Respiratory Syncytial Virus In Older Adults: A Hidden .
Respiratory Syncytial Virus in Older Adults:A Hidden Annual EpidemicA Report by the National Foundation for Infectious DiseasesSeptember 2016
Respiratory Syncytial Virusin Older Adults:A Hidden Annual EpidemicOverviewRespiratory syncytial virus (RSV) is a commoncause of acute respiratory illness in older adults,with the risk of serious infection increasing withage.1–4 The virus circulates along with many otherwinter respiratory viruses, most notably seasonalinfluenza, and is largely indistinguishable frominfluenza based on clinical presentation alone.2,5,6RSV is second only to influenza as a cause ofmedically significant respiratory tract illnessesin adults7,8 and is estimated to cause 177,000hospitalizations and 14,000 annual deaths inUS adults age 65 years and older.2,9There is no specific treatment for RSV in adultsand currently no licensed vaccine to prevent thedisease. However, several promising candidatevaccines are on the horizon to protectpopulations at increased risk of serious RSVoutcomes, including older adults.10 RSVepidemiology and burden of disease suggestvaccines should target infants younger than agesix months, infants and children age six to 24months, pregnant women (to provide passiveimmunity to newborns), and adults age 65 yearsand older.11 The focus of this report is on the olderadult population.“Recognizing and definingthe impact of RSV in olderadults is important inorder to evaluate theimpact of new preventionand treatment optionsthat will likely be availablein the US soon.”Recognizing and defining the impact of RSV inolder adults is important in order to evaluate theimpact of new prevention and treatment optionsthat will likely be available in the US soon. Publichealth and healthcare professionals (HCPs) needto educate themselves about RSV so they canadvise the general public and older patients aboutthe importance of prevention.– William Schaffner, MD1
RSV: A Pervasive Infection withLifelong ReinfectionsFigure 1: Respiratory Syncytial Virus StructureRSV is an RNA virus that was isolated in themid-1950s from a captive chimpanzee withupper respiratory tract illness.12 It is classifiedin the Paramyxoviridae family, which includesparainfluenza, meta-pneumovirus, and measlesviruses. Humans are the only known reservoir.RSV subtypes A and B co-circulate. Some dataindicate that RSV subtype A may cause moresevere disease. Two surface glycoproteins, F andG, are responsible for initiation and propagationof RSV infection in the host. The G protein differson the RSV A and B subtypes, but the F protein isantigenically stable with minimal differencebetween subtypes (Figure 1).7,13Reprinted from Current Opinion in Immunology,Volume 35, Graham BS, Modjarrad K, McLellan JS.Novel antigens for RSV vaccines, pp 30-38, 2015,with permission from Elsevier.13RSV epidemics occur annually during the wintermonths in temperate regions, with most USinfections occurring in a 22-week period fromNovember to May.14 By age two years, almost allchildren have been infected with RSV and abouthalf have been infected twice.15 Immunity isfleeting and reinfection is common throughoutthe lifespan.PathogenesisThe pathogenesis of disease associated with RSV iswell described in young children, but little is knownabout the pathogenesis in older adults. In children,RSV usually begins as an infection in the nasalmucosal epithelial cells.17 The RSV virion attachesto and penetrates ciliated nasal epithelial cells byfusing with the cell membrane, entering, andreplicating in the cytoplasm. Infectious virusbuds from and exits the infected cells via apicalmembrane on the lumenal side (the same side ofentry) of the airway, and is not released into thesystemic circulation through the basementmembrane. This restricted replication may be whyRSV is not a systemic virus, making it difficult forthe immune system to mount a very strong anddurable systemic response.Hall and colleagues16 challenged 15 healthy youngadults with RSV at two, four, eight, 14, 20, and 26months following natural infection. The rate ofreinfection was highest after the first challenge( 50 percent) showing that just two months afterRSV infection, otherwise healthy adults werealready susceptible to reinfection. The cumulativereinfection rate was two-thirds by eight monthsand over the course of the approximatelytwo-year study, 73 percent had two or moreand 47 percent had three or more infections.2
Risk Factors for More Severe RSVOutcomes with AgingVirus replication results in epithelial-cell sloughing,inflammatory cell infiltration, edema, increasedmucous secretion, and impaired ciliary action.The sloughed cells create an obstruction; duringinhalation the airway opens, but on exhalationwhen the lungs deflate, the airway can becomeobstructed, causing air trapping and wheezing.Gradual deterioration of the immune systemdue to aging (immunosenescence) is one ofseveral reasons why older adults are at increasedrisk from viral respiratory disease.20 Even the mostvital and active older adult will experience someimmunosenescence as a consequence of aging,but it is important to note that age alone is notthe only determining factor. Frailty, markedby a lack of physiologic reserve,21 may predictimmunosenescence and response to immunizationbetter than age.22,23RSV Disease: Age-Related SeverityRSV is associated with the most severe disease atthe extremes of age.2,6,18,19 In infants, RSV causesbronchiolitis, pneumonia, tracheobronchitis, andotitis media, while in older adults it can causepneumonia, as well as exacerbation of chronicobstructive pulmonary disease (COPD) andcongestive heart failure (CHF). For healthy olderchildren and young adults, clinical presentationof RSV resembles the common cold, with mild tomoderate cough and nasal congestion.As adults age, cellular immunity changes includedecreased naïve T cells, increased memory T-cellcount, decreased T-cell proliferation with Th1and Th2 imbalances, and increased levels ofinflammatory mediators. Older adults also havedecreased B-cell responses to new antigens anddecreased cytotoxic T-cell activity, resulting in lesseffective natural killer cells in the immune system.When RSV presents similar to the commoncold it is unlikely to cause significant fever,giving patients no signal to self-isolate. If theygo to work in day cares, nursing homes, hospitals,and other locations, they may unknowinglyspread RSV to others who may be more vulnerableto severe outcomes.Anatomically, older adults have decreased strengthof the respiratory muscles and diaphragm, whichimpedes lung expansion. Older adults also havedecreased protective mucus levels, lungcompliance, and elastin.Annual Attack Rate and RSV Mortalityin Adults Age 65 Years and OlderBased on data from a four-year study, the Centersfor Disease Control and Prevention (CDC)estimates 14,000 annual deaths caused by RSVin US adults age 65 years and older.9 A statisticalmodel by Thompson et al,1 encompassing a 10-yearperiod estimated more than 11,000 annualrespiratory and circulatory deaths due to RSV inthe US with 78 percent in patients age 65 years3
and older. During the surveillance period, RSV wasassociated with more deaths in this age groupthan influenza B or the influenza A (H1N1) strain,but fewer deaths than the more severe influenza A(H3N2) strain.progressively aging population, and risinghealthcare costs, the US price tag for RSV in theage 65 years and older population is likely muchgreater and may be well into the billions of dollars.A striking finding in this study was that nearlyhalf of the total cost of RSV was for outpatientoral antibiotics,24 which would only be medicallyappropriate for patients with bacterial co-infection.The study by Falsey et al,2 found that only10 percent of older and high-risk adultshospitalized with RSV infection had concomitantbacterial infection. In addition to adding tounnecessary costs, overuse of antibiotics is thesingle most important risk factor leading toantibiotic resistance.26While a hallmark of influenza is its annual seasonalvariability, RSV is more consistent in its attack rateand severity. According to a study by Falsey et al,2over four winter respiratory seasons in Rochester,NY (1999-2003), RSV infection developed annuallyin an average of 5.5 percent (range, 3 to 7 percent)of healthy adults age 65 years and older(i.e., without COPD or CHF) and 4 to 10 percentof high-risk adults age 21 years and older(i.e., diagnosed with chronic heart or lung disease).The number of patients with RSV in this study wasapproximately double the number of patients withinfluenza, but a high level of influenza vaccinationcoverage was noted in the study population.Preventing RSV in people age 65 years and oldercould reduce both short- and long-term disabilityand reduce the burden on the US healthcaresystem, resulting in: fewer acute illnesses andexacerbations of chronic conditions; less contactwith healthcare facilities, especially during thewinter respiratory season; fewer unnecessaryantibiotic prescriptions; and less financial burden.The investigators also evaluated all adults age65 years and older and those with underlyingcardiopulmonary disease at any age who wereadmitted to a local hospital with a spectrum ofacute cardiopulmonary symptoms. RSV andinfluenza were responsible for 9.6 percent and10.5 percent of these hospitalizations, respectively.Based on discharge diagnosis, RSV accounted for10.6 percent of hospitalizations for pneumonia,11.4 percent for COPD, 7.2 percent for asthma,and 5.4 percent for CHF.2Clinical Presentation, Diagnosis,and TreatmentRSV and influenza A present with strikinglysimilar symptoms in adults, making it “nearlyimpossible,” according to Walsh et al,6 todistinguish between the two infectionsbased on clinical presentation alone.2,3,5,6Nearly all RSV-infected adults (89 percent)exhibit some combination of acute respiratorysymptoms (Table 1).2The Cost of RSV in Older AdultsThere are limited data on the cost of RSV in adults.A study published in 2000 estimated the annualcost of RSV-related acute respiratory infection inadults age 65 years only at almost 103 million.24Based on Social Security Administration estimatesof an additional 19 to 21 years life expectancy forindividuals reaching age 65 years today,25 aTesting for RSV is not performed routinely inoutpatient settings because it is not widelyavailable, it is expensive, and there is no clinicalapplication for the results since there are no4
targeted RSV treatments.3,6,27 The similarity ofRSV and influenza symptoms, combined withinfrequent laboratory confirmation of RSVinfection, have contributed to a lack of awarenessof the true impact of RSV in older adults amongboth HCPs and the public. However, with therecent introduction of multiplex real-timepolymerase chain reaction (PCR) for viraltesting, the identification of RSV in adultshas begun to increase.RSV illness usually starts with nasal congestionand rhinorrhea, which progress over several days.Cough, often with sputum production, is commonand can be accompanied by dyspnea andwheezing, a hallmark of RSV infection across allages. On average, patients with RSV present to adoctor or the emergency department on day fiveto seven of the illness.6There is little difference in RSV and influenzasymptoms in adults of any age with high-riskconditions (e.g., chronic heart or lung disease)and otherwise healthy adults age 65 years andolder without high-risk conditions (Tables 1 and2).2,3 Healthy adults with RSV tend to report lessfever and dyspnea, and more wheezing than adultswith influenza. Among hospitalized adults withRSV a substantial proportion report wheezing withboth RSV (73 percent) and influenza infection(53 percent).6 Absence of fever in patientswith RSV appears to be one of the few cluesdifferentiating RSV from influenza.Table 1: Symptoms in Outpatients with LaboratoryConfirmed RSV vs. Influenza A over Four Seasons,1999-2003—Rochester, NYSymptomsHealthy,age 65 yearsHigh-Risk,*age 21 years†RSV, % Influenza A, % RSV, % Influenza A, %n 48n 18n 54n onal53725971Fever18443147Although patients with RSV and influenza reportsimilar symptoms, albeit with differing frequencies,patients with RSV do not seek medical attentionas quickly and experience a longer time fromsymptom onset to hospitalization.3,28 The morerapid symptom onset of influenza combined withhigher fever likely drives these patients to seekmedical care sooner than patients with RSV.*High risk defined as having physician-diagnosed congestive heartfailure or chronic pulmonary disease; †10 percent age 54 years,17 percent age 55-64 years, 73 percent age 65 years.Table compiled by Edward E. Walsh, MD with data from Falsey AR,et al. N Engl J Med. 2005;352(17):1749-1759.2While the data show a milder course of illness forRSV compared with influenza, it is worth notingthat influenza severity can vary substantially byseason according to the circulating strain. In thesix-year Sundaram study,3 the first four seasonswere marked by either dominant or co-circulationof the influenza A (H3N2) virus, which causes moresevere illness than influenza A (H1N1) and B viruses.Preventing RSV in adults age 65 yearsand older could reduce both shortand long-term disability and reduce theburden on the US healthcare system.Patients hospitalized with RSV have similaroutcomes as patients hospitalized with influenza.5
In the Falsey study,2 8 percent of thosehospitalized with RSV died compared to 7 percentfor influenza. In a study by Lee et al,28 9 percent ofthose hospitalized with RSV died compared with10 percent hospitalized with influenza.Table 2: Factors Associated with RSV InfectionCompared to Influenza in Adults Age 50 Yearsover Six Seasons, 2004-2010—Marshfield, WIRSV Positiven 199 (%)InfluenzaPositiven 391 (%)Adjusted OR(95% CI)Patients hospitalized with either influenza or RSVare typically admitted under a wide range ofdiagnoses, similar across both groups.2 Theseinclude pneumonia (39 to 46 percent), acuteexacerbation of COPD (23 to 35 percent), CHF(9 to 13 percent), asthma (7 to 8 percent),bronchitis (1 to 6 percent), and myocardialinfarction (1 to 3 percent).Age group (years)50-6499 (49.8)220 (56.3)Ref65-7976 (38.2)138 (35.3)2.14(1.27-3.60) 8024 (12.1)33 (8.4)5.44(2.30-12.87)121 (60.8)230 (58.8).99 (.62-1.57)GenderFemaleAccurate RSV Diagnosis Relies onLaboratory TestingAcute respiratory illness symptomsCough197 (99.0)384 (98.2)1.77 (.21-14.84)Nasalcongestion178 (89.9)315 (80.6)2.92(1.40-6.08)Wheezing131 (66.5)213 (54.8)1.26(.79-2.01)Since the clinical syndrome is nonspecific,laboratory testing is required for accurateRSV diagnosis. At the current time, PCR is thediagnostic test of choice with 85 percentsensitivity in adults. Viral shedding starts soonafter infection in adults and peaks at about daythree, followed by a two- to three-day plateau andthen a steady decline (Figure 2).29 Nasal sheddingcan last 10 days or more, making it possible todetect RSV by PCR for at least 10 or more daysin the average adult patient. Adults age 65 yearsand older tend to shed slightly higher titers thanyounger adults (2.8 1.0 vs. 2.0 1.3 log10 PFU[plaque-forming unit]/mL) and for a longerduration (11.3 5.2 vs. 8.7 4.3 days).Chronic pulmonary diseaseCOPD9 (4.5)16 (4.1)1.01(.31-3.25)CHF8 (4.0)15 (3.8)1.46(.43-4.95)Interval from symptom onset to nasal swab (days)0-19 (4.5)67 (17.1)Ref2-352 (26.1)153 (39.1)1.59(.65-3.84)4-577 (38.7)106 (27.1)2.55(1.08-6.05) 661 (30.7)65 (16.6)4.77(1.93-11.77)Unfortunately, currently available point-of-carerapid antigen tests, especially those based onenzyme immunoassay, which are widely used forinfants, have very poor sensitivity in adults due tothe relatively low titer of virus shed in respiratorysecretions. Serology is slightly more sensitive thanPCR testing for detecting RSV in older adultsAbbreviations: CHF congestive heart failure; CI confidence interval; COPD chronic obstructive pulmonary disease; OR odds ratio.From: Sundaram ME, et al, Clin Inf Dis. 2014;58(3):342-349.36
New RSV Prevention Approaches onthe HorizonFigure 2: Composite Nasal Shedding in 111RSV-Infected AdultsRSV titer (log 10 pfu/mL)3The RSV surface F protein mediates the virusentry into the host cell and is the major target forvaccines currently in late-phase clinical trials. TheF protein undergoes a conformational changeduring the fusion process, elongating from itsprefusion active version to a nonfunctionalpostfusion state. This may be important forvaccine development because the prefusionF carries a unique neutralizing epitope that isabsent in the postfusion F. Currently, bothpre- and postfusion forms of F are beingassessed as vaccine 78.910.11 12.14Days of SymptomsAdapted from: Walsh EE, et al. J Inf Dis. 2013;207(9):1424-1432.29The F protein is relatively well conserved, unlikethe hemagglutinin (HA) on influenza virus or theG (attachment protein) of RSV. F is very stable,with little antigenic change over time. An anti-Fmonoclonal antibody (palivizumab) is protectivewhen administered prophylactically to prematureinfants, suggesting that induction of neutralizingantibodies against the F protein by immunizationmay be protective in adults. The F protein alsocarries CD8 T-cell epitopes that may be importantin protection from disease severity.(85 percent vs. 82 percent, respectively).Unfortunately, serologic testing results do notreturn in a timely manner to help with clinical care.In adults, RSV infection is associated with lowerviral loads, making detection difficult, especially byrapid antigen tests and viral culture. It is expectedthat technological advances will soon providemore rapid and equally sensitive PCR-basedpoint-of-care tests with costs that allow morewidespread use. This is critical, as it will beimportant to accurately test for and diagnose RSVonce RSV-specific treatments become available.30The RSV G glycoprotein mediates virus attachmentto respiratory epithelial cells, and also cangenerate neutralizing antibodies, although they areless frequent than with F immunization. TheG glycoprotein has a short central conserveddomain but the majority of the protein carrieshypervariable domains with a wide range ofantigenic diversity. It also determines RSV subtype(A or B), and it is highly glycosylated, which mayimpair antibody binding to the antigen. Unlike F,the G protein does not contain CD8 T-cellepitopes. These factors have made the F proteinthe favored target for vaccine-induced immunity.RSV TreatmentRSV treatment in adults is supportive, includingantipyretics, supplemental oxygen, andintravenous fluids as needed.31 Inhaled or systemiccorticosteroids and bronchodilators may be usedfor elderly patients or patients with preexistingpulmonary conditions (e.g., asthma, COPD) withacute wheezing. As referenced earlier, antibioticsare not indicated for patients with RSV, except incases of concomitant bacterial infection, whichoccurs in 10 to 30 percent of RSV infections inhospitalized adults. Bacterial complication rates inoutpatients with RSV have not been studied.7
RSV Vaccines in Developmentimmunogenicity of repeat dosing (efficacy isnot assessed in Season two). The trial enrolledapproximately 1,900 participants in NorthAmerica, Europe, South Africa, and Chile (subjectswith significant ongoing illness were permitted toenroll, subjects with autoimmune disorders andsignificant immunosuppression were excluded).More than three dozen RSV vaccines for a rangeof patient populations are currently in preclinicaldevelopment and more than a dozen are inclinical trials.10 Vaccines currently in Phase 1 includegene-based vector, subunit, particle-based, andlive-attenuated. Live-attenuated vaccines are ofparticular interest for use in infants because theevidence to date suggests they do not pose a riskfor inducing more sev
Respiratory syncytial virus (RSV) is a common cause of acute respiratory illness in older adults, with the risk of serious infection increasing with age.1–4 The virus circulates along with many other winter respiratory viruses, most notably
vaccine trial. We performed a nested phylogeographic analysis of respiratory syncytial virus (RSV) positive samples and classified virus samples into distinct subgroups. The geographic coordinates of household of residence were obtained for study participants using GPS and used to link phylogenetic results to the geographic
The respiratory syncytial virus (RSV) is considered the leading cause of lower respiratory tract infections in chil-dren worldwide [1,2]. RSV also infects adults and is a major pathogen in older adults and immunocompromised individuals [3]. RSV strains are separated into two major groups (A and B) on the basis of antigenic and genetic variability.
Learning At Home: Nursing Management of Respiratory Syncytial Bronchiolitis 2 Respiratory Syncytial Virus
The phylogenetic analysis indicated the genotypes GA2, GA5, SAA1 (Group A), SAB1, SAB3 and BA (Group B) for RSV and Group B, subgroup B1, for MPV. Key-Words: Respiratory syncytial virus, metapneumovirus, genotypes, infants, clinical.
The followings are the types of computer viruses: a) Boot sector virus b) Program virus c) Multipartite virus d) Polymorphic virus e) Stealth virus f) Macro virus. Q4. What is a Boot sector virus? It is a computer virus designed to infect the boot sector of the disk. It modifies or
BAB 5 PENYAKIT YANG DISEBABKAN OLEH VIRUS DAN FITOPLASMA 159 5.1 Virus Belang Kacang Tanah Peanut Mottle Virus (dicetak miring) 159 5.2 Virus Bilur Kacang Tanah (Peanut Stripe Virus) 166 5.4 Nekrosis Tunas (Bud Necrosis) 184 5.5 Virus Roset Kacang Tanah (Groundnut Rosette Virus) 195 5.6 Virus Kerdil Kacang Tanah (Peanut Stunt Virus) 206
Fig. 2: phylogenetic analysis of the G gene of group A human respiratory syncytial virus. The C terminal third of the G gene from 37 Uruguayan strains and 30 sequences downloaded from GenBank belonging to previously described genotypes were analyzed under Maxi-mum Parsimony criterion.
2nd Grade English Language Arts Georgia Standards of Excellence (ELAGSE) Georgia Department of Education April 15, 2015 Page 1 of 6 . READING LITERARY (RL) READING INFORMATIONAL (RI) Key Ideas and Details Key Ideas and Details ELAGSE2RL1: Ask and answer such questions as who, what, where, when, why, and how to demonstrate understanding of key details in a text. ELAGSE2RI1: Ask and answer .
