The position paper is intended for use mainly by national public health officials and managers of immunization programmes. They may also be of interest to international funding agencies, vaccine advisory groups, vaccine manufacturers, health professionals, researchers, the scientific media, and the general public.
Vaccines against influenza
Influenza A and B viruses are important human respiratory pathogens which are transmitted mainly by droplets and aerosols originating from the respiratory secretions of infected people, but occasionally also through contact with virus contaminated fomites. Both A and B viruses cause seasonal influenza epidemics and out-ofseason sporadic cases and outbreaks. Influenza occurs globally with an annual attack rate estimated at 5%– 10% in adults and 20%–30% in children. In temperate climates, seasonal epidemics are experienced mainly during the winter while in tropical regions, influenza may occur throughout the year, causing outbreaks more irregularly.
Particular risk groups for influenza
Risk groups for influenza include those at increased risk of exposure to influenza virus as well as those at particular risk of developing severe disease, i.e. disease resulting in hospitalization or death. The former group includes health-care workers (HCWs) whereas groups at particular risk of severe influenza include pregnant women, children aged <5 years, the elderly, and individuals with underlying health conditions such as HIV/ AIDS, asthma, and chronic heart or lung diseases. The risk groups for influenza in low- and middle-income countries are less well defined.
Children aged <5 years, and particularly those <2 years of age, have a high burden of influenza. A systematic review of the global disease burden of influenza in children, representing studies on a total of around 8 million children <5 years of age, estimated that in 2008, there were 90 million (95%, CI 49–162 million) new cases of seasonal influenza, 20 million (95%, CI 13–32 million) cases of influenza-associated acute lower respiratory infections (ALRI), and 1–2 million cases of influenza associated severe ALRI, including 28 000–111 500 deaths. The great majority of deaths from influenza occurred in developing countries.
WHO position paper November 2012 Summary
This position paper is concerned mainly with vaccines and vaccination against seasonal (epidemic) influenza. Influenza A and B viruses are globally important human respiratory pathogens causing epidemics, usually during the winter season, and out-of-season sporadic cases and outbreaks.
Influenza A viruses may also cause worldwide pandemics. Subtypes of influenza A- viruses are determined by either haemagglutinin (HA) or neuraminidase (NA) activity. Minor mutations causing small changes (“antigenic drift”) in the HA gene enable the virus to evade immune recognition, resulting in seasonal influenza outbreaks during inter-pandemic years.
The annual attack rate of influenza is estimated at 5–10% in adults and 20–30% in children. Influenza is typically characterized by fever, cough, sore throat, runny nose, headache, muscle and joint pain and malaise. In young children, impaired respiration, dehydration, altered mental status, and irritability signify serious disease. Secondary bacterial pneumonia is a frequent complication of influenza, particularly in risk groups. Etiology-specific diagnosis of influenza requires laboratory confirmation.
Risk groups for severe influenza include pregnant women, children aged <5 years, the elderly, and individuals with underlying health conditions such as HIV/AIDS, asthma, or chronic heart or lung diseases. Infected healthcare workers may transmit influenza virus to individuals at risk of severe disease.
Currently available vaccines for the control of seasonal influenza are safe and efficacious and have the potential to prevent significant annual morbidity and mortality. Their antigenic composition is revised twice annually to ensure optimal vaccine efficacy against prevailing strains for the northern and southern hemispheres. Seasonal influenza vaccines include two influenza A-strains and one influenza Bstrain. Both trivalent inactivated influenza vaccines (TIVs) for intramuscular injection and trivalent live attenuated influenza vaccines (LAIVs) for intranasal application are available. TIVs include formulations containing an adjuvant or an increased antigen concentration for use mainly in the elderly, and in some countries an intradermally administered TIV is licensed. Recently, a quadrivalent LAIV (2 A- and 2 B-strains) became available.
TIVs are the only vaccines licensed for children aged 6 – 24 months, for persons aged ≥50 years, and for pregnant women. Non-pregnant individuals aged 2 – 49 years may receive either TIV or LAIV.
When the vaccine strains closely match the circulating influenza viruses, efficacy rates of TIV and LAIV against laboratory-confirmed influenza in healthy individuals <65 years of age typically range from 70% to 90%, whereas efficacy is at best modest in individuals aged ≥65 years, and in those with underlying medical conditions.
Pathogen, disease, treatment, and laboratory diagnosis
Influenza viruses belong to the family Orthomyxoviridae and are characterized by a single-stranded, segmented RNA genome. The influenza viruses are classified into types A, B and C on the basis of their nucleoprotein, whereas the subtypes of influenza A viruses are determined by envelope glycoproteins possessing either haemagglutinin (HA) or neuraminidase (NA) activity.
The incubation period of influenza ranges from 1 to 4 days, with an average of 2 days. In infants and young children, transmission through viral shedding may start shortly before onset of symptoms and last into the second week of clinical disease, whereas in adults, viral shedding generally lasts for a few days only. Children attending day-care centres and schools are important transmitters of influenza in the community.
Influenza illness can include any or all of the following symptoms: fever, cough, sore throat, runny nose, headache, muscle and joint pain and severe malaise. The fever and body ache may last 3–5 days and the cough for 2 or more weeks. In children, signs of severe disease include apnoea, tachypnea, dyspnea, cyanosis, poor feeding, dehydration, altered mental status, and extreme irritability. Secondary bacterial pneumonia commonly caused by Streptococcus pneumoniae, Haemophilus influenzae or Staphylococcus aureus is a frequent complication of influenza, particularly in elderly
people and individuals with certain chronic diseases.
Vaccination against Pneumococcus, or case management of severe disease with antimicrobials, may reduce mortality from influenza-associated respiratory infections.
Most of the current seasonal influenza vaccines include 2 influenza A strains and 1 influenza B strain. Trivalent inactivated vaccines (TIV) and live attenuated influenza vaccines (LAIV) are available. A quadrivalent LAIV for intranasal application containing 2 influenza A strains and 2 influenza B strains was licensed in the USA in 2012. The manufacture of influenza vaccines is based on viral propagation in embryonated eggs or appropriate cell cultures. To ensure optimal vaccine efficacy against prevailing strains in both the northern and southern hemispheres, the antigenic composition of the vaccines is revised twice annually and adjusted to the antigenic characteristics of circulating influenza viruses obtained within the WHO global influenza surveillance and response system (GISRS).
WHO position and recommendations
Internationally available vaccines for the control of seasonal influenza are safe and efficacious and have the potential to prevent significant annual morbidity and mortality.
Country-specific information about risk groups, disease burden and cost-effectiveness are important to aid national policy makers and health programme planners in making
informed decisions about target groups and timing for vaccination.
For countries considering the initiation or expansion of programmes for seasonal influenza vaccination, WHO recommends that pregnant women should have the highest priority. Additional risk groups to be considered for vaccination, in no particular order of priority, are children aged 6–59 months, the elderly, individuals with specific chronic medical conditions, and health-care workers.
Countries with existing influenza vaccination programmes targeting any of these additional groups should continue to do so and incorporate immunization of pregnant
women into such programmes.
Children <6 months of age should be protected against influenza through vaccination during pregnancy and vaccination of close contacts. Because of their high burden of severe disease, children 6 – 23 months of age are a target group for influenza immunization. Compared with younger children, those 2 – 5 years of age are at lower risk, but respond better to vaccination with TIV and in particular with LAIV.
Persons ≥65 years of age have the highest risk of mortality from influenza, and are an important target for vaccination, although the vaccines are in general less effective in elderly people. Vaccination of health-care workers should be considered as part of a broader infection control policy for health-care facilities.
Influenza vaccination is recommended every year, particularly for high risk groups. TIV is administered intramuscularly (except for intradermal formulations). Children aged 6 through 35 months should receive a pediatric dose and previously unvaccinated children aged <9 years should receive 2 injections administered at least 4 weeks apart. A single dose of the vaccine is appropriate for children aged ≥9 years and healthy adults. LAIV is given as nasal spray, one dose only, but children aged 2- 8 years should normally receive 2 doses, at least 4 weeks apart.
Successful introduction of influenza vaccines to healthy younger populations, including pregnant women and young children, will require effective educational programmes and communication. For pregnant women year-round availability of the most recent influenza vaccines is essential.
Influenza surveillance platforms are critical for monitoring and communicating the impact of introducing seasonal influenza vaccination. Strengthening of seasonal influenza programmes will assist in programmatic preparedness for pandemic vaccine introduction.
23 NOVEMBER 2012