Influenza affects 5-15 % of the population annually. Influenza typically starts with fever, sore throat, headache, myalgia, chills, anorexia, and extreme fatigue followed by rhinorrhea and dry cough. The presence of cough and fever are the best predictors of influenza in adults and children during periods of influenza circulation. Rash has been described in influenza B. Uncomplicated influenza generally lasts 7 days. Infected persons are contagious one day before symptoms and up to 7 days after onset. In the elderly, fever may be absent while the presenting signs may include anorexia, lassitude or confusion. Asymptomatic influenza occurs in 30% of cases and they are infectious and transmit the infection.
The risk of developing serious complications from influenza infection is elevated in persons at both age extremes as well as in those with certain underlying conditions. The most common serious complications of influenza include exacerbation of underlying chronic pulmonary and cardiopulmonary diseases, such as chronic obstructive pulmonary disease, asthma, and congestive heart failure, as well as development of bacterial pneumonia, usually associated with Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae. Primary viral pneumonia occurs infrequently but is often fatal. New risk factors during the 2009 pandemic included those with morbid obesity and of aboriginal origin.
Influenza vaccines form the mainstay of public health and personal protection against circulating seasonal influenza viruses. Influenza virus antigenic drift required a robust global surveillance system which monitors emergence of new strains. The World Health Organization (WHO) biannually updates the latest recommended vaccine compositions for both the Northern and Southern hemispheres. Quadrivalent influenza vaccines incorporate influenza A/H1N1, A/H3N2 strains and 2 influenza B strains representing Victoria and Yagamata lineages.
Most influenza vaccines are prepared in embryonated eggs. Cell culture influenza vaccine is produced in sterile incubators without use of eggs, antibiotics or preservatives.
Interest in the development of ‘Universal‘ influenza vaccine focuses on identifying conserved proteins that are accessible to immune recognition.
Vaccines Available in Malaysia
Egg – Based Influenza Vaccine
- Fluarix Tetra® (Inactivated influenza vaccine)
GlaxoSmithKline Pharmaceuticals (M) Sdn Bhd/GlaxoSmithKline Biologicals, Germany
- Influvac® (Inactivated influenza vaccine)
Abbott Laboratories (M) Sdn Bhd/Abbott Biologicals B.V., Netherlands
- FluQuadri Quadrivalent™
Sanofi Aventis (M) Sdn Bhd/Sanofi Pasteur Inc., USA
- Vaxigrip Tetra®
Sanofi Aventis (M) Sdn Bhd/ Sanofi Pasteur inc., France
Cell-Based Influenza Vaccine
- SKYCellflu Quadrivalent®
AJ Biologics (M) Sdn Bhd/SK Bioscience Co., South Korea
Mode of Administrations
- Inactivated influenza virus vaccines have been given by intramuscular, subcutaneous, or intradermal routes. The routes associated with the most reproducible immunogenicity and lowest reactogenicity have been the intramuscular and subcutaneous routes.
- The intradermal route requires less antigen than intramuscular injection to produce a similar immunologic response, but it results in more local erythema at the injection site than other routes. An influenza vaccine using a micro-injection device and 9µg of each hemagglutinin (HA) per dose is now approved for use on those aged 18-59 years and 15µg per HA formulation is recommended for those ≥60 years old.
Co-administrations with Other Vaccines
- Inactivated Influenza vaccine can be administered concurrently with other vaccines, including pneumococcal polysaccharide vaccine.
Contraindications and Adverse Effects
- Persons known to have an anaphylactic hypersensitivity to eggs or egg antigens or to influenza vaccine should not be vaccinated with an egg-replicated influenza vaccine until they are evaluated by a physician. Recombinant influenza vaccine may be given to persons with known egg allergies.
- The most common adverse effects are soreness at injection site, fever, myalgia and headache. Adjuvanted vaccine may be associated with more severe local reaction.
- Persons with history of Guillaine-Barre syndrome (GBS) occurring six weeks post vaccination is more likely to have subsequent GBS. It is not recommended for those with history of GBS to be vaccinated with influenza vaccine.
- To date, the most frequently reported adverse events for influenza vaccines received by the National Pharmaceutical Regulatory Agency (NPRA) are local site reactions such as injection site pain and swelling, fever, flu-like syndrome, headache, fatigue and rash.
Target Groups in Malaysia
- Annual administration of influenza vaccine is indicated for anyone who wants to decrease the risk of influenza as well as the following target groups:
>> All healthcare workers
>> Persons at high risk of developing serious complications from influenza, including:
> All persons 50 years or older
> All persons aged 18-49 years with 1 or more medical conditions
> Pregnant women
> Persons living in certain institutional settings
> Obese persons
- Persons aged 50-59 years have been identified as a target group since approximately one third of them have a high-risk medical condition and age-based recommendations have been more successful than medical-condition-based recommendations in raising vaccination rates.
- Household members in close contact with persons with high-risk conditions, including out-of-home caregivers of children <6 months of age.
- Those performing religious pilgrimages, including the Hajj and Umrah.
Implications for Healthcare Workers (HCWs)
- All healthcare workers should receive annual influenza vaccination to reduce the risk of infection for themselves and their patients. This is regarded as an issue of patient safety.
- Influenza occurs all year round in Malaysia with peaks in May-July and November –January. Thus, both Southern and Northern formulations are used. The rule of thumb is to use the latest formulation available.
Evidence for Effectiveness
- A systematic review and meta-analyses of 31 influenza vaccine studies, against circulating influenza viruses confirmed by RT-PCR or virus culture, found a trivalent inactivated vaccine (TIV) pooled efficacy of 59%. Evidence for protection in adults aged 65 years or older is lacking.
- A study among Malaysian pilgrims attending the Hajj in Saudi Arabia found that adjusted vaccine effectiveness against clinic visits for influenza-like illness was 77% while that of recipients of antibiotics was 66%. Pilgrims traveling for the Hajj in Saudi Arabia should consider influenza vaccination.
- Elderly subjects generally respond less effectively to standard dose influenza vaccines than young healthy adults. Those with chronic debilitating medical conditions generally do not respond as effectively as healthy subjects of similar age. Up to 50% of elderly vaccinees may fail to respond to standard doses of inactivated influenza vaccine, with a 4-fold increase in hemagglutinin inhibition (HI) antibodies.
- A study on the effectiveness of influenza vaccination among inhabitants of homes for the elderly was conducted in Malaysia. The vaccine effectiveness in reducing the occurrence of influenza-like illness ranged from 55-76% during the 6-month study follow-up. Vaccine recipients had fewer episodes of fever, cough, muscle ache, runny nose (p<0.001) and experienced fewer sick days due to respiratory illness.
- Bresee, J.S., Fry, A.M., Sambhara, S., Cox, N.J. (2018) Inactivated Influenza vaccine. In Plotkin S.A., Orenstein W.A., Paul A Offit, P.A. and Edwards K.M.(Eds). Vaccines. (7th Edition.)Saunders Elsevier.
- Centers for Disease Control and Prevention. (2015) The Pink Book: Epidemiology and Prevention of Vaccine Preventable Diseases. 13 th Edition
- Cox, M.M.J, Hashimoto, Y.(2011) A fast tract influenza vaccine virus produced in insect cells. J Inverteb Pathol, 107, Suppl, S31-41
- Hui, L.S., Rashwan, H., Jaafar, M.H., Hussaini, M.H., Isahak, I.(2008) Effectiveness of influenza vaccine in preventing influenza-like illness among Faculty of Dentistry staff and students in Universiti Kebangsaan Malaysia. Health Care Infect,13(1) 4–9
- I-Ching, S., Abdul-Murad, A., Karunakaran, R., Rampal, S., Chan, Y.F., Nathan, A.M., Ariffin, H. (2010) Clinical features of Malaysian children hospitalized with community-acquired seasonal influenza. Int J Infect Dis, 14S, 3,e36-e40
- Isahak, I., Mahayiddin, A.A., Ismail, R. (2007) Effectiveness of influenza vaccination in prevention of influenza-like illness among inhabitants of old folk homes. Southeast Asian J Trop Med Public Health. ,38(5),841-8
- Mustafa, A.N., Gessner, B.D., Ismail, R., Yusoff, A.F., Abdullah, N., Isahak, I., Abdullah, N., Merican, M.I.(2003) A case-control study of influenza vaccine effectiveness among Malaysian pilgrims attending the Haj in Saudi Arabia. Int J Infect Dis.,7(3),210-4
- National Pharmaceutical Regulatory Agency (NPRA), Ministry of Health Malaysia
- Osterholm. M,T., Kelly, N.S., Sommer, A., Belongia, E.A.(2012) Efficacy and effectiveness of influenza vaccines: a systemic review and meta-analysis. Lancet Infect,12(1),36-44
- Schultz-Cherry, S. Is it Possible? A Different Approach to Creating a Universal influenza vaccine. http://mbio.asm.org/content/6/5/e01580-15
- Senarai Produk Vaksin Berdaftar Dengan Pihak Berkuasa Kawalan Dadah. Received on 5 September 2019
- The Malaysian National Centre of Adverse Drug Reactions Database. Accessed: 10 October 2019