Results of The Gambia Pneumococcal
Vaccine Trial
netSPEAR 3rd Annual
Conference
November 14-15, 2005
Cutts et al, Lancet 2005;365:1139-1146
Pneumococcus causes a variety of
diseases, each of which can be caused by
other organisms
INVASIVE NON-INVASIVE
Meningitis Non-bacteraemic
Bacteraemia (sepsis) pneumonia
Bacteraemic
pneumonia Sinusitis
Otitis media
Peritonitis
Septic arthritis
Incidence of Invasive Pneumococcal
Disease in Children <2 Years by Population
Incidence, cases/100,000 pop
10000
2053
1000 458
166.9 213
100 45.3 49.1
10
1
multisite
Aboriginals
Finland
Chile
Kenya
Gambia
Australian
USA,
Sources: Robinson KA JAMA 2001; Davidson M JID 1994; O’Dempsey TJ PIDJ 1996;
Levine MM PIDJ 1998;Torzillo PJ. Med J Austr 1995;
Eskola J JAMA 1992; Berkley NEJM 2005
Bacterial infections contribute to a
disproportionately high number of ALRI deaths
Cases of ALRI ALRI Deaths
31% 31%
48%
54%
15% 21%
Bacterial Mixed Viral Bacterial Mixed Viral
Strategies such as vaccination and case management are aimed
at preventing cases of deaths due to bacterial ALRI
Earlier studies have established the high
efficacy of the conjugate vaccine against
vaccine type invasive disease
Site Vaccine Cases split Efficay %
Cont:Vac (95% CL)
NCKP PCV-7 39:1 97.4
(82.7, 99.9)
Navajo PCV-7 8:2 76.8
(-9.4, 95.1)
South Africa PCV-9 13:2 84.6
(HIV-uninfected) (32, 98.3)
South Africa PCV-9 19:8 57.9
(HIV-infected) (-0.7, 84.1)
Definitions
End point consolidation
End point consolidation: A dense opacity that may
be: (a) a fluffy consolidation of a portion or whole of
a lobe or of the entire lung, often containing air-
bronchograms and sometimes associated with pleural
effusion.
Atelectasis of an entire lobe that produces a
dense opacity and a positive silhouette sign with
the mediastinal border will be considered to be an
end point consolidation.
Pneumococcal Conjugate Vaccine
Prevents CXR Confirmed Pneumonia (all
cause)
Site Vaccine Definition/Method Efficacy %
(95% CI)
NCKP PCV-7 Infiltrate or 21 (4, 34)
empyema
Clinical radiologist
NCKP PCV-7 WHO definition 30 (11, 46)*
Radiologist and
pediatrician
South Africa PCV-9 -do- 25 (4, 41)
(HIV neg)
Refs: Black et al PIDJ 2001; Klugman et al NEJM 2003
* Black et al. ISPPD4 abstract
The Gambia Pneumococcal Vaccine Trial
Study end points
Primary
Radiologically confirmed pneumonia (WHO)
Secondary
Clinical and severe clinical pneumonia
Invasive pneumococcal disease
All-cause hospital admissions
Safety
Other a-priori analysis
All-cause mortality
Admissions with potential IPD-related clinical
syndromes
Schematic of study area, The Gambia
Study area
The Gambia Pneumococcal Vaccine Trial
Study methods : overview
Children enrolled at ~ 110 govt vaccination clinics
Vaccine: Pneumo vaccine or placebo mixed with DTP-
Hib (Tetramune®) given according to EPI schedule
Home visits every 3 months till age 30 months or 30
April 2004 for mortality surveillance
Surveillance for pneumonia and invasive
pneumococcal disease at Basse health centre (URD)
and Bansang hospital (CRD), with referrals of children
from peripheral health centres to hospitals.
General information
Recruitment dates: 18/08/00 – 07/02/03
Vaccination dates: 18/08/00 – 30/04/03
Follow-up to : age 30 months/death/withdrawal/ 30th
April 2004
• 22,170 children screened
• 17,437 (79%) participated
• 16,344 (94%) entered per-protocol analysis
• Median age at dose 1 = 11 weeks
• Median age at dose 3 = 24 weeks
Summary of efficacy results
Outcome VE % (95% CI) Rate reduction (/1000 cy)
(95% CI)
X-ray pneumonia 37 (27, 45) 15 (10,19)
Clinical pneumonia 7 (1, 12) 17 (3, 31)
Vaccine type IPD 77 (51, 79) 2 (1, 3)
All serotypes IPD 50 (21, 79) 2 (1, 3)
All-cause admissions 15 (7, 21) 15 (7, 23)
All-cause mortality 16 (3, 28) 5 (1, 9)
Per-protocol analysis
Estimated costs and benefits from
pneumococcal vaccination in The
Gambia
PCV 9 PCV 7
Deaths averted 323 193
Program costs 770,000 770,000
($ 5 per dose)
$/DALY 69 123
averted
3X PC GNI 721
Sinha A, Lieu T – Personal communication (preliminary data, work in progress)
Conclusions
Pneumococcal disease represents a significant
burden in terms of childhood morbidity in The
Gambia.
Pneumococcal vaccine can prevent a large
proportion of these illnesses and can
significantly reduce mortality among children
in a typical rural African setting, especially in
hard-to-reach populations.