Respiratory syncytial virus morbidity, premorbid factors, seasonality, and implications for prophylaxis

Hon, Kam Lun; Leung, Ting Fan; Cheng, Wing Yee; Ko, Natalie Man Wai; Tang, Wing Ki; Wong, Win Win; Yeung, Wan Hang Prisca; Chan, Paul K.S.

doi:10.1016/j.jcrc.2011.12.001

Cited by 43 publications

(41 citation statements)

References 21 publications

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“…A infecção pelo VSR parece ser significativamente mais grave se esse vírus comparada a infecções por outros vírus respiratórios 8,9,[19][20][21][22] . Os resultados do nosso estudo são consistentes com essa evidência.…”

Section: Discussionunclassified

Hospitalization due to respiratory syncytial virus infection in patients under 2 years of age with hemodynamically significant congenital heart disease

Andres¹,

Bauer²,

Rodríguez³

et al. 2012

J Pediatr (Rio J)

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Objective: To describe hospitalization rates, burden of disease, and associated risk factors of acute respiratory infections (ARI), particularly those caused by respiratory syncytial virus (RSV) and non-RSV-ARI, in a cohort of patients under 2 years of age with congenital heart disease (CHD). Methods:A prospective, observational cohort study was conducted with CHD patients discharged from the neonatal unit and followed up at a referral center. Demographic variables, type of CHD, and medical needs were recorded. Study primary outcome was hospitalization for ARI (overall, due to RSV, and due to other causes). Secondary outcome was burden of disease in hospitalized patients. Incidence rates of hospitalization were calculated for overall ARI and RSV-ARI. Incidence densities were additionally calculated. Results:Seventy-one patients with birth weight 3,043±720 g (mean ± SD) were included; 74% required surgery and 8.4% died of CHD during the study. Overall, 22/71 patients were hospitalized due to ARI (31%; 95%CI 20-43), 15 of them RSV-associated (21%; 95% CI 12-32), and there were 1.35 episodes of hospitalization for ARI/1,000 days of follow-up (0.92 episodes of hospitalization for RSV-ARI/1,000 days). Forty per cent of patients with ARI due to RSV needed admission to pediatric ICU and 30% required mechanical ventilation vs. none in non-RSV-ARI. Conclusions:In the studied population, ARI hospitalization was common, and RSV was its most frequent cause. Disease burden associated with RSV-ARI was considerable, although no patient died from ARI. Except younger age, no other biological or social risk factors were found associated with RSV-ARI hospitalization. J Pediatr (Rio J). 2012;88(3):246-52:Respiratory syncytial virus, respiratory tract infections, heart disease, infants. ResumoObjetivo: Descrever taxas de hospitalização, carga de doença e fatores de risco associados a infecções agudas respiratórias (IRAs), especialmente aquelas causadas pelo vírus sincicial respiratório (VSR) e as causadas por outros vírus, em uma coorte de pacientes menores de 2 anos com doença cardíaca congênita (DCC).Métodos: Um estudo de coorte observacional e prospectivo foi realizado com pacientes com DCC que receberam alta da unidade neonatal e foram acompanhados em um centro de referência. Foram registradas variáveis demográficas, tipo de DCC e necessidades médicas. O desfecho primário foi a internação por IRA (em valores totais e referentes apenas à infecção pelo VSR e por outras causas), e o secundário a carga da doença em pacientes hospitalizados. As taxas de internação foram calculadas considerando os valores totais de IRA e também os referentes apenas à IRA pelo VSR. Também foi calculada a densidade de incidência. Resultados:Foram incluídos 71 pacientes com peso de nascimento de 3.043±720 g (média ± DP); 74% necessitaram de cirurgia e 8,4% faleceram em decorrência da DCC. No total, 22/71 pacientes foram hospitalizados por IRA (31%; IC95% 20-43), 15 deles pelo VSR (21%; IC95% 12-32), e ocorreram 1,35 episódios de internação por IR...

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Section: Discussionunclassified

Hospitalization due to respiratory syncytial virus infection in patients under 2 years of age with hemodynamically significant congenital heart disease

Andres¹,

Bauer²,

Rodríguez³

et al. 2012

J Pediatr (Rio J)

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“…Although the antiviral drugs palivizumab and ribavirin have virucidal activity against RSV in vivo, there are no fully satisfactory therapeutic regimens or vaccines (4-6). It is estimated that 3% of RSV cases in the United States and 10% of cases worldwide result in hospitalization; the reported number of new cases of lower respiratory infection due to RSV in children under 5 years of age in 2005 was 33.8 million (7,8). Thus, there is a need for new therapies for RSV infection.…”

Section: Clinical Relevancementioning

confidence: 99%

Increased Concentration of Iodide in Airway Secretions Is Associated with Reduced Respiratory Syncytial Virus Disease Severity

Derscheid

Geelen

Berkebile³

et al. 2014

Am J Respir Cell Mol Biol

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Recent studies have revealed that the human and nonrodent mammalian airway mucosa contains an oxidative host defense system. This three-component system consists of the hydrogen peroxide (H 2 O 2 )-producing enzymes dual oxidase (Duox)1 and Duox2, thiocyanate (SCN 2 ), and secreted lactoperoxidase (LPO Clinical RelevanceThis study demonstrates that enhancement of dual oxidase/ lactoperoxidase oxidative responses by potassium iodide administration reduces respiratory syncytial virus disease severity in a lamb model that has much similarity to disease condition in human infants. The work is readily translational.Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection in infants and young children and is a leading cause of infantile bronchiolitis worldwide (1, 2). In industrialized countries, human RSV (hRSV) accounts for up to 70% of hospitalized bronchiolitis cases (1-3). Although the antiviral drugs palivizumab and ribavirin have virucidal activity against RSV in vivo, there are no fully satisfactory therapeutic regimens or vaccines (4-6). It is estimated that 3% of RSV cases in the United States and 10% of cases worldwide result in hospitalization; the reported number of new cases of lower respiratory infection due to RSV in children under 5 years of age in 2005 was 33.8 million (7,8). Thus, there is a need for new therapies for RSV infection.The host defense activity of the airway epithelium is critical for the continuous inactivation and removal of inhaled microbes from the respiratory tract. Although the role of mucociliary clearance and epithelial host defense proteins and peptidesin lung immunity is well established, the recognition that airway epithelial cells express an oxidative

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“…The mice were infected intranasally with 10 6 TCID 50 for all the viruses (study 1) or 1 ϫ 10 6 TCID 50 for the wt viruses increased to 2.0 ϫ 10 6 TCID 50 for the CX4C viruses (studies 2 and 3). The anti-RSV G MAb 131-2G [F(ab=) 2 form]-treated mice were given 300 g of the MAb intraperitoneally 2 days before infection. The weight measurements, BAL fluid cell collection, and lung tissue harvesting were done on days 3, 5, and 8 p.i.…”

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confidence: 99%

Mutating the CX3C Motif in the G Protein Should Make a Live Respiratory Syncytial Virus Vaccine Safer and More Effective

Boyoglu-Barnum

Todd

Meng

et al. 2017

J Virol

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Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Through a CX3C chemokine motif ( 182 CWAIC 186 ) in the G protein, RSV binds to the corresponding chemokine receptor, CX3CR1. Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A 186 , within the CX3C motif, mutating it to CX4C ( 182 CWAIAC 187 ), which is known to block binding to CX3CR1, might decrease disease. We studied the effect of the CX4C mutation in two strains of RSV (A2 and r19F) in a mouse challenge model. We included RSV r19F because it induces mucus production and airway resistance, two manifestations of RSV infection in humans, in mice. Compared to wild-type (wt) virus, mice infected with CX4C had a 0.7 to 1.2 log 10 -fold lower virus titer in the lung at 5 days postinfection (p.i.) and had markedly reduced weight loss, pulmonary inflammatory cell infiltration, mucus production, and airway resistance after challenge. This decrease in disease was not dependent on decrease in virus replication but did correspond to a decrease in pulmonary Th2 and inflammatory cytokines. Mice infected with CX4C viruses also had higher antibody titers and a Th1-biased T cell memory response at 75 days p.i. These results suggest that the CX4C mutation in the G protein could improve the safety and efficacy of a live attenuated RSV vaccine.IMPORTANCE RSV binds to the corresponding chemokine receptor, CX3CR1, through a CX3C chemokine motif ( 182 CWAIC 186 ) in the G protein. RSV binding to CX3CR1 contributes to disease pathogenesis; therefore, we investigated whether a mutation in the CX3C motif by insertion of an alanine, A 186 , within the CX3C motif, mutating it to CX4C ( 182 CWAIAC 187 ), known to block binding to CX3CR1, might decrease disease. The effect of this mutation and treatment with the F(ab=) 2 form of the anti-RSV G 131-2G monoclonal antibody (MAb) show that mutating the CX3C motif to CX4C blocks much of the disease and immune modulation associated with the G protein and should improve the safety and efficacy of a live attenuated RSV vaccine.

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Respiratory syncytial virus morbidity, premorbid factors, seasonality, and implications for prophylaxis

Cited by 43 publications

References 21 publications

Hospitalization due to respiratory syncytial virus infection in patients under 2 years of age with hemodynamically significant congenital heart disease

Hospitalization due to respiratory syncytial virus infection in patients under 2 years of age with hemodynamically significant congenital heart disease

Increased Concentration of Iodide in Airway Secretions Is Associated with Reduced Respiratory Syncytial Virus Disease Severity

Mutating the CX3C Motif in the G Protein Should Make a Live Respiratory Syncytial Virus Vaccine Safer and More Effective

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