Importance of vaccination in preventing diseases like pneumonia, influenza, and other Pulmonary infections. For more information, please contact us: 9779030507.

1. Adult vaccines for prevention of
pulmonary infections
Dr. Aditya Jindal
Interventional Pulmonologist & Intensivist
Jindal Clinics
SCO 21, Sec 20D, Chandigarh
DM Pulmonary and Critical Care Medicine (PGI Chandigarh),
FCCP

2. Introduction
 Pneumococcal disease
 Influenza (flu)
 Haemophilus influenzae type b (Hib)
 Measles
 Pertussis (whooping cough)
 Varicella (chickenpox)

3. Pneumococcal disease and vaccination
• Pneumococcal disease
‒ Streptococcus pneumoniae or pneumococcus
‒ Gram positive cocci
‒ Polysaccharide capsule
‒ >90 serotypes known
• The most important pathogen in CAP
• Incidence 12% - 68% (35%)
“the old man’s friend and children’s foe”
• Pneumococcal Disease in Older Adults-An Overview. Ramasubramanian V. JAPI 2015.
Classification of pneumococcal disease
Pneumococcal infection in adults: burden of disease. Drijkoningen J J C, Rohde G G U.
Clin Microbiol Infect 2014; 20 (Suppl. 5): 45–51

4.  Incidence rates CAP
‒ 1.6 – 11.6 per 1000
 Mortality rates
‒ Latin America (13.3%)
‒ Europe (9.1%)
‒ North America (7.3%)
 Invasive pneumococcal disease(IPD)
‒ Infection confirmed by the isolation of S.
pneumoniae from a normally sterile site,
such as blood or cerebrospinal fluid
 peumococcal meningitis,
 bacteraemic pneumococcal pneumonia
 pneumococcal bacteraemia without a primary
focus
 Incidence rates
‒ Europe 11 to 27 per 100 000
‒ North America  15 to 49 per 100 000
‒ Taiwan  upto 216 cases per 100 000
 Case mortality rates
‒ Western countries 11 – 30%
‒ Asia 26 – 30%
o Pneumococcal infection in adults: burden of disease.
Drijkoningen J J C, Rohde G G U. Clin Microbiol Infect
2014; 20 (Suppl. 5): 45–51
o Invasive pneumococcal disease associated with high
case fatality in India. Thomas K, Mukkai Kesavan L,
Veeraraghavan B et al. J Clin Epidemiol 2013;66:36–
43.
o Torres et al.Pneumococcal vaccination: what have we
learnt so far and what can we expect in the future?Eur
J Clin Microbiol Infect Dis (2015) 34:19–31

5. Risk factors for pneumococcal
disease
Torres et al. Pneumococcal vaccination: what have we learnt so far and what can we expect in the future?
Eur J Clin Microbiol Infect Dis (2015) 34:19–31

6. History of pneumococcal vaccination
 1911  first whole cell vaccine trial involving miners in South Africa
 1930s  capular material identified as immuninising substance; capsular
polysaccharide isolated by Fenton
 1937  Smillie et al use Fenton’s extract to make a vaccine
 World war II  vaccine with 4 serotypes prepared
 1940s onwards  discovery of penicillin leads to reduced interest in vaccination
 1960s onwards  renewed interest in vaccination

7.  1983  PPSV23, 23-valent vaccine licensed
 2000  PCV7 approved in children
 December 30, 2011 PCV13 approved by US-FDA for prevention of
pneumonia and IPD caused by PCV13 serotypes among adults ≥ 50 yrs
 June 20, 2012  PCV13 recommended by ACIP for routine use amomg
adults aged ≥ 19 years with immunocompromising conditions, functional
or anatomic asplenia, cerebrospinal fluid leak, or cochlear implants
 August 13, 2014  Routine use of PCV13 recommended by ACIP among
adults aged ≥ 65 years
• How Effective is Vaccination in Preventing Pneumococcal Disease? Musher D M.
Infect Dis Clin N Am 27 (2013) 229–241

8. Types of vaccine
 PPV23 (Pneumococcal polysaccharide vaccine)consists of capsular
material from 23 pneumococcal types that have historically caused about
75% to 85% of pneumococcal disease in children or adults
 PCV13 (Protein-conjugate pneumococcal vaccine)  contains capsular
polysaccharides from the 13 most common types that cause disease in
children covalently linked to a nontoxic protein that is nearly identical to
diphtheria toxin.
‒ Many of the types covered by PCV13 are also common causes of adult
infections

9. PPV23 (Pneumococcal polysaccharide vaccine)
 Contains capsular material from types that cause about 80% of all
pneumococcal disease
‒ Pneumococcal serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14,
15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F
 Induce type-specific IgM antibodies (by a T cell-independent mechanism)
that enhance opsonization, phagocytosis, and killing of pneumococci
 Antibody response is generally achieved (twofold or greater rise in serotype-
specific antibody within 2–3 weeks after vaccination) among
immunocompetent adults
• How Effective is Vaccination in Preventing Pneumococcal Disease? Musher DM. Infect
Dis Clin N Am 27 (2013) 229–241
• Vaccines for the Prevention of Pneumococcal Disease. Sharma OP, Sharma M. JAPI

10.  Cochrane review
‒ 18 RCTs (64,901 participants) and 7 non-RCTs (62,294 participants)
‒ Strong evidence of efficacy against IPD (OR 0.26, 95% CI 0.14 to 0.45)
‒ Low efficacy against all cause pneumonia
‒ Not associated with reduction in all cause mortality
‒ Efficacy poorer against adults with chronic illnesses
• Moberley S, Holden J, Tatham DP, Andrews RM. Vaccines for preventing pneumococcal
infection in adults. Cochrane Database of Systematic Reviews 2013, Issue 1
 Problems:
‒ Inconsistent response
 Children less than 2 years
 Immunodeficiency
 High-risk individuals  cirrhosis, chronic pulmonary diseases, diabetes mellitus, chronic
nephropathy
‒ No reduction in mucosal carriage
‒ No herd immunity
‒ No anamnestic effect
‒ Hyporesponsiveness

11. PCV13 (Protein-conjugate pneumococcal vaccine)
 Conjugate between an antigenic protein and a polysaccharide
 Induces a T cell-dependent response and thus making it capable of
stimulating antibody responses and priming for a memory response on
rechallenge
 Composition:
‒ pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F
‒ nontoxic diphtheria toxin cross-reactive material 197 protein

12. Pneumococcal vaccination: what have we
learnt so far and what can we expect in
the future? Torres et al. Eur J Clin
Microbiol Infect Dis (2015) 34:19–31
Immune response to
polysaccharide and
conjugate
vaccines

13. Key differences between
PPV23 and PCV13

14. Infections due to serotypes of pneumococcus
included in PCV7 between 1998 and 2007
occurring in
(A)children younger than 5 years
(B)adults older than 65 years
How Effective is Vaccination in Preventing Pneumococcal
Disease? Musher DM. Infect Dis Clin N Am 27 (2013) 229–241

15. Polysaccharide Conjugate Vaccine against
Pneumococcal Pneumonia in Adults (CAPITA
study - Community-Acquired Pneumonia
Immunization Trial in Adults)
 A randomized, double-blind, placebo-
controlled trial involving 84,496 adults ≥ 65
years
 Efficacy of PCV13 in preventing
‒ first episodes of vaccine-type strains of
pneumococcal CAP
‒ nonbacteremic and noninvasive pneumococcal
CAP
‒ IPD

16.  CAP occurred in 49 persons in the PCV13 group and 90 persons in the
placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8
to 62.5)
 Nonbacteremic and noninvasive CAP occurred in 33 persons in the PCV13
group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2%
CI, 14.2 to 65.3)
 IPD occurred in 7 persons in the PCV13 group and 28 persons in the
placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8)

17.  Efficacy persisted throughout the trial (mean follow-up, 3.97 years)

18. Current guidelines (ACIP)
 Both PCV13 and PPSV23 should be administered routinely in series to all
adults aged ≥ 65 years
 All adults aged ≥ 65 years who have not previously received pneumococcal
vaccine or whose previous vaccination history is unknown should receive a
dose of PCV13 first, followed by a dose of PPSV23
 Persons aged ≥ 19 years who are at high risk for pneumococcal disease
because of underlying medical conditions
• Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal
Polysaccharide Vaccine Among Adults Aged ≥65 Years: Recommendations of the Advisory
Committee on Immunization Practices (ACIP). Tomczyk S. MMWR. September 19, 2014.

19. Medical conditions or other indications for administration of PCV13 and PPSV23
for adults

20. Intervals Between PCV13 and PPSV23 Vaccines:
Recommendations of the Advisory Committee on Immunization
Practices (ACIP). Kobayashi M et al. MMWR. September 4, 2015

21. Influenza disease and vaccination
 Every year (worldwide)
‒ 5–15 % population is affected with influenza
‒ 3 to 5 million  severe illness
‒ 250,000 to 500,000  deaths
• http://www.who.int/mediacentre/factsheets/fs211/en/
 Seasonal/ pandemic/ variants or zoonotic
‒ temperate climates  winter
‒ tropical regions epidemics can occur throughout the year
 Three types  A, B and C
‒ A (subtypes) based on hemagglutinin (HA) and neuraminidase (NA) surface
antigens
‒ B (lineages)  Yamagata and Victoria
 Antigenic drift and shifts

22.  ‘Spanish Flu’ in 1918 – 1919 caused 20 – 50 million deaths worldwide
 1% - 2.5% of total world population
 7% of the population of parts of India
• Murray CJ, Lopez AD, Chin B, Feehan D, Hill KH. Estimation of potential global
pandemic influenza mortality on the basis of vital registry data from the 1918–20
pandemic: a quantitative analysis. Lancet 2006; 368:2211–2218
• Understanding influenza transmission, immunity and pandemic threats. Matthews et al.
Influenza Other Respir Viruses. 2009
 Important cause of excess mortality and morbidity in COPD
• Poole P, Chacko EE, Wood-Baker R, Cates CJ. Influenza vaccine for patients with
chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews
2006, Issue 1.
 ILIs  acute exacerbations of asthma in as many as half of adult subjects
presenting to emergency rooms
• Pesek R, Lockey R. Vaccination of adults with asthma and COPD. Allergy 2011

23. Influenza vaccines
 Combination of three or four subtypes/ lineages
‒ Two A strains and 1/2 B lineages
 Types
‒ Inactivated – trivalent/ quadrivalent; standard/ high dose; adjuvanted; cell
culture based
‒ Live attenuated
‒ Recombinant
 Given annually before the start of the influenza season

24.  Vaccine strains are recommended by WHO based on Global Influenza
Surveillance and Response System (GISRS)
 Announced 6 – 8 m in advance
 Northern hemisphere strains are announced in February (Oct – Mar)
 Southern hemisphere strains in September (Apr – June)
 India  both may be needed based on latitude, local micro-environment and
other factors
• Chadha MS et al. (2015) Dynamics of Influenza Seasonality at Sub-Regional Levels in India and Implications for
Vaccination Timing. PLoS ONE
• Influenza Seasonality by Latitude, India. Koul et al. Emerging Infectious Diseases. October 2014

25.  India
‒ Laboratory-based surveillance network established by the Indian Council of
Medical Research in 2004
‒ 7 sites
‒ Two seasons  monsoons and winters
• Chadha et al. (2012) Multi site Virological Influenza
Surveillance in India: 2004–2008. Influenza and
Other Respiratory Viruses
• Chadha MS et al. (2015) Dynamics of Influenza
Seasonality at Sub-Regional Levels in India and
Implications for Vaccination Timing. PLoS ONE
Influenza Seasonality by Latitude, India. Koul et
al. Emerging Infectious Diseases. October 2014
Srinagar
New Delhi

26. Influenza activity in referred
clinical samples 2015-16
http://niv.co.in/annual_reports/Annual_Report_15_16/Influenza.
pdf

27.  For 2017 – 2018 northern hemisphere influenza season (December 2017 – March 2018)
‒ Trivalent vaccines
 A/Michigan/45/2015 (H1N1)pdm09-like virus;
 A/Hong Kong/4801/2014 (H3N2)-like virus; and
 B/Brisbane/60/2008-like virus.
‒ Quadrivalent vaccines
 The above three viruses and
 B/Phuket/3073/2013-like virus.
 For 2018 Southern hemisphere season (Mar 2018- Oct 2018)
‒ Trivalent vaccines
 A/Michigan/45/2015 (H1N1)pdm09-like virus;
 A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus; and
 B/Phuket/3073/2013-like virus
‒ Quadrivalent vaccines
 The above three viruses and
 B/Brisbane/60/2008-like virus.
• Recommended composition of influenza virus vaccines for use in the 2016-2017 northern hemisphere influenza season.
http://www.who.int/influenza/vaccines/virus/recommendations/2016_17_north/en/
• http://www.who.int/influenza/vaccines/virus/recommendations/2017_south/en/
• Seasonal Influenza: Guidelines for Vaccination with Influenza Vaccine. Ministry of Health and Family Welfare. October 2016.
http://mohfw.gov.in/showfile.php?lid=3629

28.  Pooled efficacy against RT-PCR or culture-confirmed influenza of 59% (95%
CI = 51–67) among healthy adults aged 18–65 years
• Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of
influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012
 Immune responses reduced among healthy adults > 65 years
 Might reduce the frequency of secondary complications and risk for
influenza-related hospitalization and death among community-dwelling
adults aged ≥65 years
• Prevention and Control of Seasonal Influenza with Vaccines Recommendations of the
Advisory Committee on Immunization Practices — United States, 2016–17 Influenza
Season. Grohskopf et al. MMWR; August 26, 2016

29. Author Type of study Recommendations
Poole P, Chacko EE,
Wood-Baker R,
Cates CJ.
2006; (updated till
2010)1
Cochrane meta-
analysis
Included 11 trials. Inactivated vaccine resulted in a significant
reduction in the total number of exacerbations. There was a mild
increase in transient local adverse effects with vaccination, but
no evidence of an increase in early exacerbations.
Sehatzadeh S.
20122
Meta-analysis Vaccination associated with significantly fewer episodes of
influenza-related acute respiratory illness; the incidence density
of influenza-related ARIs was significantly reduced in the severe
COPD group but the difference was not significant in the mild
and moderate subgroups. Also, there was a non significant
decrease in the risk if hospitalization and mechanical ventilation.
Influenza vaccination in COPD
Poole P, Chacko EE, Wood-Baker R, Cates CJ. Influenza vaccine for patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006,
Issue 1.
Sehatzadeh S. Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Review. Ontario health
technology assessment series 2012;12:1-64.

30.  Asthma
‒ Evidence is less clear
‒ Main evidence from children where vaccine efficacy varies from 50 – 80 %
‒ Cochrane review  did not demonstrate any benefits or risks
 Cates CJ, Rowe BH. Vaccines for preventing influenza in people with asthma. Cochrane
Database of Systematic Reviews 2013
 Pesek R, Lockey R. Vaccination of adults with asthma and COPD. Allergy 2011

31. “Influenza & Pneumococcal vaccine is likely to
be beneficial in patients with severe COPD & or
recurrent exacerbations”
Lung India; Sept 2013.
ICS/NCCP Guidelines for vaccination in COPD patients

32. “Influenza vaccination recommended in all
patients.
PCV-13 and PPSV23 recommended for all
patients >65 years and for select younger
patients with chronic heart and lung
comorbidities.
Global strategy for the diagnosis, management, and
Prevention of chronic obstructive pulmonary disease
(updated 2017)
GOLD Guidelines for vaccination in COPD patients

33. Government of India recommendations
 Health Care workers, working in hospital / institutional settings (doctors, nurses,
paramedics) with likelihood of exposure to Influenza virus should be vaccinated.
This includes those:
‒ All medical and paramedical personnel working in casualty/ emergency department of identified
hospitals treating Influenza cases.
‒ All medical and paramedical personnel working in ICU and Isolation Wards managing influenza
patients.
‒ All personnel identified to work in screening centres that would be set up for categorization of
patients during Seasonal Influenza outbreak.
‒ Treating/managing the High Risk Group.
‒ Laboratory personnel working in virological laboratories testing suspected Influenza samples.
‒ Rapid Response Team members identified to investigate outbreaks of Influenza.
‒ Drivers and staff of vehicles/ambulances involved in transfer of Influenza patients.

34.  Pregnant women, irrespective of the duration of pregnancy.
 Persons with chronic illnesses such as COPD, Bronchial Asthma, Heart disease,
Liver disease, Kidney disease, Blood disorders, Diabetes, Cancer and for those
who are immunocompromised.
 For children having chronic diseases like Asthma; Neuro developmental condition
like cerebral palsy, epilepsy stroke, mentally challenged etc; heart disease; blood
disorders like Sickle cell disease; DM, metabolic disorder, all immunocompromised
children, malignancy receiving immuno-suppressive therapy, kidney disorder and
liver disorder.
 Vaccine is desirable for
‒ Elderly individuals (≥ 65 years of age)
‒ Children between 6 months to 8 years of age
• Seasonal Influenza: Guidelines for Vaccination with Influenza Vaccine. Ministry of Health
and Family Welfare. October 2016. http://mohfw.gov.in/showfile.php?lid=3629

35. Summary
1. Vaccination is the way forward
2. Search for better and more effective vaccines continues
3. Influenza and pneumococcal vaccination should be recommended for all
high risk individuals
4. Routine vaccination in healthy adults, though desirable, requires further
scrutiny