Fighting the FLU

This is the first of two articles on the microbiology of the influenza virus and the clinical problems presented by influenza infection. The second part will address the role of viral mutations in the onset and progression of infection and the requirement for annual vaccination against the current, most prevalent influenza strains in light of recent information demonstrating alarming genetic interactions between human and avian influenza type A strains. Part 2 will appear in a future issue.

Over the past few years, the public’s concern about influenza and protective vaccination has skyrocketed. One reason for this growing worry is the higher incidence of severe illness associated with seasonal influenza virus strains, especially in young children.¹ In addition, the effectiveness of available influenza vaccines has come into question, with current attention focused on the lack of sufficient vaccine to protect those at high risk for viral infection and its sequelae.^1,2 The accidental contamination of tissue cultures in the laboratories of a major contractor for production of the 2004-2005 trivalent vaccine has dramatically heightened both the public’s anxiety and the concern of health care professionals.

This loss of immunization material reduces the available influenza vaccine supply by approximately 50 million doses. As a result, many people both within and outside of the health care professions have attempted to learn much more about the emerging infectious disease threat posed by this common, resilient, and adaptive respiratory microbial pathogen.

Historical and current epidemiological features caused by influenza outbreaks illustrate the continuing challenge influenza viruses present to public health. The evolving nature of viral transmission, postinfluenza respiratory disease, and public health vaccination strategies are important topics in light of increasingly numerous reports of cross-species infections between certain animal virus strains and susceptible humans.

WHAT IS INFLUENZA?

Influenza is an acute respiratory tract infection caused by the influenza virus, with clinical disease occurring primarily in seasonal outbreaks each winter. Commonly referred to as the flu, it is often self-limiting. However certain viral strains can cause severe to moderate illness, predisposing infected people to potentially life-threatening pneumonia. The peak influenza season in the United States occurs from late December to the end of February or mid-March. Figure 1 shows a summary of more than 25 years of influenza activity during these months. In brief, the two most important characteristics of influenza are the epidemic nature of clinical disease and the extensive mortality resulting from secondary pulmonary complications. ³

Abrupt symptoms develop following an incubation period of about 2 days (1-5 day range). These include fever (usually 101°-102° F), myalgia (mainly in back muscles), sore throat, muscle weakness, runny nose, and a nonproductive cough. Children can manifest additional gastrointestinal symptoms such as nausea, vomiting, and diarrhea, which are only occasionally found in adults. These clinical manifestations typically last for about 2 to 3 days, followed by a rapid recovery in most instances.⁴

THE DISEASE ROLE OF INFLUENZA EPIDEMICS AND PANDEMICS

Influenza epidemics have periodically recurred every few years for more than 400 years. Many of the early recorded severe epidemics were described on the basis of rapid onset of symptoms centuries before the virus was isolated in 1933.5 Clearly, these outbreaks are considered serious, as estimates of overall attack rates among the population range from 10% to 40%. Certain high risk groups, such as elderly people 65 years of age or older, young children, and people with immune compromising conditions, are especially susceptible to the flu and severe respiratory complications.^6,7 Approximately 36,000 people die each year in the United States from complications of influenza.^2,8 The percentage of fatalities in adults over 90 years of age comprises more than 65% of these statistics.^2,8 A summary of the impact of influenza infections appears in Figure 2.

Influenza pandemics have also been recorded over the centuries, with global, devastating outbreaks responsible for millions of symptomatic cases and deaths. These pandemics are associated with new strains of influenza type A virus. The tragic statistics regarding the three influenza pandemics documented for the 20th century illustrate the extent of human suffering and mortality (Figure 3). In each instance, the disease spread throughout the world within 1 year of detection of the etiologic influenza strain.^3,9

MAJOR CHARACTERISTICS OF INFLUENZA VIRUSES

Influenza virus is a single-stranded, ribonucleic acid (RNA) microorganism classified as a member of the orthomyxovirus family. There are three types of influenza viruses—A, B, and C—based on distinct antigenic (protein, toxin, or other substance to which the body reacts by producing antibodies) differences determined by differences in viral nucleic acids. While each possess the same morphologic characteristics and intracellular replication cycle, differences are discernable in the characteristic features of each viral type. These include viral epidemiology, host range, and clinical manifestations of infection (Figure 4).

The standard nomenclature for isolated influenza viruses includes the influenza type, place of initial isolation, strain designation, and the year of isolation (Figure 5). Surface projections or spikes cover these enveloped viruses. These are the glycoproteins hemagglutinin (HA) or neuraminidase (NA), which are major antigens and periodically change as new influenza strains evolve. Although the development of cellular immune responses are the primary mechanisms for recovery from disease, protection against re-infection with the same or cross-reacting influenza strains is primarily associated with synthesis of host antibodies against HA and NA.

ANTIGENIC DRIFT AND ANTIGENIC SHIFT

The ability of influenza types A and B to undergo periodic antigenic variation is one of the most unique characteristics of these RNA viruses. Possessing the capability of altering the major structural HA and NA targets of host immune responses, influenza is continuously able to cause disease through new variants that infected hosts have little or no resistance via exposure to previous strains. ⁵

Antigenic drift is a minor change in surface antigens, resulting from point mutations in the viral genetic material. This phenomenon can result in epidemics. Antigenic shift, on the other hand, results from a different mechanism involving genetic recombination between influenza A strains. Influenza type A viruses can undergo major changes in both HA and NA at varying intervals via the integration/recombination of viral nucleic acids between human strains of influenza A viruses and those that infect birds. If the resultant new type A influenza viruses are introduced into the human population, infected persons have little or no protective immunity. When these strains can be passed efficiently from person to person, the potential for a widespread pandemic becomes a distinct possibility.

Due to the potential for an influenza pandemic, all health care professionals need to stay abreast of the latest information regarding influenza in order to protect themselves as well as their patients. The Centers for Disease Control and Prevention are a source for detailed, up-to-date information ( www.cdc.gov).

REFERENCES

1. Treanor J. Influenza vaccine—outmaneuvering antigenic shift and drift. New Engl J Med . 2004;350:218-220.
2. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory synctial virus. JAMA . 2003;289:179-186.
3. Treanor JJ. Influenza virus. In: Mandell G, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Disease . 5th ed. Philadelphia: Churchill Livingstone; 2004:1823-1849.
4. Centers for Disease Control and Prevention. Influenza (flu). Questions and answers: the disease. Available at: www.cdc.gov/flu/ about/qa/disease.htm. Accessed December 15, 2004.
5. Smith W, Andrewes CH, Laidlaw PP. A virus obtained from influenza patients. Lancet . 1933;2:66-68.
6. Monto AS, Kioumehr F. The Tecumseh study of respiratory illness. IX. Occurrence of influenza in the community. 1966-1971. Am J Epidemiol . 1975;105:553-559.
7. Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev . 1982;4:25-44.
8. Simonsen L, Clarke MJ, Schonberger LB, et al. Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J Infect Dis . 1998;178:53-60.
9. Centers for Disease Control and Prevention. Influenza (flu). Influenza pandemics. Available at: www.cdc.gov/flu/avian/gen-info/pandemics.htm. Accessed December 14, 2004.

From Dimensions of Dental Hygiene. January 2005;3(1):22-23, 25-26.