Experience with oseltamivir in the control of a nursing home influenza B outbreak.

Oseltamivir prophylaxis was very effective in protecting nursing home residents from ILI and in halting this outbreak of influenza B. A portion of the total ILI cases may have been due to influenza A, as this strain was isolated in one resident. The 10% attack rate in this facility, controlled with oseltamivir, compares favourably with another influenza B outbreak in a similar facility in the same region, over the same time frame (ILI onset 27 December to 17 January). Oseltamivir prophylaxis was not used to manage this second outbreak of laboratory-confirmed influenza B. Of the 236 residents, 45 developed ILI for an overall attack rate of 19%, nearly double the rate in the oseltamivir-controlled setting (10%). While oseltamivir was effective in controlling influenza B in this outbreak, further experience and evaluation is required before it can be routinely recommended for prophylaxis of influenza in nursing home outbreaks. Although earlier attempts by others using oseltamivir in the control of influenza A outbreaks have also met with success, it is not yet licensed for this purpose. Compared to amantadine, oseltamivir has a relatively high cost for the control of influenza A outbreaks and this may continue to limit its wider acceptance. The cost-effectiveness of oseltamivir in the control of influenza B outbreaks needs to be specifically addressed given the typically milder nature of influenza B strains. However, such a distinction is not clinically reliable and elderly residents of long-term care facilities remain vulnerable to serious complications associated with influenza infection in general. An alternate agent for influenza chemoprophylaxis that is effective against both influenza A and B, is easily administered and has few side effects, could greatly enhance current prevention and control measures and warrants serious assessment. The spread of this outbreak from the geographically separate ward to other areas of the facility in which residents had not received prophylaxis, underscores the likely role of staff as a vehicle for transmission during facility outbreaks. While accurate staff ILI rates could not be determined, their immunization rates were low, and many staff were ill during the outbreak. Isolation of residents with ILI and prophylaxis of non-ill residents on the initial outbreak wards was insufficient to prevent the spread of the outbreak, although it was subsequently halted once prophylaxis was extended to all residents. In view of the uncertainty over this medication's widespread use, in the absence of licensure or previous studies demonstrating its effectiveness in the prophylaxis and control of influenza B outbreaks, initiation of oseltamivir prophylaxis was staggered by ward. In a declared influenza A outbreak, the protocol in a long term care facility is to initiate amantadine prophylaxis on all residents, rather than ward-by-ward. While anti-viral prophylaxis may be an effective secondary control measure in the management of influenza outbreaks, optimal primary prevention would be more effective. This would require increased vaccine coverage of residents and particularly of staff, who play an important role in the importation and transmission of influenza within these facilities.     

Use of oseltamivir during influenza outbreaks in Ontario nursing homes, 1999-2000

OBJECTIVES: To describe the experience of Ontario long-term care facilities that used oseltamivir during influenza outbreaks in 1999/2000. DESIGN: Case series. SETTING: Ten Ontario long-term care facilities for older people and their residents. PARTICIPANTS: Older residents of long-term care facilities. INTERVENTION: Oseltamivir for treatment or prophylaxis during 11 influenza outbreaks in 1999/2000. MEASUREMENTS: Control of outbreaks; pneumonia, hospitalization, and death complicating acute influenza. RESULTS: All outbreaks were due to influenza A//H3N2/Sydney/05/97. One facility elected to use oseltamivir for treatment and amantadine for prophylaxis. The remaining nine facilities (10 outbreaks) recommended oseltamivir for treatment and prophylaxis (after amantadine failure in five and as primary prophylaxis in five). Use of oseltamivir was associated with termination of the outbreak in all eight evaluable outbreaks. Overall, 178/185 (96%) case-residents met the case definition of influenza and had complete data for evaluation. Of these, 63 (35%) were treated with antibiotics, 37 (21%) were diagnosed with pneumonia, 19 (11%) were hospitalized, and 16 (9%) died. Compared with residents receiving no therapy or who became ill while taking amantadine, residents who received oseltamivir within 48 hours of the onset of symptoms were less likely to be prescribed antibiotics, to be hospitalized, or to die (P <.05 for each outcome). These differences persisted and remained statistically significant when corrected for influenza immunization status. A total of 730 residents received oseltamivir prophylaxis for a median of 9 days (range 5-12). Of these, side effects were identified in 30 (4.1%), the most common being diarrhea (12 residents, 1.6%), cough (5, 0.7%), confusion (4, 0.5%) and nausea (4, 0.5%). CONCLUSIONS: Oseltamivir is safe and appears to be effective when used as treatment or prophylaxis to control outbreaks of influenza in older nursing home residents.     

The use of oseltamivir during an influenza B outbreak in a chronic care hospital

Background Residents of nursing homes and long‐term care facilities are at a higher risk of outbreaks of influenza and of serious complications of influenza than those in the community. In late July 2005, a 90‐bed chronic care psycho‐geriatric hospital in Sydney, Australia, reported cases of influenza‐like illness (ILI) occurring amongst its residents. Methods An investigation to confirm the outbreak, and its cause, was undertaken. Influenza vaccination levels amongst residents, and the effects of antiviral drugs used for prevention and treatment, were assessed. Oseltamivir was only given to the residents, in the form of both treatment and prophylaxis. Results A total of 22 out of 89 residents met the clinical case definition of ILI with onset on or after 27 July 2005. This represents an attack rate of 25%. Oseltamivir was commenced on day 9 of the outbreak. Influenza B was identified in six residents as the causative agent of the outbreak. No deaths or acute hospitalization were recorded for this outbreak and there were no further reported cases after the introduction of oseltamivir. Vaccine effectiveness was 75% and the strain of influenza B isolated was well matched to that year’s vaccine. Conclusions There are few data on the use of oseltamivir in influenza B outbreaks. Early antiviral intervention appeared to curtail this outbreak of influenza B in a chronic care facility. We found high vaccine effectiveness in this frail, institutionalized population, highlighting the importance of influenza vaccination for residents of chronic care facilities.     

Effectiveness of oseltamivir on influenza and influencing factors: age of patients,type of influenza virus and timing of initial administration

A multi-center open study using the internet was performed during the influenza season of 2001-2002 to evaluate the effectiveness of the anti-influenza agent, oseltamivir, on influenza in relation to: (1) age of patients; (2) type of influenza virus; and (3) timing of initial administration after the onset of the first symptoms of influenza. The study comprised of 779 cases of influenza confirmed by rapid detection tests from 44 clinics in Japan. Patients consisted of 4 age groups, 0-6, 7-15, 16-64 and 65-85 years. All patients were administered oseltamivir within 24 hours, at 25-48 or after 48 hours from the onset of the first symptoms of influenza. Data collected from each age group were the highest body temperature and duration of fever (> or = 37.5 degrees C). The percentage of afebrile patients was calculated at 24, 48 and 72 hours after the initial administration; data were also evaluated by the type of influenza virus A and B. The highest body temperature was higher with statistical significance as patients' age decreased. The duration of febrile period (days) was significantly longer in 0-6 years (2.57 +/- 0.95) than in 65-85 years (2.18 +/- 0.93). Evaluation of the percentage of afebrile patients revealed: the percentage at 24 hours was significantly lower in 0-6 years (28.4%) than in 16-64 years (44.0%); the percentage at 48 and 72 hours showed similar results in each age group; the percentage at 48 and 72 hours was significantly higher when administered initially within 24 hours than over 48 hours after the onset of the first symptoms of influenza; the percentage at 24 and 48 hours was significantly higher when administered within 24 hours than at 25-48 hours; and the type of influenza virus did not affect the percentage. In conclusion, effectiveness of oseltamivir seemed to be affected to an extent by the patients' age and little by the type of influenza virus. Oseltamivir was more effective when administered as early as possible after the onset of the symptoms of influenza.     

Effectiveness of oseltamivir treatment against influenza type A and type B infection in children

We investigated the effectiveness of oseltamivir treatment against influenza virus infection in children. We treated 131 patients (mean age, 5.8 +/- 3.6 years) with oseltamivir (4 mg/kg/day for 5 days) during the 2001-2002 epidemic. All of the patients had been diagnosed with influenza using a rapid diagnosis kit. When treatment was initiated within 48 hours of the onset of fever, 44% of the patients became afebrile (< 37.5 degrees C) within one day, and 86% of them recovered within two days. The average duration of fever after the initiation of oseltamivir treatment was 1.7 days. Oseltamivir was equally effective against both influenza type A and type B. No differences in the effectiveness of oseltamivir treatment were observed between young children (< 4 years of age) and school-aged children (> 6 years of age). No obvious side effects were observed.     

Emergence and transmission of amantadine-resistant influenza A in a nursing home

OBJECTIVES: To prospectively detect amantadine-resistant influenza when amantadine was used for influenza A outbreak control. DESIGN: Prospective clinical surveillance and viral culture of all new respiratory illnesses during the course of amantadine prophylaxis. SETTING: A 721-bed, 14-ward nursing home for veterans and spouses during an influenza A outbreak (1993-94). PARTICIPANTS: Residents of a veterans hospital and their spouses. MEASUREMENTS: Nasopharyngeal and throat viral culture. All residents with positive cultures who developed new respiratory symptoms while receiving or residing on a unit receiving amantadine prophylaxis had antiviral-resistance testing and polymerase chain reaction restriction analyses performed. RESULTS: Amantadine prophylaxis was administered sequentially on nine of 14 wards to all well residents for 14 to 31 days/ward to control influenza outbreaks between December 9, 1993, and January 28, 1994. Amantadine treatment was simultaneously provided to 29 ill residents. Between December 3, 1993, and January 22, 1994, 68 culture-positive cases of influenza A were detected. Twenty subjects were receiving or residing on units receiving amantadine prophylaxis. Amantadine sensitivity testing could be performed on 16 residents; 12 residents had amantadine resistant strains. Four of the 12 had not received any antiviral treatment. Illness onset ranged from 1 to 22 days after amantadine prophylaxis was begun on the individual's unit. Two ribonucleic acid (RNA) mutations in the gene coding the M2 protein transmembrane region were observed that were clustered in time and space. Isolates from two roommates, one receiving amantadine for 18 days and one on no antiviral, had identical RNA sequences. CONCLUSION: Antiviral resistance may be responsible for failure of prophylaxis in nursing home outbreaks. Strategies that use different classes of antivirals for prophylaxis and treatment may limit emergence and transmission of resistant virus.     

Amantadine usage for influenza A during an influenza outbreak in a nursing home

An outbreak of an influenza like illness was found in a nursing home in Fukuoka in January, 1999. Results of hemagglutinin inhibition tests with paired sera of patients and rapid diagnosis kit for influenza A indicated that an influenza A (H3N2) outbreak had occurred. A total of 15 patients with influenza like illness from one residential area of the nursing home were administered amantadine, 100 mg per day for five days. Clinical records of 264 residents were surveyed retrospectively from the tenth to the thirty-first of January, 1999. Influenza like illness was found in 112 residents (42.4%). The incidence of influenza like illness differed by residential area, ranging from 27.6% to 54.0%. The mean duration of fever was 3.6 days among patients administered amantadine. The mean duration was 4.4 days for patients not administered amantadine. The incidence of influenza like illness decreased rapidly after amantadine administration in the residential area where amantadine administration was done. These results suggest that amantadine is effective in mitigating influenza symptoms in the elderly. Amantadine may be useful for diminishing the influence of influenza A outbreaks in nursing homes.     

Antivirals for the treatment and prevention of epidemic and pandemic influenza

Influenza is a highly contagious and debilitating disease that imposes an excess burden of complications and mortality. Antiviral therapy is the primary intervention for treatment and post‐exposure prophylaxis (PEP) of influenza. Amantadine and rimantadine are members of the M2 class of antiviral agents and are moderately effective in influenza management. However, their utility is compromised by high levels of resistance, tolerability concerns and a lack of efficacy against influenza B. An alternative class of agents, the neuraminidase inhibitors (NIs), represent the most advanced form of antiviral therapy available, and act by specifically inhibiting the neuraminidase enzymes that are present on all influenza subtypes. Two NIs, oseltamivir and zanamivir, are currently available for clinical use. Oseltamivir, the most widely used NI, is administered orally as a prodrug (oseltamivir carboxylate) and systemically distributed to all potential infection sites. Zanamivir, a second NI, is administered by inhalation via a disk inhaler and deposited primarily in the respiratory tract. When administered within 48 hours of symptom onset, both agents significantly reduce illness duration and symptom severity, and decrease the rate of influenza‐associated complications. With oseltamivir, greater benefits are detected with earlier treatment initiation (<12 hours). In PEP, both NIs effectively protect the close contacts of index cases from symptomatic influenza. Oseltamivir and zanamivir are generally well tolerated and associated with a low level of resistance. Emerging evidence supports the activity of both NIs against the H5N1avian influenza infection, which is a pandemic candidate. However, the WHO currently recommends the use of oseltamivir for the management of suspected cases, given the systemic nature of the H5N1 challenge. Ongoing studies are exploring the effectiveness of oseltamivir, zanamivir and other NIs for pandemic management.     

Treatment and prevention of influenza: Swedish recommendations

The introduction of the 2 neuraminidase inhibitors (NAIs) zanamivir and oseltamivir has offered new options for the prevention and treatment of influenza. This article summarizes a Swedish consensus guidance document on the rational use of antiviral drugs in the management of influenza virus infections. Vaccination remains the cornerstone for influenza prophylaxis. Target groups for the annual vaccination programme are the 'at-risk' individuals, i.e. elderly patients ( > or = 65 y) and patients with chronic pulmonary disease or cardiovascular disease or other chronic diseases predisposing for a complicated course of influenza. Antiviral drugs are not a substitute for influenza vaccination, but could be used as adjuncts. Currently, 3 drugs have been approved for the treatment of influenza, including zanamivir and oseltamivir and the M2 inhibitor amantadin. Amantadin has come to very limited use, has recently been withdrawn from the Swedish market and is available only on a named patient basis. Compared with amantadin, the NAIs have clear advantages because of their broader anti-influenza activity against both type A and B, improved safety profiles and low potential for inducing drug resistance. The NAls are therefore recommended as first options in the treatment of influenza. Oseltamivir can be taken orally, whereas zanamivir is for oral inhalation. Limited in vitro and in vivo data suggest that oseltamivir is less potent against influenza B, whereas zanamivir seems equally effective against influenza A and B. In influenza-positive healthy adults and children, treated within 48 h after symptom onset, the NAIs shorten the duration of illness by about 1 d. No significant effect on the duration of symptoms has been documented in treated at-risk patients with influenza. Owing to their limited therapeutic benefit, general use of the NAIs in the treatment of influenza is not recommended, but they can be advocated on an individualized basis for patients with severe influenza who can start therapy within 48 h of the onset of symptoms. Zanamivir is the preferred choice in a confirmed influenza B epidemic. For prevention of influenza, 2 drugs are approved, oseltamivir in adults above 12 y old and amantadin in people above 10 y old. The 70-90% protective efficacy of oseltamivir for household postexposure prophylaxis and for seasonal prophylaxis is comparable to that reported for amantadin. Oseltamivir is the preferred drug for prophylactic use. Chemoprophylaxis is targeted at high-risk groups and should be considered on a case-by-case basis depending on the circumstances and the population requiring protection. A broader preventive use of oseltamivir can be advocated in at-risk groups during seasons when there is a poor antigenic match between the epidemic strains and the vaccine strains. Oseltamivir prophylaxis is otherwise recommended for patients unable to be vaccinated and for families exposed to influenza which include a member of the at-risk groups. In high-risk hospital units and in institutions caring for the elderly, oseltamivir prophylaxis, in combination with vaccination, can be recommended as measures to control an influenza outbreak.     

Emergence of rimantadine-resistant virus within 6 days of starting rimantadine prophylaxis with oseltamivir treatment of symptomatic cases

OBJECTIVES: To report on the detection of rimantadine resistance within 6 days of starting rimantadine prophylaxis. DESIGN: Observational prospective study. SETTING: Fifty-bed nursing unit during the 2004/05 influenza season. PARTICIPANTS: All residents. INTERVENTION: Clinical monitoring for new onset of respiratory illness followed by collection of nasopharyngeal swabs for Directigen AB testing and influenza culture. After outbreak identification, rimantadine was administered as prophylaxis, whereas oseltamivir was used to treat symptomatic cases. Laboratory monitoring for the emergence of rimantadine resistance was reinitiated on the fifth day of rimantadine prophylaxis. MEASUREMENTS: Tabulation of respiratory illnesses, rapid tests and cultures yielding influenza A, and rimantadine sensitivity determination in five index isolates. RESULTS: A total of 15 symptomatic cases were identified over 8 days. Amantadine sensitivity was determined in five cases. Three initial cases were sensitive to rimantadine, whereas two cases identified after 6 days of rimantadine prophylaxis were resistant to rimantadine. CONCLUSION: The Centers for Disease Control and Prevention reported that 91% of isolates collected early the following season (2005/06) were resistant to rimantadine. Rimantadine treatment is no longer recommended. This experience anticipated the new recommendations. If reemergence of sensitivity follows discontinuation of rimantadine use, using rimantadine as prophylaxis and oseltamivir for treatment of symptomatic cases might be efficacious and economical on a national scale.     

Adverse reactions to amantadine prophylaxis of influenza in a retirement home

OBJECTIVE: Controversy exists about the safety of following the recommendation of the Immunization Practice Committee of the Centers for Disease Control that nursing home residents be given amantadine prophylaxis during influenza outbreaks. This study was undertaken to define the incidence of adverse reactions to amantadine in the elderly and to identify risk factors for side effects. DESIGN: A retrospective cohort study. SETTING: A retirement home which offered amantadine prophylaxis to its residents during a presumed influenza outbreak. PARTICIPANTS: Of the 96 elderly residents, 79 accepted the offer of amantadine prophylaxis. MAIN OUTCOME MEASURES: Attributable adverse health outcomes as assessed by chart review. RESULTS: 41% of the people receiving amantadine had attributable adverse reactions, of which 22% were classified as severe. Severe adverse reactions were associated with residence in the assisted living section of the facility (P = 0.002), a greater number of underlying diagnoses (P = 0.009), congestive heart failure (P = 0.02), and high serum creatinine (P = 0.02). A person with none of these risk factors had a 7% chance of having a severe adverse outcome compared to a 70% chance for someone with all four risk factors. CONCLUSION: The findings raise concern that the prophylactic administration of amantadine to all elderly residents of nursing and retirement homes may be associated with a high incidence of unacceptable reactions, particularly among less healthy residents.     

Occurrence of adverse effects and high amantadine concentrations with influenza prophylaxis in the nursing home

Amantadine, in a dose of 100 mg/day, is recommended for influenza prevention in older nursing home residents. We studied an influenza prevention protocol in a 98-bed community nursing home (96% female; mean age = 87.4 years). Fifty-five residents received amantadine when influenza A was confirmed. Although no further influenza cases were diagnosed, 22% experienced adverse events. Dose in mg/kg/day was significantly higher in the group experiencing adverse events (2.24 +/- 0.98 vs 1.76 +/- 0.35; P less than .01). Amantadine concentrations in 32 residents ranged from 128-5,810 ng/mL. Six residents had amantadine concentrations greater than 1,000 ng/mL. Seventy-eight percent would have qualified for further dose reduction on the basis of estimated creatinine clearance. The results suggest that adverse events may be an important problem with the 100 mg/day dose, and this dose may be excessive for influenza prophylaxis in many nursing home residents.     

Efficacy of Influenza Vaccine in Elderly Persons in Welfare Nursing Homes: Reduction in Risks of Mortality and Morbidity During an Influenza A (H3N2) Epidemic

BACKGROUND: The effect of influenza vaccination on the occurrence and severity of influenza virus infection in a population residing in nursing homes was studied through a program by the Osaka Prefectural Government, which is the first and official support for influenza vaccination of the elderly population during an influenza A (H3N2) epidemic in JAPAN: METHODS: A cohort study located in the Osaka Prefecture, Japan, followed the outcomes of elderly nursing home residents who received influenza vaccinations (n = 10,739) in comparison with control subjects who did not receive influenza vaccinations (n = 11,723) and monitored clinically the onset of serious morbidity and mortality of influenza illness. Subjects were 22,462 persons older than 65 years who resided in 301 welfare nursing homes in the Osaka Prefecture, Japan during an influenza A (H3N2) epidemic in 1998 to 1999. RESULTS: Of 22,462 individuals living in 301 nursing homes, 10,739 received either one dose (2027 subjects) or two doses (8712 subjects) of inactivated, subunit trivalent influenza vaccine. Through the period from November 1998 to March 1999, there were 950 cases of influenza infection diagnosed clinically with cases by virus isolation and/or serology. There were statistically significantly fewer clinical cases of influenza, hospital admissions due to severe infection, and deaths due to influenza in the vaccinated cohort (256 cases, 32 hospital admissions, and one death) compared with the unvaccinated controls (694 cases, 150 hospital admissions, and five deaths). Vaccination was equally effective in those who received one dose of vaccine as in those who received two doses. No serious adverse reactions to vaccination were recorded. Thus, influenza vaccination is safe and effective in this population and should be an integral part of the routine care of persons aged 65 years and older residing in nursing homes. CONCLUSIONS: This study provides an analysis of the clinical efficacy of influenza vaccination in a large cohort of nursing home residents in JAPAN: Annual influenza vaccine administration requires the attention of all nursing home attendants, physicians, and public health organizations.     

An outbreak of influenza A (H3N2) in a well immunized nursing home population.

OBJECTIVE: To describe the epidemiologic features of an outbreak of influenza A that occurred in a skilled nursing home although over 90 percent of the resident population had previously received influenza vaccine. DESIGN: Retrospective cohort study. SETTING: Skilled nursing home facility in western New York State. PATIENTS: Nursing home residents and patient-care staff. MAIN OUTCOME MEASURE: Incidence of influenza-like illness among vaccinated versus unvaccinated nursing home residents and staff. RESULTS: Thirty-seven of 124 residents (attack rate = 30%) and 18 of 146 staff (attack rate = 12%) had an influenza-like illness. Staff illness began 16 days prior to onset among residents. Six cases of pneumonia and three influenza-related deaths occurred, all among the vaccinated residents. Ninety percent of the nursing home residents and 10% of the staff received the influenza vaccine prior to the outbreak. The calculated vaccine efficacies were minus 21% and plus 45% for residents and staff, respectively. CONCLUSION: While antigenic drift of the circulating influenza virus was the major factor in the apparent vaccine failure, the observed poor staff immunization rate (10%) and absence of surveillance which precluded the use of amantadine chemoprophylaxis suggest that the use of these strategies may be of importance in controlling influenza outbreaks in nursing homes.     

Effect of post-exposure prophylaxis with oseltamivir for those in contacts with influenza patients in pediatric wards

During the influenza season, outbreaks of influenza may occur in the pediatric wards due to spread from the patients hospitalized with influenza, or from those hospitalized during the latency period and develop influenza afterwards. Post-exposure prophylaxis with neuraminidase inhibitors has been reported to be effective in preventing outbreaks among household members and nursing home residents. However, for nosocomial spread, its effectiveness and possible adverse effects are to be determined. During the 2002/2003 influenza season, we experienced a total of 3 nosocomial outbreaks of influenza in the pediatric wards in two hospitals in the Kanto district, Japan. Since the number of contacts who developed influenza had been increasing despite the isolation precaution implemented, post-exposure prophylaxis with oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, once a day for 7-10 days) was implemented with a permission from the parents to terminate the outbreaks. In the outbreaks (one with influenza A, two with influenza B), a total of 29 inpatients had contact with influenza patients: among those 29, 13 were given post-exposure prophylaxis, 16 were not. Out of 16 patients who did not receive post-exposure prophylaxis, 11 (69%) developed influenza: out of 13 with post-exposure prophylaxis, none developed influenza. Those patients who developed influenza were given oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, twice a day for 5 days) and accommodated in a private room or a room with other patients with influenza of the same type. No significant adverse effects due to oseltamivir were observed among those who were enrolled in this study.     

Treatment of an influenza A outbreak in a teaching nursing home. Effectiveness of a protocol for prevention and control

The safety and efficacy of current ACIP guidelines for the prevention and control of influenza in nursing home populations are uncertain. An outbreak of influenza A/Sichuan (H3N2) in a teaching nursing home during 1988 gave us the opportunity to evaluate the effectiveness of an influenza vaccination and amantadine prophylaxis protocol. Over 13 days, 12 of 60 residents developed influenza. Prior influenza vaccination had been given to 94% of the residents. Protection from infection occurred in those tested who had antibody levels greater than or equal to 1:16 to the A/Leningrad (H3N2) antigen contained in the standard 1987-88 trivalent vaccine. However, five of 17 vaccinated residents who were tested had antibody levels less than or equal to 1:16 at the start of the outbreak. Amantadine (less than or equal to 100 mg/day) was given to all but one resident starting on the third day of the outbreak, and to employees starting on the sixth day of the outbreaks. Seven residents developed illness after the start of amantadine, although amantadine appeared to ameliorate their symptoms. Although amantadine was generally well tolerated by residents, employees receiving amantadine identified a high incidence of side effects and only 44% of employees took at least 70% of the prescribed amantadine. In our opinion, early detection and protocol-directed intervention probably abated a more severe influenza outbreak. Therefore we support existing recommendations that formal nursing home policies be established to ensure that residents and employees receive annual influenza vaccine and that chemoprophylaxis be used when outbreaks of influenza A are suspected.     

磷酸奥司他韦治疗流行性感冒的多中心临床研究

目的 观察磷酸奥司他韦在自然获得流行性感冒（以下简称流感）受试者中的临床疗效,安全性及耐受性。方法 采用随机,双盲和安慰剂对照的多中心临床试验设计。共入组478例,入组条件为年龄≥18岁,≤65岁,发热≥37.8℃,至少有两个流感样症状;出现症状后还需眼过36h,合格的受试者随机接受磷酸奥司他韦75mg或安慰剂治疗,每日2次,共5d。结果 证实为流感患者（即ITTI总体）有273例,试验组134例,对照组139例。ITTI总体试验组疾病持续时间中位数为91.6h(95%可信区间为80.2-101.3h),对照组疾病持续时间中位数为95.0h(95%可信区间为84.5-105.3h),两组疾病缓解率差异有显著性（P=0.0196),共有459例可进行安全性分析,试验组和对照组不良反应发生率差异无显著性,不良反应主要为消化系统症状。结论 磷酸奥司他韦在流感发病后早期使用可以明显缩短疾病的持续时间,减轻症状的严重程度,其安全性和耐受性较好,适合在临床中推广使用。     

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.     

Long-term use of oseltamivir for the prophylaxis of influenza in a vaccinated frail older population

OBJECTIVES: To investigate the efficacy of once-daily oral oseltamivir for 6 weeks (Tamiflu) in prophylaxis against laboratory-confirmed clinical influenza in frail older subjects living in homes for seniors and to determine the safety and tolerability of long-term oseltamivir. DESIGN: Double-blind, placebo-controlled, parallel-group, randomized, multicenter study. SETTING: Thirty-one residential homes for seniors across United States and Europe. PARTICIPANTS: Five hundred forty-eight frail older occupants (mean age 81 years, >80% vaccinated). INTERVENTION: Prophylaxis with oseltamivir 75 mg or placebo once daily for 6 weeks, beginning when influenza was detected locally. MEASUREMENTS: The primary efficacy endpoint was laboratory-confirmed clinical influenza. RESULTS: Oseltamivir administration resulted in a 92% reduction in the incidence of laboratory-confirmed clinical influenza compared with placebo (placebo 12/272 (4.4%), oseltamivir 1/276 (0.4%); P = .002). Of subjects vaccinated against influenza, oseltamivir was 91% effective in preventing laboratory-confirmed clinical influenza (placebo 11/218 (5.0%), oseltamivir 1/222 (0.5%); P = .003). Oseltamivir use was associated with a significant reduction in the incidence of secondary complications (placebo 7/272 (2.6%), oseltamivir 1/276 (0.4%); P = .037). Although nearly all subjects were taking concomitant medication both before and during the study, oseltamivir was well tolerated. A similar incidence of adverse events, including gastrointestinal effects, occurred in both groups. There was no suppression of antibody response in oseltamivir recipients. CONCLUSION: Oral oseltamivir 75 mg once daily for 6 weeks effectively prevented clinical influenza in vaccinated frail older subjects using significant concomitant medications in a residential care setting. The treatment was well tolerated and provided additional protection to that afforded by vaccination.