New Respiratory Viruses and the Elderly
Identifieur interne : 001316 ( Pmc/Corpus ); précédent : 001315; suivant : 001317New Respiratory Viruses and the Elderly
Auteurs : Laura Jartti ; Henriikka Langen ; Maria Söderlund-Venermo ; Tytti Vuorinen ; Olli Ruuskanen ; Tuomas JarttiSource :
- The Open Respiratory Medicine Journal [ 1874-3064 ] ; 2011.
Abstract
The diagnostics of respiratory viral infections has improved markedly during the last 15 years with the development of PCR techniques. Since 1997, several new respiratory viruses and their subgroups have been discovered: influenza A viruses H5N1 and H1N1, human metapneumovirus, coronaviruses SARS, NL63 and HKU1, human bocavirus, human rhinoviruses C and D and potential respiratory pathogens, the KI and WU polyomaviruses and the torque teno virus. The detection of previously known viruses has also improved. Currently, a viral cause of respiratory illness is almost exclusively identifiable in children, but in the elderly, the detection rates of a viral etiology are below 40%, and this holds also true for exacerbations of chronic respiratory illnesses. The new viruses cause respiratory symptoms like the common cold, cough, bronchitis, bronchiolitis, exacerbations of asthma and chronic obstructive pulmonary disease and pneumonia. Acute respiratory failure may occur. These viruses are distributed throughout the globe and affect people of all ages. Data regarding these viruses and the elderly are scarce. This review introduces these new viruses and reviews their clinical significance, especially with regard to the elderly population.
Url:
DOI: 10.2174/1874306401105010061
PubMed: 21760867
PubMed Central: 3134957
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">New Respiratory Viruses and the Elderly</title><author><name sortKey="Jartti, Laura" sort="Jartti, Laura" uniqKey="Jartti L" first="Laura" last="Jartti">Laura Jartti</name><affiliation><nlm:aff id="aff1">Department of Geriatrics, Turku City Hospital, Turku, Finland</nlm:aff></affiliation></author><author><name sortKey="Langen, Henriikka" sort="Langen, Henriikka" uniqKey="Langen H" first="Henriikka" last="Langen">Henriikka Langen</name><affiliation><nlm:aff id="aff1">Department of Geriatrics, Turku City Hospital, Turku, Finland</nlm:aff></affiliation></author><author><name sortKey="Soderlund Venermo, Maria" sort="Soderlund Venermo, Maria" uniqKey="Soderlund Venermo M" first="Maria" last="Söderlund-Venermo">Maria Söderlund-Venermo</name><affiliation><nlm:aff id="aff2">Department of Virology, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Vuorinen, Tytti" sort="Vuorinen, Tytti" uniqKey="Vuorinen T" first="Tytti" last="Vuorinen">Tytti Vuorinen</name><affiliation><nlm:aff id="aff3">Department of Virology, University of Turku, Turku, Finland</nlm:aff></affiliation></author><author><name sortKey="Ruuskanen, Olli" sort="Ruuskanen, Olli" uniqKey="Ruuskanen O" first="Olli" last="Ruuskanen">Olli Ruuskanen</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, Turku University Hospital, Turku, Finland</nlm:aff></affiliation></author><author><name sortKey="Jartti, Tuomas" sort="Jartti, Tuomas" uniqKey="Jartti T" first="Tuomas" last="Jartti">Tuomas Jartti</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, Turku University Hospital, Turku, Finland</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21760867</idno><idno type="pmc">3134957</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134957</idno><idno type="RBID">PMC:3134957</idno><idno type="doi">10.2174/1874306401105010061</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">001316</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001316</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">New Respiratory Viruses and the Elderly</title><author><name sortKey="Jartti, Laura" sort="Jartti, Laura" uniqKey="Jartti L" first="Laura" last="Jartti">Laura Jartti</name><affiliation><nlm:aff id="aff1">Department of Geriatrics, Turku City Hospital, Turku, Finland</nlm:aff></affiliation></author><author><name sortKey="Langen, Henriikka" sort="Langen, Henriikka" uniqKey="Langen H" first="Henriikka" last="Langen">Henriikka Langen</name><affiliation><nlm:aff id="aff1">Department of Geriatrics, Turku City Hospital, Turku, Finland</nlm:aff></affiliation></author><author><name sortKey="Soderlund Venermo, Maria" sort="Soderlund Venermo, Maria" uniqKey="Soderlund Venermo M" first="Maria" last="Söderlund-Venermo">Maria Söderlund-Venermo</name><affiliation><nlm:aff id="aff2">Department of Virology, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Vuorinen, Tytti" sort="Vuorinen, Tytti" uniqKey="Vuorinen T" first="Tytti" last="Vuorinen">Tytti Vuorinen</name><affiliation><nlm:aff id="aff3">Department of Virology, University of Turku, Turku, Finland</nlm:aff></affiliation></author><author><name sortKey="Ruuskanen, Olli" sort="Ruuskanen, Olli" uniqKey="Ruuskanen O" first="Olli" last="Ruuskanen">Olli Ruuskanen</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, Turku University Hospital, Turku, Finland</nlm:aff></affiliation></author><author><name sortKey="Jartti, Tuomas" sort="Jartti, Tuomas" uniqKey="Jartti T" first="Tuomas" last="Jartti">Tuomas Jartti</name><affiliation><nlm:aff id="aff4">Department of Pediatrics, Turku University Hospital, Turku, Finland</nlm:aff></affiliation></author></analytic><series><title level="j">The Open Respiratory Medicine Journal</title><idno type="eISSN">1874-3064</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The diagnostics of respiratory viral infections has improved markedly during the last 15 years with the development of PCR techniques. Since 1997, several new respiratory viruses and their subgroups have been discovered: influenza A viruses H5N1 and H1N1, human metapneumovirus, coronaviruses SARS, NL63 and HKU1, human bocavirus, human rhinoviruses C and D and potential respiratory pathogens, the KI and WU polyomaviruses and the torque teno virus. The detection of previously known viruses has also improved. Currently, a viral cause of respiratory illness is almost exclusively identifiable in children, but in the elderly, the detection rates of a viral etiology are below 40%, and this holds also true for exacerbations of chronic respiratory illnesses. The new viruses cause respiratory symptoms like the common cold, cough, bronchitis, bronchiolitis, exacerbations of asthma and chronic obstructive pulmonary disease and pneumonia. Acute respiratory failure may occur. These viruses are distributed throughout the globe and affect people of all ages. Data regarding these viruses and the elderly are scarce. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Open Respir Med J</journal-id><journal-id journal-id-type="iso-abbrev">Open Respir Med J</journal-id><journal-id journal-id-type="publisher-id">TORMJ</journal-id><journal-title-group><journal-title>The Open Respiratory Medicine Journal</journal-title></journal-title-group><issn pub-type="epub">1874-3064</issn><publisher><publisher-name>Bentham Open</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21760867</article-id><article-id pub-id-type="pmc">3134957</article-id><article-id pub-id-type="publisher-id">TORMJ-5-61</article-id><article-id pub-id-type="doi">10.2174/1874306401105010061</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>New Respiratory Viruses and the Elderly</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Jartti</surname><given-names>Laura</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Langen</surname><given-names>Henriikka</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Söderlund-Venermo</surname><given-names>Maria</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Vuorinen</surname><given-names>Tytti</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ruuskanen</surname><given-names>Olli</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Jartti</surname><given-names>Tuomas</given-names></name><xref ref-type="corresp" rid="cor1">*</xref><xref ref-type="aff" rid="aff4">4</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Department of Geriatrics, Turku City Hospital, Turku, Finland</aff><aff id="aff2"><label>2</label>Department of Virology, University of Helsinki, Helsinki, Finland</aff><aff id="aff3"><label>3</label>Department of Virology, University of Turku, Turku, Finland</aff><aff id="aff4"><label>4</label>Department of Pediatrics, Turku University Hospital, Turku, Finland</aff><author-notes><corresp id="cor1"><label>*</label>Address correspondence to this author at the Department of Pediatrics, Turku University Hospital, P.O. Box 52, 20520, Turku, Finland; Fax: +358 2 313 1460; E-mail: <email xlink:href="tuomas.jartti@utu.fi">tuomas.jartti@utu.fi</email></corresp></author-notes><pub-date pub-type="epub"><day>6</day><month>7</month><year>2011</year></pub-date><pub-date pub-type="collection"><year>2011</year></pub-date><volume>5</volume><fpage>61</fpage><lpage>69</lpage><history><date date-type="received"><day>3</day><month>11</month><year>2010</year></date><date date-type="rev-recd"><day>4</day><month>4</month><year>2011</year></date><date date-type="accepted"><day>17</day><month>5</month><year>2011</year></date></history><permissions><copyright-statement>© Jartti <italic>et al.</italic>; Licensee <italic>Bentham Open.</italic></copyright-statement><copyright-year>2011</copyright-year><copyright-holder>Jartti</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (<uri xlink:type="simple" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</uri>) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.</license-p></license></permissions><abstract><p>The diagnostics of respiratory viral infections has improved markedly during the last 15 years with the development of PCR techniques. Since 1997, several new respiratory viruses and their subgroups have been discovered: influenza A viruses H5N1 and H1N1, human metapneumovirus, coronaviruses SARS, NL63 and HKU1, human bocavirus, human rhinoviruses C and D and potential respiratory pathogens, the KI and WU polyomaviruses and the torque teno virus. The detection of previously known viruses has also improved. Currently, a viral cause of respiratory illness is almost exclusively identifiable in children, but in the elderly, the detection rates of a viral etiology are below 40%, and this holds also true for exacerbations of chronic respiratory illnesses. The new viruses cause respiratory symptoms like the common cold, cough, bronchitis, bronchiolitis, exacerbations of asthma and chronic obstructive pulmonary disease and pneumonia. Acute respiratory failure may occur. These viruses are distributed throughout the globe and affect people of all ages. Data regarding these viruses and the elderly are scarce. This review introduces these new viruses and reviews their clinical significance, especially with regard to the elderly population.</p></abstract><kwd-group><title>Keywords</title><kwd>Bocavirus</kwd><kwd>coronavirus</kwd><kwd>elderly</kwd><kwd>influenza virus</kwd><kwd>metapneumovirus</kwd><kwd>polyomavirus</kwd><kwd>respiratory infection</kwd><kwd>torque teno virus.</kwd></kwd-group></article-meta></front><body><sec><title>INTRODUCTION</title><p>Life expectancy has increased globally over the past two centuries by almost 30 years [<xref ref-type="bibr" rid="R1">1</xref>] and only over the last five decades by almost 20 years. This very recent phenomenon emerged as a consequence of improvements in nutrition, hygiene, antimicrobial therapy and vaccinations [<xref ref-type="bibr" rid="R2">2</xref>, <xref ref-type="bibr" rid="R3">3</xref>]. The development of antiviral therapy, has, however, lagged behind. In the elderly, respiratory viral infections still cause significant morbidity and mortality: up to 40% of non-pneumonic lower respiratory illnesses have been linked to respiratory viral infection, and in USA alone, an estimated 54,000 annual deaths have been attributed to the influenza and respiratory syncytial viruses (RSV) [<xref ref-type="bibr" rid="R4">4</xref>-<xref ref-type="bibr" rid="R1">1</xref>].</p><p>A milestone in the diagnostics of respiratory viral infections was the discovery of influenza A virus in 1933 [<xref ref-type="bibr" rid="R12">12</xref>]. After the discovery of the coronaviruses in 1965, no new respiratory viruses or significant virus strains were identified in 32 years. The development of polymerase chain reaction (PCR) techniques in the 1990s initiated a new wave in viral diagnostics. The first avian flu epidemic in humans caused by influenza virus H5N1 struck in 1997 and alerted healthcare professionals by its severity [<xref ref-type="bibr" rid="R13">13</xref>]. In the same year, a virus family never seen in humans before, was identified: the anellovirus, the torque teno virus (TTV) as a signature virus, was found, but their link to human illnesses has not been clarified [<xref ref-type="bibr" rid="R14">14</xref>-<xref ref-type="bibr" rid="R16">16</xref>]. In 2001, human metapneumovirus (MPV) was found followed by the discoveries of other new and significant respiratory viruses and virus strains: the coronaviruses SARS, NL63 and HKU1, the human bocavirus (HBoV), new human rhinovirus (HRV) strains (HRV-C and HRV-D), influenza A virus H1N1, and, as potential respiratory pathogens, the polyomaviruses KI and WU [<xref ref-type="bibr" rid="R17">17</xref>-<xref ref-type="bibr" rid="R28">28</xref>]. This review introduces these new viruses and reviews their clinical significance, especially with regard to the elderly population.</p></sec><sec><title>SEARCH STRATEGY AND SELECTION CRITERIA</title><p>We made systematical searches through the PubMed data base for articles published before March 5, 2011 and indexed with the following search terms: elderly; and influenza H5N1 virus; influenza H1N1 virus; metapneumovirus; coronavirus SARS, NL63, or HKU1; bocavirus; rhinovirus C or D; polyomavirus KI or WU; or torque teno virus. We reviewed only articles published in English.</p></sec><sec><title>INFLUENZA VIRUSES H5N1 AND H1N1</title><p>The most severe epidemics have been caused by the influenza A virus. In 1918-1919 the H1N1 virus pandemic resulted in an estimated 50 to 100 million deaths [<xref ref-type="bibr" rid="R29">29</xref>]. The mortality was surprisingly high among young adults. The most recent pandemics have usually been caused by the influenza A virus strain H1N1 and H3N2. The 2009 H1N1 virus was highly contagious from human to human [<xref ref-type="bibr" rid="R30">30</xref>, <xref ref-type="bibr" rid="R31">31</xref>]. In USA, the prevalence of H1N1-associated deaths was 12 deaths per 100 000 population. Of these, only 9% occurred in persons aged ! 65 years [<xref ref-type="bibr" rid="R31">31</xref>]. Similarly, H5N1 which had its source in birds, has infected humans since 1997, and has, by March 2011, been associated with high mortality; of 528 patients with confirmed disease, 311 (59%) have died [<xref ref-type="bibr" rid="R13">13</xref>, <xref ref-type="bibr" rid="R30">30</xref>, <xref ref-type="bibr" rid="R32">32</xref>, <xref ref-type="bibr" rid="R33">33</xref>]. The mortality rate associated with H5N1 infection has been 89% among children aged <15 years [<xref ref-type="bibr" rid="R32">32</xref>]. Elderly are often protected by pre-existing antibodies from previous illnesses, maybe even decades back [<xref ref-type="bibr" rid="R28">28</xref>, <xref ref-type="bibr" rid="R30">30</xref>, <xref ref-type="bibr" rid="R31">31</xref>]. On the other hand, the risk of severe illness is markedly increased by underlying medical conditions, especially chronic obstructive and other pulmonary diseases, immunosuppression, diabetes, obesity, or chronic heart conditions, which often accompany old age.</p><p>Influenza viruses typically cause mid-winter epidemics. The typical respiratory symptoms (cough, fever and sore throat), however, are poorly associated (43%) with confirmed influenza illnesses in older adults [<xref ref-type="bibr" rid="R34">34</xref>, <xref ref-type="bibr" rid="R35">35</xref>]. Hypoxia and chest radiographs consistent with the acute respiratory distress syndrome are characteristic of patients requiring intensive care [<xref ref-type="bibr" rid="R34">34</xref>]. If death occurs, it follows approximately more than one week after the onset of symptoms and mortality correlates with high virus titers. The cause of death is usually progressive cardiopulmonary failure. The influenza-related morbidity in the elderly is closely related to the prevalence of influenza virus infections among children (reservoir) [<xref ref-type="bibr" rid="R36">36</xref>]. The diagnosis is mainly based on antigen detection and PCR of respiratory specimen, but culture and serology are also available. Treatment options are neuraminidase inhibitors (oseltamivir and zanamivir) or adamantane derivatives (amantadine and rimantadine) [<xref ref-type="bibr" rid="R37">37</xref>]. Systemic corticosteroids are not effective and may, in fact, increase the risk of hospital-acquired pneumonia and superinfections [<xref ref-type="bibr" rid="R38">38</xref>]. Strain-specific influenza vaccination is usually available after 6 to 12 months after emergence of pandemic and has usually high immunogenicity among elderly subjects [<xref ref-type="bibr" rid="R39">39</xref>].</p></sec><sec><title>HUMAN METAPNEUMOVIRUS</title><p>Human metapneumovirus (MPV) causes upper and lower respiratory infections in patients of all ages, but mostly in children aged less than 5 years [<xref ref-type="bibr" rid="R17">17</xref>]. In healthy elderly subjects, MPV-infection is rare: one large study showed MPV RNA in nasal specimens in 1-2% of symptomatic and in 0-2% of asymptomatic elderly subjects [<xref ref-type="bibr" rid="R40">40</xref>]. In another study, MPV was only found in 2% of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) [<xref ref-type="bibr" rid="R41">41</xref>]. The prevalence of symptomatic MPV infection is higher (up to 4-7%) in residents of long-term care facilities [<xref ref-type="bibr" rid="R40">40</xref>]. During outbreaks, up to 72% of elderly institutionalized persons may fall ill, 31% may develop radiographically confirmed pneumonia and 50% may die [<xref ref-type="bibr" rid="R42">42</xref>, <xref ref-type="bibr" rid="R43">43</xref>].</p><p>In adults and elderly, MPV typically causes influenza-like symptoms, such as rhinitis, cough and sore throat, but elderly subjects are more prone to lower respiratory symptoms such as wheezing and dyspnea [<xref ref-type="bibr" rid="R40">40</xref>, <xref ref-type="bibr" rid="R42">42</xref>-<xref ref-type="bibr" rid="R44">44</xref>]. Overall, in the elderly, MPV infections are likely to be less severe than RSV infection and influenza [<xref ref-type="bibr" rid="R40">40</xref>]. The risk factors for severe illness, in addition to old age and institutionalization, include immunosuppression and chronic cardiopulmonary illness. MPV usually causes mid-winter epidemics. Asymptomatic MPV infections are rare. There seem to be two proposed genotypes, A and B, and several subgenotypes of MPV [<xref ref-type="bibr" rid="R45">45</xref>, <xref ref-type="bibr" rid="R46">46</xref>], and thus it is unlikely that infection by either genotype of MPV confers cross-protective immunity. The diagnosis of MPV infections is based on PCR, but immune fluorescence assays are also available. Several vaccine candidates are being investigated [<xref ref-type="bibr" rid="R47">47</xref>, <xref ref-type="bibr" rid="R48">48</xref>].</p></sec><sec><title>SARS-ASSOCIATED CORONAVIRUS</title><p>The pandemic caused by SARS-CoV (SARS = severe acute respiratory syndrome) initiated in November 2002 in Guangdong province, China. It affected more than 8000 patients and caused 774 (approximately 10%) deaths of all ages on 5 continents during an approximately 12 month period [<xref ref-type="bibr" rid="R20">20</xref>, <xref ref-type="bibr" rid="R49">49</xref>, <xref ref-type="bibr" rid="R50">50</xref>]. Infection by SARS-CoV was almost exclusively symptomatic resembling influenza with initial symptoms of fever, myalgia, malaise and chills or rigor [<xref ref-type="bibr" rid="R49">49</xref>]. Cough was common, but dyspnea was prominent only later in the course of the illness. Death was usually due to respiratory failure or a sepsis-related syndrome. Advanced age and co-morbidities increased markedly the risk of severe illness [<xref ref-type="bibr" rid="R50">50</xref>]. PCR tests have been rapidly developed and serology is also available [<xref ref-type="bibr" rid="R19">19</xref>, <xref ref-type="bibr" rid="R20">20</xref>, <xref ref-type="bibr" rid="R49">49</xref>]. No effective treatment is available, but interferons and ribavirin seem to inhibit virus replication [<xref ref-type="bibr" rid="R49">49</xref>]. Since the inflammation is part of the pathogenesis of this disease, corticosteroids may also be helpful if combined with antiviral medication [<xref ref-type="bibr" rid="R49">49</xref>]. Several new antivirals and vaccine candidates are being investigated.</p></sec><sec><title>CORONAVIRUSES NL63 AND HKU1</title><p>In addition to coronaviruses 229E and OC43, the new coronaviruses NL63 and HKU1 were identified in samples of patients with respiratory symptoms in 2005-2006 [<xref ref-type="bibr" rid="R18">18</xref>, <xref ref-type="bibr" rid="R21">21</xref>, <xref ref-type="bibr" rid="R22">22</xref>, <xref ref-type="bibr" rid="R44">44</xref>, <xref ref-type="bibr" rid="R51">51</xref>, <xref ref-type="bibr" rid="R52">52</xref>]. Like other coronaviruses, NL63 and HKU1 can be detected in a small percentage of individuals of all ages [<xref ref-type="bibr" rid="R53">53</xref>]. These viruses have primarily been associated with mild upper respiratory tract infections, but severe lower respiratory tract infections have also been reported [<xref ref-type="bibr" rid="R51">51</xref>, <xref ref-type="bibr" rid="R52">52</xref>]. Diarrhea and abdominal pain may also occur, but symptoms and signs relate primarily to the respiratory tract [<xref ref-type="bibr" rid="R53">53</xref>-<xref ref-type="bibr" rid="R56">56</xref>]. Chronic underlying conditions and advanced age increase the susceptibility and disease severity of CoV infections, and mortality occurs [<xref ref-type="bibr" rid="R44">44</xref>, <xref ref-type="bibr" rid="R53">53</xref>]. In a study of community-acquired pneumonia, most of the HKU1-positive patients were old (median age 72 years) and had significant underlying diseases, especially of the respiratory and cardiovascular systems [<xref ref-type="bibr" rid="R18">18</xref>]. One study reported an outbreak of acute respiratory infection in a personal-care home, where CoV NL63 was identified in 7 of 8 patients aged >50 years [<xref ref-type="bibr" rid="R57">57</xref>]. One elderly patient died 5 days after the onset of HCoV-NL63 infection. CoV-NL63 and CoV-HKU1 are distributed throughout the globe and throughout the year, although they usually peak in the winter time [<xref ref-type="bibr" rid="R54">54</xref>] and cause irregular epidemics every 2–3 years [<xref ref-type="bibr" rid="R58">58</xref>]. Since these viruses are difficult to culture, diagnostic tests other than PCR are not available. There is neither specific antiviral therapy nor vaccine available for HCoV infections [<xref ref-type="bibr" rid="R59">59</xref>].</p></sec><sec><title>HUMAN BOCAVIRUS</title><p>The prevalence of HBoV DNA in respiratory specimens ranges from 1.5-19% [<xref ref-type="bibr" rid="R23">23</xref>,<xref ref-type="bibr" rid="R60"> 60</xref>,<xref ref-type="bibr" rid="R61"> 61</xref>] and the most typical age for a primary HBoV infection is 6-48 months [<xref ref-type="bibr" rid="R62">62</xref>]. HBoV occurs world wide and throughout the year. HBoV has been associated with upper and with lower respiratory tract infections in children [<xref ref-type="bibr" rid="R62">62</xref>-<xref ref-type="bibr" rid="R66">66</xref>], but very little is known about HBoV infections among elderly people. HBoV has also been detected in the feces, in 1-9% of small children with or without gastrointestinal or respiratory symptoms [<xref ref-type="bibr" rid="R67">67</xref>-<xref ref-type="bibr" rid="R70">70</xref>] as well as in river and sewage water [<xref ref-type="bibr" rid="R71">71</xref>,<xref ref-type="bibr" rid="R72"> 72</xref>], but whether it is a true enteric pathogen is not known.</p><p>Although HBoV infections are usually diagnosed with PCR, serological studies have shown that the mere presence of HBoV DNA in the respiratory tract is not proof of an acute primary HBoV infection [<xref ref-type="bibr" rid="R62">62</xref>,<xref ref-type="bibr" rid="R73"> 73</xref>-<xref ref-type="bibr" rid="R75">75</xref>]. Studies on consecutive NPA samples have indeed shown that HBoV DNA can persist in the nasopharynx for several months [<xref ref-type="bibr" rid="R76">76</xref>,<xref ref-type="bibr" rid="R77"> 77</xref>]. Among adults, over 94% have antibodies to HBoV, indicating that they have encountered this virus during their lives [<xref ref-type="bibr" rid="R78">78</xref>,<xref ref-type="bibr" rid="R79"> 79</xref>]. The prevalence figure is high and shows that HBoV infections are extremely common. Only a limited number of HBoV DNA-positive adults have been reported, mainly among immunosuppressed subjects, an observation that is in line with the high seroprevalence of HBoV [<xref ref-type="bibr" rid="R80">80</xref>-<xref ref-type="bibr" rid="R84">84</xref>]. This age pattern was, however, interestingly contradicted by a Canadian study that did not find differences in the prevalence of HBoV among different age groups [<xref ref-type="bibr" rid="R85">85</xref>]. In adults, HBoV-DNA positivity seems to be associated with symptoms, and therefore, HBoV cannot be considered simply an innocent bystander virus [<xref ref-type="bibr" rid="R81">81</xref>,<xref ref-type="bibr" rid="R83"> 83</xref>,<xref ref-type="bibr" rid="R86"> 86</xref>]. Since the discovery of HBoV, three other related bocaviruses (HBoV2, 3 and 4) have been identified in human stool samples [<xref ref-type="bibr" rid="R69">69</xref>,<xref ref-type="bibr" rid="R87"> 87</xref>,<xref ref-type="bibr" rid="R88"> 88</xref>].</p></sec><sec><title>HUMAN RHINOVIRUS, GROUPS C AND D</title><p>Human rhinovirus, the common cold virus, is the most common respiratory pathogen in all age groups [<xref ref-type="bibr" rid="R12">12</xref>]. In the two last decades of the last millennium it was thought that two major genetic groups, A and B, and 99 HRV serotypes exist. Novel PCR-based techniques, however, have identified additionally two groups, C and D, and possibly over 150 different HRV strains [<xref ref-type="bibr" rid="R24">24</xref>, <xref ref-type="bibr" rid="R89">89</xref>, <xref ref-type="bibr" rid="R90">90</xref>]. Moreover, PCR has markedly increased the detection rates of HRV infections. HRV-infection is often associated with other pulmonary morbidity and is the most common virus (up to 60-70%) associated with exacerbations of asthma of all ages and with COPD in adults and the elderly [<xref ref-type="bibr" rid="R91">91</xref>-<xref ref-type="bibr" rid="R96">96</xref>]. In long-term care facilities HRV may cause serious morbidity and mortality, and goes often unrecognized. Louie <italic>et al.</italic> (2005) reported an epidemic of respiratory illness in a long-term care facility, which caused a mortality rate of 21% (12/56 affected residents died) [<xref ref-type="bibr" rid="R10">10</xref>]. Seven of 13 respiratory specimens were culture-positive for rhinovirus [<xref ref-type="bibr" rid="R10">10</xref>]. Hicks <italic>et al.</italic> (2006) reported two nursing home outbreaks of respiratory illness that caused the death of 7 residents out of 294 (2.4%). Of the 29 collected samples, 10 (34%) were positive for rhinovirus [<xref ref-type="bibr" rid="R11">11</xref>]. There is an overall paucity of data on HRV-infections in the elderly.</p><p>Rhinovirus may in exceptional instances cause chronic lung infections which may have a duration of more than 12 months. Such prolonged infections may occur in immunocompromized subjects with lung transplants or hypogammaglobulinemia [<xref ref-type="bibr" rid="R96">96</xref>, <xref ref-type="bibr" rid="R97">97</xref>]. The recently identified group C HRV appears to be related to high morbidity. This virus has circulated at a rate similar to those of the HRV-A and -B groups [<xref ref-type="bibr" rid="R24">24</xref>, <xref ref-type="bibr" rid="R98">98</xref>, <xref ref-type="bibr" rid="R99">99</xref>] and is the cause for almost half of all HRV-associated hospitalizations in children [<xref ref-type="bibr" rid="R100">100</xref>, <xref ref-type="bibr" rid="R101">101</xref>]. Different HRV strains circulate in the community throughout the year, but HRV epidemics typically peak in fall and spring. Diagnosis is based on PCR since these viruses are difficult to culture and serology is not feasible.</p></sec><sec><title>KI AND WU POLYOMAVIRUSES</title><p>In addition to the previously known polyomaviruses, BK and JC, seven new human polyomaviruses have been identified in rapid sequence in 2007-2011. Two of them, detected in the respiratory tract samples, have been named by the institutes where they have been found: KI (Karolinska Institute) polyomavirus (KIPyV) and WU (Washington University) polyomavirus (WUPyV) [<xref ref-type="bibr" rid="R25">25</xref>, <xref ref-type="bibr" rid="R26">26</xref>]. Two have been named by the diseases in association with which they were detected, MCPyV from a skin cancer called Merkel-cell carcinoma and TSPyV from a skin disease called <italic>trichodysplasia spinulosa</italic> [<xref ref-type="bibr" rid="R102">102</xref>, <xref ref-type="bibr" rid="R103">103</xref>]. The remaining three polyomaviruses were also detected in skin samples, and named by numbers, PyV6, 7 and 9 [<xref ref-type="bibr" rid="R104">104</xref>-<xref ref-type="bibr" rid="R106">106</xref>]. The prevalence of the respiratory KI- and WU-polyomaviruses is 2-7% in patients with respiratory symptoms [<xref ref-type="bibr" rid="R25">25</xref>, <xref ref-type="bibr" rid="R26">26</xref>]. Most patients with KI- or WUPyV DNA in their upper airways, are young children with symptoms of rhinitis, cough, bronchiolitis and even pneumonia. Serologic studies show seroprevalences of 50 to 80% for KI- and WUPyVs in healthy children and adults [<xref ref-type="bibr" rid="R108">108</xref>-<xref ref-type="bibr" rid="R110">110</xref>].</p><p>Data on the occurrence of these viruses in the elderly are lacking but are urgently needed, since PyVs are potentially oncogenic and can persist in human tissues [<xref ref-type="bibr" rid="R103">103</xref>, <xref ref-type="bibr" rid="R111">111</xref>]. KI- and WUPyV become reactivated at similar frequencies as the BK and JC viruses during immunosuppression [<xref ref-type="bibr" rid="R111">111</xref>, <xref ref-type="bibr" rid="R112">112</xref>]. Diagnostics is based on PCR and serology [<xref ref-type="bibr" rid="R107">107</xref>, <xref ref-type="bibr" rid="R109">109</xref>].</p></sec><sec><title>TORQUE TENO VIRUS</title><p>Torque teno virus DNA has been recovered from many tissues and secretions but whether this observation is causally related to clinical symptoms or not has not been demonstrated [<xref ref-type="bibr" rid="R14">14</xref>, <xref ref-type="bibr" rid="R113">113</xref>-<xref ref-type="bibr" rid="R115">115</xref>]. TTV is possibly able to replicate in airway tissues [<xref ref-type="bibr" rid="R116">116</xref>, <xref ref-type="bibr" rid="R117">117</xref>] and many other tissues e.g. liver and bone marrow [<xref ref-type="bibr" rid="R118">118</xref>]. The airways might be the primary route of transmission. TTV is very often detected in blood; the prevalence of TTV DNA in the blood of healthy individuals is approximately 70-90% [<xref ref-type="bibr" rid="R119">119</xref>]. A single TTV infection may persist for years and cause chronic viremia [<xref ref-type="bibr" rid="R120">120</xref>-<xref ref-type="bibr" rid="R122">122</xref>]. Simultaneous infections by different TTV variants may also occur. TTV might also aggravate the symptoms caused by other respiratory viruses, or then TTV may be an indicator of the disease process as implied by the findings that TTV concentrations in nasal secretions or plasma have a positive correlation with markers of eosinophilic inflammation and a negative correlation with pulmonary function in asthma [<xref ref-type="bibr" rid="R15">15</xref>]. Also, the severity of bronchiectasis and of idiopathic pulmonary fibrosis correlate with high TTV concentrations [<xref ref-type="bibr" rid="R115">115</xref>]. The association between TTV and disease, could be based on a direct viral effect or be mediated by inflammatory processes that predispose to virus replication. Indeed, TTV replication kinetics have been used as a marker of immune reconstitution after suppression [<xref ref-type="bibr" rid="R123">123</xref>]. Although multiple TTV variants cause problems in detection, the diagnosis of TTV infections is based on PCR; serology will apparently not be developed in the near future [<xref ref-type="bibr" rid="R124">124</xref>].</p></sec><sec><title>DIAGNOSIS</title><p>Making a clinical diagnosis of a respiratory viral illness for elderly patients poses a challenge. The clinical picture is much more blurred in comparison to the typical upper respiratory infection, seen in children and young adults [<xref ref-type="bibr" rid="R35">35</xref>, <xref ref-type="bibr" rid="R125">125</xref>-<xref ref-type="bibr" rid="R127">127</xref>]. Viral infections are usually due to reinfection, and elderly adults usually have some degree of immunity [<xref ref-type="bibr" rid="R128">128</xref>]. Because of pre-existing systemic and mucosal antibodies, elderly adults have probably lower amounts of respiratory secretions and lower viral loads as compared to children. Among elderly patients respiratory viral illness may accompany symptoms of lower respiratory tract involvement, pulmonary and cardiac failure, and nonspecific or atypical symptoms such as confusion, anorexia, dizziness, falls and lack of fever [<xref ref-type="bibr" rid="R125">125</xref>-<xref ref-type="bibr" rid="R128">128</xref>]. Finally, some elderly may also be unable to articulate their symptoms clearly, something they have in common with infants [<xref ref-type="bibr" rid="R128">128</xref>].</p><p>A further challenge to the diagnostics of viral illness is optimal sampling. Nasopharyngeal swabs, aspirates or washes are traditionally used in children but they are not well tolerated in older adults or older people. The best way and time to take samples for viral diagnostics are not known for the elderly. Although nasopharyngeal swab sampling is a sensitive and sufficient method for children [<xref ref-type="bibr" rid="R129">129</xref>, <xref ref-type="bibr" rid="R130">130</xref>], this simplest sampling method may be difficult to apply to adults [<xref ref-type="bibr" rid="R131">131</xref>]. To obtain a sufficient sample and viral load, optimal sampling probably requires both nasopharyngeal and oropharyngeal sampling. Taking swab samples is probably the quickest way and causes the least discomfort while nasopharyngeal washing may collect more viruses [<xref ref-type="bibr" rid="R128">128</xref>, <xref ref-type="bibr" rid="R131">131</xref>].</p><p>Of the conventional diagnostic methods available for these new respiratory viruses, serology is available for the influenza virus, MPV, HBoV and PyVs [<xref ref-type="bibr" rid="R62">62</xref>, <xref ref-type="bibr" rid="R73">73</xref>, <xref ref-type="bibr" rid="R109">109</xref>, <xref ref-type="bibr" rid="R132">132</xref>, <xref ref-type="bibr" rid="R133">133</xref>]. However, serology is not often practical in the acute phase. Of the other conventional methods, a rapid antigen detection test is available for the influenza virus. Some reports suggest that a rapid antigen detection test is relatively sensitive for detection of the influenza virus in elderly patients; during outbreaks up to 77% are detected by rapid antigen testing of culture positive samples [<xref ref-type="bibr" rid="R133">133</xref>, <xref ref-type="bibr" rid="R134">134</xref>]. Other studies have reported much lower sensitivities (38-43% compared with PCR) [<xref ref-type="bibr" rid="R135">135</xref>, <xref ref-type="bibr" rid="R136">136</xref>]. The sensitivity may be only 8-22% in patients !80 years of age [<xref ref-type="bibr" rid="R137">137</xref>]. Despite a poor sensitivity, the rapid antigen detection test is highly specific for detecting influenza viruses in the elderly</p><p>All new respiratory viruses can be diagnosed by sensitive PCR methods [<xref ref-type="bibr" rid="R44">44</xref>]. When diagnosing acute HBoV or SARS-CoV infection, PCR needs to be complemented with serology. Currently, up to 85-95% of all viruses in respiratory samples of children with respiratory symptoms may be detected [<xref ref-type="bibr" rid="R61">61</xref>, <xref ref-type="bibr" rid="R138">138</xref>-<xref ref-type="bibr" rid="R142">142</xref>]. PCR is the best choice also for the elderly since it is the most sensitive method for detection of viruses in this age group as well [<xref ref-type="bibr" rid="R136">136</xref>, <xref ref-type="bibr" rid="R143">143</xref>-<xref ref-type="bibr" rid="R147">147</xref>], although the detection rates, probably due to the difficulties in sampling, decline with age. The detection rates among elderly patients have remained below 40% even in exacerbations of chronic pulmonary disease [<xref ref-type="bibr" rid="R91">91</xref>, <xref ref-type="bibr" rid="R92">92</xref>, <xref ref-type="bibr" rid="R95">95</xref>, <xref ref-type="bibr" rid="R148">148</xref>] and viral pneumonia [<xref ref-type="bibr" rid="R149">149</xref>]. The rates in the intermediate age groups, i.e., adults with exacerbations of COPD or asthma have been up to 64% [<xref ref-type="bibr" rid="R150">150</xref>-<xref ref-type="bibr" rid="R152">152</xref>]. The actual prevalences of the new viruses among the elderly population are not known [<xref ref-type="bibr" rid="R5">5</xref>, <xref ref-type="bibr" rid="R7">7</xref>, <xref ref-type="bibr" rid="R10">10</xref>, <xref ref-type="bibr" rid="R11">11</xref>, <xref ref-type="bibr" rid="R148">148</xref>, <xref ref-type="bibr" rid="R153">153</xref>].</p><p>The interpretation of positive PCR results is complicated by multiple co-existing viruses especially in symptomatic children (up to 43%) and by high virus detection rates in asymptomatic subjects (up to 40-68% in young children) [<xref ref-type="bibr" rid="R139">139</xref>, <xref ref-type="bibr" rid="R154">154</xref>-<xref ref-type="bibr" rid="R157">157</xref>]. In a review of the literature that goes back to 1965 and stretches to 2008, the prevalence of viruses in 15000 samples from asymptomatic subjects was higher by PCR than by conventional methods [<xref ref-type="bibr" rid="R158">158</xref>]. This casts some doubt on the clinical significance of PCR-positive viral findings overall. Several studies have, on the other hand, demonstrated that positive PCR results are clinically relevant at least as far as HRV is concerned. Identification of HRV correlates with respiratory symptoms, dual HRV infections are rare and overall, the prevalence of recurrent or persistent respiratory viral infections (excluding TTV and HBoV) is low (3-4%) [<xref ref-type="bibr" rid="R96">96</xref>, <xref ref-type="bibr" rid="R158">158</xref>-<xref ref-type="bibr" rid="R160">160</xref>]. Positive findings with PCR correlate with systemic or local immune responses in children and in adults [<xref ref-type="bibr" rid="R161">161</xref>-<xref ref-type="bibr" rid="R163">163</xref>]. These findings, which mainly apply to HRV and not to HBoV, suggest that HRV-PCR positivity probably reflects a true, current respiratory infection with or without symptoms, rather than residual nucleic acids from some other distant infection. Of course, any findings in upper airway samples do not necessarily reflect the situation in lower airways [<xref ref-type="bibr" rid="R164">164</xref>]. Multiple PCR analyses of single samples (multiplex PCR) may sound attractive, but the sensitivity for identification of individual viruses may be lost compared to single virus PCR [<xref ref-type="bibr" rid="R165">165</xref>]. Of note, most of these data are from studies on children and adults, and data on new respiratory viruses in the elderly are scarce.</p></sec><sec><title>IMMUNOSENESCENCE</title><p>The term immunosenescence describes the deleterious age-associated changes in the immune system that render elderly individuals susceptible to infectious disease and increases morbidity and mortality [<xref ref-type="bibr" rid="R3">3</xref>, <xref ref-type="bibr" rid="R166">166</xref>]. With age, all components of immunity are affected, but the T cells are the most susceptible [<xref ref-type="bibr" rid="R167">167</xref>]. Although the adaptive function of immunity appears to be more seriously affected than the innate immune system, the increased susceptibility to lower respiratory tract viral infections relates particularly to defective innate immunity [<xref ref-type="bibr" rid="R163">163</xref>, <xref ref-type="bibr" rid="R168">168</xref>]. The weakening immune responses could be linked to the over-all long-term poor outcome in the elderly [<xref ref-type="bibr" rid="R166">166</xref>]. Immunosenescence is a multifactorial process and is associated with thymic involution, chronic antigenic stimulation (predominantly attributable to persistent infections), signal transduction changes in immune cells, and protein-energy malnutrition [<xref ref-type="bibr" rid="R169">169</xref>]. There is a paucity of accurate data on the link between the causes of death of elderly and the age-associated changes in the immune system.</p></sec><sec><title>TREATMENT</title><p>With the exception of the influenza viruses, there are no specific treatments or vaccines available to combat the new viruses. In this sense, there is no clinical need for a viral diagnosis. Viral detection may still have practical importance with regard to isolating practices of infected patients in hospitals or in long-term care settings to prevent transmission of disease [<xref ref-type="bibr" rid="R128">128</xref>] and for proper supportive treatment, including avoidance of unnecessary antibiotic treatments [<xref ref-type="bibr" rid="R146">146</xref>].</p><p>An increased susceptibility to viral infections could be a marker of a pulmonary inflammatory processes, and indicate a need for intensified treatment of chronic pulmonary illness. For example, TTV and AdV infections are associated with a chronic inflammatory state of the lungs [<xref ref-type="bibr" rid="R15">15</xref>, <xref ref-type="bibr" rid="R170">170</xref>-<xref ref-type="bibr" rid="R173">173</xref>]. In children, there is a link between susceptibility to HRV-induced wheezing and the development of asthma [<xref ref-type="bibr" rid="R174">174</xref>-<xref ref-type="bibr" rid="R178">178</xref>], and in adults, HRV is the most important trigger of exacerbations of COPD [<xref ref-type="bibr" rid="R91">91</xref>,<xref ref-type="bibr" rid="R95"> 95</xref>].</p><p>Current knowledge on bacterial-viral coinfections in the elderly is very limited. In community-acquired pneumonia of adults, there is evidence of mixed viral-bacterial infection in up to 15% of cases and in children up to 45 % of cases [<xref ref-type="bibr" rid="R179">179</xref>]. The most frequent combinations have been <italic>Streptococcus pneumoniae </italic>with influenza A virus or HRV. Bacterial and viral infections may act deleteriously through synergistic mechanisms. There may be destruction of the respiratory epithelium by the viral infection, which may increase bacterial adhesion; virus-induced immunosuppression may cause bacterial superinfections; and the inflammatory response to viral infection may up-regulate the expression of molecules that are suitable for bacteria as receptors [<xref ref-type="bibr" rid="R180">180</xref>].</p><p>Vaccines are being developed against these new viruses. The most promising preclinical results have been reported for vaccine candidates for MPV and SARS-CoV, but their efficacy have not been studied in humans [<xref ref-type="bibr" rid="R181">181</xref>, <xref ref-type="bibr" rid="R182">182</xref>].</p></sec><sec sec-type="conclusions"><title>CONCLUSIONS</title><p>The new respiratory viruses or viral strains include influenza A virus H5N1 and H1N1, MPV, SARS-, NL63- and HKU1-CoV, HBoV, HRV-C and –D and the possible respiratory pathogens, KI- and, WU-PyV and TTV [<xref ref-type="bibr" rid="R13">13</xref>, <xref ref-type="bibr" rid="R14">14</xref>, <xref ref-type="bibr" rid="R17">17</xref>-<xref ref-type="bibr" rid="R28">28</xref>]. All these new viruses are distributed throughout the globe and affect people of all ages, but data on these viruses and the elderly are scarce. These new viral infections can be diagnosed by sensitive PCR methods. The viruses may be detectable in the airways for varying periods of time also after the acute phase and this leads to a diagnosis of several concomitant viruses. The classical predisposing factors to viral infections include advanced age, chronic illnesses and poor immune responses. The elderly often have partial immunity and chronic illnesses; these circumstances modify their responses to viruses and thus respiratory viral infections may manifest themselves as atypical symptoms or as exacerbation of chronic illnesses. Serious outbreaks have been reported in long-term care facilities. Vaccination is the most effective way to prevent serious disease, but it is only available for the influenza virus. Virus-specific treatment is also available only for the influenza virus. Early identification of a viral pathogen through improved viral diagnostics is crucial for successful treatment of viral illnesses. Preventive measures are also important, such as vaccinations, hand-washing and isolation of the affected individuals in hospitals and long-term care facilities. The ultimate clinical significance of the new respiratory viruses is still poorly unknown in the elderly population but probably these infections are greatly underestimated.</p></sec></body><back><ack><title>ACKNOWLEDGEMENTS</title><p>Supported by the EVO funds by Turku City Hospital, Turku, and the Academy of Finland, Helsinki, both in Finland.</p></ack><ref-list><title>REFERENCES</title><ref id="R1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Christensen</surname><given-names>K</given-names></name><name><surname>Doblhammer</surname><given-names>G</given-names></name><name><surname>Rau</surname><given-names>R</given-names></name><name><surname>Vaupel</surname><given-names>JW</given-names></name></person-group><article-title>Ageing populations: the challenges ahead</article-title><source>Lancet</source><year>2009</year><volume>374</volume><fpage>1196</fpage><lpage>208</lpage><pub-id pub-id-type="pmid">19801098</pub-id></element-citation></ref><ref id="R2"><label>2</label><element-citation publication-type="book"><collab>World Health Organization</collab><article-title></article-title><source>The European Health Report 2002. 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