A cluster of cases of severe influenzal disease was recognized in HIV-infected individuals during the 1997–1998 influenza season. Both primary influenza pneumonia and concomitant viral and bacterial pneumonia were found.
In spite of the profound impact of HIV infection on the immune system, influenza has not been recognized as a major clinical problem in HIV-infected patients; only a few case series have been reported [1–4]. However, during the 1997–1998 influenza season, 7 patients with HIV infection were diagnosed with influenza A at the University of Massachusetts Medical Center. We describe the spectrum of disease observed in these patients and compare it with the classic description of pulmonary complications of influenza in the pandemic of 1957–1958 by Louria and coworkers . They distinguished 4 syndromes among 33 patients with documented influenza who were admitted to New York Hospital: influenza with physical signs of lower respiratory tract involvement without roentgenographic evidence of pneumonia (3 cases, no deaths); influenza virus infection followed by secondary bacterial pneumonia (usually after an intervening period of improvement; 15 cases, 8 deaths); acute, rapidly progressive pneumonia apparently due to influenza virus alone (also termed primary influenza virus pneumonia; 6 cases, 5 deaths); and concomitant viral and bacterial pneumonia (9 cases, 4 deaths).
We identified persons with influenza virus isolated from respiratory samples by review of virology laboratory records from October 1997 through April 1998. Respiratory viral cultures had been requested by the patients' physicians for clinical purposes. Specimens were inoculated into rhesus monkey kidney cell cultures (Viromed, Minneapolis) and tested for the presence of respiratory viruses after 48 h of incubation with Bartels Viral Respiratory Screening and Identification Kit (Bartels, Issaquah, WA). From January to March 1998, a total of 80 specimens from 73 patients were submitted for respiratory virus testing, including 19 samples from 14 HIV-infected persons. Influenza A virus was isolated from 14 patients. There were no isolates of influenza B virus. Three isolates were further identified as H3N2 Sydney-like strains at the Massachusetts State Laboratory.
Seven of the 14 patients with influenza A had HIV infection. Details of their background, diagnostic testing, and clinical courses are presented in table 1. Three of these patients had uncomplicated influenza, with typical symptoms of fever and cough, no abnormalities during lung auscultation, and normal chest radiographs. They did not require hospitalization, although patient 6, a 56-year-old man with chronic obstructive lung disease, had mild dyspnea and an oxygen saturation of 93% while breathing room air. The 4 patients admitted to the hospital had radiographically verified pneumonia (figure 1). Patients 1, 2, and 4 had the syndrome of primary influenza virus pneumonia. At presentation, they had dyspnea, productive cough, and abnormal results of chest examination (wheezes in case 1, focal crackles and egophony in case 2, and diffuse crackles and wheezes in case 4). Blood cultures were sterile, and sputum cultures yielded no bacterial pathogens. Studies for other pathogens, including direct fluorescent antibody testing of induced sputum for Pneumocystis carinii, acid-fast smears and cultures, and urine analysis for Legionella antigen, were negative.
Patient 3 presented with fever, cough, dyspnea, and right lower lobe crackles, and lung examination revealed egophony. One month before, the patient had been admitted to the hospital for pneumonia; during that hospitalization, diagnostic testing, including bronchoscopy but not respiratory virus cultures, had failed to yield a diagnosis. Her condition had improved with a 1-week course of intravenous ceftriaxone therapy in the hospital, and her chest radiograph before discharge had showed partial clearing of bibasilar interstitial infiltrates. At the time of the second admission, she had dense airspace consolidation in the areas previously involved (figure 1C); influenza A virus was isolated from an induced sputum sample, and Streptococcus pneumoniae was recovered from blood. Her clinical course suggests the syndrome of secondary bacterial pneumonia, but isolation of influenza virus at the time of the second admission makes concomitant viral and bacterial pneumonia the more likely diagnosis.
None of these patients required mechanical ventilation; patients 1 and 4 received steroid therapy for bronchospasm. All patients recovered and were discharged after 6–7 days.
Louria et al.  stressed that their seriously ill patients often had underlying cardiovascular disease (particularly rheumatic heart disease) or were pregnant; however, 1 had multiple myeloma, and 3 had mild diabetes. Two years later at the same hospital, Kaye et al.  described 3 cases of severe primary viral pneumonia in persons with rheumatic heart disease and 3 previously healthy patients with “mild segmental influenza virus pneumonia.” Our cases seem to lie between these two extremes. All of the patients had definite pulmonary infiltrates in more than 1 location. By current standards, they required prolonged hospitalization. Influenza is known to exacerbate asthma, which may have contributed to the length of stay for 2 of these patients.
This cluster of influenza in HIV-infected patients occurred in the winter of 1997–1998, during an influenza season when the vaccine failed to protect against the predominant circulating H3N2 strain (A/Sydney/5/97) . In the following influenza season, despite heightened clinical suspicion as a result of these cases and participation in the Centers for Disease Control and Prevention Influenza Surveillance Program, we identified only 2 cases of influenza A (1 patient was hospitalized with pneumonia) and 1 case of influenza B (hospitalized patient with no pneumonia) in HIV-infected persons. Six of the 7 patients from 1998 and all 3 from 1999 had received influenza virus vaccine the preceding fall. The difference in the number of cases between the 2 years may reflect the inclusion of the 1999 outbreak strains in the 1998 vaccine, the effect of recent natural exposure, or chance variation. Recent work supports the clinical efficacy of influenza virus vaccine in this population despite reduced immunogenicity .
Clinicians evaluating HIV-infected patients with fever and respiratory symptoms need to consider the diagnosis of influenza. The entities of primary influenza virus pneumonia and concomitant viral and bacterial pneumonia, although less severe than classically described, produce considerable morbidity in these patients and are a worthy target for prevention by immunization.