the epidemiology and burden of pneumococcal … for invasive disease. ... nepal & sri lanka ......

The Epidemiology and Burden of Pneumococcal Disease

Thomas Cherian

ISPPD 2014, Hyderabad2 |

Febrile bacteraemia Meningitis

ArthritisPeritonitis

Osteomyelitis

Pneumonia

Otitis

Sinusitis

Diseases caused by Streptococcus pneumoniae (Pneumococcus)

NP carriage

Invasive pneumococcal disease


NP colonization occurs earlier in lower socioeconomic settings

0102030405060708090

100

Prop

ortio

n co

loni

zed

(%)

Age (months)

O’Brien et al. Pediatr Infect Dis J. 2003; 22(2): e1-11

Papua New Guinea Australian Aborigines

India Costa Rica

Sweden & Finland

Israeli Jews


Surveillance for laboratory confirmed disease only provides part of the picture

Culture positive Spn disease

Culture negative meningitis and pneumonia

Identified by surveillance for invasive disease

Additional cases preventable with

vaccination


Incidence of IPD

050

100150200250300350400450500

Finland Chile USA Kenya The Gambia Bangladesh -urban

Bangladesh-rural

Inci

denc

e/ 1

00,0

00 c

hild

ren

Incidence < 2 years Incidence < 5 years

Sources: Robinson KA JAMA 2001; Davidson M JID 1994; O’Dempsey TJ PIDJ 1996;Levine MM PIDJ 1998; Eskola J JAMA 1992; Berkley NEJM 2005; Brooks Am J Trop Med Hyg 2007; Arifeen SE CID 2009


Invasive Pneumococcal Disease Rates, by Age, USA 1997

0

50

100

150

200

250

< 12 12–23 24–48 5–17 18–34 35–49 50–64 > 65

Available at: www.cdc.gov/ncidod/dbmd/abcs/survreports/spneu98.pdf. Age

Rat

e pe

r 100

,000

pe

rson

s

Months Years


Age distribution of pneumococcal meningitis cases(Bangladesh, India)

Russel F et al. http://blogs.lshtm.ac.uk/vaccineschedules/files/6.-Russel-review-age-specific-epidemiology-PCV-schedules-session-nov11.pdf


Pneumococcus is a significant cause of bacterial meningitis

05

101520253035404550

Mozambique(10)

Vietnam (11) Burkina Faso(12)

PneumococcusHibMeningococcus

Perc

ent o

f iso

late

s

1Peltola H. Clin Inf Dis 2001; 32: 64-75.2Ciana G, Parmar N, et al. J Trop Pediatr 1995; 41: 164-8.3Tram TT, Thinh LQ, et al. Ped Inf Dis J 1998; 17(9 Suppl): S192-S194.4du Chatelet IP, Traore Y, et al. Clin Inf Dis 2005; 40: 17-25.

In low-income countries about 45% of people with pneumococcal meningitis die, compared to 29% with Hib meningitis and 8% with meningococcal meningitis


Proportion of meningitis caused by pneumococcus

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

Bangladesh (n=356) Pakistan (n=274) Burkina Faso(n=121)

Kenya (n=66) Nigeria (n=37)

Proportion of CSF specimens positive for S. pneumoniae, culture, latex or Binax ICT, children <5 y.o.

Binax ICTLatexCulture

17.2% 17.4%16.2% 16.2%

21.6%

Asia Africa


Serotypes causing IPD in India, Nepal & Sri Lanka(n = 735)

0

10

20

30

40

50

60

70

80

90

100

0

2

4

6

8

10

12

14

16

18

20

146A

/B/C

/D 19F

23F

9A/V

18A/

B/C/

F 4 1 57A

/F 319

A15

B/C 2

23A 8

47F

12A

22A/

F11

A/D

25F 38

9N/L 13 15A 16 19B 20 39 10A

17F

19C

23B

24F 27 29 33C

33F 34

35,4

2 45 10F

11C 15 16A

16 F

24B 32 33 33B

35B

35C

PCV7 PCV10 PCV13 NVT

%

Cummlative

% V

accin

e Ty

pe

Vaccine Type Cummlative

Data for the period of 2005-2013


Differences in serotype prevalence between India, Nepal & Sri Lanka

0

10

20

30

40

50

60

70

80

90

100

0

2

4

6

8

10

12

14

16

18

20

6A/B

/C/D 14 19

F 4

18A/

B/C/

F

23F

9A/V 5 1

7A/F

19A

15B/

C 27

11A/

D

22A/

F

33C

33F 8 29 34 39 10A

10F

16 F

17F

19B

19F

23A

24B

24F

47F

9N/L


%

Cummlative

% V

accin

e Ty

pes

Vaccine Type Cummlative 0

10

20

30

40

50

60

70

80

90

100

0

4

8

12

16

20

24

28

32

36

40

14

9A/V

18A/

B/C/

F

23F

19F

6A/B

/C/D 4 1 5

7A/F 3

19A 2 8

12A

25F 16 20 39 45 19B

23A

23B

47F 13 32 33 34 38

12A

15A 10

A


%

Cummlative

% V

accin

e Ty

pes


0

10

20

30

40

50

60

70

80

90

100

0

2

4

6

8

10

12

14

16

18

20

14 19F

6A/B

/C/D 23

F

9A/V

18A/

B/C/

F 4 5 1 3

19A

15B/

C

23A

47F 38 13

11A/

D

15A

22A/

F 8 15 16 20 29 11C

16A

17F

19C

33B

35,4

2

35C

9N/L


%

Cummlative

% V

acci

ne T

ypes


INDIANEPAL

SRI LANKA

The image part with relationship ID rId2 was not found in the file.

-20 -10 0 10 20 30 40 50 60 70

114

56B

23F7F

19F18C6A

49V

19A2

12A18F

458

3818A12F10F

2033F

347B

10A11A11F

1315A15F16F17F23A24F25F28A33B35B35F22F

29212731

33C6C

Nonmenin

Meningitis Culture Positive

Meningitis Culture Negative

PCV

PCV-10 Coverage

Meningitis 44%

Non-Meningitis 47%

Overall 45%

Non-meningitis (N= 105) (Meningitis (N=336)

Figure: Distribution of Meningitis and Non-meningitis Cases with Their Vaccine Coverage(2007-2013)

Source: S K Saha, personal communication


All Countries (India, Nepal, Sri Lanka) by Year

11.3

7.6

10.7

3.1 3.4

1.50.6

18.7

7.3

1.22.4

0.6

25.4

14.7

16.9

9.0

5.6

2.8 2.81.7

11.9

7.9

1.1

2.81.7

20.9

0.0

5.0

10.0

15.0

20.0

25.0

30.0

14 6A/B/C/D 19F 23F 9A/V 18A/B/C/F 4 1 5 7A/F 3 19A


% V

accin

e Ty

pe

2005-2009 2010-2013

13

Figure: PCV-10 Coverage for IPD Cases in Bangladesh, 2007 - 2013

PCV-10 CoverageMeningitis 44%Non-Meningitis 47%Overall 45%

39% 40%

57%

29%

38%

54%

47%

0%

10%

20%

30%

40%

50%

60%

70%

80%

2007 2008 2009 2010 2011 2012 2013

PCV-10

PCV-10

Source: Samir Saha 14


Outcome and age range (months)

India (cases per 1000 child-years)

Neighboring countries(per 1000)

Developingcountries globally(per 1000)

ALRI 0-59 290, 370 510 290

ALRI 1-59 310

Severe ALRI 0-59 50 20

Severe ALRI 1-59 165

Severe ALRI 2-59 10

Severe ALRI 0-35 43

Severe ALRI 1-23 27, 31, 79

Incidence of pneumonia


S. pneumoniae—The Most Common Cause of Bacterial Pneumonia

0

10

20

30

40

50

60

Papua NewGuinea (1)

The Gambia(2)

Zimbabwe (3) The Gambia(4)

Perc

ent o

f asp

irate

s

% of bacterial isolates

S. pneumoniae

H. influenzae

Other bacteria

1Shann F, Gratten M, Germer S, et al. Lancet. 1984; 2(8402):537-541.2Wall RA, Corrah PT, Mabey DC, Greenwood BM. Bull World Health Org. 1986; 64(4):553-558.3Ikeogu MO. Arch Dis Child. 1989; 64(8):1207.4Forgie IM, Campbell H, Lloyd-Evans N, et al. Pediatr Infect Dis J. 1992; 11(6):466-473.


Lung aspirate studies from S Asia

Author Year N No. pos S pneumo H inf S aureus Others

Sinha 1966 25 11 3 7 0 1

Hughes 1966 17 5 2 5 0 0Hughes 1969 18 7 2 6 0 0Kalra 1981 70 36 18 2 5 11

Tewari 1991 100 50 5 0 25 20

Prakash 1996 35 17 4 1 2 12

Patwari 1996 12 6 2 0 4 0All studies

1966-96 277 132 (48%) 36 (13%) 21 (8%) 36 (13) 44 (16)

Source: Vuori-Holopainen E, Peltola H. CID 2001Included older children


Proportion of pneumonia attributable to pneumococcus, based on vaccine impact data

8 %

3 3 %

2 1 %

-30%

-20%

-10%

0%

10%

20%

30%

40%

50%

60%Cl

inica

l Pne

umon

ia

NCKP

Sout

h Afri

ca

Gamb

ia

Philip

pines

Seve

re Pn

eumo

nia

NCKP

Sout

h Afri

ca

Gamb

ia

Philip

pines

CXR+

Pne

umon

ia

NCKP

Sout

h Afri

ca

Gamb

ia

Philip

pines

Clinical Pneumonia

Severe Pneumonia

CXR+ Pneumonia


Causes of death in children, 2010

Liu et al. Lancet 2012


Pneumonia mortality trends, SEAR

Liu et al. Lancet 2012


Country and age range (months)

Study design Outcome measure

Outcome-specific mortality reduction

India 0-47 Case-control, village randomized

Fatal pneumonia 54%

Pakistan 0-59 Observational, community based

Fatal ALRI 55%

Pakistan 0-59 Observational, hospital based

ARI case fatality rate

51%

Bangladesh 0-23 Case-control, village randomized

Fatal pneumonia 54%

Nepal 0-59 Observational, community based

Fatal ARI 69%

Etiology - bacterial “probe” studies


Estimates of pneumococcal deaths(WHO, 2008 unofficial)

CountryPneumococcal deaths

Pneumonia Meningitis NPNM Total

Bangladesh 7165 1311 371 8846

Bhutan 82 7 2 91India 73292 9850 2786 85928

Maldives 6 3 3 12

Nepal 1378 278 79 1735

Pakistan 18799 1595 451 20845

Sri Lanka 133 10 10 153

TOTAL 100854 13054 3701 117609


Top 10 high burden countriesPopulation size vs mortality rate

Feb/08 analysis

India

NigeriaEthiopia

DR Congo Afghanistan

China

Pakistan

AngolaBangladesh Uganda-10

10

30

50

70

90

110

130

150

0 200 400 600 800 1000

Pneumococcal deaths per 100,000 children under 5 years

Und

er 5

pop

ulat

ion

(mill

ion)


Summary

Pneumococcus is an important cause of serious disease in children, especially pneumonia and meningitis.

Establishing pneumococcal etiology of childhood pneumonia is a challenge and limits the ability to get a direct estimation of burden of disease

Synthesis of available data shows that pneumococcal disease is an important cause of childhood morbidity and mortality worldwide, as well as in South Asia.

No reason to suspect that the epidemiology of pneumococcal disease in South Asia is different from that in other countries with similar socio-economic & mortality profile.

EXTRA SLIDES


IPD serotypes, India (2005-213)(n=349)

0

10

20

30

40

50

60

70

80

90

100

0

2

4

6

8

10

12

14

16

18

20

6A/B

/C/D 14 19

F 4

18A/

B/C/

F

23F

9A/V 5 1

7A/F

19A

15B/

C 27

11A/

D

22A/

F

33C

33F 8 29 34 39 10A

10F

16 F

17F

19B

19F

23A

24B

24F

47F

9N/L


%

Cummlative

% V

accin

e Ty

pes




IPD serotypes, Nepal (2005-13)(n=210)

0

10

20

30

40

50

60

70

80

90

100

0

4

8

12

16

20

24

28

32

36

40

14

9A/V

18A/

B/C/

F

23F

19F

6A/B

/C/D 4 1 5

7A/F 3

19A 2 8

12A

25F 16 20 39 45 19B

23A

23B

47F 13 32 33 34 38

12A

15A 10

A


%

Cummlative

% V

accin

e Ty

pes




IPD serotypes, Sri Lanka (2005-13)( n=176)

0

10

20

30

40

50

60

70

80

90

100

0

2

4

6

8

10

12

14

16

18

20

14 19F

6A/B

/C/D 23

F

9A/V

18A/

B/C/

F 4 5 1 3

19A

15B/

C

23A

47F 38 13

11A/

D

15A

22A/

F 8 15 16 20 29 11C

16A

17F

19C

33B

35,4

2

35C

9N/L


%

Cummlative

% V

accin

e Ty

pes




India by Year


Nepal by Year

3.1 3.11.9 1.3 1.9 1.9

0.6

35.8

12.6

2.5 2.50.6

32.1

7.8

3.9 3.95.9

2.00.0 0.0

33.3

11.8

0.0

5.9

2.0

23.5

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

40.0

14 9A/V 18A/B/C/F 23F 19F 6A/B/C/D 4 1 5 7A/F 3 19A


% V

accin

e Ty

pe

2005-2009 2010-2013



Sri Lanka by Year

17.6

21.4

13.0

6.1

3.8

1.50.8

0.00.8

3.1

0.8

31.3

24.4

8.9

28.9

8.9

2.2

0.0 0.0

4.4

0.0

4.4

0.0

17.8

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

14 19F 6A/B/C/D 23F 9A/V 18A/B/C/F 4 5 1 3 19A


% V

accin

e Ty

pe

2005-2009 2010-2013


the epidemiology and burden of pneumococcal … for invasive disease. ... nepal & sri lanka ......

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