Good morning all! Today, The Blogmocracy General Hospital Presents Grand Rounds Influenza. There are entirely too many ailments called the ‘Flu’. That norovirus that made you vomit is not The Flu. That nasty cold that turned into bronchitis is not The Flu. Please read the following lecture on Influenza as prepared by the CDC.
How Flu Spreads
Person to Person
People with flu can spread it to others up to about 6 feet away. Most experts think that flu viruses are spread mainly by droplets made when people with flu cough, sneeze or talk. These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs. Less often, a person might also get flu by touching a surface or object that has flu virus on it and then touching their own mouth or nose.
(To avoid this, people should stay away from sick people and stay home if sick. It also is important to wash hands often with soap and water. If soap and water are not available, use an alcohol-based hand rub. Linens, eating utensils, and dishes belonging to those who are sick should not be shared without washing thoroughly first. Eating utensils can be washed either in a dishwasher or by hand with water and soap and do not need to be cleaned separately. Further, frequently touched surfaces should be cleaned and disinfected at home, work and school, especially if someone is ill.)
The Flu Is Contagious
Most healthy adults may be able to infect others beginning 1 day before symptoms develop and up to 5 to 7 days after becoming sick. Children may pass the virus for longer than 7 days. Symptoms start 1 to 4 days after the virus enters the body. That means that you may be able to pass on the flu to someone else before you know you are sick, as well as while you are sick. Some persons can be infected with the flu virus but have no symptoms. During this time, those persons may still spread the virus to others.
Influenza Prevention & Control Recommendations
Signs and Symptoms
Influenza viruses are spread from person to person primarily through large-particle respiratory droplet transmission (e.g., when an infected person coughs or sneezes near a susceptible person). Transmission via large-particle droplets requires close contact between source and recipient persons, because droplets do not remain suspended in the air and generally travel only a short distance (less than or equal to 1 meter) through the air. Contact with respiratory-droplet contaminated surfaces is another possible source of transmission. Airborne transmission (via small-particle residue [less than or equal to 5µm] of evaporated droplets that might remain suspended in the air for long periods of time) also is thought to be possible, although data supporting airborne transmission are limited. The typical incubation period for influenza is 1—4 days (average: 2 days). Adults shed influenza virus from the day before symptoms begin through 5—10 days after illness onset. However, the amount of virus shed, and presumably infectivity, decreases rapidly by 3—5 days after onset in an experimental human infection model. Young children also might shed virus several days before illness onset, and children can be infectious for 10 or more days after onset of symptoms. Severely immunocompromised persons can shed virus for weeks or months.
Uncomplicated influenza illness is characterized by the abrupt onset of constitutional and respiratory signs and symptoms (e.g., fever, myalgia, headache, malaise, nonproductive cough, sore throat, and rhinitis). Among children, otitis media, nausea, and vomiting also are commonly reported with influenza illness. Uncomplicated influenza illness typically resolves after 3—7 days for the majority of persons, although cough and malaise can persist for >2 weeks. However, influenza virus infections can cause primary influenza viral pneumonia; exacerbate underlying medical conditions (e.g., pulmonary or cardiac disease); lead to secondary bacterial pneumonia, sinusitis, or otitis media; or contribute to coinfections with other viral or bacterial pathogens. Young children with influenza virus infection might have initial symptoms mimicking bacterial sepsis with high fevers, and febrile seizures have been reported in 6%—20% of children hospitalized with influenza virus infection. Population-based studies among hospitalized children with laboratory-confirmed influenza have demonstrated that although the majority of hospitalizations are brief (2 or fewer days), 4%—11% of children hospitalized with laboratory-confirmed influenza required treatment in the intensive care unit, and 3% required mechanical ventilation. Among 1,308 hospitalized children in one study, 80% were aged <5 years, and 27% were aged <6 months. Influenza virus infection also has been uncommonly associated with encephalopathy, transverse myelitis, myositis, myocarditis, pericarditis, and Reye syndrome.
Respiratory illnesses caused by influenza virus infection are difficult to distinguish from illnesses caused by other respiratory pathogens on the basis of signs and symptoms alone. Sensitivity and predictive value of clinical definitions vary, depending on the prevalence of other respiratory pathogens and the level of influenza activity. Among generally healthy older adolescents and adults living in areas with confirmed influenza virus circulation, estimates of the positive predictive value of a simple clinical definition of influenza (acute onset of cough and fever) for laboratory-confirmed influenza infection have varied (range: 79%—88%).
Young children are less likely to report typical influenza symptoms (e.g., fever and cough). In studies conducted among children aged 5—12 years, the positive predictive value of fever and cough together was 71%—83%, compared with 64% among children aged <5 years. In one large, population-based surveillance study in which all children with fever or symptoms of acute respiratory tract infection were tested for influenza, 70% of hospitalized children aged <6 months with laboratory-confirmed influenza were reported to have fever and cough, compared with 91% of hospitalized children aged 6 months—5 years. Among children who subsequently were shown to have laboratory-confirmed influenza infections, only 28% of those hospitalized and 17% of those treated as outpatients had a discharge diagnosis of influenza.
Clinical definitions have performed poorly in some studies of older patients. A study of nonhospitalized patients aged 60 and older years indicated that the presence of fever, cough, and acute onset had a positive predictive value of 30% for influenza. Among hospitalized patients aged 65 years and older with chronic cardiopulmonary disease, a combination of fever, cough, and illness of <7 days had a positive predictive value of 53% for confirmed influenza infection. In addition, the absence of symptoms of influenza-like illness (ILI) does not effectively rule out influenza; among hospitalized adults with laboratory-confirmed infection in two studies, 44%—51% had typical ILI symptoms. A study of vaccinated older persons with chronic lung disease reported that cough was not predictive of laboratory–confirmed influenza virus infection, although having both fever or feverishness and myalgia had a positive predictive value of 41%. These results highlight the challenges of identifying influenza illness in the absence of laboratory confirmation and indicate that the diagnosis of influenza should be considered in patients with respiratory symptoms or fever during influenza season.
Hospitalizations and Deaths from Influenza
In the United States, annual epidemics of influenza typically occur during the fall or winter months, but the peak of influenza activity can occur as late as April or May (Figure 1). Influenza-related complications requiring urgent medical care, including hospitalizations or deaths, can result from the direct effects of influenza virus infection, from complications associated with age or pregnancy, or from complications of underlying cardiopulmonary conditions or other chronic diseases. Studies that have measured rates of a clinical outcome without a laboratory confirmation of influenza virus infection (e.g., respiratory illness requiring hospitalization during influenza season) to assess the effect of influenza can be difficult to interpret because of circulation of other respiratory pathogens (e.g., respiratory syncytial virus) during the same time as influenza viruses.
During seasonal influenza epidemics from 1979—1980 through 2000—2001, the estimated annual overall number of influenza-associated hospitalizations in the United States ranged from approximately 55,000 to 431,000 per annual epidemic (mean: 226,000). The estimated annual number of deaths attributed to influenza from the 1990—91 influenza season through 1998—99 ranged from 17,000 to 51,000 per epidemic (mean: 36,000). In the United States, the estimated number of influenza-associated deaths increased during 1990—1999. This increase was attributed in part to the substantial increase in the number of persons aged 65 years and older who were at increased risk for death from influenza complications. In one study, an average of approximately 19,000 influenza-associated pulmonary and circulatory deaths per influenza season occurred during 1976—1990, compared with an average of approximately 36,000 deaths per season during 1990—1999. In addition, influenza A (H3N2) viruses, which have been associated with higher mortality (54), predominated in 90% of influenza seasons during 1990—1999, compared with 57% of seasons during 1976—1990.
Influenza viruses cause disease among persons in all age groups. Rates of infection are highest among children, but the risks for complications, hospitalizations, and deaths from influenza are higher among persons aged 65 years and older, young children, and persons of any age who have medical conditions that place them at increased risk for complications from influenza. Estimated rates of influenza-associated hospitalizations and deaths varied substantially by age group in studies conducted during different influenza epidemics. During 1990–1999, estimated average rates of influenza-associated pulmonary and circulatory deaths per 100,000 persons were 0.4–0.6 among persons aged 0–49 years, 7.5 among persons aged 50–64 years, and 98.3 among persons aged 65 years and older.NOTE: The text above is taken from Prevention & Control of Influenza – Recommendations of the Advisory Committee on Immunization Practices (ACIP) 2008. MMWR 2008 Aug 8; 57(RR07);1-60. (Also available as PDF , 586K).
Vaccine Virus Selection for the 2012-2013 Influenza Season
Each year, experts from Food and Drug Administration (FDA), World Health Organization (WHO), U.S. Centers for Disease Control and Prevention (CDC) and other institutions study virus samples collected from around the world. They identify the influenza viruses that are the most likely to cause illness during the upcoming flu season so that people can be protected against them through vaccination.
On February 23, 2012 the WHO recommended that the Northern Hemisphere’s 2012-2013 seasonal influenza vaccine be made from the following three vaccine viruses:
- an A/California/7/2009 (H1N1)pdm09-like virus;
- an A/Victoria/361/2011 (H3N2)-like virus;
- a B/Wisconsin/1/2010-like virus (from the B/Yamagata lineage of viruses).
While the H1N1 virus used to make the 2012-2013 flu vaccine is the same virus that was included in the 2011-2012 vaccine, the recommended influenza H3N2 and B vaccine viruses are different from those in the 2011-2012 influenza vaccine for the Northern Hemisphere.
Who participates in vaccine virus selection for the flu vaccine used in the United States?
The WHO vaccine virus decision meetings include WHO representatives from the WHO Collaborating Centers, Essential Regulatory Laboratories, and others from the Global Influenza Surveillance and Response System (GISRS). After WHO makes its recommendations, the U.S. FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) meets to concur with or modify WHO’s recommendation for the United States.
On February 28, 2012, the U.S. Food and Drug Administration’s (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) met to discuss the WHO recommendation. VRBPAC voted to adopt the same recommendation for the U.S. as WHO did for the Northern Hemisphere.
How are the viruses selected to make flu vaccine?
The influenza (flu) viruses selected for inclusion in the seasonal flu vaccines are updated each year based on information about which influenza viruses are being found, how they are spreading, and how well the previous season’s vaccine viruses might protect against any that are being newly identified. Currently, more than 100 national influenza centers in more than 100 countries conduct year-round surveillance for influenza viruses and disease activity. These laboratories then send influenza viruses for additional analyses to the five WHO Collaborating Centers for Reference and Research on Influenza, which are located in the following places:
- Atlanta, Georgia, USA (Centers for Disease Control and Prevention, CDC);
- London, United Kingdom (National Institute for Medical Research);
- Melbourne, Australia (Victoria Infectious Diseases Reference Laboratory);
- Tokyo, Japan (National Institute for Infectious Diseases); and
- Beijing, China (National Institute for Viral Disease Control and Prevention).
Vaccine viruses are chosen to maximize the likelihood that the influenza vaccine will protect against the viruses most likely to spread and cause illness among people during the upcoming flu season. WHO recommends specific vaccine viruses for influenza vaccine production, but then individual countries make their own decisions for licensing of vaccines in their country. In the United States, the FDA determines what viruses will be used in U.S.-licensed vaccines.
Since the early 1980s, the seasonal flu vaccine has been trivalent (a three-component vaccine) with each component selected to protect against one of the three main groups of influenza viruses circulating in humans.
Will a quadrivalent vaccine be available for the 2012-2013 season?
Flu vaccine for the US market is produced and distributed by the private sector. While some manufacturers are planning to produce a quadrivalent (four component) vaccine in the future, quadrivalent vaccine is not expected to be available for the 2012-2013 season. Of note, on February 29, 2012, quadrivalent flu vaccine manufactured by MedImmune, LLC was licensed by FDA for use in the United States.
Overview of Influenza Surveillance in the United States
The Epidemiology and Prevention Branch in the Influenza Division at CDC collects, compiles and analyzes information on influenza activity year round in the United States and produces FluView, a weekly influenza surveillance report, from October through mid-May. The U.S. influenza surveillance system is a collaborative effort between CDC and its many partners in state, local, and territorial health departments, public health and clinical laboratories, vital statistics offices, healthcare providers, clinics, and emergency departments. Information in five categories is collected from eight different data sources that allow CDC to:
- Find out when and where influenza activity is occurring
- Track influenza-related illness
- Determine what influenza viruses are circulating
- Detect changes in influenza viruses
- Measure the impact influenza is having on deaths in the United States
Five Categories of Influenza Surveillance
1. Viral Surveillance — Approximately 80 U.S. World Health Organization (WHO) Collaborating Laboratories and 60 National Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories located throughout the United States participate in virologic surveillance for influenza. All state public health laboratories participate as U.S. WHO collaborating laboratories along with some county public health laboratories and some large tertiary care or academic medical centers. Most NREVSS laboratories participating in influenza surveillance are hospital laboratories. The U.S. WHO and NREVSS collaborating laboratories report the total number of respiratory specimens tested and the number positive for influenza types A and B each week to CDC. Most of the U.S. WHO collaborating laboratories also report the influenza A subtype (H1 or H3) of the viruses they have isolated and the ages of the persons from whom the specimens were collected. The majority of NREVSS laboratories do not report the influenza A subtype. Reports from both sources are combined and the weekly total number of positive influenza tests, by virus type/subtype, and the percent of specimens testing positive for influenza are presented in the weekly influenza update, FluView. A subset of the influenza viruses collected by U.S. WHO collaborating laboratories are sent to CDC for further characterization, including gene sequencing, antiviral resistance testing and antigenic characterization. This information is presented in the antiviral resistance and antigenic characterization sections of the FluView report.
Surveillance for Novel Influenza A Viruses – In 2007, human infection with a novel influenza A virus became a nationally notifiable condition. Novel influenza A virus infections include all human infections with influenza A viruses that are different from currently circulating human influenza H1 and H3 viruses. These viruses include those that are subtyped as nonhuman in origin and those that are unsubtypable with standard laboratory methods and reagents. Rapid reporting of human infections with novel influenza A viruses will facilitate prompt detection and characterization of influenza A viruses and accelerate the implementation of effective public health responses.
2. Outpatient Illness Surveillance — Information on patient visits to health care providers for influenza-like illness is collected through the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet). ILINet consists of more than 3,000 healthcare providers in all 50 states, the District of Columbia and the U.S. Virgin Islands reporting over 30 million patient visits each year. Each week, approximately 1,800 outpatient care sites around the country report data to CDC on the total number of patients seen and the number of those patients with influenza-like illness (ILI) by age group (0-4 years, 5-24 years, 25-49 years, 50-64 years, and ≥ 65 years). For this system, ILI is defined as fever (temperature of 100°F [37.8°C] or greater) and a cough and/or a sore throat in the absence of a KNOWN cause other than influenza. Sites with electronic records use an equivalent definition as determined by state public health authorities.
- The percentage of patient visits to healthcare providers for ILI reported each week is weighted on the basis of state population. This percentage is compared each week with the national baseline of 2.4%. The baseline is the mean percentage of patient visits for ILI during non-influenza weeks for the previous three seasons plus two standard deviations. Due to wide variability in regional level data, it is not appropriate to apply the national baseline to regional data; therefore, region specific baselines are calculated. Regional baselines for the 2011-12 influenza season are:
Regional baselines for the 2011-12 influenza season are:Region 1 — 1.1%
Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and VermontRegion 2 — 2.5%
New Jersey, New York, Puerto Rico, and the U.S. Virgin Islands
Region 3 — 2.5%
Delaware, District of Columbia, Maryland, Pennsylvania, Virginia, and West Virginia
Region 4 — 2.3%
Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee
Region 5 — 1.6%
Illinois, Indiana, Michigan, Minnesota, Ohio, and Wisconsin
Region 6 — 4.3%
Arkansas, Louisiana, New Mexico, Oklahoma, and Texas
Region 7 — 2.3%
Iowa, Kansas, Missouri, and Nebraska
Region 8 — 2.1%
Colorado, Montana, North Dakota, South Dakota, Utah, and Wyoming
Region 9 — 3.9%
Arizona, California, Guam, Hawaii, and Nevada
Region 10— 2.2%
Alaska, Idaho, Oregon, and Washington
- ILI Activity Indicator Map: — Data collected in ILINet are used to produce a measure of ILI activity for all 50 states, the District of Columbia, and New York City. Activity levels are based on the percent of outpatient visits in a jurisdiction due to ILI compared to the average percent of ILI visits that occur during weeks with little or no influenza virus circulation (non-influenza weeks). Because the number of sites reporting each week is variable, baselines are adjusted each week based on which sites within each jurisdiction provide data. To perform this adjustment, provider level baseline ratios are calculated for those that have a sufficient reporting history. Providers that do not have the required reporting history are assigned the baseline ratio for their practice type. The jurisdiction level baseline is then calculated using a weighted sum of the baseline ratios for each contributing provider.
The activity levels correspond to the number of standard deviations away from the mean the percent of visits due to ILI is each week. There are 10 activity levels classified as minimal (levels 1-3), low (levels 4-5), moderate (levels 6-7), and high (levels 8-10). An activity level of 1 corresponds to values that are below the mean, level 2 corresponds to an ILI percentage less than 1 standard deviation above the mean, level 3 corresponds to ILI more than 1, but less than 2 standard deviations above the mean, and so on, with an activity level of 10 corresponding to ILI 8 or more standard deviations above the mean.
- 122 Cities Mortality Reporting System —Each week, the vital statistics offices of 122 cities across the United States. report the total number of death certificates received and the number of those for which pneumonia or influenza was listed as the underlying or contributing cause of death by age group (Under 28 days, 28 days –1 year, 1-14 years, 15-24 years, 25-44 years, 45-64 years, 65-74 years, 75-84 years, and ≥ 85 years). The percentage of deaths due to pneumonia and influenza (P&I) are compared with a seasonal baseline and epidemic threshold value calculated for each week. The seasonal baseline of P&I deaths is calculated using a periodic regression model that incorporates a robust regression procedure applied to data from the previous five years. An increase of 1.645 standard deviations above the seasonal baseline of P&I deaths is considered the “epidemic threshold,” i.e., the point at which the observed proportion of deaths attributed to pneumonia or influenza was significantly higher than would be expected at that time of the year in the absence of substantial influenza-related mortality.
- Influenza-Associated Pediatric Mortality Surveillance System — Influenza-associated deaths in children (persons less than 18 years) was added as a nationally notifiable condition in 2004. Any laboratory-confirmed influenza-associated death in a child is reported through this system. Demographic and clinical information are collected on each case and are transmitted to CDC.
- Influenza Hospitalization Network (FluSurv-NET) — FluSurv-NET conducts surveillance for population-based, laboratory-confirmed influenza related hospitalizations in children (persons less than 18 years) and adults. The network covers over 80 counties in the 10 Emerging Infections Program (EIP) states (CA, CO, CT, GA, MD, MN, NM, NY, OR, and TN) and four additional states (MI, OH, RI and UT). Cases are identified by reviewing hospital laboratory and admission databases and infection control logs for children and adults with a documented positive influenza test (viral culture, direct/indirect fluorescent antibody assay (DFA/IFA), reverse transcription-polymerase chain reaction (RT-PCR), or a rapid influenza diagnostic test (RIDT)) conducted as a part of routine patient care. FluSurv-NET estimated hospitalization rates are reported each week during the influenza season.
5. Summary of the Geographic Spread of Influenza — State health departments report the estimated level of spread of influenza activity in their states each week through the State and Territorial Epidemiologists Reports. States report influenza activity as no activity, sporadic, local, regional, or widespread. These levels are defined as follows:
- No Activity: No laboratory-confirmed cases of influenza and no reported increase in the number of cases of ILI.
- Sporadic: Small numbers of laboratory-confirmed influenza cases or a single laboratory-confirmed influenza outbreak has been reported, but there is no increase in cases of ILI.
- Local: Outbreaks of influenza or increases in ILI cases and recent laboratory-confirmed influenza in a single region of the state.
- Regional:Outbreaks of influenza or increases in ILI and recent laboratory confirmed influenza in at least two but less than half the regions of the state with recent laboratory evidence of influenza in those regions.
- Widespread:Outbreaks of influenza or increases in ILI cases and recent laboratory-confirmed influenza in at least half the regions of the state with recent laboratory evidence of influenza in the state.
Together, the five categories of influenza surveillance are designed to provide a national picture of influenza activity. Human infections with novel influenza A viruses, pneumonia and influenza mortality from the 122 Cities Mortality System, and influenza-associated pediatric deaths are reported on a national level only. FluSurv-NET data provides population-based, laboratory-confirmed estimates of influenza-related hospitalizations but are reported from limited geographic areas. Outpatient influenza-like illness and laboratory data are reported on a national level and by influenza surveillance region. The state and territorial epidemiologists’ reports of the geographic spread of influenza activity and the ILI activity indicator display state-level information.
It is important to maintain a comprehensive system for influenza surveillance for several reasons:
- Influenza viruses are constantly changing which requires ongoing collection and characterization of the strains.
- Influenza strains can rapidly undergo changes leading to pandemics of influenza; surveillance of viruses will detect these changes.
- Vaccines must be administered annually and are updated regularly based on surveillance findings.
- Treatment for influenza is guided by laboratory surveillance for antiviral resistance.
- National responses to emerging pandemic strains are triggered by surveillance data.
- Varying segments of the population are affected by influenza and may require targeted interventions. These groups are determined through influenza surveillance.
It is important to remember the following about influenza surveillance in the United States:
- All influenza activity reporting by public health partners and health-care providers is voluntary.
- The reported information answers the questions of where, when, and what influenza viruses are circulating. It can be used to determine if influenza activity is increasing or decreasing, but cannot be used to ascertain how many people have become ill with influenza during the influenza season.
- The system consists of eight complementary surveillance components in five categories. These components include reports from more than 140 laboratories, 3,000 outpatient health care providers, vital statistics offices in 122 cities, research and health-care personnel at the FluSurv-NET sites, and influenza surveillance coordinators and state epidemiologists from all 50 state health departments, the District of Columbia, Guam, Puerto Rico, and U.S. Virgin Islands health departments.
- Influenza surveillance data collection is based on a reporting week that starts on Sunday and ends on Saturday of each week. Each surveillance participant is requested to summarize weekly data and submit it to CDC by Tuesday afternoon of the following week. Those data are then downloaded, compiled, and analyzed at CDC. The FluView surveillance report is distributed and posted on this Web site each Friday from October through mid-May.