OPTIMUNISE Reports and publications


  1. Becher H, Muller O, Dambach P, Gabrysch S, Niamba L, Sankoh O, Simboro S, Schoeps A, Stieglbauer, Ye Y, Sie A. Decreasing child ,mortality spatial clustering and decreasing disparity in North-Western Burkina Faso. Trop Med Int Health 2016;epub
  2. Byberg S, Fisker AB. Is the introduction of IPV really “Good news for billions of children”? Lancet Inf Dis 2016 Apr;16(4):409. doi: 10.1016/S1473-3099(16)00147-X
  3. Saadatian-Elahi M, Aaby P, Shann F, Netea MG, Levy O, Louis J, Picot V, Greenberg M, Warren WL.  Off-target effects of vaccination. Vaccine (in press)
  4. Aaby P, Ravn H, Benn CS. The WHO review of the possible non-specific effects of diphtheria-tetanus-pertussis vaccine. PIDJ (in press) 
  5. Aaby P, Ravn H, Benn CS, Rodrigues A, Samb B, Ibrahim SA, Libman M, Whittle HC. Child mortality after inactivated vaccines versus standard measles vaccine at nine months of age: a combined analysis of five cross-over randomised trials. PIDJ (in press)
  1. Fisker A. The question should be whether the timing of vaccination optimises the impact on child health. BMJ2016;352:i1713 doi: 10.1136/bmj.i1713
  2. Klein SL, Shann F, Moss WJ, Benn CS, Aaby P. RTS,S malaria vaccine and increased mortality in girls. mBio 7(2):e00514-16. doi:10.1128/mBio.00514-1. http://mbio.asm.org/content/7/2/e00514-16.full.pdf+html
  3. Benn CS, Aaby P, Arts RJW, Jensen KJ, Netea MG, Fisker AB. An enigma: Why vitamin A supplementation does not always reduce mortality even though vitamin A deficiency is associated with increased mortality. Int J Epidemiol. 2015 Jun;44(3):906-18. doi: 10.1093/ije/dyv117. Epub 2015 Jul 2.
  4. Kristoffer J Jensen, Christine S Benn, Reinout van Crevel. Unravelling the nature of non-specific effects of vaccines – a challenge for innate immunologists. Semin Immunol 2016;28:377-83
  5. Benn CS, Fisker AB, Whittle HC, Aaby P Hypothesis: Revaccination with live attenuated vaccines confer additional beneficial non-specific effects on overall survival. eBioMedicine 2016;10:32-7
  6. Frankel H, Byberg S, Bjerregaard-Andersen M, Martins CL, Aaby P, Benn CS, Fisker AB. Different effects of BCG strains – A natural experiment evaluating the impact of the Danish and the Russian BCG strains on morbidity and scar formation in Guinea-Bissau. Vaccine 2016;34:4586-93
  7. Fisker AB, Biering-Sørensen S, Lund N, Djana Q, Rodrigues A, Martins CL, Benn CS. Contrasting female-male mortality ratios after routine vaccinations with pentavalent vaccine versus measles and yellow fever vaccine in urban Bissau. Vaccine 2016:34:4551-7
  8. Aaby P, Nielsen J, Benn CS, Trape JF. Sex-differential effects of BCG and diphtheria-tetanus-pertussis vaccine in a rural area with high vaccination coverage: Observational study from Senegal. TRSTMH 2016;epub
  9. Byberg S, Fisker AB, Rodrigues A, Balde I, Enemark U, Aaby P,Benn CS,Griffiths UK . Household experience and costs of seeking measles vaccination in rural Guinea-Bissau. TMIH 2016;doi: 10.1111/tmi.12793
  10. Do VA, Biering-Sørensen S, Fisker AB, Balé C,Rasmussen SM, Christensen LD, Jensen KJ, Martins C, Aaby C, Benn CS. The effect of early measles vaccination on morbidity between 18 weeks and 9 months of age: A randomised controlled trial in Guinea-Bissau. JID 2016 (in press)
  11. Aaby P, Ravn H, Fisker AB, Rodrigues A, Benn CS. Is DTP associated with increased female mortality? Testing the TMIH-hypotheses of the non-specific effects of vaccines. TRSTMH 2016 (in press)


  1. Schoeps A, Lietz H, Sié A, Savadogo G, De Allegri M, Müller O, Sauerborn R, Becher H, Souares A. Health insurance and child mortality in rural Burkina Faso. Glob Health Action. 2015 Apr 28;8:27327. doi: 10.3402/gha.v8.27327. eCollection 2015
  2. Aaby P, Martins CL, Ravn H, Rodrigues A, Whittle HC, Benn CS. Is early measles vaccination better than later measles vaccination? Trans R Soc Trop Med Hyg. 2015 Jan;109(1):16-28. doi: 10.1093/trstmh/tru174
  3. Storgaard L, Rodrigues A, Martins C, Nielsen BU, Ravn H, Benn CB, Aaby P, Fisker AB. Development of BCG scar and subsequent morbidity and mortality in rural Guinea-Bissau. Clin Infect Dis. 2015 Sep 15;61(6):950-9. doi: 10.1093/cid/civ452. Epub 2015 Jun 9.
  4. Fisker AB, Rodrigues A, Martins C, Ravn H, Byberg S, Thysen S, Storgaard L, Pedersen M, Fernandes M, Benn CS, Aaby P. Reduced All-Cause Child Mortality After General Measles Vaccination Campaign in Rural Guinea-Bissau. Pediatr Infect Dis J. 2015 Dec;34(12):1369-76. doi: 10.1097/INF.0000000000000896. (PR)(CO)
  5. Aaby P, Nielsen J, Benn CS, Trape JF. Sex-differential and non-specific effects of routine vaccinations in a rural area with low vaccination coverage: an observational study from Senegal. Trans R Soc Trop Med Hyg. 2015 Jan;109(1):77-84. doi: 10.1093/trstmh/tru186
  6. Aaby P, Rodrigues A, Kofoed PE, Benn CS. RTS,S/AS01 malaria vaccine and child mortality. Lancet. 2015 Oct 31;386(10005):1735-6. doi: 10.1016/S0140-6736(15)00693-5. (PR)(CO)(OA) http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00693-5/fulltext
  7. Mutua M, Welaga P, Zandoh C, Kagoné M, Hanifi MA, Martins C, Fisker A, Andersen A, Benn CS, Aaby P, Ravn H. Analysis of Coverage of Fully Immunized Child (FIC), Associated Factors, Outcomes, and Impact Using Routinely Collected Population Cohort Data 2001-2014. INDEPTH 2015 (Report submitted to GAVI).
  8. Larsen MT. Vaccines, hospitalization and mortality in Urban Guinea-Bissau. Master Thesis in Statistics; 2015; University of Copenhagen, Denmark
  9. Schoeps A, Kynast-Wolf G, Nesbitt RC, Müller O, Sié A, Becher H. Decreasing disparities in infant survival using surveillance data from Burkina Faso.  Am J Trop Med Hyg. 2015 May;92(5):1038-44. doi: 10.4269/ajtmh.14-0390.


  1. Fisker AB, Ravn H RodriguesA, ØstergaardMD, Bale C, BennCS, Aaby P. Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau. Vaccine. 2014 Jan 23;32(5):598-605. doi: 10.1016/j.vaccine.2013.11.074. Epub 2013 Dec 8.
  2. Martins CL, Benn CS, Andersen A, Balé C, Schaltz-Buchholzer F, Do VA, Rodrigues A, Aaby P, Ravn H, Whittle H, Garly ML. A randomized trial of a standard dose of Edmonston-Zagreb measles vaccine given at 4.5 months of age: effect on total hospital admissions. J Infect Dis. 2014 Jun 1;209(11):1731-8. doi: 10.1093/infdis/jit804. epub 2014 Jan 16. (PR)(CO)
  3. Martins C, Garly ML, Bale C, Rodrigues A, Njie-Jobe J, Benn CS, Whittle H, Aaby P. Measles virus antibody responses in children randomly assigned to receive standard-titer edmonston-zagreb measles vaccine at 4.5 and 9 months of age, 9 months of age, or 9 and 18 months of age. J Infect Dis. 2014 Sep 1;210(5):693-700. doi: 10.1093/infdis/jiu117. epub 2014 Mar 31. (PR)(CO)(OA)
  4. 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. The non-specific effects of vaccines and other childhood interventions: the contribution of INDEPTH Health and Demographic Surveillance Systems. Int J Epidemiol. 2014 Jun;43(3):645-53. doi: 10.1093/ije/dyu101. Epub 2014 May 30.
  5. Fisker AB, Benn CS, Ravn H, Aaby P. Reply to Dr Schmid et al. Vaccine. 2014 May 13;32(23):2668-9. doi: 10.1016/j.vaccine.2014.03.060. Epub 2014 Apr 1.
  6. Aaby P, Martins CL, Garly ML, Andersen A, Fisker AB, Claesson MH, Ravn H, Rodrigues A, Whittle HC, Benn CS. Measles vaccination in the presence or absence of maternal measles antibody: impact on child survival. Clin Infect Dis. 2014 Aug 15;59(4):484-492. doi: 10.1093/cid/ciu354. Epub 2014 May 14.
  7. Schoeps A, Ouedraogo N, Kagoné M, Sié A, Müller O, Becher H. Socio-demographic determinants of timely adherence to BCG, Penta3, measles, and complete vaccination schedule in Burkina Faso. Vaccine. 2013 Dec 17;32(1):96-102. doi: 10.1016/j.vaccine.2013.10.063. Epub 2013 Oct 30.
  8. Andersen A, Jensen KJ, Erikstrup C, Ravn H, Fisker AB, Lisse IM, Sartono E, Aaby P, Yazdanbakhsh M, Benn CS. Both very low- and very high in vitro cytokine responses were associated with infant death in low-birth-weight children from Guinea Bissau. PLoS One. 2014 Apr 8;9(4):e93562. doi: 10.1371/journal.pone.0093562. eCollection 2014.
  9. Welaga P. Determinants and consequences of delayed BCG vaccination on child survival in Northern Ghana. MPHIL thesis.
  10. Fisker AB, Hornshøj L, Rodrigues A, Balde I, Fernandes M, Benn CS, Aaby P. Effects of the introduction of new vaccines in Guinea-Bissau on vaccine coverage, vaccine timeliness, and child survival: an observational study. Lancet Glob Health. 2014 Aug;2(8):e478-87. doi: 10.1016/S2214-109X(14)70274-8. Epub 2014 Jul 23.
  11. Aaby P, Kollmann TR, Benn CS. Non-specific effects of neonatal and infant vaccination: public health, immunological, and conceptual challenges. Nat Immunol. 2014 Oct;15(10):895-99. doi: 10.1038/ni.2961
  12. Thysen SM, Byberg S, Pedersen M, Rodrigues A, Ravn H, Martins C, Benn CS, Aaby P, Fisker AB. BCG coverage and barriers to BCG vaccination in Guinea-Bissau: an observational study. BMC Public Health. 2014 Oct 4;14:1037. doi: 10.1186/1471-2458-14-1037
  13. Schoeps A, Souares A, Niamba L, Diboulo E, Kynast-Wolf G, Müller O, Sié A, Becher H. Childhood Mortality and its Association with Household Wealth in Rural and Semi-urban Burkina Faso. Trans R Soc Trop Med Hyg. 2014 Oct;108(10):639-47. doi: 10.1093/trstmh/tru124. Epub 2014 Aug 16.


  1. Ouédraogo N, Kagoné M,  Sié A,  Becher H,  Müller O. Immunization coverage in young children: A study nested into a health and demographic surveillance system in Burkina Faso. J Trop Pediatr (2013) 59 (3): 187-194. doi:10.1093/tropej/fms075. Epub 2013 Jan 29.
  2. Ouédraogo N, Kagoné M, Sié A, Becher H,  Müller O. Timeliness and Out-of-Sequence Vaccination among Young Children in Burkina Faso – Analysis of Health and Demographic Surveillance System (HDSS) Data. Int J Trop Dis Hlth 2013;3(1): 45-56. doi: 10.9734/IJTDH/2013/2920
  3. Martins CL, Garly ML, Bale C, Rodrigues A, Benn CS, Whittle H, Aaby P. Measles antibody levels after vaccination with Edmonston-Zagreb and Schwarz measles vaccine at 9 months or at 9 and 18 months of age: A serological study within a randomised trial of different measles vaccines. Vaccine. 2013 Nov 19;31(48):5766-71. doi: 10.1016/j.vaccine.2013.08.044. Epub 2013 Aug 28.
  4. Benn CS, Netea MG, Selin LK, Aaby P. A small jab – a big effect: nonspecific immunomodulation by vaccines. Trends Immunol. 2013 Sep;34(9):431-9.doi: 10.1016/j.it.2013.04.004.epub 2013 May 14.(PR)(CO)
  5. 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 immunologic mechanisms. Clin Inf Dis. 2013 Jul; 57(2):283-9. doi:10.1093/cid/cit209. epub 2013 Apr 9. (PR)(CO)(OA) http://cid.oxfordjournals.org/content/57/2/283.long


  1. 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
  2. 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
  3. Aaby P, Martins C, Benn CS, Whittle H. The new decade of vaccines. Lancet 2012;379:25-26
  4. Benn CS. Combining Vitamin A and Vaccines: Convenience or Conflict? Dan Med J 2012;59(1):B4378 (DMSc thesis)
  5. 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
  6. 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 
  7. http://adc.bmj.com/cgi/rapidpdf/archdischild-2011-300646?ijkey=JHSPmLz0mzmEXRG&keytype=ref
  8. Aaby P, Whittle HC, Benn CS. Vaccine programmes must consider their effect on general resistance. BMJ. 2012;344:e3769. doi: 10.1136/bmj.e3769.
  9.  http://bmj.com/cgi/content/full/bmj.e3769?ijkey=I14MzuSShQ8WJrk&keytype=ref
  10. 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.
  11.  http://bmjopen.bmj.com/cgi/content/full/bmjopen-2011-000707
  12. Benn CS, Aaby. Diphtheria-tetanus-pertussis vaccination administered after measles vaccine: Increased female mortality? Pediatr Inf Dis J 2012;31:1095-7
  13. 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           http://bmjopen.bmj.com/cgi/content/full/bmjopen-2011-000761
  14. Welega P, Nielsen J, Adjuik M, Debpuur C, Ross DA, Ravn H, Benn CS, Aaby P. Non-specific effects of diphtheria-tetanus-pertussis and measles vaccinations? An analysis of surveillance data from Navrongo, Ghana. Trop Med Int Health 2012;epub
  15. Hirve S, Bavdekar A, Juvekar S, Benn CS, Nielsen J, Aaby P. Non-specific and sex-differential effects of vaccinations on child survival in rural western India. Vaccine 2012;30:7300-7308
  16. Lund N, Andersen A, Monteiro I, Aaby P, Benn CS. No effect of oral polio vaccine administered at birth on mortality and immune response to BCG. A natural experiment. Vaccine 2012;30:6694-9
  17. Aaby P, Benn CS. Saving lives by training innate immunity with bacille Calmette-Guérin vaccine. Proc Natl Acad Sci U S A 2012;109:17317-8
  18. Hornshøj L, Benn CS, Fernandes M, Rodrigues A, Aaby P, Fisker AB. Vaccination Coverage and Out-of-Sequence Vaccinations in Rural Guinea-Bissau: an observational cohort study. BMJ Open 2012;e001509


  1. 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
  2. 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
  3. 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
  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
  5. 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
  6. Benn CS, Fisker A, Aaby P. Heterogeneous effects on child survival in neonatal  vitamin A supplementation trials. Lancet 2011;377:1314-5
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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.



  1. Shann F. The non-specific effects of vaccines and the expanded programme on immunisation. JID 2011;204:182-4
  2. Shann F. Commentary: BCG vaccination halves neonatal mortality. Pediatr Inf Dis J 2012;31:308-9
  3. Pollard AJ. Non-specific effects of vaccines: RCTs, not observational studies, are needed. Arch Dis Child 2012: doi:10.1136/archdischild-2012-301873
  4.  Shann F. Australia, immunisation, GAVI, and the non-specific effects of vaccines. Aust N Z J Public Health. 2012 Dec;36(6):569-71. doi: 10.1111/j.1753-6405.2012.00957.x. No abstract available. PMID: 23216499 [PubMed - in process]
  5. Shann F. Nonspecific effects of vaccines and the reduction of mortality in children. Clin Ther 2013;35:109-114
  6. Brooks M. Small shot, big impact. New Scientist, 17 August 2013, 39-41
  7. New Scientist. Silence isn’t golden. Only openness can secure public trust in vaccines. New Scientists, 17 August 2013, 5
  8. Goldblatt D, Miller E. Nonspecific effects of vaccines. JAMA 2014;311:804-805
  9. Sachdev HS. Commentary: Potential implications of non-specific effects of childhood vaccines Int J Epidemiol 2014;epub

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

  1.   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
  2. 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