Hospitalized Patients With Novel Influenza A (H1N1) Virus Infection—California, April-May, 2009

Article Outline

• Summary of Hospitalized Patients
• Case Reports
  • Patient 3
  • Patient 16
  • Patient 18
  • Patient 29
• References

[Centers for Disease Control and Prevention. Hospitalized patients with novel influenza A (H1N1) virus infection—California, April-May, 2009. MMWR Morb Mortal Wkly Rep. 2009;58:536-541.]

Since April 15 and 17, 2009, when the first 2 cases of novel influenza A (H1N1) infection were identified from 2 southern California counties, novel influenza A (H1N1) cases have been documented throughout the world, with most cases occurring in the United States and Mexico.¹, ², ³ In the United States, early reports of illnesses associated with novel influenza A (H1N1) infection indicated the disease might be similar in severity to seasonal influenza, with the majority of patients not requiring hospitalization and only rare deaths reported, generally in persons with underlying medical conditions.², ³ As of May 17, 2009, 553 novel influenza A (H1N1) cases, including 333 confirmed and 220 probable cases, had been reported in 32 of 61 local health jurisdictions in California. Of the 553 patients, 30 have been hospitalized. No fatal cases associated with novel influenza A (H1N1) infection had been reported in California. This report summarizes the 30 hospitalized patients as of May 17, including a detailed description of 4 cases that illustrate the spectrum of illness severity and underlying risk factors. This preliminary overview indicates that, although the majority of hospitalized persons infected with novel influenza A (H1N1) recovered without complications, certain patients had severe and prolonged disease. All hospitalized patients with novel influenza A (H1N1) infection should be monitored carefully and treated with antiviral therapy, including patients who seek care greater than 48 hours after illness onset.⁴, ⁵

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Summary of Hospitalized Patients 

Beginning April 20, 2009, the California Department of Public Health (CDPH) and local health departments in Imperial and San Diego Counties worked with hospital infection control practitioners to initiate enhanced surveillance for patients hospitalized for laboratory-confirmed or probable novel influenza A (H1N1) infection at all 25 hospitals in the 2 counties. Three days later, on April 23, 2009, CDPH extended this surveillance statewide. Cases are reported as either probable (defined as detection of influenza A by real-time reverse transcription–polymerase chain reaction [rRT-PCR] that is unsubtypable for human influenza virus subtypes H1 or H3) or confirmed (defined as positive by Centers for Disease Control and Prevention [CDC] protocol for rRT-PCR for novel influenza A H1N1). Approximately 96% of unsubtypable California specimens subsequently have been confirmed as novel influenza A (H1N1) at the CDC or at the CDPH Viral and Rickettsial Disease Laboratory (VRDL).

For this report, a hospitalized patient was defined as one with confirmed or probable novel influenza A (H1N1) infection, who was hospitalized for greater than or equal to 24 hours. Of the 30 hospitalized patients, 26 had confirmed infection and 4 had probable infection (confirmatory testing is in progress); symptom onset ranged from April 3 to May 9. The cases were reported from 11 counties, most of which are located in southern or central California. The largest number of patients (15 [50%]) resided in San Diego and Imperial Counties. Of the 26 patients for whom information on ethnicity was available, 17 (65%) were Hispanic. Ages of the 30 patients ranged from 27 days to 89 years, with a median age of 27.5 years; 21 (70%) were female patients. Four (13%) patients had traveled to Mexico in the 7 days before onset of illness. None of the 30 patients reported exposure to swine or a known confirmed case of novel influenza A (H1N1) infection.

The most common admission diagnoses were pneumonia and dehydration. Nineteen patients (64%) had underlying medical conditions; the most common were chronic lung disease (eg, asthma and chronic obstructive pulmonary disease), conditions associated with immunosuppression, chronic cardiac disease (eg, congenital heart disease and coronary artery disease), diabetes, and obesity. The most common symptoms were fever, cough, vomiting, and shortness of breath; diarrhea was uncommon. Of the 25 patients who had chest radiographs, 15 (60%) had abnormalities suggestive of pneumonia, including 10 with multilobar infiltrates and 5 with unilobar infiltrates. Six patients were admitted to the ICU, and 4 required mechanical ventilation. Five patients were pregnant. Two of these developed complications, including spontaneous abortion and premature rupture of the membranes; the fetuses were at 13 and 35 weeks' gestation, respectively.

Of the 24 patients tested for influenza A in the hospital, the rapid antigen test was positive in 16 and negative in 5; 3 patients tested positive by other methods (direct immunofluorescent antibody [2 patients] and culture [1 patient]). None of the 30 patients had microbiologic evidence of secondary bacterial infection by blood, urine, or sputum cultures (or endotracheal aspirate or bronchoalveolar lavage cultures in the case of tracheally intubated patients). Fifteen (50%) received antiviral treatment with oseltamivir; for 5 patients, treatment was initiated within 48 hours of onset of symptoms. Among the 15 not treated with antivirals, 6 sought care greater than 48 hours after illness onset. Of the 22 patients with available history, 6 (27%) had received seasonal influenza vaccination. As of May 17, 23 patients had been discharged to home, with a median length of hospital stay of 4 days (range 1 to 10 days). Seven patients remained in the hospital, with median lengths of stay of 15 days (range 4 to 167 days).

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Case Reports 

Patient 3 

An infant girl aged 5 months was born prematurely at 27 weeks in early December 2008, with intrauterine growth retardation and congenital heart disease with patent ductus arteriosus and ventricular septal defect. The infant had a complicated hospital course in the neonatal ICU after birth, including development of bronchopulmonary dysplasia and respiratory distress syndrome requiring prolonged mechanical ventilation and multiple courses of steroids, several episodes of clinical sepsis and pneumonia, and chronic anemia and thrombocytopenia. By the fifth month, the infant had been weaned from the ventilator and was doing well on high-flow nasal cannula oxygen. However, on hospital day 150, she developed a new nonproductive cough and fever, with a new infiltrate of the right lung on chest radiograph that progressed to complete opacification of both lung fields. Multiple blood, urine, and sputum cultures were unrevealing; rapid antigen test was positive for influenza A, with subsequent confirmation at the CDPH VRDL for novel influenza A (H1). The source of the infant's infection is still under investigation. The infant was tracheally reintubated and began receiving broad-spectrum antibiotics and oseltamivir at 2 mg/kg every 12 hours, 3 days after fever. As of May 14, the patient remained hospitalized in critical condition.

Patient 16 

A previously healthy woman aged 29 years, who was 28 weeks pregnant, sought care at an emergency department (ED) on April 26, with complaints of subjective fever, productive cough, and increasing shortness of breath during the preceding 10 days. On initial evaluation, the patient's vital signs were notable for low-grade fever (temperature 99.6°F [37.6°C]), a respiratory rate of 38 breaths/min, blood pressure of 112/57 mm Hg, pulse rate of 104 beats/min, and oxygen saturation of 87% on room air. A chest radiograph revealed bilateral perihilar interstitial infiltrates with mediastinal lymphadenopathy. Her CBC count and chemistry results were normal, except for an increased WBC count of 11.4 cells/mm³, with a differential of 42% segmented neutrophils, 45% bands, and 9% lymphocytes. The patient was admitted to the ICU and began receiving broad-spectrum antibiotics (azithromycin and ceftriaxone). Serial fetal ultrasonographic results were normal. Multiple blood, urine, and sputum cultures were unrevealing; rapid antigen test was positive for influenza A, with subsequent confirmation of novel influenza A (H1N1) at the CDPH VRDL. She was not treated with antiviral medications. She gradually improved and was discharged, receiving amoxicillin, after 9 days.

Patient 18 

A man aged 32 years and with a history of obstructive sleep apnea sought care at an ED on May 5, with a 3-day history of fever, chills, and productive cough. The patient reported he had been receiving amoxicillin for a diagnosis of sinusitis, after complaints of vertigo and dizziness, for the past 2 weeks. His vital signs showed a temperature of 99.1°F (37.3°C), blood pressure of 89/58 mm Hg, and pulse rate of 84 beats/min. Physical examination of the chest showed good air movement bilaterally, although chest radiograph revealed bilateral infiltrates. His CBC count and chemistry results were normal, except for an increased WBC count of 13.8 cells/mm³, with a differential of 94% segmented neutrophils and 4% lymphocytes. An arterial blood gas result showed respiratory acidosis and hypoxemia, with Po₂ of 80 mm Hg on room air. The patient was admitted to the ICU, receiving empiric broad-spectrum antibiotics, and required tracheal intubation on the second hospital day for worsening hypoxemia. Initial microbiologic evaluation and influenza rapid antigen test results were negative; the patient began receiving oseltamivir on hospital day 2. A repeated rapid antigen test and bronchoalveolar lavage viral culture showed positive results for influenza A, with subsequent confirmation of novel influenza A (H1N1). The patient improved, was extubated on hospital day 5, and was discharged on hospital day 10.

Patient 29 

A woman aged 87 years and with multiple medical problems, including recently diagnosed breast cancer with possible abdominal metastasis, hypertension, diabetes mellitus, coronary artery disease, cerebrovascular disease, chronic renal insufficiency, and obesity, was brought for care at an ED on April 21 after being found unconscious by her daughter. The patient had reported onset of fever, cough, and weakness 2 days before admission and also new onset of orthopnea and bilateral leg swelling. She was wheelchair bound and had no recent history of travel or known contact with ill persons. In the ED, the patient was afebrile, with a blood pressure of 57/39 mm Hg, pulse 57 beats/min, respiratory rate of 14 breaths/min, and oxygen saturation of 87% on room air. ECG was suggestive of non-Q-wave myocardial infarction. Chest radiograph showed bilateral pneumonia and congestive heart failure with marked cardiomegaly. Her laboratory abnormalities included an increased WBC count of 13.4 cells/mm³, mild anemia with a hematocrit level of 34%, a mildly increased creatinine level at 1.8 mg/dL, alanine aminotransferase level of 36 units/L and aspartate aminotransferase level of 160 units/L, and markedly increased troponin and creatinine kinase levels of 29.43 ng/mL and 653 IU/L, respectively. The patient went into respiratory arrest, was subsequently tracheally intubated, began receiving low-dose dopamine, and was admitted to the ICU with a diagnosis of myocardial infarction, congestive heart failure, pneumonia, and presumed sepsis. A chest computed tomography scan showed complete atelectasis of the right middle lobe, bilateral ground-glass opacities of the upper lobes, and bilateral pleural effusions. A subsequent bronchoscopy identified a large cauliflower-shaped mass in the right lower lobe airway. Multiple blood, urine, and sputum cultures were unrevealing; rapid antigen test was positive for influenza A, with subsequent confirmation novel influenza A (H1N1) at the CDPH VRDL. The patient remains hospitalized in critical condition under intensive care.

Initial surveillance for hospitalized patients with of novel influenza A (H1N1) infection in California indicates that the majority of patients were discharged after short hospital stays. Previously healthy patients without underlying chronic medical conditions recovered, with an uncomplicated hospital course and a median length of stay of 2.5 days (range 1 to 7 days). Although one-third of hospitalized patients had abnormal chest radiograph results with multilobar infiltrates, only 9% were treated with oseltamivir; nonetheless, most had favorable outcomes. Of 5 pregnant women, 2 developed serious sequelae; however, the role that preceding infection with novel influenza A (H1N1) played in these outcomes is unclear.

Certain hospitalized patients in California experienced severe disease and prolonged hospital courses. Of note, 3 of the 6 California patients admitted to an ICU continue to require prolonged intensive care. Extremes in age and multiple and debilitating underlying medical conditions might be contributing to the severity of illness in these patients. Although chronic underlying medical conditions and pregnancy classically are associated with a greater risk for complications for seasonal influenza,⁶ one patient (patient 18) who was relatively healthy, with only mild chronic pulmonary disease, required intensive care and mechanical ventilation. More data are needed about which populations are at greatest risk for hospitalization and severe sequelae after infection with novel influenza A (H1N1).

As of May 15, 2009, 9% of approximately 11,600 clinical specimens submitted for testing to California public health laboratories since April 27, 2009, were positive by rRT-PCR for influenza A; of those, 23% and 28% were subtyped as seasonal influenza A/H1 and A/H3, respectively. These results indicate that seasonal influenza viruses continue to circulate throughout California and might be a cause of influenza-like illness and positive results from rapid antigen tests. Although rapid antigen test results were positive in 67% of tested cases in this series, anecdotal reports from other cases confirmed at the CDPH VRDL, tested mostly in the outpatient setting, suggest that false-positive and -negative results are common. Accordingly, the CDPH has emphasized the importance of testing influenza viruses in the state with rRT-PCR. The CDPH also has advised clinicians in California to collect respiratory specimens for rRT-PCR testing, subtyping, and further characterization at public health laboratories from patients who are hospitalized or who die with febrile respiratory illness.

Additional information about novel influenza A (H1N1) treatment guidance and other CDC recommendations is available at http://www.cdc.gov/h1n1flu/guidance.

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References 

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