Short summary

Studies suggest that vaccines may have non-specific effects (NSE), i.e. health effects which go beyond the specific protective effects against the targeted diseases.  Live attenuated vaccines, such as BCG and Measles, though protective against the target diseases, may also be associated with strong survival benefits for children. Inactivated vaccines, such as diphtheria-tetanus-pertussis (DTP), though protective against the target diseases, may be associated with increased mortality, especially for females. This study intends to carry out an evaluation of the non-specific effects of BCG, DTP and measles vaccines on child survival in northern Ghana.

Rationale

The overall aim of all childhood intervention programmes is to reduce mortality and morbidity. The introduction of the WHO childhood immunization programme is one of the key strategies of preventive health care in poor countries and much of the decline in child mortality and morbidity in developing countries can be attributed to the impact of immunizations.

In the current paradigm, vaccines are typically assessed based on the antibody response or clinical protection against the target disease. Their overall effects on child health outcomes are estimated from the proportion of morbidity and mortality due to the target diseases. The time of administering a vaccine is based on creating an optimal antibody response and to protect children from being infected by the specific disease. There is no consideration of the possibility that vaccines may interact because they all affect the immune system and result in unintended positive or negative effects on child survival.

Observational studies and randomized controlled trials have shown that live attenuated vaccines may be associated with improved child survival which cannot merely be explained by their prevention of the target disease. In contrast, non-live vaccines may be associated with increased susceptibility to unrelated pathogens. Vaccines interact, and the timing and sequence of administering the vaccines may be important for child survival.

The World Health Organization (WHO), UNICEF and other organisations have been strategizing on ways to improve the coverage levels of vaccines over the years. This has yielded some significant improvement with increasing coverage levels in many low- and middle-income countries. Despite the improvement in vaccination coverage, vaccines are still delayed and sometimes administered out of the WHO recommended sequence.

This study intends to evaluate the non-specific effects of three of the most used routine vaccines (BCG, DTP and Measles) on all-cause mortality, and assess how changes in vaccine administration over the period contributed to reducing child mortality in a health and demographic surveillance system site in Navrongo, Northern Ghana. 

Description of the cohort

The study participants were all children under five years observed from the interview date in which their vaccination status were assessed till they either died or were censored. The children were recruited from the communities using the Navrongo Health and Demographic Surveillance System (HDSS) in the Kassena-Nankana Districts in Northern Ghana.

Data and biological material

We document demographic events such as births, deaths, pregnancies and migrations 3-4 times a year since 1993 for the entire population in the study area using the Navrongo Health and Demographic Surveillance System. From 1996-2010, we collected routine vaccination data once annually in the October-December round of data collection from health cards of children aged two years or below. From 2011 to 2015, we increased the frequency of the routine vaccination data collection to three times in a year (every four months) from children aged three years or below. We also analysed vaccination and survival data collected in 1989-1991 in relation to a vitamin A trial for children aged 6 months to five years.

Collaborating researchers and departments

Bandim Health Project, Guinea-Bissau

• Peter Aaby, MSc, DMSc

Statens Serum Institut, Denmark

• Christine Stabell Benn

Navrongo Health Research Centre, Ghana

Publications associated with the project

Fewer out-of-sequence vaccinations and reduction of child mortality in Northern Ghana Welaga P, Oduro A, Debpuur C, Aaby P, Ravn H, Andersen A, Binka F, Hodgson A. Vaccine. 2017 Apr 25;35(18):2496-2503. doi: 10.1016/j.vaccine.2017.03.004. Epub 2017 Mar 22

Non-specific effects of diphtheria-tetanus-pertussis and measles vaccinations? An analysis of surveillance data from Navrongo, Ghana. Welaga P, Nielsen J, Adjuik M, Debpuur C, Ross DA, Ravn H, Benn CS, Aaby P.Trop Med Int Health. 2012 Dec;17(12):1492-505. doi: 10.1111/j.1365-3156.2012.03093.x. Epub 2012 Sep 24. Analysis of Coverage of Fully Immunized Child (FIC), Associated Factors, Outcomes, and Impact Using Routinely Collected Population Cohort Data. Mutua M, Welaga P, Zandoh C, Kagoné M, Hanifi MA, Martins C, Fisker A, Andersen A, Benn CS, Aaby P, Ravn H. 2001-2014. INDEPTH 2015 (Report submitted to GAVI).

The non-specific effects of vaccines and other childhood interventions: the contribution of INDEPTH Health and Demographic Surveillance Systems. Sankoh O, Welaga P, Debpuur C, Zandoh C, Gyaase S, Poma MA, Mutua MK, Hanifi SM, Martins C, Nebie E, Kagoné M, Emina JB, Aaby P. Sankoh O, Welaga P, Debpuur C, Zandoh C, Gyaase S, Poma MA, Mutua MK, Hanifi SM, Martins C, Nebie E, Kagoné M, Emina JB, Aaby P.Int J Epidemiol. 2014 Jun;43(3):645-53. doi: 10.1093/ije/dyu101. Epub 2014 May 30.