Infectious Diseases

Influenza

BY: PHYSICIANS COMMITTEE FOR RESPONSIBLE MEDICINE

Risk Factors and Diagnosis

Influenza viruses A and B cause acute respiratory infection. Influenza may present with symptoms similar to the common cold (see Upper Respiratory Infection), but also often causes more severe systemic symptoms, such as high fever, myalgias, weakness, and severe pulmonary involvement.

Symptoms may begin abruptly after a 1- to 4-day incubation. However, an infected person can pass the virus to others before symptoms begin and for approximately 1 week after symptom onset. Uncomplicated influenza is self-limiting. In high-risk populations, however, influenza can cause significant morbidity and mortality.

Influenza has become a matter of increasing concern due to the recent outbreaks of H5N1 avian influenza and the confirmation that the pandemic of 1918, which killed 40 million to 50 million people, was caused by an avian virus with properties similar to H5N1.1,2 Wild birds may carry influenza viruses in their digestive tracts and are believed to pass them to domesticated birds, typically in poultry farms, where viruses may replicate and be transmitted to humans. H5N1 has proven fatal to nearly 100% of infected chickens and about 50% of infected humans.3

Risk Factors

Contact with infected individuals. Direct contact with persons who have an upper respiratory infection permits viral transfer. Coughing or sneezing aerosolizes respiratory droplets containing influenza virus. The droplets commonly make contact with hands and household surfaces and can be easily transmitted to uninfected persons. They can also be directly inhaled. Saliva, however, is not an effective mode of transmission.

Closed settings. Homes and schools have higher transmission rates, compared with typical work settings.

Immunocompromise. Persons with compromised immune systems, including those with malnutrition, diabetes, and chronic respiratory disease, generally have a higher risk of mortality if they are infected by influenza. However, the influenza pandemic of 1918 and the recent H5N1 outbreaks have led to a high rate of mortality in young, otherwise healthy persons.

Winter season. Influenza infections more commonly occur in the winter, but cold climates are not necessarily a risk factor for disease occurrence or severity.4

Contact with infected birds. Risk for H5N1 influenza is principally related to contact with infected domesticated birds or bird feces, secretions, and products.

Diagnosis

Influenza typically has few physical findings and, in mild cases, may be indistinguishable from common colds.

Patients with symptoms or signs of lower-respiratory infection, such as dyspnea and rales, should be evaluated for pneumonia or exacerbation of chronic lung disease. Persons who appear seriously ill may require hospitalization and antibiotic treatment when bacterial pneumonia or systemic infection is suspected.

Rapid influenza tests that distinguish influenza A and B are valuable diagnostic tools when influenza is suspected in the clinic and when antiviral therapy could shorten the course and reduce symptoms. Note: Rapid tests should not be used during outbreaks, because the probability of flu is high and testing is not cost-effective. Individuals who present with flu-like illnesses during an outbreak are treated accordingly without further testing. Clinical judgment is paramount in these situations.

Cultures help track the specific strains of viruses circulating in a certain region or during a particular season.

Prevention and Treatment

Covering the mouth and nose when coughing and sneezing, washing hands appropriately, and avoiding touching one's eyes and nose are the most effective preventive strategies to avoid infection.

Phenol/acetate sprays for household use have virucidal qualities.

Vaccines produced annually do not always prevent influenza and will not protect against emerging strains of avian influenza. However, annual vaccines help avert epidemics, because they reduce the risk of coinfection. The combination of 2 influenza virus infections in a single individual allows the sharing of genetic material, a process called reassortment, which can produce more virulent strains.

Exercise appears to improve vaccine response, particularly in the elderly. The efficacy of influenza vaccine is reduced in older people, partly because of the immunosenescence that occurs with aging.5 Moderate exercise (>20 minutes, 3 times/week) significantly improved antibody response to influenza vaccine in this population.5,6

In older individuals, levels of perceived stress have been shown to affect certain immune responses to flu vaccine (eg, production of antibodies and interleukin-2).5,7 A limited body of evidence suggests that stress-management interventions can produce significant increases in antibody titer after flu vaccination.8 However, further research is required before such interventions can be recommended universally.

Treatment

Influenza is a self-limited illness, except in high-risk individuals or when a highly pathogenic strain is involved. In general, symptoms can be prevented or reduced in duration with antivirals if started within 48 hours, although drugs are most effective when started within 24 hours of exposure or symptom development. It is not clear whether these drugs prevent complications or are effective in high-risk populations.9

The following antivirals may reduce symptoms and shorten the course of disease.

Amantadine and rimantadine (M2 ion channel blockers). These drugs are only effective against influenza A. Rimantadine may have fewer central nervous system side effects. Resistance may develop, and if one drug is ineffective, the other drug is also ineffective. The current H5N1 avian influenza is resistant to these drugs, as were most strains of influenza A in the 2005/2006 flu season. Sensitivity patterns should be known before prescribing these drugs.

Oseltamivir (Tamiflu) and zanamivir (Relenza). These neuraminidase inhibitors are generally effective for prevention and treatment of influenza A and B, but only oseltamivir is approved for prevention. Most H5N1 infections have been sensitive to oseltamivir, although resistance has been reported.10 Oseltamivir is generally well-tolerated, but zanamivir may cause respiratory side effects, including bronchospasm, in those with respiratory problems.

Probenecid. This gout medication, when taken simultaneously with one-half the normal oseltamivir dose may provide an effective serum concentration for influenza treatment, thus extending the supply of a potentially scarce medicine.11 This is an off-label use of probenecid.

Acetaminophen, aspirin, and ibuprofen. These common medications may improve myalgias. Their use for mild fever is unnecessary. Aspirin should not be used in children with an acute viral illness, due to the risk of Reye's syndrome. When cold symptoms occur, only symptomatic treatment is beneficial (see Upper Respiratory Infection).

Complications of influenza include viral and/or bacterial pneumonia, myositis, rhabdomyolysis, Reye's syndrome, and toxic shock syndrome (when S. aureus combines with influenza B infection). All of these require specialized treatment.

Nutritional Considerations

The nutritional status of the host can affect immunity in a variety of ways, and deficiencies of most micronutrients can impair immunity, including antibody response.12 However, the immune response to vaccination in older patients, was not associated with plasma levels of several micronutrients known to affect immunity, such as retinol and zinc.13 Nor was immune response improved by supplementation with a combination multiple vitamin/trace element formula.14

A botanical extract may be of benefit. The berries of black elder contain high levels of naturally occurring flavonoids that have been shown to markedly stimulate proinflammatory cytokine production.15 These flavonoids also act against herpes simplex virus type 1, respiratory syncytial virus, and the parainfluenza and influenza viruses.16 Two randomized, placebo-controlled clinical trials found that black elderberry extract reduced the duration of influenza by > 50%.15,16 Further research is necessary to confirm its effectiveness.

Orders

See Basic Diet Orders chapter.

What to Tell the Family

Influenza is easily transmitted within a household or closed living environments, such as nursing homes. Covering one's mouth and nose while coughing and sneezing, and prompt hand washing should be encouraged. Refraining from touching the eyes and nose may also help prevent respiratory infections. A flu vaccine is important for older persons and anyone with a chronic disease, such as diabetes and asthma. In addition, when flu occurs in the family, prescription medicines may be effective for treatment or prevention if they are received within 48 hours of symptom onset.

References

1. Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature. 2005;437;889-893.

2. Belshe RB. The origins of the pandemic influenza lessons from the 1918 virus. N Engl J Med. 2005;353:2209-2211.

3. World Health Organization. Epidemic and Pandemic Alert and Response (EPR): Avian influenza. Available at: www.who.int/csr/disease/avian_influenza/en/index.html. Accessed February 3, 2006.

4. Warshauer DM, Dick EC, Mandel AD, Flynn TC, Jerde RS. Rhinovirus infections in an isolated antarctic station. Transmission of the viruses and susceptibility of the population. Am J Epidemiol. 1989;129:319-340.

5. Kohut ML, Cooper MM, Nickolaus MS, Russell DR, Cunnick JE. Exercise and psychosocial factors modulate immunity to influenza vaccine in elderly individuals. J Gerontol A Biol Sci Med Sci. 2002;57:M557-M562.

6. Kohut ML, Arntson BA, Lee W, et al. Moderate exercise improves antibody response to influenza immunization in older adults. Vaccine. 2004;22:2298-2306.

7. Moynihan JA, Larson MR, Treanor J, et al. Psychosocial factors and the response to influenza vaccination in older adults. Psychosom Med. 2004;66:950-953.

8. Vedhara K, Bennett PD, Clark S. Enhancement of antibody responses to influenza vaccination in the elderly following a cognitive-behavioural stress management intervention. Psychother Psychosom. 2003;72:245-252.

9. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2004;53(RR-6):1-40.

10. Le QM, Kiso M, Someya K, et al. Avian flu: isolation of drug-resistant H5N1 virus. Nature. 2005;437:1108.

11. Butler D. Wartime tactic doubles power of scarce bird-flu drug. Nature. 2005;438:6.

12. Cunningham-Rundles S, McNeeley DF, Moon A. Mechanisms of nutrient modulation of the immune response. J Allergy Clin Immunol. 2005;115:1119-1128.

13. Gardner EM, Bernstein ED, Popoff KA, Abrutyn E, Gross P, Murasko DM. Immune response to influenza vaccine in healthy elderly: lack of association with plasma beta-carotene, retinol, alpha-tocopherol, or zinc. Mech Ageing Dev. 2000;117:29-45.

14. Allsup SJ, Shenkin A, Gosney MA, et al. Difficulties of recruitment for a randomized controlled trial involving influenza vaccination in healthy older people. Gerontology. 2002;48:170-173.

15. Barak V, Halperin T, Kalickman I. The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines. Eur Cytokine Netw. 2001;12:290-296.

16. Zakay-Rones Z, Thom E, Wollan T, Wadstein J. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. J Int Med Res. 2004;32:132-140.


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