Continuing Education Activity

Influenza viruses belong to Orthomyxoviridae RNA virus family and classify into three distinct types based on their major antigenic differences; influenza A, influenza B and influenza C. Influenza viruses cause the annual human epidemics, seasonal and pandemic. Seasonal influenza epidemics caused by influenza A and B viruses result in 3 to 5 million severe cases and thousands of deaths globally each year. This activity describes the mode of action of influenza vaccine, including modes of administration, formulations, adverse event profiles, eligible patient populations, monitoring, and highlights the role of the interprofessional team in the management of these patients.

Objectives:

• Identify the types of influenza viruses requiring vaccinations.
• Summarize the absolute and relative contraindications of the vaccine.
• Review the methods of administering influenza vaccination and eligible patients for each type of vaccine.
• Explain interprofessional team strategies for improving care coordination and communication to advance influenza vaccination and improve patient outcomes.

Indications

Influenza viruses belong to the Orthomyxoviridae RNA virus family and classify into three distinct types based on their significant antigenic differences; influenza A, influenza B, and influenza C.  Influenza viruses cause the annual human epidemics, seasonal and pandemic. Seasonal influenza epidemics caused by influenza A and B viruses result in 3 to 5 million severe cases and thousands of deaths globally each year. Influenza pandemics caused by the influenza A virus emerge at unpredictable intervals. The influenza A virus will cause epidemics and pandemics because of its spread from migrating birds, pigs, horses, and humans. Transmission can be human to human from fomites, coughing, and sneezing. Pandemics are responsible for increased morbidity and mortality compared with seasonal influenza. Four such pandemics have occurred in the past century, during 1918, 1957, 1968, and 2009. Influenza B causes only human to human spread with a particular emphasis on the fact that no other hosts are involved, therefore, not involved in pandemics. Influenza C is a mild disease.[1] It causes seasonal episodes of influenza, such as Northern infections when they happen from September to March, while Southern infections occur from May to September. Due to the variation in viruses responsible for infections in these two seasons, it requires two different sets of vaccines. Influenza generally has an incubation period of 2 days, ranging from 1 to 4 days.  

FDA-approved Indications

1. Prevention of Influenza A in persons aged six months and above
2. Prevention of Influenza B in persons aged six months and above

The Centers for Disease Control and Prevention (CDC) recommends administering an annual influenza vaccine for all persons older than six months of age.

The influenza vaccination is the most effective method for the prevention and control of influenza. It is most effective in children greater than two years old and healthy adults. The efficacy of the seasonal influenza vaccine ranges between 10% and 60%. The lowest efficacy occurs when vaccine strains are not well matched to circulating strains. Both the trivalent and quadrivalent vaccines are FDA approved.[2]

Regarding immunization in pregnancy, a randomized controlled trial conducted in South Africa has shown that when pregnant women receive the influenza vaccine, it halves their risk of developing influenza while reducing the risk of their infants (up to 24 weeks) contracting the illness.[3]

Data shows the trivalent influenza vaccine provides protection in HIV-infected adults without severe immunosuppression, while the effectiveness in HIV-infected children aged <5 years is somewhat uncertain. In certain groups, including the elderly, immune-compromised individuals, and infants, the influenza vaccine is less effective, but it is beneficial by reducing the incidence of severe disease, like bronchopneumonia, and reduces hospital admission and mortality.[4]

Mechanism of Action

Influenza viruses express two types of antigens; hemagglutinin (HA) and neuraminidase (NA). Influenza A virus has 18 HA and 11 NA subtypes, and these antigens are critical for the virulence of the organism. The trimeric hemagglutinin glycoprotein acts by promoting attachment of the virus to the host cell surface resulting in fusion and thereby releasing virions into the cytoplasm.[1] 

Differently combined H and N antigens are seen in influenza A, which in turn undergo antigenic drifts and shifts resulting in antigenic variation and thereby the necessity for vaccine strain types to vary accordingly. Antigenic drifts are genetic changes occurring in the virus due to various actions of polymerases leading to gradual antigenic changes in both HA and NA, producing new variant strains. An antigenic shift takes place when the currently circulating virus disappears and gets replaced by a new subtype with novel glycoproteins to which antibodies against the previously circulating subtype do not cross-react.[5]

Influenza vaccine conveys immunity against the influenza virus by stimulating the production of antibodies specific to the disease. Antibodies to NA act by effectively aggregating viruses on the cell surface and reducing the amount of virus released from infected cells. Regarding the induction of immunity, the surface HA protein of the influenza virus contains two structural elements, head, and stalk, wherein the head is the primary target of antibodies that confer protective immunity against influenza viruses.[1]

Flu shots offer protection against three or four strains of the flu virus. Trivalent flu vaccines provide protection against two influenza A strains, H1N1 and H3N2, and one influenza B strain. Quadrivalent flu vaccines protect against the same strains as the trivalent vaccine as well as an additional strain of influenza B.[6]

The mechanism of immune protection is more complicated, as while primarily humoral, cell-mediated immunity also plays an essential role in immunity to influenza. After vaccination, it takes two weeks to build up an immune response against the flu. The effectiveness of a vaccine depends on several host factors such as age, underlying health status, genetic status, and antigenic matches between the vaccine and circulating viruses.[7]

Administration

Influenza vaccine administration can vary regarding both the dose form and the patient's age.

Flu shots are available in several forms[8][9][10]:

• Intramuscular vaccine 
• High-dose vaccine (> 65 years)
• Intradermal vaccine (18 to 64years)
• Egg-free vaccine (>4 years)
• Nasal spray (2 to 49 years)
• A needle-free vaccine as a jet injector (18 to 64 years)

Dosage:

• Age 6 months to 3 years;

0.25 - 0.5 ml: 2 doses four weeks apart.

• Age 3 to 8 years:

Not previously vaccinated: 2 doses, 0.5 ml four weeks apart.

Vaccinated previous season; 0.5 ml one or two doses four weeks apart.

• Age 9 years and above[11]:

Single-dose;  0.5 ml

Adverse Effects

Adverse events associated with the influenza vaccine include the following:

• Injection site reactions
• Fever
• Irritability
• Drowsiness
• Myalgia
• Nasal spray 
  • Upper respiratory symptoms
  • Fever, headache, vomiting
  • Lower respiratory symptoms
• Rare 
  • Allergic reaction
  • Urticaria/anaphylaxis[12]

Contraindications

The following are contraindications to receiving the influenza vaccine:

• History of allergy or hypersensitivity to any component of the vaccine (i.e., egg protein allergy)
• Infants less than six months of age
• High fever
• Guillain–Barre syndrome[13]

Monitoring

CDC and FDA continuously monitor vaccine safety and will inform health officials, health care providers, and the public when necessary.

CDC uses three systems of vaccine safety monitoring:

1. The Vaccine Adverse Event Reporting System (VAERS): an early warning system that helps CDC and FDA monitor problems following vaccination.  Anyone can report possible vaccine side effects to VAERS.
2. The Vaccine Safety Data link (VSD): This is a collaborative effort between the CDC and nine other health care organizations, which allows ongoing monitoring and proactive searches of vaccine-related data.
3. The Clinical Immunization Safety Assessment (CISA) Project: a partnership between CDC and several medical centers that conduct clinical research on vaccine-associated health risks.[14]

Inactivated flu vaccine and pneumococcal vaccine administered at the same time may show an increased risk for febrile seizures.

Toxicity

The vaccine does not manifest any dose-dependent toxicity.

The toxicity regarding carcinogenicity and infertility has undergone extensive study and shown to be negative. 

The components of the influenza vaccine are: 

• Formaldehyde is used to inactivate toxins from viruses and bacteria. 
• Thimerosal safeguards against contamination, and it is only present in multi-dose vials.
• Aluminum salts act as adjuvants and impart a stronger immune response.
• Gelatin is present as a stabilizer. 
• Antibiotics, such as gentamicin or neomycin, are present in the flu vaccine to keep bacteria from growing.

Toxicity due to the components of the vaccine is not present due to the inconspicuous amounts present in the vaccine.[15][16]

Enhancing Healthcare Team Outcomes

Vaccination is the primary strategy for the prevention and control of influenza. The success of the vaccination depends upon the promotion by the health workers, including clinicians (MDs, DOs, NPs, PAs), nurses, pharmacists, and other health care professionals. A proper understanding of the vaccine benefits is mandatory. Discouraging the vaccination for trivial reasons should be avoided.

Encourage health professionals at risk to vaccinate themselves.

Pregnant women should be protected either by individual vaccination or by cocoon protection by vaccinating the surrounding people. Vaccinating pregnant women is preferable. Influenza infection after vaccination tends to be less severe, and complications are also reduced. And it helps to protect the baby against flu during the crucial first six months of life as the mother passes the immune protection to her newborn.[17][3]

With all 50 states in the USA permitting pharmacists to administer influenza vaccines, patient access to the vaccine has never been more prevalent or easy to obtain. Pharmacists need to coordinate their efforts with other interprofessional healthcare team members to ensure patients are appropriate candidates for receiving the vaccine and that the patient's vaccine record is updated so that all team members operate from the same patient data. This information sharing is one example of how interprofessional teamwork can enhance patient outcomes and minimize adverse events. [Level 5]

The real challenge in the primary strategy for prevention and control of the influenza virus is the antigenic drifts and shifts. Annual vaccination is the current recommendation due to waning immunity.

A universal influenza vaccine is undergoing trials and serves the purpose of building a single vaccine that targets all strains of the virus; this will, in turn, minimize the need for frequent vaccination and be the bright future of this vaccination.[18][19]