C Detection Among Patients Hospitalized with Severe Acute Respiratory Illness, Minnesota, 2014-2015 Hannah Friedlander 1 1 1 1 1 2 2 2 2 1 Minnesota Department of Health Hannah Friedlander, MPH ; Kathryn Como-Sabetti, MPH ; Sarah Bistodeau ; Anna Strain, PhD ; Dave Boxrud, MS ; Ashley Fowlkes, MPH ; Andrea Steffens, MPH ; Sandra S. Chaves, MD, MSc ; Stephen Lindstrom PhD ; Ruth Lynfield, MD PO Box 64975, St. Paul, MN 55164 1 2 651-201-5414, www.health.state.mn.us Minnesota Department of Health, Saint Paul, MN; U.S. Centers for Disease Control, Influenza Division, Atlanta, GA [email protected]

• 27 (69%) influenza C-positive SARI cases had additional viral pathogens detected. ABSTRACT Figure 1. Influenza C Demonstrating Cytopathic Effect in Tissue Culture (Table 1) Table 3. Influenza C SARI Case Clinical Characteristics Background: Influenza C are thought to be non- and cause mild illness. However, - 20 cases had 1 other pathogen detected (6 , 4 HMV, 3 RSV, 2 N (%) respiratory diagnostic assays do not commonly include detection of influenza C . Methods: N=39 The MN Dept of Health (MDH) initiated surveillance for severe acute respiratory illness (SARI) parainfluenza virus 3, 1 parainfluenza virus 1, 1 parainfluenza virus 2, 1 in April 2013 at 3 hospitals (1 pediatric hospital) in the Minneapolis/St. Paul metro area. Cases NL63, 1 influenza A (H3), 1 influenza B). Presenting symptoms (not mutually exclusive) include hospitalized MN residents with acute onset of respiratory symptoms (e.g., ) with a Shortness of breath/respiratory distress 30 (77%) - 5 cases had 2 other pathogens detected. All 5 were positive for influenza respiratory specimen collected. Residual respiratory specimens are submitted to MDH and tested Cough 25 (64%) for 20 viral and bacterial pathogens by RT-PCR, including influenza C as of 9/2014. Medical records C, rhinovirus, and one other additional pathogen (2 RSV, 1 adenovirus, 1 are reviewed to obtain demographic and clinical data. Results: Influenza C was detected in 39 of , 1 parainfluenza virus 3). (measured or subjective) 22 (56%) 3474 (1.0%) SARI specimens submitted from 9/2014 – 4/2015; specimens collected in December Congestion 17 (44%) (n=3), January (n=6), February (n=11), March (n=17), April (n=2) were positive. Respiratory - 2 cases had 3 other pathogens detected: distress/shortness of breath was the most common admission symptom (n=30) followed by cough . 1 case had adenovirus, coronavirus C229E, and parainfluenza virus 3 Wheezing 14 (36%) (n=25) and congestion (n=17). 1 case had influenza C detected twice during the same admission, detected. Vomiting 12 (31%) 20 days apart. Among SARI cases with influenza C detected, median age was 1.5 years (range Hospital length of stay (median) 2 days 0-84 years); most (85%) were <10 years old. Median hospital stay was 2 days; 4 cases had ICU . 1 case had adenovirus, parainfluenza virus 4, and RSV detected. admission (2 with no co-detections). There were no deaths. Underlying medical conditions were 1-2 days 21 (54%) Photo credit: Jaime Christensen reported for 23 (59%) cases, most commonly prematurity (n=8), asthma (n=5), and neurological/ 3-4 days 10 (26%) neuromuscular disease (n=4). 12 (31%) SARI cases with influenza C had no other pathogens Table 2. Influenza C SARI Case Demographic Characteristics 5-6 days 4 (10%) detected; 27 (72%) had co-detections, including rhinovirus (n=11), RSV (n=6), parainfluenza (n=7) Results and metapneumovirus (n=4). 7 cases had >2 pathogens detected. 1 influenza C positive 7-20 day 3 (8%) N (%) case was hospital-acquired in a 16 month old patient who had been admitted since birth; no other N=39 >20 days 1 (3%) pathogens were detected in this patient. Conclusions: Influenza C was detected among patients, Testing Results primarily children, hospitalized for SARI. Cases occurred during influenza A/B season. Continued • 3,474 SARI specimens were submitted between September 1, 2014 and April 30, Age (median) 1.5 years ICU 4 (10%) surveillance for influenza C will help to better understand the epidemiology, including seasonality, 2015. < 6 months 10 (26) Mechanical ventilation 1 (3%) severity and risk factors for disease. - 39 (1.0%) were positive for influenza C by rRT-PCR. 6 months – < 2 years 16 (41) ECMO 0 . 1 case had influenza C detected twice during the same admission, with 2 – 4 years 5 (13) Died 0 specimens collected 20 days apart. 5 – 11 years 2 (5) Presence of underlying medical condition (all ages) 23 (59%) • Influenza C detections were observed during the typical influenza season, from 12 – 17 years 1 (3) Presence of underlying medical condition (pediatric; not mutually exclusive) 20 (59%)

December 2014 through April 2015, with most cases (43%) detected in March 2015. 18+ years 5 (13) History of prematurity 8 (40%) Background (Figure 2) Sex 6 (30%) No cases were detected from September through November 2014 and after Male 22 (56) Asthma 5 (25%) • Influenza C viruses, though not well-characterized epidemiologically, cause mild - April 2015. Female 17 (44) Abnormality of upper airway 4 (20%) illness and are non-epidemic.1 (Figure 1) Race Neurologic/neuromuscular disease 4 (20%) • Figure 2. Influenza C Detections Among SARI Cases, Minnesota, Seroepidemiological studies of influenza C have indicated the virus is widely White 19 (49) Chronic metabolic disease 1 (5%) distributed throughout the world and that occur early in life.2 September 2014 – April 2015 Black 12 (31) Limitations • 18 Respiratory diagnostic assays do not commonly include detection of influenza C Other 3 (8) virus. 17 Unknown 5 (13) • SARI hospitals over-represent pediatric patients. Additionally, at institutions with both • In 2013, the Minnesota Department of Health (MDH), in collaboration with the 16 pediatric and adult patients, clinicians may be more likely to test younger, previously Centers for Disease Control and Prevention (CDC), initiated surveillance for severe Characteristics of Cases 15 healthy patients. acute respiratory illness (SARI) at 3 sentinel hospitals in the Minneapolis- St. Paul • Among patients with influenza C detected, the median age was 1.5 years 14 • Influenza C was detected from an upper respiratory swab sample and the specific role Metropolitan area. (0 – 84 years), with most cases < 5 years old (79%). (Table 2) of influenza C in a patient’s illness is unknown. Sentinel hospitals included 1 pediatric hospital, 1 hospital that serves both adults 13 • 22 (56%) influenza C cases were male; 19 (49%) were white and 12 (31%) were - • Because SARI specimens were not tested for influenza C prior to September 2014, and children, and 1 hospital that primarily serves adults. 12 black. (Table 2) we cannot determine the burden or seasonality of influenza C in Minnesota 11 • 30 (77%) presented with shortness of breath or respiratory distress, 25 (64%) during past seasons. Objective 10 presented with cough, and 22 (56%) presented with fever. (Table 3) However, we retrospectively tested specimens submitted during the previous • 31 (79%) were hospitalized for 4 days or less. (Table 3) - 9 influenza season (October 2013 – April 2014) for influenza C in both hospitalized • To utilize the MN SARI Surveillance Program to identify and describe patients • 4 (10%) SARI cases with influenza C were admitted to an intensive care unit (ICU). 8 and outpatient settings; no detections of influenza C were found in hospitalized (Table 3) hospitalized for respiratory illness with an influenza C detection. of Number Cases 7 patients. All were < 27 months old and had at least 1 underlying medical condition. 6 - Methods - 2 (50%) had only influenza C detected; 2 (50%) had influenza C and one 5 Conclusions additional pathogen detected. • SARI cases included patients presenting with respiratory symptoms (e.g. cough, 4 1 (25%) patient was dependant on mechanical ventilation. - • We were able to detect influenza C among 39 hospitalized patients during the 2014-15 wheeze, shortness of breath), with or without fever, hospitalized, and had an upper 3 • No SARI cases with influenza C were placed on ECMO or died. (Table 3) surveillance year, and for 12 patients it was the sole pathogen detected. respiratory specimen submitted to the MDH Public Health Laboratory (PHL). 2 • 23 (59%) influenza C cases had at least one underlying medical condition; many had • Influenza C cases occurred during the influenza A/B season (October-April), indicating • Medical records of SARI cases were reviewed to obtain demographic and clinical 1 multiple underlying conditions. (Table 3) concurrent circulation of the three viruses is likely. Of the 20/34 (59%) pediatric (< 18 years) cases with underlying condition(s): information, including: presenting symptoms, hospital course, underlying chronic 0 - September October November December January February March April • Most cases identified were < 2 years old, and many had underlying conditions. conditions, clinical microbiology results, discharge diagnosis, and outcome. . 8 (40%) had a history of prematurity; 6 cases with a history of prematurity Month of Specimen Collection • Continued surveillance for influenza C will help to better understand the epidemiology, • SARI specimens were tested by real-time polymerase chain reaction (RT-PCR) at the had at least one pathogen in addition to influenza C detected. seasonality, severity, and risk factors for infections with influenza C. PHL for 20 viral and bacterial pathogens including: . 6 (30%) had cardiovascular disease; 5 cases with cardiovascular disease had Table 1.Co-Detection of Influenza C and Additional Pathogens at least one pathogen in addition to influenza C detected. - Viral: rhinovirus, adenovirus, respiratory syncytial virus (RSV), influenza A References . 5 (25%) had asthma; all cases with asthma had at least one pathogen in 1. http://www.cdc.gov/flu/about/viruses/types.htm (subtypes [H1N1]pdm09, H1, and H3), influenza B, N (%) addition to influenza C detected. 2. Matusauaki Y, Katsushima N, Nagai Y, et al. Clinical Features of Infection in Children. J Infect (HMV), coronavirus (C229E, HKU1, NL63, and OC43), parainfluenza viruses 1-4. Total Influenza C Detections N=39 Dis. 2006; 193 (9):1229-35. 3/5 (60%) adult cases had the following underlying condition(s): - Bacterial: Bordetella spp., Mycoplasma pneumoniae, Chlamydophila Influenza C only 12 (31%) - Acknowledgements pneumoniae, and Legionella pneumophila. + 1 additional pathogen detected 20 (51%) . 1 had chronic lung disease Children’s Hospitals and Clinics of Minnesota: Patricia Stinchfield, Helen Stefan. Council of State and Territorial Epidemiologists: Nicole Bryan, Jennifer Lemmings, Jeff Engel. Hennepin County Medical Center: Kathleen Steinman, • Influenza C testing using a CDC-developed rRT-PCR assay was added to the SARI + 2 additional pathogens detected 5 (13%) . 1 had cardiovascular disease and HIV Molly Biscigla. Minnesota Department of Health: Jaime Christensen, Erica Bye, Richard Danila, Kelli Rogers, Jennifer testing panel on September 1, 2014. + 3 additional pathogens detected 2 (5%) . 1 case was pregnant at time of illness Sees, Nathan Wright. Regions Hospital: Robert Bergsbacken, Denise Kramer, Keith Mason, Gregory Siwek. Funding provided through CSTE contract and CSTE cooperative agreement with CDC.