decades of vaccines vaccine trials: some highs and lows

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DECADES OF VACCINES Vaccine trials: some highs and lows 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 Peter Smith

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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 Presentation

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Page 1: DECADES OF VACCINES Vaccine trials: some highs and lows

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

Page 2: DECADES OF VACCINES Vaccine trials: some highs and lows

DTP3 COVERAGE 1980- 2008

GAVI 2011

Page 3: DECADES OF VACCINES Vaccine trials: some highs and lows

MRC TEG: INVOLVEMENT IN VACCINE TRIALS

• DENGUE• HAEMOPHILUS INFLUENZA• HEPATITIS B• HIV• HPV• HOOKWORK• HSV2• LEISHMANIASIS• LEPROSY• MALARIA• PNEUMOCOCCAL DISEASE• ROTAVIRUS• SCHISTOSOMIASIS (BOVINE)• TUBERCULOSIS

Page 4: DECADES OF VACCINES Vaccine trials: some highs and lows

MRC TEG: INVOLVEMENT IN VACCINE TRIALS

• DENGUE• HAEMOPHILUS INFLUENZA HEPATITIS B• HIV• HPV• HOOKWORK• HSV2 LEISHMANIASIS LEPROSY• MALARIA PNEUMOCOCCAL DISEASE• ROTAVIRUS• SCHISTOSOMIASIS (BOVINE)• TUBERCULOSIS

Page 5: DECADES OF VACCINES Vaccine trials: some highs and lows

LEPROSY VACCINE TRIALSVaccine trials• Venezuela• Malawi • South India

Nine-banded armadillo

Page 6: DECADES OF VACCINES Vaccine trials: some highs and lows

STUDY YEAR Latitude 0 Relative risk 1 RR (95% CI)

STUDIES OF THE PROTECTIVE EFFECT OF BCG VACCINATION AGAINST LEPROSYMerle, Cunha & Rodrigues, 2010

Page 7: DECADES OF VACCINES Vaccine trials: some highs and lows

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

Page 8: DECADES OF VACCINES Vaccine trials: some highs and lows

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

Page 9: DECADES OF VACCINES Vaccine trials: some highs and lows

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

Page 10: DECADES OF VACCINES Vaccine trials: some highs and lows

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

Page 11: DECADES OF VACCINES Vaccine trials: some highs and lows

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

Page 12: DECADES OF VACCINES Vaccine trials: some highs and lows

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

Page 13: DECADES OF VACCINES Vaccine trials: some highs and lows

Efficacy of killed whole parasite vaccines against leishmaniasis

Noazin et al, 2009

Iran

Page 14: DECADES OF VACCINES Vaccine trials: some highs and lows

GLOBAL BURDEN OF PNEUMOCOCCAL DISEASE

Page 15: DECADES OF VACCINES Vaccine trials: some highs and lows

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)

Page 16: DECADES OF VACCINES Vaccine trials: some highs and lows

.

.

.

.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)

Page 17: DECADES OF VACCINES Vaccine trials: some highs and lows

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.

Page 18: DECADES OF VACCINES Vaccine trials: some highs and lows

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

Page 19: DECADES OF VACCINES Vaccine trials: some highs and lows

Thank you