutropenia and lymphocytopenia at RSV diagnosis was also a risk factor for death at 90 days after RSV diagnosis (adjusted OR = 4.32, 95% CI = 1.24-15.0, P = 0.021). Conclusions: Patients with haematological malignancies and RSV infections, especially those with immunodeficiency, may be at risk of LRTI and death; treatment with ribavirin during RSV URTI may prevent these outcomes.


Assuntos
Antivirais/uso terapêutico , Neoplasias Hematológicas/complicações , Leucopenia/complicações , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Ribavirina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/virologia , Humanos , Leucopenia/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções Respiratórias/mortalidade , Infecções Respiratórias/virologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
13.
Pediatrics ; 142(3)2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30093540

RESUMO

CONTEXT: Down syndrome (DS) is the most common chromosomal condition in live-born infants worldwide, and lower respiratory infection caused by respiratory syncytial virus (RSV) is a leading cause of hospital admissions. OBJECTIVE: To evaluate RSV-associated morbidity among children with DS compared with a population without DS. DATA SOURCES: Four electronic databases were searched. STUDY SELECTION: All cohorts or case-control studies of DS with an assessment of RSV infection and the associated morbidity or mortality were included without language restriction. DATA EXTRACTION: Two reviewers independently reviewed all studies. The primary outcomes were hospital admission and mortality. Secondary outcomes included length of hospital stay, oxygen requirement, ICU admission, need for respiratory support, and additional medication use. RESULTS: Twelve studies (n = 1 149 171) from 10 different countries met the inclusion criteria; 10 studies were cohort studies, 1 study was retrospective, and 1 study had both designs. DS was associated with a higher risk of hospitalization (odds ratio [OR]: 8.69; 95% confidence interval [CI]: 7.33-10.30; I2 = 11%) and mortality (OR: 9.4; 95% CI: 2.26-39.15; I2 = 38%) compared with what was seen in controls. Children with DS had an increased length of hospital stay (mean difference: 4.73 days; 95% CI: 2.12-7.33; I2 = 0%), oxygen requirement (OR: 6.53; 95% CI: 2.22-19.19; I2 = 0%), ICU admission (OR: 2.56; 95% CI: 1.17-5.59; I2 = 0%), need for mechanical ventilation (OR: 2.56; 95% CI: 1.17-5.59; I2 = 0%), and additional medication use (OR: 2.65 [95% CI: 1.38-5.08; I2 = 0%] for systemic corticosteroids and OR: 5.82 [95% CI: 2.66-12.69; I2 = 0%] for antibiotics) than controls. LIMITATIONS: DS subgroups with and without other additional risk factors were not reported in all of the included studies. CONCLUSIONS: Children with DS had a significantly higher risk of severe RSV infection than children without DS.


Assuntos
Síndrome de Down/complicações , Infecções por Vírus Respiratório Sincicial/epidemiologia , Adolescente , Criança , Pré-Escolar , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Oxigenoterapia/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/etiologia , Infecções por Vírus Respiratório Sincicial/mortalidade , Fatores de Risco
14.
Vaccine ; 36(31): 4693-4700, 2018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-29941327

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of infant mortality. Here, we estimated the potential impact of maternal vaccination against RSV on life-threatening RSV infection in infants. METHODS: We developed a mathematical model for maternal vaccine-induced antibody dynamics and used characteristics of a maternal RSV vaccine currently in phase 3 of clinical development. The model was applied to data from two cohorts of children younger than 12 months with RSV-related paediatric intensive care unit (PICU) admission in the United Kingdom (n = 370) and the Netherlands (n = 167), and a cohort of 211 children younger than 12 months with RSV-related in-hospital death from 20 countries worldwide. RESULTS: Our model predicted that, depending on vaccine efficiency, maternal vaccination at 30 weeks' gestational age could have prevented 62-75% of RSV-related PICU admissions in the United Kingdom and 76-87% in the Netherlands. For the global mortality cohort, the model predicted that maternal vaccination could have prevented 29-48% of RSV-related in-hospital deaths. Preterm children and children with comorbidities were predicted to benefit less than (healthy) term children. CONCLUSIONS: Maternal vaccination against RSV may substantially decrease life-threatening RSV infections in infants.


Assuntos
Anticorpos Antivirais/sangue , Formação de Anticorpos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinação/métodos , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Teóricos , Países Baixos/epidemiologia , Gravidez , Infecções por Vírus Respiratório Sincicial/mortalidade , Análise de Sobrevida , Reino Unido/epidemiologia
15.
Transpl Infect Dis ; 20(3): e12882, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29573141

RESUMO

BACKGROUND: Hematopoietic cell transplant (HCT) may be a risk factor for morbidity and mortality from respiratory syncytial virus (RSV). Previous studies have been limited by small sample size. We took a multicenter approach with the goal of better understanding the epidemiology, risk factors, treatment, morbidity, and mortality associated with RSV infections among children with HCT in the United States. METHODS: A retrospective, multicenter, cohort study of pediatric HCT recipients were diagnosed with RSV infection between January 2010 and December 2014. RESULTS: Of the 1522 HCT, 47 (3%) patients were diagnosed with RSV. Of those with RSV, 9 (19.1%) were admitted to the pediatric intensive care unit (PICU), 6 (12.8%) received invasive mechanical ventilation, and 1 died. Prophylactic palivizumab was uncommon. All who required critical care received ribavirin vs 7.3% of those who did not (P = .004). Cobacterial infections were found in 16 patients and were not associated with the need for critical care. We examined potential risk factors for severity of RSV disease. In those who received invasive ventilation, 100% had one of the preidentified risk factors. Half of those requiring mechanical ventilation were diagnosed with RSV during their conditioning for transplant as opposed to only 2.4% of those that did not require invasive mechanical ventilation (P = .005). CONCLUSIONS: In this multicenter cohort, RSV was not common in children following HCT. Few children infected with RSV required critical care and mortality was low. Those diagnosed with RSV during conditioning for transplant were at higher risk for invasive mechanical ventilation.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Adolescente , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Criança , Criança Hospitalizada/estatística & dados numéricos , Pré-Escolar , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Masculino , Palivizumab/uso terapêutico , Respiração Artificial/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/etiologia , Infecções por Vírus Respiratório Sincicial/mortalidade , Estudos Retrospectivos , Ribavirina/uso terapêutico , Fatores de Risco , Estados Unidos/epidemiologia
16.
Antivir Ther ; 23(6): 523-527, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29424696

RESUMO

BACKGROUND: Community respiratory viruses (CRVs) are associated with upper respiratory viral infections (URI), pneumonia or life-threatening respiratory disease in patients with allogeneic haematopoietic stem cell transplantation (allo-HSCT). Our aim is to demonstrate our URI experience related to CRVs after allo-HSCT. METHODS: From January 2013 to November 2015, 39 post allo-HSCT patients with acute URI symptoms were included in the study. We evaluated CRVs by multiplex PCR from nasopharyngeal wash and throat swabs. RESULTS: The median age of the patients was 39 (range 20-67 years). A total of 25 patients (64%) had viral panel positivity at a median 140 days post-transplant (range 3-617 days). The most common agents detected were respiratory syncytial virus (32%) and parainfluenza (32%). The patients with viral panel positivity had significantly lower lymphocyte count (1.05×109/l versus 3.09×109/l; P=0.013). During follow-up, 20 patients (80%) were diagnosed with pneumonia. Patients with concurrent bacterial or fungal infections were more likely to have pneumonia (100% versus 68%; P=0.023). 10 patients (40%) died due to pneumonia and related complications. Lower lymphocyte counts and higher C-reactive protein levels at the time of viral panel positivity were risk factors for mortality (1.5×109/l versus 0.39×109/l, P=0.007; 74.2 versus 199.7, P=0.006). CONCLUSIONS: The viral panel was positive in 64% of patients with acute URI symptoms. Lower lymphocyte count was detected in CRV-positive patients. The onset of concomitant bacterial or fungal infections increased the risk of lower respiratory infection disease. Indeed, prospective studies should be designed for risks and outcomes of CRVs in allo-HSCT recipients.


Assuntos
Neoplasias Hematológicas/virologia , Infecções por Paramyxoviridae/virologia , Pneumonia Viral/virologia , Infecções por Vírus Respiratório Sincicial/virologia , Infecções Respiratórias/virologia , Adulto , Idoso , Proteína C-Reativa/metabolismo , Feminino , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Paramyxoviridae/imunologia , Paramyxoviridae/isolamento & purificação , Infecções por Paramyxoviridae/imunologia , Infecções por Paramyxoviridae/mortalidade , Infecções por Paramyxoviridae/terapia , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções por Vírus Respiratório Sincicial/terapia , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções Respiratórias/imunologia , Infecções Respiratórias/mortalidade , Infecções Respiratórias/terapia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Homólogo
17.
Pediatr Pulmonol ; 53(5): 664-667, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29461021

RESUMO

Respiratory syncytial virus (RSV), responsible for more than three million yearly hospitalizations and up to 118 000 deaths in children under 5 years, is the leading pulmonary cause of death for this age group that lacks a licensed vaccine. Ninety-nine percent of deaths due to the virus occur in developing countries. In-hospital RSV fatalities affect previously healthy term infants in association with bacterial sepsis, clinically significant pneumothoraxes and, to a lesser extent, comorbid conditions. Community deaths affect low-income children from socially vulnerable families and appear to be as frequent as inpatient fatalities. In industrialized countries, RSV deaths occur almost exclusively in children with premorbid conditions. In a sense, RSV is an "opportunistic" killer. It needs a synergistic premorbid, medical practice-related, infectious, or social co-factor to cause a fatal outcome. But while the complex problems associated with these co-factors await solutions, candidate vaccines, long-lived monoclonal antibodies and antivirals against RSV are under clinical evaluation. It seems reasonable to predict that the landscape of RSV infections will look different in the next decade.


Assuntos
Infecções por Vírus Respiratório Sincicial/mortalidade , Países Desenvolvidos , Países em Desenvolvimento , Mortalidade Hospitalar , Humanos , Vírus Sincicial Respiratório Humano
18.
Hum Vaccin Immunother ; 14(1): 234-244, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29194014

RESUMO

With maternal and infant vaccines against respiratory syncytial virus (RSV) in development, it is timely to consider how the deployment of these vaccines might vary according to local RSV disease seasonality. In temperate regions RSV infection is predictably limited to a period of 3 to 5 months, while in tropical regions disease seasonality is often both more variable and more prolonged. Accordingly, in tropical regions a year-round immunisation schedule for both maternal and infant immunisation might be appropriate. In contrast, in temperate regions the benefit of year-round maternal immunisation would be heavily dependent on the duration of protection this provided, potentially necessitating a strategy directed at children due to be born in the months immediately prior to the RSV season. This review will consider the impact of seasonality on maternal and infant immunisation strategies against RSV, and the potential of an alternative approach of passive immunisation for all infants immediately prior to the RSV season.


Assuntos
Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/uso terapêutico , Vírus Sincicial Respiratório Humano/imunologia , Estações do Ano , Vacinação/métodos , Feminino , Carga Global da Doença , Humanos , Lactente , Recém-Nascido , Mães , Floresta Úmida , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/mortalidade , Fatores de Tempo , Clima Tropical
19.
Clin Infect Dis ; 66(1): 95-103, 2018 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-29040527

RESUMO

Background: Estimates of influenza- and respiratory syncytial virus (RSV)-associated mortality burden are important to guide policy for control. Data are limited on the contribution of out-of-hospital deaths to this mortality. Methods: We modeled excess mortality attributable to influenza and RSV infection by applying regression models to weekly deaths from national vital statistics from 2009 through 2013, using influenza and RSV laboratory surveillance data as covariates. We fitted separate models for in- and out-of-hospital deaths. Results: There were 509791 average annual deaths in South Africa, of which 44% (95% confidence interval [CI] 43%-45%) occurred out-of-hospital. Seasonal influenza and RSV all-cause mortality rates were 23.0 (95% CI 11.0-30.6) and 13.2 (95% CI 6.4-33.8) per 100000 population annually (2.3% [95%CI 2.3%-2.4%] and 1.3% [95% CI 1.2%-1.4%] of all deaths respectively). The peak mortality rate was in individuals aged ≥75 years (386.0; 95% CI 176.5-466.3) for influenza and in infants (143.4; 95% CI 0-194.8) for RSV. Overall, 63% (95% CI 62%--65%) of seasonal influenza and 48% (95% CI 47%-49%) of RSV-associated deaths occurred out-of-hospital. Among children aged <5 years, RSV-associated deaths were more likely to occur in-hospital, whereas influenza-associated deaths were more likely to occur out-of-hospital. The mortality rate was 6.7 (95% CI 6.4-33.8) in the first influenza A(H1N1)pdm09 wave in 2009 and 20.9 (95% CI 6.4-33.8) in the second wave in 2011, with 30% (95% CI 29%-32%) of A(H1N1)pdm09-associated deaths in 2009 occurring out-of-hospital. Discussion: More than 45% of seasonal influenza- and RSV-associated deaths occur out-of-hospital in South Africa. These data suggest that hospital-based studies may substantially underestimate mortality burden.


Assuntos
Influenza Humana/mortalidade , Infecções por Vírus Respiratório Sincicial/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fatores de Risco , África do Sul/epidemiologia , Análise de Sobrevida , Adulto Jovem
20.
BMC Infect Dis ; 17(1): 785, 2017 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-29262784

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) infection constitutes a substantial disease burden in the general population. However, the risk of death for RSV infection has been rarely evaluated with confounders or comorbidities adjusted. We aimed to evaluate whether RSV infection is associated with higher mortality than seasonal influenza after adjusting for confounders and comorbidities and the effect of oseltamivir on the mortality in patients with influenza infection. METHODS: A retrospective cohort study was conducted on adult (≥18 years) patients admitted to the emergency department and ward of a university teaching hospital for suspected viral infection during 2013-2015 (N = 3743). RSV infection was diagnosed by multiplex PCR (N = 87). Adults hospitalized for seasonal influenza during the study period were enrolled as a comparison group (n = 312). The main outcome was 20-day all-cause mortality.We used Cox proportional hazard regression analyses to calculate the relative risk of death. RESULTS: Adult patients were less likely to be diagnosed with RSV than with influenza (2.3 vs 8.3%, respectively), were older and more likely to be diagnosed with pneumonia, chronic obstructive pulmonary disease, hypoxemia, and bacterial co-infection. In patients with RSV infection, the 20-day all-cause mortality was higher than that for influenza, (18.4 vs 6.7%, respectively). RSV infection showed significantly higher risk of death compared to the seasonal influenza group, with hazard ratio, 2.32 (95% CI, 1.17-4.58). Oseltamivir had no significant effect on mortality in patients with influenza. CONCLUSIONS: RSV infection was significantly associated with a higher risk of death than seasonal influenza, adjusted for potential confounders and comorbidities.


Assuntos
Influenza Humana/mortalidade , Infecções por Vírus Respiratório Sincicial/mortalidade , Adulto , Hospitais de Ensino , Humanos , Estudos Retrospectivos
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