Non-Specific Effects of Standard Titre Measles Vaccination
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.
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.
Study Design
Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Conditions
Measles
Intervention
Measles and inactivated polio vaccine
Location
Bandim Health Project
Bissau
Apartado 861
Guinea-Bissau
1004 Bissau Codex
Status
Completed
Source
Bandim Health Project
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00168662
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Measles Vaccine
A live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had measles or been immunized with live measles vaccine and have no serum antibodies against measles. Children are usually immunized with measles-mumps-rubella combination vaccine. (From Dorland, 28th ed)
Measles-mumps-rubella Vaccine
A combined vaccine used to prevent MEASLES; MUMPS; and RUBELLA.
Measles Virus
The type species of MORBILLIVIRUS and the cause of the highly infectious human disease MEASLES, which affects mostly children.
Mumps Vaccine
A live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had mumps or been immunized with live mumps vaccine. Children are usually immunized with measles-mumps-rubella combination vaccine.
Rubella Vaccine
A live attenuated virus vaccine of duck embryo or human diploid cell tissue culture origin, used for routine immunization of children and for immunization of nonpregnant adolescent and adult females of childbearing age who are unimmunized and do not have serum antibodies to rubella. Children are usually immunized with measles-mumps-rubella combination vaccine. (Dorland, 28th ed)
Clinical Trials
The present study will explore the immunogenicity of AVAXIM™ 80U-Pediatric in 12-13 months Turkish children and check if the administration of the MMR trivalent vaccine on the same day b...
Immunology of Non-Specific Effects of Vaccine
OBJECTIVES - General: To investigate the immunological background for the non-specific effects of diphtheria-tetanus-pertussis (DTP) and measles vaccines on child mortality...
Early Two-Dose Measles Vaccination Trial
The specific aims are to examine in Guinea-Bissau: - whether the standard titre Schwarz (SW) or standard-titre Edmonston-Zagreb (EZ) measles vaccine will be the best vaccine strai...
The purpose of this study is to demonstrate that an investigational refrigerated vaccine with measles, mumps, rubella, and varicella is well tolerated and has similar immune response when...
Ontogeny of Measles Immunity in Infants
This is an immunogenicity study evaluating the development of the immune response of healthy infants following primary vaccination with Attenuvax at 6 or 9 months of age compared with resp...
PubMed Articles
Global control and regional elimination of measles, 2000-2011.
Widespread use of measles vaccine since 1980 has led to a substantial decline in global measles morbidity and mortality; measles elimination* has been achieved and sustained in the World Health Organi...
Nosocomial transmission of measles: An updated review.
Despite a decrease in global incidence, measles outbreaks continue to occur in developed countries as a result of suboptimal vaccine coverage. Currently, an important mode of measles transmission appe...
Measles vaccine in early infancy followed by a dose at 9 months of age protects against measles and enhances child survival through non-specific effects. Little is known of immune responses in the sho...
Measles control in Sub-Saharan Africa: South Africa as a case study.
Due to intensified measles immunization efforts, measles mortality has decreased substantially worldwide, particularly in Sub-Saharan Africa (SSA). The World Health Organization (WHO) estimated a 92%...
Despite the use of measles vaccine, measles virus continues to circulate and cause severe disease. Immune responses to the measles vaccine are variable between individuals, with up to 10% failing to p...
