Clinical trial NCT00168662: Non-Specific Effects of Standard Titre Measles Vaccination
Official title: Trial of Two-Dose Standard Measles Vaccination Schedule: Long-Term Impact on Morbidity and Mortality of a Two-Dose Vaccination Schedule at 6 and 9 Months of Age Compared With a Standard Regimen of One Dose at 9 Months of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Measles
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
Lead sponsor: Bandim Health Project
Sponsor class: OTHER
Collaborators: name: International Cooperation with Developing Countries
name: Danish Council for Development Research
name: Medical Research Council Unit, The Gambia
First posted: 2005-09-15
Enrollment: 7800
Sex: ALL
Minimum age (years): 6
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: Inclusion Criteria: Infants of 6 months of age registered in the Bandim Health Project registration system and currently living in the Bandim Health Project areas: Bandim I, Bandim II, Belem and Mindará

Exclusion Criteria: Severe illness requiring hospitalisation

Primary outcomes:
measure: Vaccination coverage
measure: Vaccine efficacy
measure: Measles specific mortality
measure: All cause mortality until 3 years of age
Secondary outcomes:
measure: Measles antibodies at 6, 7½, 9, 10½ and 18 months of age
measure: T-cells at 6, 7½, 9, 10½ and 18 months of age
measure: Thymus size at 6, 7½, 9, 10½ months of age
measure: Neopterin level at 7½ months of age
measure: Beta-2-microglobulin level at 7½ months of age
measure: Hepatitis B antibodies at 7½, 9 and 10½ months of age
measure: Tetanus antibodies at 9 months og age
measure: Delayed type hypersensitivity at 7½ months of age
measure: Skin prick test (allergy) at 7½ months of age
measure: Morbidity from 6 to 18 months of age
measure: Anthropometric measures at 6, 7½, 9, 10½ and 18 months of age
Other outcomes:
Locations:
city: Bissau
country: Guinea-Bissau
facility: Bandim Health Project
state: Apartado 861
Study officials:
affiliation: Bandim Health Project
name: PETER AABY, MSc, Dr. Med
role: STUDY_DIRECTOR
References:
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