Influenza vaccine

Abstract

The influenza virus A, B and C causes disease in humans, birds and animals. The influenza type A causes moderate to severe illness in all age groups of humans while the illness caused by type B is of milder and it is primarily affects children. Among many subtypes of influenza A viruses, currently influenza A(H1N1) and A(H3N2) subtypes are circulating among humans. Influenza is a serious public health problem that causes severe illnesses and deaths for higher risk populations. Influenza virus is characterized by frequent mutations—antigenic drifts (minor antigenic change, both A and B) and antigenic shifts (major antigenic change, only A). The current human pandemic A/H1N1 is an example of antigenic shift. It slowly established circulation globally; subsequently endemic/seasonal viruses in both hemi-spheres are H3N2 and H1N1. The novel influenza A (H1N1) 2009 virus was first identified by US Centers for Disease Control and Prevention (US CDC) on April 17, 2009 in samples from two Californian children. As of August 2010, 18,000 people had died globally due to the pandemic flu. The illness rates were highest in children and young adults (20–40% of the population), the hospitalization rates highest in children below the age of one. The case fatality rates varied tremendously and were estimated to be between 0.0004–1.5% (0.05% in US, 0.025% in UK, lowest in children). The most effective way to prevent the disease or severe outcomes from the illness is vaccination. The trivalent inactivated vaccines (TIV) are of three types: whole virus, split-product, subunit surface-antigen formulations and they are grown in embryonated hen's eggs. Whole-virus vaccines, because of adverse reactions, especially in children, are not currently used. Most influenza vaccines are split-product vaccines, produced from detergent treated, highly purified influenza virus or surface-antigen vaccines containing purified hemagglutinin and neuraminidase.

Keywords: :

• influenza
• antigenic drifts
• antigenic shifts
• surveillance
• vaccines

The Influenza virusA, B and C causes disease in humans, birds and animals. The influenza type A causes moderate to severe illness in all age groups in humans while the illness caused by type B is of milder and it is primarily affects children. Among many subtypes of influenza A viruses, currently influenza A(H1N1) and A(H3N2) subtypes are circulating among humans. The type C influenza virus rarely causes illness hence it does not cause epidemics. That is why only influenza A and B viruses are included in seasonal influenza vaccines.¹ Influenza is a serious public health problem that causes severe illnesses and deaths for higher risk populations. Influenza causes annual epidemics that peak during winter in temperate regions. An epidemic can take an economic toll through lost workforce productivity, and strain health services.²

Yearly influenza epidemics can seriously affect all age groups, but the highest risk of complications occur among children younger than age two, elder persons age 65 or older, and people of any age with certain medical conditions, such as chronic heart, lung, kidney, liver, blood or metabolic diseases (such as diabetes) or weakened immune systems.³

Influenza virus is characterized by frequent mutations—antigenic drifts (minor antigenic change, both A and B) and antigenic shifts (major antigenic change, only A). The current human pandemic A/H1N1 is an example of antigenic shift.⁴ The 20th century pandemics were in 1918 (H1N1), 1957 (H2N2) and 1968 (H3N2). The new virus tends to replace endemic/seasonal influenza viruses and post pandemic; it continues to circulate as the new seasonal virus. Thereafter it would exhibit antigenic drift; thus more than one drifted variant may co-circulate. H1N1 virus circulated globally from 1918 till 1957 and was replaced by H2N2 virus; in 1968, H3N2 virus replaced H2N2. The seasonal H3N2 viruses that continue to be isolated globally are descendants of the 1968 pandemic virus. In 1977, a descendant of the 1918 pandemic H1N1 virus reappeared in northern hemisphere; it might have been accidentally released from a laboratory.⁵

It slowly established circulation globally; subsequently endemic/seasonal viruses in both hemi-spheres are H3N2 and H1N1. The novel influenza A (H1N1) 2009 virus was first identified by US Centers for Disease Control and Prevention (US CDC) on April 17, 2009 in samples from two Californian children. The cause of outbreaks of respiratory illness in Mexico during March and April 2009 was also the same virus.³ This virus was transmitted in communities across North America within few weeks and was identified in many parts of the world by May, 2009. On June 11, 2009, the World Health Organization (WHO) declared a worldwide influenza pandemic, indicating community level transmission of the novel influenza A (H1N1) virus in several parts of the world. The transmission of novel Influenza A (H1N1) virus continued in both the Northern and Southern Hemispheres. Influenza epidemics occur yearly during autumn and winter in temperate regions. Illnesses result in hospitalizations and deaths mainly among high-risk groups (the very young, elderly or chronically ill). Worldwide, these annual epidemics result in about three to five million cases of severe illness, and about 250,000 to 500,000 deaths.³

A high case-fatality ratio has often been associated with outbreaks of influenza virus but is less commonly reported in association with seasonal influenza. Nevertheless, in developing countries, seasonal influenza has been associated with a high proportion of deaths, especially among remote populations. In Madagascar, seasonal influenza mortality rates of 2.5% have been reported,⁶ with even higher rates (15%) reported in Indonesia⁷ and in the highlands of Papua New Guinea (9.5%).⁸ High mortality rates during influenza outbreaks in the developing setting have been ascribed to a lack of access to antimicrobial drugs to treat cases of secondary pneumonia and lack of access to health care in general.⁶

In Southeast Asia, pandemic influenza virus transmission remains active but variable across the region. Thailand continues to report the most active circulation of pandemic virus in the region; however, disease activity may have recently peaked and begun to decline. Approximately half of all provinces in Thailand reported that > 10% outpatient visits were due to influenza like illness (ILI). Bangladesh also reported regional spread of pandemic influenza virus in association with an increase in new cases since late February 2010.⁹

As of August 2010, 18,000 people had died worldwide more than 213 countries and overseas territories or communities due to the pandemic flu. The illness rates were highest in children and young adults (20–40% of the population), the hospitalization rates highest in children below the age of one. The case fatality rates varied tremendously and were estimated to be between 0.0004–1.5% (0.05% in US, 0.025% in UK, lowest in children).¹⁰ The risk factors for severe disease and death were pregnancy, morbid obesity, asthma, children below 2; however 25–30% of those who died had no underlying risk factor. Apart from very rapid transmissibility and high attack rates, the affection of predominantly of children and young adults, sparing of the elderly and deaths in those with no risk factors differentiated pandemic flu from seasonal flu.

In India, samples from 201,804 persons who have been tested for influenza A H1N1, 46,065 (23%) of them have been found positive with 2727 deaths in the year 2010. A study from the National Institute of Virology Pune (India) demonstrated that in India, the severity of pandemic flu was higher than seasonal flu (CFR of 0.89% vs. 0.13%) with highest attack rates in those aged below 30 and deaths in those aged 20–50 y.¹⁰

Though WHO has declared that pandemic is over, the virus continues to circulate and causes waves of infections leading to hospitalization and complications in different parts of India even in the second half of 2010. The behavior of the H1N1 (2009) virus as a seasonal virus cannot be reliably predicted. Once the pandemic settles down, the virus is most likely to become the predominant agent of endemic/seasonal influenza.¹⁰ Antigenic changes in seasonal A/H1N1 and H3N2 occur by mutations and genetic recombination between co-circulating viruses of the same subtype. Reassortment with co-circulating viruses of a different subtype may also occur; the fear is that viruses with greater pathogenicity and efficient transmissibility may thus emerge. Continuous surveillance of influenza cases, particularly severe or atypical, is essential for the early detection of such variants.¹⁰

The most effective way to prevent the disease or severe outcomes from the illness is vaccination. Influenza vaccination is most effective when circulating viruses are well-matched with vaccine viruses. Safe and effective vaccines have been available and used for more than 60 years. Influenza viruses are constantly changing, and the WHO Global Influenza Surveillance Network (GISN), a partnership of National Influenza Centres around the world, monitors the influenza viruses circulating in humans. WHO annually recommends a vaccine composition that targets the three most representative strains in circulation.³

Influenza Vaccine

Trivalent inactivated vaccines (TIV)

The trivalent inactivated vaccines (TIV) are of three types: whole virus, split-product, subunit surface-antigen formulations and they are grown in embryonated hen's eggs. Whole-virus vaccines, because of adverse reactions, especially in children, are not currently used. Most influenza vaccines are split-product vaccines, produced from detergent treated, highly purified influenza virus, or surface-antigen vaccines containing purified hemagglutinin and neuraminidase. TIV contains 15 µg each of the WHO recommended two influenza A strains (H1N1 and H3N2) and one influenza B strain.¹¹

They should be stored at 2 to 8°C and never be frozen. These vaccines are licensed for use in children aged 6 mo and older. The vaccines provide 70–90% efficacy in healthy adults, 25–40% reduction in hospitalizations in elderly non institutionalized patients and 40–75% reduction in mortality in influenza seasons. The efficacy of vaccine is lower and around 50% in children below 5 y and in individuals with high risk conditions.¹²

Doses and schedule of TIV

doses

The vaccine is administered intramuscularly and the dose is 0.25 ml in children age between 6 mo to three years and 0.5 ml thereafter. The link between influenza vaccines and Gullain Barre syndrome (GBS) is equivocal and if present is less than 1 case per million people vaccinated. However the vaccine should be avoided in patients with history of GBS and who are not at high risk of severe influenza related complications.¹³

Schedule

When the vaccine is used first time, in children 6 mo to less than 9 y of age the vaccines (TIV) are given as 2 doses, 1 mo apart. Only one dose is sufficient at 9 y and above. Revaccination is recommended with a single annual dose irrespective of age and even if the vaccine’s antigenic composition does not change.¹⁴

Timing for vaccination

The influenza vaccines are given before the peak Influenza season. However, in tropical countries like India where illness occurs all year round, the vaccine should therefore be given as soon as possible. Data from WHO global Influenza surveillance network in India shows a trend of Influenza peaks in the month of June to September which is related with the monsoon across major parts of the country. It is worth noting that these trends correlate closely with the southern hemisphere Influenza virus circulation. The vaccine that is currently available in India is based on the northern hemisphere influenza circulation and it arrives a bit late in the monsoon (August–September).¹⁰

Contraindication

It is contraindicated in the persons who have a severe allergy to chicken eggs, have had a severe reaction to an influenza vaccination in the past and also those who developed Guillain-Barre syndrome (GBS) within 6 weeks of getting an influenza vaccine previously. Influenza vaccine is not recommended in < 6 mo of age and who have a moderate or severe illness with a fever till symptoms subsides.¹

WHO recommends annual vaccination for (in order of priority)³

• Nursing-home residents (the elderly or disabled)

• Elderly individuals

• People with chronic medical conditions

• Other groups such as pregnant women, health care workers, those with essential functions in society, as well as children from ages six months to two years.

Live attenuated influenza vaccines (LAIV)

The live attenuated Influenza vaccine (LAIV) has been approved by United State Food and Drugs Administration (US FDA) for use in healthy non-pregnant individuals 2–49 y of age. The vaccine is composed of the live attenuated reassortment of the three WHO recommended strains and is administered as a nasal spray. It is stored at 2 to 8°C. This vaccine has superior efficacy as compared with the inactivated vaccines in young healthy children especially below 5 y of age. This vaccine should also be avoided in children less than 5 y of age with history of reactive airway disease, those with history of hypersensitivity to eggs or vaccines components and those with history of GBS in the past. If anti-viral agents and the LAIV are administered concomitantly, revaccination should be considered. Nasal discomfort, sneezing, stuffy nose, running nose, loss of smell, red eyes and lacrimation are local reactions. Systemic reactions following LAIV are also known such as headache, chills, fatigue, sore throat, myalgia, arthralgia, irritability, loss of appetite, etc. Most of the reactions are mild and resolve within 2 to 3 d without any sequelae.¹⁰

Live attenuated monovalent novel H1N1 2009

Influenza vaccine (human, live attenuated) pandemic (H1N1), freeze-dried is a live monovalent vaccine for administration by intranasal spray. The Influenza vaccine contains Influenza virus cultivated on embryonated eggs. Each single dose (0.5 ml) contains A/17/California/2009/38 > 107 EID50. It is available in form of one dose vial (with 0.5 ml diluent) and five dose vial (with 2.5 ml diluent). The contraindications are same as those of the trivalent attenuated vaccine. The lyophilized vaccine is reconstituted using 2.5 ml of sterile water for inhalation with the vaccine, using the supplied syringe and vial adaptor. A dose of 0.5 ml is administered as 0.25 ml per nostril using 0.5 ml or 1 ml syringe and spray device. The spray device creates a fine spray that primarily deposits the vaccine in the nose and pharynx.¹⁰