Non-Specific Effects of Standard Titre Measles Vaccination
Condition: Measles
MeSH terms: Measles
Study type: Interventional
Phase: Phase 4

Summary: 
      The general objectives of the proposed research work are:

      A1) to reduce childhood mortality in developing countries through better control of measles
      infection by finding the best immunization strategy, and A2) to investigate the hypothesis
      that standard titre measles immunization is associated with non targeted beneficial effects
      on childhood morbidity and mortality in developing countries.

      The measurable, specific objectives of the present proposal are:

      B1) to examine whether a two-dose strategy for measles immunization at 6 and 9 months of age
      can reduce measles incidence by 50% through better coverage or improved seroconversion, and
      B2) to examine whether a two-dose strategy for measles immunization at 6 and 9 months of age
      can reduce childhood mortality by 20% through better coverage, better protection against
      measles or non targeted beneficial effects, and B3) to determine the magnitude and duration
      of non-measles related changes in morbidity patterns after standard titre measles
      immunization, in particular to test whether measles immunization is associated with a 15%
      reduction in the risk of diarrhoea, and B4) to determine non-measles related immunological
      changes among recipients of measles vaccine in order to establish possible pathways for the
      non targeted effects of standard titre measles immunization.
    

Detailed description: 
      Background. Measles is the major killer among vaccine preventable diseases with an estimated
      one million deaths/year in developing countries. Though a good vaccine exists, the current
      immunization strategy of one dose at 9 months is far from optimal; too many children get
      measles before the age of immunization, coverage is too low when immunization has to wait
      until 9 months of age, and the protective efficacy is insufficient with the current vaccine
      given at 9 months of age. There is therefore a need for alternative immunization strategies
      or new vaccines.

      Evaluations of vaccines have usually been based on a disease specific perspective; i.e.
      evaluation of specific immunity, and protective efficacy against the specific disease, its
      complications and mortality. However, our research from Guinea-Bissau, Senegal and Bangladesh
      has indicated that measles immunization and measles infection may have non-specific
      beneficial effects. The present protocol is an attempt to assess the magnitude and possible
      mechanisms of the non targeted beneficial effects of measles immunization and measles
      infection as well as an attempt to assess some of the practical implications of the
      hypothesis about non-specific beneficial effects.

      Approach and methodologies. We tested a two dose measles immunization strategy at 6 and 9
      months compared with the currently recommended strategy of one dose at 9 months. The children
      were be randomized to receive measles immunization at 6 and 9 months of age or inactivated
      polio at 6 months and measles at 9 months of age.

      The non targeted effects of measles immunization on mortality and morbidity are best studied
      within a randomized trial comparing immunized and unimmunized children. In order to study the
      impact on non-measles related morbidity, some children recruited for the immunization trial
      will be included in weekly morbidity surveillance for diarrhoea, respiratory infections and
      malaria which are the most important disease complexes for childhood mortality in
      Guinea-Bissau.

      Possible immunological differences between measles immunized and unimmunized children will be
      examined through measurements of T-lymphocyte levels, neopterin, beta2-microglobulin, delayed
      hypersensitivity (Multitest), allergic reactions (skin prick tests), antibody responses to
      other antigens (tetanus) and thymus growth (by sonography). Functional differences will be
      tested by response to a second vaccine antigen (HBV) at 7½ and 9 months of age when only one
      group has received measles vaccine.
    

Intervention name(s): Measles and inactivated polio vaccine
Intervention type(s): Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Non-specific effects of vaccines; Infant mortality; Child mortality; Mortality; Morbidity; Measles vaccine; Measles; Immunisation; Low income country; Guinea-Bissau; Bandim Health Project; Immunology