1. Vaccines For Older Person
Dr Chua Hock Hin
MD, MRCP
Infectious Disease Physician
Sarawak General Hospital

2. Outline Of This Talk
1. What is the aim of vaccination in elderly patients ?
2. What is the burden of disease in elderly patients?
3. Immuno-senescence : How it impacts on the elderly ?
4. Few common VPDs.

4. Aim of Vaccination Death Well Managing Well Very Fit
Promoting Independence and Preventing Disability
Death

5. Aim of Vaccination Death
Promoting Independence and Preventing Disability
Death

6. Background : The collaborators estimated the incidence, prevalence, and years lived with
disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
Findings : A total of 9·3 billion estimates were generated from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year.
Interpretation : Ageing of the world’s population is increasing the number of people living with sequelae of diseases and injuries.
People aged 60 and older represent over 11% of the world population and it is expected to rise 22%by 2050.

7. Disorders of less than 3 months duration and injuries with incidence of more than 1 million cases per year in
2015 are listed in table 1.

9. Immunosenescence
Immunose-nescence refers to the decline of the immune system associated to aging.
The effects of ageing on the immune system are manifest at multiple levels that include reduced production of B and T cells in bone marrow and thymus and diminished function of mature lymphocytes in secondary lymphoid tissues.
It affects both innate and adaptive immunity, limiting the response to pathogens and to vaccines.
Population aging is associated to an increased frequency of age-related diseases including higher susceptibility to infections, cancer, cardiovascular and neurodegenerative diseases.
Pera A, et al. Immunosenescence: Implications for response to infection and vaccination in older people. Maturitas (2015),
Encarnacion Montecino-Rodriguez, Beata Berent-Maoz and Kenneth Dorshkind J Clin Invest. 2013;123(3):958–965.

10. Immuno-senescence
Recent work has shown that despite a lack of naïve CD8+ T cell numbers in the elderly, the functionality of CD8+ T cells during acute and chronic viral infections does not correlate with age.As such,CD8+T cell-mediated responses appear to remain intact even in individuals as old as 85

11. Herpes Zoster Or Shingles

12. Herpes Zoster Or Shingles
Is caused by varicella zoster virus ( VZV ).
Pathogenesis :
VZV migrates from skin lesions via nerve axons and viremic spread to spinal and cranial sensory ganglia where it becomes dormant.
Later in life, VZV is reactivated ( usually within single ganglion ) to cause shingles or herpes zoster ( HZ ).
Individuals with HZ can transmit VZV to their contacts, who may develop varicella.
Household transmission rate of HZ is around 15%.

13. Majority of HZ cases in those ≥ 50 years of age.
BMJ Open 2014;4:e004833

14. Incidence of HZ
The lifetime risk of developing HZ is between 25% and 30%, rising to 50% in those aged at least 80 years old. Studahl et al. 2013; Yawn and Gilden, 2013; Chen et al. 2014a.
The estimated average overall incidence of HZ is about 3.4–4.82 per 1000 person years which increases to more than 11 per 1000 person years in those aged at least 80 years old.
HZ-associated mortality is rare, with reported incidence ranging from 0 to 0.47 per 100,000 person year. Kawai et al. 2014; Bricout et al

15. Post Herpetic Neuralgia ( PHN )
Pain present for ≥ 90 days after HZ rash onset.
PHN is the most common complication of HZ.
Although the pain often resolves within a few weeks, it can last for several months or even years.
Factors associated with the development of PHN :
Greater severity of acute pain
Older age
Greater rash severity
Immuno-compromised patients
Restricted activities of daily living prior to HZ
It is a debilitating complication that is challenging to treat and is responsible for most of the
HZ-related burden of disease

16. Herpes Zoster Opthalmicus ( HZO )
It accounts in 10-20% of HZ cases.
The lifetime risk of developing HZO is approximately 1%.
Ocular complications typical of HZO can occur even when there is no visible rash. (zoster sine herpete )
It can lead to blepharitis, kerato-conjunctivitis, iritis, scleritis, opthalmoplegia, optic neuritis and ptosis in 20 to 70% of HZO cases.

17. Viral reactivation in the first branch of the trigeminal nerve

18. Treatment Of HZO
Oral antiviral drugs ( Acyclovir or Valacyclovir ) preferably within 72 h after rash onset.
However if > 72 hours and new lesions are present, treatment may still be useful.
Duration of treatment : 7 days ( maybe longer in older or immuno-compromised patient ).
Refer to opthalmologist for eye assessment.
Despite antiviral treatment, chronic disease can persist in 30% of patients with HZO, increasing to 70% in patients over 80 years old.
there is no evidence that longer treatment is beneficial, except in older or immunocompromised
patients in whom viral activity has been shown to be ongoing for up to 34 days.
The prodrugs
valacilovir and famciclovir have a more convenient dosing schedule and more constant blood concentrations than acyclovir.

19. What is the impact of HZ ?
It has an adverse impact on quality of life (QoL) and activities of daily living.
Some patients, particularly older patients, lose their independence and require help from their families or paid caregivers.
Sleep and social activities are most severely affected.
Patients rarely recover to the same level as before the occurrence of HZ episode.
Side effects of medications.

20. Prevention of HZ
A large pivotal study - Shingles Prevention Study which was a randomized, double-blind, placebo-controlled trial involving approximately 40,000 adults aged 60 years or more.
SPS – Live attenuated Oka/Merck VZV Vaccine.

21. Prevention of HZ
A live attenuated zoster vaccine has been developed to boost the VZV-specific cell-mediated immunity of older adults and, therefore protect the individual against HZ and its complications.
It will improve the life of older people and also reduce the societal impact of HZ.

22. Demographics

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Benefit Of HZ Vaccine
↓ Burden of HZ-related interference with daily life activities.
Attenuates the severity of HZ and PHN when they occur in individuals of all ages  ↓Disease burden.
↓ Risk of HZO and other complications in those aged over 60 years old.
If HZO occurs, despite vaccination, the risk of PHN is significantly lower.
Ther Adv Vaccines 2015, Vol. 3(4) 109 –120

27. Ther Adv Vaccines 2015, Vol. 3(4) 109 –120
HZ Vaccination
It does not induce herd protection (as HZ is not transmitted between individuals).
Protection may persist for up to 10 years, although efficacy ↓ with the recipients’ age.
After its introduction in the US, HZ vaccination has been reported to be associated with lower HZ incidence in vaccinated individuals.
Ther Adv Vaccines 2015, Vol. 3(4) 109 –120

28. Ther Adv Vaccines 2015, Vol. 3(4) 109 –120
Cost effectiveness decreases after this age because vaccine efficacy declines with age and life expectancy is shorter.
Ther Adv Vaccines 2015, Vol. 3(4) 109 –120

29. Influenza Infection
It is associated with considerable yearly morbidity.
Those aged ≥65 years are among those at highest risk of serious outcomes.
Annual influenza vaccination is considered the most effective strategy to prevent influenza, is recommended for elderly in many developed countries.
Schanzer DL et al , Epidemiol Infect 2007; 135:
Thompson WW et al, JAMA 2004;292:
WHO position paper – November Wkly Epidemiol Rec 2012;87:461-76

30. All year round with seasonal variability
All year round with seasonal variability. It affects mostly those age < 4 years old and those > 60 years old.

32. Objective : To determine the efficacy of influenza vaccination in elderly people.
Setting : Fifteen family practices in the Netherlands during influenza season
Participants : A total of 1838 subjects aged 60 years or older, not known as belonging to those high-risk groups in which vaccination was previously given.
Main Outcome Measures.  —Patients presenting with influenza like illness up to 5 months after vaccination; self-reported influenza in postal questionnaires 10 weeks and 5 months after vaccination; serological influenza (fourfold increase of antibody titer between 3 weeks and 5 months after vaccination).
Results :
The incidence of serological influenza was 4% in the vaccine group and 9% in the placebo group (relative risk [RR], 0.50; 95% confidence interval [CI], 0.35 to 0.61).
The incidences of clinical influenza were 2% and 3%, respectively (RR, 0.53; 95% CI, 0.39 to 0.73).
The effect was strongest for the combination of serological and clinical influenza (RR, 0.42; 95% CI, 0.23 to 0.74). The effect was less pronounced for self-reported influenza.
Conclusion :
In the elderly, influenza vaccination may halve the incidence of serological and clinical influenza (in periods of antigenic drift).
Intervention.  —Purified split-virion vaccine containing A/Singapore/6/86(H1N1), A/Beijing/353/89(H3N2), B/Beijing/1/87, and B/Panama/45/90 (n=927) or intramuscular placebo containing physiological saline solution (n=911).

36. At the end of the day
Most seasonal influenza vaccines for elderly showed statistically significant efficacy or effectiveness, the magnitude of which, however, largely varied.

37. Pneumonia- The Old Enemy
Sir William Osler described, “Pneumonia remains now, as then, the most serious acute disease with which physicians have to deal; serious because it attacks the old, the feeble … persons who are not able to withstand the sudden sharp onset of the malady,” still stands the test of time.

38. Pneumonia
Pneumonia is the fourth-leading cause of death globally, and Streptococcus pneumoniae is the most important causative pathogen. World Health Statistics 2014.
In developed countries, such as Japan, > 95% of deaths from pneumonia occur in the elderly (≥ 65 years old).

39. IPD is a pneumococcal disease in which Streptococcus
pneumoniae is detected in a sterile space. IPD consists of bacteraemic
pneumonia, pleuritis, meningitis, arthritis, and bacteraemia, and non-IPD
consists of non-bacteraemic pneumonia, otitis media, sinusitis, and bronchitis.
Although bacteraemia occurs in only 10–30% of pneumococcal
pneumonia cases, bacteraemic pneumonia is the most common IPD
owing to the clinical frequency of pneumococcal pneumonia. In clinical
settings, pleuritis usually occurrs with pneumonia.

40. S. pneumoniae
Different serotypes have different pathogenicities, including colony forming ability, severity, invasiveness, and drug resistance profile.
Serotype 3 is one of the most invasive serotypes since it has the thickest capsule.
Despite a considerably lower incidence of IPD than pneumococcal pneumonia, the prognosis is poorer, and the after effects result in greater patient burden.
More than 90 serotypes.

41. Burden Of Disease
Mortality rates for bacteremic pneumococcal pneumonia and meningitis in adult is around 10% to 30%, and 16% to 37% respectively.
Mortality rates are substantially higher in the elderly and in patients with co-morbidities.
One of the factor associated with poor outcome is age > 65 years old.
Hospitalization rates due to pneumococcal disease in a Singapore study ( ) was 56.4/100,000. Pneumococcal pneumonia was the most common presentation. ( 97.9% )
Semin Respir Crit Care Med 2009;30:189–209.
Singapore Med J 2007;48:824–9.

42. Overall CFR Pre & Post Vaccine
2 IPD Surveillance Study in Taiwan using 7 valent pneumococcal conjugated vaccine

43. Overall CFR

44. Types of Pneumococcal Vaccine
1. Polysaccharide Vaccine
23-valent PPV ( Pneumovax )
2. Conjugate Vaccine
7-valent PCV ( Prevnar 7 )
13-valent PCV ( Prevnar 13 )

45. PPV23 (Cochrane review - 2013 )
PPV23 vaccine is effective for preventing invasive pneumococcal disease ( IPD ) with ( OR 0.26, 95% CI 0.14–0.45 ,I2 statistic = 0% ) with no statistical heterogeneity.
No compelling evidence to support routine use for the prevention of all-cause pneumonia or mortality.
Efficacy against all-cause pneumonia was shown in low-income countries (OR 0.54, 95% CI 0.43–0.67, I2 statistic = 19%).
11RCT-among adults and immuno-competent elderly subjects aged ≥55 years. high I2 statistic values, there was obvious heterogeneity
in those randomized clinical trials. PPV23 does not appear to prevent all-cause pneumonia in general population or adults with chronic diseases in high income country.

46. CAPiTA
In a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65
years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate
vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal
community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal
community-acquired pneumonia, and invasive pneumococcal disease.

49. Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group.

50. Conclusion
Among older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and non-bacteremic community-acquired pneumonia and vaccine type invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause.

51. Serotypes 1, 3, 4, 5, 6A, 7F, 6B, 9V, 14, 18C, 19A, 19F, and 23F
On December 30, 2011, the FDA approved PCV13 for prevention of pneumonia and invasive disease caused by PCV13 serotypes among adults aged 50 years and older
Serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10,
11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F
Serotypes 1, 3, 4, 5, 6A, 7F, 6B, 9V, 14, 18C, 19A, 19F, and 23F

52. What is the advantage of PCV-13?
PCV13 evokes better immunogenicity than PPV23 in a subset of serotypes.
PCV13 also reportedly reduces nasopharyngeal carriage of the vaccine type of pneumococci, especially in children.
As a result, the incidence of pneumococcal disease in adults is reportedly reduced in some regions owing to herd immunity with PCV13.
Human Vaccines & Immunotherapeutics 12:2, ; February 2016

53. What is the effect of vaccination?
The pneumococcal serotype distribution have shifted from vaccine-type to non-vaccine-type serotypes since the introduction of PCVs.
The more PPV23 and PCV13 become prevalent both in infants and adults, the further the coverage of vaccine-type serotypes is expected to decrease in the future.
reports from Japan of the serotype distribution of CAP and
IPD indicate that the proportions of CAP serotypes covered by
PPV23 and PCV13 are 62.7% and 49.3%, respectively, and the
proportions of IPD serotypes covered by PPV23 and PCV13 are
69.6% and 48.0%, respectively.
Human Vaccines & Immunotherapeutics 12:2, ; February 2016

54. 2017 ACIP Recommendation

55. Conclusions Vaccine protection is not 100%.
Immuno-senescence plays a role in determining vaccine efficacy.
Considering the morbidity and mortality caused by these vaccine preventable diseases, we should opt for a better “Prevention” approach rather than “Cure” , as the later approach may proved more costly.