title: Prolonged influenza virus infection during lymphocytopenia and frequent detection of drug-resistant viruses.
abstract: The factors that cause prolonged human influenza virus respiratory tract infection and determine its clinical impact and the development of drug-resistant viruses are unclear. During a 3-year period, symptomatic influenza virus excretion for 2 weeks was observed among 8 immunocompromised patients and found to be associated with lymphocytopenia at onset (8 of 8 patients) more often than with granulocytopenia (2 of 8 patients) or monocytopenia (2 of 8 patients). Six (75%) of 8 patients developed influenza lower respiratory tract infection (10 episodes), and receipt of oseltamivir treatment was significantly associated with clinical improvement (8 of 8 episodes vs. 0 of 2 untreated episodes; P = .02). Complete viral clearance was strongly correlated with lymphocyte reconstitution (P = .04) but was never observed during the first 2 weeks after oseltamivir treatment. Neuraminidase inhibitor-resistant influenza viruses emerged in 2 (67%) of 3 patients eligible for resistance analysis. In conclusion, prolonged influenza virus infection was associated with lymphocytopenia, influenza lower respiratory tract infection, and frequent development of drug resistance during antiviral therapy. Clinical improvement in influenza lower respiratory tract infection is observed during oseltamivir treatment, but complete viral clearance is dependent on lymphocyte reconstitution, irrespective of receipt of antiviral medication.
authors.affiliation: Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. j.gooskens@lumc.nl
authors.forename: Jairo
authors.initials: J
authors.lastname: Gooskens
authors.forename: Marcel
authors.initials: M
authors.lastname: Jonges
authors.forename: Eric C J
authors.initials: EC
authors.lastname: Claas
authors.forename: Adam
authors.initials: A
authors.lastname: Meijer
authors.forename: Aloys C M
authors.initials: AC
authors.lastname: Kroes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000235:genetics; D009980:Influenza A virus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics; D008231:Lymphopenia / Q000150:complications*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D053139:Oseltamivir / Q000627:therapeutic use; D012367:RNA, Viral / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000453:epidemiology; D012189:Retrospective Studies; D017201:Virus Shedding
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D053139:Oseltamivir