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      An evaluation of the emerging interventions against Respiratory Syncytial Virus (RSV)-associated acute lower respiratory infections in children

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          Abstract

          Background

          Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization.

          Methods

          We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against RSV relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.

          Results

          In the case of candidate vaccines for active immunization of infants against RSV, the experts expressed very low levels of optimism for low product cost, affordability and low cost of development; moderate levels of optimism regarding the criteria of answerability, likelihood of efficacy, deliverability, sustainability and acceptance to end users for the interventions; and high levels of optimism regarding impact on equity and acceptance to health workers. While considering the candidate vaccines targeting pregnant women, the panel expressed low levels of optimism for low product cost, affordability, answerability and low development cost; moderate levels of optimism for likelihood of efficacy, deliverability, sustainability and impact on equity; high levels of optimism regarding acceptance to end users and health workers. The group also evaluated immunoprophylaxis against RSV using monoclonal antibodies and expressed no optimism towards low product cost; very low levels of optimism regarding deliverability, affordability, sustainability, low implementation cost and impact on equity; moderate levels of optimism against the criteria of answerability, likelihood of efficacy, acceptance to end-users and health workers; and high levels of optimism regarding low development cost. They felt that either of these vaccines would have a high impact on reducing burden of childhood ALRI due to RSV and reduce the overall childhood ALRI burden by a maximum of about 10%.

          Conclusion

          Although monoclonal antibodies have proven to be effective in providing protection to high-risk infants, their introduction in resource poor settings might be limited by high cost associated with them. Candidate vaccines for active immunization of infants against RSV hold greatest promise. Introduction of a low cost vaccine against RSV would reduce the inequitable distribution of burden due to childhood ALRI and will most likely have a high impact on morbidity and mortality due to severe ALRI.

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          Most cited references61

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          Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years.

          The relation between lower respiratory tract illnesses in early life caused by the respiratory syncytial virus (RSV) and the subsequent development of wheezing and atopy in childhood is not well understood. We studied this relation in children who had lower respiratory tract illnesses that occurred before 3 years of age. Children were enrolled at birth and cases of lower respiratory tract illness were ascertained by a physician. Viral tests were done for specimens collected at the time of the illness. Children were classified into five groups according to type and cause of lower respiratory tract illness. Children were then followed prospectively up to age 13, and we measured frequency of wheezing, pulmonary function, and atopic status (allergy skin-prick tests, serum IgE concentrations). RSV lower respiratory tract illnesses were associated with an increased risk of infrequent wheeze (odds ratio 3.2 [95% CI 2.0-5.0], p < 0.001), and an increased risk of frequent wheeze (4.3 [2.2-8.7], p < or = 0.001) by age 6. Risk decreased markedly with age and was not significant by age 13. There was no association between RSV lower respiratory tract illnesses and subsequent atopic status. RSV lower respiratory tract illnesses were associated with significantly lower measurements of forced expiratory volume (2.11 [2.05-2.15], p < or = 0.001) when compared with those of children with no lower respiratory tract illnesses, but there was no difference in forced expiratory volume after inhalation of salbutamol. RSV lower respiratory tract illnesses in early childhood are an independent risk factor for the subsequent development of wheezing up to age 11 years but not at age 13. This association is not caused by an increased risk of allergic sensitisation.
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            Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13.

            We have prospectively studied wheezing disorder and allergy in 47 children hospitalized with respiratory syncytial virus (RSV) bronchiolitis in infancy and 93 matched control subjects. Subjects with at least three episodes of wheezing were defined as recurrent wheezers and as having asthma if the episodes were doctor verified. Here we report the outcome at age 13 years in 46/47 children with RSV and 92/93 control subjects. Wheezing disorder and clinical allergy were estimated using a questionnaire. Skin prick tests were performed and serum IgE antibodies measured. Spirometry was undertaken at rest, after dry air challenge, and after beta2-agonist inhalation. The occurrence of symptoms over the previous 12 months was significantly higher in the RSV group than among the control subjects, 43% versus 8% for asthma/recurrent wheezing and 39% versus 15% for allergic rhinoconjunctivitis. Sensitization to common inhaled allergens was more frequent in the RSV group than in the control subjects, judged by skin prick tests (50% versus 28%; p = 0.022), or by serum IgE antibodies (45% versus 26%; p = 0.038). Compared with the control subjects, the RSV group showed mild airway obstruction both at rest and after bronchodilation, and had slightly more reactive airways. RSV bronchiolitis in infancy severe enough to cause hospitalization is a risk factor for allergic asthma in early adolescence.
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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
                BMC Public Health
                BMC Public Health
                BioMed Central
                1471-2458
                2011
                13 April 2011
                : 11
                : Suppl 3
                : S30
                Affiliations
                [1 ]Centre for Population Health Sciences, Global Health Academy, The University of Edinburgh, UK
                [2 ]Public Health Foundation of India, New Delhi, India
                [3 ]International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh
                [4 ]University of Colorado Denver and The Children’s Hospital, Denver, CO, USA
                [5 ]Division of Infectious Disease and International Health, Dartmouth Medical School, Lebanon, NH, USA
                [6 ]Croatian Centre for Global Health, University of Split Medical School, Croatia
                Article
                1471-2458-11-S3-S30
                10.1186/1471-2458-11-S3-S30
                3231904
                21501449
                b36c0ac6-a80b-438c-a559-fca49fd4543d
                Copyright ©2011 Nair et al; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Public health
                Public health

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