Influenza, Tracking Seasonal Influences and Virus Mutation
Influenza, Tracking Seasonal Influences and Virus Mutation
Influenza is an important disease because of the rapidity with which epidemics spread, the widespread morbidity, and the severity of complications, including viral and bacterial pneumonias. During major epidemics, severe illness and death occur, mainly among the elderly and people with compromised immune systems. In the United States, between 10,000 and 40,000 people die each year from influenza complications. However, in the 1918 pandemic, most of those who died were young and healthy adults. Given the potential for serious complications and high mortality rates with influenza, it is critical that public health agencies develop a system for tracking influenza epidemics from their origin each year in order to mount defensive measures such as vaccines and educational programs for potential victims.
Influenza is an acute viral disease of the respiratory tract characterized by fever, headache, myalgia (muscle aches), prostration, nasal inflammation and discharge, sore throat, and cough. Cough can often be severe and protracted, but other manifestations are usually self-limiting, with recovery in two to seven days. The recognition of influenza is usually based on epidemiological characteristics as part of a general epidemic; otherwise it is difficult to distinguish influenza from a severe cold or other viral respiratory diseases such as viral pneumonia. Viral pneumonia can also be caused by influenza virus, although gastrointestinal tract symptoms (nausea, vomiting, diarrhea) have been reported in about 25% of children in school outbreaks. The spread of influenza virus is predominantly airborne among crowded populations in confined spaces, especially school buses and barracks. Transmission may also occur by indirect contact, as the influenza virus may persist for hours, particularly in cold and dry weather. The viral incubation period is short; usually one to three days. Influenza is communicable for about three to five days after onset in adults and up to a week in young children.
There are three types of influenza virus currently recognized: types A, B, and C. Type A includes three subtypes (H1N1, H2N2, and H3N2) that have been associated with widespread epidemics and pandemics. Type B has been associated with regional or widespread epidemics. Type C is typically associated with sporadic cases and minor localized outbreaks. The viral type is determined by the antigenic properties of two relatively stable structural proteins, the nucleoprotein and the matrix protein.
The emergence of a completely new subtype, the process of known as antigenic shift, occurs at unpredictable intervals and only with type A viruses. Viruses characterized by antigenic shift are responsible for the pandemics that result from the unpredictable recombination (new combinations of genetic material) of human and swine or avian (usually duck) antigens. Relatively minor antigenic changes—known as “drift”—of type A and type B viruses that are responsible for frequent epidemics and regional outbreaks occur constantly, necessitating periodic (almost annually) reformulation of influenza vaccine. During the past 125 years, pandemics occurred in 1889, 1918, 1957, and 1968.
WORDS TO KNOW
ANTIGENIC DRIFT: Antigenic drift describes the gradual accumulation of mutations in genes (e.g. in genes coding for surface proteins) over a period of time.
COHORTING: Cohorting is the practice of grouping persons with like infections or symptoms together in order to reduce transmission to others and keep patients under close observation for a particular condition.
EPIDEMIC: From the Greek epidemic, meaning “prevalent among the people,” is most commonly used to describe an outbreak of an illness or disease in which the number of individual cases significantly exceeds the usual or expected number of cases in any given population.
REASSORTMENT: A condition resulting when two or more different types of viruses exchange genetic material to form a new, genetically different virus.
PANDEMIC: Pandemic, which means all the people, describes an epidemic that occurs in more than one country or population simultaneously.
PROSTRATION: A condition marked by nausea, disorientation, dizziness, and weakness caused by dehydration and prolonged exposure to high temperatures; also called heat exhaustion or hyperthermia.
Once an epidemic is underway, case attack rates range from 10% to 20% in the general population and can range up to 50% in confined populations such as boarding schools, military bases, or nursing homes. Influenza epidemics caused by type A viruses, type B viruses, or both occur in the United States almost every year. In temperate zones, epidemics usually occur in winter. In the tropics, they often occur during the rainy season, but outbreaks or sporadic cases may occur in any month. Influenza also occurs naturally in swine, horses, mink, and seals, and in many domestic and wild bird species all over the world. Transmission between species and reassortment (exchanging genetic material inside a host) of influenza A viruses have been reported to occur between swine, humans, ducks, and turkeys. The human influenza viruses responsible for the 1957 and 1968 pandemics contained gene segments closely related to those of avian influenza viruses.
Humans are the primary reservoir for human infections, though mammalian reservoirs such as swine and avian reservoirs such as ducks are likely sources of new human subtypes thought to emerge through genetic reassortment. New virulent subtypes cause pandemic influenza by spreading through a population that has little or no immunity because of lack of exposure to the new viral surface antigens.
When a new viral subtype appears, all children and adults are equally susceptible except for individuals who have lived through earlier epidemics of the same subtype. Infection produces immunity to the specific infecting virus but the duration of immunity depends on the degree of antigenic drift and the number of previous infections. Flu vaccines produce responses that are specific for the included viruses and also boost responses to related strains to which the individual has been exposed before. Attack rates tend to be age specific; people that have lived long enough to experience earlier epidemics of the same subtype usually have at least partial immunity years later, and this partial immunity protects them from closely related subtypes.
Because any outbreak of influenza has important and sometimes catastrophic implications, all cases must be reported to local health authorities in order to assist disease surveillance. The identity of the disease agent by viral subtype as determined by laboratory testing should be provided if possible. Although annual vaccination is the primary strategy for preventing complications of influenza virus infections, the CDC notes that antiviral medications with activity against influenza viruses can be effective for the chemoprophylaxis and treatment of influenza. Four licensed influenza antiviral agents are available in the United States: amantadine, rimantadine, zanamivir, and oseltamivir. These treatments should be started within 48 hours of the onset of symptoms. Influenza A virus resistance to amantadine and rimantadine can emerge rapidly during treatment. On the basis of antiviral testing results conducted at the CDC and in Canada indicating high levels of resistance, the CDC recommends that neither amantadine nor rimantadine be used for the treatment or chemoprophylaxis of influenza A in the United States until susceptibility to these antiviral medications has been re-established among circulating influenza A viruses. Oseltamivir (Tamiflu®) may have caused delirium in some pediatric patients.
Since influenza is usually self-limiting in healthy adults under age 65, the CDC generally advises against personal stockpiling of the drugs. Federal and state health authorities and healthcare institutions are creating stockpiles of antiviral influenza medications for persons at greatest risk for complications from influenza. A potential consequence of personal stockpiling is depletion of existing supplies of antivirals so that they will not be available to those persons who most need them. In addition, widespread personal stockpiling and inappropriate use of antivirals (e.g., as a daily regimen regardless of the degree of influenza risk) might compound the risk for influenza by creating conditions for the emergence of resistant strains of influenza. Widespread resistance to oseltamivir could be catastrophic in the event of an avian flu pandemic on the scale of the 1918 pandemic.
Influenza vaccination remains the cornerstone for the control and treatment of influenza, and antiviral influenza medications should serve as an adjunct to vaccine. In addition, the public and healthcare personnel need to be trained to avoid unprotected coughs and sneezes as well as proper handwashing. Patient isolation is impractical in most cases because of the viral incubation period during which victims are infectious without symptoms. However, during an epidemic it would be desirable to isolate patients, especially infants and children, by putting them in the same room (“cohorting”) during the first five to seven days of illness.
Immunization may provide 70% to 80% protection against infection in healthy young adults when the vaccine antigen closely matches circulating viruses. Vaccine programs have been less successful in preventing disease, but have reduced the hospitalization of people over 65 for complications such as pneumococcal pneumonia by 30% to 50%. The CDC recommends that influenza vaccination for the elderly be supplemented with immunization against pneumococcal pneumonia. Immunization can benefit any individual, but it should especially be considered for emergency responders, people performing essential services, and military personnel.
Influenza vaccine should be provided each year before influenza is expected in the community (November through March in the United States). Travelers should be immunized attending on the different seasonal patterns of influenza in various parts of the world. The single dose suffices for persons with prior exposure to Influenza A and B. Two doses of vaccine one month apart are required for younger persons with no previous immunization history. Routine immunization programs should be directed primarily at those with the greatest risk of serious complications or death, and those who might spread infection to them, such as Health Care personnel and household contacts of high-risk people.
Influenza is a disease that is under surveillance by the World Health Organization (WHO); the following procedure is recommended:
- 1. Influenza epidemics within a country should be reported to the WHO.
- 2. The viral subtype should be reported and prototype strains should be submitted to one of the three WHO centers for reference and research on influenza (Atlanta, London, and Melbourne). Throat secretion specimens, aspirates, and paired blood samples may also be sent to any WHO-recognized national influenza center.
- 3. Conduct epidemiological studies and promptly identify viruses at the national health agencies.
- Ensure sufficient commercial and/or governmental facilities for the production of adequate quantities of vaccine and programs for vaccine administration to high-risk people and essential personnel.
In view of the seriousness of the threat of an avian flu pandemic, the stockpiling of adequate supplies of antiviral medications should be added to this list of national health agency responsibilities.
Recent news media publicity regarding the possibility of another avian flu epidemic on the scale of the 1918 pandemic stimulated many members of the public to purchase, privately stockpile, and consume pharmaceutical products, especially oseltamivir, as a way to ward off a supposed “imminent” outbreak of H5N1 influenza. This consumption amounted to a waste of valuable anti-viral supplies and has increased the probability of the emergence of resistant viral strains. During treatment, drug resistant viruses may emerge late in the course of therapy and be transmitted to others. Therefore, the cohorting of people on antiviral therapy should be considered, especially in closed populations with many highrisk individuals. Antibiotics should be administered only if patients develop bacterial complications. However, if government agencies are to ask individuals to forgo private stockpiles of antivirals, government must assure adequate supplies of antivirals for the public in case of a severe outbreak of type A influenza. In the case of a severe outbreak, aggregations of people in emergency shelters should be avoided, since this will favor outbreaks of the disease if the virus is introduced.
Heymann, David L. Control of Communicable Diseases Manual, 18th ed. Washington, DC: American Public Health Association, 2004.
Centers for Disease Control and Prevention. “Increased Antiviral Medication Sales before the 2005-06 Influenza Season—New York City.” <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5510a3.htm> (accessed June 13, 2007).