An Appropriate Lower Respiratory Tract Specimen Is Essential for Diagnosis of Middle East Respiratory Syndrome (MERS)
Identifieur interne : 000012 ( Pmc/Corpus ); précédent : 000011; suivant : 000013An Appropriate Lower Respiratory Tract Specimen Is Essential for Diagnosis of Middle East Respiratory Syndrome (MERS)
Auteurs : Jae Hoon Lee ; Chang-Seop Lee ; Heung-Bum LeeSource :
- Journal of Korean Medical Science [ 1011-8934 ] ; 2015.
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DOI: 10.3346/jkms.2015.30.8.1207
PubMed: 26240502
PubMed Central: 4520955
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">An Appropriate Lower Respiratory Tract Specimen Is Essential for Diagnosis of Middle East Respiratory Syndrome (MERS)</title><author><name sortKey="Lee, Jae Hoon" sort="Lee, Jae Hoon" uniqKey="Lee J" first="Jae Hoon" last="Lee">Jae Hoon Lee</name><affiliation><nlm:aff id="A1">Department of Internal Medicine and Institute of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Korea.</nlm:aff></affiliation></author><author><name sortKey="Lee, Chang Seop" sort="Lee, Chang Seop" uniqKey="Lee C" first="Chang-Seop" last="Lee">Chang-Seop Lee</name><affiliation><nlm:aff id="A2">Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju, Korea.</nlm:aff></affiliation></author><author><name sortKey="Lee, Heung Bum" sort="Lee, Heung Bum" uniqKey="Lee H" first="Heung-Bum" last="Lee">Heung-Bum Lee</name><affiliation><nlm:aff id="A2">Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju, Korea.</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26240502</idno><idno type="pmc">4520955</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520955</idno><idno type="RBID">PMC:4520955</idno><idno type="doi">10.3346/jkms.2015.30.8.1207</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000012</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000012</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">An Appropriate Lower Respiratory Tract Specimen Is Essential for Diagnosis of Middle East Respiratory Syndrome (MERS)</title><author><name sortKey="Lee, Jae Hoon" sort="Lee, Jae Hoon" uniqKey="Lee J" first="Jae Hoon" last="Lee">Jae Hoon Lee</name><affiliation><nlm:aff id="A1">Department of Internal Medicine and Institute of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Korea.</nlm:aff></affiliation></author><author><name sortKey="Lee, Chang Seop" sort="Lee, Chang Seop" uniqKey="Lee C" first="Chang-Seop" last="Lee">Chang-Seop Lee</name><affiliation><nlm:aff id="A2">Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju, Korea.</nlm:aff></affiliation></author><author><name sortKey="Lee, Heung Bum" sort="Lee, Heung Bum" uniqKey="Lee H" first="Heung-Bum" last="Lee">Heung-Bum Lee</name><affiliation><nlm:aff id="A2">Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju, Korea.</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Korean Medical Science</title><idno type="ISSN">1011-8934</idno><idno type="eISSN">1598-6357</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lee, J" uniqKey="Lee J">J Lee</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Korean Med Sci</journal-id><journal-id journal-id-type="iso-abbrev">J. Korean Med. Sci</journal-id><journal-id journal-id-type="publisher-id">JKMS</journal-id><journal-title-group><journal-title>Journal of Korean Medical Science</journal-title></journal-title-group><issn pub-type="ppub">1011-8934</issn><issn pub-type="epub">1598-6357</issn><publisher><publisher-name>The Korean Academy of Medical Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26240502</article-id><article-id pub-id-type="pmc">4520955</article-id><article-id pub-id-type="doi">10.3346/jkms.2015.30.8.1207</article-id><article-categories><subj-group subj-group-type="heading"><subject>Opinion</subject><subj-group subj-group-type="heading"><subject>Infectious Diseases, Microbiology & Parasitology</subject></subj-group></subj-group></article-categories><title-group><article-title>An Appropriate Lower Respiratory Tract Specimen Is Essential for Diagnosis of Middle East Respiratory Syndrome (MERS)</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Jae Hoon</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Lee</surname><given-names>Chang-Seop</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Heung-Bum</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Internal Medicine and Institute of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Korea.</aff><aff id="A2"><label>2</label>Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea.</aff><aff id="A3"><label>3</label>Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju, Korea.</aff><author-notes><corresp>Address for Correspondence: Chang-Seop Lee, MD. Department of Internal Medicine, Chonbuk National University Medical School, 567 Baekje-daero, Deokjin-gu, Jeonju 561-756, Korea. Tel: +82.63-250-2391, Fax: +82.63-254-1609, <email>lcsmd@jbnu.ac.kr</email></corresp></author-notes><pub-date pub-type="ppub"><month>8</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>15</day><month>7</month><year>2015</year></pub-date><volume>30</volume><issue>8</issue><fpage>1207</fpage><lpage>1208</lpage><permissions><copyright-statement>© 2015 The Korean Academy of Medical Sciences.</copyright-statement><copyright-year>2015</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions></article-meta></front><body><p>The editorial, "Better understanding on MERS Coronavirus (MERS-CoV) outbreak in Korea," was previously published by Lee (<xref rid="B1" ref-type="bibr">1</xref>). He briefly summarized the ongoing status of the Middle East Respiratory Syndrome (MERS) outbreak and emphasized close monitoring of medical staffs, patients, and visitors, and timely well-designed briefings to mass media. He pointed out critical aspects to control the MERS-CoV outbreak in Korea. The present opinion proposes a topic on MERS by focusing on early diagnosis of patients via appropriate specimen collection.</p><p>As on July 2, 2015, there have been 183 confirmed cases of MERS and 33 fatalities reported in the Republic of Korea (<xref rid="B2" ref-type="bibr">2</xref>). This national outbreak of MERS has not been controlled yet but there is a rapid decrease in the number of current infections and fatalities. All patients in Korea acquired their disease in hospital settings where they came in direct or indirect contact with MERS patients. The Ministry of Health and Welfare and the Korea Centers for Disease Control and Prevention have carried out strong enforcement measures including quarantine care for up to 14 days (the maximum incubation period of the disease) in cases of symptomatic travelers from the Arabian Peninsula who arrived in Korea within the past 2 weeks and individuals who came in close contact with confirmed cases of MERS (<xref rid="B2" ref-type="bibr">2</xref>). Suspicious cases are transferred to an assigned hospital if symptoms occur during the observation period. Real-time reverse-transcription polymerase chain reaction (RT-PCR) assay conducted in 48-hour-intervals using respiratory samples is the standard diagnostic tool for MERS.</p><p>A 63-year-old man developed fever, chills, and myalgia on June 10, 2015. On May 27, he visited the emergency department of a hospital that had previously reported several cases of MERS. During this time, he stayed in close contact with a laboratory-confirmed MERS patient. He was quarantined on May 27, 2015 at his home and he developed fever and chills, nausea, anorexia, and myalgia after the quarantine isolation. He was then moved to an institutional isolation care unit where real-time RT-PCR was conducted twice on sputum samples in 48-hour-intervals and resulted in negative findings. He was afebrile but his gastrointestinal discomfort and myalgia continued, and the isolation location was changed to his home on June 2, 2015 because he was improving. On June 8, he became febrile with symptoms of cough, dyspnea, and myalgia, which gradually deteriorated. He was tested again and the results returned positive for MERS-CoV on June 10. Radiographic findings revealed far-progressed bilateral peripheral radio-opacities.</p><p>Some reasons that could be considered for the delayed diagnosis of MERS include: 1) low initial viral load and shedding, and 2) poor sample collection in patients with "no cough" or dry cough. Rapid and correct diagnosis of infection and control measures are critical in preventing the possible spread of MERS-CoV. However, the early symptoms of MERS are non-specific and are the same as those of common pneumonia. In this context, it is very important to conduct thorough and careful patient interviews with a high interest of MERS in mind and to obtain optimal samples for diagnosis. In the clinical findings of patients infected with MERS-CoV, patients with dry cough are more common than patients with productive sputum (<xref rid="B3" ref-type="bibr">3</xref><xref rid="B4" ref-type="bibr">4</xref>). Therefore, optimal sample collection is frequently limited, particularly in patients with no cough or dry cough.</p><p>Dipeptidyl peptidase 4 (DPP4) has been identified as the receptor for MERS-CoV (<xref rid="B5" ref-type="bibr">5</xref>). DPP4 is expressed in type I and II alveolar cells, ciliated or non-ciliated bronchial epithelium, and bronchial submucosal glands (<xref rid="B5" ref-type="bibr">5</xref><xref rid="B6" ref-type="bibr">6</xref>). This corresponds with viral tropism in ex vivo human lung cultures (<xref rid="B5" ref-type="bibr">5</xref><xref rid="B6" ref-type="bibr">6</xref><xref rid="B7" ref-type="bibr">7</xref>). In studies with rhesus macaques, intra-tracheally inoculated virus was present in the lungs but neither in the upper respiratory tracts, trachea, nor other organs (<xref rid="B8" ref-type="bibr">8</xref><xref rid="B9" ref-type="bibr">9</xref>). All of marmosets infected with a high dose of MERS-CoV via various routes showed multifocal to coalescing, moderate to marked acute broncho-interstitial pneumonia centered on small calibre and terminal bronchioles which further extended into the adjacent pulmonary parenchyma. In summary, in vitro and in vivo studies concluded that MERS-CoV had adherence to the lower respiratory tract and high viral loads were mainly detected in distal respiratory tissues. Therefore, lower respiratory tract specimens such as bronchoalveolar lavage fluid, deep tracheal aspirates, and induced sputum contain the highest viral loads which are optimal for increasing diagnostic accuracy (<xref rid="B10" ref-type="bibr">10</xref><xref rid="B11" ref-type="bibr">11</xref><xref rid="B12" ref-type="bibr">12</xref><xref rid="B13" ref-type="bibr">13</xref>).</p><p>In re-evaluating the patient's diagnostic history, his viral load could have been low due to the early phase of disease and/or could have been falsely negative due to inadequate dry cough-linked respiratory samples. In any occasion, his diagnosis was quite delayed. Delayed diagnosis of patients is inevitably linked to delayed quarantine care of persons with contact history.</p><p>To obtain an accurate diagnosis, the circumstances in the early phase of MERS-CoV infection should be considered and at least two repeated diagnostic tests during the late incubation period should be considered for patients with less severity but persistent symptoms. The nationwide pneumonia census has been conducted to identify hidden MERS-CoV infections. However, inadequate sputum specimens must have resulted in false negatives. For accurate surveying, appropriate specimens should have been obtained by collecting sputum from the lungs or bronchi and not saliva. In suspicious patients who are unable to produce sputum for examination, aerosol administration of a hypertonic saline solution may be used to increase the flow of secretions and stimulate coughing. However, during the procedure of induced specimen collection, clinicians must consider the high risk of contamination of the surroundings because the procedure would create a large amount of aerosols and increase the risk of transmitting the virus to other individuals. The optimum time for collection of a sputum specimen is in the early morning before eating or drinking. At this time secretions accumulated in the bronchi through the night are more readily available.</p><p>In conclusion, to control the MERS-CoV infection completely, delicate history taking related with MERS is very important, and appropriate specimen collection is essential as well. Moreover, even two real-time RT-PCR tests in negative results during the early stage of the disease process cannot rule out silent MERS-CoV infections. Clinicians should consider the possibility of false negative real-time RT-PCR findings resulting from inappropriate sample collection. Finally, a sufficient period and strict quarantine of suspected cases are critical for control of the MERS outbreak in Korea.</p></body><back><ref-list><ref id="B1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>J</given-names></name></person-group><article-title>Better understanding on MERS Corona virus outbreak in Korea</article-title><source>J Korean Med Sci</source><year>2015</year><volume>30</volume><fpage>835</fpage><lpage>836</lpage><pub-id pub-id-type="pmid">26130942</pub-id></element-citation></ref><ref id="B2"><label>2</label><element-citation publication-type="webpage"><collab>Korea Centers for Disease Control and Prevention</collab><source>Middle East respiratory syndome Information</source><date-in-citation content-type="access-date">accessed on July 2 2015</date-in-citation><comment>Available at <ext-link ext-link-type="uri" 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