Amantadine prophylaxis during an institutional outbreak of type A (H1N1) influenza.

In January 1984, an outbreak of influenza caused by A/Victoria/7/83-like virus, a new H1N1 variant, occurred in an institution for mentally handicapped children and adults. During the first 18 days of the outbreak, 35 (81%) of 43 residents in two housing modules became ill, nearly all of whom had received influenza vaccine the previous autumn. Amantadine hydrochloride prophylaxis was initiated in two other housing modules and was continued for 28 days. While factors influencing the risk of introduction and secondary spread of influenza virus were comparable in all four modules, only ten (16%) of 63 residents who received amantadine were infected, only one of whom became symptomatic. Most side effects associated with amantadine were mild, but residents with active, preexisting major-motor seizure disorders demonstrated an increase in seizure activity compared with the previous eight-month period; those who took the maximum daily dose of amantadine hydrochloride (200 mg) and those who were also taking anticonvulsants other than phenobarbital were at highest risk.

The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home.

An outbreak caused by influenza A/Philippines/2/82 (H3N2)-like viruses occurred in a partially vaccinated nursing home population in January 1985. During the first six days of the outbreak, 14 (25%) of 55 residents developed influenzalike illness. The risk of illness was most strongly associated with undetectable levels of antibody against the epidemic strain, with unvaccinated case-patients having more severe illnesses and a higher rate of hospitalization than vaccinated case-patients (5/8 vs 0/6). During the period of amantadine hydrochloride prophylaxis (100 mg/d) from days 7 to 35, only two (5%) of the remaining 41 residents became ill, even though 11 (27%) had no detectable antibody. Serum amantadine levels obtained on day 35 ranged from 117 to 737 ng/mL (mean 309 ng/mL), similar to therapeutic levels documented in younger adults who have taken the standard regimen of 200 mg/d; there were few clinically significant side effects. These findings illustrate the benefits of influenza vaccination and support the use of amantadine hydrochloride at a dosage of 100 mg daily for outbreak control among elderly persons.

Control of influenza in the long-term-care facility: a review of established approaches and newer options.

Influenza infections pose a serious threat to residents of nursing homes and other long-term-care facilities. Annual vaccination of residents and staff with the currently licensed inactivated influenza vaccine continues to be the mainstay of prevention. Live attenuated influenza vaccine, which is expected to be licensed in the United States in the near future, may offer added protection for elderly persons when administered in conjunction with inactivated vaccine. Antiviral agents also can be useful as an adjunct to vaccination, especially for control of institutional outbreaks. Two new antiviral agents that appear to be less toxic than amantadine and rimantadine have recently been approved.

Effectiveness of inactivated influenza vaccine among nursing home residents during an influenza type A (H3N2) epidemic.

OBJECTIVES: To evaluate the use of influenza vaccine in nursing homes and its effectiveness in reducing the likelihood of influenza-like illness. DESIGN: A retrospective case-control study with active identification of influenza infection. SETTING: All nursing homes in a seven-county study area in southern lower Michigan were eligible for participation. Analyses were based on data collected from 23 homes with documented influenza transmission. PARTICIPANTS: Persons aged 65 years or older who were residents of the nursing homes under study during the influenza type A(H3N2) outbreak in 1989-1990. MEASUREMENTS: Residents were identified as cases or controls based on occurrence of febrile respiratory illness meeting a case definition. Demographic and underlying illness information were gathered as were data on the use of influenza vaccine, antibiotics, and antivirals. Characteristics of the nursing homes were also recorded. Logistic regression analyses were carried out to determine vaccine effectiveness. MAIN RESULTS: Determinants of vaccine use were different from those observed in a parallel community-based study. In a multivariate model that considered the effects of resident and nursing home characteristics, vaccinated residents were significantly less likely than those who were not vaccinated to have an influenza-like illness (OR = .58 (95% CI, .43-.78), P < .001, imputed vaccine effectiveness estimate of 42%). Vaccination was more effective in younger residents (those aged 65 to 84) then in older residents (those older than 84 years). CONCLUSIONS: Influenza vaccination was effective in reducing the likelihood of influenza-like illness in nursing home residents. Effectiveness appeared to be related to age, which may function as a surrogate for related immunologic factors. Older nursing home residents should be targeted for newer vaccines and/or potential prophylactic use of antivirals.

Influenza outbreak detection and control measures in nursing homes in the United States.

OBJECTIVE: To evaluate the use of influenza vaccine, rapid influenza testing, and influenza antiviral medication in nursing homes in the US to prevent and control outbreaks. METHODS: Survey questionnaires were sent to 1017 randomly selected nursing homes in nine states. Information was collected on influenza prevention, detection and control practices, and on outbreaks during three influenza seasons (1995-1998). RESULTS: The survey response rate was 78%. Influenza vaccine was offered to residents and staff by 99% and 86%, respectively, of nursing homes. Among nursing homes offering the influenza vaccine, the average vaccination rate was 83% for residents and 46% for staff. Sixty-seven percent of the nursing homes reported having access to laboratories with rapid antigen testing capabilities, and 19% reported having a written policy for the use of influenza antiviral medications for outbreak control. Nursing homes from New York, where organized education programs on influenza detection and control have been conducted for many years, were more likely to have reported a suspected or laboratory-confirmed influenza outbreak (51% vs 10%, P = .01), to have access to rapid antigen testing for influenza (92% vs 63%, P = .01), and to use antivirals for prophylaxis and treatment of influenza A for their nursing home residents (94% vs 55%, P = .01) compared with nursing homes from the other eight states. CONCLUSIONS: Influenza outbreaks among nursing home residents can lead to substantial morbidity and mortality when prevention measures are not rapidly instituted. However, many nursing homes in this survey were neither prepared to detect nor to control influenza A outbreaks. Targeted, sustained educational efforts can improve the detection and control of outbreaks in nursing homes.

Control of influenza outbreaks in the nursing home: guidelines for diagnosis and management.

A well coordinated plan that includes a mechanism for surveillance, rapid antigen detection testing and viral culture, infection control techniques and chemoprophylaxis is effective for aborting outbreaks of influenza A in the nursing home. Amantadine has been better studied in this situation, and experience with rimantadine is limited. The safety and efficacy of our dose guidelines for nursing home residents need to be studied and directly compared with rimantadine dose guidelines. Except for chemoprophylaxis, these guidelines can be applied to outbreaks of influenza B as well.

Use of influenza vaccine in nursing homes.

The organization and outcome of influenza immunization programs were studied in 67 randomly or systematically selected nursing homes (8354 residents) in six states during the autumn of 1982 and/or 1983. In each home, influenza vaccine was usually offered to all residents on a voluntary basis, independent of their age, level of required nursing care, or underlying medical conditions. However, the proportion of residents who were vaccinated ranged from 8 to 98% (mean, 62% overall), with significantly lower rates in homes that also required consent from relatives (usually by return mail) than in homes that did not (P less than .00001; median, 57 versus 90%, respectively). These observations suggest that distribution of educational materials about the risks and benefits of influenza vaccine and systematic follow-up of relatives who fail to return the consent form may be useful strategies to further increase the number of nursing home residents who are immunized.

Implications of viral resistance to amantadine in control of influenza A.

Antiviral agents are valuable adjuncts to vaccine in the control of type A influenza. Amantadine has been available for many years for prophylaxis and therapy, but there have been concerns about side effects, particularly in the elderly. Thus, the anticipated licensure of rimantadine, an antiviral with the same efficacy as amantadine but with fewer side effects, has been viewed as a major advance. Rimantadine has thus far remained unlicensed, and attention has become focused on antiviral resistance to these drugs, an issue previously recognized but not considered important in decisions concerning drug use. The major implications of antiviral resistance relate to questions of whether there are differences in pathogenicity and transmissibility of resistant influenza type A viruses in comparison with sensitive ones. Resistant viruses have not been found to be more virulent than sensitive ones. The extent to which they may be transmitted or perpetuated has not been established. In light of this situation, it is suggested that drug use not be sharply restricted and that recommendations be periodically reviewed as more definitive data become available. As with any infectious disease, attempts should be made to limit exposure of uninfected individuals to those infected with the influenza A virus, regardless of whether they are receiving an antiviral drug.

Policies and outcomes for control of influenza among the elderly in the USA.

For about 20 years official recommendations have been made to provide influenza vaccine to elderly persons in the USA because they are high risk of complications if infected during epidemics. Residents of homes for the aged (Nursing Homes) are of particular concern and we have studied this subgroup in greater detail than before. A prospectively organized surveillance programme of about 7000 residents of more than 65 homes in several states indicated that vaccination rates varied from about 9 to 98%, with the average about 60%. Biases in vaccinating residents according to age and medical condition were not detected. Vaccine use was greatest when the policy of the homes was to administer vaccine without requesting consent of relatives. In separate studies of influenza A(H3N2) outbreaks in homes for the elderly during 1982/83, influenza vaccine was found to reduce influenza-associated mortality by about 75% although febrile respiratory illness rates were reduced less than 50%. The frequency of outbreaks was lowest in homes having fewest residents, and highest vaccination rates. Professional Educational Programmes are no being developed to assist homes for the elderly to improve the organization of their influenza vaccination activities in an attempt to further reduce influenza mortality.

New aspects of influenza viruses.

Influenza virus infections continue to cause substantial morbidity and mortality with a worldwide social and economic impact. The past five years have seen dramatic advances in our understanding of viral replication, evolution, and antigenic variation. Genetic analyses have clarified relationships between human and animal influenza virus strains, demonstrating the potential for the appearance of new pandemic reassortants as hemagglutinin and neuraminidase genes are exchanged in an intermediate host. Clinical trials of candidate live attenuated influenza virus vaccines have shown the cold-adapted reassortants to be a promising alternative to the currently available inactivated virus preparations. Modern molecular techniques have allowed serious consideration of new approaches to the development of antiviral agents and vaccines as the functions of the viral genes and proteins are further elucidated. The development of techniques whereby the genes of influenza viruses can be specifically altered to investigate those functions will undoubtedly accelerate the pace at which our knowledge expands.

Prevention and control of type A influenza infections in nursing homes. Benefits and costs of four approaches using vaccination and amantadine.

We developed a model to project morbidity, mortality, and costs attributable to type A influenza virus infections in nursing homes and to evaluate the relative benefits and costs of programs for prevention and control. Influenza vaccination was the most cost-effective intervention under various simulations in the model but usually allowed for higher rates of morbidity and mortality compared with other alternatives. The combined use of previous vaccination and chemoprophylaxis during outbreaks in the nursing home was associated with significantly fewer cases than use of vaccination alone, with only modest increases in net program costs. The use of chemoprophylaxis throughout the influenza season (without vaccination) resulted in the fewest number of illnesses, hospitalizations, and deaths but would cost at least 650% more than alternatives involving vaccination. Regardless of which strategy is chosen, our model suggests that influenza control programs in nursing homes are both beneficial and cost-effective and should be considered a part of standard care.

Three summertime outbreaks of influenza type A.

In the Northern Hemisphere, sporadic cases of influenza occur during the summer, yet summertime outbreaks are rare. From 12 August through 2 September 1993, three influenza outbreaks in Louisiana were investigated using medical-record review, interviews, viral cultures, serology, and active surveillance for influenza-like illness in Louisiana. Attack rates in the outbreaks were 61% (69/114), 42% (24/57), and 45% (23/51). Viruses isolated were most closely related to influenza A/Beijing/32/92 (H3N2). The identification of influenza A as the cause of the first two outbreaks led to the recommendation for amantadine use in the third outbreak. Active surveillance did not detect any other outbreaks of influenza-like illness during August or September 1993. Out-of-season influenza A outbreaks can therefore occur when little influenza-like illness is present in a community. Evaluation of outbreaks of acute, febrile respiratory illness outside the influenza season should include this possibility, since rapid detection can lead to the timely use of amantadine or rimantadine.

The impact of influenza epidemics on mortality: introducing a severity index.

OBJECTIVES: The purpose of this study was to assess the impact of recent influenza epidemics on mortality in the United States and to develop an index for comparing the severity of individual epidemics. METHODS: A cyclical regression model was applied to weekly national vital statistics from 1972 through 1992 to estimate excesses in pneumonia and influenza mortality and all-cause mortality for each influenza season. Each season was categorized on the basis of increments of 2000 pneumonia and influenza excess deaths, and each of these severity categories was correlated with a range of all-cause excess mortality. RESULTS: Each of the 20 influenza seasons studied was associated with an average of 5600 pneumonia and influenza excess deaths (range, 0-11,800) and 21,300 all-cause excess deaths (range, 0-47,200). Most influenza A(H3N2) seasons fell into severity categories 4 to 6 (23,000-45,000 all-cause excess deaths), whereas most A(H1N1) and B seasons were ranked in categories 1 to 3 (0-23,000 such deaths). CONCLUSIONS: From 1972 through 1992, influenza epidemics accounted for a total of 426,000 deaths in the United States, many times more than those associated with recent pandemics. The influenza epidemic severity index was useful for categorizing severity and provided improved seasonal estimates of the total number of influenza-related deaths.

A method for timely assessment of influenza-associated mortality in the United States.

Influenza-associated mortality has traditionally been estimated as the excess mortality above a baseline of deaths during influenza epidemic periods. Excess mortality estimates are not timely, because national vital statistics data become available after a period of 2-3 years. To develop a method for timely reporting, we used the 121 Cities Surveillance System (121 Cities), maintained at the Centers for Disease Control and Prevention, as an alternative data source. We fit a cyclical regression model to time series of weekly 121 Cities pneumonia and influenza deaths for 1972-1996 to estimate the excess pneumonia and influenza mortality and to compare these figures with national vital statistics estimates for 20 influenza seasons during 1972-1992. Seasonal excess mortality based on 121 Cities correlated well with the national data: for 18 (90%) of 20 seasons, our influenza epidemic severity index category approximated the result based on national vital statistics. We generated preliminary severity categories for the four recent seasons during 1992-1996. We conclude that the 121 Cities Surveillance System can be used for the timely assessment of the severity of future influenza epidemics and pandemics. Timely pneumonia and influenza mortality reporting systems established in sentinel countries worldwide would help alert public health officials and allow prompt prevention and intervention strategies during future influenza epidemics and pandemics.

Pandemic versus epidemic influenza mortality: a pattern of changing age distribution.

Almost all deaths related to current influenza epidemics occur among the elderly. However, mortality was greatest among the young during the 1918-1919 pandemic. This study compared the age distribution of influenza-related deaths in the United States during this century's three influenza A pandemics with that of the following epidemics. Half of influenza-related deaths during the 1968-1969 influenza A (H3N2) pandemic and large proportions of influenza-related deaths during the 1957-1958 influenza A (H2N2) and the 1918-1919 influenza A (H1N1) pandemics occurred among persons <65 years old. However, this group accounted for decrementally smaller proportions of deaths during the first decade following each pandemic. A model suggested that this mortality pattern may be explained by selective acquisition of protection against fatal illness among younger persons. The large proportion of influenza-related deaths during each pandemic and the following decade among persons <65 years old should be considered in planning for pandemics.

Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly.

During the winter of 1989-1990, influenza type A(H3N2) circulated widely, causing excess morbidity and mortality nationwide. From November through April, 1989-1990, hospitalized cases of pneumonia and influenza occurring among noninstitutionalized individuals 65 or more years of age were identified by 20 acute care hospitals in southern lower Michigan. These cases were group matched on age, sex, race, and zip code to randomly sampled, community-based controls from a comprehensive listing of Medicare beneficiaries residing in the study area. Self-reported data were collected from cases and controls on influenza vaccine status for the 1989-1990 season and on a number of other factors which could have influenced vaccination status or outcome. Questionnaires were completed by 1,907 individuals, 449 of whom were cases, resulting in an overall response rate of 76%. A community-based influenza surveillance system was implemented to determine the timing and intensity of viral activity and influenza-like illness. Vaccine effectiveness in preventing overall pneumonia and influenza hospitalizations was estimated by logistic regression. During the 3-month period of surveillance-confirmed peak influenza type A(H3N2) circulation, vaccine effectiveness was 45% (95% confidence interval 14-64, p = 0.009). However, during the 3-month period of low or absent virus activity, identical methodology and model specification resulted in an effectiveness estimate of 21% that was not statistically different from zero (p = 0.36). The effectiveness determined during the peak period of virus circulation is felt to be a conservative estimate, since agents other than influenza are responsible for pneumonia and influenza hospitalizations, even during times of peak influenza activity.

Swine influenza virus infections. Transmission from ill pigs to humans at a Wisconsin agricultural fair and subsequent probable person-to-person transmission.

In September 1988, a previously healthy 32-year-old pregnant woman was hospitalized for pneumonia and died 8 days later. The only pathogen detected was an influenza virus antigenically related to the swine influenza virus (SIV). Four days before illness onset, the patient visited a county fair swine exhibition where there was widespread influenzalike illness among the swine. To detect other persons who were possibly infected by contact with the ill swine, we measured serum SIV hemagglutination-inhibition antibody titer in 25 swine exhibitors who were 9 to 19 years old. Nineteen (76%) had SIV hemagglutination-inhibition titers of 20 or greater. Antibody was undetectable in serum samples from 25 swine exhibitors from a neighboring county. Additional studies suggest that one to three health care personnel who had contact with the patient developed influenzalike illnesses with laboratory evidence of SIV infection. An outbreak of apparent SIV infection in swine resulted in multiple human infections, and, although no recognized community outbreak resulted, there was evidence of virus transmission from the patient to health care personnel.