Amantadine

Outbreaks of influenza A virus infection can cause substantial morbidity and mortality among residents of nursing homes. Surveillance for the 1991-92 influenza season indicates that the dominant circulating viruses are influenza A [1], for which amantadine hydrochloride is effective for prevention and treatment [2]. This report describes the use of amantadine as an adjunct to influenza vaccine for controlling an influenza A(H3N2) outbreak that occurred in a Washington nursing home during the 1989-90 influenza season.

The outbreak occurred at a four-wing (lettered A-D), skilled-nursing facility with 201 residents. Most residents were ambulatory, although the movement of those in wing C was restricted. Residents' ages ranged from 40 years through 99 years (median: 85 years); 141 (70%) were female. Influenza vaccine had been administered by the deltoid intramuscular route to 113 (56%) residents during November and the first 2 weeks of December 1989: 21 (46%) in wing A, 26 (58%) in wing B, 39 (85%) in wing C, and 27 (42%) in wing D. Vaccinated and unvaccinated residents were similar in age, sex distribution, and prevalence of congestive heart failure and chronic obstrucive pulmonary disease.

Cases of influenza-like illness (ILI) (*) among residents occurred from December 26 through January 30 (Figure 1). Overall, 35 (17%) of the 201 residents became ill: 10 (22%) in wing A, seven (16%) in wing B, 15 (33%) in wing C, and three (5%) in wing D. Influenza A(H3N2) viruses were isolated from nasopharyngeal specimens obtained from three ill residents; CDC characterized one of these isolates antignically as similar to influenza A/Shanghai/11/87(H3N2), a component of the 1989-90 vaccine.

(*) Illness with oral temperature [is greater than or equal to]100 F ([is greater than or equal to]38 C) and cough or sore throat with onset from December 15, 1989, through January 31, 1990.

ILI occurred among 21 (19%) of 113 vaccinated residents and 14 (16%) of 88 unvaccinated residents (17 [15%] of 113 vaccinated residents and 12 [14%] of 88 unvaccinated residents before January 13). When the analysis was stratified by nursing home wing, the efficacy of vaccine for preventing ILI was 20% (95% confidence limits = -60%, 60%). The median duration of symptoms was 6.0 days for vaccinated ill residents and 8.5 days for unvaccinated ill residents (p = 0.2, Wilcoxon rank sum test).

On January 12, the Washington State Department of Health was notified of the outbreak and recommended that all residents receive amantadine, 100 mg orally in a single dose each day for 10 days. Nursing home physicians ordered amantadine preventive therapy for 186 (93%) residents; doses were not adjusted for renal function. During the 18-day period following the institution of amantadine therapy (January 13-30), the daily average rate of ILI was 0.3 cases per day compared with an average rate of 1.6 cases per day for the 18-day period preceding use of the drug (December 26-January 12) (p<0.01, 2-sample test of equality of Poisson parameters).

Residents were monitored three times each day for signs and symptoms of amantadine toxicity. Five (3%) persons had probably side effects (one each with hallucinations, anorexia, agitation, insomnia, and dizziness); each manifestation resolved after discontinuation of the drug (four persons) or withholding one dose (one person).

Editorial Note: Because nuring home residents are at high risk for complications from influenza, the Immunization Practices Advisory Committee (ACIP) recommends that they receive annual vaccination against influenza [3]. However, the efficacy of vaccine in preventing influenza among nursing home residents has varied [4]. For example, in this report, the efficacy of vaccination against ILI during outbreak was 20%; in comparison, during the same influenza season, vaccine efficacy was 31%-70% in nursing home outbreaks in four other states (D. Wells, Florida Department of Health and Rehabilitative Services, unpublished data, 1980). Although vaccination may not always prevent illness among nursing home residents, it can reduce the duration of illness [5], incidence of hospitalization [6], and risk for death [6,7]. When vaccine antigens closely match circulating strains, the vaccine may be more than 70% effective in preventing influenza-related pneumonia, hospitalization, and death [6].

Although the impact of amantadine in uncontrolled situations cannot be determined with certainty, its apparent effect on this outbreak is consistent with other that indicate amantadine can be used as an adjunct approach to control outbreaks of influenza A among nursing home residents [8]. Moreover, the duration and impact of this outbreak might have been attenuated further had contingency plans existed for using amantadine earlier in the outbreak [3]. Such contingency plans may include preapproving medication orders by physicians or ensuring a means of obtaining them on short notice, ensuring an adequate supply of the drug, and developing a system to monitor for drug side effects. If an outbreak is recognized, all residents should receive amantadine, regardless of their vaccination status.

In addition to outbreak control, amantadine can also protect residents for whom vaccination is contraindicated, those who are expected to have a poor antibody response to vaccination, and newly vaccinated residents during the 14-day period following vaccination while immunity develops. Although amantadine can reduce the severity and duration of influenza A illness in healthy adults, no data are available about its efficacy in preventing complications of influenza A among nursing home residents [3]. If amantadine is used to treat residents who develop illness consistent with influenza, therapy should be initiated within 48 hours of onset, even if laboratory confirmation is not available.

In this outbreak, the incidence of potential side effects of amantadice was low--even without dose adjustment for each resident--and is consistent with the shift in 1987 to a reduction of daily dosage from 200 mg to 100 mg for persons [is greater than or equal to]65 years of age [3]. However, dosage should be modified for age, weight, renal function, and the presence of other medical conditions accoding to manufacturers' recommendations.

Nursing home officials should monitor state and local influenza surveillance findings and initiate amantadine prophylaxis if influenza A activity is reported in their community and ILI occurs in the nursing home. Amantadine should also be offered to unvaccinated staff who provide care to residents. Unvaccinated nursing home residents, including newly admitted residents, should continue to be vaccinated until the reason ends.

References

[1] CDC. Update: influenza activity - United States, 1991-92. MMWR 1991;40:809-10.

[2] Douglas RG Jr. Prophylaxis and treatment of influenza. N Engl J Med 1990;322:443-9.

[3] ACIP. Prevention and control of influenza: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(no. RR-6).

[4] Strassburg MA, Greenland S, Sorvillo F, Lieb LE, Habel LA. Influenza in the elderly: report of an outbreak and a review of vaccine effectiveness reports. Vaccine 1986;4:38-44.

[5] Ruben FL, Johnston F, Streiff EJ. Influenza in a partially immunized aged population: effectiveness of killed Hong Kong vaccine against infection with the England strain. JAMA 1974;230:863-6.

[6] Patriarca PA, Weber JA, Parker RA, et al. Efficacy of influenza vaccine nursing homes: reduction in illness and complications during an influenza A(H3N2) epidemic. JAMA 1985;253:1136-9.

[7] Gross PA, Quinnan GV, Rodstein M, et al. Association of influenza immunization with reduction in mortality in an elderly population; a prospective study. Arch Intern Med 1988;148:562-5.

[8] Arden NH, Patriarca PA, Fasano MB, et al. The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A(H3N2) in a nursing home. Arch Intern Med 1988;148:865-8.

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