Nosocomial Pandemic (H1N1) 2009, United Kingdom, 2009–2010

To determine clinical characteristics of patients hospitalized in the United Kingdom with pandemic (H1N1) 2009, we studied 1,520 patients in 75 National Health Service hospitals. We characterized patients who acquired influenza nosocomially during the pandemic (H1N1) 2009 outbreak. Of 30 patients, 12 (80%) of 15 adults and 14 (93%) of 15 children had serious underlying illnesses. Only 12 (57%) of 21 patients who received antiviral therapy did so within 48 hours after symptom onset, but 53% needed escalated care or mechanical ventilation; 8 (27%) of 30 died. Despite national guidelines and standardized infection control procedures, nosocomial transmission remains a problem when influenza is prevalent. Health care workers should be routinely offered influenza vaccine, and vaccination should be prioritized for all patients at high risk. Staff should remain alert to the possibility of influenza in patients with complex clinical problems and be ready to institute antiviral therapy while awaiting diagnosis during influenza outbreaks.

On June 11, 2009, the World Health Organization reported the first influenza pandemic of the 21st century (21,22). Although most cases of pandemic (H1N1) 2009 have been mild or subclinical, patients with severe disease have considerably affected hospital systems (23). Three nosocomial outbreaks of pandemic (H1N1) 2009 were reported in hemopoietic transplantation units and oncology wards. One outbreak was reportedly mild (24), and the other 2 involved aggressive illness, severe complications, and deaths (25,26).
In addition to outbreaks of nosocomial influenza, sporadic nosocomial influenza  (27).
Data included demography, symptoms, medical history, influenza vaccination history, relevant timelines, investigations and results, treatment (e.g., antiviral and antibacterial drugs), outcome, and cause of death when available. Trained health care workers abstracted data from case notes. We included transfers from other hospitals when a transfer was for a reason other than influenza and when the history of influenza clearly indicated that it had been acquired at another hospital.
FLU-CIN procedures were reviewed and approved by the Ethics and Confidentiality Committee of the National Information Governance Board for Health and Social Care in England for collection, storage, and use of personal data for surveillance purposes.

Concurrent Conditions and Reasons for Admission
Twelve (80%) adults and 14 (93%) children had serious underlying illnesses. The most common illnesses were hematologic malignancy for adults (5), and congenital abnormality or prematurity (7) or malignancy (4) for children.
Of the 15 adults, 2 had been admitted for elective surgical procedures; 1 for emergency surgery; and 8 for deterioration of chronic conditions, including complications caused by chemotherapy, malignancy, or transplantation. Two patients were admitted for pancreatitis (1 of whom had underlying myeloma); 1 patient was admitted for obstetric complications, and another patient was admitted for psoriasis. Of 15 children, 3 were admitted for elective procedures, 6 had been in the hospital since birth (because of prematurity or congenital abnormality), 1 was transferred from another hospital, and 5 had acute conditions ( Table 2).

Pandemic Vaccination Status and Use of Antiviral and Antibacterial Drugs
None of the patients had received pandemic influenza vaccine. Although 14 adults were eligible because of concurrent conditions, influenza symptoms developed in 11 either before vaccine became available or before they would have seroconverted if vaccinated at the earliest opportunity (vaccine became available in the United Kingdom at the end of October 2009). Four children were eligible because of age and concurrent conditions, and symptoms developed in 3 before vaccine became available or before they would have seroconverted Only 2 patients (both adults) had received seasonal influenza vaccine.
Twenty-one (72%) of 29 patients (10 children) received antiviral medication as inpatients (data were unknown for 1 patient); all initially received oseltamivir as monotherapy. Therapy for 1 patient (no. 18) was switched to zanamivir after 10 days of oseltamivir therapy because drugresistant virus carrying the H275Y mutation was identified. Administration of antiviral drugs ranged from 0 to 8 days after symptom onset; 12 (57%) of 21 patients who received therapy did so within 48 hours. Sixteen patients were already receiving antibacterial drugs when influenza symptoms began. Two of these patients had a bacterial co-infection: coagulase-negative staphylococci in a blood culture for 1 patient and Pseudomonas aeruginosa in an unspecified intravenous line in 1 patient. Twelve patients received antibacterial drugs during their respiratory illness, 2 of whom had Haemophilus influenzae in sputum samples and 1 (co-infected with rhinovirus) who had had a blood culture positive for Klebsiella sp.

Course of Illness
Median length of hospitalization before onset of influenza symptoms was 11 days for adults (range 4-78 days) and 13 days (range 6-54 days) for children, excluding infants in a hospital since birth. For infants in a hospital since birth, the interval from birth to onset of influenza signs ranged from 41 to 123 days (median = 78 days).
Results of chest radiography ≤3 days after onset of influenza symptoms were documented for 8 adults and 5 children (43%). Of these patients, 4 adults and 1 child (38%) had radiologically confirmed pneumonia.
Level 0 is care given to patients whose care needs can be met through normal ward care.
Level 1 care is given to patients at risk for a deteriorating condition or recently relocated from higher levels of care whose needs can be met in an acute-care ward with additional advice and support from the critical-care team. Level 2 care is given to patients requiring more detailed observation or intervention, including support for a single failing organ system and those changing from higher levels of care (high dependency unit). Level 3 care is given to patients requiring advanced respiratory support alone or basic respiratory support and support for >2 organ systems. This level includes all patients with complex conditions requiring support for multiorgan failure (ICU).
Seven adults and 8 children (50%) required level 3 care (ICU, pediatric ICU, or neonatal ICU). One (3%) adult required level 2 care. Six adults required mechanical ventilation and 1 required noninvasive ventilation (data for ventilatory support were unknown for 1 adult). Three children required mechanical ventilation and 1 required noninvasive ventilation. The remaining 4 children who received level 3 care were 3 infants and 1 child, each of whom required a period of close monitoring, but did not ultimately require ventilation. The remaining 7 adults and 7 children required level 0 or 1 care.

Outcomes and Mortality Rates
Five (33%) of 15 adults died in the acute-care hospital that provided treatment, 2 within 30 days of symptom onset. Of adults who died, 3 had underlying malignancy (1 noted to be terminal) or were immunocompromised and 2 had diabetes (type I and type II respectively).
Pandemic (H1N1) 2009 was included in the recorded causes of death for all 5 adults. Although some patients had a prolonged hospital stay of <7 months, all remaining adults recovered from influenza and were discharged from the hospital.
Of 15 children, 3 (20%) were known to have died, although only 1 (a neonate with multiple congenital problems) died at the hospital where surveillance was conducted; acute respiratory distress syndrome/lower respiratory tract infection was stated as a cause of death.
Another child, with malignancy, whose death was expected, died at home shortly after discharge.
The third child was transferred to another hospital, and cause of death is unknown. All other children recovered from pandemic (H1N1) 2009. Two children remained in the hospital for treatment of their underlying malignancy, and the other children were discharged.

Discussion
Although pandemic (H1N1) 2009 produced a generally mild illness, in the United Kingdom, as elsewhere, severe illness developed in a small proportion of relatively young patients who required hospitalization (28). Although nosocomial outbreaks of pandemic (H1N1)

have been described, (24-26) sporadic nosocomial cases of pandemic (H1N1) 2009
identified during surveillance activities have not been described. The present case series has the advantage of being derived from a larger cohort of hospital inpatients in whom confirmation of pandemic (H1N1) 2009 was obtained by using nationally standardized PCR criteria, from settings where clinical management and infection control precautions were driven by national guidelines (29, 30), and with data abstracted by trained nurses (27).
We based our definition of nosocomial influenza on a recent study of health careassociated influenza in children (31). A recent systematic review of incubation periods of acute respiratory viral infections found that the median incubation period for influenza was 1.4 days for influenza A, and symptoms developed in 95% of patients in <2.8 days (32). These findings suggest that our cutoff point, 3 days after admission, make inclusion of community cases unlikely. In addition, in no patients did onset of respiratory illness occur <4 days after hospital admission; median length of hospitalization before symptom onset was 11 days for adults and 13 days for infants. Therefore, inadvertent inclusion of community-acquired cases is highly unlikely.
On the basis of information obtained in the study, we cannot determine where and from whom patients acquired influenza. However, 3 routes are possible. First, infection could have been acquired from other patients; 1 patient shared a bay with a patient who was presymptomatic at the time but for whom influenza was diagnosed 1 day later. Second, transmission from visitors of patients cannot be ruled out. Although national guidelines strongly discourage persons with influenza-like symptoms from visiting patients (29), this recommendation may have been difficult to implement, particularly for parents of sick children who often provide most hands-on care in a hospital. Third, transmission may have occurred from an infectious health care worker (because staff continue to work when infected with influenza [33]) or from contaminated hands of a health care worker. Transmission from asymptomatic persons might occur in all 3 instances (34).
Nosocomial cases in this study occurred equally in adults and children. Consistent with previous findings (3), most patients had >1 serious underlying illnesses, notably hematologic malignancies, congenital disorders, or prematurity. Staff and caregivers of patients with hematologic malignancy and prematurity are often particularly vigilant for symptoms suggestive of infectious disease. Although we detected nosocomial influenza in patients admitted to nonmedical areas (for emergency or elective surgery), many cases of nosocomial infection in other patient groups probably have been overlooked, particularly because influenza in these groups is likely to have been milder. Additionally, some patients are likely to have been discharged from a hospital during the incubation period of nosocomially acquired pandemic influenza. Thus, in this case series, detecting such patients would not have been possible.
More than half of patients required level 2 or level 3 care, which is higher than that required by the source cohort (12%) (27). Approximately one fifth of children and one third of adults died. Although the deaths of 2 patients were expected because of the stage of their underlying malignancy, this case-fatality rate is far higher than that for patients with pandemic (H1N1) 2009 and concurrent conditions in the source cohort (5%) (27). The combined factors of increased host susceptibility (18)(19)(20), prolonged virus shedding in immunocompromised children (35), and increased likelihood of development of drug resistance (36)