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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.
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INTERVENTION RESEARCH TO IMPROVE HEALTH IN DEVELOPING COUNTRIES: PROGRESS AND FUTURE CHALLENGESCelebrating 40 years of the MRC Tropical Epidemiology Group29-30 March 2012 DECADES OF VACCINESVaccine trials: some highs and lows 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 TRIALS Vaccine trials • Venezuela • Malawi • South India Nine-banded armadillo
STUDIES OF THE PROTECTIVE EFFECT OF BCG VACCINATION AGAINST LEPROSY Merle, Cunha & Rodrigues, 2010 STUDY YEAR Latitude 0 Relative risk 1 RR (95% CI)
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 Convit et al 1992
RISK OF LEPROSY ACCORDING TO NUMBER OF BCG SCARS AT ENTRY TO THE TRIAL 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 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 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 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
Efficacy of killed whole parasite vaccines against leishmaniasis Iran Noazin et al, 2009
Introduction of Hepatitis B vaccine in The Gambia (Stepped-wedge design) . . . . 9 8 7 6 5 4 3 2 1 Usual EPI vaccines given Vaccination team Usual EPI vaccines given plus HBV 1 2 3 4 5 Time since start of programme (years)
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 Van de Sande et al, 2007