Flu वह सब जो आपको FLU VACCINATION in Pregnancy के बारे में पता होना चाहिए

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CME/ PROGRAM NAME 1
वह सब जो आपको
FLU
VACCINATION
in Pregnancy
क
े बारे में पता होना चाहहए
F
L
U Dr Sharda Jain

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1.Fondly known as Teacher of Teachers
2.Director Lifecare Centre & Lifecare IVF
3.Founder & Secretary general of Delhi Gynaecologist forum , a body of over 2500 members .
4.Founder & Chairperson of North India Gynaecologist forum (NIGF) , body cover 10 sates .
5.NMC / MCI : Ethical committee member ,an apex body of 14 lacs modern Medicine doctors
since 2018
6.Business World : Included her in Top 20 Most Influential women in Healthcare in INDIA
(8/03/22)
7.DMC Expert since 2009 to till date
8.Passionate medical activist..has given leadership role in removing Female Feticide ,
Movement of Anemia, Save Uterus Campaign, Save ovary Campaign and Every Mother
Counts etc.
9.Given concept of JANANI SURAKSHA YOJNA & ASHA WORKER to GOI.
10. Spearheading movement of Doctors safety /Medico legal Awareness Unity of North India
Gynaecologists
11.Decorated with many Lifetime achievement & Living Legend Award from many bodies
including LHMC AA, FOGSI ,DMA ,DGF , WOW India
Dr. Sharda Jain
M.D. (PGIMER),
MNAMS,FICOG,FIMSA,DHM, QM
&AHO
PGDMLS (SYMBIOSIS)

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CME/ PROGRAM NAME 3
INSPITE OF
RECOMMENDATIONS20%COMPL I ANCE
CDC
Centers for Disease Control and
Prevention1
ACIP
Advisory committee on
Immunization Practices1
WHO2
FOGSI3
API
The Association of Physicians of
India5
The American College of
Obstetricians and Gynecologists6
Source: 1. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6332a3.htm as accessed on 5th August 2015, at 11:47am. 2. http://www.who.int/immunization/newsroom/newsstory_seasonal_influenza_vaccination_pregnancy/en/ 3.
http://www.fogsi.org/images/stories/pdf/vaccination_women.pdf 4. http://www.nhlbi.nih.gov/files/docs/guidelines/06_sec3_comp3.pdf as accessed on 5th August 2015, at 12:05pm. 5. https://www.essentialknowledgebriefings.com/downloads/adult-immunization-
in-india-changing-the-immunization-paradigm/ 6. https://www.acog.org/~/media/Committee%20Opinions/Committee%20on%20Obstetric%20Practice/co468.pdf?dmc=1&ts=20140702T0616350498
NIH
National Heart, lung and Blood
institute4
…..Caring hearts, healing hands

4. Agenda
4
Recommendations, When & How to vaccinate?
Influenza vaccination in Pregnancy: Evidence
Influenza vaccination in Pregnancy: Rationale
Influenza burden in Pregnancy

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CME/ PROGRAM NAME 5
MAGIC OF VACCINATIONS
With the exception of clean drinking
water, vaccines are the most
effective intervention in reducing
and preventing infectious diseases
Clean Drinking Water
Vaccination
…..Caring hearts, healing hands
World Health Organisation (WHO),

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CME/ PROGRAM NAME 6
IMPACT OF
VACCINES
IN THE USA
AA
Out of these small pox has
been eradicated globally .
Polio is on the verge of
eradication from World.
COVID: Magic U have seen
…..Caring hearts, healing hands

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Enter title via "insert>header and footer>footer" | | 7
Spanish Flu
1918 FLU pandemic

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B
Infected 500 million III Deaths 100 million

9. The emergence of H1N1 has demonstrated the difficulty in predicting pandemics
 The circulation of H5N1 in poultry and its high fatality rate have raised concerns over an H5N1
pandemic if this virus acquires the capacity for sustained human-to-human transmission
…..Caring hearts, healing hands

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Influenza Burden and Epidemiology

11. Influenza Virus subtypes
11
Different influenza A subtypes result from different
combinations of the HA and NA proteins
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
 HA and NA genes can be reassorted (switched) between strains
generating novel subtypes
H1N1
H1N2
H2N1
H2N2
Orthomyxovirida
e family
A 18 HA
proteins
11 NA
proteins
B
C
H1
H2
N1
N2

12. 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/about/qa/coldflu.htm ;
https://www.cdc.gov/flu/consumer/symptoms.htm

13. Influenza: global prevalence and impact
• Influenza A and B viruses can cause seasonal influenza epidemics, as well as
out-of-season sporadic cases and outbreaks1
• Globally, about 5–10% of adults and 20–30% of children develop
influenza A or B each year1
• Worldwide, seasonal influenza epidemics are estimated to result in
approximately:
– 3 000 000–5 000 000 cases of severe illness2
– 290 000–650 000 associated respiratory deaths2,3
• Globally, influenza-associated respiratory deaths are estimated to correspond
to approximately 2% of all annual respiratory deaths4
WHO, World Health Organization
1. WHO. Wkly Epidemiol Rec 2012;87:461–76;
2. WHO. 2018. Available from: https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal) (Accessed 24 June 2020);
3. Iuliano AD, et al. Lancet 2018;391:1285–300; 4. Paget J, et al. J Glob Health 2019;9:020421

14. Influenza burden of disease is greater in low- to middle-
income countries than in high-income countries (1/3)
• A study performed by the
Global Burden of Disease 2017
Influenza Collaborators
estimated the influenza-
attributable burden of lower
respiratory tract infections
(LRTIs) for every country
globally1
– In 2017, influenza LRTI
mortality was typically higher
in low- to middle-income
countries than in high-income
countries1
Influenza LRTI mortality per 100 000 population1
ATG, Antigua and Barbuda; FSM, Federated States of Micronesia; Isl, islands; LCA, Saint Lucia; LRTI, lower respiratory tract infection;
TLS, Timor-Leste; TTO, Trinidad and Tobago; VCT, Saint Vincent and the Grenadines
1. Global Burden of Disease 2017 Influenza Collaborators. Lancet Respir Med 2019;7:69–89

15. Influenza burden of disease is greater in low- to middle-income
countries than in high-income countries (2/3)
• A study performed by the Global Burden of Disease 2017 Influenza Collaborators estimated the influenza-attributable
burden of LRTIs for every country globally1
– In 2017, influenza LRTI incidence and hospitalizations were typically higher in low- to middle-income countries
than in high-income countries1
Country Incidence (95% UI) Hospitalizations
Pakistan 1894·2 (1269·6–2681·5) 58·8 (17·6–176·5)
United Arab Emirates 595.2 (410.6–829.8) 76.6 (25.1–221.6)
Brazil 268·6 (181·4–378·6) 77·3 (31·9–180·6)
Egypt 609.5 (409.2–848.3) 101.1 (30.8–291.1)
Bahrain 692.0 (471.3–972.9) 101.2 (32.1–294.5)
Qatar 687.1 (470.4–961.9) 102.7 (32.7–298.7)
Iran 587·0 (404·4–820·9) 102·7 (35·1–280·3)
Saudi Arabia 773·8 (526·7–1086·8) 103·9 (33·6–303·0)
Vietnam 3710.5 (2537.3–5141.6) 139.9 (49.7–370.3)
Chile 768·5 (517·9–1102·3) 153·8 (60·7–377·0)
Taiwan 976.6 (681.4–1315.9) 338.8 (119.7–874.4)
Country Incidence (95% UI) Hospitalizations
Australia 125·2 (86·6–171·7) 38·3 (14·0–94·1)
USA 287·9 (201·8–391·7) 55·0 (22·5–125·4)
France 134·6 (95·1–182·0) 55·2 (20·8–133·8)
Germany 121·6 (86·5–164·9) 58·4 (23·7–134·0)
UK 222·4 (158·1–297·9) 100·7 (45·6–207·6)
Indonesia 1285.0 (876.0–1789.3) 15.7 (5.6–41.8)
Malaysia 1116.8 (752.2–1567.2) 20.2 (6.6–56.9)
Philippines 1129.6 (771.3–1561.5) 20.9 (7.3–55.9)
Thailand 1231·1 (861·4–1682·8) 28·4 (10·1–74·9)
India 1011·6 (684·4–1416·3) 42·6 (14·2–116·7)
Turkey 425.2 (296.9–578.6) 54.7 (20.7–136.6)
Colombia 539.1 (361.3–761.8) 55.0 (17.7–156.4)
Data are reported as number per 100 000 population, ordered from lowest to highest hospitalization rate,
from a selection of high-income (grey) and low- to middle-income (blue) countries
LRTI, lower respiratory tract infection; UI, uncertainty interval
1. Global Burden of Disease 2017 Influenza Collaborators. Lancet Respir Med 2019;7:69–89

16. Certain groups of people face higher risk of serious influenza
complications, hospitalization or death
AIDS, acquired immunodeficiency virus; BMI, body mass index; COPD, chronic obstructive pulmonary disease; HIV, human
immunodeficiency virus
1. World Health Organization. Wkly Epidemiol Rec 2012;87:201–16;
2. Centers for Disease Control and Prevention. 2018. Available from: https://www.cdc.gov/flu/highrisk/index.htm (Accessed 14 July 2020)
Pregnant women at any stage of
pregnancy and for up to 2 weeks after
the end of pregnancy
Children (aged < 5 years, but
especially those aged < 2 years)
Elderly (aged ≥ 65 years)
People with certain high-risk chronic
medical conditions:
Asthma, chronic obstructive pulmonary
disease (COPD), cystic fibrosis, diabetes,
heart disease, kidney, liver and metabolic
disorders,
neurological/neurodevelopmental
conditions, sickle cell disease
People living in nursing homes and
other long-term care facilities2
Healthcare workers
People who are obese (BMI ≥ 35
kg/m2)
People with a weakened immune system
• Due to disease (e.g. people with
HIV/AIDS, leukaemia)
• Due to medications (e.g. Chemotherapy
or radiotherapy, long-term
corticosteroids etc.)

17. Pregnant Women Tops
AT-RISK GROUPS

18. Factors affecting influenza infection in pregnancy
Anatomical factors:
• Respiratory function is altered due to diaphragmatic elevation from the pregnant uterus
• Changes in chest-wall dimensions and
• Increased progesterone and β-human chorionic gonadotropin levels
Physiological factors:
• Increase in maternal oxygen consumption by 15–20% and lung tidal volumes by 30–40%
• Reduced residual volume, expiratory reserve volume and functional residual capacity
Immunological factors:
• Suppressed cytotoxic T lymphocyte response
• Local and systemic immune system changes result in increased maternal susceptibility to severe
infection from influenza virus
• Increased pulmonary inflammation due to cellular immune responses  increased morbidity and
mortality
Somerville LK, Basile K, Dwyer DE, Kok J. The impact of influenza virus infection in pregnancy. Future
microbiology. 2018 Feb;13(2):263-74.

19. For internal use only, do not distribute
GLO2158985 │ OCT 2020
Burden of Influenza in Pregnancy5-20%
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
…..Caring hearts, healing hands
Source: Creanga AA, Johnson TF, Graitcer SB, et al. Severity of 2009 Pandemic
Influenza A (H1N1) Virus Infection in Pregnant Women. O
bstet Gynecol 2010;115:717-26.

20. For internal use only, do not distribute
GLO2158985 │ OCT 2020
Impact of influenza on pregnancy outcomes
Pregnancy
hospitalizations over
four influenza seasons,
Respiratory illness was
associated with
4-fold in rise in odds of preterm
delivery
2.5-fold rise in odds of fetal
distress
Influenza and Pregnancy
Source: Creanga AA, Johnson TF, Graitcer SB, et al. Severity of 2009 Pandemic Influenza A (H1N1) Virus Infection in
Pregnant Women. Obstet Gynecol 2010;115:717-26.
Still birth or
premature birth, Spontaneous
abortion1
4-fold increase in odds of
Cesarean delivery2
…..Caring hearts, healing hands

21. Pregnancy increases the risk of influenza-related
hospitalization
• A systematic review and meta-
analysis of 152 studiesa evaluated
whether pregnancy was a risk factor
for severe outcomesb following
influenza infection1
AT-RISK GROUPS PREGNANT WOMEN
Forest plot for pregnancy as a risk factor for hospitalization
following influenza1
ADVERSE OUTCOMES
aMost studies (n = 136; 95.8%) were conducted during the 2009 H1N1 influenza pandemic
bCommunity-acquired pneumonia, death from all causes or related to influenza, hospitalization from all causes or related to influenza,
admission to an intensive care unit related to influenza, and/or need for mechanical ventilatory support
CI, confidence interval; OR, odds ratio
1. Mertz D, et al. Vaccine 2017;35:521–8
– Of the 13 studies included
in the analysis of risk of
hospitalization, risk was
significantly higher for
pregnant women than for
non-pregnant individuals
(odds ratio [OR] 2.44 [95%
CI: 1.22–4.87];
I2 = 95%)1

22. Pregnancy increases the risk of respiratory-
associated hospitalization during influenza
seasons
• A Canadian study analysed 13 years of data (1990–2002) from the Nova Scotia Atlee Perinatal
Database to determine whether hospitalization rates among pregnant women with and without
comorbidities differed compared with the year before pregnancy1
• Hospital admissions due to respiratory illness during the influenza season ranged from two to eight
times higher during pregnancy, compared with the year before pregnancy1
– Rates were higher regardless of comorbidity status, but were most pronounced in women with ≥ 1 comorbidtya,1
AT-RISK GROUPS PREGNANT WOMEN
Period Women with no comorbidity Women with ≥ 1 comorbidity
Hospital
admissions
during influenza
season, n
Rate per
10 000 woman
months
Rate ratio
(95% CI)*
Hospital
admissions
during influenza
season, n
Rate per
10 000 woman
months
Rate ratio
(95% CI)*
Year before
pregnancy
49 1.4 1.0 23 5.7 1.0
Pregnancy
First trimester 22 2.4 1.7 (1.0–2.8) 17 16.3 2.9 (1.5–5.4)
Second trimester 30 3.0 2.1 (1.3–3.3) 22 19.4 3.4 (1.9–6.0)
Third trimester 76 7.4 5.1 (3.6–7.3) 49 44.9 7.9 (5.0–12.5)
ADVERSE OUTCOMES
aDefined as pre-existing diabetes, pulmonary disease (including asthma), heart disease, renal disease or anaemia (haemoglobin < 10 g/dL)
*Rate ratio of admissions during pregnancy compared with admissions in the year before pregnancy.
CI, confidence interval
1. Dodds L, et al. CMAJ 2007;176:463–8

23. Hospitalized pregnant women with influenza have
increased odds of perinatal adverse outcomes
• A US study analysing data from the Healthcare Cost and Utilization Project Nationwide Inpatient
Database determined the morbidity of influenza-related hospitalizations in pregnant women during
10 influenza seasons (1998–2008)1
AT-RISK GROUPS PREGNANT WOMEN
Outcome Respiratory illnessa
(n = 17 136)
No respiratory illnessa
(n = 1,57,22,564)
Adjusted OR
(95% CI)
Preterm birth, n (%) 4 420 (25.8) 1 140 648 (7.3) 3.82 (3.53–4.14)
Caesarean delivery, n (%) 10 185 (59.4) 4 415 731 (28.1) 3.47 (3.22–3.74)
Fetal distress, n (%) 4 700 (27.4) 2 093 426 (13.3) 2.33 (2.15–2.52)
Outcome Respiratory illness
(n = 17 468)
No respiratory illness
(n = 15 825 557)
Adjusted OR
(95% CI)
Intrauterine fetal demise, n (%) 333 (1.9) 102 993 (0.7) 2.50 (1.97–3.18)
ADVERSE OUTCOMES
aDefined using codes for pneumonia and influenza (International Classification of Diseases Clinical Modification, 9th Revision codes 480–8)
CI, confidence interval; OR, odds ratio
1. Martin A, et al. Matern Child Health J 2013;17:1325–31

24. Pregnant women are disproportionately affected by
H1N1, with increased risk of serious adverse outcomes
• A systematic review of 120 studies performed in 29 countries evaluated the effects of
the 2009 H1N1 influenza pandemic on pregnant women (N = 3110)1
– Although only approximately 1% of women in the USA and Australia are typically pregnant at any
given time, pregnant women represented 6% of individuals with serious adverse influenza
outcomes1
• 6.3% of H1N1-related hospitalizations (835/13 322)1
• 5.9% of H1N1-related intensive care unit (ICU) admissions (236/3989)1
• 5.7% of H1N1-related deaths (188/3295)1
AT-RISK GROUPS PREGNANT WOMEN ADVERSE OUTCOMES
ICU, intensive care unit
1. Mosby LG, et al. Am J Obstet Gynecol 2011;205:10–18

25. 1. Mosby LG, et al. Am J Obstet Gynecol 2011;205:10–18
2. Mertz D, et al. Vaccine 2017;35:521–8
3. Wen T, et al. Obstet Gynecol 2021;138:218–227
4. Martin A, et al. Matern Child Health J 2013;17:1325–31
Maternal and fetal effects of Influenza: recap
Increased
hospitalization1,2
Increased ICU
admissions1
Higher influenza
related
complications3
Increased mortality3
Increased preterm
birth4
Higher intrauterine
fetal demise4
Increased fetal
distress4
Maternal
complications
Fetal
complications

26. Influenza vaccination of pregnant women reduces the risk of
adverse influenza outcomes during pregnancy
• In a retrospective analysis of data from the Pregnancy Influenza Vaccine Effectiveness Network (covering healthcare
systems in Australia, Canada, Israel and the USA; 2010–2016), vaccination provided moderate, significant
protection against influenza-associated hospitalization during pregnancy, with an adjusted vaccine effectiveness
(VEa) of 40% (95% CI: 12%–59%) vs no vaccination1
• In the case–control ‘Pregnancy and Influenza Project’ study of US pregnant women (N = 492; 2010/2011 and
2011/2012), vaccination reduced the rate of influenza-associated ARI by about a half, with adjusted VEb values of
44% (95% CI: 5%–67%) vs influenza-negative women and 53% (95% CI: 24%–72%) vs ARI-negative women2
• In a prospective, blinded, controlled study of Bangladeshi pregnant women (N = 340; 2004–2005), the rate of
respiratory illness with fever was significantly lower in women who had received the influenza vaccination than in
those who had not (50 vs 77 episodes, respectively; VE of 35.8% [95% CI: 3.7%–57.2%]; p < 0.05)3
• In a Norwegian national registry study of pregnant women (N = 117 347; 2009–2010), vaccination reduced the risk of
influenza during pregnancy (adjusted hazard ratio [HR] 0.30 [95% CI: 0.25–0.34])4
AT-RISK GROUPS PREGNANT WOMEN VACCINE BENEFITS
aVE was assessed using the test-negative design, whereby VE equals (1 − odds ratio [the ratio of the odds of vaccination among
influenza-positive cases to the odds of vaccination among influenza-negative controls]) × 100% using logistic regression
bVE was estimated as (1 – odds ratio [the ratio of the odds of vaccination among cases to the odds of vaccination among controls])
× 100% using unconditional logistic regression for the influenza-negative control analyses and using conditional logistic regression for the matched ARI-negative control analyses. A 95% CI was calculated
for each estimate. It was estimated that 89 cases were needed to achieve 80% power (α = 0.05) to detect a VE of 50% with 2 controls per case and a vaccination rate of 50% among controls
ARI, acute respiratory illness; CI, confidence interval; HR, hazard ratio; VE, vaccine effectiveness
1. Thompson MG, et al. Clin Infect Dis 2019;68:1444–53; 2. Thompson MG, et al. Clin Infect Dis 2014;58:449–57;
3. Zaman K, et al. N Engl J Med 2008;359:1555–64; 4. Håberg SE, et al. N Engl J Med 2013;368:333–40

27. Influenza vaccination of pregnant women
reduces the risk of infant influenza
• A systematic review and meta-analysis of four RCTs and
three observational studies found that influenza
vaccination during pregnancy was associated with a 48%
(95% CI: 33%-59%; p-values < 0.05 were considered to be statistically
significant in the meta-analysis) reduction in the risk of infant
influenza (aged < 6 months)1
– The pooled effect of all studies included in the analysis
indicated a 48% (95% CI: 33%–59%) reduction in
laboratory-confirmed influenza among infants whose
mothers were vaccinated during pregnancy1
– No significant heterogeneity was detected among the
chosen studies (I2 = 45.3%; p = 0.09)1
• This analysis strengthens the evidence that maternal
vaccination provides passive protection against influenza
to infants during the vulnerable period before they are old
enough to receive active immunization1
AT-RISK GROUPS PREGNANT WOMEN
Forest plot of VE of influenza vaccination during
pregnancy in preventing laboratory-confirmed influenza
in infants aged < 6 months, stratified by study type1
VACCINE BENEFITS
CI, confidence interval; RCT, randomized controlled trial; RR, relative risk; VE, vaccine effectiveness
1. Nunes MC and Madhi SA. Hum Vaccin Immunother 2018;14:758–66

28. Influenza vaccination of pregnant women has a
beneficial effect on infant weight and size
• A Canadian population-based study (N = 11 293 pregnant women; 2010–2012) found that the rate of low birthweight
infants was significantly lower in vaccinated than in unvaccinated women (adjusted ORa 0.73 [95% CI: 0.56–0.95])1
• In a separate Canadian population-based study (N = 55 570 pregnant women; 2009/2010 H1N1 pandemic), infants
born to vaccinated mothers were significantly less likely to be small for gestational age than were infants born to
unvaccinated mothers, in both the 10th and 3rd growth percentiles (adjusted relative risk [RR]b 0.90 [95% CI: 0.85–
0.96] and 0.81 [95% CI: 0.72–0.92], respectively)2
• In the Bangladeshi Mother’s Gift study, which was a prospective, blinded, controlled trial (N = 340 pregnant women),
mean birthweight was significantly higher among infants whose mothers had received the influenza vaccine than in
infants of mothers who had received a control vaccine (3.178 kg vs 2.978 kg, respectively; p = 0.02)3
– The proportion of infants who were small for gestational age was also significantly lower in those born to vaccinated women
than in infants born to the control group of women (25.9% vs 44.8%, respectively; p = 0.03)3
AT-RISK GROUPS PREGNANT WOMEN VACCINE BENEFITS
aThe χ2 test was used to compare characteristics between women who received the seasonal influenza vaccine and those who did not. A backward stepwise approach was
then used to determine which maternal characteristics were significantly associated with vaccine receipt. The final model included maternal characteristics that, when
removed, caused a significant change in the likelihood ratio for the model (p < 0.05)
bThe χ2 test was used to evaluate associations between potential confounders and exposure (H1N1 vaccination). If a resultant p-value was below 0.05 (indicating an
association between the factor and exposure) and the factor was associated with a given outcome (based on the literature), it was considered a confounder of the
relationship between H1N1 vaccination and the outcome
CI, confidence interval; OR, odds ratio; RR, relative risk
1. Legge A, et al. CMAJ 2014;186:E157–64; 2. Fell DB, et al. Am J Public Health 2012;102:e33–40; 3. Steinhoff MC, et al. CMAJ 2012;184:645–53

29. Influenza vaccination of pregnant women reduces
incidence of infant influenza-associated illness
• In the Bangladeshi Mother’s Gift study,
which was a prospective, blinded,
controlled randomized trial (N = 340
pregnant women), vaccination
significantly reduced the rate of infant
respiratory illness with fever
(110 vs 153 episodes, respectively; VE
28.9%
[95% CI: 6.9–45.7]; p < 0.05)1
– Reductions in rates of respiratory illness
with fever were observed from birth to 6
months of age1
AT-RISK GROUPS PREGNANT WOMEN
Episodes of respiratory illness with fever in
infants whose mothers received influenza
vaccine, compared with control infants,
according to age1
VACCINE BENEFITS
CI, confidence interval; VE, vaccine effectiveness
1. Zaman K, et al. N Engl J Med 2008;359:1555–64

30. Influenza vaccination during pregnancy reduces
incidence of preterm birth and infant mortality
• A Canadian population-based study (N = 11 293 pregnant women; 2010–2012) found that the odds of preterm birth
(< 37 weeks’ gestation) were significantly lower for infants of vaccinated women than for infants of non-vaccinated
women (adjusted ORa 0.75 [95% CI: 0.60–0.94])1
• In a separate Canadian population-based study (N = 55 570 pregnant women; 2009/2010 H1N1 pandemic), infants of
vaccinated mothers were significantly less likely to be born preterm (< 32 weeks’ gestation) than were infants of
unvaccinated mothers (adjusted RRb 0.73 [95% CI: 0.58–0.91])2
– Fetal death (intrauterine death at ≥ 20 weeks’ gestation) was also significantly less likely in vaccinated than in unvaccinated
mothers (adjusted RR 0.66 [95% CI: 0.47–0.91])2
• An Australian population-based retrospective cohort study (N = 58 008 births; 2012/2013 season) found that
stillbirth was 51% significantly less likely in vaccinated than in unvaccinated mothers (adjusted HR 0.49 [95% CI:
0.29–0.84]; p < 0.01)3
• A US retrospective cohort study (N = 84 843 pregnant women; 2003–2008 seasons) found that vaccinated women
had a significantly lower rate of stillbirth (0.3% vs 0.6%, respectively; p = 0.006) and neonatal death (0.2% vs
0.4%, respectively; p = 0.01) than unvaccinated women4
AT-RISK GROUPS PREGNANT WOMEN VACCINE BENEFITS
aThe χ2 test was used to compare characteristics between women who received the seasonal influenza vaccine and those who did not. A backward
stepwise approach was then used to determine which maternal characteristics were significantly associated with vaccine receipt. The final model
included maternal characteristics that, when removed, caused a significant change in the likelihood ratio for the model (p < 0.05)
bThe χ2 test was used to evaluate associations between potential confounders and exposure (H1N1 vaccination). If a resultant p-value was below
0.05 (indicating an association between the factor and exposure) and the factor was associated with a given outcome (based on the literature), it
was considered a confounder of the relationship between H1N1 vaccination and the outcome
CI, confidence interval; HR, hazard ratio; OR, odds ratio; RR, relative risk
1. Legge A, et al. CMAJ 2014;186:E157–64; 2. Fell DB, et al. Am J Public Health 2012;102:e33–40;
3. Regan AK, et al. Clin Infect Dis 2016;62:1221–7; 4. Sheffield JS, et al. Obstet Gynecol 2012;120:532–7

31. Influenza vaccination during pregnancy reduces infant
healthcare resource utilization
• A systematic review and meta-analysis of four
observational studies found that maternal vaccination
was associated with a pooled VE for preventing infant
influenza-associated hospitalizations of 72%
(95% CI: 39%–87%) in infants aged < 6 months1
– The level of heterogeneity across the studies was
moderate (I2 = 58.3%; p = 0.07)1
• In the Bangladeshi Mother’s Gift study, which was a
prospective, blinded, controlled trial (N = 340
pregnant women; 2004–2005), vaccination
significantly reduced the number of febrile
respiratory illness-associated clinic visits for
infants of vaccinated vs unvaccinated mothers (54 vs
92 visits, respectively; clinical effectiveness 42.0%
[95% CI: 18.2%–58.8%])2
AT-RISK GROUPS PREGNANT WOMEN
Forest plot of VE of influenza vaccination during
pregnancy in preventing hospital admissions with
laboratory-confirmed influenza in infants aged
< 6 months1
VACCINE BENEFITS
CI, confidence interval; VE, vaccine effectiveness
1. Nunes MC and Madhi SA. Hum Vaccin Immunother 2018;14:758–66;
2. Zaman K, et al. N Engl J Med 2008;359:1555–64

32. Influenza vaccination during pregnancy
. Peppa M, et al. Clin Infect Dis 2021;73:e4296–e4304
32
A UK population-based historical cohort study of 78 150 pregnancies
showed that
seasonal influenza vaccination any time during pregnancy did not increase
the risk of major congenital malformations in offspring, particularly when
vaccinated during the first trimester2
Trimester 1 (HR 1.07 [99% CI: 0.95–1.20]; p = 0.16)2
Trimester 2 (HR 1.02 [99% CI: 0.92–1.13]; p = 0.65)2
Trimester 3 (HR 0.99 [99% CI: 0.90–1.09]; p = 0.73)2
Any trimester (HR 1.02 [99% CI: 0.94–1.09]; p = 0.56)2

33. RATIONALE FOR INFLUENZA VA CCINA TION
• Flu is more likely to cause severe illness in pregnant women
• Changes during pregnancy make pregnant women (and women who have given
birth during the past 2 weeks) more prone to severe illness from flu, including
illness resulting in hospitalization
• Vaccinating a pregnant woman also can protect a baby after birth
from flu
Source: Centers for Disease Control and Prevention, Flu Vaccine Safety and Pregnancy. Available from: https://www.cdc.gov/flu/protect/vaccine/qa_vacpregnant.htm ;
accessed on 17th April 2018.

34. WHY IS COCOONING IMPORTANT?
• Infants < 6 mths old are too young to receive influenza vaccine
• No Influenza vaccine is approved for the use in < 6 mths of age
• Unvaccinated mother & family members, are often the ones who unknowingly spread
dangerous diseases to infants
• Influenza outbreaks are unpredictable and happen every year
34
Easy & effective way that people
can adopt to prevent the spread of
whooping cough and flu to babies
Cocooning
Source: http://www.immunize.org/catg.d/p4039.pdf as accessed on 29th June 2016 at 2:31pm

35. 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
35
Outcomes in Infants
Acute
Respiratory
illness
Febrile
episode
Influenza-like
illness
Healthcare
seeking
Administratio
n of antibiotics
37.7%
Reduction
50.3%
Reduction
53.5%
Reduction
41.8%
Reduction
45.4%
Reduction

36. Influenza virus and vaccine
development journey

37. The Influenza Virus (Schematic)
37
Hemagglutinin (HA)
Neuraminidase (NA)
Ribonucleoprotein (RNP)
M2 protein
M1 protein
Lipid membrane
Components Of The Influenza Virus
Hemagglutinin (HA or H):
• Surface protein that protrudes from the
membrane (forms spikes)
• Responsible for the attachment of the virus to
a surface receptor on epithelial cells
Neuraminidase (NA or N):
• Surface protein that protrudes from the
membrane (forms spikes)
• Responsible for
o Reducing viscosity of the mucus layer in the
trachea allowing the virus to pass through and
reach the epithelial cells
o Release of new virus particles from the infected
cell

38. 38
Type of Influenza vaccines

39. Subunit vaccines are less reactogenic, with fewer
adverse reactions - Influvac Tetra is Subunit Vaccine
• Inactivated influenza antigens are available as
whole, split and subunit vaccines1
• Whole virus vaccines contain intact virus
particles1
– Highest level of reactogenicity and adverse
reactions (e.g. injection site pain)1
• Split vaccines contain fragmented virus
particles (viral proteins like matrix proteins,
lipid membrane etc., as well as surface
antigens)1
– Fewer adverse reactions than whole virus vaccines1
• Subunit vaccines contain mostly surface
antigens (e.g. HA and neuraminidase [NA])1
– Better tolerability and lower reactogenicity
than other vaccine types1,2
Structural difference in whole, split and subunit
influenza vaccine formulations1
HA, haemagglutinin; NA, neuraminidase
1. Shah R and Prabhu S. Asian J Paediatr Pract 2018;1:19–28;
2. Beyer WE, et al. Clin Drug Investig 1998;15:1–12

40. ‘Why the subunit vaccines came into existence?’
40
• What is the role of NA & HA specific antibodies?? They bind to the virus and neutralize it
so that attachment does not take place and therefore viral replication is prevented in the
host.
• What is the role of Viral Protein/Matrix Protein?? They take part in viral replication,
infection and disease propagation.
• They have no role to play in immunogenicity.
• Their presence in the vaccine leads to local and systemic reactogenicity.
• Low incidence of reactogenicity with subunit vaccine is the fallout of absence of other viral parts, which
is further established through evidences.

41. Subunit vaccines have similar immunogenicity as
split vaccines but are less reactogenic
• Subunit and split vaccines are immuno-equivalent1
• Subunit vaccines are associated with a lower frequency of local and systemic reactions than are split
and whole vaccines1
– Suggests that viral components are more abundant in split and whole vaccines than in subunit vaccines
Paper
number
Meta-
analysis
group
Subunit
vaccine
(n/N)
Split
vaccine
(n/N)
1 SR-1 0/8 2/10
2 SR-2 2/29 7/50
3 SR-3 17/33 16/34
10 SR-9 1/27 7/36
11 SR-10 9/25 13/25
12 SR-11 7/16 4/15
Reactogenicity: any local reaction1,a Reactogenicity: any systemic reaction1,a
Paper
number
Meta-
analysis
group
Subunit
vaccine
(n/N)
Split
vaccine
(n/N)
1 LR-1 5/8 7/10
3 LR-2 13/33 18/34
11 LR-8 6/25 7/25
12 LR-9 15/16 13/15
aMeta-analysis comparing subunit vaccines and either split or whole virus vaccines
CI, confidence interval; LR, local reaction; SR, systemic reaction
Source: Beyer WE, et al. Clin Drug Investig 1998;15:1–12.

42. Subunit vaccines are associated with significantly
fewer local adverse reactions than split vaccines
• Rates of local adverse reactions were significantly lower with a subunit vaccine (Influvac TIV) than
with a split vaccine (TIV)1
• Split TIV was a significant independent predictor of muscle pain and/or swelling
• In addition, use of anti-fever/pain medication was significantly lower with Influvac TIV (2%) than
with the other TIV
12
18
24
3
7 8
0
5
10
15
20
25
30
Muscle pain Swelling Muscle pain and/or swelling
Proportion
of
patients
(%)
Split TIV (n = 156)
Influvac TIV (n = 127)
Local adverse reaction1
Retrospective interviews (N = 283 adults aged ≥ 18 years)
CI, confidence interval; OR, odds ratio; TIV, trivalent influenza vaccine
Source: Leeb A, et al. Vaccine 2011;29: 7920–4.

43. Fever reaction is less frequent with subunit
vaccines than with split vaccines
• Fever reaction (≥ 37.5℃) occurred significantly more often with a split vaccine than
with a subunit vaccine1
p < 0.05
2.4
6.4
0
1
2
3
4
5
6
7
8
9
10
Subunit (n = 249) Split (n = 250)
Proportion
of
patients
(%)
Source: 1. Dong PM, et al. Zhonghua Liu Xing Bing Xue Za Zhi 2003;24:570–3
Fever reaction1

44. SAFETY OF INFLUENZA VACCINE
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.

45. TIME TO VACCINATE AND
RECOMMENDATIONS

46. Need for Latest Influenza Vaccine
46
https://www.who.int/influenza/vaccines/tropics/vaccination_formulation/en/
Continuous change of
circulating influenza viruses
leads to change of Influenza
vaccines strains
recommended annually(for
both the NH and the SH) to
closely match currently
circulating virus strains

47. GISRS: GLOBAL INFLUENZA SURVEILLANCE & RESPONSE SYSTEM
Mumbai, Pune & Kasauli
106 Member countries
136 NIC
6 WHO CCS
4 ERLS
11 H5 Ref Labs
Source: 1. WHO GISRS. Available from: https://www.who.int/influenza/gisrs_laboratory/updates/GISRS_one_pager_2018_EN.pdf?ua=1 ; accessed on 21st
Aug 2019 @ 12:20 PM. 2. WHO National Influenza Centres. Available from:
https://www.who.int/influenza/gisrs_laboratory/national_influenza_centres/list/en/index4.html ; accessed on 21st Aug 2019 @ 1:00 PM.

48. Seasonality of Flu

49. Importance of Latest Influenza Vaccine
49
https://www.who.int/influenza/vaccines/tropics/vaccination_formulation/en/
As per WHO, “the most
recent WHO influenza virus
vaccine recommendation
should be used, independent
of the hemisphere in which
the country is situated”

50. As per IAP Guidebook on
Immunization 2018–2019
“Latest available Influenza
vaccines should be offered
about 2 weeks before
beginning of the flu season.”
Importance of Latest Influenza Vaccine
50
https://iapindia.org/pdf/124587-IAP-GUIDE-BOOK-ON-IMMUNIZATION-18-19.pdf ; accessed on 28th July 2020 @ 7:20 PM.

51. Latest SH strains 2023
51
Recommended composition of influenza virus
vaccines for use in the 2023 Southern
hemisphere influenza season
• an A/Sydney/5/2021 (H1N1)pdm09-like virus;
• an A/Darwin/9/2021 (H3N2)-like virus;
• a B/Austria/1359417/2021 (B/Victoria lineage)-
like virus; and
• a B/Phuket/3073/2013 (B/Yamagata lineage)-
like virus.
Recommended composition of influenza virus
vaccines for use in the 2022-23 northern
hemisphere influenza season
https://www.who.int/publications/m/item/recommended-composition-of-influenza-virus-vaccines-for-use-
in-the-2022-southern-hemisphere-influenza-season
One major change between NH 2022-2023 and SH 2023
• an A/Victoria/2570/2019 (H1N1)pdm09-like
virus;
• an A/Darwin/9/2021 (H3N2)-like virus;
• a B/Austria/1359417/2021 (B/Victoria lineage)-
like virus; and
• a B/Phuket/3073/2013 (B/Yamagata lineage)-
like virus.

52. • CDC recommends that pregnant women get a flu
shot during any trimester of their pregnancy
to protect themselves and their newborn babies
from flu
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
Influenza Vaccine Recommendation:
Pregnancy
Source: Centers for Disease Control and Prevention, Flu Vaccine Safety and Pregnancy. Available from: https://www.cdc.gov/flu/protect/vaccine/qa_vacpregnant.htm ;
accessed on 17th April 2018. http://www.who.int/immunization/newsroom/newsstory_seasonal_influenza_vaccination_pregnancy/en/ as accessed on 06/07/2014, 4:30
pm. https://www.rcog.org.uk/en/news/flu-vaccination-in-pregnancy-protects-both-mothers-and-babies-say-doctors-and-midwives/?_sm_byp=iVVJ6F2ngqJZSHR6 , as
accessed 06/07/14. http://http://www.fogsi.org/wp-content/uploads/2015/11/vaccination_women.pdf

53. • Women who are or will be pregnant during
influenza season should receive an inactivated
influenza vaccine
ACOG
American College of
Obstetricians and
Gynecologists
• Recommended from 26 weeks onwards
FOGSI
Federation of Obstetric and
Gynecological Societies of
India
MOHFW
Ministry of Health & Family
Welfare
Influenza Vaccine Recommendation:
Pregnancy
Source: Centers for Disease Control and Prevention, Flu Vaccine Safety and Pregnancy. Available from: https://www.cdc.gov/flu/protect/vaccine/qa_vacpregnant.htm ;
accessed on 17th April 2018. http://www.who.int/immunization/newsroom/newsstory_seasonal_influenza_vaccination_pregnancy/en/ as accessed on 06/07/2014, 4:30
pm. https://www.rcog.org.uk/en/news/flu-vaccination-in-pregnancy-protects-both-mothers-and-babies-say-doctors-and-midwives/?_sm_byp=iVVJ6F2ngqJZSHR6 , as
accessed 06/07/14. http://http://www.fogsi.org/wp-content/uploads/2015/11/vaccination_women.pdf
• Vaccine is recommended for pregnant women,
irrespective of the duration of pregnancy

54. WHA T IS THE BEST VA CCINA TION STRA TEGY TO PROTECT
INFANTS <6 MONTHS?
Maternal immunity is the only effective strategy in newborns
because the vaccine is not approved for use in infants younger
than 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

55. HOW TO VACCINATE???
• Dose: 0.5 ml
• Route: Intramuscular (IM)

56. SUMMARY
• Influenza – more likely to cause severe illness in pregnant women
• Changes during pregnancy make pregnant women more prone to severe
illness from influenza
• Risk of premature labor and delivery is increased in pregnant women with
influenza
• Influenza hospitalization rates in infants <6 mths of age are up to 10 times
that of older children
• No influenza vaccines are licensed for use in children <6 mths of age
Source: http://www.cdc.gov/flu/pdf/nivw/influenza-pregnancy-letter.pdf as accessed on 02/07/2014, 4:34 pm

57. SUMMARY
• Vaccination during pregnancy has been shown to protect both the mother &
her infant (up to 6 mths of age) from - Influenza illness
- Influenza hospitalizations and
- Influenza-related preterm birth
• Influenza vaccine can be given to pregnant women in any trimester
• Postpartum women, even if they are breastfeeding, can receive flu vaccine
Source: http://www.cdc.gov/flu/pdf/nivw/influenza-pregnancy-letter.pdf as accessed on 02/07/2014, 4:34 pm

58. Proprietary and confidential — do not distribute
H3N2 cases on the rise in India
SEASONAL INFLUENZA
58
In India, influenza cases of H3N2 & H1N1 subtypes are increasing leading to increased complications/ hospitalizations1
Annual influenza vaccination is recommended by:4-9
• World Health Organization
• CDC (Centers for Disease Control & Prevention)
• Indian Academy of Pediatrics
• FOGSI (Federation of Obstetric and Gynecological Societies of India)
• RSSDI & ESI (Research Society for the Study of Diabetes in India –
Endocrine Society of India)
• Indian Chest Society
• Indian Society of Nephrology
• API (Association of Physicians of India)
Advanced generation subunit Quadrivalent Influenza vaccine:10
• Protects against both H3N2 and H1N1 influenza subtypes
• Additional step of purification leads to less impurities and
lower injection site reactions/ systemic reactions (e.g., fever,
muscle pain)
Groups at risk of severe disease/ complications:2
• Children less than 5 years of age
• Pregnant women
• Elderly > 65 years of age
• Co-morbid conditions:
Healthcare professionals (increased risk of exposure)
WHO states that vaccination is the most effective way to
prevent infection and severe outcomes caused by influenza3
o Diabetes
o Pulmonary disease (e.g.; Asthma/
COPD)
o Cardiovascular disease (e.g.,
Myocardial infarction/ Heart failure)
o Chronic Kidney Disease
o Immunosuppressive
conditions
COPD: Chronic Obstructive Pulmonary Disease

59. Proprietary and confidential — do not distribute
Pledge to Start From Today
59
Do you give Flu vaccination to
your pregnant patient?
if No

60. Proprietary and confidential — do not distribute
Pledge to take flu vaccination
8 weeks before flu season
& give it to your family
60
Do you take yearly flu vaccination
If not

61. Proprietary and confidential — do not distribute
Lifecare family strongly advocates you & your
family to take flu vaccination & share your
experience year after year
61

62. For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory
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400051
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