Non-Specific Effects of Standard Titre Measles Vaccination

This study has been completed.
Sponsor:
Collaborators:
International Cooperation with Developing Countries
Danish Council for Development Research
Medical Research Council Unit, The Gambia
Information provided by:
Bandim Health Project
ClinicalTrials.gov Identifier:
NCT00168662
First received: September 9, 2005
Last updated: February 25, 2008
Last verified: February 2008
  Purpose

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.


Condition Intervention Phase
Measles
Biological: Measles and inactivated polio vaccine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Bandim Health Project:

Primary Outcome Measures:
  • Vaccination coverage
  • Vaccine efficacy
  • Measles specific mortality
  • All cause mortality until 3 years of age

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 7800
Study Start Date: March 1995
Study Completion Date: January 2006
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   6 Months to 8 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00168662

Locations
Guinea-Bissau
Bandim Health Project
Bissau, Apartado 861, Guinea-Bissau, 1004 Bissau Codex
Sponsors and Collaborators
Bandim Health Project
International Cooperation with Developing Countries
Danish Council for Development Research
Medical Research Council Unit, The Gambia
Investigators
Study Director: PETER AABY, MSc, Dr. Med Bandim Health Project
  More Information

Additional Information:
Publications:

Responsible Party: May-Lill Garly, Bandim Health Project
ClinicalTrials.gov Identifier: NCT00168662     History of Changes
Other Study ID Numbers: IC18-CT95-0011-Twodose1, EU grant: IC18-CT95-0011
Study First Received: September 9, 2005
Last Updated: February 25, 2008
Health Authority: Guinea-Bissau: Ministry of Health
Gambia: MRC Ethics Committee

Keywords provided by Bandim Health Project:
Non-specific effects of vaccines
Infant mortality
Child mortality
Mortality
Morbidity
Measles vaccine
Measles
Immunisation
Low income country
Guinea-Bissau
Bandim Health Project
Immunology

Additional relevant MeSH terms:
Measles
Morbillivirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on September 15, 2014