Influenza

Influenza is a contagious viral disease of the airways

Influenza (ICD-9 code 487,ICD-10 code J10-11), often also called the flu, is an infectious disease of the airways. It is caused by infection with RNA viruses of the family Orthomyxiviridae. These viruses can infect both birds and mammals. The infection spreads a.o. through droplets (aerosols) that originate from coughing and sneezing (Tellier, 2006; Weber & Stilianakis, 2008).

Seasonal outbreaks occur especially during the cold seasons. The incubation period of influenza is one to four days. During the first week of the disease it is contagious in close contact. Outbreaks in humans are caused by influenza viruses type A or B (Nicholson et al., 2003).

Influenza begins with acute fever

The disease often begins with fever and chills, accompanied by headache and sore throat, myalgias, malaise, anorexia, and a dry cough. Fever (38–40°C) peaks within 24 h of onset and lasts 1–5 days. Other symptoms include nausea, abdominal pain, and diarrhea (Betts, 1995, Douglas, 1975, Nicholson, 1992). In children, symptoms are similar to those in adults; however, gastrointestinal problems, such as vomiting, abdominal pain, and diarrhea, are more frequent. Maximum temperatures also tend to be higher in children than in adults, and febrile convulsions can occur (Price et al., 1976). The patients can still feel not fit few days or weeks after the fever is gone. Healthy people overcome influenza within 1 to 2 weeks without sequelae (Cox & Fukuda, 1998, Cox & Subbarao, 1999).

Influenza sometimes associated with severe complications

Influenza may be associated with the following complications (CDC, 2009a):

• Pneumonia (usually additional bacterial infections)
• Worsening of chronic medical conditions, such as congestive heart failure, asthma, or diabetes.
• Acute otitis media and sinus problems in children

Those aged 65 years and older and persons of any age with chronic medical conditions, i.e. asthma, diabetes, or heart disease, are at highest risk for serious complications. Therefore these groups are in many countries advised to be vaccinated. See also:Causes and risk factors.

Respiratory infections are not always influenza

On clinical grounds it is difficult to make a clear distinction between infections caused by influenza viruses and those caused by other viruses or some bacteria. In practice, the diagnosis stated is often “influenza-like illness” (ILI) or ”acute respiratory infection” (ARI). For more information see European Union definition of influenza. Confirmation of the presence of the virus with a laboratory test may confirm a case of ILI to be a case of influenza.

Almost every year new virus variants appear

The influenza virus family has 3 types: A B and C. Only the A and B types cause widespread outbreaks of flu among humans (Nicholson et al., 2003). Type A is more important than type B in terms of disease severity and mortality. The type A viruses are characterized by a high degree of variation in two of their surface antigens, the so-called haemagglutinins (HA; subtypes H1-H16) and neuraminidases (NA; subtypes N1-N9).

From time to time new virus variants emerge due to genetic changes in the virus that cause alterations in the antigens on the surface of the virus (antigenic drift). Because the human body defends against surface antigens, the virus in this way partially circumvents the body-immunity that was build up by a previous natural infection or vaccination. Therefore, the influenza virus is able to cause a new epidemic almost every year.

There is also a possibility that a completely new subtype of influenza A virus will emerge (antigenic shift). Since it is completely new, people are naturally not immune protected against it at all, and therefore such a virus variant can lead to a widespread influenza pandemic.

Epidemics and pandemics of influenza among humans since 1889 have been caused by viruses with haemagglutinins of the H1, H2, and H3 subtypes (Cox & Fukuda, 1998). These subtypes can circulate simultaneously during an epidemic and simultaneously with influenza B viruses as well.

See also What is an influenza pandemic?

Seasonal influenza is very common

During ‘average’ seasonal influenza epidemics 5-15% of the population in the Northern hemisphere are affected (WHO, 2009e). When a seasonal outbreak is ‘average’ we speak about an epidemic. When the outbreak is more intense, we speak of a pandemic, i.e. a worldwide and very serious outbreak.

ECDC coordinates the EISN and CNRL

Since September 2008 the coordination of the EISN has been transferred to ECDC . It is assisted in its task by a Coordination Group of experts from the network.

ECDC has surveillance tasks such as to collect, collate, validate, analyse and disseminate relevant data at EU level, operate the dedicated surveillance networks, maintain the database(s) for epidemiological surveillance etc. (For more information see ECDC website).

In addition from September 2008, ECDC is responsible for the coordination of the CNRL. The CNRL has its roots in a collaborative effort to perform influenza surveillance through sentinel networks, which started in 1996 with seven European countries. Over the years, the collaboration was further intensified leading to the creation of the CNRL. The CNRL currently includes the reference laboratories for influenza from all EU Member States and Norway.

The CNRL is closely associated with the WHO through its network of National Influenza Centres (NICs) and collaboration with the WHO-Collaborating Centre for Reference and Research on Influenza.

How the network reports?

The ECDC publishes a weekly surveillance report which is based on data covering a total population of 500 million inhabitants. The weekly surveillance report provides a weekly overview of influenza activity in Europe in the form of a map, a table, graphs and a commentary written by experts from ECDC.

The clinical surveillance of influenza in the EISN is generally based on reports made by sentinel general practitioners. Some of the sentinel surveillance systems also include paediatricians (e.g. the Czech Republic, France and Germany) and physicians with other specialisations (e.g. Slovenia, Lithuania). The physicians usually represent 1-5% of physicians working in the country or region. Most sentinel surveillance systems report data on the number of new cases of ILI and few report the number of new cases of ARI. Some networks report both ILI and ARI (ECDC, 2009b).

The sentinel physicians are asked to take nose and/or throat swabs from patients with ILI or ARI. Some sentinel surveillance systems also collect blood samples (e.g. the Czech Republic, Romania and the Slovak Republic). The specimens are sent to the national reference laboratory and are tested for influenza viruses (if positive, subtypes are determined) and other respiratory viruses. These results are used to validate the clinical reports of ILI and ARI.

The National Reference Laboratories also report influenza test results from non-sentinel surveillance physicians to EISN. Specimens (nose swabs, throat swabs and blood samples) can come from a wide range of sources: hospitals, non-sentinel physicians, homes for the elderly, clinics, etc. These data are collected to validate the data provided by the sentinel surveillance systems and to better describe the epidemiology and virology of influenza in each network (ECDC, 2009c).

Trends: no clear trends in peak number of influenza cases since 1996-1997

In Europe there is no clear increase or decrease in the peak incidence of ILI and ARI since 1996-1997. Some developments could have contributed to a decreasing trend, such as a better general health, increased vaccination coverage among risk groups, reduced transmission of the virus due to a decrease in the number of persons per household, and introduction of new antiviral drugs that can reduce the severity of the disease and shorten its duration. On the other hand some developments could have increased the spread of the virus by increasing contacts between people, such as more children visiting day-care facilities, and larger attendance of big events, and a generally increased global mobility as well as an increase of the aging population, which is a known risk group. In addition, the number of people in risk groups increases due to improvements in the (early) diagnosis by GP’s of diseases such as diabetes mellitus and cardiovascular disease. In the coming years the risk population for influenza complications is expected to continue to increase further (Tacken et al., 2008).

Current trends in Novel Influenza A(H1N1) in EU countries

All EU-27 and 4 EFTA countries are reporting cases of pandemic (H1N1) 2009 influenza. On 27 April 2009 the first four confirmed cases of novel influenza A (H1N1) virus were detected in Europe, i.e. in Spain and the United Kingdom. Since then the number of confirmed cases has continued to increase.

For more details see our interactive map with the developments in the number of confirmed novel influenza A(H1N1) cases.

WHO Europe and ECDC are providing constant updated numbers of confirmed cases.

Deaths attributable to influenza difficult to estimate

The numbers of deaths that are attributable to influenza are difficult to estimate directly for several reasons (Thompson et al., 2003):

• Influenza is typically not confirmed virologically as an influenza virus infection or specified on hospital discharge forms or death certificates.
• Many influenza-associated deaths occur from secondary complications such as congestive heart failure, COPD, pneumonia, and bacterial superinfections, when influenza viruses are no longer detectable (Bisno et al., 1971; Douglas, 1976).
• Respiratory syncytial virus (RSV) epidemics often overlap with influenza epidemics. It is likely that some deaths previously attributed to influenza are actually associated with RSV infection (Nicholson, 1996; Zambon et al., 2001; Fleming & Cross, 1993).

Slight increase in deaths from flu over the last decades

Some countries, including Germany and the United States, have reported an increase in absolute mortality numbers by influenza since the early eighties. This is probably, or at least in part, due to aging of their populations (Thompson et al., 2003 and Zucs et al., 2005) as mortality rates for influenza are higher in the elderly.

Vaccination is associated with reduced mortality

Influenza is an infectious disease that can induce inflammatory responses (Naghavi et al., 2003; Julkunen et al., 2000). Inflammation is highly associated with increasing mortality from cardiovascular diseases, diabetes mellitus, and stroke (Nathan, 2002; Libby, 2002; Engstrom et al., 2003).

Several studies have found that influenza vaccination is strongly associated with reducing lung disease-specific mortality, including deaths by pneumonia and COPD. In addition, vaccination is associated with a reduction in all-cause mortality and in other major causes of death, such as stroke, diabetes mellitus, and renal disease.

In a study by Wang et al. it was suggested that the protective effect of vaccination might extend beyond the influenza season to the rest of the year. Therefore, the influenza vaccination not only reduces the mortality risk for influenza-related pneumonia and COPD, which occur mainly during influenza season, but also long-term complications such as stroke, cardiovascular diseases, or other major causes of death. These long term complications might occur during or after the influenza season, or in later months, due to secondary complications from influenza (Wang et al., 2007).

Highest pandemic excess mortality rates during the 1918 Spanish flu

Pandemics have occurred three times in the previous century. The 1918 `Spanish flu' A(H1N1) pandemic was particularly severe. Medical historians have generated estimates of mortality of about 50 million and ranging from 20 million to 100 million. These estimates are based on reviews of various historical documents, including national commissions, eye-witness accounts, and local government reports (Murray et al., 2006). The more recent pandemics, A(H2N2) `Asian flu' in 1957 and A(H3N2) `Hong Kong flu' in 1968, were associated with moderately increased mortality rates (Simonsen, 1999).

Influenza affects patients, health systems and economies

The burden from influenza is manifold:

• There are numerous disease cases that may be fatal or cause hospitalisation.
• There are even larger numbers of mild to moderate cases that result in a multiplication of working days called off sick causing loss of productivity in the working population.

These effects are often of great economic impact. The burden of influenza varies from year to year, however, which makes it hard to estimate the annual number of deaths. The costs caused by an illness are mainly calculated by computing the sum of all direct, indirect and intangible costs.

Direct costs are influenced by chronic underlying conditions and other risk factors (e.g. age), which may lead to increases in hospital admissions and prolonged treatments. Influenza constitutes a substantial socioeconomic burden for society in terms of medical treatments, increases in consultations, hospitalisations, clinical complications and drug use as well as increased work absenteeism (Commission of the European Communities, 2009).

Visits to clinics, physicians’ offices, or hospital emergency rooms may increase greatly during epidemics and pandemics. Lower-respiratory tract and cardiac complications can lead to substantial increases in hospital admissions and deaths, and healthcare resources can be severely strained during influenza epidemics (Cox & Subbarao, 1999).

There are different estimates of the total economic impact of an influenza epidemic. For example, the total impact of an influenza epidemic in industrialised countries may reach 56.7 million € per million people. In several different studies a total costs of 987.8 million € was estimated for Germany in1996-1997 influenza epidemic; the total cost of influenza was estimated at more than 1,796 million € in France; and in the United States, the yearly total costs have been calculated at approximately 10,000–17,000 million € (Commission of the European Communities, 2009).

Influenza is a contagious viral disease

Influenza viruses are spread primarily by small particle aerosols of virus-laden respiratory secretions that are expelled into the air by an infected person during coughing, sneezing, or talking (Tellier, 2006; Weber & Stilianakis, 2008). Spread by direct contact may also occur. Influenza epidemics and pandemics often occur explosively with simultaneous onset of illness in many persons within a relatively short period of time. This occurs because the incubation period for influenza is short (1-4 days) and a single infected person can transmit virus to a large number of susceptible individuals (Cox & Fukuda, 1998).

Risk groups for influenza

Some groups of patients are at increased risk for severe complications and deaths due to influenza (WHO, 2009f). These include:

• Residents of institutions for elderly people and the disabled;
• People of any age with certain chronic health conditions (such as chronic heart or lung disease, metabolic or renal disease or immunodeficiencies);
• Elderly people
• Very young children.

Influenza as a special risk to the elderly

The risk of complications and mortality from influenza increases significantly in elderly. Elderly people have an increased risk of a permanent reduction in their physical and mental capabilities (Sprenger et al., 1993b). In some cases their death is attributed to secondary bacterial pneumonia, but sometimes death occurs without any apparent complication. Relatively many influenza patients have an abnormal ECG (Karjalainen et al., 1980; Greaves et al., 2003). This symptom can be fatal even after long time especially in chronic heart patients. Influenza patients may develop several types of encephalopathy (brain disorders) (Mizuguchi et al., 2007). Usually it heals quickly and completely. Sometimes, however, brain haemorrhage arises that could have lasting repercussions. Approximately 20% of children 6 months to 5 years of age that were hospitalized with influenza A infections had febrile seizures (Chiu et al., 2001). Pregnant women are at slightly increased risk of serious pneumonia (Laibl & Sheffield, 2005).

Developments that have reduced the risk of influenza

In the recent decades, a number of developments have led to a reduction in the number of influenza cases and deaths due to influenza. The physical resistance of populations has increased by improved general health status. In addition, a decrease in the number of persons per household has probably resulted in a reduced transmission rate and spread of the influenza virus. Finally, the seasonal flu epidemics have been fought by increased vaccination in particular risk groups.

Increased mobility and social contacts increase the risk

In contrast to developments that have reduced the risk of influenza, there are developments that have increased this risk. One of these developments is the rise of social contacts, for example by disco visits, participation in major (sports) events and the accommodation of young children in nurseries. In addition, increased (global) mobility may have led to a greater or faster spread of the influenza virus.

Serious consequences of influenza can be avoided by vaccination

In healthy young persons a short-term influenza respiratory disease caused by the influenza virus may cure itself. The disease itself lasts 1-5 days but full recovery can take 1-2 weeks (Cox & Fukuda, 1998). The most efficient way to prevent influenza is by vaccination. Influenza vaccination has the objective to prevent influenza risk and thereby serious illness, complications and death. There are still chances, however, that people who are vaccinated will get influenza but the chance of complications and mortality is lower (Wang et al., 2007).

Vaccination is recommended for risk groups

Although complications from flu can occur in anyone, they are far more common among the high-risk groups. A survey by ECDC in 2006 of EU Member States and associated EEA countries found that countries were recommending annual vaccination to the two largest groups highlighted by the WHO:

• The elderly
• People with chronic medical conditions, such as lung and heart disease, and people whose immune systems are weak

There are different approaches in the various European countries regarding the groups to be vaccinated. As for the elderly, the specific age range for people in this group may vary from one country to another. A majority of countries recommend vaccination for people aged 65 and over, however some recommend it for people aged 60 and over or even 50 and over. The WHA , which includes all EU/EEA countries, has supported a proposal in 2003 that there should be targets for uptake of influenza vaccination in the elderly of 50% by 2006 and 75% by 2010. Currently, most EU/EEA countries fall short of this standard.

Many countries especially emphasise the importance of annual immunisation of people living in residential care settings for the elderly and disabled. The majority of countries in Europe recommend that all health care staff should be immunised against influenza. In this way staff that are more likely to be exposed through their work are protected, as well as the patients they are dealing with. Few EU countries recommend immunization of children or offering vaccines to pregnant women. An expert panel convened by ECDC considered there was as yet insufficient evidence on the burden of infection in children to take any view for or against immunization.

Recommendations on influenza vaccinatioin adopted by the European Commission

The European Commission has adopted recommendations regarding seasonal influenza vaccination. These recommendations include improving vaccination coverage rates in order to reach, as early as possible, however, no later than by the winter season 2014/2015, vaccination coverage rate of 75% in all at risk groups. These are older age groups (65 years and older) and people with underlying medical conditions. Member States should organise annual uptake surveys in all at risk groups and foster education, training, and information exchange on seasonal influenza (Commission of the European Communities, 2009).

Influenza vaccination is effective and cost saving

Influenza vaccination reduces the morbidity and mortality of influenza. The chance to get influenza decreases with 70-80% in adults younger than 65 years. In the elderly it reduces the risk somewhat less, namely 30-70%, and it reduces the risk of complications with 20-50 % (NHG & LVG, 2008). A serial cohort study has shown that among elderly people living in the community, vaccination against influenza was associated with less frequent hospitalizations for complications of influenza, with fewer deaths during the influenza season, and with direct savings in health care costs. These findings were consistent over three consecutive seasons among cohorts of more than 25,000 elderly men and women (Nichol et al., 1994).

Vaccination of people outside the risk groups

It has been investigated whether influenza vaccination of individuals outside the risk groups is cost effective. Influenza vaccination in healthy individuals aged 50 to 64 years has been estimated to be cost effective (Turner et al., 2006). Other cost-effectiveness analyses were focusing on all healthy adults younger than 65 years. In this total group, the conclusion was that vaccination is cost effective and cost saving. Also vaccination of health personnel has been shown to be cost effective and cost saving (Burls et al., 2006).

How effective is influenza vaccination in the elderly?

There is no doubt that influenza vaccines are effective in preventing influenza infection in healthy adults (Demicheli et al., 2004). There is however a debate about how effective the influenza vaccine in elderly really is. Some scientists claim that there is no sufficient evidence that shows that vaccination substantially reduces the risk of influenza-related mortality among elderly people. This claim is based on the following (Simonsen et al., 2007):

• There is no randomised clinical trial (placebo-controlled) data conclusively showing a benefit in those aged 70 years or more, the age-group that accounts for nearly all influenza-related deaths.
• The vaccine effectiveness declines sharply after age 70 years (Govaert et al., 1994). Immunologists have shown that immune responses to novel antigens are seriously impaired in the oldest age-groups (Vallejo, 2007). Placebo-controlled RCTs find that antibody responses to influenza vaccine in elderly people are only about one-quarter to one-half as strong as responses found in younger adults (Goodwin et al., 2005). Some studies have shown lower efficacy among the elderly, for example, a vaccine effectiveness of 29% for prevention of hospital admission with laboratory-confirmed influenza (Falsey et al., 2005).

Though doubting the effectiveness of the vaccine in elderly Simonsen et al. recommend that this group should continue to be vaccinated because even a partly effective vaccine is better than no vaccine at all (Simonsen et al., 2007).

Low coverage of influenza vaccination in the elderly in many European countries

The countries of the European Region of WHO, including all EU Member States, have committed themselves to the goal of attaining vaccination coverage of the elderly population of at least 50% by 2006 and 75% by 2010. In 2007 the Netherlands is the only country to reach the WHA 2010 target of 75% coverage in the elderly with 77% coverage. See Increase in influenza vaccination rate for the population aged 65 and above in selected countries between the years 2001 and 2007. The United Kingdom reached a percentage just below this target at 74%. There is low vaccination coverage especially in the new Member States of the EU (Mereckiene et al., 2008). For other risk groups than older people, it is difficult to compare vaccination rates among countries (Kroneman et al., 2003).

See also: Trends in influenza vaccination rate for the population aged 65 and above in selected countries, 2000-2007.

Prevention or treatment of influenza by anti-virals

Uncomplicated influenza is not treated with antibiotics. These are only given when there is evidence of a secondary bacterial infection. Recently, new antiviral drugs for prevention and treatment of influenza have been developed. The M2 ion channel blockers or adamantanes (amantadine and rimantadine) have been available since the sixties of the previous century, however, its use is limited because of rapid development of resistance, serious adverse effects, and being only active against influenza A viruses. The newer neuraminidase inhibitor drugs oseltamivir and zanamivir are active against influenza viruses type A and B, and development of resistance is slow. Both types of drug reduce the severity of illness and shorten the disease duration by half to one day. These drugs should be taken within 48 hours after the onset of first symptoms (Cooper et al., 2003a). These antivirals are prescribed only in special cases, e.g. risk patients with influenza. Vaccination remains the best way to prevent influenza. Most of currently circulating seasonal A(H1N1) viruses are resistant against oseltamivir but sensitive for zanamivir and the adamantanes, whilst most of currently circulating seasonal A(H3N2) viruses are resistant against the adamantanes but sensitive for the neuraminidase inhibitors.

Tests on viruses obtained from patients in Mexico and the United States have indicated that the 2009 novel influenza virus A(H1N1) is sensitive to neuraminidase inhibitors, but that the virus is resistant to the other class of drugs, the adamantanes (WHO, 2009g).

Prevention by individual protection and hygienic measures

The WHO has drawn up advice on how to protect oneself from Influenza A(H1N1). For example, cover the nose and mouth with disposable tissue when coughing; dispose of used tissues immediately after use, etc. For more information see: “Influenza A(H1N1) How to protect yourself and others”.

General hygiene measures are applied to determine contamination or spread of infections with influenza prevention. In particular, washing hands with soap and water is effective in the reduction of live virus particles to virus undetectable in culture (Grayson et al., 2009). The use of masks, as in Asian countries, may also help to limit spread (MacIntyre et al., 2009).

Four pandemic influenza A (H1N1) 2009 vaccines are soon available on the European market. For more details see the ECDC website.

An influenza pandemic is a global outbreak

An influenza pandemic is an almost simultaneous outbreak of influenza in all areas of the world. An influenza pandemic is caused by an influenza virus that is new to people. Therefore, almost nobody has a sufficient immunologic defence against it. This is different from the normal annual influenza outbreaks. Although the ordinary influenza virus changes slightly from year to year, healthy people still have acquired partial protection against it by previous contacts with the influenza virus or vaccination. During annual influenza outbreaks the main concerns are the risk of a severe course of influenza in young children or in the elderly and in people with reduced immunity.

In a pandemic one can speak less about special risk groups for a serious course of the disease because nobody is immune. Historically, about every 25-50 years an influenza pandemic has occurred. In the last century this has happened three times: in 1918 (Spanish influenza), 1957 (Asian influenza) and 1968 (Hong Kong influenza). The severity varied with an estimated 1-50 million excess deaths during the pandemics. The time and place of the next pandemic are impossible to forecast. However, in 2009 the WHO declared a pandemic with A(H1N1) virus from swine origin, which causes in general mild influenza (WHO, 2009a).

Conditions for a pandemic influenza outbreak

WHO has defined the characteristics of a new influenza virus that can cause a pandemic (WHO, 2009b) as follows:

• A new influenza virus subtype emerges
• It infects humans, causing serious illness
• It spreads easily and sustainable among humans.

The WHO global influenza preparedness plan has defined 6 phases of an influenza outbreak in which phase 6 defines the stage of a pandemic outbreak (WHO, 2009c).

The A (H1N1) virus source

The present influenza A(H1N1) virus is a new virus subtype of influenza affecting humans, which contains segments of genes from pig, bird and human influenza viruses in a combination that has never been observed before anywhere in the world. New viruses are often the result of a re-assortment of genes from two other viruses (swap of genes). This A(H1N1) virus is the result of a combination of two swine influenza viruses that contained genes of avian and human origin.

Typical swine influenza is an acute viral infection of the respiratory tract in pigs, caused by type A influenza virus. The mortality rate in pigs is low and recovery usually occurs within 7–10 days. Swine-origin influenza virus infections also occur in wild birds, poultry, horses and humans, but interspecies transmission is considered a rare event. So far three influenza type A virus subtypes have been found in pigs: H1N1, H1N2 and H3N2. Human infections with swine influenza have been detected occasionally since the late 1950s usually in persons with direct exposure to pigs (e.g. people working in pig farms, etc.). In Europe, since 1958 a total of 17 cases have been reported (ECDC, 2009a).

First appearance in Mexico and the USA

Novel influenza A(H1N1) was first detected in Mexico and the United States in March and April, 2009 (CDC, 2009b).

Similar transmission routes as normal influenza

People become infected with Influenza A(H1N1) virus in the same way as for normal seasonal influenza. It spreads from person to person via droplets from an infected person who is coughing and sneezing; indirectly when droplets or secretions from the nose and throat settle on objects (including hands) which then are touched by other people who touch their own mouth or nose (ECDC, 2009a).

The usual influenza symptoms

Symptoms of influenza A(H1N1) virus in humans are usually similar to regular human seasonal influenza symptoms, involving fever of sudden onset and respiratory symptoms; diarrhoea might also occur. However, severe complications could occur even in normally healthy persons who become infected with the virus (ECDC, 2009a). At this time, most people who have become ill with novel A(H1N1) in the United States have recovered without requiring medical treatment and have experienced typical influenza symptoms (CDC, 2009c).

Increasing severity according to WHO’s pandemic alert system

WHO uses a series of six phases of pandemic alert to inform the world of the seriousness of the threat of an influenza outbreak and the need to launch progressively more intense preparedness activities (WHO, 2009c).

Based on the assessment of all available information and following several expert consultations on influenza A(H1N1), on 11 June 2009 WHO had raised the existing level of influenza pandemic alert to phase 6, i.e. to the pandemic stage. At that moment sustained community-level transmission of the virus was taking place in more than one region of the world. The pandemic was characterized as being of moderate severity. Most of the cases had been mild, but a large spread of mild cases together with even a low fraction of severe cases can have a very significant impact on global health systems and society (WHO, 2009d).

Any person with at least one of the following clinical forms:

Influenza-like illness (ILI)

Sudden onset of symptoms

AND

At least one of the following four systemic symptoms:

• Fever or feverishness
• Malaise
• Headache
• Myalgia

AND

At least one of the following three respiratory symptoms:

• Cough
• Sore throat
• Shortness of breath

Acute respiratory infection (ARI)

Sudden onset of symptoms

AND

At least one of the following four respiratory symptoms:

• Cough
• Sore throat
• Shortness of breath
• Coryza

AND

A clinician's judgement that the illness is due to an infection

At least one the following four:

• Isolation of influenza virus from a clinical specimen
• Detection of influenza virus nucleic acid in a clinical specimen
• Identification of influenza virus antigen by DFA test in a clinical specimen
• Influenza specific antibody response

Sub typing of the influenza isolate should be performed, if possible

An epidemiological link by human to human transmission

• Possible case: any person meeting the clinical criteria (ILI or ARI)
• Probable case: any person meeting the clinical criteria (ILI or ARI) and with an epidemiological link
• Confirmed case: any person meeting the clinical (ILI or ARI) and the laboratory criteria

An influenza pandemic is a global outbreak

An influenza pandemic is an almost simultaneous outbreak of influenza in all areas of the world. An influenza pandemic is caused by an influenza virus that is new to people. Therefore, almost nobody has a sufficient immunologic defence against it. This is different from the normal annual influenza outbreaks. Although the ordinary influenza virus changes slightly from year to year, healthy people still have acquired partial protection against it by previous contacts with the influenza virus or vaccination. During annual influenza outbreaks the main concerns are the risk of a severe course of influenza in young children or in the elderly and in people with reduced immunity.

In a pandemic one can speak less about special risk groups for a serious course of the disease because nobody is immune. Historically, about every 25-50 years an influenza pandemic has occurred. In the last century this has happened three times: in 1918 (Spanish influenza), 1957 (Asian influenza) and 1968 (Hong Kong influenza). The severity varied with an estimated 1-50 million excess deaths during the pandemics. The time and place of the next pandemic are impossible to forecast. However, in 2009 the WHO declared a pandemic with A(H1N1) virus from swine origin, which causes in general mild influenza (WHO, 2009a).

Conditions for a pandemic influenza outbreak

WHO has defined the characteristics of a new influenza virus that can cause a pandemic (WHO, 2009b) as follows:

• A new influenza virus subtype emerges
• It infects humans, causing serious illness
• It spreads easily and sustainable among humans.

The WHO global influenza preparedness plan has defined 6 phases of an influenza outbreak in which phase 6 defines the stage of a pandemic outbreak (WHO, 2009c).

Highest pandemic excess mortality rates during the 1918 Spanish flu

Pandemics have occurred three times in the previous century. The 1918 `Spanish flu' A(H1N1) pandemic was particularly severe. Medical historians have generated estimates of mortality of about 50 million and ranging from 20 million to 100 million. These estimates are based on reviews of various historical documents, including national commissions, eye-witness accounts, and local government reports (Murray et al., 2006). The more recent pandemics, A(H2N2) `Asian flu' in 1957 and A(H3N2) `Hong Kong flu' in 1968, were associated with moderately increased mortality rates (Simonsen, 1999).

Influenza vaccination in the elderly

ECDC Weekly Influenza Surveillance

ECDC Pandemic (H1N1) 2009

WHO Europe Pandemic (H1N1) 2009

OECD Influenza vaccination in the elderly

WHO Europe World Health Organization Regional Office for Europe

ECDC European Centre for Disease Prevention and Control

EISN European Influenza Surveillance Network

CNRL Community Network of Reference Laboratories for Human Influenza in Europe

CDC Centers for Disease Control and Prevention

Increase in influenza vaccination rate for the population aged 65 and above in selected countries between the years 2001 and 2007.

Trends in influenza vaccination rate for the population aged 65 and above in selected countries, 2000-2007.

Developments in the number of confirmed novel influenza A(H1N1) cases.

Author: Eliyahu H, Meijer A (RIVM, Bilthoven, the Netherlands)

Editor: Verschuuren M, Achterberg PW (RIVM, Bilthoven, the Netherlands)

Reviewer: -