Drugs Aging 2005; 22 (7): 577-587

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577 1. Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578 1.1 Elderly in Long-Term Care Facilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578 1.2 Community-Dwelling Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 579 2. Clinical Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 580 3. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 581 4. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582 5. Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583 6. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 584 Respiratory syncytial virus (RSV) infection is now recognised as a significant Abstract problem in elderly adults. Epidemiological evidence indicates the impact of RSV in older adults may be similar to nonpandemic influenza, both in the community and in long-term care facilities. Attack rates in nursing homes are approximately 5–10% per year with significant rates of pneumonia (10–20%) and death (2–5%). Estimates using US healthcare databases and viral surveillance results over a 9-year period indicate that RSV infection causes approximately 10 000 all-cause deaths annually among persons >64 years of age. In contrast, influenza A accounted for approximately 37 000 yearly deaths in the same age group. The clinical features of RSV infection may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing and low-grade fever. Older persons with underlying heart and lung disease and immunocompromised patients are at highest risk for RSV infection-related pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably because of low viral titres. The combination of serology and reverse transcriptase polymerase chain reaction assay offers the best sensitivity and specificity for the diagnosis of RSV but unfortunately these techniques are not widely available; consequently, most adult RSV disease goes unrecognised. Although treatment of RSV infection in the elderly is largely supportive, early therapy with ribavirin and intravenous γ-globulin improves survival in immunocompromised persons. An effective RSV vaccine has not yet been developed. Therefore, prevention of RSV is limited to standard infection control practices, such as hand washing and the use of gowns and gloves. T H IS M A N U S C R IP T IS P R O V ID E D IN C O N F ID E N C E T O D E T E R M IN E R E P R IN T IN T E R E S T O N LY A N D S H O U L D N O T B E D IS T R IB U T E D E IT H E R IN T E R N A L LY O R E X T E R N A L LY V IA P R IN T O R E L E C T R O N IC M E D IA F O R O T H E R T H A N T H E S TA T E D P U R P O S E . 578 Falsey & Walsh Human respiratory syncytial virus (RSV) is an titre (10–14 days at ~105–6 pfu/mL).[10,11] Although quantitative virus shedding has not been measured enveloped, single-stranded, negative sense RNA viin older adults, it is likely that titres are generally rus. It is a member of the Paramyxoviridae family low since diagnosis by viral culture or antigen detecand is classified in the genus Pneumovirus.[1] RSV tion is difficult.[12] isolates can be divided into two major groups, A and B, based upon antigenic and genetic analysis.[2-4] 1. Epidemiology Other members of the paramyxovirus family that have similar structural and genetic organisation include the closely related parainfluenza viruses and 1.1 Elderly in Long-Term Care Facilities the recently described human metapneumovirus.[5] The first reports of RSV infections in nursing Together, these viruses cause a substantial proporhome residents appeared in the 1970s, and since tion of severe respiratory illnesses in paediatric then there have been at least 20 published accounts populations, but RSV is recognised as the most of RSV in long-term care facilities.[13-30] Some reimportant of these pathogens. Bronchiolitis, maniports described RSV outbreaks involving between 8 fested by wheezing and hypoxia, is the characteristic and 52 residents, with overall attack rates ranging clinical syndrome caused by RSV in infants and from 12% to 89%. In 11 prospective surveillance results in approximately 100 000 paediatric hosstudies, attack rates were considerably lower, rangpitalisations annually in the US.[6] Shortly after its ing from 1.4% to 40%. Much of this inconsistency initial identification in 1956, RSV infection was can be attributed to the use of relatively insensitive reported in adults and it is now firmly established serological assays and/or culture for diagnosis, and that reinfections occur frequently throughout life, to the fact that case definitions varied substantially. and into old age.[7,8] Although most reinfections are In the prospective studies, pneumonia rates were relatively mild, the frail elderly, those with underly0–33% and death occurred in 0–5%. In one prospecing high-risk cardiopulmonary diseases, and the setive winter surveillance study conducted in a large verely immunosuppressed are at significant risk of Rochester, NY, USA nursing home, RSV infection severe respiratory illness.[8,9] Failure of RSV infecwas documented in 40 persons by culture and sensition to induce solid immunity is a major impediment tive enzyme immunoassay (EIA).[17] The overall to the development of an efficacious RSV vaccine attack rate was 7% and RSV was identified as the for both infants and adults. cause of 27% of the illnesses. Although the presence RSV predictably circulates each winter in temof both group A and B viruses indicated at least two perate climates and during the rainy season in the separate virus introductions, the room locations of tropics. Yearly epidemics generally last for 4–5 infected patients and the clustering of RSV strain months, typically beginning in autumn and lasting types strongly suggested nosocomial transmission until late winter or early spring. Although minor by healthcare workers. In most of the outbreaks variations in viral activity are seen from year to year, reported, RSV circulated simultaneously with other the epidemic curve for RSV is fairly constant, unlike viruses, most notably influenza A virus, thus highthe more dramatic paroxysmal activity of influenza lighting the error of attributing all respiratory tract virus. After an incubation period of 3–5 days, sympillnesses to influenza when a few cases are identitomatic respiratory illness develops in the majority fied. of persons with either primary or repeat infections. As noted, the composite of nursing home reports In adults inoculated by experimental challenge, suggest that RSV attack rates are quite variable and RSV is shed at relatively low titre (~102–3 plaque the overall scope of the problem is thus difficult to forming units [pfu]/mL of secretions) for 3–6 days, estimate. In order to obtain a broader view of RSV in contrast with infants with natural infection who disease burden in nursing home residents, Ellis et shed for a considerably longer time and at higher al.[31] conducted a population-based analysis of the  2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (7) T H IS M A N U S C R IP T IS P R O V ID E D IN C O N F ID E N C E T O D E T E R M IN E R E P R IN T IN T E R E S T O N LY A N D S H O U L D N O T B E D IS T R IB U T E D E IT H E R IN T E R N A L LY O R E X T E R N A L LY V IA P R IN T O R E L E C T R O N IC M E D IA F O R O T H E R T H A N T H E S TA T E D P U R P O S E . Respiratory Syncytial Virus Infection in Elderly Adults 579 effect of influenza and RSV infections in 81 885 RSV-infected persons were admitted to the intennursing home residents in Tennessee, USA. This sive care unit, 10% required ventilatory support and retrospective cohort study estimated rates of cardi10% died. Discharge diagnoses included pneumonia opulmonary hospitalisation, medical care utilisation in 44%, exacerbation of chronic obstructive pulmoand death during 4 consecutive years by linking nary disease (COPD) in 19% and congestive heart them to viral activity in the general community. On failure (CHF) in 20%. In a recent report, the same average, RSV accounted for 15 hospitalisations, 76 investigators identified 61 RSV infections among courses of antibacterials, and 17 deaths per 1000 625 persons (10%) admitted to a large Rochester, persons, and for 7% and 9% of all cardiopulmonary NY, USA hospital for acute cardiopulmonary dishospitalisations and deaths, respectively. In conease.[36] In this study, reverse transcriptase polymertrast, influenza was responsible for 28 hospitalisaase chain reaction (RT-PCR) assay was used in tions and 15 deaths per 1000 persons. Notably, addition to culture and serology to detect viral aetimorbidity but not mortality was higher among those ology. In another analysis of 1195 adults of all ages with co-morbid conditions. admitted to Ohio, USA hospitals with pneumonia, RSV is also a relatively common cause of illness Dowell et al.[37] found that RSV was the third most among frail elderly attending senior daycare common aetiology (4.4%), behind Streptococcus programmes.[32] In one 15-month study, 10% of 165 pneumoniae (6.2%) and influenza virus (5.4%). Of elderly attendees developed respiratory infections the 57 RSV-infected persons, 68% were >64 years caused by RSV. This virus, along with influenza and of age. In another study using culture and a virus coronaviruses, was among the most commonly idenneutralisation assay, Glezen et al.[38] identified only tified pathogens. two RSV infections in 150 hospitalised elderly persons with acute cardiopulmonary syndromes, al1.2 Community-Dwelling Elderly though interestingly the rate was approximately 4% among adults 45–64 years of age. A limited number of published studies describe Prospective studies that have assessed the incithe epidemiology of RSV infection among commudence of RSV infection in community-dwelling eldnity dwelling elderly. Data are available from three erly persons also suggest that this infection is relatypes of analyses: those describing RSV infection tively common.[38-41] Despite a steady decline in the among hospitalised persons with respiratory illness; overall incidence of respiratory tract infections with prospective cohort studies that define infection rates advancing age, there is ample evidence that the in various elderly or high-risk groups; and statistiseverity of infection increases.[41] Nicholson et al.[39] cally derived population-based studies that link renoted that 3% of 497 illnesses in 533 elderly persons spiratory illness rates in large populations to virus followed for 2 years were a result of RSV. This activity in the community. compared with infection rates of 7% for influenza The first report of RSV among older hospitalised and 52% for rhinovirus, but it should be noted that patients with pneumonia was from Sweden in different diagnostic tests were used to detect the 1967.[33] In this report, 18 cases of RSV infection in three viruses. In another study from the UK, persons >55 years of age, representing 7.4% of Zambon et al.[41] used a sensitive nested RT-PCR to pneumonia cases, were included. A second publicaidentify RSV in 15% of nasopharyngeal swab samtion from Sweden encompassing a 10-year period ples collected from 167 patients >64 years of age described 57 RSV-infected adults with a mean age with acute respiratory illnesses seen by general pracof 75 years, of whom two-thirds had pneumonia.[34] titioners over a 3-year period. Influenza was identiA more recent 3-year analysis of elderly persons fied in 28% of the same subjects. These results are hospitalised during the winter with acute cardisimilar to our finding that 11% of 287 winter illnessopulmonary symptoms identified RSV serologically es in persons >65 years of age were a result of RSV in 10% and influenza in 13%.[35] Eighteen percent of  2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (7) T H IS M A N U S C R IP T IS P R O V ID E D IN C O N F ID E N C E T O D E T E R M IN E R E P R IN T IN T E R E S T O N LY A N D S H O U L D N O T B E D IS T R IB U T E D E IT H E R IN T E R N A L LY O R E X T E R N A L LY V IA P R IN T O R E L E C T R O N IC M E D IA F O R O T H E R T H A N T H E S TA T E D P U R P O S E . 580 Falsey & Walsh infection when culture, EIA and RT-PCR were used should be noted that these results were not calculated using virus-confirmed illnesses but rather were for diagnosis.[40] dependent upon several assumptions, including that Although not limited to elderly subjects, several viral circulation among infants reflects viral activity earlier reports that used culture and serology also in elderly populations and that other winter time described RSV infection in 0–17% of persons with respiratory viruses do not confound the results. COPD.[42-51] In one of these studies that spanned 2 In all of the studies reported, the highest risk of years, we documented eight RSV infections in 134 severe disease from RSV appeared to be persons subjects with underlying cardiopulmonary disease with underlying chronic medical conditions. In a (4.3 infections per 100 subject-winters).[36] Illness prospective analysis of RSV infections in elderly was significant as three of the eight required hosadults and those with high-risk conditions (mean age pitalisation. More recently, several investigations 74 years), we found that the presence of underlying have used more sensitive RT-PCR for diagnoCOPD (odds ratio [OR] 3.97; 95% CI 1.18, 13.37), sis.[52-55] Rohde et al.[53] evaluated the presence of incremental functional impairment (OR 1.67; 95% respiratory viruses in 85 subjects with a mean age of CI 1.23, 2.26) and low neutralising antibody titres 70 years admitted to hospital with acute exacerba(OR 5.89; 95% CI 1.69, 20.57) were independently tions of COPD and in 42 stable COPD patients associated with severe outcome, defined as hospitaladmitted for other reasons. RSV was detected in isation during infection.[40] 22% of exacerbations, and in none of the controls. Finally, although relatively infrequent in this age RSV was the third most frequent virus detected after group, elderly persons rendered severely imrhinovirus and influenza A virus. Although other munocompromised by cytotoxic therapy for acute investigators have also detected RSV by RT-PCR in leukaemia or solid malignancy are at significant risk patients with COPD exacerbations, they have also of fatal outcome during RSV infection. Despite the noted the equivalent presence of RSV RNA in clinilack of published studies, it is reasonable to extrapocally stable COPD patients.[55] These recent findings late the poor outcome seen in younger immunocomraise the possibility that RSV may persist in certain promised adults, in which mortality can exceed 90% adults, a concept supported by recent observations with lower respiratory infection, to older persons.[9] by Schwarze et al.[56] using a murine model of RSV. The impact of RSV infection among HIV-infected Population-based calculations of the proportion elderly persons is not known, although other than of acute respiratory illnesses attributable to RSV prolonged virus shedding, RSV does not appear to have also provided estimates of disease burden in be excessively virulent in younger HIV-infected elderly persons.[6,57,58] In two studies from the UK, persons.[60,61] RSV was linked to a significant proportion of excess winter time respiratory morbidity, and in one esti2. Clinical Manifestations mate by Nicholson[58] RSV had a greater impact than nonpandemic influenza.[57] Using US healthUnlike infants in whom RSV produces the readicare databases and viral surveillance results over a ly recognisable syndrome of bronchiolitis, the 9-year period, Thompson et al.[6] estimated that RSV clinical manifestations of infection with this virus in infection causes approximately 10 000 all-cause the elderly are nonspecific and quite variable. deaths annually among persons >64 years of age. In Symptoms range from a mild cold-like illness to contrast, influenza A accounted for approximately severe respiratory failure.[62] The full spectrum of 37 000 yearly deaths in the same age group. Using disease is best delineated from analysis of prospecsimilar methods, Griffin et al.[59] estimated that tively documented infections in senior daycare cenamong patients with chronic lung disease in Tennestres or in outpatient elderly populations.[32,39] In see, USA, RSV caused 17.7 hospitalisations per general, the clinical picture is indistinguishable from 1000 persons and 46.5 deaths per 10 000 persons. It that of any of the other viral respiratory pathogens,  2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (7) T H IS M A N U S C R IP T IS P R O V ID E D IN C O N F ID E N C E T O D E T E R M IN E R E P R IN T IN T E R E S T O N LY A N D S H O U L D N O T B E D IS T R IB U T E D E IT H E R IN T E R N A L LY O R E X T E R N A L LY V IA P R IN T O R E L E C T R O N IC M E D IA F O R O T H E R T H A N T H E S TA T E D P U R P O S E . Respiratory Syncytial Virus Infection in Elderly Adults 581 with the exception that fever is less pronounced than Adults with reinfection shed considerably less for influenza. Rhinorrhoea and nasal congestion are virus than infants with primary RSV (≤103 vs ~106 seen in the majority, whereas sore throat is reported pfu/mL) and shed virus for a shorter duration (3–4 by about one-quarter of subjects. Similar to influendays).[52,64,69,70] The thermolability of RSV comza infection, cough is nearly universal, being reportpounds the problems of viral isolation. Thus, viral ed by >90% of infected subjects. Dyspnoea is reculture that is used successfully in children is insenported by 11–20%, whereas gastrointestinal sympsitive in elderly adults. Culture is approximately toms are extremely uncommon. On examination, the 50% sensitive when performed under ideal circumtemperature exceeds 38°C in half or less of patients. stances and compared with a highly sensitive seroloRales are noted in about one-third of patients and gy. In a nursing home study in which transit time of RSV is more apt to be associated with wheezing specimens to the laboratory was <1 hour, RSV was than is influenza, even in those without underlying isolated in 45% of serologically proven RSV obstructive lung disease. Radiographic abnormalicases.[17] When tissue culture inoculation was perties can be seen in patients with lower respiratory formed at the bedside in another study, viral culture signs and symptoms, and are usually unilateral or performed better and was 67% sensitive.[65] Unforbilateral patchy subsegmental alveolar infiltrates.[29] tunately, in clinical practice, such methodology is However, lobar consolidation was described by not feasible and viral culture is only 20–30% sensiDowell et al.[37] in hospitalised patients with pneutive compared with serology. monia as a result of RSV. The role of bacterial Detection of RSV antigens in nasopharyngeal superinfection during RSV infection in the elderly is secretions by immunofluorescence assay (IFA) or not fully understood. We have noted bacterial pathoEIA obviates the need for viable virus but requires a gens occasionally, and isolated S. pneumoniae from substantial viral load for adequate detection. These the blood from several RSV-infected hospitalised methods are 75–95% sensitive in young children but patients (personal observation). are of limited value in adults.[12,71] In a study of 60 older persons with documented RSV, IFA was posi3. Diagnosis tive in 23% and EIA by commercial assay in only 10% of cases.[12] Given the low prevalence of RSV Diagnosis of RSV infection in elderly adults is in older adult populations, the positive predictive problematic. Whereas in young children RSV revalue of these tests is very poor, and they cannot be sults in the distinctive syndrome of bronchiolitis, recommended for general use in the elderly. In infection in adults does not produce a characteristic immunocompromised older persons in whom viral illness distinguishable from other winter time viload may be higher, rapid antigen testing may be ruses.[30,63] Therefore, diagnosis of RSV requires appropriate.[64] laboratory confirmation. This may be accomplished Because of the previously described problems of by viral culture, detection of viral antigens in respirviral lability and low titres in secretions, new molecatory secretions, molecular techniques or serology. ular techniques that detect very small amounts of RSV can be detected in a variety of respiratory viral RNA by amplification are currently regarded secretions including nasopharyngeal swabs, nasal as the optimal method of diagnosis of acute RSV washes, sputum or bronchial alveolar lavage fluinfection.[66,72] RT-PCR has now been used successid.[64-68] Although nasal washes are most commonly fully in both paediatric and adult populations.[41,73,74] used in children, they are poorly tolerated in frail Primers from the F and N genes of RSV are comelderly persons and are not practical. Although viral monly used and strain-specific RT-PCR can differtitres may be slightly lower from nasopharyngeal entiate RSV group A and B viruses.[75,76] In a large swabs than from nasal washes, nasopharyngeal study in which 1112 illnesses were evaluated by swabs are an acceptable method of specimen collection in the elderly. three methods (viral culture, one-tube nested RT 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (7) T H IS M A N U S C R IP T IS P R O V ID E D IN C O N F ID E N C E T O D E T E R M IN E R E P R IN T IN T E R E S T O N LY A N D S H O U L D N O T B E D IS T R IB U T E D E IT H E R IN T E R N A L LY O R E X T E R N A L LY V IA P R IN T O R E L E C T R O N IC M E D IA F O R O T H E R T H A N T H E S TA T E D P U R P O S E . 582 Falsey & Walsh PCR and serology), RT-PCR was 73% sensitive and actually be a better method for diagnosing RSV in the old than in the young. Although sensitive and 99% specific, whereas viral culture was 39% sensispecific, serology based on IgG is limited by the tive and 100% specific.[66] In addition, quantitative need for convalescent specimens and, thus, diagnoRT-PCR has been shown to correlate very well with sis is retrospective. Serology is primarily a research viral titres calculated by tissue culture in RSV chaltool, but it may be useful in outbreak investigations lenge studies.[10] In such experiments, prolonged in long-term care facilities. detection of viral RNA following infection was not Detection of IgM in acute phase sera has been found. In addition, detection of RSV RNA in used for the immediate diagnosis of RSV infection asymptomatic adults even when RSV is prevalent in but, at present, these assays are not readily availathe community is uncommon.[77] ble.[37,82,83] RSV-specific IgM was detected in 81% Method of diagnosis becomes an issue not only in of RSV-infected hospitalised adults, appearing 6–40 clinical care but also when evaluating epidemiologidays after the onset of symptoms in one study.[83] In cal studies. Studies which utilise viral culture and/or another study of adult community-acquired pneuantigen detection only are likely to vastly underestimonia, RSV IgM was detected in 58% of confirmed mate the incidence of RSV, whereas those employRSV cases.[37] Unfortunately, at the present time, the ing RT-PCR provide a more accurate assessment of practising physician is limited to the insensitive adult disease. For example, a recent Swedish study techniques of viral culture and antigen detection for using culture and IFA identified RSV in 2% of the diagnosis of RSV in the elderly adult. Hopefully, elderly persons with respiratory illness, whereas RT-PCR will become more widely available in the 4.8–11% of illnesses were identified as caused by future. RSV in a French study using RT-PCR.[72,78] RTPCR is commercially available on a limited basis 4. Treatment and is primarily a research tool at the present time. Various serological methods to detect RSV-speTreatment of RSV infection in elderly adults is cific IgM and IgG including complement fixation primarily supportive and includes fluids, oxygen (CF) and EIA have been used in adults with variable and antipyretics. Although use of corticosteroids results. A single high-CF titre has been used in a and bronchodilators in adults with RSV infection number of studies as indicative of acute RSV infechas not been examined in controlled studies, their tion with some success, but this technique has not use in the acutely wheezing patient is reasonable. In been rigorously studied.[18,23,24] When a ≥4-fold rise most instances, patients are not specifically diagin titre is required for diagnosis, CF serology is nosed with RSV but rather are considered as having approximately 50% sensitive when compared with asthma or COPD exacerbations. Since a bacterial EIA serology using purified viral proteins.[79] In a pathogen will be found in sputum culture in approxinursing home study using IgG EIA with purified F mately 10–30% of RSV-infected persons, antibacteand G glycoproteins as antigens, 85% of subjects rials may be prudent in selected patients.[24,34,35,84] with culture-confirmed disease demonstrated Specific antiviral treatment is rarely considered ≥4-fold rises in RSV IgG.[17] When using preseason for older adults. This is in part due to the difficulty baseline sera, the sensitivity of serology EIA is of rapid diagnosis of acute RSV infection in adults. closer to 90–95%.[80] Nonetheless, false-negatives In addition, the pathogenesis of severe RSV in the may occur, particularly in hospitalised patients in elderly is not well understood. It remains a question whom acute sera is frequently obtained many days as to whether or not antivirals will be of benefit into illness. An interesting yet unexplained observasince viral load in the nasopharynx is low and pation is that elderly adults have a significantly more tients typically seek medical attention after 5–6 days vigorous serum antibody response to RSV than of illness. The amount of virus in the lower airways healthy young adults.[81] Therefore, serology may of immunocompetent adults has been rarely studied.  2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (7) T H IS M A N U S C R IP T IS P R O V ID E D IN C O N F ID E N C E T O D E T E R M IN E R E P R IN T IN T E R E S T O N LY A N D S H O U L D N O T B E D IS T R IB U T E D E IT H E R IN T E R N A L LY O R E X T E R N A L LY V IA P R IN T O R E L E C T R O N IC M E D IA F O R O T H E R T H A N T H E S TA T E D P U R P O S E . Respiratory Syncytial Virus Infection in Elderly Adults 583 Using quantitative RT-PCR, German investigators antiviral treatment since mortality rates are very high. Although much of the data on the use of found no difference in the titres of RSV in nasal ribavirin and immunoglobulin comes from patients lavage fluid of immunocompetent adults compared with bone marrow transplants, an uncommon procewith induced sputum in COPD patients; however, dure in the elderly, these results can be generalised respiratory viruses were more often detected in sputo other conditions, such as leukaemia, lymphoma tum.[52] Nonetheless, it may be reasonable to considand immunosuppression secondary to chemotherapy er antiviral treatment in selected patients who prefor solid tumours. The use of aserosolised ribavirin sent early with severe disease in whom a specific alone to treat RSV pneumonia in bone marrow diagnosis of RSV infection has been made. Pretransplant recipients was not associated with signifiemptive therapy may also be considered in high-risk cantly different mortality to the 70% rate observed patients or patients who are immunocompromised in historical controls.[106,107] However, when comsince a high percentage of these patients will develbined with high-titred RSV immunoglobulin, morop serious lower respiratory tract disease.[85-87] tality decreased to 50%.[86] Initiation of treatment At the present time, aserosolised ribavirin is the prior to the onset of respiratory failure is considered only licensed antiviral for the treatment of to be critical to success.[103] RSV.[88,89] Ribavirin is a guanosine analogue and inhibits the replication of a wide range of viruses, 5. Prevention including RSV. A number of other anti-RSV agents, such as fusion inhibitors and antisense molecules, RSV is believed to be transmitted primarily by are currently in development.[90-92] Ribavirin is aplarge droplets and fomites.[108,109] Thus, close perproved for use in infants although its use is someson-to-person contact or contact with contaminated what controversial. Placebo-controlled, randomised environmental surfaces and autoinoculation are nectrials have not always shown clear benefit although essary for transmission.[70,110] Unlike influenza, most show a beneficial trend.[93-95] In addition to which spreads efficiently via small particle aerosols ribavirin, two immunoglobulin preparations (polyand causes explosive outbreaks in nursing homes, clonal high-titred RSV IgG and a humanised FRSV tends to spread slowly with a steady trickle of specific monoclonal antibody) are approved for procases.[20] Various infection control strategies, principhylactic use in high-risk children.[96-99] Data on the pally hand washing, have been employed to limit use of ribavirin and immunoglobulin in adults denosocomial spread of RSV.[111] Since compliance rived primarily from small, uncontrolled studies and with hand washing is frequently poor, use of gowns anecdotal reports of treatment of the elderly do not and gloves has been advocated in paediatric provide enough data to make general recommendawards.[112] Masks are not necessary but cohorting tions.[100-103] In one report, one of two adult patients and isolation of infected patients is desirable if poswith nosocomial RSV died despite treatment with sible. Education of staff regarding transmission of ribavirin.[101] The safety of aerosolised ribavirin was respiratory viruses and the value of hand washing evaluated in eight uninfected elderly volunteers and was associated with a significant decrease in rates of treatment was well tolerated, even in those with acute respiratory tract infections in adult daycare COPD.[104] It may be difficult to administer ribavirin centres.[113] by face mask for the prolonged recommended periImmunisation may provide the best option for ods (20 mg/mL for 18 hours a day) in confused older prevention of severe RSV disease in elderly and patients. Therefore, high-dose, short-duration therhigh-risk adults. Low serum neutralisation antibody apy (60 mg/mL for 2 hours three times daily) is an has been demonstrated to be a risk factor for both alternative and may be better tolerated.[105] infection and severe disease.[40,114] Unfortunately, at Immunocompromised patients with lower respirthe present time, there is no licensed RSV vaccine atory symptoms should always be considered for although several candidate vaccines are in develop 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (7) T H IS M A N U S C R IP T IS P R O V ID E D IN C O N F ID E N C E T O D E T E R M IN E R E P R IN T IN T E R E S T O N LY A N D S H O U L D N O T B E D IS T R IB U T E D E IT H E R IN T E R N A L LY O R E X T E R N A L LY V IA P R IN T O R E L E C T R O N IC M E D IA F O R O T H E R T H A N T H E S TA T E D P U R P O S E . 584 Falsey & Walsh 7. Hall CB. Respiratory syncytial virus and parainfluenza virus. ment. Immunisation with a purified F protein N Engl J Med 2001; 334: 1917-28 subunit vaccine was successful in inducing a 4-fold 8. Falsey AR, Walsh EE. Respiratory syncytial virus infection in adults. Clin Microbiol Rev 2000; 13: 371-84 rise in antibody in 61% of healthy elderly and 47% 9. Englund JA, Sullivan CJ, Jordan MC, et al. Respiratory syncytiof institutionalised elderly vaccine recipients.[115,116] al virus infection in immunocompromised adults. Ann Intern However, the immunogenicity of a live attenuated Med 1988; 109: 203-8 10. Falsey AR, Formica MA, Treanor JJ, et al. Comparison of RSV vaccine was poor in healthy elderly persons, quantitative reverse transcription-PCR to viral culture for aspresumably because of low infection rates.[117] sessment of respiratory syncytial virus shedding. J Clin Microbiol 2003; 41: 4160-5 11. Hall CB, Geiman JM, Biggar R, et al. Respiratory syncytial 6. Conclusion virus infections within families. 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