Ann R. Falsey

Human Metapneumovirus Infections in Young and Elderly Adults

Human metapneumovirus virus (hMPV) is a newly discovered respiratory pathogen with limited epidemiological data available. Cohorts of young and older adults were prospectively evaluated for hMPV infection during 2 winter seasons. Patients hospitalized for cardiopulmonary conditions during that period were also studied. Overall, 44 (4.5%) of 984 illnesses were associated with hMPV infection, and 9 (4.1%) of 217 asymptomatic subjects were infected. There was a significant difference in rates of hMPV illnesses between years 1 and 2 (7/452 [1.5%] vs. 37/532 [7.0%]; P<.0001). In the second year, 11% of hospitalized patients had evidence of hMPV infection. Infections occurred in all age groups but were most common among young adults. Frail elderly people with hMPV infection frequently sought medical attention. In conclusion, hMPV infection occurs in adults of all ages and may account for a significant portion of persons hospitalized with respiratory infections during some years.

Randomized, Double-Blind Controlled Phase 3 Trial Comparing the Immunogenicity of High-Dose and Standard-Dose Influenza Vaccine in Adults 65 Years of Age and Older

BACKGROUND Influenza-associated morbidity and mortality has not decreased in the last decade, despite increased receipt of vaccine. To improve the immunogenicity of influenza vaccine, a high-dose (HD) trivalent, inactivated influenza vaccine was developed. METHODS A multicenter, randomized, double-blind controlled study was conducted to compare HD vaccine (which contains 60 microg of hemagglutinin per strain) with the licensed standard-dose (SD) vaccine (which contains 15 microg of hemagglutinin per strain) in adults > or = 65 years of age. RESULTS HD vaccine was administered to 2575 subjects, and SD vaccine was administered to 1262 subjects. There was a statistically significant increase in the rates of seroconversion and mean hemagglutination inhibition titers at day 28 after vaccination among those who received HD vaccine, compared with those who received SD vaccine. Mean postvaccination titers for individuals who received HD vaccine were 116 for H1N1, 609 for H3N2, and 69 for B strain; for those who received SD vaccine, mean postvaccination titers were as 67 for H1N1, 333 for H3N2, and 52 for B strain. The HD vaccine met superiority criteria for both A strains, and the responses for B strain met non-inferiority criteria. Seroprotection rates were also higher for those who received HD vaccine than for those who received SD vaccine vaccine, for all strains. Local reactions were more frequent in individuals who received HD vaccine, but the reactions were mild to moderate. CONCLUSIONS There was a statistically significant increase in the level of antibody response induced by HD influenza vaccine, compared with that induced by SD vaccine, without an attendant increase in the rate or severity of clinically relevant adverse reactions. These results suggest that the high-dose vaccine may provide improved protective benefits for older adults. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00391053 .

Viral Respiratory Infections in the Institutionalized Elderly: Clinical and Epidemiologic Findings

To prospectively evaluate the incidence and impact of viral respiratory infection in the institutionalized elderly during a winter season.

Asthma in the elderly: Current understanding and future research needs—a report of a National Institute on Aging (NIA) workshop

Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity of knowledge on the subject. The National Institute on Aging convened this workshop to identify what is known and what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of asthma in the elderly. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger patients, but comorbid illnesses and the psychosocial effects of aging might affect the diagnosis, clinical presentation, and care of asthma in this population. At least 2 phenotypes exist among elderly patients with asthma; those with longstanding asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the elderly are likely to be different from those seen in young asthmatic patients, and these differences might influence the clinical course and outcomes of asthma in this population.

Viral Pneumonia in Older Adults

Abstract Viruses account for a substantial portion of respiratory illnesses, including pneumonia, in the elderly population. Presently, influenza virus A H3N2 and respiratory syncytial virus are the most commonly identified viral pathogens in older adults with viral pneumonia. As diagnostic tests such as reverse-transcription polymerase chain reaction become more widely used, the relative importance of additional viruses (such as parainfluenza, rhinoviruses, coronaviruses, and human metapneumovirus) will likely increase. Influenza virus should be considered as a cause of pneumonia during the winter months, especially during periods of peak activity. Patients with high-grade fever, myalgias, and cough should arouse the highest suspicion. Respiratory syncytial virus pneumonia should also be suspected during the winter in patients with coryza, wheezing, low-grade fever, and patchy infiltrates, especially if negative for influenza on rapid testing. Because clinical features and periods of activity for many viruses overlap, laboratory confirmation of influenza is recommended for cases involving seriously ill or institutionalized patients.

Rhinovirus and Coronavirus Infection-Associated Hospitalizations among Older Adults

Abstract Rhinoviruses and coronaviruses are recognized as the major causes of the common cold syndrome. The role of these viruses in more serious respiratory illnesses resulting in hospitalization is less well defined. During a winter when influenza A infection was prevalent, 100 elderly adults hospitalized because of cardiopulmonary illnesses were evaluated for rhinovirus and coronavirus infection. Patients who tested negative for influenza or respiratory syncytial virus had nasal swab samples tested for rhinovirus, coronavirus OC43, and coronavirus 229E by reverse-transcription polymerase chain reaction and for coronaviruses by serologic testing. Twelve percent of patients had rhinovirus or coronavirus identified (rhinovirus, 4 patients; coronavirus 229E, 4 patients; coronavirus OC43, 3 patients; and mixed rhinovirus/coronavirus 229E infection, 1 patient). All patients had significant underlying diseases. Although all patients recovered, the mean length of stay was 8 days; 4 persons had pneumonia, and 1 required ventilator support. These data suggest that rhinoviruses and coronaviruses may be associated with serious respiratory illnesses in frail older adults.

Diagnosis of Respiratory Syncytial Virus Infection: Comparison of Reverse Transcription-PCR to Viral Culture and Serology in Adults with Respiratory Illness

ABSTRACT Diagnosis of respiratory syncytial virus (RSV) during acute infection in adults is difficult because of the poor sensitivity of viral culture and antigen detection. A recently developed single-tube nested reverse transcription-PCR (RT-PCR) was compared to viral culture and serology by enzyme immunoassay for the diagnosis of RSV in adults with respiratory illness. Nasal swab samples were collected during respiratory illnesses from five groups of subjects: healthy young adults, healthy elderly adults, adults with chronic heart and lung disease, nursing home residents, and adults admitted to the hospital during the winter with cardiopulmonary illnesses. Of 1,112 samples for which all three tests were available, 117 were positive by at least one method and 995 were negative by all methods. One hundred ten were considered true positives because culture and/or serology was positive. Of these, 80 (73%) were PCR positive compared to 43 (39%) that were culture positive. Seven PCR results were considered false positives due to negative culture and serology. The overall RT-PCR sensitivity was 73%, and specificity was 99%. These data indicate that RT-PCR is an excellent method for the diagnosis of acute RSV infection in adults.

Lack of sensitivity of rapid antigen tests for the diagnosis of respiratory syncytial virus infection in adults

The diagnosis of respiratory syncytial virus (RSV) infection in older individuals and adults with cardiopulmonary diseases using available rapid antigen detection tests may be difficult due to the low virus shedding in this population. These tests have been extensively evaluated in hospitalized infants, but there is only limited data on their usefulness in adult populations. We evaluated the performance of three different rapid antigen detection tests: Becton Dickinson Directigen RSV (BD), Bartels RSV Direct Fluorescent Antibody Test (DFA) and the VIDAS RSV assay (VIDAS) in nasopharyngeal specimens from 60 older persons with RSV infection documented by cell culture, serology or reverse transcription polymerase chain reaction (RT-PCR). The three rapid antigen assays tested on all 60 samples performed poorly. DFA detected 14 (23%), VIDAS detected 12 (20%) and BD detected only 6 (10%) of the RSV infected persons. Rapid antigen detection tests for the diagnosis of RSV respiratory illness in adults are of limited value.

Relationship of Serum Antibody to Risk of Respiratory Syncytial Virus Infection in Elderly Adults

The relationship of serum antibody to respiratory syncytial virus (RSV) and risk of RSV infection was prospectively evaluated in frail elderly persons. Baseline blood samples from 22 subjects who developed symptomatic RSV infection during the 26-month study and from 22 control subjects who did not become infected with RSV were compared. The mean serum IgG titer to RSV fusion protein was significantly lower in the RSV-infected group than in the controls (15.4 +/- 1.6 vs. 16.4 +/- 1.8, P = .05), as were the neutralizing titers to group A RSV (12.4 +/- 2.2 vs. 14.2 +/- 2.2, P = .008) and group B virus (9.1 +/- 2.1, vs. 10.3 +/- 1.5, P = .01). These results suggest that older adults with low titers of serum neutralizing antibody may be at greater risk of developing symptomatic RSV infection than those who have high antibody titers.

Human Metapneumovirus Infections in Adults Another Piece of the Puzzle

BACKGROUND Each winter respiratory viruses account for a significant proportion of serious respiratory illness, including hospitalization, in older adults and those with underlying medical conditions. We describe the incidence and clinical impact of human metapneumovirus (HMPV), a newly identified virus, in adults. METHODS Infection with HMPV was identified in 3 prospectively enrolled adult cohorts (young persons 19-40 years old, healthy adults > or =65 years old, and high-risk adults) and a hospitalized cohort for 4 consecutive winters (November 15 through April 15 for the years 1999 through 2003). The incidence and clinical impact were compared with those of influenza A and respiratory syncytial virus infection in the same groups. RESULTS Using reverse transcriptase-polymerase chain reaction and serologic testing, we identified HMPV infection in 2.2% to 10.5% of the 3 prospectively followed-up outpatient cohorts annually. Asymptomatic infection was common, accounting for at least 38.8% of infections in each of the cohorts. Symptoms, when they occurred, were typical of an upper respiratory tract illness, although a few high-risk persons required hospitalization. Among 1386 hospitalized patients, HMPV was identified in 8.5% (range, 4.4%-13.2%), depending on the year. Dual viral infection was identified in 22.9%. Wheezing was frequent (80%) and more common than with influenza. Twelve percent required intensive care unit admission and 11% ventilatory support, rates similar to those for influenza and respiratory syncytial virus infection. CONCLUSIONS In adults of all ages, HMPV is a common infection, and, although often asymptomatic, it can result in serious infection that requires hospitalization. Like influenza A and respiratory syncytial virus, HMPV is also a major contributor to the burden of wintertime respiratory illnesses in older adults.