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.

Host immunity dictates influenza A(H1N1)pdm09 infection outcome in hematology–oncology patients

“…The findings from this study confirm that influenza virusinfected hematology-oncology patients develop a wide clinical spectrum ranging from mild 1 to severe respiratory symptoms [2][3][4] during prolonged viral excretion. Innate and adaptive host immune responses appear to be major determinants of virusassociated outcome and viral clearance.…”

“…[1][2][3][4][5][6] These patients often develop mild virus-associated symptoms and occasional bacterial or fungal pneumonic coinfections, but significant numbers of cases develop severe influenza virus-associated lower respiratory tract infection (LRTI) and acute respiratory distress syndrome (ARDS). Risk factors for influenza LRTI include profound lymphopenia, lack of early antiviral treatment and old age.…”

“…Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation and lymphocyte subsets were quantified by flow cytometry using CD3, CD4, CD8, CD16, CD19 and CD56 fluorochrome-labeled antibodies. 9 Minimum absolute cell count references were defined for granulocytes (500/ mm 3 3 ). T-cell counts ⩽ 20% of minimum reference were defined as profound T-cell lymphopenia.…”

Faut-il avoir peur de la grippe chez la femme enceinte ?

“…Le nombre de lymphocytes T cytotoxiques spécifiques atteint son acmé 14 jours après le début de l'infection, et redescend progressivement jusqu'à son niveau basal. La lymphopénie est associée dans des contextes d'immunosuppression à une excrétion virale prolongée [8], et il existe une corrélation démontrée entre le nombre de lymphocytes T mémoires spécifiques et le taux de clairance virale respiratoire (revue dans [7]). Il existe une lymphopénie physiologique pendant la grossesse.…”

“…Surtout, la moitié des femmes âgées de 15 à 45 ans décédées de grippe étaient enceintes. En période épidémique, les femmes enceintes de plus de 6 mois déve-loppent plus fréquemment que les femmes non enceintes une morbidité liée à la grippe (10,5/10 000, IC 95 [6,[7][8][9][10][11][12][13][14]3] [16], versus < 1 % dans la population géné-rale). Il s'agit d'une complication sévère y compris en dehors de la grossesse, avec une mortalité rapportée de 12 à 40 % [17,18].…”