Benefit and harm from immunity to respiratory syncytial virus

RSV Respiratory syncytial virus (RSV) is the major cause of bronchiolitis, itself the commonest single cause of hospitalization during infancy. The WHO estimates that RSV infects 34 million children under 5 years of age every year, accounts for 22% of all acute lower respiratory tract infections (RTIs), and results in 3.4 million hospital admissions and 160,000 deaths, with 99% of RSV-related deaths occurring in developing countries. In older children and in adults, RSV is associated with acute exacerbations of both asthma and chronic obstructive pulmonary disease (COPD), and has been implicated in adult hospitalization for pneumonia and exacerbations of congestive cardiac failure. The age-specific mortality rate of RSV disease in those over 75 years of age appears to exceed that in children aged 0–4 years by about 100-fold. Immunosuppressed people, especially those receiving allogeneic stem cell transplants, may experience severe disease with high mortality.

Treatment of RSV with antiviral drugs is currently of limited efficacy and toxicity. Although there are drugs in preclinical development, there is still no vaccine and the previous formalin-inactivated vaccine produced actually enhanced disease. The monoclonal antibody palivizumab is effective for prevention of infection, but is costly and must be given by monthly injection, limiting its use to only the most high-risk babies. As many of those admitted with RSV infection are ineligible for prophylaxis, palivizumab is unlikely to substantially reduce admissions for bronchiolitis.

 

Benefit and harm from immunity to respiratory syncytial virus: implications for treatment. Curr Opin Infect Dis. 18 Oct 2012
Human respiratory syncytial virus (RSV) infection is a major cause of morbidity in children and of morbidity and mortality in elderly or immunocompromised adults. Given prophylactically, antibody can protect against infection, but natural levels are poorly protective. Vaccination may enhance disease, and there is no well tolerated and effective vaccine or antiviral treatment. Despite over 50 years of research, therapy remains nonspecific and supportive. Experimental human challenge in adult volunteers is beginning to elucidate the dynamics of viral shedding and causes of disease, but investigations of naturally infected children remain logistically challenging. RSV was known to bind several surface ligands, but the recent demonstration that nucleolin acts as a receptor for the RSV fusion protein was unexpected. Recent studies increasingly emphasize the relevance of innate immune responses and the dysregulation of inflammation as key factors in causing the pathological effects of infection. Studies in both human infants and mice indicate that interleukin-17 plays a role in some forms of RSV disease and regulatory T cells may be important in controlling inflammation. Improved understanding of the human immune response to RSV infection continues to be needed in order to accelerate the development of vaccines and new treatments for bronchiolitis.

 

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