Transcript Hib Disease Burden – Review of literature

Hib Disease Burden
– Review of literature
Dr Raju Shah
1
Causes of under-five deaths
India: WHO 2008
Neonatal 54%
(1.003 million)
Diarrhea 12.9%
(0.237 million)
Others 12.8%
(0.218 million)
Pneumonia 20.3%
(0.371 million)
1.829 million under-five deaths (20.8% of world)
Black RE et al, Lancet 2010;375:1969-87
2
Pneumonia deaths: Top 10 countries
Number
Country
Pneumonia
% of world
deaths (N) (2008)
01
India
371,605
23.5%
02
Nigeria
177,212
11.2%
03
DR Congo
112,655
7.1%
04
Pakistan
084,210
5.3%
05
Afghanistan
080,694
5.1%
726,376
52.3%
06
China
062,229
3.9%
07
Ethiopia
048,892
3.1%
08
Angola
033,078
2.1%
09
Kenya
030,406
1.9%
10
Indonesia
038,331
2.4%
Total
1,031,392
65.8%
World
1,575,257
100%
Black RE et al, Lancet 2010;375:1969-87
3
Clinical Pneumonia burden – Top 15 countries
Country
Predicted no. of
new cases (millions)
Estimated incidence
(epi/child yr)
India
43.0
0.37
China
21.1
0.22
Pakistan
09.8
0.41
Bangladesh
06.4
0.41
Nigeria
06.1
0.34
Indonesia
06.0
0.28
Ethiopia
03.9
0.35
Democratic Republic of the Congo
03.9
0.39
Viet Nam
02.9
0.35
Philippines
02.7
0.27
Sudan
02.0
0.48
Afghanistan
02.0
0.45
United Republic of Tanzania
01.9
0.33
Myanmar
01.8
0.43
Brazil
01.8
0.11
World
155.84
0.26
Rudan I Bull WHO 2008;86:408-16
4
• In India, data on Hib particularly on
population-based incidence is sparse
• There is marked variability in reported burden
of Hib disease in India
• However, a number of hospital-based studies
have shown that, as in other parts of the
world, Hib is the most common endemic
cause of bacterial meningitis in children
5
Challenges in establishing
Hib disease burden
•
•
•
•
•
Fastidious organism, difficult to grow
High threshold for cultures
Lack of good microbiology services
Antibiotic treatment before culture
Only severe cases reach the hospitals
6
There is marked variability in reported
burden of Hib disease in India
• A study by Panjarathinam R, Shah RK. (Pyogenic meningitis in
Ahmedabad Indian J Pediatr 1993; 60:669–73) - of 135 CSF samples
obtained from children with meningitis - cultures
yielded no Hib organisms at all
• Study by Venkatesh VC, Steinhoff MC, Moses P, Jadhav
M, Pereira SM. (Latex agglutination: an appropriate technology
for the diagnosis of bacterial meningitis in developing countries.
Ann Trop Paediatr 1985; 5:33–6) have shown Hib to be a
common cause of meningitis in infants and young
children
7
Incidence of Hib meningitis in India
S. Minz, V. Balraj, M. K. Lalitha*, N. Murali**, T. Cherian**, G. Manoharan†, S.
Kadirvan†, A. Joseph & M.C. Steinhoff††
Indian J Med Res 128, July 2008, pp 57-64
•
•
•
•
•
Prospective study
1997 to 99 – for 24 months
Vellore district with 56,153 U5 children
97 possible meningitis
Annual incidence Rate per 100,000 (AIR)
– (86 for 0-4y while 357 for 0 to 11 m)
• 18 ABM (AIR 15.9 for 0-59 months)
• 8 Hib (AIR 7.1 for 0-59m - 32 for 0-11m,
- 19 for 0-23m )
• Vellore study site is well-served and not typical of all of
India – Vellore data would be underestimating for most
other regions*
*Indian J Med Res 132, October 2010, pp 450-455
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Hib Meningitis in India
• 0.5 to 2.6% of all hospital admissions
(Kabra SK, et al. Bacterial meningitis in India: an
IJP survey. Indian J Pediatr 1991; 58: 505-511)
• 25% (range: 14-35%) of bacterial meningitis
attributable to Hib in India
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Good published studies
Author/year
Syndrome
Age range Study Site
Study Size
% Hib
positive
Deivanayaga suspected
m, et al. 1993 meningitis
2 mo - 11
y
Chennai
114
25
Singhi, et al.
2002
1 mo - 12
y
Chandigarh 107
35
Suvarna Devi, acute
et al. 1982
meningitis
<15 y
Behrampur
70
19
Mani, et al.
2007
bacterial
meningitis
<5 y
Bangalore
51
14
Chinchankar,
et al. 2002
bacterial
meningitis
1 mo - 5 y
Pune
54
26
suspected
meningitis
10
The proportion of Haemophilus influenzae Type B isolates
in case series of endemic bacterial meningitis
S.N.
1
2
3
4
5
6
7
8
Study ID
State
Year
Achar and Rao
(1953)
Taneja and Ghai
(1955)
Ahmed et al.
(1964)
Paul
(1963)
Srivastava et al.
(1968)
Tamil
Nadu
Delhi
Age group
No. of cases
Haemophilus
Influenza (%)
1950–1951 Paeds
98
45 (45.9)
1953–1955 <12 years
33
0 (0.0)
Tamil
Nadu
Delhi
1953–1960 < 12 years
87
33 (37.9)
1956–1959 <12 years
48
10 (20.8)
Uttar
Pradesh
1964
<12 years
33
0 (0.0)
Gandhi
(1969)
Reddi et al.
(1973)
Gujarat
1966–1967 <12 years
60
4(6.7)
Andrha
Pradesh
1970–1971 Paeds
85
5(5.9)
Tamaskar and
Bhandari
(1976)
Madhya
Pradesh
1971–1972 <12 years
21
3(14.3)
11
The proportion of Haemophilus influenzae Type B isolates
in case series of endemic bacterial meningitis (cont)
S.N
.
Study ID
State
Year
Age group
No. of cases Haemophilus
Influenza (%)
9
Kalra and Dayal
(1977)
Uttar
Pradesh
1966–1969
1 month–12
years
196
0(0.0)
10
Ayyagari et al.
(1980)
Kumar et al.
(1980)
Chandigarh
1976–1978
Paeds
176
11(6.3)
Chandigarh
1977–1979
1 month–12
years
66
17(25.8)
Suvarna Devi et
al.
(1982)
Pal and Sant
(1982)
Venkatesh et al.
(1985)–
Orissa
1978–1981
<15 years
70
13(18.6)
Maharashtr
a
Tamil Nadu
-
-
64
0(0.0)
1982
9 day–12
years
44
8(18.2)
Bhat
(1991)
Vincent et al.
(1987)
Pondicherry 1972–1980
Paeds
256
6(2.3)
Kerala
1 month–12
years
51
0(0.0)
11
12
13
14
15
16
1983–1984
12
The proportion of Haemophilus influenzae Type B isolates
in case series of endemic bacterial meningitis (cont)
S.N.
State
Year
Age group
No. of cases
Haemophilus
Influenza (%)
Kabra et al.
(1991)
Deivanayagam
(1993)
Various
1989
<12 years
852
8(0.9)
Tamil Nadu
1989–1990
2 months–11
years
114
28(24.6)
19
Panjarathinam and
Shah (1993)
Gujarat
1990
<10 years
135
0(0.0)
20
Javadekar et al.
(1997)
Gujarat
-
Paeds
50
1(2.0)
21
Bhaumik
(1998)
Jain et al.
(2000)
Delhi
-
12–75 years
30
-
Delhi
-
3 months–12
years
32
7(21.9)
23
Sahai et al.
(2001)
Pondicherry 1994–1996
1 month–12
years
100
17(17.0)
24
John et al.
(2001)
Singhi et al.
(2002a)
Tamil Nadu
1997–1998
0–60 years
61
1(1.6)
Chandigarh
–
1 month–12
years
107
23(21.5)
Singhi et al.
(2002b)
Chandigarh
1998–1999
3 months–12
years
69
6(8.7)
17
18
22
25
26
Study ID
13
The proportion of Haemophilus influenzae Type B isolates
in case series of endemic bacterial meningitis (cont)
S.N
Study ID
State
Year
Age group
No. of cases Haemophilus
Influenza (%)
26
Singhi et al.
(2002b)
Chandigarh
1998–1999
3 months–12
years
69
6(8.7)
27
Chinchankar et al.
(2002)
Maharashtr
a
1997–1999
1 month–5
years
54
14(25.9)
28
Hemalatha et al.
(2002)
Andrha
Pradesh
1998–2000
1–5 years
120
6(5.0)
29
Shivaprakash et al.
(2004)
Karnataka
–
Paeds
204
3(1.5)
30
Singhi et al.
(2004)
Mani et al.
(2007)
Shameem et al.
(2008)
Chandigarh
1993–1996
1–12 years
88
9(10.2)
Karnataka
1996–2005
All ages
385
7(1.8)
Karnataka
2003–2007
Paeds
236
61(25.8)
Minz et al.
(2008)
Tamil Nadu
1997–1999
0–4 years
97
6(6.2)
31
32
33
14
Case Fatality Rates
Author/Year
Syndrome
Site
CFR (%)
Kabra 1991
Hib meningitis
25
Steinhoff 1998
Hib meningitis
Jaipur,Jodhpur,
Delhi , Kolkata
Vellore
Thomas 2002
Hib meningitis
IBIS
20
Chinchankar 2002
Hib meningitis
Pune
21
Thomas 2002
Any invasive Hib
disease
IBIS/1994-1997
16
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CFR in Hib Meningitis – 20-29%
Hib invasive disease CFR – 16%
• In ICMR study even the 0.03 per cent death rate in spite of hospital treatment amounts to
1 per cent case fatality; 50 times higher would be 50 per cent case fatality (~15 deaths/1000)
– very likely if untreated *
• UNICEF projection of 14 deaths due to pneumonia per 1000 under-five children is not at all
inconsistent with the ICMR study data – even though they derive through
different routes and from different denominators*
*Indian J Med Res 132, October 2010, pp 450-455
15
Bacterial Pneumonia
• A similar pattern is observed in Indian studies of
pneumonia also
• A study by Kumar L, Ayyagari A. (The etiology of lobar
pneumonia and empyema thoracis in children. Indian Pediatr 1984;
21:133–137) found no blood or pus cultures positive
for Hib for 64 children with acute pneumonia or
empyema,
- but 2 (8%) of 26 blood and 6 (16%) of 38
pleural fluid specimens were positive for Hib by
use of antigen detection methods
16
Hib Pneumonia in India
Author/Year Syndrome
Location
Age
Delhi
0-5 years
110*
19
%
isolation
rate of any
organism
55
Kumar 1984 Pneumonia Chandigar < 11 years
h
64*
13
42
132*
15
88
Bahl 1995
Patwari
1996
Pneumonia
Pneumonia
Delhi
< 12 years
Study Size % disease
due to Hib
13% to 19% of pneumonia and LRTI due to Hib
17
Multi-center surveillance for pneumonia & meningitis
among children (<2 yr) for Hib vaccine probe trial
preparation in India
Indian J Med Res 131, May 2010, pp 649-658
•
•
•
•
Chandigarh, Vellore, Kolkata
18 m to 24 m – N 17951
Enrollment from July 05 to Dec 06
Parents explained about s/s of pneuonia and
meningitis
• Pneumonia and meningitis admitted to
hospitals also enrolled
• CSF culture, PCR, LAT, Bl culture, CXR
18
• Severe clinical pneumonia
– 2717 to 7890 per 100,000 child-years
• Suspected meningitis
– 1971 to 2433 per 100,000 child-years
• NP carriage
– 6 to 7.6 %
• Incidence of clinical pneumonia comparable
with other studies from India and a higher
incidence of suspected meningitis
19
Drug Resistant Hib
•
•
•
•
1st cases of Drug resistant Hib from Chandigarh (1990)1
Vellore study (1992) reported – 42.5% of Hib isolate
MDR strains2
Nagpur study (1996) reported – 80% MDR srains3
IBIS (1999) reported – 56% resistance to Chloramphenicol
- 40% resistance to Ampicillin4
1. Singh N et al. Multiple resistant Hib meningitis. Indian Pediatrics 1990;27:502-04.
2. John TJ et al. Hib disease in children in India.Pediatric Infec Dis J. 1998;17(9):5169-71
3. Agarwal v et al. Characterisation of invasive hemophilus Influenza isolated in Nagpur,
Central India. Indian J Med Res. 1996;103:296-98
4. Invasive Hemophillus Influenza disease in India: a preliminary report of prospective
multihospital surveillance IBIS. Pediatr Infect Dis J. 1998; 17:3172-75
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HIB-Multicentric Study (IBIS)
Antimicrobial
agents
% of Isolates
Resistant
Ampicillin
33
Cefotaxime
0
Chloramphenicol
43
Trimetho.-sulfamethox 38
Erythromycin
5
Intermediate
7
0
10
3
33
Total
40
0
53
41
38
Antibiotic Resistance of 57 Haemophilus influenzae isolates from
6 IBIS centres, 1993 to 1995
21
Nasopharyngeal Carriage
• Hib nasopharyngeal carriage among infants was
found to be common in India
• Study from Chandigarh, researchers found 11.2%
of 1000 children below 2 years were carriers of H.
influenza - 69% belonged to type b and the rest
were non-typable*
• Hib carriage rates increases throughout infancy
and into the second year of life, peaking at age
18-21 months at a prevalence of 20.3%*
* Sekhar S, Chakraborti A, Kumar R. Haemophilus influenzae colonization and its risk factors
in children aged <2 years in northern India. Epidemiol Infect. 2009; 137:156-60
22
Estimates
• From available studies reviewers estimated that there
may be as many as 75 to 100 cases of meningitis
caused by this organism per year per 100,000 children
<5 years of age1
• Hib vaccine probe - total pneumonia cases caused by
Hib would be 2,083,333 or 2 million cases per year.
These are crude extrapolations from the multi-centre
study2
1.
John TJ, Cherian T, Raghupathy P. Haemophilus influenzae disease in children in India:
a hospital perspective. Pediatr Infect Dis J 1998; 9: S169–71
2. Gupta M, Kumar R, Deb AK, Bhattacharya SK, Bose A, John J et al.
A multi-centre surveillance for pneumonia and meningitis among children (<2 yr)
for Hib vaccine probe trial preparation in India. Indian J Med Res 2010; 131; 649-658.
23
Prospective culture based studies for
pneumonia in world
• Pneumococcus: 30-50%
• Hib: 10-30%
• Others:
– NTHi:
• New Papua Guinea (Lung culture)
• Pakistan (Blood isolates)
– S. Aureus:
• Chile (Lung aspirate)
• WHO 42% (Blood aspirate)
– Non-typhoid salmonella:
• Africa, Malawi (severe pneumonia)
• Viruses: 30-50%
– RSV: 15-40%
– Others:
Rudan I Bull WHO 2008;86:408-16
24
Vaccine probe studies
• Pneumococcus and Hib are two important vaccine
preventable causes of pneumonia
• Vaccine effectiveness against radiological proven pneumonia
studies in developing countries
– Hib: 15-30% (Hib conjugate vaccine)
Rudan I Bull WHO 2008;86:408-16
25
3 Hib probe studies
• Pilot or Probe introduction of specific vaccine,
with measurement of syndromes pre-and
post-vaccination, necessary to quantify the
pre-vaccination prevalence/incidence
• Gambia , Chile, Indonesia
– 21- 23% of hospitalized pneumonia cases with
radiographic infiltrates were prevented
26
Hib impact studies
• >95% efficacy- Europe, US and Gambia
• Also in Chile, Brazil, Columbia, Kenya, Malawi
• Lombok
– Measurable impact on clinical pneumonia but no
impact on radiological pneumonia
• Bangladesh (SEA)
– Meningitis reduced by 90%
– Radiological pneumonia reduced by 16-32%
27
The Gambia Hib vaccine program resulted in virtual
disease elimination
Incidence of Hib Meningitis/ 100,000 (children <5 years) in the Western Region of the Gambia
Hib trial
National Immunization with Hib
Despite supply
interruptions, disease
has been virtually
eliminated
Adapted from Adegbola R et al. Lancet, 2005
28
Hib Cases and Incidence
CHILE, 1996-2000
Children <5 years of age
180
12
160
10
140
8
100
6
80
60
INCIDENCE
CASES
120
4
40
2
20
0
0
1996
1997
1998
Cases
1999
2000
Incidence/100,000
Source: Notificación
Obligatoria, MINSAL.
29
WHO statement
The lack of local surveillance data
should not delay the introduction of
the vaccine especially in countries
where regional evidence indicates a
high burden of disease
30
THANKS
31