Influenza is an acute respiratory disease caused by influenza virus infection. In Korea, epidemic occurs mostly in winter. The characteristic symptoms of influenza consist of abrupt fever, cough, fatigue and other constitutional and respiratory symptoms. Influenza is usually a self-limiting illness without complications, but some patients at higher risk can experience severe complications or die. Influenza is a contagious disease that infects many patients in a short period, so the spread of influenza in the community can lead to public health issues or socioeconomic problems.

Influenza within a medical institution has a different epidemiology and effects compared to influenza in the community. Medical institutions have high number of visits from influenza patients and wards are crowded with high risk patients. Therefore, there is a high possibility that influenza can spread between patients in a medical institution, and influenza can cause more complications and mortality in this setting. Hence, to minimize the damage from influenza in a medical institution, the effective infection control measures are important to prevent influenza and its spread. The purpose of this guideline is to prevent and control seasonal influenza in a medical institution based on the evidences and current situation in Korea.

The subject institutions of the guideline are private clinics, general hospitals, tertiary hospitals, and long term care hospitals. The scope of the guideline is seasonal influenza, and it cannot be applied in the same manner to pandemic influenza or highly pathogenic avian influenza. The epidemiology, clinical symptoms, diagnosis, tests, and treatment of influenza are addressed as an introduction, but the recommendations suggested by the guideline are limited to prevention and control of influenza in a medical institution. Guideline on the use of antivirals other than infection control purposes is discussed in a seperate guidelline [1].

As the first step, a guideline development committee was organized consisting of six professionals including infectious disease specialists, an infectious control nurse, and a methodology specialist, so that specialists from multiple disciplines could participate in the development process. The second step was to systematically examine the related guidelines. The influenza related guidelines published from 2009 to 2013, only those in English and Korean were included. The guidelines were limited to those developed by Government or professional associations, and were searched from four databases. The databases and search words are presented in Table 1. The retrieved treatment guidelines were reviewed by two members of the development committee to select eight treatment guidelines appropriate to the scope of this guideline, and the selected guidelines are presented in Table 2. The third step was to create a table of contents for the guideline based on the published guidelines. Due to the characteristics of the guideline on the prevention and control of infection, the relevant content was described rather than listing key questions. The fourth step was to construct contents according to domestic and foreign guidelines, related literature searches, and specialist opinions. The level of the recommended items was not ranked, and the recommendations were proposed and composed through discussion by the development committee. In the fifth step, the recommendations were reviewed by three specialists and also approved by Korean Society of Infectious Diseases and Korean Society for Nosocomial Infection Control.

Generally, influenza-like illness (ILI) is defined as acute respiratory symptoms accompanying fever, and influenza can be suspected when it occurs during influenza season. The case definition used in the influenza surveillance system of the Korea Centers for Disease Control and Prevention is a case with sudden-onset fever of 38℃ or more accompanied by cough or sore throat [2].

The definition of high risk groups is slightly different between various clinical guidelines, but the following persons are commonly included [3-6].

'Healthcare workers' used in this guideline is defined as any person who can be exposed to the patients' surrounding environment or have contact with patients, by visiting regularly or residing in a medical institution. This includes staff employed by the medical institution or a related institution to work at the medical institution, students in practical training, trainees, and volunteers.

Example: doctors, nurses, assistant nurses, medical technicians, pharmacists, administrative staff, clerical staff, students, trainees, facility managers, cooks, central supply department workers, laundry workers, cleaners, security staff, volunteers, etc.

In the domestic medical environment, there are many cases where caregivers or guardians of patients reside in the medical institution. Considering this situation, applying the recommendation of this guideline to caregivers and guardians is helpful to manage influenza effectively in a medical institution though they are not employed by the medical institution or related institutions.

In Korea, an influenza epidemic usually occurs from October to April of the following year, and the peak of the epidemic is usually in December and January. Influenza occurs most frequently in children and adolescents between 5 and 14 years of age. Hospitalization from influenza occurs mostly in children aged less than 5 years and the elderly aged 65 years or older, and mortality is highest among the elderly aged 65 years or older. There are no domestic epidemiologic data on influenza, but it is estimated that excess death from influenza and pneumonia is 1.36 to 1.53 per 100,000 population and it is accounts for approximately 1% of the total death [8].

The occurrence of influenza within the medical institution increases during influenza season because many influenza patients are hospitalized from community and healthcare workers or visitors also get influenza. Influenza among hospitalized patients is known to occur at a mean ratio of 0.3 to 0.8 cases per 100 hospitalized patients [9-11]. In a medical institution where an outbreak of influenza occurs, the attack rate increases to 0.7% to 20%, and it can increase to more than 30% in the ward where the outbreak occurred [11-16]. When an influenza outbreak occurs in a long-term care facility with many elderly patients, the attack rate can increase up to 70% [17]. In healthcare workers taking care of influenza patients, the attack rate is diverse from 11% to 59% [13,14]. When aggressive infection control measures were implemented on healthcare workers such as vaccination, reporting and monitoring of respiratory symptoms, and exclusion from work when developing symptoms, the attack rate in healthcare workers was reported to be maintained at less than 2% [18].

The mortality of influenza occurring in medical institution is diverse according to the characteristics of the patients. The mortality is not high in infants without severe cardiovascular diseases, but the mortality of patients in general hospitals or long-term care hospitals was 16%, and especially, the mortality of intensive care unit patients, hematopoietic stem cell transplantation patients, or acquired immune deficiency syndrome patients is reported up to 33% to 71% [15,16,18-20]. Therefore, infection control to reduce influenza and its outbreak within a medical institution is very important.

The influenza virus is spread through 1) direct contact with a patient, 2) contact with the surrounding environment of a contaminated patient, and 3) inhalation of a droplet that includes the virus. The influenza virus can survive for 5 minutes on a contaminated hand, 8 to 12 hours on contaminated clothing or tissue, and 24 to 48 hours on contaminated metal or plastic. The virus can move onto a hand after staying up to 15 minutes on contaminated clothing or tissue, and up to 2 to 8 hours on contaminated metal or plastic [21]. In animal models, influenza has been transmitted in close, separated spaces without direct contact with infected animal or its surroundings and outbreak of influenza in confined spaces such as aircrafts have been reported, which suggest the possibility of airborne transmission in certain circumstances.

When the influenza virus is transmitted, influenza symptoms develop in approximately 50% of patients, and even asymptomatic persons can shed influenza virus. Young adults and middle aged adults are infectious 1 day before the onset of symptoms, and infectivity rapidly decreases at 3 to 5 days after symptoms onset, and 20% to 30% of cases can shed the virus up to 5 to 10 days after the initial day of symptoms [22]. Young children can spread the virus up to 3 weeks [23]. Use of antiviral agents can decrease the period of viral shedding. In severe influenza patients requiring hospitalization, the ratio of detecting virus RNA 1 week after developing symptoms was 57.1% when antiviral agents were not used, while it was 14.3% when antiviral agents were used within 48 hours of symptom onset [24]. Immunocompromised patients are known to shed the virus for a longer period than healthy people. In elderly patients or patients with underlying conditions, around 30% were confirmed to shed the virus for 1 week or more after developing symptoms. In the 2009 influenza outbreak, prolonged viral shedding for 2 weeks or more was reported in severely immunocompromised patients even when antiviral agents were used.

After transmission of the influenza virus, symptoms occur after approximately 1 to 4 days of a latent period. Around 50% are asymptomatic infections, but there is a higher rate of developing symptoms in children.

Typical influenza show sudden-onset fever accompanied by cough or sore throat, and there could be systemic symptoms such as lethargy, headache, myalgia, and joint pain, or respiratory symptoms such as cough, sore throat, rhinorrhea, and dyspnea. Gastrointestinal symptoms like diarrhea or vomiting, or ocular symptoms like ocular pain or photosensitivity can also accompany the infection.

In uncomplicated influenza, the symptoms usually improve after 3 to 7 days even without treatment, but cough and lethargy can continue for more than 2 weeks. In high risk groups, severe complications can accompany the infection or underlying diseases can worsen (high risk groups; refer to "Definitions" section). The most common complication is pneumonia, and other complications such as otitis media, sinusitis and the aggravation of underlying cardiovascular diseases, chronic liver diseases, or chronic renal diseases can be occurred.

When ILI develops during influenza season, it can be clinically diagnosed as influenza. When ILI is defined as sudden fever accompanied by cough or sore throat, the positive predictive value is reported to be in the 79% to 88% range in adults in community [25]. Therefore, influenza should be suspected in medical institutions during influenza season when any hospitalized patient has new-onset fever or respiratory symptoms, underlying respiratory symptoms worsen in elderly patients, there are no symptoms other than fever in infant and patients in serious condition with fever or hypothermia.

Laboratory methods to diagnose influenza include rapid antigen test (RAT), reverse transcriptase-polymerase chain reaction (RT-PCR), serology, and virus culture. RAT and RT-PCR are used in clinical situations where results need to be confirmed quickly. The optimal clinical specimen for children or adults is nasopharyngeal aspirate or swab, and for infants, nasal aspirate or swab [26-28]. Time-wise, detection rate is higher when it is collected closer to the illness onset (within 72 hours). Endotracheal suction and the broncho-alveolar lavage have a high detection rate when a lower respiratory tract infection is accompanied.

RAT can be used easily in all medical institutions because it is point-of-care testing using the diagnostic kit without any other laboratory equipment and provides results in less than 15 minutes. It has high specificity of more than 90%, but its sensitivity is lower than that of RT-PCR (children 70%-90%, adult < 40%-60%), so it cannot be used as confirmation of a diagnosis [6,29-31]. RT-PCR has high sensitivity and specificity, so it can be used as a confirmation test. The results can be obtained within 4 to 6 hours when tested in the laboratory of a medical institution, but it may be difficult to obtain prompt results when samples are sent to an external laboratory [5].

Guideline for antiviral treatment and chemoprophylaxis of seasonal influenza and guideline for treatment of severe influenza have been developed separately [1].

Vaccination is the most effective way to prevent influenza. Vaccination on healthcare workers and hospitalized patients is a basic element for preventing influenza outbreak in a medical institution.

Vaccination against seasonal influenza should be undertaken every year before upcoming influenza season. Subjects for vaccination in a medical institution are all hospitalized patients older than 6 months and healthcare workers without contraindications. Especially, for high risk patients such as those mentioned below, who are at higher risk of developing severe or complicated influenza, vaccination should be carried out meticulously. And vaccination should be delivered to healthcare workers to minimize the possibility of exposure of influenza to high risk patients.

Influenza is usually transmitted through droplet of large particles generated by cough or sneezing of an influenza patient. In some cases, it can spread through smaller aerosols. Droplet can travel less than 1 m, and therefore it is spread by close contact. Indirect contact can also transmit influenza virus from contaminated surfaces to eyes or mouth through hands. Thus, standard and droplet precautions should be implemented. During procedures which generate aerosols, airborne precautions should be followed [38].

For early detection and response to occurrence of influenza within a medical institution, infection control activities are required during the influenza season to monitor the occurrence of ILI and to facilitate laboratory tests when ILI occurs. When an ILI occurs in a medical institution, laboratory tests should be actively performed for patient management and prevention of transmission.

A RAT is performed on patients who have an ILI. When the RAT results are positive in patients who have an ILI during influenza season, additional laboratory testing is not needed. However when the results are negative, RT-PCR can be considered due to the possibility of false negative results of RAT. Because the laboratory test for patients who have ILI during influenza season is to manage influenza patients and prevent transmission within a medical institution, the use of therapeutic antiviral agents for treatment of individual patients can be considered whether influenza tests are taken or not. However, a diagnostic method for surveillance can be chosen according to the situation of each institution.

Influenza virus is usually spread through droplet while coughing, sneezing, or talking, but it can survive for 1 to 2 days on an environmental surface, and it can spread by contacting an environmental surface contaminated with influenza virus [39]. However, it is possible to remove with heat at 75℃ or higher, chlorine, hydrogen peroxide, iodophors (iodine-based antiseptics), and disinfectants such as alcohol [40].

This guideline was designed to provide recommendations by searching as many literatures as possible with a systematic literature review. However, there were not many study results which might be used as a basis for the recommendations was particularly insufficient. Therefore, this guideline may need to be revised by continuously conducting relevant studies in the future. In addition, when this guideline is applied to the individual institution, the range of applying this guideline may be dependent on the state of each institution.

Up-to-date results with respect to the recommendations in this guideline will be periodically reviewed every 3 years. The guideline will be revised if there are new research results which may provide an appropriate basis for the recommendations.