Publications on the non-specific effects of vaccines and other childhood interventions from INDEPTH centres


Andersen A, Roth A, Jensen KJ, Erikstrup C, Lisse IM, Whittle H, Sartono E, Yazdanbakhsh M, Aaby P, Benn CS. The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age. Vaccine. 2013 Mar 6. pii: S0264-410X(13)00239-9. doi: 10.1016/j.vaccine.2013.02.050

Benn CS, Fisker AB, Aaby P. Changes in the effect of vitamin A supplementation on child mortality? 2013, Lancet (in press)       

Benn CS, Netea MG, Selin LK, Aaby P. A small jab – a big effect: nonspecific immunomodulation by vaccines. Trends Immunol, 2013 May 13. pii: S1471-4906(13)00058-6. doi: 10.1016/

Biering-Sørensen S, Fisker AB, Ravn H, Camala L, Monteiro I, Aaby P, Benn CS. The effect of neonatal vitamin A supplementation on growth in the first year of life among low-birth-weight infants in Guinea-Bissau: two by two factorial randomised controlled trial. BMC Pediatr, 2013 May 23;13(1):87 

Danneskiold-Samsøe N, Fisker AB, Jørgensen MJ, Ravn H, Andersen A, Balde ID, Leo-Hansen C, Rodrigues A, Aaby P, Benn CS. Determinants of vitamin A deficiency in children between 6 months and 2 years of age in Guinea-Bissau. BMC Public Health, 2013 13:172. doi: 10.1186/1471-2458-13-172.

Fisker AB, Bale C, Jørgensen MJ, Balde I, Hornshøj L, Bibby BM, Aaby P, Benn CS.  High-dose vitamin A supplementation administered with vaccinations after 6 months of age: sex-differential adverse reactions and morbidity. Vaccine, 2013 31(31):3191-8. doi: 10.1016/j.vaccine.2013.04.072. Epub 2013 May 14.

Flanagan KL, van Crevel R, Curtis N, Shann F, Levy O.  Heterologous ("Non-specific") and Sex-differential Effects of Vaccines: Epidemiology, Clinical Trials, and Emerging Immunological Mechanisms. Clinical Infectious Diseases, 2013 doi:10.1093/cid/cit209

Kiraly N, Benn CS, Biering-Sørensen S, Rodrigues A, Jensen KJ, Ravn H, Allen KJ, Aaby P. Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood: long-term follow-up of randomised controlled trials. 2013 Allergy (in press) 



Aaby P, Benn CS, Nielsen J, Lisse IM, Rodrigues A, Ravn H. Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries. BMJ Open 2012;2:e000707.

Aaby P, Martins C, Benn CS, Whittle H. The new decade of vaccines. Lancet 2012;379:25-26

Aaby P, Martins CL, Garly ML, Rodrigues A, Benn CS, Whittle HC. The optimal age of measles immunization in low-income countries: A secondary analysis of the assumptions underlying the current policy. BMJ Open 2012:2:e000761

Aaby P, Ravn H, Roth A, Rodrigues A, Lisse IM, Diness BR, Lausch KR, Lund N, Biering-Sørensen S, Whittle H, Benn CS. Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial. Arch Dis Child 2012: doi:10.1136/archdischild-2011-300646

Aaby P, Roth A, Biering-Sørensen S, Ravn H, Rodrigues A, Whittle H, Benn CS. No evidence of bias in trial showing BCG reduces neonatal mortality. JID 2011;epub; 2012;205:515-7

Aaby P, Whittle HC, Benn CS. Vaccine programmes must consider their effect on general resistance. BMJ. 2012;344:e3769. doi: 10.1136/bmj.e3769.

Benn CS. Combining Vitamin A and Vaccines: Convenience or Conflict? Dan Med J 2012;59(1):B4378 (DMSc thesis)

Benn CS, Aaby. Diphtheria-tetanus-pertussis vaccination administered after measles vaccine: Increased female mortality? Pediatr Inf Dis J (in press)

Biering-Sørensen S, Aaby P, Napirna BM, Roth A, Ravn H, Rodrigues A, Whittle H, Benn CS. Small randomized trial among low-birth-weight children receiving bacillus Calmette-Guérin vaccination at first health center contact. Pediatr Inf Dis J 2011;epub;2012;31:306-8

Fisker AB, Aaby P, Bale C, Balde I, Biering-Sørensen S, Agergaard J, Martins C, Bibby BM, Benn CS. Does the effect of vitamin A supplements depend on vaccination status? An observational study from Guinea-Bissau. BMJ Open 2012:2:e000448

Welega P, Nielsen J, Adjuik M, et al. Non-specific effects of routine vaccinations? Testing the hypothesis with data from Navrongo, Ghana. Trop Med Int Hlth 2012 (in press)



Aaby P, Benn CS. Non-specific and sex-differential effects of routine vaccines: What evidence is needed to take these effects into consideration in low-income countries? Human Vaccine 2011;7:120-4

Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A, Lisse IM, Stensballe L, Diness BR, Lausch KR, Lund N, Biering-Sørensen S, Whittle H, Benn CS.Randomised trial of BCG vaccination at birth to low-birth-weight children: Beneficial non-specific effects in the neonatal period? JID 2011;204:245-52

Agergaard J, Nante E, Poulstrup G, Nielsen J, Flanagan KL, Østergaard L, Benn CS, Aaby P Diphtheria-tetanus-pertussis vaccine administered simultaneously with measles vaccine is associated with increased morbidity and poor growth in girls. A randomised trial from Guinea-Bissau. Vaccine 2011;29:487-500

Benn CS, Fisker A, Aaby P. Heterogeneous effects on child survival in neonatal vitamin A supplementation trials. Lancet 2011;377:1314-5

Biai S, Rodrigues A, Nielsen J, Sodemann M, Aaby P. Vaccination status and sequence of vaccinations as risk factors for hospitalisation among outpatients in a high mortality country Vaccine 2011; 29:3662-9

Diness B, Martins CL, Bale C, Garly ML, Ravn H, Rodrigues A, Whittle H, Aaby P, Benn CS. The effect of high-dose vitamin A supplementation at birth on measles incidence during the first 12 months of life in boys and girls. An unplanned study within a randomized trial. Br J Nutr 2011; 105:1819-1822

Fisker AB, Aaby P, Rodrigues A, Frydenberg M, Bibby BM, Benn CB. Vitamin A supplementation at birth might prime the response to subsequent vitamin A supplements in girls. Three year follow-up of a randomized trial. PLoS ONE 2011;6(8):e23265

Fisker AB, Benn CS, Diness BR, Martins C, Rodrigues A, Aaby P, Bibby BM. The effect of 50,000 IU vitamin A with BCG vaccine at birth on growth in the first year of life. J Trop Med 2011;2011;570170

Flanagan KL, Klein SL, Skakkebæk NE, Marriott I, Marchant A, Selin L, Fish EN, Prentice A, Whittle H, Benn CS, Aaby P. Sex differences in the vaccine-specific and non-targeted effects of vaccines. Vaccine 2011;13:2349-54

Jørgensen MJ, Fisker A, Erikstrup C, Claesson MN, Benn CS. SNP may modify the effect of vitamin A supplementation at birth on cytokine production in a whole blood culture assay. Br J Nut 2011;1-6 epub

Sørup S, Villumsen M, Ravn H, Benn CS, Sørensen TIA, Aaby P, Jess T, Roth A. Smallpox Vaccination and all-cause Infectious Disease Hospitalization: a Danish register-based cohort study. Int J Epidemiol 2011;40:955-63

Yakymenko D, Benn CS, Martins C, Diness BR, Fisker A, Rodrigues A, Aaby P. The impact of different doses of vitamin A supplementation on male and female mortality. A randomised trial from Guinea-Bissau. BMC Pediatrics 2011;11:77.


Pollard AJ. Non-specific effects of vaccines: RCTs, not observational studies, are needed. Arch Dis Child 2012: doi:10.1136/archdischild-2012-301873
Shann F. The non-specific effects of vaccines and the expanded programme on immunisation. JID 2011;204:182-4
Shann F. Commentary: BCG vaccination halves neonatal mortality. Pediatr Inf Dis J 2012;31:308-9

Cross-site publications of the vaccine WG: Data sharing or multi-site analyses

Aaby P, Jensen H, Walraven G. Age-specific changes in female-male mortality ratio related to the pattern of vaccinations: An observational study from rural Gambia. Vaccine 2006; 24:4701-08

Benn CS, Aaby P, Nielsen J, Binka FN, Ross DA. Does vitamin A supplementation interact with routine vaccinations? An analysis of the Ghana vitamin A supplementation trial. Am J Clin Nutr 2009;90:629-39

1st Report to the European Union

Title: Optimising the impact and cost-effectiveness of child health intervention programmes of vaccines and micronutrients in low-income countries