Determining the Seasonality of Respiratory Syncytial Virus in the United States: The Impact of Increased Molecular Testing.

Background: In the United States, the seasonality of respiratory syncytial virus (RSV) has traditionally been defined on the basis of weeks during which antigen-based tests detect RSV in >10% of specimens (hereafter, the "10% threshold"). Because molecular testing has become more widely used, we explored the extent of polymerase chain reaction (PCR)-based RSV testing and its impact on determining the seasonality of RSV. Methods: We assessed antigen- and PCR-based RSV reports submitted to the National Respiratory and Enteric Virus Surveillance System during July 2005-June 2015. To characterize RSV seasons by using PCR-based reports, we assessed the traditional 10% threshold; subsequently, we developed 3 methods based on either PCR-based detections or the percentage of positive test results. Results: The annual number of PCR-based reports increased 200-fold during 2005-2015, while the annual number of antigen-based reports declined. The weekly percentage of specimens positive for RSV by PCR was less than that for antigen-detection tests; accordingly, the 10% threshold excluded detections by PCR and so was imprecise for characterizing RSV seasons. Among our PCR-specific approaches, the most sensitive and consistent method captured 96%-98% of annual detections within a season, compared with 82%-94% captured using the traditional method. Conclusions: PCR-based reports are increasingly relevant for RSV surveillance and determining the seasonality of RSV. These PCR-specific methods provide a more comprehensive understanding of RSV trends, particularly in settings where testing and reporting are most active. Diagnostic practices will vary by locality and should be understood before choosing which method to apply.

Environmental drivers of the spatiotemporal dynamics of respiratory syncytial virus in the United States.

Epidemics of respiratory syncytial virus (RSV) are known to occur in wintertime in temperate countries including the United States, but there is a limited understanding of the importance of climatic drivers in determining the seasonality of RSV. In the United States, RSV activity is highly spatially structured, with seasonal peaks beginning in Florida in November through December and ending in the upper Midwest in February-March, and prolonged disease activity in the southeastern US. Using data on both age-specific hospitalizations and laboratory reports of RSV in the US, and employing a combination of statistical and mechanistic epidemic modeling, we examined the association between environmental variables and state-specific measures of RSV seasonality. Temperature, vapor pressure, precipitation, and potential evapotranspiration (PET) were significantly associated with the timing of RSV activity across states in univariate exploratory analyses. The amplitude and timing of seasonality in the transmission rate was significantly correlated with seasonal fluctuations in PET, and negatively correlated with mean vapor pressure, minimum temperature, and precipitation. States with low mean vapor pressure and the largest seasonal variation in PET tended to experience biennial patterns of RSV activity, with alternating years of "early-big" and "late-small" epidemics. Our model for the transmission dynamics of RSV was able to replicate these biennial transitions at higher amplitudes of seasonality in the transmission rate. This successfully connects environmental drivers to the epidemic dynamics of RSV; however, it does not fully explain why RSV activity begins in Florida, one of the warmest states, when RSV is a winter-seasonal pathogen. Understanding and predicting the seasonality of RSV is essential in determining the optimal timing of immunoprophylaxis.

Human Adenovirus Surveillance - United States, 2003-2016.

Human adenoviruses (HAdVs) are nonenveloped, double-stranded DNA viruses in the family Adenoviridae; seven species (A-G) and >60 genotypes are known to cause human infection (1). Clinical manifestations associated with HAdV infection include fever, acute respiratory illness, gastroenteritis, and conjunctivitis. HAdV infection can be severe, particularly among immunocompromised patients, and can cause respiratory failure, disseminated infection, hemorrhagic cystitis, neurologic disease, and death (1,2). Illness tends to occur sporadically and without demonstrated seasonality. Outbreaks of HAdV have been reported globally in communities (3), and in closed or crowded settings, including dormitories, health care settings, and among military recruits, for whom a vaccine against HAdV type 4 (HAdV-4) and HAdV type 7 (HAdV-7) has been developed (4,5). CDC summarized HAdV detections voluntarily reported through the National Adenovirus Type Reporting System (NATRS) after initiation of surveillance in 2014 to describe trends in reported HAdVs circulating in the United States. Reporting laboratories were also encouraged to report available results for specimens collected before surveillance began. Overall, the number of reporting laboratories and HAdV type identifications reported to NATRS has increased substantially from the start of official reporting in 2014 through 2016; this report describes specimens collected during 2003-2016. The most commonly reported HAdV types were HAdV type 3 (HAdV-3) and HAdV type 2 (HAdV-2), although HAdV types reported fluctuated considerably from year to year. In the United States, information on recently circulating HAdV types is needed to inform diagnostic and surveillance activities by clinicians and public health practitioners. Routine reporting to NATRS by all U.S. laboratories with the capacity to type HAdVs could help strengthen this surveillance system.

Sustained decrease in laboratory detection of rotavirus after implementation of routine vaccination­United States, 2000-2014.

Rotavirus infection is the leading cause of severe gastroenteritis among infants and young children worldwide. Before the introduction of rotavirus vaccine in the United States in 2006, rotavirus infection caused significant morbidity among U.S. children, with an estimated 55,000-70,000 hospitalizations and 410,000 clinic visits annually. The disease showed a characteristic winter-spring seasonality and geographic pattern, with annual seasonal activity beginning in the West during December-January, extending across the country, and ending in the Northeast during April-May. To characterize changes in rotavirus disease trends and seasonality following introduction of rotavirus vaccines in the United States, CDC compared data from CDC's National Respiratory and Enteric Virus Surveillance System (NREVSS), a passive laboratory reporting system, for prevaccine (2000-2006) and postvaccine (2007-2014) years. National declines in rotavirus detection were noted, ranging from 57.8%-89.9% in each of the 7 postvaccine years compared with all 7 prevaccine years combined. A biennial pattern of rotavirus activity emerged in the postvaccine era, with years of low activity and highly erratic seasonality alternating with years of moderately increased activity and seasonality similar to that seen in the prevaccine era. These results demonstrate the substantial and sustained effect of rotavirus vaccine in reducing the circulation and changing the epidemiology of rotavirus among U.S. children.

Respiratory syncytial virus--United States, July 2012-June 2014.

Respiratory syncytial virus (RSV) causes lower respiratory infection among infants and young children worldwide. Annually in the United States, RSV infection has been associated with an estimated 57,527 hospitalizations and 2.1 million outpatient visits among children aged <5 years. In temperate climate zones, RSV generally circulates during the fall, winter, and spring. However, the exact timing and duration of RSV seasons vary by region and from year-to-year. Knowing the start of the RSV season in any given locality is important to health care providers and public health officials who use RSV seasonality data to guide diagnostic testing and the timing of RSV immunoprophylaxis for children at high risk for severe respiratory infection. To describe RSV seasonality (defined as onset, offset, peak, and duration) nationally, by U.S. Department of Health and Human Services (HHS) regions and for the state of Florida, CDC analyzes RSV laboratory detections reported to the National Respiratory and Enteric Virus Surveillance System (NREVSS). Florida is reported separately because it has an earlier season onset and longer season duration than the rest of the country. For 2012-13, the RSV season onset ranged from late October to late December, and season offset ranged from late December to late April, excluding Florida. For 2013-14, the RSV season onset ranged from late October to late January, and season offset from late January to early April, excluding Florida. Weekly updates of RSV national, regional, and state RSV trends are available from NREVSS at http://www.cdc.gov/surveillance/nrevss.

Acute neurologic illness of unknown etiology in children - Colorado, August-September 2014.

On September 12, 2014, CDC was notified by the Colorado Department of Public Health and Environment of a cluster of nine children evaluated at Children's Hospital Colorado with acute neurologic illness characterized by extremity weakness, cranial nerve dysfunction (e.g., diplopia, facial droop, dysphagia, or dysarthria), or both. Neurologic illness onsets occurred during August 8-September 15, 2014. The median age of the children was 8 years (range = 1-18 years). Other than neck, back, or extremity pain in some patients, all had normal sensation. All had a preceding febrile illness, most with upper respiratory symptoms, occurring 3-16 days (median = 7 days) before onset of neurologic illness. Seven of eight patients with magnetic resonance imaging of the spinal cord had nonenhancing lesions of the gray matter of the spinal cord spanning multiple levels, and seven of nine with magnetic resonance imaging of the brain had nonenhancing brainstem lesions (most commonly the dorsal pons). Two of five with magnetic resonance imaging of the lumbosacral region had gadolinium enhancement of the ventral nerve roots of the cauda equina. Eight children were up to date on polio vaccination. Eight have not yet fully recovered neurologically.

Respiratory syncytial virus circulation in seven countries with Global Disease Detection Regional Centers.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children globally, with the highest burden in low- and middle-income countries where the association between RSV activity and climate remains unclear. METHODS: Monthly laboratory-confirmed RSV cases and associations with climate data were assessed for respiratory surveillance sites in tropical and subtropical areas (Bangladesh, China, Egypt, Guatemala, Kenya, South Africa, and Thailand) during 2004-2012. Average monthly minimum and maximum temperatures, relative humidity, and precipitation were calculated using daily local weather data from the US National Climatic Data Center. RESULTS: RSV circulated with 1-2 epidemic periods each year in site areas. RSV seasonal timing and duration were generally consistent within country from year to year. Associations between RSV and weather varied across years and geographic locations. RSV usually peaked in climates with high annual precipitation (Bangladesh, Guatemala, and Thailand) during wet months, whereas RSV peaked during cooler months in moderately hot (China) and arid (Egypt) regions. In South Africa, RSV peaked in autumn, whereas no associations with seasonal weather trends were observed in Kenya. CONCLUSIONS: Further understanding of RSV seasonality in developing countries and various climate regions will be important to better understand the epidemiology of RSV and for timing the use of future RSV vaccines and immunoprophylaxis in low- and middle-income countries.

Human parainfluenza virus circulation, United States, 2011-2019.

BACKGROUND: Human parainfluenza viruses (HPIVs) cause upper and lower respiratory tract illnesses, most frequently among infants and young children, but also in the elderly. While seasonal patterns of HPIV types 1-3 have been described, less is known about national patterns of HPIV-4 circulation. OBJECTIVES: To describe patterns of HPIVs circulation in the United States (US). STUDY DESIGN: We used data from the National Respiratory and Enteric Virus Surveillance System (NREVSS), a voluntary passive laboratory-based surveillance system, to characterize the epidemiology and circulation patterns of HPIVs in the US during 2011-2019. We summarized the number of weekly aggregated HPIV detections nationally and by US census region, and used a subset of data submitted to NREVSS from public health laboratories and several clinical laboratories during 2015-2019 to analyze differences in patient demographics. RESULTS: During July 2011 - June 2019, 2,700,135 HPIV tests were reported; 122,852 (5 %) were positive for any HPIV including 22,446 for HPIV-1 (18 %), 17,474 for HPIV-2 (14 %), 67,649 for HPIV-3 (55 %), and 15,283 for HPIV-4 (13 %). HPIV testing increased substantially each year. The majority of detections occurred in children aged ≤ 2 years (36 %) with fluctuations in the distribution of age by type. CONCLUSIONS: HPIVs were detected year-round during 2011-2019, with type-specific year-to-year variations in circulation patterns. Among HPIV detections where age was known, the majority were aged ≤ 2 years. HPIV-4 exhibited an annual fall-winter seasonality, both nationally and regionally. Continued surveillance is needed to better understand national patterns of HPIV circulation.

Timing of respiratory syncytial virus and influenza epidemic activity in five regions of Argentina, 2007-2016.

BACKGROUND: Within-country differences in the timing of RSV and influenza epidemics have not been assessed in Argentina, the eighth largest country in the world by area. OBJECTIVE: We aimed to compare seasonality for RSV and influenza both nationally and in each of the five regions to inform Argentina's prevention and treatment guidelines. METHOD: The Argentine National Laboratories and Health Institutes Administration collected respiratory specimens from clinical practices, outbreak investigations, and respiratory virus surveillance in 2007-2016; these were tested using immunofluorescence or RT-PCR techniques. We calculated weekly percent positive (PP) and defined season onset as >2 consecutive weeks when PP exceeded the annual mean for the respective year and region. Median season measures (onset, offset and peak) and the established mean method were calculated for each virus. RESULTS: An annual median 59 396 specimens were tested for RSV and 60 931 for influenza; 21-29% tested positive for RSV and 2-7% for influenza. National RSV activity began in April; region-specific start weeks varied by 7 weeks. Duration of RSV activity did not vary widely by region (16-18 weeks in duration). National influenza activity started in June; region-specific start weeks varied by 3 weeks. Duration of influenza epidemic activity varied more by region than that of RSV (7-13 weeks in duration). CONCLUSION: In Argentina, RSV and influenza activity overlapped during the winter months. RSV season tended to begin prior to the influenza season, and showed more variation in start week by region. Influenza seasons tended to vary more in duration than RSV seasons.

Respiratory syncytial virus testing capabilities and practices among National Respiratory and Enteric Virus Surveillance System laboratories, United States, 2016.

BACKGROUND: Laboratory tests to detect respiratory syncytial virus (RSV) vary in sensitivity and specificity. Diagnostic testing practices can impact RSV disease diagnosis and burden estimates. OBJECTIVES: We surveyed a sample of laboratories that participated in the National Respiratory and Enteric Virus Surveillance System (NREVSS) in 2015-2016 to understand RSV testing, diagnostic capabilities, and practices. STUDY DESIGN: We distributed surveys in fall 2016 to NREVSS laboratories using an internet survey platform. We conducted a descriptive analysis of survey responses and stratified results by self-identified children's hospital laboratories (CHL, i.e. laboratories affiliated with or in a children's hospital) or general hospital laboratories (GHL, i.e. laboratories that performed analysis on specimens from only adults or adults and children). RESULTS: We sampled 367 (82.5%) of 445 eligible NREVSS laboratories with a 35.7% response rate; 11.5% (n = 15) were CHLs. All CHLs had PCR-based assay capability to test for RSV compared to 48.7% of GHLs (p < 0.001), and it was the most frequent method used by CHLs (n = 9, 75.0%). GHLs used rapid antigen detection tests most frequently (n = 65, 60.2%) to detect RSV compared to CHLs (p = 0.02, n = 3, 25.0%). Almost half (n = 41, 48.2%) of GHLs reported specimen submission from adults ≥50 years for RADTs. CONCLUSIONS: Laboratory testing and diagnostic capabilities differed by whether laboratories self-identified as a CHL or GHL. Many GHLs reported use of RADTs in adults ≥50 years, a less sensitive diagnostic method for this population compared to PCR-based assays. RADT use in adults might miss RSV cases and affect diagnoses and disease burden estimates.

Human Metapneumovirus Circulation in the United States, 2008 to 2014.

BACKGROUND: Human metapneumovirus (HMPV) infection causes respiratory illness, including bronchiolitis and pneumonia. However, national HMPV seasonality, as it compares with respiratory syncytial virus (RSV) and influenza seasonality patterns, has not been well described. METHODS: Hospital and clinical laboratories reported weekly aggregates of specimens tested and positive detections for HMPV, RSV, and influenza to the National Respiratory and Enteric Virus Surveillance System from 2008 to 2014. A season was defined as consecutive weeks with ≥3% positivity for HMPV and ≥10% positivity for RSV and influenza during a surveillance year (June through July). For each virus, the season, onset, offset, duration, peak, and 6-season medians were calculated. RESULTS: Among consistently reporting laboratories, 33 583 (3.6%) specimens were positive for HMPV, 281 581 (15.3%) for RSV, and 401 342 (18.2%) for influenza. Annually, 6 distinct HMPV seasons occurred from 2008 to 2014, with onsets ranging from November to February and offsets from April to July. Based on the 6-season medians, RSV, influenza, and HMPV onsets occurred sequentially and season durations were similar at 21 to 22 weeks. HMPV demonstrated a unique biennial pattern of early and late seasonal onsets. RSV seasons (onset, offset, peak) were most consistent and occurred before HMPV seasons. There were no consistent patterns between HMPV and influenza circulations. CONCLUSIONS: HMPV circulation begins in winter and lasts until spring and demonstrates distinct seasons each year, with the onset beginning after that of RSV. HMPV, RSV, and influenza can circulate simultaneously during the respiratory season.