Clinical management of pandemic 2009 influenza A(H1N1) infection

Abstract

Antiviral therapy and vaccination are important strategies for controlling pandemic 2009 influenza A(H1N1) but efficacy depends on the timing of administration and is often limited by supply shortage. Patients with dyspnea, tachypnea, evidence of hypoxemia, and pulmonary infiltrates on chest radiograph should be hospitalized. Patients with severe illness or underlying medical conditions that increase the risk of more severe disease should be treated with oseltamivir or zanamivir as soon as possible, without waiting for the results of laboratory tests. Lung-protective ventilation strategy with a low tidal volume and adequate pressure, in addition to a conservative fluid management approach, is recommended when treating adult patients with ARDS. Extracorporeal membrane oxygenation has emerged as an important rescue therapy for critically ill patients. Use of systemic steroids was associated with delayed viral clearance in severe acute respiratory syndrome and H3N2 infection. Low-dose corticosteroids may be considered in the treatment of refractory septic shock. Passive immunotherapy in the form of convalescent plasma or hyperimmune globulin may be explored as rescue therapy. More data are needed to explore the potential role of IV gamma globulin and other drugs with immunomodulating properties, such as statins, gemfibrozil, and N-acetyl-cysteine. Health-care workers must apply strict standard and droplet precautions when dealing with suspected and confirmed case and upgrade to airborne precautions when performing aerosol-generating procedures. Nonpharmacologic measures, such as early case isolation, household quarantine, school/workplace closure, good community hygiene, and restrictions on travel are useful measures in controlling an influenza pandemic at its early phase.

Figure 1

(A) Chest radiograph of an obese, 23-year-old woman (BMI 31 kg/m²). She had influenza symptom onset on July 8, 2009, and was treated by a general practitioner with antibiotics. A chest radiograph taken on July 15, 2009, showed bilateral mid and lower zone patchy infiltrates. Reverse transcription-polymerase chain reaction (RT-PCR) from the nasopharyngeal aspirate was positive for the pandemic A(H1N1) virus. Oseltamivir 150 mg bid was started on July 15, 2009. (B) Despite treatment with high-dose oseltamivir and supplemental oxygen, her condition deteriorated, and a chest radiograph taken on July 18, 2009, showed bilateral and extensive consolidation. She required invasive mechanical ventilation (IMV) on July 18, 2009, with lung-protective ventilation strategy and conservative fluid management. (C) Her condition improved following intensive care support and high-dose oseltamivir for 10 days. She was extubated on July 24, 2009. Chest radiograph taken on July 29, 2009, showed marked clearing of the lung consolidation.

Figure 2

Virus-shedding profile of the same 23-year-old obese woman as shown in Figure 1 with pandemic A(H1N1) infection. Although the concentration of virus shed from the upper respiratory tract decreased after a few days of antiviral therapy, very high viral loads were detected from the lower respiratory tract specimens (tracheal aspirates) from July 18-22, 2009. Viral copy numbers were determined by real-time RT-PCR targeting the matrix protein gene. Specimens with undetectable viral copy number (lower detection limit = 62.6 viral copies/μL) were plotted at zero. Dotted line represents virus concentrations detected from upper respiratory tract specimens, and solid line represents virus concentrations detected from lower respiratory tract specimens. See Figure 1 legend for definition of abbreviation.

Figure 3

Virus-shedding profile of a 68-year-old man who was hospitalized with acute exacerbation of COPD on July 6, 2009, with a 2-day history of cough, fever, and increased dyspnea. His chest radiograph showed no consolidation. He was given prednisolone 30 mg daily for 10 days and amoxicillin-clavulanate 1 g bid for acute exacerbation of COPD. RT-PCR from his nasopharyngeal aspirate taken on July 6, 2009, was positive for the pandemic A(H1N1) virus. Oseltamivir 75 mg bid was started on July 7, 2009, for 5 days. He developed hypercapnic respiratory failure on July 8, 2009, and required noninvasive positive pressure ventilation (NPPV) support for 2 days in a negative pressure isolation room. His nasopharyngeal flocked swab was still positive by RT-PCR on July 16, 2009, although clinically he was well. The use of systemic steroid for COPD might have prolonged his viral shedding. He was discharged from hospital well on July 26, 2009. Viral copy numbers were determined by real-time RT-PCR targeting the matrix protein gene. Specimens with undetectable viral copy number (lower detection limit = 62.6 viral copies/μL) were plotted at zero. See Figure 1 legend for definition of abbreviation.