Flu Vaccination Dr Sharda Jain Contents What is Influenza Influenza outbreaks and pandemics Impact of Influenza Influenza vaccine: Rationale Influenza vaccine safety & effectiveness When, whom & how to vaccinate?

1. FLU
Vaccination
Dr Sharda Jain

2. CONTENT
What is Influenza
Influenza outbreaks and pandemics
Impact of Influenza
Influenza vaccine: Rationale
Influenza vaccine safety & effectiveness
When, whom & how to vaccinate?
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3. Influenza
From Italian
Influentia2
Respiratory
disease
Epidemics described by
Hippocrates 5th century BC1
Source: 1. Martin. Emerg .Inf. 2006;12:976-980. 2. Online Etymology Dictionary
1933: Discovery of
influenza virus4
1173-74
First description of
influenza epidemic in
Europe3
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4. HA, hemagglutinin; NA, neuraminidase
Influenza is a member of the Orthomyxoviridae family of viruses
 Influenza A and B cause seasonal epidemics, C mainly causes
mild respiratory illness
 Influenza A is divided into subtypes based on the HA and NA
proteins
H1N1
H1N2
H2N1
H2N2
Orthomyxovirida
e family
A 18 HA
proteins
11 NA
proteins
B
C
H1
H2
N1
N2
INFLUENZA VIRUS HAS
SEVERAL SUBTYPES!
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5. INFLUENZA INFECTION HAS A
VARIETY OF SYMPTOMS!
Clinical symptoms
Asymptomatic in 30–50% of cases
• Common symptoms include abrupt onset
of fever (38–40°C), sore throat,
unproductive cough, runny or stuffy nose,
headache, myalgia, chills, anorexia and
extreme fatigue
• Uncommon symptoms include
photophobia, abdominal pain and
diarrhea
• Illness improves in under 7 days, cough
and malaise may persist for weeks
Virus shedding
• Adults: from the day before symptoms
appear until 5 days after illness onset
• Young children: several days before
illness onset until >10 days afterwards
• Severely immunocompromised patients:
weeks to months
Symptoms associated with seasonal influenza are well defined
and can vary between individuals
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6. CLINICAL DIFFERENTIATION:
COMMON COLD & FLU
High fever lasting 3 to 4 days
Headache
Myalgia
Fatigue and weakness
Extreme exhaustion
Severe chest discomfort and cough
• Stuffy nose is common
• Sneezing is common
• Cough is generally mild to moderate
• Symptoms such as fever, headache,
aches and pains and exhaustion are rare
in those with colds
More common in influenza than
common cold
More common in common cold
than Influenza
Sources:https://www.cdc.gov/flu/consumer/symptoms.htm
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7. INFLUENZA VIRUSES ARE SPREAD BY
VIRUS-LADEN AEROSOLS!
Spread:
• Respiratory droplet transmission
• droplets only travel <1m
• By contact with surfaces
contaminated with respiratory
droplets
• By airborne transmission of
evaporated droplets that may
remain in the air for long periods
of time
Virus transmission may be slowed by social distancingCDC
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8. RESERVOIRS OF INFLUENZA VIRUSES
MIGRATING AQUATIC BIRDS
Source: http://www.aht.org.uk/cms-display/science_eqflu.html as accessed on 12 June 2014, 11:06 am IND1134295

9. INFLUENZA VIRUS:
DRIFT AND SHIFT
Shift: Reassortant;
pandemic flu
Avian flu
Source: Doherty and Turner Journal of Biology 2009 8:46 doi:10.1186/jbiol147. http://jbiol.com/content/8/5/46/figure/F1?highres=y as accessed on 12 June 2014, 11:10 am
Drift: seasonal flu
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10. HUMAN INFLUENZA: APPEARANCES
Seasonal Influenza
(A: H3N2, H1N1; B)*
Avian Influenza
(A: H7N7, H5N1….)
Pandemic Influenza
(A: H1N1, H2N2, H3N2, …..?)
Less
Severity
Higher
Frequency
Source: http://www.who.int/mediacentre/factsheets/fs211/en/ as accessed on 12 June 2014, 11:12 am
Lower
FrequencyGreater
Severity
*Type C seasonal disase is rarely reported
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11. INFLUENZA PANDEMICS & EMERGING NEW
PANDEMIC THREATS EXIST SINCE 1900!
The emergence of H1N1 has demonstrated the difficulty in predicting pandemics
Source: Nicholson KG, Wood JM, Zambon M. Lancet 2003; 362:1733-1745; WHO, Cumulative number of confirmed human cases of avian influenza A/(H5N1), available at:
http://www.who.int/csr/disease/avian_influenza/country/cases_table_2008_09_10/en/index.html (accessed 5 November 2008); CDC, Avian Influenza, available at:
http://www.cdc.gov/flu/avian/outbreak.htm as accessed 12 June 2014, 11:14 am.
Pandemic outbreaks Recent outbreaks of influenza
1918 1957 1977 2000 2008
>50
million
deaths
H1N1
1918
Spanish
1957
Asian
~2
million
deaths
H2N
2
1968
Hong
Kong
~1
million
deaths
H3N
2
<1
million
deaths
H1N1
1977
Russia
n
H9N
2
1999
Hong
Kong
2
cases
H5N1
1997
Hong
Kong
18
cases
Six
deaths
H7N7
82
cases
One
death
H5N1
2003-
2008
Global
387
cases
245
deaths
2003
Dutch
1968
H1N1
2009
Global
~30,00
0 cases
145
deaths
2009
Pandemic
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12. Sources: 1. Integrated Disease Surveillance Programme; Seasonal Influenza (H1N1)– State/UT- wise, Year- wise number of cases and deaths from 2010 to
2017. Available from http://www.idsp.nic.in/showfile.php?lid=3933 ; accessed on 28th June 2018 .
2. Integrated Disease Surveillance Programme; Seasonal Influenza (H1N1)– State/UT- wise, Year- wise number of cases and deaths from 2012 to 2019.
Available from https://ncdc.gov.in/showfile.php?lid=280 ; accessed on 20th Jan 2020
Year Cases (Lab confirmed) Deaths
2010 20604 1763
2011 603 75
2012 5044 405
2013 5253 699
2014 937 218
2015 42592 2990
2016 1786 265
2017 38811 2270
2018 15266 1113
2019 (As on 22nd Dec 2019) 28714 1216
INDIA - SEASONAL INFLUENZA
CASES - 2 0 1 0 TO 2 0 1 9

13. Recent Lab-confirmed Indian Flu Data
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14. DESCRIPTIVE STATISTICS OF
SAMPLE POPULATION
Sample population 12,825
Mean age 35.9 Years
Standard deviation 23.9
Range (Age) 8 months – 100 years
Males 6,608 (51.5%)
Time interval Apr 2014 – Dec 2017
State wise sample mix Maharashtra: 8,553 (66.7%)
Delhi: 2,192 (17.1%)
Tamilnadu: 1,169 (9.1%)
Uttar Pradesh / Uttarakhand: 558 (4.4%)
Haryana: 313 (2.4%)
Rajasthan: 40 (0.3%)
Source: Jain D, Singh M, Budhiraja S, Arora S, Tarai B and Singhal B. Influenza in India. Lab-based real world evidence insights. Data on file.
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15. Maharashtra: 8,553 (66.7%)
Delhi: 2,192 (17.1%)
Tamilnadu: 1,169 (9.1%)
Uttar Pradesh / Uttarakhand: 558 (4.4%)Haryana: 313 (2.4%)
Rajasthan: 40 (0.3%)
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16. 0-3 years
9%
3-5 years
6%
5-18 years
10%
18-30 years
14%
30-50 years
32%
50-60 years
14%
60-70 years
9%
>70 years
6%
Percentage H1N1 burden across age
0-3 years 3-5 years 5-18 years 18-30 years 30-50 years 50-60 years 60-70 years >70 years
P E R C E N T A G E D I S T R I B U T I O N O F T O T A L B U R D E N
( P O S I T I V E C A S E S ) B Y A G E C A T E G O R Y
30-50 years group (Adults) shows the highest (almost one third)
contribution of total H1N1 burden
Source: Jain D, Singh M, Budhiraja S, Arora S, Tarai B and Singhal B. Influenza in India. Lab-based real world evidence
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17. Influenza vaccines
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18. Whole virus
vaccine (1945)
Split virus vaccine
(1964)
3rd generation
1st generation
2nd generation
Subunit vaccine (1976)
1. Wood JM, Williams MJ. Textbook of Influenza 1998; pg no 317-323.
2. Shah R et al. Asian Journal of Paediatric Practice. 2018; 1(5): 19-28.
HISTORICAL DEVELOPMENT IN
INFLUENZA VACCINATION
SUV presents better tolerability and lower
reactogenicity as compared to other vaccine types
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19. Influenza:
QIV – for Whom is it Must?
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20. WHY NOT TIV?
Shasha D et al, where QIV was compared with TIV over 2 flu seasons:
• protection offered by the TIV is unsatisfactory.
• transition from the TIV to QIV should be considered, similar to the
transition from a bivalent vaccine (A/H3N2 and B) to a trivalent
vaccine (A/H1N1, A/H3N2 and B) in 1977 due to lack of cross protection
and adequate coverage by the bivalent vaccine.
• the inclusion of a fourth antigen in the vaccine is feasible and safe, and
does not reduce immunogenicity to the other antigens in the TIV, or the
overall manufacturing capacity of influenza vaccines.
Source: Shasha D et al. Quadrivalent versus trivalent influenza vaccine: clinical outcomes in two influenza seasons, historical cohort study. Clin
Microbiol Infect. 2019 May 17. pii: S1198-743X(19)30216-2.
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21. RATIONALE
FOR
QUADRIVALENT
INACTIVATED INFLUENZA
VACCINE (QIV)
Sources: 1) Beyer WEP et al. Rationale for two influenza B lineages in seasonal vaccines: A meta-regression study
on immunogenicity and controlled field trials. Vaccine. 2017 Jul 24;35(33):4167-4176. 2) Tisa V et al.
Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden. J Prev Med Hyg. 2016 Mar;
57(1): E28–E33.
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22. IMPACT OF QIV
• QIV can prevent 11.2% of all influenza B infections
which still occur with TIV, thus reducing the
influenza burden on the community.
• QIVs could reduce both direct costs in term of
medical visits, hospitalizations and antibiotic
prescriptions, and indirect costs related to working
days lost by affected people and their caregivers.
Source: Tisa V et al. Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden. J Prev Med Hyg.
2016;57(1):E28-33.
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23. DIFFERENCES IN STRAIN COMPOSITIONS
SH 2020:
 an A/Brisbane/02/2018 (H1N1)
pdm09-like virus
 an A/South Australia/34/2019
(H3N2)-like virus
 a B/Washington/02/2019-like
(B/Victoria lineage) virus
 a B/Phuket/3073/2013-like
virus (B/Yamagata/16/88
lineage)
NH 2020-21:
 an A/Guangdong-Maonan/
SWL1536/2019 (H1N1) pdm09-like
virus
 an A/Hong Kong/2671/2019 (H3N2)-
like virus
 a B/Washington/02/2019 (B/Victoria
lineage)-like virus
 a B/Phuket/3073/2013 (B/Yamagata
lineage)-like virus
Source: 1) WHO Recommended composition of influenza virus vaccines for use in the 2020 southern hemisphere influenza season. Available from:
https://www.who.int/influenza/vaccines/virus/recommendations/2020_south/en/ ; accessed on 11th August 2020 @ 11:30 AM. 2) WHO
Recommended composition of influenza virus vaccines for use in the 2020 - 2021 northern hemisphere influenza season. Available from:
https://www.who.int/influenza/vaccines/virus/recommendations/2020-21_north/en/ ; ; accessed on 11th August 2020 @ 11:30 AM.

24. High Risk
Groups
Pregnant
women/women
trying to
conceive
Children
(6 mths - 5 yrs
old)
Elderly
(≥65 yrs)
Health-care
workers
Individuals with
chronic medical
conditions
Source: http://www.cdc.gov/flu/about/disease/high_risk.htm as accessed on 02/07/2014 12:30 pm
HIGH RISK GROUPS

25. 26
INFLUENZA: PREGNANT WOMEN
Burden
• Pregnant women are at particular risk of severe
complications and death from influenza
• And the risk is exacerbated by co-morbidities such as
asthma, diabetes mellitus, and obesity, and late
trimester pregnancy.
• May also lead to complications such as stillbirth,
neonatal death, pre-term delivery, and decreased birth
weight.
SAGE Working Group. Background paper on influenza vaccines and immunization. 2012. Mosby LG. et al. 2009 pandemic influenza A (H1N1) in pregnancy: a systematic
review of the literature. Am J Obstet Gynecol. 2011; 205:10–18. CDC. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on
Immunization Practices (ACIP), 2010. MMWR 2010;59(RR-8):1-62. Omer SB. et al. Maternal influenza immunization and reduced likelihood of prematurity and small for
gestational age births: a retrospective cohort study. PLoS Medicine 2011;8:e1000441.
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26. 27
INFLUENZA: PREGNANT WOMEN
Benefits
• Maternal immunization against influenza not only
protects the women but also prevents negative effects
on fetal development due to maternal influenza
infections and reduces rates of illness in infants for at
least the first 6 months of life.
• Inactivated vaccines have been shown to be safe and
effective in pregnant women and their offspring when
given at any trimester.
SAGE Working Group. Background paper on influenza vaccines and immunization. 2012.
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27. 28
INFLUENZA: HEALTH CARE WORKERS
Burden:
• Health care workers are additional risk of being exposed to influenza
compared to the general population.
• They risk passing on influenza to patients who are at increased risk of severe
disease and may respond less well to vaccine.
• Transmission of influenza from HCW to patients was given as a principle
source of infection for patients in a review of nosocomial influenza infection.
• Last, staff absences due to influenza can impact and disrupt health services.
• Vaccination rates of HCW remain low in many countries.
• A review on health care workers attitudes to influenza vaccination found lack
of knowledge and lack of convenient access to the vaccine as the main
reasons for lack of vaccine uptake.
SAGE Working Group. Background paper on influenza vaccines and immunization. 2012. Kuster SP. et al. Incidence of influenza in healthy adults and healthcare workers: a
systematic review and meta-analysis. PLoS One 2011 6:e26239. Hollmeyer HG. et al. Influenza vaccination in health care workers in hospitals – a review of studies on
attitudes and predictors. Vaccine 2009 27:3935-44.
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28. 29
INFLUENZA: HEALTH CARE WORKERS
Benefits
• Vaccination not only protects health care workers and it
also protects vulnerable patients.
• It also may reduce work absenteeism and consequent
disruption to health services.
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29. BURDEN OF INFLUENZA IN PREGNANCY
31
Disease burden of influenza among pregnant women is significant, particularly in low-
resource environments/developing countries1
4.3% of deaths due to the 2009 pandemic were of pregnant women (previously
healthy prior to onset of the disease)2
Up to 18-fold increase in likelihood of hospitalization due to RI during flu season
among pregnant women (vs year preceding pregnancy)3
Source: 1. Mulholland EK et al. Etiology of serious infections in young Gambian infants. The Pediatric Infectious Disease Journal 1999;18(October (10 Suppl.)):S35–41. 2.
Creanga AA, Johnson TF, Graitcer SB, Hartman LK, Al-Samarrai T, Schwarz AG, et al. Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women.
Obstetrics and Gynecology 2010;115 (April (4)):717–26. 3. Mark H Yudin. Risk management of seasonal influenza during pregnancy: current perspectives. Int J Womens
Health. 2014; 6: 681–689.

30. IMPACT OF INFLUENZA ON PREGNANCY
OUTCOMES
34
Influenza during pregnancy
Spontaneous abortion1 Still birth or
premature birth1
4-fold increase in odds of
Cesarean delivery2
Women who delivered preterm were more likely to be infected by flu virus during 3rd trimester, to
have a secondary pneumonia and to have been admitted to an ICU2
Source: 1. Pierce M, Kurinczuk JJ, Spark P, Brocklehurst P, Knight M. Perinatal outcomes after maternal 2009/ H1N1 infection: national cohort study. BMJ 2011; 342:d3214; 2.
Cox S, Posner SF, McPheeters M, Jamieson DJ, Kourtis AP, Meikle S. Hospitalizations with respiratory illness among pregnant women during influenza season. Obstet Gynecol
2006; 107:1315-22;

31. RISK OF INFLUENZA INFECTION IN INFANTS
Infants & young
children (particularly <
6 mths of age) have the
highest rate of influenza
infection &
hospitalization rates
amongst the pediatric
population
Factors involved
include
Immaturity of the
infant’s immune
system
Absence of prior
immunity/exposur
e to the virus
Increased
vulnerability to
cardiorespiratory
conditions
Source: Blanchard-Rohner and Siegrist. Vaccination during pregnancy to protect infants against influenza: Why and why not? Vaccine 2011. 29: 7542–7550.

32. Source: 1. Poehling KA, Edwards KM, Weinberg GA, Szilagyi P, Staat MA, Iwane MK, et al. The underrecognized burden of influenza in young children. The New England
Journal of Medicine 2006;355(July (1)):31–40.) 2. Bhat N, Wright JG, Broder KR, Murray EL, Greenberg ME, Glover MJ, et al. Influenza-associated deaths among children in the
United States, 2003–2004. The New England Journal of Medicine 2005;353(December (24)):2559–67. 3. Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect
of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 2000; 342:225-31.
IMPACT OF INFLUENZA IN YOUNG
INFANTS
36
Population-based surveillance study
found hospital admission rates for
laboratory-confirmed influenza
US National Assessment of pediatric
mortality associated with lab-confirmed
influenza in 4 flu season
0-5 mths of age = 4.5/1000 children
6-23 mth of age = 0.9/1000 children1
Highest in children <6 mths of
age2

33. • Reduces number of influenza-related hospitalizations & deaths
• Vaccination of pregnant women reduces the burden of influenza in
children <6 mths old in 2 ways:
• Reduce the risk of being infected after delivery, thus also reducing the risk
of transmission to the child during the 1st mths of life
• Transmission of influenza antibodies from the mother to the child
RATIONALE FOR INFLUENZA VACCINATION
Because both the use of antiviral therapy as well as influenza
vaccine are not indicated for use in children < 6 mths, there is lack
of alternatives to protect these children against influenza
Source: http://ecdc.europa.eu/en/publications/Publications/Seasonal%20influenza%20vaccination%20of%20children%20and%20pregnant%20women.pdf as accessed on
12th December 2015, at 2:28pm

34. Source: Maltezou HC1 et al. Impact of postpartum influenza vaccination of mothers and household contacts in preventing febrile episodes,influenza-like illness, healthcare
seeking, and administration of antibiotics in young infants during the 2012-2013 influenza season. Clin Infect Dis. 2013 Dec;57(11):1520-6.
POST-PARTUM INFLUENZA
VACCINATION OUTCOMES: IN INFANTS
38
Outcomes in Infants
Acute Respiratory
illness Febrile episode
Influenza-like
illness
Healthcare seeking
Administration of
antibiotics
37.7%
Reduction
50.3%
Reduction
53.5%
Reduction
41.8%
Reduction
45.4%
Reduction

35. SAFETY
OF INFLUENZA VACCINE
39
Conclusions: Results do not indicate that
maternal influenza vaccination is associated
with an increased risk of fetal death,
spontaneous abortion, or congenital
malformations.2
Excellent and robust safety profile of multiple inactivated
influenza vaccine preparations over many decades, and the potential
complications of influenza disease during pregnancy, support WHO
recommendations that pregnant women should be vaccinated.1
This systematic review did not indicate an increased risk
for congenital anomalies after maternal influenza
immunization consolidating the safety of influenza
vaccination in pregnancy.3
Source: 1. http://www.who.int/vaccine_safety/publications/safety_pregnancy_nov2014.pdf. 2. McMillan M, Porritt K, Kralik D, Costi L, Marshall H.
Influenza vaccination during pregnancy: a systematic review of fetal death, spontaneous abortion, andcongenital malformation safety outcomes. Vaccine. 2015 Apr
27;33(18):2108-17. 3. Polyzos KA1, Konstantelias AA, Pitsa CE, Falagas ME. Maternal Influenza Vaccination and Risk for Congenital Malformations: A Systematic Review and
Meta-analysis. Obstet Gynecol. 2015 Nov;126(5):1075-84.

36. HOW TO VACCINATE ?

37. • All persons 6 mths & older should be vaccinated
annually
CDC
Centers for Disease Control and
Prevention
• All women who are pregnant during influenza season
receive inactivated influenza vaccine
ACIP
Advisory committee on
immunization practices
• Recommends seasonal influenza vaccination to
pregnant women as the highest priority
WHO
World Health Organization
• Recommends all women who are pregnant during
influenza season receive inactivated influenza vaccine
ACOG
The American College of
Obstetricians and Gynecologists
• Recommended from 26 weeks onwardsFOGSI
INFLUENZA VACCINE RECOMMENDATION:
PREGNANCY
Source: http://www.who.int/immunization/newsroom/newsstory_seasonal_influenza_vaccination_pregnancy/en/ as accessed on 06/07/2014, 4:30 pm.
https://www.acog.org/~/media/Committee%20Opinions/Committee%20on%20Obstetric%20Practice/co468.pdf?dmc=1&ts=20140702T0616350498, as accessed
06/07/14. http://www.fogsi.org/images/stories/pdf/vaccination_women.pdf

38. Maternal immunity is the only effective strategy in newborns
because the vaccine is not approved for use in infants younger
than 6 months
WHAT IS THE BEST VACCINATION
STRATEGY TO PROTECT INFANTS
<6 MONTHS?
Source: http://www.ecdc.europa.eu/en/publications/publications/seasonal%20influenza%20vaccination%20of%20children%20and%20pregnant%20women.pdf as
accessed on 02/07/2014, 3:30 pm
Protecting the mother and her unborn
child from serious illness by vaccinating
pregnant women

39. Source: http://gamapserver.who.int/mapLibrary/Files/Maps/GISRS_20130425_1.png as accessed on 11 June 2014, 5:51 pm
106 Member countries
136 NIC
6 WHO CCS
4 ERLS
11 H5 Ref Labs
GLOBAL SURVEILLANCE
NETWORK: WHO
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40. SEASONALITY OF FLU
• India has distinct seasonality
• Rainfall correlates with influenza peaks in many of the cities
• Recent surveillance data from tropical regions of Asia have
revealed a seasonal pattern characterized by year round low-
level influenza virus circulation with peaks occurring
during the monsoon (rainy) season
Source: 1) Chadha MS et al. Dynamics of influenza seasonality at sub-regional levels in India and implications for vaccination timing. PLoS One. 2015 May
4;10(5):e0124122. 2) Saha S et al. Divergent seasonal patterns of influenza types A and B across latitude gradient in Tropical Asia. Influenza Other Respir Viruses. 2016
May;10(3):176-84.
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41. LIMITED INFLUENZA ACTIVITY IS
USUALLY SEEN THROUGHOUT THE
YEAR
• Limited influenza activity is usually seen throughout the
year in India with a clear peaking during the rainy
season.
• The rainy season in the country lasts from June to
August in all the regions except Tamil Nadu where it
occurs from October to December.
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42. THANK YOU