Pediatric influenza-associated deaths in Arizona,

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1 Pediatric influenza-associated deaths in Arizona, (Poster is shared here as an 8.5 x11 document for easier viewing. All content is identical, though graphs and tables are formatted differently.) Laura M. Erhart, MPH Arizona Department of Health Services Abstract: Background: Each year, 3,000 to 49,000 people die in the U.S. from influenza-associated illness. While the majority of these deaths are among the elderly, the rate of influenza-related hospitalizations among children can be high, especially for those under the age of five years or who have pre-existing medical conditions, and fatalities among children do occur. In 2004, pediatric influenza-associated mortality became nationally notifiable, with the goal of better characterizing the burden and epidemiology of influenza-associated deaths among children. Arizona has been conducting surveillance for these cases since that time. In this report we describe the characteristics of reported Arizona cases from eight influenza seasons. Methods: Influenza has been a laboratory-reportable condition in Arizona since Influenza-associated pediatric mortality became specifically reportable by health care providers in Arizona in Cases are classified and investigated using the national case definitions and investigation form. Descriptive analysis has been conducted here on information available through those investigations. Results: Thirty-eight deaths were identified during , with a range of one to 13 deaths in each of the eight seasons. Eight cases were initially identified through reporting and investigations of unexplained deaths with a history of fever. Twenty-three (61%) cases were associated with the influenza A (H1N1 pdm09) virus, 11 (29%) with influenza B virus, and 4 (10%) with influenza A viruses of unknown subtype. Eleven (29%) cases were under the age of five years. The duration of illness was one week or less for half of the cases. Invasive bacterial infections were identified in ten (32%) of those tested, and viral coinfections in four of 38 children. Twenty-two (63%) of 35 cases had one or more known underlying medical conditions, with moderate or severe developmental delays most frequently cited. Eight of the 13 cases with no preexisting conditions had other viral or invasive bacterial infections. Most of the children had not received an influenza vaccination. Conclusions: More than half of Arizona s pediatric influenza-associated deaths occurred during the 2009 pandemic, but Arizona has had at least one case each year since surveillance began. Infections with influenza B viruses contributed substantially. Thirty-five percent of the children were not covered by age- or comorbidity-specific vaccine recommendations at the time; the current universal recommendation and continued vaccination campaigns should help to increase coverage and protect more children from severe consequences of influenza illness.

2 Background: Each year, 3,000 to 49,000 people die in the U.S. from influenza-associated illness. While the majority of these deaths are among the elderly, the rate of influenza-related hospitalizations among children can be high, especially for those under the age of five years or who have preexisting medical conditions, and fatalities among children do occur. During the influenza season, reports of pediatric influenza-associated deaths raised concerns among the public and the public health community, with more than 140 cases identified by March In October 2004, pediatric influenza-associated mortality became nationally notifiable, with the goal of better characterizing the burden and epidemiology of influenza-associated deaths among children. Arizona has been conducting surveillance and investigations for influenza-associated pediatric mortality since The objectives of this report are to: Characterize the influenza-associated deaths among Arizona children from eight influenza seasons ( ); Describe factors that may have contributed to the severity of the illnesses; and Assess the applicable influenza vaccination recommendations. Methods: Influenza has been a laboratory-reportable condition in Arizona since October, 2004, under Arizona Administrative Code (AAC) R , requiring reporting of positive influenza tests and allowing for investigation into reported cases. Influenza-associated pediatric mortality became specifically reportable by health care providers in Arizona in 2008 (AAC R ). Influenzaassociated pediatric fatalities are investigated in Arizona using national case definitions and forms. A pediatric influenza-associated death is defined as a death resulting from a clinically compatible illness that is confirmed to be influenza by an appropriate laboratory or rapid diagnostic test in a person aged <18 years. Unexplained deaths with a history of fever have also been reportable by health care providers since 2004 (AAC R ). Laboratory testing for compatible morbidities are conducted during the investigations; pediatric influenza-associated deaths may be identified through this process. Information presented here reflects descriptive analysis of data collected during pediatric influenza-associated morbidity investigations. Vaccine recommendations of the Advisory Committee on Immunization Practices were reviewed in the MMWR for each year. Results:

3 Season, virus type, and demographics (Figures 1 and 2, Tables 1 and 2) 38 pediatric influenza-associated deaths were identified in Arizona in these 8 influenza seasons. 8 (21%) cases were originally identified through Unexplained Death investigations. 1 to 13 cases were identified each season. 27 (71%) were influenza A infections. 11 (29%) were influenza B. Of influenza A cases: 20 (74%) influenza A (H1N1 pdm09) cases were identified during the pandemic period, and 3 (11%) in the season. Subtype was not identified for 4 (15%) influenza A viruses. An influenza B-associated death was identified in every season except (63%) deaths were among boys; 14 (37%) were among girls. 11 (29%) children were less than 5 years old. Children of all ages were affected. 15 (41%) cases were Hispanic/Latino; 13 (35%) were non-hispanic White. Course of illness (Table 3) Duration of illness (illness onset to death) was one week or less for 19 (51%) of 37 cases. (Range 2-83 days, mean = 17, median = 7) Pneumonia (23 (64%)) and acute respiratory distress (19 (53%)) were the most commonly reported clinical complications. Invasive bacterial coinfections were identified for 10 (32%) of 31 cases tested: Staphylococcus aureus (Methicillin-resistant, 5, and Methicillin-sensitive, 2) and Streptococcus pneumoniae (3). Viral coinfections were identified for 4 (11%) of the 38 cases: adenovirus, cytomegalovirus, enterovirus, and Epstein-Barr virus. 14 (37%) of 38 children were given oseltamivir. However, we do not known when or for how long it was taken. Underlying medical conditions (Table 4) 22 (63%) of 35 cases had known underlying medical conditions; 13 (37%) had no known medical condition. 15 (43%) cases had moderate to severe developmental delays, 12 (34%) had seizure disorders, and 11 (31%) had neuromuscular disorders. Of the 13 cases with no known preexisting medical conditions, 5 had invasive bacterial infections (2 MRSA, 2 Streptococcus pneumoniae, 1 MSSA); 3 others had viral coinfections (adenovirus, enterovirus, Epstein-Barr virus). 4 of 13 were <5 years. Vaccination status of cases (Figures 3-4) 4 (11%) children were too young to be vaccinated (<6 months old).

4 7 (18%) children had received the current season s influenza vaccine, all at least 2 weeks before illness onset. o 4 of 7 vaccinated children received the seasonal vaccine but were laboratory-confirmed with influenza A (H1N1 pdm09), which was not in the vaccine. o 3 of 7 vaccinated children were of the age recommended to receive 2 doses but had only received (37%) children were old enough to be vaccinated but did not receive the current season s influenza vaccine. Vaccination status was unavailable for 13 (34%) of 38 children. 11 of 13 were infected with influenza A (H1N1 pdm09), with illness onset before mid-october 2009, when the H1N1 vaccine was first available. Pediatric flu vaccine recommendations changed during these years (Table 5). Of 34 cases old enough to be vaccinated: (Figure 4) o Vaccine was recommended for 19 (56%) based on high-risk medical conditions. o Vaccine was recommended for an additional 3 (9%) based on young age. o 12 (35%) children were not covered by comorbidity- or young age-based recommendations. 9 (26%) cases were covered by the universal pediatric recommendation; 3 (9%) cases occurred before the recommendation. Figure 1. Number of influenza-associated pediatric deaths, by influenza season and type, Arizona Figure 2. Influenza type and subtype associated with pediatric deaths, Arizona

5 Influenza Type and Subtype Influenza A (subtype unknown), 4, 10% Influenza A (H1N1 pdm09), 23, 61% Influenza B, 11, 29% Table 1. Sex and age, flu-assoc. pediatric deaths, Arizona Number of cases (%) (N=38) Sex Male 24 (63%) Female 14 (37%) Age <1 year 5 (13%) Mean = 7.9 years 1-4 years 6 (16%) Median = 7.5 years 5-9 years 11 (29%) years 8 (21%) years 8 (21%) Table 2. Race/ethnicity of influenza-associated pediatric deaths, Arizona Race/ethnicity of cases Number of cases (%), Arizona population (0-17 years, 2010, census) N=37 Hispanic or Latino 15 (41%) 41% White, non-hispanic 13 (35%) 42% Black 5 (14%) 5% American Indian 3 (8%) 6% Asian 1 (3%) 3% Table 3. Complications, coinfections, and location of death for influenza-associated pediatric deaths, Arizona Number of cases (%)

6 Complications* (N=38) Pneumonia (confirmed by 23 (61%) chest x-ray) Acute respiratory disease 19 (50%) syndrome (ARDS) Shock 4 (11%) Seizures 3 (8%) Invasive bacterial infections Invasive bacterial infection 10 (32%) (N=31 tested) identified Methicillin-resistant 5 Staphylococcus aureus (MRSA) Methicillin-sensitive 2 Staphylococcus aureus (MSSA) Streptococcus pneumoniae 3 Viral coinfections (N=38) Viral coinfection identified 4 (11%) Location of death (N=38) Intensive care unit 23 (60%) Emergency department 5 (13%) Inpatient 1 (3%) Outside hospital (incl. home or in transit) 9 (24%) *Each case can have multiple complications. Also, no answers cannot be distinguished from missing. Table 4. Underlying medical conditions, influenza-associated pediatric deaths, AZ Medical condition* Number of cases (%) (N=35) One or more underlying medical conditions 22 (63%) No known underlying conditions 13 (37%) Moderate to severe developmental delay 15 (43%) Seizure disorder 12 (34%) Neuromuscular disorder 11 (31%) Cerebral palsy 9 (26%) Chronic pulmonary disease 10 (29%) Immunosuppresive condition 4 (11%) Cardiac disease/congenital heart disease 4 (11%) Asthma/reactive airway disease 4 (11%) *Only conditions listed for four or more cases are shown. Many children had multiple known underlying medical conditions. Figure 3. Flu vaccination status

7 Vaccination status of cases Unknown**, 13, 34% Vaccinated*, 7, 18% Too young to be vaccinated, 4, 11% Not vaccinated, 14, 37% * 4 of 7 cases received the seasonal vaccine but were laboratory-confirmed with the A (H1N1 pdm09) virus. ** 11 of 13 cases with unknown vaccination status were infected with influenza A (H1N1pdm09) before the H1N1 vaccine was available. Fig. 4. Relevant flu vaccine recommendations Applicable vaccine recommendations No recommendation, 3, 9% All children (non- HR, 5+ years), 9, 26% Age (6-59 mo., non-hr), 3, 9% High-risk (HR) condition, 19, 56% N = additional children were too young to be vaccinated (<6 mo.) Table 5. Pediatric influenza vaccination recommendations Category Seasons recommended High-risk medical Throughout this period

8 conditions* Age 6-23 months Starting Age 6-59 months Starting All children > 6 Starting months *Includes chronic pulmonary, cardiovascular, renal, hepatic, or metabolic conditions; immunosuppression; any condition (including neuromuscular disorders) that can compromise respiratory function. Discussion: More than half of Arizona s pediatric influenza-associated deaths occurred during the 2009 pandemic, but Arizona has had at least one case each year since surveillance began in Influenza B has often been thought to be milder than influenza A, but was associated with 29% of cases. Children of all ages and many races/ethnicities have been affected. Almost two-thirds of children had known underlying medical conditions that put them at higher risk of complications of influenza. In many cases, children had more than one high-risk condition and the conditions tended to be fairly severe. However, more than one-third of children did not have known underlying conditions. These children were somewhat more likely to have a coinfection with invasive bacteria (38%) or other viruses (23%). Only 7 (18%) children had received any doses of the current season s influenza vaccine. Accounting for vaccine-virus mismatch during the 2009 pandemic, and receiving only one dose when two were recommended, only 1 child had been fully vaccinated using a vaccine considered to offer substantial protection. Vaccine recommendations based on young age or high-risk comorbidities did not cover 35% of these children at the time of illness onset. Limitations: The number of cases involved is too small to make strong statistical statements. While case definitions and investigation forms are standardized, there may be variation in interpretation of questions and answers by the multiple investigators across the eight years. Information collected was not complete for all questions. Testing for influenza, other viruses, and bacterial infections varied for each case (laboratory, tests conducted, methods, timing of specimens). Conclusions:

9 Influenza-associated pediatric mortality surveillance and investigations are important for better understanding which children are most affected by influenza, allowing for more effective public health recommendations. While many of the pediatric fatalities in Arizona over this eight-year period had risk factors for complications to influenza, few had received influenza vaccine. Additionally, several children not considered high-risk were affected. Public health needs to continue to emphasize the importance of influenza vaccination for children of all ages, and especially, but not limited to, those with high-risk medical conditions. The universal influenza vaccination recommendation for all children should help to clarify this message, but sustained work is needed to increase vaccination coverage and protect more children from severe outcomes. Acknowledgements: We wish to thank the public health investigators at the local and state health departments who collected much of the information presented here, the healthcare facilities involved in the public health investigations, the virology laboratory staff, and especially the families who worked with us while suffering the loss of a child. References: Update: Influenza-Associated Deaths Reported Among Children Aged <18 Years United States, Influenza Season. MMWR January 9, 2004 / 52(53); Update: Influenza Activity United States, Season. MMWR April 9, 2004 / 53(13); CSTE Position Statement: Influenza-Associated Pediatric Mortality. Cited 5/22/ Notice to Readers: Mid-Year Addition of Influenza-Associated Pediatric Mortality to the List of Nationally Notifiable Diseases, MMWR October 15, 2004 / 53(40);