Malaysian Healthy Ageing Society Adul dult t im immu muni nizat - - PowerPoint PPT Presentation

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Adul dult t im immu muni nizat atio ion: n: The e val alue ue of

• f preven

enti tion

• n

Dr Chris istoph pher er Lee ee

Infectious ctious Diseases ases Uni Unit Depar artme tment nt of Medicine ine Hospi spita tal l Sungai ai Buloh

Microbial exposures & diseases throughout life

Prenatal Neonatal < 5 years 5-18 Adult Elderly

Rubella CMV VZV HSV HPV HIV HBV RSV Influenza PIV AV RV Measles-virus Mumps-virus Rubella-Virus HPV HBV HPV HIV Influenza RSV HAV Listeria GBS Enterobacteria C.tetani C.diphtheriae

• H. influenzae b

N.meningitidis S.pneumoniae Salmonella

• B. pertussis

Mycoplasma

• B. pertussis

B.pertussis S.pneumoniae M.tuberculosis

• B. pertussis

Toxoplasma Plasmodium

Schmitt: Based on Mandell, Bennett Dolin 7th ed, 2010

Infectious pressure, colonization, immune response & burden of disease

Immunity: B cells and age

Guideline for Adults

Infections: a major concern in the elderly

• Infectious diseases account for 1/3 of all deaths

in people > 65 yrs .

• Early detection more difficult in elderly because

typical signs & symptoms, eg. fever and leukocytosis, are frequently absent. A change in mental status or decline in function may be only presenting problem.

• An estimated 90% of deaths resulting from

pneumonia occur in people > 65 yrs.

• Mortality resulting from influenza also occurs

primarily in the elderly.

Mouton CP et al. American Family Physician, Jan 15, 2001 / VOL 63, No 2

1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 9 10 Rank Deaths (millions)

WHO Global Burden of Disease Report, 2004 Update. http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf.

LRTIs=lower respiratory tract infections

Leading Causes of Death, All Ages, 2004

LRTI (the majority of which includes CAP in adults) are a leading cause of death worldwide

Pneumonia in Elderly

• 3rd common site of infection after UTI & pressure sores.
• Mortality rate 30-50%
• Risk factors: emphysema, chronic bronchitis, COPD
• Pathogens:

Pneumococcus, most common bacterial cause H. influenzae, other H.spp, S.aureus Gram- bacilli (Enterobacteriaceae, Pseudomonas,

• K. pneumoniae) Legionella & other atypicals

Viruses esp. influenza

• Transmission

 Endogenous flora /aspiration: S. aureus, pneumococci  Droplet: eg influenza  L. pneumophila if aerosolized: air conditioning, cooling towers, showerheads

Strept pneumoniae The old bug that won’t go away …

Age1 Underlying Medical Conditions2-4 Living Conditions3-5

• Children <2 years
• Adults >65 years
• Congenital or acquired

immunodeficiency

• Sickle cell disease, asplenia, HIV
• Chronic heart, lung (including

asthma), renal, or liver disease

• Cancer
• Cerebrospinal fluid (CSF) leak
• Diabetes
• Chronic alcoholism or

cigarette smoking

• Organ or hematopoietic cell

transplantation

• Cochlear implants
• Childcare outside of the

home ≥4 hours per week, and in the presence of ≥2 other children other than siblings

• Residence in a nursing

home or other long-term care facility

• CDC. Morb Mortal Wkly Rep. 1997;46(RR-8):1-24. WHO. Wkly Epidemiol Rec. 2008;83:373-384. CDC. Morb Mortal Wkly Rep. 2000;49(RR-9):1-35. CDC. Morb Mortal Wkly Rep.

2009;57(53):Q1-Q4. Levine OS et al. Pediatrics. 1999;103:1-5.

Age is the most important risk factor for pneumococcal disease1

Risk factors for pneumococcal disease

12

• Pneumococcal disease can be classified as either

invasive (IPD) or mucosal1

• IPD is defined as any condition in which S. pneumoniae is

present in the blood, cerebrospinal fluid, or another normally sterile body site2

• IPD is less common than pneumococcal pneumonia;

however, its microbiological diagnosis is unambiguous2

• The incidence of IPD is therefore frequently used as

an indicator of the overall burden of pneumococcal disease2

• 1. World Health Organization (WHO). Acute Respiratory Infections (Update February 2009).

http://www.who.int/vaccine_research/diseases/ari/en/print.html. Accessed May 27, 2009.

• 2. WHO. Wkly Epidemiol Rec. 2008;83:373-384.

Incidence of IPD is used as a surrogate indicator

18.8 12.8 1.2 10.2 1.0 0.5

2 4 6 8 10 12 14 16 18 20 0-2 3-5 6-14 15-34 35-64 ≥65 Age (years)

Rate/100,000 persons/year

Ho PL et al. Pediatr Infect Dis J. 2006;25:454-455.

IPD by Age (China, Hong Kong, 1995-2004)

Incidence is greatest at the extremes of age

200 400 600 800 1000 1200 0-1 2-4 5-14 15-39 40-64 ≥65

Age (years) Cases by Disease (Total No.)

Other focal Meningitis Pneumonia Bacteremia 617 319 100 376 482 1105

aActive: specific activities to identify cases (eg, telephone calls) vs passive (review of routine reports from healthcare facilities). bOther focal diseases included cellulitis, arthritis, and epiglottitis.

Active Surveillancea of Manifestations of IPD by Age, Metropolitan New South Wales, 1997-2001

McIntyre P et al. NSW Public Health Bull. 2003;14:85-89.

b

More bacteremia in the young and more pneumonia in older adults

Risk of invasive pneumococcal disease in elderly adults, by age group and chronic illness category.

Plotkin S et al. Clin Infect Dis. 2008;47:1328-1338

Blue bars, aged 65–79 years; red bars, aged >80 years

Influenza: Virus of the Year 2009 !

Influenza-related Mortality in the U.S.

• Between 1976 and 2006, estimates of flu-associated

deaths range from a low of about 3,000 to a high of about 49,000 people.

• During 2009-10, the novel 2009 Influenza A/ H1N1

spread worldwide causing the 1st. flu pandemic in > 40 yrs.

• It is estimated that the 2009 H1N1 pandemic resulted in

more than 12,000 flu-related deaths in the U.S. In contrast to seasonal flu, nearly 90% of the deaths

• ccurred among people younger than 65 yrs of age.

CDC

% Distribution of Deaths from Severe Pneumonia during the 2009 Study Period, as Compared with Influenza Seasons from 2006 to 2008, in Mexico, According to Age Group.

Sever ere e Res espi pirator

• ry

y Dis isea ease e Concurre rrent t wit ith the e Cir ircul ulation ation of Influen enza za

Gerardo Chowell et al NEJM, No 7; Volume 361:674-679, 2009

Estimated Annual Influenza-associated Mortality Rates per 100,000 Person-yrs from 1990 to 1999 seasons

Thompson WW, Shay DK, Weintraub E, et al. JAMA. 2003;289(2):176-186

Age Group (years) Mortality Rate per 100,000 person-years Underlying Pneumonia & Influenza deaths Underlying resp. & circulatory deaths All-cause deaths < 1 0.3 0.6 2.2 1-4 0.2 0.4 1.1 5-49 0.2 0.5 1.5 50-64 1.3 7.5 12.5 > 65 22.1 98.3 132.5 Total 3.1 13.8 19.6

Influenza in Tropics

Influenza-associated mortality rate / 100,000 person-years Author Country All cause Underlying pneumonia & influenza deaths Underlying circulatory & resp deaths Chow et al * S’pore All ages: 14.8 > 65yrs: 167.8 All ages: 2.9 > 65yrs: 46.9 All ages: 11.9 > 65yrs: 155.4 Wong et al ** Hong Kong All ages: 16.4 > 65yrs: 136.1 All ages: 4.1 > 65yrs: 39.3 All ages: 12.4 > 65yrs: 102.0

* Chow et al. Emerging Infectious Diseases, Vol 12, No 1, Jan 2006. Pg. 114-121 ** Wong et al. Clinical Infectious Diseases 2004; 39: 1611-7

The Cost of Pneumonia!

61.2 0.1 1 0.3 1.1 2.7 3.9 18.6 6.6 40.6 5.2 0.5 0.2 0.4 0.7 1.5 4.2 12

10 20 30 40 50 60 70 <1 1-4 5-14 15-24 25-34 35-44 45-54 55-64 65-74 Age (years) Rate/100,000 population Female Male

WHO Statistics. Mortality Database. http://apps.who.int/whosis/database/mort/table1_process.cfm. Accessed June 10, 2009.

United Kingdom, Mortality Rate by Age Group, 2005 The rates for age group 75+ years (609.9 for females and 570.9 for males) are not shown to facilitate examination of the trend in rates for younger age groups

Mortality from pneumonia, including CAP, starts to increase around age 45 years

2 4 6 8 10 12 14 16 18 20 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

CC=cell culture

Thousands of dollars

Estimated cost per day has increased 207% since 1993

Estimated Total Charges, United States Diagnosis-related Group 89: Simple Pneumonia and Pleurisy, >17 years of age with CC 9,550 9,585 9,749 9,593 9,945 10,885 14,951 16,435 17,897 18,734 19,603 13,241

Average length of stay=5.0 days Average length of stay=7.5 days

10,535 12,219

Health Care Cost and Utilization Project Nationwide Inpatient Sample (NIS), Agency for Healthcare Research and Quality (AHRQ). Based on data collected, and provided to the AHRQ, by individual states. http://hcupnet.ahrq.gov/HCUPnet.jsp. Accessed June 10, 2009.

There has been an upward trend in total costs per pneumonia hospitalization, despite a downward trend in total inpatient days per hospitalization

Hospital treatment for pneumonia has a substantial economic impact

Metlay et al. Respir Med. 1998;(9)92:1137-1142.

Symptom Median time to resolution (days) Inter-quartile range (days) % with unresolved symptom at day 28 Fever 3 2-4 3.5 Myalgia 5 4-6 13.5 Dyspnea 6 5-14 16.8 Cough 14 7-21 19.9 Fatigue 14 6-21 25.7 All symptoms 21 21-28 35.0

aMedian time to symptom resolution and inter-quartile range were estimated by the Kaplan-Meier survival

analysis

Time to resolution of symptoms in patients with pneumoniaa

Pneumonia symptoms may take weeks to resolve

Pneumonia is something worth preventing. Keep it Out!

Efficacy of influenza vaccination in elderly and high-risk persons

Prevention of illness and death

Among high-risk adults (e.g. patients with chronic cardiovascular, respiratory or renal disease) 18–64 years, vaccination prevented:

• 78% of deaths
• 87% of hospitalisations
• 26% of GP visits

Among elderly individuals (> 65 years), vaccination prevented:

• 50% of deaths
• 48% of hospitalisations

Hak E et al. Arch Intern Med 2005; 165: 274–80

Influenza deaths versus vaccination history

WHO Collaborating Centre for Influenza, Melbourne.

Odds ratio – influenza death 1.2 1.0 0.8 0.6 0.4 0.2 1.4

Previous only 1985–88 First vaccination 1989 Vaccinated 1989 and previously

Regular annual vaccination improves protection

Pneumococcal vaccine effectiveness against invasive pneumococcal disease by age of recipient and time since vaccination.

Plotkin S et al. Clin Infect Dis. 2008;47:1328-1338

Within each age group, 3 data points represent the vaccine effectiveness at <3 yrs, 3–5 yrs, and >5 yrs since vaccination, from left to right

Years of life bought for US$1 million (1990)

Pap smear every 3 years 52 life-years Bypass surgery for left main 134 life-years coronary artery disease Pneumococcal pneumonia 100 life-years vaccination Influenza vaccination 11,100 life-years

Vaccination for respiratory pathogens is a highly cost-effective healthcare intervention

Russell LB. Health Aff (Millwood) 1992; 11: 162–9.

Source: McCarthy and Leatherman, Performance Snapshots, 2006. ww

Percentage of Community-Dwelling Adults Ages > 65 yrs Who Received Recommended Vaccinations, 1989–2005

31 42 52 56 59 63 63 65 65 63 66 66 65 60 14 22 29 30 35 43 46 50 53 54 56 56 57 56

20 40 60 80 100

1 9 8 8 1 9 8 9 1 9 9 1 9 9 1 1 9 9 2 1 9 9 3 1 9 9 4 1 9 9 5 1 9 9 6 1 9 9 7 1 9 9 8 1 9 9 9 2 2 1 2 2 2 3 2 4 2 5 Influenza vaccination in past year Pneumococcal vaccination ever

Data: National Health Interview Survey (National Center for Health Statistics 2004, 2006). Rates were age-adjusted to the 2000 U.S. standard population.