18-ID-01 Committee: Infectious Disease Title: Standardized Case Definition for Surveillance of RSV-Associated Mortality Check this box if this position statement is an update to an existing standardized surveillance case definition. I. Statement of the Problem In the United States, respiratory syncytial virus (RSV) is a leading cause of serious acute lower respiratory tract infection in young children and older adults and adults with chronic medical conditions. There are several RSV vaccines, immunoprophylaxis products, and anti-viral therapies targeting a variety of age groups in preclinical and clinical stages of development [PATH, McKimm-Breschkin JL, DeVincenzo JP(1), DeVincenzo JP(2)]. Based on the results of an RSV surveillance assessment conducted by the CSTE RSV Surveillance workgroup, variation in surveillance case definitions and case classification methods were identified across jurisdictions. Without a standardized case definition, the ability to compare and combine data across jurisdictions is limited. This standardized case definition represents a first step towards utilizing RSV surveillance data in a meaningful way. In addition, the standardized case definition will aid in understanding the burden of RSV in the United States and the evaluation of the potential impact of future RSV vaccines, anti-virals, and immunoprophylaxis products as they enter the market. II. Background and Justification ver 57,000 hospitalizations, 500,000 emergency department visits and 1.5 million outpatient clinic visits among children <5 years of age are attributed to RSV infections each year in the United States [Hall CB]. RSV-associated deaths among children <5 years of age are thought to be uncommon, estimated at 100-500 per year [Shay DK]. Among US adults, an estimated 177,000 hospitalizations and 14,000 deaths associated with RSV infections occur annually [Falsey AR]. However, these are likely underestimates of RSV-associated deaths as the studies were done in children or adults 65 years. In recent years, laboratory testing for RSV has increased in availability and practice. A more accurate assessment of RSVassociated deaths is important for establishing a baseline level of mortality ahead of the potential licensures of vaccines, immunoprophylaxis products, and anti-viral therapies. Additionally, better understanding who is at risk of RSV-associated deaths may help identify populations to target for interventions. Some progress has been made in addressing the challenges in measuring RSV-associated deaths described in a previous CSTE position statement [CSTE]. The ational Center for Health Statistics (CHS/CDC) now provides the ational Center for Immunization and Respiratory Diseases (CIRD/CDC) with quarterly reports showing the number of deaths in the United States with three codes (J12.1 for RSV pneumonia, J20.5 for acute bronchitis due to RSV, and J21.0 for acute bronchiolitis due to RSV) as either the immediate or underlying cause. While this has allowed for accounting of deaths that are coded with RSV-specific ICD-10 codes, there may be some misclassification and undercounting. RSV-coded deaths likely underestimate the true number of laboratory-confirmed RSV-associated deaths because a death occurring in a person with laboratory-confirmed RSV infection may not be assigned an RSV-specific code on the death certificate. In addition to death certificate surveillance for RSV-associated deaths, some jurisdictions conduct surveillance for respiratory infections that may help identify RSV-associated deaths,, e.g., syndromic surveillance from healthcare facilities or hospital discharge data, but signs and symptoms of RSV cannot always be distinguished from other infections, so laboratory confirmation is important. ther recent initiatives by jurisdictions and CDC seek to gain a better understanding of RSV-associated deaths. Many states conduct some type of RSV surveillance; however, the type and format of collected 18-ID-01 1
data are not standardized and are difficult to compare from jurisdiction to jurisdiction. As jurisdictions move towards enhancing their RSV surveillance activities, having a standardized case definition for RSVassociated deaths will help make this component of case-based RSV surveillance activities more comparable across jurisdictions. Based on results from the CSTE RSV Surveillance workgroup assessment, not all jurisdictions are conducting surveillance for RSV deaths among all ages and populations. This case definition is intended to allow jurisdictions conducting surveillance for RSV mortality to do so in a way that is consistent with other jurisdictions. Jurisdictions might also choose to develop their own probable case definitions to capture additional cases not included in the confirmed case definition. III. Statement of the desired action(s) to be taken CSTE recommends the following actions: 1. Utilize standard sources (e.g. reporting*) for case ascertainment for RSV-associated deaths. Surveillance for RSV-associated deaths should use the following recommended sources of data to the extent of coverage presented in Table III. Table III. Recommended sources of data and extent of coverage for ascertainment of cases of RSV-associated deaths. Coverage Source of data for case ascertainment Population-wide Sentinel sites Clinician reporting Laboratory reporting Reporting by other entities (e.g., hospitals, veterinarians, pharmacies, poison centers), specify: Hospitals, medical examiners, coroners Death certificates Hospital discharge or outpatient records Extracts from electronic medical records Telephone survey School-based survey ther, specify: syndromic surveillance 2018 Template *Reporting: process of a healthcare provider or other entity submitting a report (case information) of a condition under public health surveillance T local or state public health. ote: notification is addressed in a ationally otifiable Conditions Recommendation Statement and is the process of a local or state public health authority submitting a report (case information) of a condition on the ationally otifiable Conditions List T CDC. 2. Utilize standardized criteria for case ascertainment and classification (Sections VI and VII and Technical Supplement) for RSV-associated deaths. ote: this action does T add RSV-associated deaths to the ationally otifiable Condition List. If requested by CDC, jurisdictions (e.g., States and Territories) conducting surveillance according to these methods may voluntarily submit case information to CDC. IV. Goals of Surveillance To be able to enumerate RSV-associated deaths across jurisdictions and describe their characteristics to inform public health policy regarding the use and impact of future RSV vaccines, immunoprophylaxis, and antiviral products. 18-ID-01 2
V. Methods for Surveillance: Surveillance for RSV-associated deaths should use the recommended sources of data and the extent of coverage listed in Table III. Surveillance for RSV-associated deaths can utilize available recommended sources of data and the extent of coverage listed in Table III. Death certificate data from young children have been shown to mostly represent laboratory-confirmed RSV-associated deaths [Prill MM], but under-reporting from this source alone is unknown. Identification of RSV-associated deaths from the listed sources that includes the clinical or laboratory elements of the case definition should be considered as potential sources for identifying suspect RSV-associated deaths. Despite contributions from these sources, there is likely to be undercounting of RSV-associated deaths since clinical guidelines do not necessarily recommend RSV testing [Ralston SL]. VI. Criteria for case ascertainment A death in a person who had: 1) an illness clinically compatible with RSV infection AD an RSV-positive laboratory test; R 2) RSV noted in the description as an active problem in a clinical record (e.g., medical record, syndromic surveillance, medical examiner record) or RSV listed as a cause or as contributing to the cause of death on the death certificate; R 3) an RSV-positive laboratory test identified within 60 days of death, should be considered for investigation as a possible RSV-associated death. Jurisdictions may use one or more of these ascertainment methods, depending on available data and resources, to best meet surveillance goals. A. arrative: A description of suggested criteria for case ascertainment of a specific condition. The following criteria can be used by jurisdictions who elect to make RSV-associated deaths reportable, or who wish to use surveillance systems to track RSV-associated deaths. At least one of the following three sets of criteria should be met: 1. Death resulting from a clinically compatible illness, such as the following: a. Signs and symptoms of upper or lower respiratory infection R b. Signs of respiratory distress, such as apnea (absence of breathing) AD Illness confirmed to be RSV by any of the following diagnostic tests: a. Isolation of respiratory syncytial virus (RSV) by tissue cell culture b. Detection of respiratory syncytial virus (RSV) nucleic acid by reverse-transcriptase polymerase chain reaction (RT-PCR) or other nucleic acid detection assay c. Detection of respiratory syncytial virus (RSV) antigen by immunofluorescent antibody staining (direct or indirect) d. Detection of respiratory syncytial virus (RSV) antigens by immunochromatographic or similar rapid laboratory test e. Detection of respiratory syncytial virus (RSV) antigens from autopsy specimens by immunohistochemical (IHC) staining 2. Death AD a. Respiratory syncytial virus (RSV) infection, or suspected infection, as a diagnosis or active problem in a clinical record, e.g., medical record, syndromic surveillance, medical examiner record R b. Respiratory syncytial virus (RSV) infection as a cause of death or a significant condition contributing to death on the death certificate 3. Death AD A positive laboratory result for respiratory syncytial virus (RSV) from one of the following diagnostic tests within 60 days of death: a. Isolation of respiratory syncytial virus (RSV) by tissue cell culture 18-ID-01 3
b. Detection of respiratory syncytial virus (RSV) nucleic acid by reverse-transcriptase polymerase chain reaction (RT-PCR) or other nucleic acid detection assay c. Detection of respiratory syncytial virus (RSV) antigen by immunofluorescent antibody staining (direct or indirect) d. Detection of respiratory syncytial virus (RSV) antigens by immunochromatographic or similar rapid laboratory test e. Detection of respiratory syncytial virus (RSV) antigens from autopsy specimens by immunohistochemical (IHC) staining B. Disease-specific data elements to be included in the initial report Disease-specific data elements to be included in the initial report are listed below. In addition to the core data elements, include the following if available: Date of death List of RSV-specific diagnoses (e.g., RSV bronchiolitis) included in the medical Records or death certificate List of RSV-compatible signs and symptoms Collection date of laboratory test for RSV Type of RSV laboratory test conducted Result of the RSV laboratory test VII. Case Definition for Case Classification A. arrative: Description of criteria to determine how a case should be classified. Clinical Criteria A respiratory syncytial virus (RSV)-associated death is defined for surveillance purposes as a death resulting from a clinically compatible illness that was confirmed to be RSV by an appropriate laboratory or rapid diagnostic test. There should be no period of complete recovery between the illness and death. A death should not be categorized as an RSV-associated death if: 1. There is no laboratory confirmation of RSV infection. 2. The RSV illness is followed by full recovery to baseline health status prior to death. 3. After review and consultation, it is determined that RSV infection did not contribute to death. Laboratory Criteria Confirmatory laboratory evidence: Laboratory testing for RSV infection may be done on pre- or postmortem clinical specimens, and include identification of RSV (A, B, or unspecified) infection by a positive result by at least one of the following: a. Isolation of respiratory syncytial virus (RSV) by tissue cell culture b. Detection of respiratory syncytial virus (RSV) nucleic acid by reverse-transcriptase polymerase chain reaction (RT-PCR) or other nucleic acid detection assay c. Detection of respiratory syncytial virus (RSV) antigen by immunofluorescent antibody staining (direct or indirect) 18-ID-01 4
d. Detection of respiratory syncytial virus (RSV) antigens by immunochromatographic or similar rapid laboratory test e. Detection of respiratory syncytial virus (RSV) antigens from autopsy specimens by immunohistochemical (IHC) staining Presumptive laboratory evidence: /A Supportive laboratory evidence: /A Epidemiologic Linkage /A Case Classifications Confirmed: A death meeting the clinical and laboratory criteria. Probable: /A Suspect: /A B. Criteria to distinguish a new case of this disease or condition from reports or notifications which should not be enumerated as a new case for surveillance /A VIII. Period of Surveillance Surveillance should be ongoing. I. Data sharing/release and print criteria CSTE recommends the following case statuses be included in the CDC Print Criteria: Confirmed Probable Suspect Unknown. Revision History /A I. References CSTE. RSV-Associated Pediatric Mortality. 2013. DeVincenzo JP(1), McLure MW, Symons JA, et al. ral GS-5806 Activity in a Respiratory Syncytial Virus Challenge Study. ew England Journal of Medicine 2015; 373:2048-2058. DeVincenzo JP(2), Whitley RJ, Mackman RL, et al. ral GS-5806 Activity in a Respiratory Syncytial Virus Challenge Study. ew England Journal of Medicine 2014; 371:711-722. Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. Engl J Med. 2005;352(17):1749-1759 18-ID-01 5
Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. Engl J Med 2009; 360(6): 588-98. McKimm-Breschkin JL, Jiang S, Hui DS, Beigel JH, Govorkova EA, Lee. Prevention and treatment of respiratory viral infections: Presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference. Antiviral Res. 2017. Shay DK, Holman RC, Roosevelt GE, Clarke MJ, Anderson LJ. Bronchiolitis-associated mortality and estimates of respiratory syncytial virus-associated deaths among US children, 1979-1997. J Infect Dis 2001; 183(1): 16-22. PATH (ovember 2017). RSV Vaccine and mab Snapshot. Retrieved: March 7, 2018, From: https://www.path.org/publications/files/cvia_rsv_snapshot_fs.pdf. Prill MM, Iwane MK, Little D, Gerber SI. Investigation of Respiratory Syncytial Virus-Associated Deaths Among US Children Aged <2 Years, 2004-2007. J Pediatric Infect Dis Soc 2016; 5(3): 333-6. doi: 10.1093/jpids/piv006. Epub 2015 Feb 17. Ralston SL, Lieberthal AS, Meissner HC, et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics 2014; 134(5): e1474-502. doi: 10.542/peds.2014-742. II. Coordination Subject Matter Expert (SME) Consultants: (1) Gayle Langley Lead, RSV Team Centers for Disease Control and Prevention, Division of Viral Diseases 404-639-8092 fez7@cdc.gov (2) Mila Prill Epidemiologist Centers for Disease Control and Prevention, Division of Viral Diseases 404-639-8292 Gik8@cdc.gov (3) Susan Gerber Medical Epidemiologist Centers for Disease Control and Prevention, Division of Viral Diseases 404-639-3002 Bhx1@cdc.gov Agencies for Response (1) Centers for Disease Control and Prevention Robert Redfield Director, Centers for Disease Control and Prevention 1600 Clifton Rd., E Atlanta, GA 30333 404-639-7000 olx1@cdc.gov 18-ID-01 6
Agencies for Information: /A III. Author Information Submitting Author: (1) Erin Murray Epidemiologist Supervisor California Department of Public Health 850 Marina Bay Parkway Building P, 2 nd Floor Richmond, CA 94804 510-620-3782 Erin.Murray@cdph.ca.gov Presenting Author: (1) Karen Martin Influenza Surveillance Coordinator Minnesota Department of Health 625 Robert St. orth St. Paul, M 55155 651-201-5537 Karen.Martin@state.mn.us Co-Author: (1) Active Member Associate Member Audrey Kunkes Influenza Surveillance Coordinator Georgia Department of Public Health 2 Peachtree St., W 14 th Floor Atlanta, GA 30303 404-463-4625 Audrey.Kunkes@dph.ga.gov 18-ID-01 7
Technical Supplement Table VI. Table of criteria to determine whether a case should be reported to public health authorities. Criterion Reporting Disease or Condition Subtype Clinical Evidence Death Signs and symptoms of upper or lower respiratory infection Signs of respiratory distress, such as apnea (absence of breathing) Respiratory syncytial virus (RSV) infection, or suspected infection, as a diagnosis or active problem in a clinical record Respiratory syncytial virus (RSV) infection as a cause of death or a significant condition contributing to death listed on the death certificate Laboratory Evidence Any laboratory test indicating RSV isolation or detection (e.g., isolation of RSV by tissue cell culture, detection of RSV nucleic acid by RT-PCR or other nucleic acid detection assay; or detection of RSV antigen by immunofluorescent antibody staining [direct or indirect], immunochromatographic or similar rapid laboratory test, or from autopsy specimens by IHC staining) Isolation or detection of respiratory syncytial virus (RSV) within 60 days of death otes: = All criteria in the same column are ECESSARY to report a case. = At least one of these (E R MRE) criteria in each category (categories=clinical evidence, laboratory evidence, and epidemiological evidence) in the same column in conjunction with all criteria in the same column is required to report a case. Table VII. Classification Table: Criteria for defining a case of RSV-associated mortality. Criterion Confirmed Clinical Evidence Death Illness clinically compatible with RSV infection o alternative agreed upon cause of death o recovery to baseline health status prior to death Laboratory evidence Isolation of respiratory syncytial virus (RSV) by tissue cell culture Detection of respiratory syncytial virus (RSV) nucleic acid by reverse-transcriptase polymerase chain reaction (RT-PCR) or other nucleic acid detection assay Detection of respiratory syncytial virus (RSV) antigen by immunofluorescent antibody staining (direct or indirect) Detection of respiratory syncytial virus (RSV) antigen by immunochromatographic or similar rapid laboratory test Detection of respiratory syncytial virus (RSV) antigens from autopsy specimens by immunohistochemical (IHC) staining 2018 Template otes: = All criteria in the same column are ECESSARY to classify a case. A number following an indicates that this criterion is only required for a specific disease/condition subtype (see below). If the absence of a criterion (i.e., criterion T present) is required for the case to meet the classification criteria, list the absence of criterion as a necessary component. = At least one of these (E R MRE) criteria in each category (categories=clinical evidence, laboratory evidence, and epidemiologic evidence) in the same column in conjunction with all criteria in the same column is required to classify a case. A number following an indicates that this criterion is only required for a specific disease/condition subtype. 18-ID-01 8