Session:

Update on Influenza

Abstract No.:

24.002

Title:

Clinical features and pathogenesis of H5N1 influenza in humans

Author(s):

T. T. Hien; Oxford University Clinical Research Unit (OUCRU) Vietnam, Wellcome Trust Overseas Major Programme (MOP), Hoi Chi Minh/VN

Abstract:

Avian influenza A (H5N1) occurred in poultry throughout Asia has had major economic and health repercussions. Infections with this virus have been identified since January 2004 and despite intensive clinical management the case fatality is still unacceptably high.  We report the clinical findings among patients with confirmed cases of avian influenza A (H5N1) who presented to hospitals in Vietnam. In all 67 cases, the diagnosis of influenza A (H5N1) was confirmed by means of viral culture or reverse transcriptase–polymerase chain reaction (RT-PCR). Patients presented to hospitals after a median duration of illness of 6 days with fever (75%) cough (89%) and dyspnea (98%). Diarrhea and mucosal bleeding at hospital admission were more common in fatal than in non fatal cases. Common findings were bilateral pulmonary infiltrates on chest X-Ray (72%), lymphopenia (73%), and increased serum transaminase levels (ALT69%, ALT 61%). The most reliable predictor of a fatal outcome was the presence of both neutropenia and raised ALT level on admission (correctly predicted 91% of death and 82% of survival). Treatment of oseltamivir showed benefit but use of corticosteroid is associated with increased risk of death.  Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads. Our observations indicate that high viral load, and the resulting intense inflammatory responses, is central to influenza H5N1 pathogenesis. The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment.  Despite recent progress, knowledge of the epidemiology, natural history, and management of influenza A (H5N1) disease in humans is still incomplete. There is an urgent need for more coordination in clinical and epidemiologic research among institutions in countries with cases of influenza A (H5N1) and internationally.