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      Risk Factors for Severe Respiratory Syncytial Virus Lower Respiratory Tract Infection

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          Abstract

          RSV infection is a leading cause of lower respiratory tract infection, especially in High-risk infants with a history of prematurity, bronchopulmonary dysplasia (BPD), congenital heart disease (CHD), neuromusculair impairment, immunodeficiency, and Down syndrome. Host related risk factors that have been identified to be associated with severe RSV related lower respiratory tract infection include young age below 6 months at the beginning of RSV season, multiple birth, male sex, low socioeconomic status and parental education, crowded living conditions, young siblings, maternal smoking and indoor smoke pollution, malnutrition/small for gestational age, family history of atopy or asthma, low cord serum RSV antibody titers, and living at altitude.

          Risk factors increasing the risk of acquisition of RSV have been identified to be birth before and/or during RSV season, day care attendance, presence of older siblings in school or day-care, and lack of breast feeding. Some of these risk factors are discussed controversially and some of them are found continuously throughout the literature.

          Given the high cost of RSV prophylaxis, especially for the large population of late preterm infants, algorithms and risk score systems have been published that could identify high-risk infants for treatment with palivizumab out of this gestational age group. Several models reported on an average sensitivity and specificity of 70 percent and, thus, are helpful to identify infants at high risk for severe RSV infection and need for prophylaxis with palivizumab.

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          Most cited references64

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          Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease

          To evaluate the safety, tolerance, and efficacy of palivizumab in children with hemodynamically significant congenital heart disease (CHD). A randomized, double-blind, placebo-controlled trial included 1287 children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular injections of 15 mg/kg palivizumab or placebo. Children were followed for 150 days. The primary efficacy end point was antigen-confirmed respiratory syncytial virus (RSV) hospitalization. Palivizumab recipients had a 45% relative reduction in RSV hospitalizations (P=.003), a 56% reduction in total days of RSV hospitalization per 100 children (P=.003), and a 73% reduction in total RSV hospital days with increased supplemental oxygen per 100 children (P=.014). Adverse events were similar in the treatment groups; no child had drug discontinued for a related adverse event. Serious adverse events occurred in 55.4% of palivizumab recipients and 63.1% of placebo recipients (P<.005); none were related to palivizumab. Twenty-one children (3.3%) in the palivizumab group and 27 (4.2%) in the placebo group died; no deaths were attributed to palivizumab. The rates of cardiac surgeries performed earlier than planned were similar in the treatment groups. Monthly palivizumab (15 mg/kg IM) was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in young children with hemodynamically significant CHD.
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            Lack of antibody affinity maturation due to poor Toll stimulation led to enhanced RSV disease

            Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants. A formalin-inactivated RSV vaccine was used to immunize children in 1966 and elicited non-protective, pathogenic antibody. Two immunized infants died and 80% were hospitalized after subsequent RSV exposure. No vaccine was licensed since. A widely accepted hypothesis attributed vaccine failure to formalin disruption of protective antigens. Instead, we show that lack of protection was not due to alterations caused by formalin, but to low antibody avidity for protective epitopes. Lack of antibody affinity maturation followed poor Toll-like receptor stimulation. This study explains why the inactivated RSV vaccine failed to protect and consequently led to severe disease, hampering vaccine development for forty-two years. Also, it suggests that inactivated RSV vaccines may be rendered safe and effective by inclusion of TLR-agonists in their formulation. In addition, it identifies affinity maturation as a critical factor for the safe immunization of infants.
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              Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level.

              The risk for hospitalization with respiratory syncytial virus infection during the first year of life was about five per 1,000 live births per year for infants born to low-income families in Houston from 1975 to 1979. The risk varied depending upon the intensity of the epidemic for a given season, the month of birth of the infant, and the level of passively acquired maternal antibody at the time of birth. Over 80% of the children hospitalized were less than 6 months of age; thus, most were born during the six months preceding the peak of RS virus activity. The neutralizing antibody titers in cord sera of 68 infants with culture-proven infections before 6 months of age were significantly lower than those of 575 randomly selected cord samples of infants born during the same period. The level of antibody at the time of birth was directly correlated with age at the time of infection. In addition, infants with more severe illnesses had lower levels of antibody in serum collected near onset of illness than did infants with milder illnesses. These observations demonstrate protection against RS infection in early infancy that is correlated with the level of maternal antibody, but it is not known if this protection is mediated directly by the passively acquired antibody or by some other mechanism.
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                Author and article information

                Journal
                Open Microbiol J
                TOMICROJ
                The Open Microbiology Journal
                Bentham Open
                1874-2858
                30 December 2011
                2011
                : 5
                : 144-154
                Affiliations
                [1 ]Medical University Graz, Austria
                [2 ]University of Colorado, Denver, and Children’s Hospital Colorado, USA
                [3 ]University of Padjadjaran, Bandung, Indonesia
                Author notes
                [* ]Address correspondence to this author at the Division of Neonatology, Pediatric Department Medical University hospital Graz Auenbruggerplatz 30, A- 8036 Graz, Austria; Tel: 0043 316 385 81134; Fax: 0043 316 385 2678; E-mail: bernhard.resch@ 123456medunigraz.at
                Article
                TOMICROJ-5-144
                10.2174/1874285801105010144
                3258650
                22262987
                089c8290-6b22-47fa-a59f-6e22f823a716
                © Sommer et al.; Licensee Bentham Open.

                This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 28 June 2011
                : 12 October 2011
                : 27 October 2011
                Categories
                Article
                Suppl 2

                Microbiology & Virology
                cellular immunity.,iga antibodies,syncytial virus,immune complex reaction,rsv disease

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