• Vaccination coverage
  
• Vaccine efficacy
  
• Measles specific mortality
  
• All cause mortality until 3 years of age
  

• Measles antibodies at 6, 7½, 9, 10½ and 18 months of age
  
• T-cells at 6, 7½, 9, 10½ and 18 months of age
  
• Thymus size at 6, 7½, 9, 10½ months of age
  
• Neopterin level at 7½ months of age
  
• Beta-2-microglobulin level at 7½ months of age
  
• Hepatitis B antibodies at 7½, 9 and 10½ months of age
  
• Tetanus antibodies at 9 months og age
  
• Delayed type hypersensitivity at 7½ months of age
  
• Skin prick test (allergy) at 7½ months of age
  
• Morbidity from 6 to 18 months of age
  
• Anthropometric measures at 6, 7½, 9, 10½ and 18 months of age
  

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.