Invasive Pneumococcal Disease in Thailand

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Invasive Pneumococcal Disease in Thailand

Invasive Pneumococcal Disease in Thailand

Building Capacity to Document Disease Burden

and Guide Interventions

Susan A. Maloney, MD, MHSc

International Emerging Infections Program (IEIP)

Thailand MOPH-U.S. CDC Collaboration (TUC)


Global burden of pneumococcal disease

716 000 deaths

worldwide each year

among children


Pneumococcal disease is responsible for 8 -

10% of all deaths in children < 5 years of age

Deaths (millions)

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0

3.5

Source: WHO

2.7

Pneumococcal disease kills 1.6M annually,

including ~0.7-1M in children 5 years old

0.9


Pneumococcal Disease

Opportunities and Challenges

• WHO recommends including pneumococcal conjugate

vaccine (PCV) in national vaccine programs

• Cost-effectiveness studies support use of PCV in high

& low income (LI) countries

Pneumococcal vaccines expensive; recent donor

support for vaccine implementation to LI countries

• Surveillance and disease burden data limited in much

of the world, particularly in SE Asia

• Optimally, surveillance should be established before

vaccine implementation


Thailand Situational Analysis

• As middle income country, not eligible for PCV donor support

• PCV7 not part of EPI, but vaccine available in the private sector

• Could play important role in expanding market

• Competing health priorities, including other VPDs, make

decisions about vaccine introduction complex

• Local/regional data needed to make “evidence-informed”

vaccine implementation and policy decisions

– Age-stratified Incidence, mortality, disease burden

– Serotype distribution

– Cost and cost-effectiveness

– Vaccine impact and safety

– Global situation and status of vaccine: vaccine supply, introduction

and recommendations, experience of other countries


Streptococcus pneumoniae

in Thailand

Phongsamart, et al. (Vaccine 2007;25:1275)

• 115 IPD isolates from children


Thai MOPH-

US CDC Collaboration

• IEIP Thailand started in 2002

• Core activity is active, enhanced surveillance

for pneumonia (population-based)

– Identify important cases of hospitalized pneumonia

– Estimate disease burden

– Develop laboratory capacity

– Build platform/model for evaluating interventions

to prevent pneumonia


IEIP Surveillance Network

• Active, enhanced surveillance for

pneumonia requiring hospitalization

– Sa Kaeo, pop 526,000 (33,000


Case Definition Clinical Pneumonia

• Resident of Sa Kaeo or Nakhon Phanom province

• Evidence of acute infection (38.2 °C), or

– Chills or documented temperature 11,000/mm 3 or


Annual Incidence of Clinical Pneumonia (All Ages)

Requiring Hospitalization, 2004 – 2008

Incidence/100,000

1200

1000

800

600

400

200

0

2004

2005

2006

2007

Sa Kaeo

Nakhon Phanom

2008


Incidence per 100,000

Annual Incidence of CXR-Confirmed

Pneumonia--Sa Kaeo, Thailand

Sep 2002- Aug 2003

7000

6000

5000

4000

3000

2000

1000

0

0

1~4

5~9

10~14

15-19

20-24

25-29

30-34

35-39

Age in years

Olsen et al. Int J Infect Dis. 2006;10:439.

Observed Incidence

Adjusted for hosp access

and incomplete CXRs

40-44

45-49

50-54

55-59

60-64

65-69

70-74

>=75


Building an Enhanced Surveillance Platform

An Integrated Model

Pneumonia surveillance

~4,600 cases


Building an Enhanced Surveillance Platform

An Integrated Model

Respiratory Pathogens Study

(RPS)

•Enrolled, consented

•Began Aug. 2003

•Eligibility:

•Clinical pneumonia

•X-ray

•~830


Building an Enhanced Surveillance Platform

An Integrated Model

Respiratory Pathogens Study

(RPS)

•Began Aug. 2003

•Enrolled, consented

•Eligibility:

•Clinical pneumonia

•X-ray

•~830


Building an Enhanced Surveillance Platform

An Integrated Model

Respiratory Pathogens Study

(RPS)

•Enrolled, consented

•Began Aug. 2003

•Eligibility:

•Clinical pneumonia

•X-ray

•~830


IEIP Microbial Surveillance (2005)

• IEIP encourages blood cultures in target groups

– Suspected pneumonia, all ages

– Children


S. pneumoniae (Pneumococcal)

Bacteremia Case Definition

Clinically compatible illness in patient with:

(1) S. pneumoniae isolated from blood; OR

(2) Positive blood culture that failed to grow pathogen on

subculture AND had media positive by Binax rapid test


Sa Kaeo

Nakhon

Phanom

Impact of Laboratory Capacity

Enhancements

Time relative to

start of project

4 years prior

(2001-04)

22 months after start

(May 2005)

2 years prior

(2003-05)

16 months after start

(Nov 2005)

Hemo-

Cultures

7986

5864

4813

7884

S. pneumoniae

isolates

3

27

13

34


Annualized incidence of pneumococcal bacteremia requiring hospitalization,

Nov 2005- June 2008 – Sa Kaeo and Nakhon Phanom, Thailand

Incidence per 100,0

25

20

15

10

5

-

Antigen detection only

Blood Culture


Serotype distribution of pneumococcal bacteremia isolates

according to vaccine serotypes

Number of isolates

14

12

10

8

6

4

2

0

4%

14%

1%

18%

Age ≥5 years

Age


Antibiotic susceptibility of pneumococcal bacteremia

isolates according to vaccine serotypes

Percent Non-Susceptible

90

80

70

60

50

40

30

20

10

0

All isolates

Penicillin

Susceptible*

All Serotypes

PCV7

PCV10

PCV13

Non-vaccine

Penicillin Co-Trimoxazole

Antibiotic

Erythromycin Clindamycin

*According to 2008 CLSI cut points for non-meningitis isolates


Reported Antibiotic Use During

72 Hours Pre-Culture

All Ages

33%

(5505/16449)

Age


Blood Culture Yield by Reported Antibiotic

Use During 72 Hours before Blood Culture

Culture positive

Pathogen isolated

S. pneumoniae

isolated*

Antibiotic Use

Yes

n (%)

681 (12)

342 (6)

5 (0.1)

No

n (%)

1664 (17)

937 (9)

Total

n (%)

2574 (15)

1400 (8)

p-value


Blood Culture Yield by Serum Antimicrobial

Activity at the Time of Blood Culture

Culture positive

Pathogen isolated

S. pneumoniae

isolated*

Antibiotic Use

Yes (N=3313)

n (%)

397 (12)

220 (7)

1 (0.03)

No (N=8781)

n (%)

1460 (17)

64 (10)

p-value


Impact of antibiotic use before blood culture

on pneumococal bacteremia incidence

Incidence per 100,000

16

14

12

10

8

6

4

2

0

Observed

Adjusted for antibiotic use-reported

Adjusted for antibiotic use-serum activity

0-4 5-19 20-49 50-64 65+ Total

Age Category


Incidence of Invasive Pneumococcal Disease

Among Children Age


Documented pneumococcal

disease only “tip of the iceberg”

• Diagnostic challenges and limitations

– Many patients with indications not tested

– Fastidious organism; specimen handling

and transport issues

– Majority pneumonia cases not bacteremic

• Focus on pneumococcal bacteremia

requiring hospitalization

– Universe of invasive disease not

measured (e.g. meningitis, etc.)

– Outpatient burden not measured


Next Steps

• Review burden of disease estimates

– ? Meningitis or other data requirements

• Cost-effectiveness analysis

• Economic and supply analysis

• Decision-making framework

• Vaccine introduction ?

• Post-introduction surveillance, monitoring vaccine

impact, other studies

Disease trends

– Vaccine schedules (and other programmatic issues)

– Indirect vaccine effects (i.e. herd immunity)

– Serotype shifting

– Re-emergence of disease

– Vulnerable groups


Surveillance

•Active, enhanced

(population-based)

•Syndrome or

pathogen-specific

Human

Resources

•Dedicated staff

•Local and national

partnerships

Lab Capacity

•Viral/bacterial etiology

•Practical experience

(lessons learned)

Intervention Evaluation Infrastructure

Risk factor analysis

Cost-effectiveness analysis

Pharmaceutical interventions

Vaccines: S. Pneumo, influenza, etc.:

Post-introduction surveillance, vaccine impact, other studies

Non- pharmaceutical interventions

Rapid diagnostics, clinical guidelines, rational antibiotics

Community handwashing and education campaigns


Acknowledgments

• Ministry of Public Health, Thailand

– National Institute of Health

– Bureau of Epidemiology

– Bureau of Emerging Infectious

Diseases

– Bamrasnaradura Institute

– National TB Reference Center

• PneumoADIP, Johns Hopkins

University, USA

• Global Alliance for Vaccines and

Immunization (GAVI)

• Sa Kaeo Provincial Health Office

• Nakhon Phanom Provincial Health

Office

• U.S. CDC

– Sonja Olsen, Scott Dowell

– Matt Moore, Alicia Fry

– Dean Erdman, Bernie Beall,

Barry Fields

IEIP Sa Kaeo

Sathapana Naorat

Possawat Jorakate

IEIP Nakhon Phanom

Prabda Prapasiri

Anek Kaewpan

IEIP Bangkok

Somsak Thamthitiwat

Kip Baggett

Prasert Salika

Prasong Srisaengchai

Puangtong Tungpruchayakul

Kittisak Noonsate

Pornpak Khunatorn

Wanna Wongjindanon

Pongpun Sawatwong

Julie Fischer

Julia Rhodes

Leonard Peruski

Susan Maloney

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