decades of vaccines vaccine trials: some highs and lows
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INTERVENTION RESEARCH TO IMPROVE HEALTH IN DEVELOPING COUNTRIES: PROGRESS AND FUTURE CHALLENGES Celebrating 40 years of the MRC Tropical Epidemiology Group 29-30 March 2012. DECADES OF VACCINES Vaccine trials: some highs and lows. Peter Smith. DTP3 COVERAGE 1980- 2008. GAVI 2011. - PowerPoint PPT PresentationTRANSCRIPT
DECADES OF VACCINESVaccine trials: some highs and
lows
INTERVENTION RESEARCH TO IMPROVE HEALTH IN DEVELOPING COUNTRIES: PROGRESS AND FUTURE CHALLENGESCelebrating 40 years of the MRC Tropical Epidemiology Group29-30 March 2012
Peter Smith
DTP3 COVERAGE 1980- 2008
GAVI 2011
MRC TEG: INVOLVEMENT IN VACCINE TRIALS
• DENGUE• HAEMOPHILUS INFLUENZA• HEPATITIS B• HIV• HPV• HOOKWORK• HSV2• LEISHMANIASIS• LEPROSY• MALARIA• PNEUMOCOCCAL DISEASE• ROTAVIRUS• SCHISTOSOMIASIS (BOVINE)• TUBERCULOSIS
MRC TEG: INVOLVEMENT IN VACCINE TRIALS
• DENGUE• HAEMOPHILUS INFLUENZA HEPATITIS B• HIV• HPV• HOOKWORK• HSV2 LEISHMANIASIS LEPROSY• MALARIA PNEUMOCOCCAL DISEASE• ROTAVIRUS• SCHISTOSOMIASIS (BOVINE)• TUBERCULOSIS
LEPROSY VACCINE TRIALSVaccine trials• Venezuela• Malawi • South India
Nine-banded armadillo
STUDY YEAR Latitude 0 Relative risk 1 RR (95% CI)
STUDIES OF THE PROTECTIVE EFFECT OF BCG VACCINATION AGAINST LEPROSYMerle, Cunha & Rodrigues, 2010
TRIAL OF LEPROSY VACCINE IN VENEZUELA
• Conducted in 29,000 close contacts of leprosy cases in 3 States of Venezuela• Individually randomised to BCG or BCG+M.leprae (double-blind)• Followed for 5 years post-vaccination, with yearly examination for disease• 150,000 person-years-at-risk – 59 post vaccination cases by July 1991
BCG alone BCG + M. leprae
Cases of leprosy 31 28Cases with onset >1 y post vaccination and M. leprae soluble antigen skin test negative
11 9
Convit et al 1992
RISK OF LEPROSY ACCORDING TO NUMBER OF BCG SCARS AT ENTRY TO THE TRIAL
No. of BCG scars No. of contacts Cases of leprosy Cases/1000 Relative risk
0 10890 34 3.12 1.0
1-2 11450 17 1.48 0.47
3-4 4433 6 1.35 0.43
5+ 2275 2 0.88 0.28
Convit et al 1992
TRIAL OF LEPROSY VACCINE IN MALAWI• Conducted in 121,000 residents of Karonga District, Malawi• Individually randomised to BCG or BCG+M.leprae or Placebo (depending on
BCG status)• Followed for 5 -9 years post-vaccination, with enhanced passive case
detection of cases of leprosy and tuberculosis
BCG Scar +ve BCG Scar -ve BCG Scar –ve and +veRandomised group
No. of persons
BCG
23,456
Placebo
23,307
RR BCG+KML
38,251
BCG
27,904
RR BCG+KML (Hi
dose)30,262
BCG
31,971
RR
Cases of leprosy 16 29 0.54* 54 37 1.09 30 30 1.05
Karonga Prevention Trial Group 1996
TRIAL OF LEPROSY VACCINE IN MALAWI• Conducted in 121,000 residents of Karonga District, Malawi• Individually randomised to BCG or BCG+M.leprae or Placebo (depending on
BCG status)• Followed for 5 -9 years post-vaccination, with enhanced passive case
detection of cases of leprosy and tuberculosis
BCG Scar +ve BCG Scar -ve BCG Scar –ve and +veRandomised group
No. of persons
BCG
23,456
Placebo
23,307
RR BCG+KML
38,251
BCG
27,904
RR BCG+KML (Hi
dose)30,262
BCG
31,971
RR
Cases of leprosy 16 29 0.54* 54 37 1.09 30 30 1.05
Cases of TB 65 62 1.04 162 101 1.21 108 92 1.25
Karonga Prevention Trial Group 1996
TRIAL OF LEPROSY VACCINES IN SOUTH INDIA• Conducted in 171,000 residents of Chingleput District, Tamilnadu• Individually randomised to BCG or BCG+KML or ICRC or Myco.W or Placebo (5-arm trial)• Initially followed for 5-6 years post-vaccination with two surveys for leprosy cases• Incidence of leprosy in trial much lower than expected• Protective efficacy in 2nd resurvey – 5-6 years post vaccination
BCG Myco.W BCG+KML ICRC0
10
20
30
40
50
60
70
80
90
Gupte et al 1998
Trial of single dose of autoclave-killed Leishmania major + BCG against cutaneous leishmaniasis in Bam, Iran
• 3600 school children (6-15y), LST-ve, randomised to BCG or BCG+ALM
• Followed for lesions 2y post-vaccination
BCG BCG+ALM
Cases of leishmaniasis
63 53
Efficacy of killed whole parasite vaccines against leishmaniasis
Noazin et al, 2009
Iran
GLOBAL BURDEN OF PNEUMOCOCCAL DISEASE
Cutts et al, 2005
EndpointVaccine (n=8189) Placebo (n=8151)
Vaccine efficacy (95%CI)Number Rate/1000 years Number Rate/1000 years
Radiographic pneumonia 207 22.1 323 35.1 37 (25 – 48)
Deaths 330 25.2 389 30.1 16 (3 – 28)
Hospital admissions 1065 89.4 1216 104.7 15 (7 – 21)
Clinical pneumonia 2172 231.5 2284 248.5 7 (1 – 12)
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.
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.987654321
Vaccinationteam
1 2 3Time since start of programme (years)
Usual EPI vaccinesgiven plus HBV
Usual EPIvaccines given
4 5
Introduction of Hepatitis B vaccine in The Gambia
(Stepped-wedge design)
Introduction of Hepatitis B vaccine in The Gambia
(Stepped-wedge design)
• 1986-1990: 60,000 infants received EPI vaccines, 60,000 received EPI vaccines + HBV vaccine
• Long term aim (40 years+) is to compare incidence of liver cancer and liver diseases in the two groups
• Sample of study population examined at age 15 years to assess long-term protective effect of vaccination against HB carrier state.
Protective effect of infant HBV vaccination against HBV chronic carriage at age 15 years
Unvaccinated Fully vaccinated Partially vaccinated
Chronic carriers/ No. examined
51/420 2/492 1/84
Vaccine efficacy (95%CI)
96.6% (91.5-99.9) 90.1% (69.9 – 99.9)
Van de Sande et al, 2007
Thank you