Randomized Study of Not Giving Diphteria-tetanus-pertussis Vaccination With or After Measles Vaccination

Diphteria-tetanus-pertussis (DTP) Vaccination and Child Survival: Randomized Study of Not Providing DTP Vaccination Together With or After Measles Vaccination

In non-randomized studies, routine childhood vaccinations have been observed to have non-targeted effects. Difteria-tetanus-pertussis (DTP) vaccine provided with or after measles vaccine (MV) is associated with increased mortality in areas with herd immunity to pertussis.

We will examine in a randomised study of 6000 children the effect of not administering DTP simultaneously with or after MV on overall child mortality, hospitalization rates, and the immunological responses after vaccination. We will also examine potential sex-differential effects in the outcomes and interactions with other vaccines, other health interventions and season.

Study Overview

• Status: Completed
• Conditions: Mortality; Hospitalization; Adverse Events
• Intervention / Treatment: Biological: DTP3/4+OPV+MV versus OPV+MV or DTP4+OPV4 versus OPV4

Detailed Description

Background: Infectious diseases are the main cause of high child mortality in Africa. In several non-randomised studies, routine childhood vaccinations have been observed to have non-targeted effects. Live vaccines like measles vaccine (MV) seem to protect against overall mortality, whereas killed vaccines, like DTP, may have no beneficial effects, especially for girls. DTP provided with or after MV may be associated with increased mortality. The mechanisms behind these effects are unknown.

Hypothesis: Not providing DTP together with or after MV is associated with a 35 % reduction in overall mortality and 23% reduction in hospitalizations.

Objectives: To examine in a randomised study of 6000 children the effect of not administering DTP simultaneously with or after MV on

1. Overall child mortality
2. Hospitalization rates and major causes of hospitalization
3. The immunological profile after vaccination
4. Sex-differences in the above mentioned outcomes

Methods:

Surveillance system: BHP's demographic surveillance system in Bissau covers 6 districts with a population of 90,000; 3,500 children are born each year.

Hospitalizations: There is only one pediatric ward in Bissau and all hospitalizations are identified in the BHP register.

Vaccinations: Vaccinations are provided and registered at the 3 health centres in the study area.

Intervention: In this study 6000 children are randomised as they come to receive DTP3 or DTP booster with or after measles vaccination (MV) at the local health centres. Children will be randomised to DTP3+OPV3 and MV versus OPV3 and MV or DTP4+OPV4 versus OPV4 (booster doses).

Follow-up: The children will be followed until 4 years of age or end of study.

1. Adverse effects: In the first month after vaccination, 1000 children will be visited daily for three days and then weekly to register morbidity and consultations.
2. Hospitalizations: The children will be followed at the pediatric ward.
3. Mortality: Children will be followed by the routine surveillance system. Furthermore, all children will be visited yearly and finally when they reach four years of age. When a death is detected, a physician will conduct a verbal autopsy.

Sample size: With a total of 7500 person-years of follow-up, we will be able to document a 35% reduction in mortality and a 23% reduction in hospitalizations. A subgroup of children will be examined for possible differences in immunological profile after vaccination.

Ethical considerations: Herd immunity to pertussis should not be affected as, due to the intervention, more children is vaccinated.

• Study Type: Interventional
• Enrollment (Actual): 6534
• Phase: Phase 4

Contacts and Locations

Study Locations

• Guinea-Bissau
  • Bissau, Guinea-Bissau
    • Bandim Health Project, Apartado 861

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 months to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The child should be missing DTP3 or DTP4
2. The child should have received DTP2
3. The child should have received MV already or receive MV on the day of enrolment

Exclusion Criteria:

Normally applied contraindications for receiving vaccinations, including high fever

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality till 4 years of age	June 2011
Hospitalisations till 4 years of age	June 2011
Adverse events 1 month after intervention	December 2008

Secondary Outcome Measures

Outcome Measure	Time Frame
Immunological responses	July 2008
Morbidity	June 2011

Collaborators and Investigators

• Sponsor: Bandim Health Project
• Collaborators: Aarhus University Hospital; Rigshospitalet, Denmark
• Investigators: Principal Investigator: Peter Aaby, DMSc, Bandim Health Project

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: October 25, 2005
• First Submitted That Met QC Criteria: October 25, 2005
• First Posted (Estimate): October 27, 2005

Study Record Updates

• Last Update Posted (Estimate): February 28, 2012
• Last Update Submitted That Met QC Criteria: February 25, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Vaccination; Non-specific effects; Sex; Child mortality; DTP
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Corynebacterium Infections; Diphtheria
• Other Study ID Numbers: CVEK2005-7041-45-DTPMV; CVEK2005-7041-45