Reintroduction of influenza A to a nursing building.

We report an outbreak of influenza A from a four-building veterans' facility in King, Wisconsin. Influenza was isolated in 154 of 721 residents over a 121-day period. Building A had 2 cases, no isolates for 40 days, followed by 27 cases. Building B had 25 cases, no isolates for 75 days, followed by 4 cases. Building C had 23 cases, no isolates for 14 days, followed by 17 cases. Influenza A may be reintroduced to a nursing building. Surveillance with contingency plans for restarting of prophylaxis must continue for the duration of influenza in the community.

A serious outbreak of parainfluenza type 3 on a nursing unit.

OBJECTIVE: To report a serious outbreak of respiratory illness in a nursing home, with isolation of parainfluenza type 3 in four cases. DESIGN: Viral respiratory cultures from a sample of symptomatic residents, and retrospective chart review. SETTING: A 50-bed nursing unit/floor in a skilled nursing facility. PARTICIPANTS: All residents of the nursing unit. MEASUREMENTS: Respiratory viral cultures and clinical chart review. RESULTS: Twenty-five of 49 residents developed new respiratory symptoms between September 2 and September 25, 1999. Ten cases (40%) had a tympanic temperature of 100 degrees F or greater. Eighteen (72%) had a chest X-ray with 11 (44%) new infiltrates. Sixteen (64%) were treated with antibiotics. Three cases were hospitalized and four died (16%) within 1 to 9 days after onset of symptoms. Four of 10 viral cultures yielded parainfluenza type 3. CONCLUSIONS: Parainfluenza type 3 may cause outbreaks complicated by pneumonia and fatal outcome. Clinicians should consider uniform secretion precautions to contain all viral URIs in nursing homes.

Surveillance for respiratory illness in long-term care settings: detection of illness using a prospective research technique.

BACKGROUND: The overall frequency and severity of viral respiratory infections affecting residents of long-term care facilities (LTCFs) is not well described. This is due primarily to the cumbersome and expensive techniques required for adequate surveillance of respiratory illnesses and the associated costs and availability of a laboratory capable of the relevant and timely report of diagnostic tests. Here we describe our technique for surveillance of respiratory illness in the LTCF. Elements of it may serve as strategies for routine care. METHODS: Nurses were trained to record respiratory complaints and to track them using a histogram-based calendar charting system. For the research technique, all new illnesses during the winter months, no matter how minor, were sampled for viral culture. RESULTS: Influenza A and B, parainfluenza types 1 through 4, herpes simplex virus types 1 and 2, rhinovirus, and respiratory syncytial virus (RSV) were detected in the nursing homes studied. Outbreaks of influenza were documented annually by prospective surveillance. Outbreaks of parainfluenza type 1 and RSV indistinguishable clinically from influenza were detected. CONCLUSIONS: Intense surveillance for respiratory illness and viral pathogens using the described research technique identified viral activity reliably on an annual basis in several large LTCFs. Elements of the research protocol may be adapted for general use to create a cost-effective surveillance program for LTCFs that have limited resources. Such a technique is essential for implementing effective measures for outbreak prevention and control.

Mortality following isolation of various respiratory viruses in nursing home residents.

OBJECTIVE: To compare mortality following isolation of influenza A to mortality following isolation of other respiratory viruses in a nursing home. SETTING: The Wisconsin Veterans Home, a 688-bed skilled nursing facility for veterans and their spouses. PARTICIPANTS: All residents with respiratory viral isolates obtained between 1988 and 1999. DESIGN: Thirty-day mortality was determined following each culture-proven illness. RESULTS: Thirty-day mortality following isolation of viral respiratory pathogens was 4.7% (15/322) for influenza A; 5.4% (7/129) for influenza B; 6.1% (3/49) for parainfluenza type 1; 0% (0/26) for parainfluenza types 2, 3, and 4; 0% (0/26) for respiratory syncytial virus (RSV); and 1.6% (1/61) for rhinovirus. CONCLUSIONS: Mortality following isolation of certain other respiratory viruses may be comparable to that following influenza A (although influenza A mortality might be higher without vaccination and antiviral agents). The use of uniform secretion precautions for all viral respiratory illness deserves consideration in nursing homes.

Non-influenza respiratory viruses may overlap and obscure influenza activity.

OBJECTIVE: To report the number and timing of influenza A isolates, as well as overlapping respiratory viruses. Co-circulating respiratory viruses may obscure the determination of influenza activity. DESIGN: Prospective clinical surveillance for the new onset of respiratory illness followed by viral cultures during seven separate influenza seasons. SETTING: The Wisconsin Veterans Home, a skilled nursing facility for veterans and their spouses. RESULTS: Influenza A isolates were encountered in greater numbers than non-influenza A isolates during three seasons. Seasonal variability is striking. In December 1992, we identified a large outbreak of respiratory illness. Influenza type B was cultured from 102 residents. In December 1995, influenza A was cultured from 285 people in Wisconsin. At that time, we identified outbreaks of respiratory illness in two of our four buildings. Based on statewide data, we suspected an influenza outbreak; however, 26 isolates of parainfluenza virus type 1 were cultured with no influenza. The potential importance of culturing at the end of the season was demonstrated in 1991-1992 when an outbreak of respiratory syncytial virus (RSV) overlapped and extended beyond influenza A activity. CONCLUSIONS: When interpreting new clinical respiratory illnesses as a basis for declaring an outbreak of influenza A, clinicians should realize that co-circulating respiratory viruses can account for clinical illnesses. Clinicians might utilize healthcare dollars efficiently by performing cultures to focus the timing of influenza A chemoprophylaxis. Cultures could be performed when clinical outbreak criteria are approached to confirm an outbreak. Culturing of new respiratory illness could begin again before the anticipated discontinuation of prophylaxis (approximately 2 weeks).

Effects of viral respiratory disease education and surveillance on antibiotic prescribing.

BACKGROUND AND OBJECTIVES: We describe a partnership between family practice residency clinics and a state public health virology laboratory that has produced comprehensive viral respiratory disease education and surveillance. Family practice residents have been provided with education on respiratory viruses and the results of ongoing viral surveillance. The preliminary effects of this program on antibiotic prescribing by senior residents are evaluated in this paper. METHODS: We used a questionnaire to assess the acceptance by family practice residents of the educational component and the utility of ongoing viral surveillance. We used chart review to evaluate rates of antibiotic prescribing and the number of patients diagnosed per year with acute upper respiratory infection and acute bronchitis by senior residents in 1992 (preexposure) and 1996 (postexposure). RESULTS: By the third year of training, most residents (79%) reported receiving adequate training regarding common viral respiratory diseases. Moreover, residents reported that they were less likely to prescribe antibiotics to patients presenting with respiratory infections when provided with specific information on circulating viral pathogens. Antibiotic prescribing in the postexposure group was 68% lower for upper respiratory infection (URI) and 45% lower for a composite of URI and bronchitis. CONCLUSIONS: Education and monitoring of circulating respiratory viruses can result in familiarity with common disorders in primary care and reduce unnecessary antibiotic use.

Duration of antiviral prophylaxis during nursing home outbreaks of influenza A: a comparison of 2 protocols.

BACKGROUND: We performed a randomized trial of 2 protocols guiding the duration of antiviral chemoprophylaxis during outbreaks of influenza A in a rural, 700-bed nursing home for veterans and their spouses with 14 nursing units in 4 buildings. METHODS: Half of all residents volunteered to participate. Nursing units were randomized, and the effectiveness of short-term (minimum, 14 days and 7 days without the onset of a case in the building) vs long-term (minimum, 21 days and 7 days without the onset of a case in the 4-building facility) prophylaxis was compared using amantadine hydrochloride in the influenza seasons of 1991-1992 and 1993-1994 and rimantadine hydrochloride in the influenza season of 1994-1995. A "case" is defined as an incident of a respiratory tract illness and the isolation of an influenza virus organism. We compared the number of cases after the discontinuation of short- vs long-term chemoprophylaxis. Prospective surveillance identified residents with new respiratory tract symptoms, and specimens for viral cultures were obtained even in the absence of temperature elevation. RESULTS: We documented influenza A virus activity during 3 seasons (32, 68, and 12 patients, respectively). During the 1991-1992, 1993-1994, and 1994-1995 influenza seasons, the patients on 11 floors were assigned to receive short-term chemoprophylaxis and those on 10 floors were assigned to long-term chemoprophylaxis. Only in 1993-1994 did chemoprophylaxis extend beyond 14 or 21 days when new cases continued beyond 14 days. Amantadine-resistant strains were circulating at that time. None of the participants in the prospective, controlled study had influenza develop after the termination of short- or long-term chemoprophylaxis. CONCLUSION: Antiviral chemoprophylaxis can be administered for the longer duration of 14 days or, in the absence of new culture-confirmed illness in the nursing building, for 7 days.

Efficacy of zanamivir for chemoprophylaxis of nursing home influenza outbreaks.

Despite vaccination, influenza remains a common of morbidity in nursing homes. Chemoprophylaxis of residents with currently available antivirals is not always effective and new agents effective against both influenza A and B are needed. In a randomized, unblinded pilot study, we compared 14 day chemoprophylaxis with zanamivir, an antiviral which inhibits influenza neuraminidase, to standard of care during sequential influenza A and influenza B outbreaks in a 735 bed nursing home. Influenza A outbreaks were declared on 6/14 epidemic units. Sixty-five volunteers on four epidemic units were randomized to zanamivir and on two epidemic units, 23 volunteers were randomized to rimantadine. During the 14 days of prophylaxis, only four new febrile respiratory illnesses were detected. One volunteer receiving rimantadine prophylaxis developed laboratory-confirmed influenza. Influenza B outbreaks were declared on 3/14 epidemic units. Thirty-five volunteers on two epidemic units were randomized to zanamivir and 18 volunteers on one epidemic unit were randomized to no drug. During the 14 days of prophylaxis, only one new febrile respiratory illness was detected. One volunteer randomized to receive no drug developed laboratory-confirmed influenza. Zanamivir appears comparably effective to standard of care in preventing influenza-like illness and laboratory-confirmed influenza in nursing homes, but requires further testing.

Outbreaks of influenza A and B in a highly immunized nursing home population.

BACKGROUND: Large outbreaks of influenza A and B may occur in nursing homes despite high resident vaccination rates, even when the vaccine strain is matched to the circulating strain. This study reports the occurrence of separate influenza A and B outbreaks in a nursing home where more than 85% of residents were vaccinated. METHODS: Prospective surveillance was used to identify symptomatic residents in a rural Wisconsin nursing home with 680 residents. Viral cultures were obtained from all consenting residents identified with new respiratory symptoms even in the absence of temperature elevation. A "case" refers to a resident with a respiratory illness and an influenza isolate. RESULTS: During the 1992-93 season, 86% of 670 total residents were vaccinated, 104 (15.5%) were cases with influenza B. During the 1993-94 season, 89% of 690 total residents were vaccinated, 68 (9.8%) were cases with influenza A. The antigenic matches between vaccine and epidemic strains were characterized as "identical or minimal difference" by the Centers for Disease Control and Prevention. CONCLUSIONS: There is still a need to protect residents from infectious secretions and for contingency plans to permit the rapid use of antiviral agents. Future efforts are needed to develop vaccines that provide greater protection and to improve staff vaccination rates.

Report of an outbreak: nursing home architecture and influenza-A attack rates.

OBJECTIVE: To determine factors that might account for a significantly lower attack rate in a newly constructed nursing building during an epidemic of type A influenza. SETTING: A four-building, long-term care facility for veterans and their spouses, with an average daily census of 690. DESIGN: Prospective surveillance with retrospective analysis. PARTICIPANTS: Symptomatic residents submitting to viral culture. MEASUREMENTS: Number of respiratory illnesses and influenza cultures in consenting symptomatic residents. Building characteristics. RESULTS: An influenza A (H3N2) outbreak was culture-confirmed in 68 nursing home residents. Influenza A was isolated in 3/184 (2%) residents in Building A, 31/196 (16%) in Building B, 18/194 (9%) in Building C, and 16/116 (14%) in Building D. Denominators are average daily census during the outbreak. Building A had significantly fewer culture-confirmed cases than the other buildings (P < .001). Fewer residents in Building A, 47% compared with 61% in Buildings B, C, and D, were participants in a formal study of influenza. Eight of 15 respiratory illnesses identified during the outbreak that were not cultured occurred in Building A. These factors could not account for the difference in attack rates. Building A has a unique ventilation system, more square feet of public space per resident, and does not contain office space that serves the entire four-building facility. CONCLUSION: Our retrospective observation suggests that architectural design may influence the attack rate of influenza A in nursing homes.

Prolonged shedding of amantadine-resistant influenzae A viruses by immunodeficient patients: detection by polymerase chain reaction-restriction analysis.

Consecutive A (H3N2) influenza virus isolates from 2 influenza virus-infected immunodeficient patients treated with amantadine were examined using a novel polymerase chain reaction (PCR)-restriction analysis for resistance to this antiviral compound. The data indicate that immunodeficient patients may shed resistant viruses for prolonged periods and with different drug resistance mutations present at different times. This PCR-restriction technique allows rapid detection of amantadine- or rimantadine-resistant strains.

A rhinovirus outbreak among residents of a long-term care facility.

OBJECTIVE: To describe the epidemiology of and clinical findings associated with a rhinovirus outbreak that occurred among institutionalized elderly persons. DESIGN: Retrospective review of medical records and nursing surveillance reports. SETTING: A 685-bed, long-term care facility for veterans and their spouses. PATIENTS: 33 persons from whom rhinovirus was cultured. MEASUREMENTS: Throat and nasopharyngeal virus culture; review of medical records to determine underlying diseases, signs and symptoms of respiratory illness, illness duration, and interventions during illness; and review of nursing surveillance reports to determine room locations of ill persons. RESULTS: Between 14 August and 2 September 1993, the number of respiratory illnesses increased. Throat and nasopharyngeal virus cultures were taken from 67 ill residents; 33 cultures yielded rhinovirus, and no other respiratory virus was isolated. Geographic clustering of persons infected with rhinovirus was observed. Of those persons with rhinovirus infections, 100% had upper respiratory symptoms, 34% had gastrointestinal symptoms, 71% had systemic symptoms, 66% had lower respiratory symptoms (including productive cough), and 52% had new abnormalities on lung auscultation. The 17 persons with rhinovirus infection who had chronic obstructive pulmonary disease had more severe illnesses: Five (29%) required glucocorticoid or bronchodilator therapy for illness-associated bronchospasm; 2 required transfer out of the facility; 1 developed a radiographically documented infiltrate; and 1 died of respiratory failure. CONCLUSIONS: Rhinovirus may cause epidemic, clinically important respiratory illness in nursing homes residents. A large proportion of residents may become ill, and infection may be severe in persons with underlying lung disease.

Adenovirus 21 infection in an isolated antarctic station: transmission of the virus and susceptibility of the population.

Natural dissemination of viral respiratory illness to susceptible men may occur with surprising difficulty. This was especially evident during a 1977 outbreak of adenovirus type 21 (Ad-21) at McMurdo Station, a US research base in Antarctica. The unique circumstances at McMurdo allowed 125 men from the US to join and intermingle with 75 men who had wintered for 6 months in complete isolation. For an additional 5-week (September 2 to October 4, 1977) isolation period, respiratory illness etiology and transmission were monitored in the combined population. A total of 89% of the population was susceptible (neutralizing antibody titer, less than 1:3) to Ad-21 but only 15.0% were infected. Illness spread very slowly (1.5 cases/100 persons/week) with no epidemic peak and was much less severe than Ad-21 outbreaks in other settings. The incidence of infection (17.3%) and illness (9.6%) was low even in men who had wintered over, with values very similar to those of the newcomers (13.9% and 8.9%, respectively). Thus, despite a harsh environment and frequent prolonged gatherings of susceptible personnel, even a respiratory virus type with known epidemic potential was surprisingly difficult to transmit.

A survey of virus infections in New Zealand, 1982-6.

Between 1982 and 1986 virus infections were identified in 16,372 cases. These identifications were based on virus isolation and/or serological evidence of infection by the main virus diagnostic laboratories at Auckland, Waikato, Christchurch and Dunedin hospitals, and at the National Health Institute. The most frequent virus identifications reported were herpes simplex (46.7%), rotavirus (11.8%), respiratory syncytial virus (5.7%), and adenovirus (5.6%). During this period of surveillance, the most prominent feature has been the high incidence of herpes simplex which reached a peak in 1983 but which has abated only slightly since. Significant trends and virus outbreaks or epidemics were detected with the regular reporting of monthly virus identifications in the New Zealand Virus Report (NZVR); these included a measles epidemic in Auckland in 1984/85, major influenza A outbreaks in 1983, 1985 and 1986, the respiratory syncytial virus epidemic in the winter of 1986, the increased incidence of rotavirus predominantly in young infants and children during the winter months, outbreaks of enterovirus type 71 and parainfluenza type 3 infections in 1986, and rubella in 1984.

Release of lysosomal enzyme beta-glucuronidase from isolated human eosinophils.

The human eosinophil contains lysosomal enzymes that can contribute directly to tissue injury and inflammation. Characterization of lysosomal-enzyme release from the eosinophil has been largely limited to isolates from patients with hypereosinophilia. Because eosinophils from such individuals may not demonstrate normal functional responses, we established a method to obtain purified, normal human eosinophils with a Percoll gradient. With this method, it is possible to isolate eosinophils (95.5 +/- 3.9%) and neutrophils (greater than 99%) in high purity from normal subjects. With these granulocyte isolates, we evaluated and compared release of the lysosomal enzyme, beta-glucuronidase (BG), after cell activation with opsonized zymosan particles. Neutrophils released 33.0 +/- 1.2% (mean +/- SEM; n = 5) of total BG (30 minutes of incubation with zymosan), whereas eosinophil secretion was 24.2 +/- 1.7% (n = 5). The fungal metabolite, cytochalasin B (CB), which inhibits microfilament activity, enhanced BG secretion from neutrophils (33.0 +/- 1.2% to 42.8 +/- 2.8% with CB; p less than 0.01). In contrast, CB had no effect on eosinophil BG release. Interestingly, BG content in eosinophils is 101.2 +/- 3.9 micrograms phenolphthalein per 10(6) cells per 18 hours, which compares to a neutrophil level of 51.0 +/- 3.2 (p less than 0.001). Thus, although eosinophils and neutrophils release a similar percentage of total cellular BG on stimulation with zymosan particles, the absolute amount of enzyme per cell is greater in the eosinophil than in the neutrophil. Study of eosinophil function promises to elicit a more complete insight into its contribution to tissue injury.

The presence of hypodense eosinophils and diminished chemiluminescence response in asthma.

Although peripheral blood eosinophilia is a prominent feature of asthma, the contribution of eosinophils to asthma has yet to be fully comprehended. Furthermore, study of isolated eosinophil function in asthma has been complicated by difficult purification methods and, now, the presence of hypodense eosinophils. In our study, eosinophils were isolated from normal subjects and patients with asthma. Two principal evaluations were performed: (1) a comparison of the density-gradient profiles on peripheral blood leukocytes from normal subjects and patients with asthma and (2) a comparison of the chemiluminescence (CL) response with normal dense eosinophils from these two study groups. Granulocyte preparations were initially isolated from Ficoll-Hypaque gradients and were then applied to a continuous Percoll density gradient. In asthma, 40.8 +/- 5.8% of the peripheral blood eosinophils were hypodense (defined as a density less than 1.081 gm/ml), whereas normal subjects had only 9.1 +/- 1.9% of this subpopulation (p less than 0.01). Functional assessment of purified (greater than 90%) normal dense eosinophils was made by measurement of CL to opsonized zymosan particles and the soluble stimulus phorbol myristate acetate. In asthma, eosinophil CL to zymosan, but not phorbol myristate acetate, was significantly less. Differences in eosinophil CL between normal subjects and subjects with asthma did not correlate with the severity of airway obstruction or the peripheral blood eosinophil count. The reasons for the appearance of hypodense eosinophils and diminished metabolic activity in asthma are not established but raise the possibility that their presence represents previous eosinophil activation.

Enhanced eosinophil luminol-dependent chemiluminescence in allergic rhinitis.

Eosinophils were isolated from patients with seasonal allergic rhinitis, and their functional activity was evaluated by their luminol-dependent chemiluminescence (CL) response to opsonized zymosan and phorbol 12-myristate 13-acetate (PMA). We found that eosinophils from patients with allergic rhinitis produced a significantly greater CL response to opsonized zymosan than did normal cells. Eosinophils from both subjects with allergic rhinitis and control subjects were isolated to a purity of 95% and elicited peak values of 1,101, 901 +/- 133,708 cpm/5 X 10(5) cells (n = 7) and 417,278 +/- 25,910 cpm/5 X 10(5) cells (n = 5), respectively. The enhanced eosinophil CL to zymosan was found at times when the patients were maximally symptomatic with hay fever symptoms to ragweed pollen and again when they were asymptomatic. Eosinophils from these patients with allergic rhinitis also had enhanced CL to PMA (0.01 mcg/ml), but this increased activity was largely limited to times of hay fever symptoms. No correlation was found between enhanced eosinophil CL activity and the number of circulating eosinophils in allergic individuals. In contrast to the increased eosinophil activity, neutrophil CL to zymosan and PMA was similar in allergic and normal individuals throughout the study. These data provide evidence for the existence of enhanced oxidative metabolic function in eosinophils from patients with allergic rhinitis and raise the possibility that this particular activity is important in hay fever.

Comparison of superoxide generation and luminol-dependent chemiluminescence with eosinophils and neutrophils from normal individuals.

Although eosinophilia is found in many allergic and hypersensitivity diseases, the function of the eosinophil is not clearly established. To evaluate and characterize this function, anticoagulated blood from normal subjects was separated into purified populations of both eosinophils and neutrophils by a modified method for Percoll gradients. With this separation procedure, highly purified populations of eosinophils (95.0% +/- 2.1%) and neutrophils (97.2% +/- 0.4%) were obtained. Functional response of these two isolated granulocyte cell types was measured by luminol-dependent chemiluminescence (CL) and superoxide generation to opsonized zymosan and phorbol 12-myristate 13-acetate (PMA). Both the eosinophil and neutrophil peak CL response and superoxide generation to zymosan (1 mg), in the presence of autologous serum (10%), were identical. In contrast, when PMA (10(-4) to 10(0) micrograms/ml) was the stimulant, eosinophil CL was at least twofold greater than the neutrophil light emission (1,595,741 +/- 122,435 cpm/5 X 10(5) cells vs. 765,448 +/- 24,171 cpm/5 X 10(5) cells; n = 6). This same differential in responsiveness was seen in superoxide generation. Thus, under certain conditions the eosinophil's respiratory burst may be greater than that of the neutrophil, and this differential in metabolic activity may contribute directly to the eosinophil's inflammatory potential.