UPDATE ON PNEUMOCOCCAL DISEASE
SEROTYPES:
TOWARDS THE INTRODUCTION OF VACCINATION
IN NIGERIA
PROFESSOR G.C. ONYEMELUKWE (MON)
Ahmadu Bello University Teaching Hospital, Zaria
EXPERT PANEL MEETING ABUJA JUNE 16TH 2010 ON INVASIVE
PNEUMOCOCCAL DISEASE (IPD)
1. Honourable Minister of Health, Prof. Onyebuchi Christian Chukwu Represented
by
Dr. Michael Anibueze, Director Public Health FMoH
2. Executive Secretary/CEO NPHCDA, Dr. Mohammed Ali pate Represented by
Dr. E. Abanida, Director, Disease Control and Immunization
3. Prof. G.C Onyemelukwe MON Professor of Medicine and Immunology
Member National Certification Committee (NCC) on Polio Eradication
4. Dr. Amgad Gamil
Regional Medical Director; Vaccines
Pfizer, Africa and Middle East Region
5. Prof William Ogala
Professor of Paediatrics and Immediate Past President, Paediatric Association of
Nigeria (PAN)
6. Prof. Alice Nte
Represented by Dr. Yaguo Ide, University of Port Harcourt Teaching Hospital
7. Prof. A.G Falade
Professor of Paediatrics
Represented by Dr. Regina Oladokun, University College Hospital, Ibadan
8. Dr. U. Nnebe – Agumadu
Paediatrician, University of Abuja
Member HERFON Committee on Non-Communicable Diseases
9. Dr. Abdulrazaq G. Habib
Aminu Kano Teaching Hospital, Kano
President, Nigeria infectious Diseases Society
10. Dr. Stephen Obaro
Associate Professor of infectious Diseases
Michigan State University, USA
11. Dr. Beckie Tagbo
Institute of Child Health, University of Nigeria Teaching Hospital, Enugu
Member, PAN Immunization Committee
12. Dr. Adejumoke Ayede
Peadiatrician, University College Hospital, Ibadan
13. Dr. Kodjoh Soroh
Medical Director, Pfizer NEAR
14. Dr. Wadzani Gashau
Chairman, National Teaching Working Group (TWG), Antiretroviral Treatment
WORLD WIDE DISTRIBUTION OF
PNEUMOCOCCAL DISEASE.
Brien K O et al. Lancet 2009; 347:893-902
PNEUMOCOCCAL BUBBLE OF DEATHS
IN CHILDREN < 5 YEARS OF AGE.
Brien K O et al. Lancet 2009; 347:893-902
Numbers of cases of disease by
regions
•
Syndrome
Global
AFRO
PAHO
EMRO
EURO
SEARO
WPRO
•
Pneumonia
13.8m
3.81m
648k
1.45m
238K
5.33m
2.34m
•
Meningitis
103k
43k
9500
9700
3300
24k
13k
•
NonP-NonM
538k
215k
55k
51k
19k
122k
76k
•
Total
14.5m
4.06m
713k
1.51m
260k
5.48m
2.43k
JUSTIFICATION
Director General (WHO) Dr. Margaret Chan (2009),
Pneumonia and Malaria kill More Children.
pneumonia, a “Forgotten Disease “
2. MDG 4- Child and Maternal mortality reduction by
(2015)
3. Global burden – India 27%
China 17%
Nigerian 5%
4. 7million Nigerians with IPD – 380/100,000 mortality
5. 57% Pneumococcal deaths in Africa
6. Nigeria in Pneumococcal belt of Africa with high child
and adult mortality despite antibiotics
1.
Pneumococcal Global Serotype Project (< 5
years age) 1980 – 2007.
Johnson et al 2010
Justification: 800,000 children die per year
*
IPD > 90% developing countries (Africa, Asia,
Latin America).
*
Findings
1. Six to eleven serotypes cause more than 70% IPD
2. Seven commonest
1,5,6A,6B, 14, 19F, 23F.
3. Serotype global ranking 14, 6B, 1, 23F, 5, 19F, 6A,
19A, 9V, 18C, 2, 4, 7F, 12F, 3, 12A. 8, 46, 15B, 45
4. Africa 14, 1,5, 23F, 19F, 3, 6B
5. 19A most common antibiotic resistance
Pneumococcal Conjugate Vaccines
(PCV)
Capsular polysaccharide + CRM197 = PCV
1. PCV 7 (4,6B, 9V, 14, 18C, 19F, 23F)
2. PCV 10 (Addition: 1, 5, 7F)
3. PCV 13 (Addition: 3, 6A, 19A)
- Conjugate vaccine immunogenic in 2 months of age
- Serotype specific efficacy after 4th dose
- Vaccine schedule: 2, 4, 6, months of age, 4th dose at 15
months (USA)
- Protects against meningitis, pneumonia, bacteremia,
otitis media.
Black et al., 2002.
UNITED KINGDOM PCV HISTORY
2002 PCV available, recommended for at risk
groups under 2 years
2003 PCV recommended for > 65 years old
2004 PCV for at risk children under 5 years of
age
2006 PCV added to routine childhood
immunization program
POST LICENSE SURVEILLANCE (USA)
(as part of universal infant
immunization)
1.Reduction in invasive and non-invasive
disease due to vaccine serotypes in
vaccinated
and
older
unvaccinated
population (herd immunity)
2. Fall in rate of penicillin-resistant
pneumococcal infections.
3. Small increase in invasive disease due to nonvaccine serotypes (Serotype Replacement)
Black et al., 2004; Whitney et al., 2003
UN ASSEMBLY 2010 22ND SEPTEMBER
MDG RESOLUTION
“Every woman, Every child” – Mr. Ban Ki – moon
1. Saving sixteen million women by 2015, prevent 33 million
unwanted pregnancies
2. Protect 120 million children from pneumonia, 88 million
from stunting.
- Stakeholders – governments, policy makers, donor countries,
NGO’s, communities, health workers, business sector,
professional associations, academic/ research institutions.
Nigerian commitment and endorsement 2010 – 2015 as part
of National Health Plan: 20-2020 National Vision 31.63 US
dollars per capital, 5% - 15% Federal, State, Local
Government Budget.
EXPERT COMMITTEE RECOMMENDATION
PCV 13 VACCINATION IN NIGERIA
1. Routine immunization of children in Nigeria in a
three or four dosage schedule at 6 weeks to 5 years
of age
2. Vulnerable population such as sickle cell disease
patients at any age
3. HIV infected children and adults
4. Elderly people aged 65 years and above
5. Other major disease conditions such as
malignancies, renal failure, nephrotic syndrome,
liver cirrhosis, diabetes mellitus, alcoholism and
chronic lung diseases
CURRENT WORLD STATUS OF PCV USE (JANUARY 2010)
introduced into
NIP: Universal 41
countries 21%
Widespread
coverage through
private market 2
countries 1%
Introduced into
NIP: risk 16
countries 8%
No current
program 134
countries
* NIGERIA
AFRICA: RESISTANCE OF 375 Isolates of S.
Pneumoniae
Antibiotics
Ivory coast
(n = 138)
Morocco
(n = 98)
Senegal Tunisia
(n = 58) (n = 58)
Total
(n = 375)
Penicillin G
Susceptible
77.5
90.8
38.3
58.6
69.9
Intermediate
18.1
8.2
53.1
34.5
25.6
Resistant
4.3
1
8.6
6.9
4.8
Amoxicillin
3.6
1
3.7
8.6
3.7
Cefotaxime-ceftriaxone 8.8
1
15
3.6
7.3
14.8
5.2
8.6
Chloramphenicol
11
2
CONTINUED
Erythromycin
52.6
4.1
11.4
32.8
28
Tetracycline
67.5
12.2
29
34.5
38.3
Rifampicin
5.8
0
0
0
2.1
Cotrimoxazole
60.5
29
19.4
36.4
*Ibadan
14.8
Hospitals Study .. Intermediate resistant to tetracycline
and all fully resistant to cotrimoxazole
• Jos Study 70.27% sensitive to penicillin
29.72% resistant to penicillin
Streptococcus pneumoniae is a gram
positive diplococcus
See Capsule
FOUR MAJOR VIRULENCE FACTORS
1. Capsular polysaccharides – Antiphagocytic
and Anti-complement
2. Pneumolysin
–
Inhibits
lymphocyte
proliferation and neutrophil chemotaxis
3. IgA1 protease – Cleaves submucosal IgA
4. Autolysin – breaks down peptidoglycan of
cell wall to aid release of pneumolysin
STREPTOCOCCUS PNEUMONIAE
STRUCTURE
PNEUMOCOCCAL SEROTYPES IN
ZARIA, NORTHERN NIGERIA
S
T
1
2
MN
23 3
10
2
PN
20 4
12 2
10 1
PP
1
CJ
3
4
5
9
10
11
1
12
15
17
2
18
19
21
2
1
3
5
4
23
25
41
45
46
48
T
2
2
1
1
1
1
51
1
4
2
1
1
70
1
2
1
PID
1
1
BC
8
3
6
T
53 7
28 2
18 1
1
4
2
1
1
1
4
1
3
7
4
1
3
3
5
1
1
3
2
KEY
ST=SEROTYPES, MN=MENINGITIS, PN= PNEUMONIA, PP=PRIMARY PERITONITS,
CJ=PRIMARY CONJUCTIVITIS, PID= PELVIC INFLAMATORY DISEASE,
BC= BACTEREMIA/ANTIGENEMIA, T=TOTAL
20
1
DISRIBUTION OF SEROTYPES IN CHILDREN
UNDER 12 YEARS (NUMBER OF CASES - 40)
SEROTYPE
%
1
47.5
3
17.5
2, 46 , 5
8.3 each
48
2.5
23
2.5
41
2.5
12
2.5
MORTALITY RELATED TO SEROTYPES IN
ADULTS AND CHILDREN
Serotype
Meningitis
Case Fatality
(%)
Pneumonia
Case Fatality
(%)
1
23
48
20
20
3
10
50
12
41.6
5
2
50
10
20
25
2
50
1
100
45
1
100
2
100
*G.C. ONYEMELUKWE AND B.M. GREENWOOD
JOURNAL OF INFECTION (1982) 5, 157-163
CONDITIONS ASSOCIATED WITH
PNEUMOCOCCAL DISEASE
1. YOUNG AGE
2. MEASLES – 15 (CHILDREN )
3. SICKLE CELL DISEASE (3 CHILDREN)
4. PREGNANT WOMEN (6 ADULTS)
5. CIRRHOSIS (2 ADULTS)
6. PERIPARTUM HEART FAILURE (1 ADULT)
*G.C. ONYEMELUKWE AND B.M. GREENWOOD
JOURNAL OF INFECTION (1982) 5, 157-163
AGES OF SEROTYPED PNEUMOCOCCAL
MENINGITIS PATIENTS
• Two year study of pneumococcal meningitis with
39% mortality
1. 50% : under 10 years
2. 32.5% : 1- 10 years
3. 17.6% : < 1 year
4. 2.65% < 2 weeks of age
Seasonality of infection- All year round
Peak periods- Drier Months: January, February,
March, April
*G.C. ONYEMELUKWE AND B.M. GREENWOOD
JOURNAL OF INFECTION (1982) 5, 157-163
Falade et al 2009 (Ibadan)
(Clin Infect Dis. 2009 Mar 1;48 Suppl
2:S190-6.)
• 2 year hospital surveillance (Age 2-59 months)
for pneumonia and meningitis- 1210 cases
• 481 (49.8%)- Meningitis
• 399 (33%) – Pneumonia
• 330 (27.2%) – Bacteremia
• 11 out of 23 Streptococcus pneumonia isolates
were typed
 Type 4 – 3 cases
 Type 5 – 5 cases
 Type 19 F- 3 cases
REFERENCES
1.
2.
3.
4.
5.
6.
Onyemelukwe GC, Greenwood BM. Pneumococcal serotypes, epidemiological
factors and vaccine strategy in Nigerian Patients. Journal of Infection (1982) 5,
157-163.
Onyemelukwe GC. Polymorph function, complement and immunoglobulins in
Nigerian patients with pneumococcal infections. Journal of Infection (1983) 7,
118-124
Taqi AM, Onyemelukwe GC. Serotypes and pneumococcal meningitis in
Nigerian Children. East African Medical Journal of Infection. (1986) 63 (1), 42-47
Onyemelukwe GC,Leinoen, M MakelaH, Greenwood BM. Response to
pneumococcal vaccination in normal and post-infected Nigerians. J Infect. 1985
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Falade AG, lagunja IA, Bakare RA, Odekanmi AA, Adegbola RA. Invasive
pneumococcal disease in children aged <5 years admitted to 3 urban hospitals
in Ibadan, Nigeria. Clin Infect Dis. 2009 Mar 1;48 Suppl 2:S190-6.
Bradford D Gessner, Judith E Mueller, Seydou Yaro. African meningitis belt
pneumococcal disease epidemiology indicates a need for an effective serotype
1 containing vaccine, including for older children and adults. BMC Infectious
Diseases 2010, 10:22. http://www.biomedcentral.com/1471-2334/10/22.
cont. REFERENCES
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Mulholland K, Levine OS, Cherian T. Burden of Streptococcus pneumoniae in
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8. Cutts FT, Zaman SMA, Jaffar S, Levine OS, Oluwalana C, Obaro SK, Leach A,
McAdam KP, Biney E, Saaka M, Onwuchekwa U, Yallop F, Pierce NF, Adegbola
RA.
Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia
and invasive pneumococcal disease in The Gambia: randomized doubleblind, placebo controlled trial.
Lancet 2005; 365: 1239-46
9. Traore Y, Tameklo TA, Njanpop-Lafourcade B-E, Lourd M, Yarou S, Niamba D,
Drabo A, Mueller JE, Koeck J-L, Gessner BD. Incidence, seasonality, age
distribution and mortality of pneumococcal Meningitis in Burkina Faso and
Togo.
Clin Inf Dis 2009; 48: S181-9
7
cont. References
10. French N, Gordon SB, Mwalukomo T, White SA, Mwafulirwa G, Longwe H,
Mwaiponya M, Zijlstra, EE, Molyneux ME, Gilks C. A trial of a 7-valent Pneumococcal
Conjugate Vaccine in HIV-Infected Adults. N Engl J Med 2010; 362: 812-22
11. Johnson H.L, Deloria – Knoll M, Levine OS, Stoszek S.K, Hance LF, Reithinger R, Muenz
LR, O’Brien KL. Systematic evaluation and serotypes causing invasive pneumococcal
disease among children under five: The Pneumococcal Global Serotype Project.
PLoS Medicine 2010. 7(10). E1000348.
12. Black S, Shinefield HR, Ling S et al. effectiveness of heptavalent pneumococcal
conjugate vaccine in children younger than five years of age for prevention of
pneumonia. Pediatr Infect Dis J. 2002, 21; 810 – 815.
13. Black S. et al., Post licensure surveillance for pneumococcal invasive disease after use
of heptavalent pneumococcal conjugate vaccine in Northern California Kaiser
Permanente. Pediatr Infect Dis J. 2004, 23; 485 – 489.
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the introduction of protein – polysaccharide conjugate vaccine
N. Eng. J. Med 2003, 348 (18); 1737 - 46
REMOVE MY BITING
TEETH AND OF THE
PNEUMOCOCCUS WITH
VACCINATION
THANK YOU
FOR
LISTENING.