Major respiratory viruses of childhood: Illness and prevention

Respiratory illnesses are a major cause of morbidity and mortality worldwide, and respiratory viruses are a major contributor to the burden of respiratory illnesses. In industrialized countries, influenza viruses, respiratory syncytial virus and human rhinoviruses are the major respiratory viral agents causing significant morbidity and mortality. Each of these major pathogens has a well-defined epidemiology, impact overlapping age-groups and is often associated with unique constellation of symptoms and signs.

Influenza virus infection often causes fever, cough and fatigue, otherwise known as influenza-like-illness. Annual influenza outbreaks normally occur in the winter months and are associated with peaks in cardiorespiratory-related hospitalization and deaths among all age groups.

Viral co-infection

Respiratory syncytial virus (RSV) causes annual outbreaks in the fall and winter months. It is the major cause of bronchiolitis and hospitalization in children younger than 1 year of age. Human rhinovirus (hRV) is detected year-round. It is perhaps the most ubiquitous of all respiratory viral pathogens. Although hRV is associated with the common cold, in recent years it has been strongly linked to bronchiolitis and acute exacerbations of chronic respiratory disease such as asthma, chronic obstructive airway disease and cystic fibrosis.

Other respiratory viruses such as adenovirus, human metapneumovirus, parainfluenza viruses, coronaviruses, enteroviruses, human bocavirus and human respiratory polyomaviruses contribute to the overall societal impact, both in disability-adjusted life year (DALY) and financial cost. It is important to note that most human respiratory viruses circulate during the fall, winter and spring months and that coinfection with two or more respiratory viral pathogens occurs frequently.

Improvement in viral diagnostics with use of new molecular diagnostic platforms such as the real-time polymerase chain reaction will improve our understanding of the full spectrum of diseases associated with respiratory viral infections and their links to diseases such as asthma, chronic lung disease and cardiorespiratory-related deaths.

A common thread

Common features related to most of the human respiratory viral pathogens include: 1) infection rates are highest in children; 2) recurrent infections occur throughout life and are milder except in elderly adults and those with comorbid conditions; 3) illness burden and disease severity is greatest at the extremes of life — the young and the elderly; 4) virus-specific serum neutralizing antibody (maternally derived, passively administered or infection-induced) protects against severe lower respiratory tract illness; and 5) comorbid conditions such as chronic lung disease, heart disease and immunodeficiency increase the likelihood of severe respiratory disease. Increasing age in children normally reduces the risk for severe respiratory disease related to viral infections.

The exception occurs in children with chronic lung disease, particularly children with cystic fibrosis who experience frequent bouts of viral respiratory exacerbations that lead to long-term deterioration in lung function parameters.

Currently, we have limited capabilities in preventing respiratory virus infections. The approved products are vaccines against influenza infection, antiviral drugs against influenza and RSV, and a humanized monoclonal antibody, palivizumab (Synagis, MedImmune), administered prophylactically during the RSV season for the prevention of RSV-related hospitalization. In general, influenza vaccines are underutilized in all age groups, and underutilization is more pronounced in racial and ethnic minorities. Antiviral drugs against influenza are often not considered because a diagnosis is not made, the person presents too late in the disease for treatment to be effective or the physician decides treatment is not necessary.

The neuraminidase inhibitors — oseltamivir (Tamiflu, Genentech) and zanamivir (Relenza, GlaxoSmithKline) A and B viruses, whereas the adamantanes — amantadine and rimantadine — are currently not used because of their very narrow antiviral activity. Unfortunately, all too often, antibiotics are prescribed unnecessarily to children presenting with these respiratory viral infections.

Ribavirin is the only antiviral agent against RSV and its use is restricted primarily to significantly immunocompromised patients. Palivizumab is recommended for a highly select group of infants and young children with medical conditions that increase the risk for severe RSV disease, such as prematurity, chronic lung disease of prematurity and congenital heart disease. Palivizumab is used for prevention and not treatment of RSV disease. It does not prevent RSV infection but does significantly reduce the likelihood of RSV-related hospitalization. Most children hospitalized with RSV do not fit the current recommendation for palivizumab prophylaxis.

Influenza vaccine is the only approved vaccine for the prevention of a respiratory viral infection. In the United States, the current influenza vaccine recommendation by the Advisory Committee on Immunization Practices of the CDC is annual influenza vaccination for all patients aged 6 months and older. There are currently two major types of influenza vaccine that are FDA approved: the live-attenuated influenza vaccine and the trivalent inactivated vaccine. LAIV is approved for patients aged 2 years to younger than 50 years who are in good health, and TIV is approved for all patients aged 6 months and older. It is important to note that there are a number of vaccine manufactures that produce TIV, and most are not approved for children aged younger than 4 years.

LAIV and TIV are safe and efficacious, with LAIV having superior efficacy compared with TIV in children. The efficacy of LAIV and TIV vary from year to year and, in general, ranges from 60% to 90%. This is partially dependent on how well the vaccine antigens antigenically match the circulating viruses and on the immunocompetence of the host.

Influenza vaccination strategies

There are at least three major vaccination strategies to reduce influenza infection and its complications. Vaccination of the individual has a direct benefit by providing immunologic protection. A second strategy is maternal immunization. Vaccination of pregnant women has a direct benefit to pregnant women and an indirect benefit to the newborn infant. Infants born to mothers who are vaccinated during pregnancy have a significantly lower risk for influenza infection during their first 6 months of life. Recall that the influenza vaccine is not approved for use in infants aged younger than 6 months.

Maternal vaccination against influenza, unfortunately, has been a neglected practice, accounting for the lowest vaccination coverage of all target populations. Another strategy is vaccination of select groups that spread the virus efficiently to others such as school-age children, those who care for or live with those at high risk, and health care workers. This strategy has a direct benefit to the vaccinated person and an indirect benefit to his contacts. Vaccination of school-age children has been associated with indirect protection against influenza-related complication in unvaccinated household members and the community, whereas vaccination of health care workers has been associated with decrease morbidity and mortality in their patients.

Surprisingly, health care workers have suboptimal coverage. Mandatory influenza vaccination programs, although controversial, appear to be the most effective way to significantly improve influenza vaccination coverage among health care workers.

For more information:

• CDC. MMWR. 2011;60(33):1128-1132.
• Fiore AE. MMWR Recomm Rep. 2010;59(RR-8):1-62.
• Hall CB. N Engl J Med. 2009;360:588-598.
• Lee WM. PLoS One. 2007:2:e966.
• Miron D. Pediatr Infect Dis J. 2010;29:e7-e10.
• Poehling KA. N Engl J Med. 2006;355:31-40.

Pedro A. Piedra, MD, is a professor in the department of molecular virology and microbiology at Baylor College of Medicine in Houston. He also is a member of the Infectious Diseases in Children Editorial Board. Disclosure: Dr. Piedra reports no relevant financial disclosures.

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