Severe Influenza Among Children and Young Adults with Neurologic and Neurodevelopmental Conditions — Ohio, 2011

Children with neurologic and neurodevelopmental conditions are at increased risk for severe outcomes from influenza, including death (1–3). In April 2011, the Ohio Department of Health and CDC investigated an influenza outbreak that began in February 2011 in a residential facility for 130 children and young adults with neurologic and neurodevelopmental conditions. This report summarizes the characteristics and clinical courses of 13 severely ill residents with suspected or confirmed influenza; 10 were hospitalized, and seven died. Diagnosis is challenging in this population, and clinicians should consider influenza in patients with neurologic and neurodevelopmental conditions who have respiratory illness or a decline in baseline medical status when influenza is circulating in the community. Prompt testing, early and aggressive antiviral treatment, and antiviral chemoprophylaxis are important for these patients (4,5). When influenza is suspected, antiviral treatment should be given as soon as possible after symptom onset, ideally within 48 hours. Treatment should not wait for laboratory confirmation of influenza (4). During outbreaks, antiviral chemoprophylaxis should be provided to all residents of institutional facilities (e.g., nursing homes and long-term– care facilities), regardless of vaccination status (5). Residential facilities for patients with neurologic and neurodevelopmental conditions are encouraged to vaccinate all eligible residents and staff members against influenza.

As part of the investigation, the Ohio Department of Health and CDC reviewed medical records of all residents of the facility. A confirmed influenza case was defined as laboratory-confirmed influenza (by reverse transcriptase−polymerase chain reaction [RT-PCR] or rapid influenza diagnostic test [RIDT]) in a facility resident. Because the majority of residents were severely neurologically impaired and had difficulty communicating, a suspected case was broadly defined as 1) an increase in the frequency or severity of respiratory abnormalities (e.g., labored breathing, coughing, or wheezing) or 2) an abnormal temperature plus increased crying, irritability/fussiness, refusing feeding, vomiting, or diarrhea in a resident without laboratory confirmation of influenza. Temperature abnormalities included fever (≥100.4°F [≥38.9°C]) or a 2°F temperature deviation from the mean of three previously recorded quarterly temperatures. A severe case of influenza was a laboratory-confirmed or suspected case that resulted in hospitalization or death. For case ascertainment, the outbreak duration was defined as February 1–28, 2011, a period designated to include all confirmed cases and begin at least 1 week before identification of the first confirmed case.

The residential facility provides medical, recreational, and educational services for children and young adults with neurologic and neurodevelopment conditions that affect their ability to perform basic skills of daily living. At the time of the outbreak, the facility provided beds for 130 long-term residents. Median resident age on February 1, 2011, was 21 years (range: 2–41 years). Common diagnoses among residents included severe to profound intellectual disability, epilepsy, cerebral palsy, scoliosis, quadriplegia, visual impairment, recurrent pneumonia, and gastroesophageal reflux.

During the outbreak, 76 residents had acute onset of respiratory illness; 13 were severely ill, including seven with confirmed influenza and six with suspected influenza (Figure). Median age of the severely ill residents was 22 years (range: 14−33 years). Mean duration of illness for severely ill residents was 18 days (range: 6–35 days). All 13 residents with severe influenza had severe to profound neurologic and neurodevelopmental disabilities, including physical limitations (e.g., scoliosis, hemiplegia or quadriplegia, or cerebral palsy) (Table 1), and nine had "do not resuscitate" orders. All 13 severely ill residents received 2010–11 seasonal influenza vaccine during October–November 2010. No temperature data were available for the facility's refrigerator, which was used for vaccine storage during October–November 2010, when facility residents were vaccinated, but the mean recorded temperature of this unit during the investigation was 27°F (range: 10°–42°F) (-2.8°C, range: -12.2°–5.6°C). Fever was the most common clinical sign at illness onset and respiratory failure was the most common hospital discharge diagnosis/cause of death (Table 2). Of nine severely ill residents tested, six were positive for influenza A virus infection by RIDT and one for 2009 influenza A (H1N1)* by RT-PCR. Eight of 13 (62%) severely ill residents received oseltamivir treatment; four (31%) received treatment within 48 hours of illness onset. No facility resident received oseltamivir prophylaxis until February 28, 2011. Ten hospitalizations and seven deaths occurred among the 13 severely ill residents.

Selected Case Reports

Patient A. On February 19, 2011, patient A had fever of 101.2°F (38.4°C), and his oxygen saturation was 88% on room air; empiric treatment with ciprofloxacin was initiated. With his neurologic impairment he was able to make sounds but unable to speak or move on his own volition. He had multiple prior admissions for aspiration pneumonia and a history of abnormalities noted on chest radiography. On illness day 2, he developed mild cough and wheezing and was given supplemental oxygen. On illness day 3, he became tachypneic and required increased respiratory suctioning. On illness day 5, he was hospitalized with fever of 101.3°F (38.5°C) and respiratory rate of 24 breaths-per-minute; empiric treatment with piperacillin/tazobactam and vancomycin was initiated. On illness day 6, he tested positive for influenza A by RIDT and was treated with oseltamivir (60 mg twice daily). On the same day, he developed both acute respiratory distress syndrome requiring mechanical ventilation and sepsis with hypotension requiring vasopressor support. On illness day 7, chest radiography showed diffuse lung opacities that progressed to complete opacity of both lungs. He died on illness day 8.

Patient B. On February 24, 2011, patient B developed fever of 102.2°F (39.0°C), nonproductive cough, rhonchi, tachypnea, increased tracheostomy secretions, and oxygen saturation of 84% on room air. His neurologic impairment rendered him unable to move, make sounds, or speak. On illness day 2, he developed wheezing and had diminished left lower lung breath sounds. He was hospitalized with temperature of 98.8°F (37.1°C), elevated white blood cell count, tachycardia, and respiratory failure requiring mechanical ventilation. Chest radiography showed hazy opacities with low lung volume. He tested positive for influenza A, and treatment with oseltamivir (75 mg once daily) was initiated. He recovered from the acute illness and was discharged to the residential facility after 8 days of hospitalization.

Reported by

Mary DiOrio, MD, Sietske de Fijter, MS, Mindy Schwartz, Shannon L. Page, Ohio Dept of Health. Michael A. Jhung, MD, Lyn Finelli, DrPH, Influenza Div, National Center for Immunization and Respiratory Diseases; Georgina Peacock, MD, Lorraine F. Yeung, MD, Margaret A. Honein, PhD, Cynthia A. Moore, MD, Div of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities; Alejandro Azofeifa, DDS, Loren Rodgers, PhD, Samuel E. Graitcer, MD, EIS officers, CDC. Corresponding contributors: Alejandro Azofeifa, aazofeifa@cdc.gov, 404-498-3858; Loren Rodgers, lrodgers@cdc.gov, 614-728-5976.

Editorial Note

The 13 children and young adults with severe influenza illnesses in this outbreak likely would have benefited from earlier treatment with influenza antiviral medications. Although eight residents received antiviral treatment, oseltamivir was initiated within 48 hours of illness onset in only four cases. Treatment with a neuraminidase inhibitor is best started within 48 hours of symptom onset; however, recent observational data indicate that, even when started more than 48 hours after illness onset, treatment can help prevent influenza-related complications and death in persons at higher risk or with more severe illness (4). The 13 cases in this report highlight two important considerations for influenza in persons with neurologic and neurodevelopmental conditions: 1) the challenges of early diagnosis and treatment, and 2) the increased risk for severe illness in this population.

Clinicians might encounter challenges in diagnosing influenza in persons with severe neurologic or neurodevelopmental conditions because patients might have only subtle deviations from their baseline medical status and be unable to communicate symptoms effectively. Patients with neurologic and neurodevelopmental conditions also might exhibit impaired pulmonary function resulting from muscle abnormalities or conditions such as severe scoliosis. They might, therefore, be less able to clear pulmonary secretions and be at increased risk for subsequent lower respiratory tract infection (1,5). Clinicians who care for these patients should be alert to potential signs and symptoms of influenza during influenza season and administer early and aggressive antiviral treatment if influenza is suspected. Because influenza can appear as a nonspecific respiratory infection, clinicians should consider coadministration of empiric antiviral and antibiotic treatment, if warranted. Side effects such as nausea, vomiting, dizziness, runny or stuffy nose, cough, diarrhea, headache, and some behavioral side effects have been associated with the use of influenza antiviral drugs; however, these are uncommon, and use of antiviral medications is still recommended, especially in this high-risk group.

All 13 severely ill residents reportedly were vaccinated with the influenza vaccine recommended for the 2010−11 influenza season. Although vaccination is the best method for preventing influenza and its complications (4,5), its effectiveness varies depending on vaccine virus match and the age and health of the person vaccinated. Preliminary data for the 2010−11 influenza season indicate that influenza vaccine effectiveness was approximately 60% for all age groups combined, and that almost all influenza viruses isolated were well-matched to the vaccine strains (CDC, unpublished data, 2011). Influenza vaccine effectiveness, however, can be considerably lower in immunosuppressed persons or those with underlying medical conditions (6,7). Influenza can spread rapidly among patients and staff members in residential settings, and outbreaks are not uncommon. Vaccination of health-care personnel has been associated with a decrease in influenza and related mortality in patients in long-term care facilities (8,9). Because persons with neurologic and neurodevelopmental disorders are at high risk for complications and the vaccine might not protect them fully, vaccination should be one part of a larger program of influenza prevention in these settings. The program should include vaccination of residents of long-term care facilities, health-care personnel, and others who might transmit influenza to residents. The program also should include use of infection control precautions, and early use of influenza antiviral medications for treatment of persons with suspected or confirmed influenza and for prevention in other residents and staff members as soon as an outbreak is identified (4).

Low temperatures for vaccine storage can lead to less than optimal vaccine potency. Influenza vaccine should be stored at 35°–46°F (2°–8°C). Although vaccine storage temperature data were not available for the period when the residents were vaccinated, the vaccine refrigerator temperature was considerably below optimal temperature during the investigation. Vaccines must be stored properly from the time they are manufactured until they are administered. Many vaccines can be inactivated by exposure to temperatures colder than 33°F (0.6°C) (10). Temperatures in all refrigerators and freezers used to store vaccine should be read and recorded twice daily.†

The findings in this report are subject to at least two limitations. First, a broad case definition was used to identify suspected cases, and not all ill residents underwent diagnostic testing; thus, respiratory pathogens other than influenza might have contributed to this outbreak. Second, residents of this facility are considerably more medically fragile than patients with mild neurologic and neurodevelopmental conditions; therefore, this report is not generalizable to all patients with neurologic and neurodevelopmental conditions or all patients in residential-care centers.

Clinicians caring for patients with neurologic and neurodevelopmental conditions should be vigilant for signs and symptoms that might indicate early respiratory illness and should initiate influenza antiviral treatment as soon as warranted, especially during influenza season. Prompt testing for influenza and empiric antiviral treatment are recommended for these patients when influenza is suspected (4,5). Antiviral chemoprophylaxis also should be provided to all eligible residents of long-term–care facilities during influenza outbreaks (4,5). Health-care personnel should be vaccinated, and clinicians should continue to encourage influenza vaccination in these patients, given the challenges posed by diagnosis and their increased risk for severe influenza-related outcomes.

Acknowledgments

Rosemary E. Duffy, Brian Fowler, Kim Quinn, Kathleen Duffy, David Feltz, Ohio Dept of Health; Sally Ann Iverson, Shayna Rich, CDC Epi-Elective students; Jessica Citronberg, Emory Univ Rollins School of Public Health; Yvette Dominique, Jean B. Kamgang, National Center on Birth Defects and Developmental Disabilities; Miguel H. Torres-Urquidy, National Center for Immunization and Respiratory Diseases, CDC.

References

1. Cox CM, Blanton L, Dhara R, et al. 2009 pandemic influenza A (H1N1) deaths among children—United States 2009–2010. Clinical Infec Dis 2011;52(Suppl 1):S69–74.
2. Keren R, Zaoutis TE, Bridges CB, et al. Neurological and neuromuscular disease as a risk factor for respiratory failure in children hospitalized with influenza infection. JAMA 2005;294:2188–94.
3. Bhat N, Wright JG, Broder KR, et al. Influenza-associated deaths among children in the United States, 2003–2004. N Engl J Med 2005;353:2559–67.
4. CDC. Antiviral agents for the treatment and chemoprophylaxis of influenza—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2011;60(No. RR-1).
5. Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children—diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1003–32.
6. Herrera GA, Iwane MK, Cortese M, et al. Influenza vaccine effectiveness among 50–64-year-old persons during a season of poor antigenic match between vaccine and circulating influenza virus strains: Colorado, United States, 2003–2004. Vaccine 2007;25:154–60.
7. Michiels B, Govaerts F, Remmen R, Vermeire E, Coenen S. A systematic review of the evidence on the effectiveness and risks of inactivated influenza vaccines in different target groups. Vaccine 2011;29:9159–70.
8. Bridges CB, Kuehnert MJ, Hall CB. Transmission of influenza: implications for control in health care settings. Clin Infect Dis 2003;37:1094–101.
9. Carman WF, Elder AG, Wallace LA, et al. Effects of influenza vaccination of health-care workers on mortality of elderly people in long-term care: a randomised controlled trial. Lancet 2000;355:93–7.
10. CDC. General recommendations on immunization—recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2011;60(No. RR-2).