Clinical and Health Affairs
Novel H1N1 Influenza Hospitalizations
Minneapolis-St. Paul Metropolitan Area, 2008-2009
By Laura Fleege, Emily Hallberg, Craig Morin, M.P.H., Richard Danila, Ph.D., M.P.H., and Ruth Lynfield, M.D.
Abstract
The influenza season of 2008-2009 will be remembered for the initial wave of novel influenza A (nH1N1) that was noted in the spring. This strain of influenza rapidly spread throughout the United States and Minnesota. Notable features in Minnesota include a higher incidence rate among children, a higher proportion of patients who also had asthma, and a higher incidence rate of pneumonia at discharge among hospitalized nH1N1 cases compared with seasonal influenza A cases.
The first novel influenza A (nH1N1) influenza cases, which heralded the first influenza pandemic in more than 40 years, were identified as an outbreak of respiratory illness in Mexico in March and early April of 2009, with the earliest case report of illness onset on March 17.1 The first laboratory-confirmed case of nH1N1 in the United States was identified in California on April 14.2 Within two weeks, nearly 100 cases had been documented across the country.3 In response to the growing number of cases, Health and Human Services Secretary Kathleen Sebelius declared a public health emergency on April 26.4 In June, the Centers for Disease Control and Prevention (CDC) reported that all 50 states and major territories had laboratory-confirmed nH1N1 cases.5 By mid-July, there were more than 43,000 reported cases of nH1N1 in the United States.6 On July 24, the CDC stopped collecting and reporting individual case counts. By that time, a number of states were focusing on hospitalized cases only, rather than trying to identify all cases. As of September 4, more than 9,000 persons had been hospitalized with nH1N1 influenza in the United States and 593 deaths had been attributed to the virus.7
Other parts of the world were encountering similar outbreaks. By April 29, nH1N1 was identified in Europe, the Middle East, and New Zealand.3 The number of cases continued to climb and exceeded 27,000 by the beginning of June.8 On June 11, the World Health Organization (WHO) increased the pandemic threat level for nH1N1 to phase 6, its highest level.9 This declaration of a global influenza pandemic was recognition that nH1N1 had spread through multiple countries and continents; but it was not an indication of severity of illness. Between April 19 and August 1, 59% of influenza cases reported by more than 73 countries and territories to the WHO through FluNet, an Internet-based data query and reporting tool for global influenza surveillance, were nH1N1.10 As of September 13, the cumulative number of cases reported to the WHO reached nearly 300,000; by that time, nearly 3,500 people had died as a result of nH1N1.11
In Minnesota, the first case of nH1N1 was confirmed on April 30, 2009. Interestingly, this individual had no epidemiological connection to Mexico, suggesting that nH1N1 was already circulating in the community. The Minnesota Department of Health has a number of influenza surveillance systems in place including population-based surveillance for laboratory-confirmed cases of hospitalized influenza (begun in 2003 in the seven-county Minneapolis-St. Paul [MSP] metropolitan area); weekly reports from 27 sentinel outpatient clinics on the number of patients seen with influenza-like illness; school and long-term care facility reporting of outbreaks of influenza-like illness; reporting of deaths caused by influenza or pneumonia in Minneapolis, St. Paul, and Duluth; and reporting of deaths caused by influenza in children throughout the state. We describe the epidemiology of laboratory-confirmed nH1N1 infections in patients hospitalized in the MSP area and compare the clinical and epidemiological characteristics of hospitalized nH1N1 cases to seasonal influenza A cases during the 2008-2009 influenza season.
Methods
Surveillance for laboratory-confirmed, hospitalized cases of influenza in Minnesota was established in 2003 as part of the CDC’s Emerging Infections Program (EIP). The EIP is a network of health departments, academic institutions, and medical centers that provide national surveillance. Laboratory-confirmed cases of influenza are reported to the Minnesota Department of Health, with the focus of surveillance being hospitalized cases. Medical record reviews are conducted for hospitalized cases in the MSP area. The MSP area includes Anoka, Carver, Dakota, Hennepin, Ramsey, Scott, and Washington counties, which represent more than 2.7 million persons, approximately 200,000 of whom are children younger than 5 years of age.12 Surveillance is conducted in all 23 acute-care hospitals located within the MSP area.
For this study, a case was defined as an MSP-area resident hospitalized in an MSP-area hospital with laboratory-confirmed influenza. Laboratory confirmation of influenza includes viral culture, direct or indirect immunofluorescent antibody staining, reverse transcriptase polymerase chain reaction (RT-PCR), or results of a commercially available rapid antigen test. A patient must have been hospitalized within 14 days of a positive influenza test or had a positive influenza test result within three days of admission to be considered a case.
Medical records were requested and a case report form was completed by the Department of Health for persons meeting the definition of a case. Demographic information as well as information about laboratory test results, underlying medical conditions, intensive care unit (ICU) admission, use of mechanical ventilation, bacterial coinfection, antiviral medication use, discharge diagnoses, outcome, and influenza vaccination status were recorded on the form. Although case report forms were completed for hospitalized influenza A and influenza B patients, for this report, analysis was limited to nH1N1 influenza and seasonal influenza A cases.
The incidence of hospitalized, laboratory-confirmed influenza was calculated using 2008 population estimates.13 Data analyses were conducted using SAS 9.2. Comparisons between age groups and influenza types were made using chi-square statistics for categorical variables; Fisher’s Exact Test was used when cell counts were less than five. Two-sided P values less than 0.05 were considered statistically significant.
Results
The first hospitalized, laboratory-confirmed case of seasonal influenza A in the MSP area occurred on December 8, 2008. The first hospitalized case of seasonal influenza B occurred on January 9, 2009 (Figure 1). Peak seasonal influenza A activity lasted from mid-January to late February. During this time, seasonal influenza A (seasonal H1N1 and H3N2) accounted for 78% (73/93) of all influenza hospitalizations. Peak seasonal influenza B activity occurred from late February through early May, accounting for 57% (34/60) of all influenza hospitalizations. The first laboratory-confirmed nH1N1 hospitalization occurred on May 2. Hospitalizations for nH1N1 influenza peaked during early to late June and then decreased significantly through July. Since May 2, 93% (209/224) of all hospitalized influenza cases were caused by nH1N1.
〉Incidence of Hospitalized nH1N1 and Seasonal Influenza A
From October 2008 through August 2009, the incidence rate of hospitalized nH1N1 influenza in the MSP area was 7.5 cases per 100,000 persons compared with 4.3 cases for seasonal influenza A. The incidence rate of nH1N1 influenza was highest in children younger than 1 year of age (50 hospitalizations per 100,000 persons), followed by those 1 year to 4 years (27 per 100,000) and those 5 years to 9 years (20 per 100,000). The incidence of seasonal influenza A was highest among children younger than 1 year of age (60 per 100,000), followed by those 1 year to 4 years of age (12 per 100,000) and persons 65 years of age and older (5 per 100,000) (Figure 2).
〉 Characteristics of Hospitalized nH1N1 Influenza Cases
From May 2 through August 31, 2009, 209 hospitalized nH1N1 cases were reported in the MSP area. Of those, 129 (62%) were children younger than 18 years of age and 80 (38%) were adults. The median age was 11 years (range: 0 years to 91 years). Males accounted for 49% of all cases; however, pediatric cases (57%) were significantly more likely than adult cases to be male (38%, P<0.01). Residents of Hennepin County accounted for 53% (111/209) of cases (54% of adults and 53% of children).
Overall, 64% (133/209) of people who were hospitalized with nH1N1 had at least one documented underlying medical condition that put them at increased risk for severe influenza complications. Adults (75%) were significantly more likely than children (57%) to have an underlying medical condition (P<0.01). Asthma was the most common underlying condition reported among both adults (41%) and children (40%). Other conditions frequently reported among adults included metabolic disease such as diabetes (20%), chronic lung disease (18%), and chronic cardiovascular disease (13%). Among children, other common underlying medical conditions included developmental delays (7%), chronic lung disease (6%), and neuromuscular disorders (6%) (Table 1). Among females of childbearing age (13 to 49 years of age), 40% (18/45) were documented as pregnant upon admission.
Thirty-six percent (n=76) of nH1N1 cases had a diagnosis of pneumonia at discharge (38% of adults and 36% of children). Four adults (5%) and one child (1%) had evidence of invasive bacterial coinfection (Table 1). Adults (18%) were significantly more likely than children (4%) to have needed mechanical ventilation (P<0.01). The median length of hospitalization was four days for adults and three days for children. Twenty-six percent of adults (n=21) required ICU admission compared with 16% (n=20) of children (P=0.06) (Table 1). Two deaths occurred during hospitalization: a 5-year-old female and a 59-year-old male, both of whom had multiple underlying medical conditions. Two additional nH1N1-related deaths occurred outside the hospital setting: a 91-year-old male who had been recently discharged from the hospital and a previously healthy 2-year-old who was coinfected with nH1N1 and Streptococcus pneumoniae.
〉 Hospitalized nH1N1 and Seasonal Influenza A Cases
A total of 327 nH1N1 and seasonal influenza A hospitalizations were reported to the Minnesota Department of Health between October 2008 and August 2009. Of those, 209 (64%) were caused by nH1N1 and 118 (36%) were due to seasonal influenza A. The median age at admission for patients with nH1N1 was 11.1 years as compared with 16.9 years for seasonal influenza A (Table 2). Those hospitalized for nH1N1 (67%) were as likely as those hospitalized for seasonal influenza A (64%; P=0.70) to have had at least one underlying medical condition. However, patients with nH1N1 were significantly more likely to have had asthma (41%) than those with seasonal influenza A (20%; P<0.01). Among adults, those with seasonal influenza A were significantly more likely to have documentation of chronic cardiovascular disease (15% vs. 7%; P=0.01) and seizure disorder (5% vs. 1%; P=0.03) than those with nH1N1. Among females of childbearing age, a higher proportion of those who had nH1N1 (40%) were documented as pregnant upon admission than those who had seasonal influenza A (27%; P=0.31) (Table 2).
There were no significant differences between nH1N1 and seasonal influenza A regarding the proportion of patients who had undergone a chest X-ray (81% vs. 83%; P=0.62) or required mechanical ventilation (9% vs. 9%; P=0.85). However, patients with nH1N1 (36%) were significantly more likely to have been diagnosed with pneumonia at discharge than those with seasonal influenza A (20%; P=<0.01). Patients hospitalized for nH1N1 (20%) also had a higher rate of ICU admission than those hospitalized for seasonal influenza A (13%; P=0.11). There was no significant difference between the proportion of nH1N1 patients with invasive bacterial coinfections (2%) and those with seasonal influenza A (4%; P=0.35). The median length of hospitalization (three days) was the same for people with nH1N1 and those with seasonal influenza A (Table 2).
Conclusion
Between October 2008 and August 2009, more than 300 laboratory-confirmed, hospitalized nH1N1 and seasonal influenza A cases were reported to the Minnesota Department of Health. Of those, the majority were nH1N1, indicating that circulation of the virus was widespread in the MSP area. Incidence of hospitalization for nH1N1 was 7.4/100,000 population, which was higher than seasonal influenza A. The majority of nH1N1 hospitalizations occurred among children, with the incidence highest among those younger than 1 year of age. The incidence rate of nH1N1 among children 1 year to 17 years of age was higher than that for seasonal influenza A, suggesting that children older than 1 year of age are at greater risk for nH1N1 infection than seasonal influenza A. However, it should be noted that a vaccine for seasonal influenza A was widely available prior to the 2008-2009 influenza season and the seasonal influenza vaccine is recommended for all children 6 months to 18 years of age. An nH1N1 vaccine, which became available in October 2009, may reduce the incidence in children during the 2009-2010 influenza season.
Interestingly, although approximately half of nH1N1 cases were reported in males, upon stratification by age, children with nH1N1 were significantly more likely to be male than adults. Slightly less than two-thirds of patients hospitalized with nH1N1 had at least one underlying medical condition, with a large majority of those cases having been diagnosed with asthma. The proportion of adults and children with asthma was similar. Comparison of nH1N1 and seasonal influ-enza A reveals that people hospitalized with nH1N1 were significantly more likely to have had asthma, indicating that asthma is a predominant risk factor for nH1N1 influenza.13
More than 35% of patients hospitalized with nH1N1 had a diagnosis of pneumonia at discharge. There was no difference between the proportion of adults and the proportion of children diagnosed with pneumonia. However, nH1N1 cases were significantly more likely than seasonal influenza A cases to have had a discharge diagnosis of pneumonia. This finding suggests that infection with nH1N1 influenza results in a higher incidence rate of lower respiratory disease.14 Pregnancy was also an important risk factor among females who were hospitalized with influenza, especially among those hospitalized with nH1N1 influenza.
Among nH1N1 cases, some of the data suggest children and adults experienced similar levels of severity. Median length of hospital stay and death prior to discharge were similar among children and adults. These finding were also similar when nH1N1 cases were compared with seasonal influenza A cases. However, higher proportions of adults with nH1N1 were admitted to the ICU or had a bacterial coinfection than children with nH1N1. Adults with nH1N1 were also significantly more likely to have required mechanical ventilation than children with nH1N1. This finding may be related to more severe and multiple underlying medical conditions among adults with nH1N1.
The influenza season of 2008-2009 will be remembered for the initial spring wave of nH1N1. This strain of influenza rapidly spread throughout the United States and Minnesota. Notable features included higher rates of hospitalizations among children 1 year to 17 years of age, and a higher incidence rate of asthma and pneumonia among nH1N1 cases compared with seasonal influenza A cases. Pregnancy was a risk factor among females of childbearing age who were hospitalized with nH1N1. The Minnesota Department of Health is carefully tracking a second wave of nH1N1 that began in September 2009 and is evaluating whether there are changes in the severity or in the epidemiology of this new influenza strain. MM
Laura Fleege and Emily Hallberg are second-year master’s degree students in the School of Public Health at the University of Minnesota and are student worker paraprofessionals in the Minnesota Department of Health’s Emerging Infections Program; Craig Morin is a senior epidemiologist in the Emerging Infections Program, Richard Danila is the section manager of the Acute Disease Investigation and Control Section and Deputy State Epidemiologist, and Ruth Lynfield is state epidemiologist and medical director of the Infectious Disease Epidemiology, Prevention, and Control Division at the Minnesota Department of Health.
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