Prophylactic Oseltamivir for Prevention of Nosocomial Influenza A Virus Infection

Influenza can be transmitted between patients and medical staff in a hospital setting, resulting in increased morbidity and mortality, especially in immunocompromised patients.^1,2 The World Health Organization and the CDC recommend vaccination for medical staff, with particular emphasis on persons who care for members of high-risk groups.^3,4 However, even though the staff has been vaccinated against influenza, it is impossible to prevent all nosocomial influenza virus infections. We describe the usefulness of prophylactic administration of oseltamivir to prevent nosocomial influenza virus infection during an outbreak in the community at large.

Methods

In a survey conducted during the 2005 influenza season, influenza virus infections were identified in several wards in a 604-bed university hospital. For the purpose of the epidemiological investigation, a case is defined as any person who had an acute respiratory illness with 2 or more of the following symptoms: cough, sore throat, myalgia, and fever (temperature greater than 37.7C [99.9F]). The survey recorded demographic data (name, sex, age, and profession), date of first symptoms, current therapy, and major symptoms (fever, cough, sore throat, myalgia, and headache). Data concerning staff influenza vaccinations were obtained from the employee health service records.

A throat swab was obtained from all symptomatic persons and immediately examined using a rapid diagnostic test kit for influenza. The diagnosis of influenza was made based on clinical symptoms and a positive result of the rapid diagnostic test.

Results

The Table provides information on episodes of influenza A virus infection among staff and patients at the university hospital.

Table

In February 2005, 9 staff members in the Award complained of a respiratory illness that met the case definition for influenza Avirus infection. Oseltamivir (75 mg/d for 5 days) was prophylactically administered to the remaining 15 staff members who gave written informed consent. There was no occurrence of influenza A virus infection in admitted patients. From April 28 to May 2, 2005, 18 staff members in the B ward were infected with the influenza A virus. The venues of infection were believed to be 2 private parties that occurred outside the hospital (Figure). To prevent the spread of influenza A virus infection within the hospital, prophylactic treatment of staff and patients with oseltamivir was again initiated.

Figure -

An episode of influenza A virus infection at our university hospital (in the B ward).

Fifteen staff members and 1 patient who gave written informed consent received oseltamivir (75 mg/d for 5 days). One staff member, a nurse, refused prophylactic oseltamivir therapy because she believed that her contact with infected staff members was relatively low, although she had been a guest at a party suspected of being the site of viral transmission. Five days later, influenza A virus infection was diagnosed in the nurse (Figure). Fortunately, influenza did not develop in any inpatients (Table). Indeed, prophylactic use of oseltamivir may have prevented a significant spread of infection to patients in wards C, D, and E.

Almost all of the 30 infected staff members had been vaccinated against influenza A virus in November 2004. Among the 99 staff members who received oseltamivir, influenza A virus infection developed in 2 persons within 12 hours of initial prophylaxis. This suggests that timing of prophylactic treatment with oseltamivir is important.

Control measures
Symptomatic staff members were sent home for 1 week. Inpatients with influenza were isolated under respiratory precautions (single room, gloves, mask), and the number of staff and visitors entering the rooms of patients with influenza was minimized. Oral oseltamivir at a dosage of 75 mg/d for 5 days was administered to all asymptomatic staff and inpatients who had contact with infected patients.

Discussion
This report emphasizes the usefulness of oseltamivir in preventing nosocomial outbreaks of influenza during epidemic periods. Health care workers (HCW) occasionally have been identified as index cases in nursing home outbreaks.^5,6 Up to 23% of HCW might have clinical or subclinical influenza virus infections at the time of epidemics.⁷

The influenza vaccine may be effective in preventing influenza in HCW and may reduce the number of days of absence from work in those who become infected.⁸ In addition, it has been demonstrated that the attack rate of influenza outbreaks in nursing homes and long-term- care facilities depends to some extent on the vaccination status of residents and staff members.⁹ However, in our university hospital, it became clear that vaccinating against influenza A virus alone would not completely prevent infection; most staff members, including those who became infected with influenza A virus, had been vaccinated in November 2004.

In the present study,we used the neuraminidase inhibitor oseltamivir to prevent the nosocomial spread of influenza. No clinically relevant adverse reactions to oseltamivir were detected among patients or staff. Although neuraminidase inhibitors are being introduced in clinical practice and will probably be useful in controlling outbreaks,¹⁰ little information is available about their efficacy in controlling outbreaks. Therefore, they cannot be recommended for general use. Because our present study was not randomized, it was not possible to definitively evaluate the efficacy of prophylactic use of oseltamivir. However, our findings suggest that oseltamivir might be an effective prophylactic agent for preventing nosocomial influenza virus infection when used in combination with rapid infection control measures.

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• Coles FB, Balzano GJ, Morse DL. An outbreak of influenza A (H3N2) in a well-immunized nursing home population. J Am Geriatr Soc. 1992;40:589-592.

• Yassi A, McGill M, Holton D, Nicolle L. Morbidity, cost and role of health care worker transmission in an influenza outbreak in a tertiary care hospital. Can J Infect Dis. 1993;4:52-56.

• Elder AG, O’Donnell B, McCruden EA, et al. Incidence and recall of influenza in a cohort of Glasgow healthcare workers during the 1993-4 epidemics: results of serum testing and questionnaire. BMJ. 1996;313:1241-1242.

• Wilde JA, McMillan JA, Serwint J, et al. Effectiveness of influenza vaccine in health care professionals:a randomized trial. JAMA. 1999;281: 908-913.

• Morens DM, Rash VM. Lessons from a nursing home outbreak of influenza A. Infect Control Hosp Epidemiol. 1995;16:275-280.  Hayden FG, Atmar RL, Schilling M, et al. Use of selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med.1999;341:1336-1343.