OT - Why does flu peak in winter? (answer: dunno) from Scientific American, and a U.S. mortality study, and editorial, from JAMA (referenced in Science News). Biggest surprise: that flu & RSV kill a lot of people.
More surprising is the apparent magnitude of the problem - as many as 50,000 to 70,000 annual influenza deaths are estimated to occur in the United States.
Lots more references (and full mortality study) in JAMA.
Doc
sciam.com
Why do we get the flu most often in the winter? Are viruses more virulent in cold weather?
Marc Airhart
Austin, Texas
Hugh D. Niall is a medical doctor and Chief Executive Officer at Biota Holdings Limited in Melbourne, Australia. He heads a scientific team that developed a flu drug known as Zanamivir, which is now in clinical trials in the United States. Niall offers the following explanation.
FLU VIRUS
Every winter in the United States and other countries with largely temperate climates, there is a sharp rise in the incidence of respiratory infections, the milder of which are popularly described as "colds" and the more severe as "flu." These are caused by quite different viruses, but the distinction is blurred by an understandable tendency of some people who have colds to exaggerate the severity of their illness and lay claim to the status of being a victim of influenza.
This means that true "flu" is really a less common but a much more severe illness than many people realize. It nevertheless infects about 10 percent of the population each year. This percentage can rise to 25 or 30 percent in an epidemic year. For comparison, adults in the United States average two to four colds per year, and children six to eight.
Flu is characterized by the quite sudden onset of feverishness, with a sore throat and nasal discharge, chills, headache, muscle aches and loss of appetite, usually with fever of 100 to 104 degrees Fahrenheit. Over the next few days, the general symptoms may improve but the local symptoms (sore throat, cough) get worse. In an uncomplicated case the patient will be much improved after five to seven days but may take up to two weeks or even longer to recover completely. Flu can lead to serious complications, including bronchitis, viral or bacterial pneumonia and even death in elderly and chronically ill patients. Twenty-thousand or more people die of flu in the U.S. each year.
The winter flu epidemic in a given locality reaches its peak in two to three weeks and lasts five to six weeks. Then it disappears as quickly as it arrived. The reason for this is not completely clear. The usual pattern is for a rise in the incidence of flu in children, which precedes an increase in the adult population. Presumably children are infected at school or kindergarten, bring the virus home and infect their siblings and parents. The parents then pass on the flu to their friends and fellow workers, with a second generational leap upwards to the elderly. Nursing home epidemics are common, and that is where most of the serious complications and deaths due to flu occur.
This vertical transmission model is a reasonable description of events but begs some questions and leaves others unanswered. It does not explain how the virus entered the pool of school-age children in the first place. Of course, children will be more susceptible to infection as they will have, as a group, a low level of immunity to flu from not having encountered it previously. The virus will therefore be able to spread readily. If there is a low level of flu in the community, a school would be a logical site for an explosion of the viral population. If the strain of flu is one that has not circulated for many years, there may be a large enough population of susceptible adults to sustain the epidemic.
Another problem with the vertical upwards transmission model is that it does not explain how flu can break out simultaneously in areas that are far from one another geographically, when there is no apparent possibility of transmission between the sites. One theory is that the virus may be present in a latent form in asymptomatic carriers, who reactivate virus (one wonders why) and infect susceptible contacts.
But the frequency of human contact across the world and the highly infectious nature of the virus make this explanation difficult to accept. Moreover, there is no evidence of persistent or latent infection with influenza viruses. In any case, this idea is not really very different from the notion that the virus circulates at a low level throughout the year and seizes its opportunity to cause an outbreak when conditions allow. Even harder to explain is why the flu disappears from a community when there are still a large number of people susceptible to infection.
The answer as to why flu is a winter disease is not fully known. However, flu is spread largely by droplet (aerosol) infection from individuals with a high viral level in their nasal and throat secretions, sneezing and coughing on anyone close at hand. The aerosol droplets of the "right" size (thought to be about 1.5 micrometers in diameter) remain airborne and are breathed into the nose or lungs of the next victim. Situations in which people are crowded together are more common in cold or wet weather--and so perhaps this contributes to spreading the flu at these times. It is interesting that in equatorial countries, flu occurs throughout the year, but is highest in the monsoon or rainy season.
Several recent developments promise to increase our understanding of flu. There are now drugs for influenza (neuraminidase inhibitors) that will potentially treat all strains of this virus; and new tests in development will provide an on-the-spot diagnosis in 15 minutes or less. These advances should lead to flu being accurately diagnosed and treated in the community. This new focus on flu should provide more reliable worldwide data on its incidence and spread.
Until we know much more, flu will remain an unpredictable source of danger to public health worldwide. This fact is well illustrated by the alarming recent identification of an unusual avian strain of flu in Hong Kong in four patients, two of whom died. At the time of writing, this small outbreak is under intensive study by expert groups from the World Health Organization and the Centers for Disease Control and Prevention.
Answer posted on December 15, 1997
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sciencenews.org
Week of Feb. 1, 2003; Vol. 163, No. 5
As population ages, flu takes deadly turn
The annual U.S. toll of influenza has risen dramatically since the late 1970s, in part because of the advancing age of the population.
References:
Morens, D.M. 2003. Influenza-related mortality: Considerations for practice and public health. Journal of the American Medical Association 289(Jan. 8):227-228. Available at jama.ama-assn.org.
Thompson, W.W., et al. 2003. Mortality associated with influenza and respiratory syncytial virus in the United States. Journal of the American Medical Association 289(Jan. 8):179-186. Abstract available at jama.ama-assn.org.
Sources:
David M. Morens
National Institute of Allergy and Infectious Diseases
National Institutes of Health
6700-B Rockledge Dr., Room 3149
Bethesda, MD 20892-7630 (e-mail: dm270q@nih.gov)
William W. Thompson
Immunization Safety Branch
National Immunization Program
Centers for Disease Control and Prevention
1600 Clifton Road, NE
Mailstop E61
Atlanta, GA 30333
From Science News, Vol. 163, No. 5, Feb. 1, 2003, p. 78.
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[ABSTRACT]
Mortality Associated With Influenza and Respiratory Syncytial Virus in the United States
William W. Thompson, PhD; David K. Shay, MD, MPH; Eric Weintraub, MPH; Lynnette Brammer, MPH; Nancy Cox, PhD; Larry J. Anderson, MD; Keiji Fukuda, MD, MPH
Context Influenza and respiratory syncytial virus (RSV) cause substantial morbidity and mortality. Statistical methods used to estimate deaths in the United States attributable to influenza have not accounted for RSV circulation.
Objective To develop a statistical model using national mortality and viral surveillance data to estimate annual influenza- and RSV-associated deaths in the United States, by age group, virus, and influenza type and subtype.
Design, Setting, and Population Age-specific Poisson regression models using national viral surveillance data for the 1976-1977 through 1998-1999 seasons were used to estimate influenza-associated deaths. Influenza- and RSV-associated deaths were simultaneously estimated for the 1990-1991 through 1998-1999 seasons.
Main Outcome Measures Attributable deaths for 3 categories: underlying pneumonia and influenza, underlying respiratory and circulatory, and all causes.
Results Annual estimates of influenza-associated deaths increased significantly between the 1976-1977 and 1998-1999 seasons for all 3 death categories (P<.001 for each category). For the 1990-1991 through 1998-1999 seasons, the greatest mean numbers of deaths were associated with influenza A(H3N2) viruses, followed by RSV, influenza B, and influenza A(H1N1). Influenza viruses and RSV, respectively, were associated with annual means (SD) of 8097 (3084) and 2707 (196) underlying pneumonia and influenza deaths, 36 155 (11 055) and 11 321 (668) underlying respiratory and circulatory deaths, and 51 203 (15 081) and 17 358 (1086) all-cause deaths. For underlying respiratory and circulatory deaths, 90% of influenza- and 78% of RSV-associated deaths occurred among persons aged 65 years or older. Influenza was associated with more deaths than RSV in all age groups except for children younger than 1 year. On average, influenza was associated with 3 times as many deaths as RSV.
Conclusions Mortality associated with both influenza and RSV circulation disproportionately affects elderly persons. Influenza deaths have increased substantially in the last 2 decades, in part because of aging of the population, underscoring the need for better prevention measures, including more effective vaccines and vaccination programs for elderly persons.
JAMA. 2003;289:179-186
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Influenza-Related Mortality
Considerations for Practice and Public Health
David M. Morens, MD
In this issue of THE JOURNAL, the article by Thompson and colleagues estimates the burden of annual influenza mortality and provides much new and challenging information. The basic mortality question under consideration is what causes excess deaths during annual winter influenza "seasons"? Such mortality excesses can be estimated reasonably well from available data, but it is another problem entirely to determine what proportion is actually due to influenza. Traffic deaths, fire deaths, and other death categories can also increase during the same months.
Cause-of-death data are not very helpful because death certificate recordings are inaccurate for many conditions and probably more so for elderly persons, for institutionalized individuals, and for those who succumb to the combined effects of different medical conditions. Population mortality data cannot determine who did and did not have influenza. Traditional influenza mortality accounting is therefore insensitive (ie, unable to detect all influenza deaths that occur).
However, national mortality calculations and "real-time" calculations of combined influenza-plus-pneumonia mortality (so-called P & I mortality)generated by the Centers for Disease Control and Prevention's weekly 122-city mortality surveillance system2depend on such imperfect data. Reduced sensitivity may be acceptable for the 122-city system, the principal aim of which is to detect mortality excesses quickly enough to institute public health measures, but it seriously impairs quantifying total influenza mortality. This shortcoming impacts the direction of effort and allocation of resources to deal with whatever mortality excesses occur. To compound the problem, traditional P & I mortality detection may be not only insensitive but also nonspecific, subsuming deaths caused by other viruses and by primary bacterial pneumonias. Although it has long been clear that too many people die during influenza seasons, it is difficult to be sure just who is dying from what.
Thompson et al1 approach this fundamental problem by constructing more refined statistical models that incorporate national mortality data, and data on isolation or detection of influenza virus types and of respiratory syncytial virus (RSV), a cause of adult mortality not fully appreciated until recently.3, 4 In addition, Thompson et al1 go beyond P & I mortality to measure excess respiratory and circulatory disease (R & CD) mortality. This provides a range of influenza mortality estimates, from the familiar P & I data (probably underestimates), to the intermediate R & CD data, to the all-cause mortality data (probably overestimates).
The results most immediately apparent from these still-speculative but improved efforts are depressingly familiar. As has been known since the late 1800s, influenza is a major cause of mortality, its greatest burden falling on elderly persons, with a lesser but significant mortality peak in infancy. More surprising is the apparent magnitude of the problem - as many as 50 000 to 70 000 annual influenza deaths are estimated to occur in the United States. By comparison, this range may approach or exceed each year the total number of US lives lost during the entire decade-long Vietnam War, surely placing influenza in the forefront of public health priorities.
Worse is the revelation that annual influenza deaths have been and still are increasing dramatically. Thompson et al1 speculate reasonably that the approximate doubling in excess influenza season deaths during the past 2 decades resulted from aging of the population. In support of this belief, the authors note that age-specific death rates (ie, deaths per 100 000 persons within specific 5-year age-ranges) have not changed significantly from 1976. It is to be hoped that influenza-specific death rates in the older age groups have in fact declined during the past few decades of increasing influenza vaccination rates,5 but such an effect, if present, might not be easy to detect in mortality models.
Thompson et al1 also draw attention to a lesser-appreciated problem, that a significant component of excess mortality during influenza seasons (25% P & I mortality, 23% R & CD mortality) may be due to RSV and not to influenza. Adding to its well-deserved reputation as a significant cause of childhood illness and mortality, RSV seems also to mimic influenza in predominantly accounting for deaths in older adults. Influenza season mortality is thus a result of at least 2 important causes, each of which will require its own specific responses.
Another important finding by Thompson et al,1 infrequently discussed but long apparent to some observers,6 is the extraordinary burden of influenza mortality in the "elderly elderly," including the demonstration that persons 85 years or older are 32 times more likely than persons 65 to 69 years to die of (probable) influenza. Although it used to be whispered that influenza is "the old man's friend," it is hard to imagine anyone of any age choosing to "befriend" it. The average life expectancy for men and women reaching age 65 years in the United States now exceeds 81 and 84 years, respectively,7 and is still increasing steadily.
What then should be done with such troubling information about extreme risk to elderly persons? The data of Thompson et al1 suggest the need to rethink influenza prevention strategies. These strategies have traditionally grouped all persons older than 65 years into a one-size-fits-all risk group. In recent years, the targeted risk groups have laudably expanded from elderly and chronically ill persons to also include those with lesser but significant risks, such as persons aged 50 to 64 years, pregnant women, and infants and toddlers.8, 9 However, these newer strategies also should probably reflect stronger consideration of the substantial influenza risk to the oldest individuals, the "litmus test" group for new vaccines and for drugs used in treatment and prevention.
The findings of Thompson et al1 thus mix good news with bad. The results provide a clearer picture of the nature and burden of influenza-associated mortality but a bigger and much different problem than imagined. The challenge seems especially daunting in the face of 50 years of mixed evidence that influenza-prevention approaches, aimed more at personal protection than community control, have been sufficient. Annual influenza vaccination is and must remain among the most important public health priorities. However, current vaccines are not highly immunogenic in the very target groups (the "elderly elderly" and those with serious chronic conditions) that need them most.2, 8
Nearly 40 years ago, Centers for Disease Control and Prevention luminaries Alexander Langmuir, D.A. Henderson, and Robert Serfling10 lamented that influenza vaccines were insufficiently protective to constitute a sound basis for national prevention policy. Today's vaccines may be somewhat better, but they still pose the difficulty of trying to reduce influenza deaths by relying primarily on imperfect preventive agents, never fully embraced by the public. Now the medical and public health communities must also face the looming confrontation between an unstoppable force and an immovable object, the aging of the baby boom generation and the predictability of annual influenza. Simple demographics practically ensure an impending public health disaster of great proportion.
Hope lies in the realization that until better influenza and RSV vaccines become available, there still remains much good to be performed in clinical practice. This includes ending the many missed opportunities in the community, the office, and the institution to prevent influenza-associated death and severe illness.11 Endorsement by health care professionals appears to be the strongest determinant of a patient's acceptance of influenza vaccine.12 Active and organized approaches to prevention strategies (eg, patient calls and mailings) may also help to optimize patient vaccination rates.13
An important related role for clinicians is educating patients about the benefits and risks of annual influenza vaccination. Decades of misinformation need to be overcome, especially for older individuals who remember the reactogenic vaccines of 1957-1958 and the "swine flu affair" of 1976-1977, and who commonly hold to a tenacious belief that flu shots can cause the flu.14 Clinicians must be able to convey the well-documented reality that despite imperfect immunogenicity (not very good at preventing infection, fairly good at preventing severe disease and death2) influenza vaccines offer a substantial benefit-to-risk ratio and, for those at risk, represent the chief means of significantly reducing the chance of influenza death, hospitalization, and illness.5, 15-17 Even an imperfect vaccine, used optimally, can prevent many thousands of deaths. The enormous additional opportunity to prevent hospitalization and severe morbidity,8, 15, 16 although not addressed by Thompson et al,1 strengthens the case.
Physicians and other health care professionals can do even more to protect patients by receiving annual influenza vaccinations. Clinician vaccination prevents transmission to patients (a significant risk factor in many patient care situations6, 18), prevents the temporary loss of their services, sets a powerful example, and might even make a small contribution to community "herd immunity."
The article by Thompson et al1 presents a fresh look at influenza mortality. Now may be the time to take a fresh look at what can be done about it. While awaiting better vaccines and revitalized policies, the best immediate means of reducing the enormous burden of influenza mortality appears to be the focused attention of physicians and other health care professionals, who can play a uniquely life-saving role.
Editorials represent the opinions of the authors and THE JOURNAL and not those of the American Medical Association. |
