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Table 1 Examples of ‘internal’ and ‘external’ person consequences using immunization(s)

From: A comprehensive framework for considering additional unintended consequences in economic evaluation

Perspective Type ‘Internal’ ‘External’ Example
Health effects Biology Non-specific effects   A marked reduced risk of dying from sepsis and pneumonia was observed in low-birthweight neonates who received BCG immunization at birth in an RCT in Guinea-Bissau [22]
Non-specific effects   In a Dutch randomized placebo-controlled human challenge study BCG vaccination was found to induce genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated
yellow fever virus vaccine strain [23]
  Transmission Marked declines in the diagnoses of genital warts in young Australian Aboriginal and Torres Strait Islander (Indigenous) men in Australia after the introduction of the HPV bivalent vaccination programme for females suggests that female vaccination offered indirect herd protection for men [25]
Pathogen response   The change in patterns of serotype replacement or shifting causing invasive pneumococcal disease (IPD) produced marked declines in the incidence of IPD in children and moderate declines in adults following the replacement of the PCV7 vaccine by the PCV13 vaccine in Spain [27]
Pathogen response   A comparison of the impact against IPD in PCV10 and PCV13 vaccinated counties in Sweden observed an increase in serotype 6C in PCV10 counties but not in PCV13 counties. This was assumed to indicate that serotype 6A, which is included in PCV13 but not in PCV10, offers carry-over protective effects against serotype 6C [28]
Demand-side Change in health behaviour   A universal immunization programme in Nepal (which aside from providing childhood vaccinations) also educates mothers on vaccination has been found to result in positive changes in other individual health behaviours, such as hygiene and sanitation practices and behaviours [34]
Change in health services consumption   Following maternal tetanus vaccination in Bangladesh the consumption of health care services was markedly reduced indicating a positive change in the need to seek health care services [35]
Supply-side   Health Systems Hib vaccination prevents disease and thus reduces the need for antibiotic use for treatment which in turn reduces the development of antimicrobial resistance (secondary effects) [30]
Non-health effects Demand-side Education   PCV vaccination prevents pneumococcal pneumonia in children in South Africa. This has been associated with children improving their educational attainment [9]
Productivity   Hib vaccination reduces child mortality. This allows mothers of vaccinated children achieve their target family size through fewer births. This has been shown to result in increased adult labour productivity for women [10]
  Intra household A study from Belgium suggests that the caregiver burden within households in which children were not vaccinated against rotavirus was markedly severe; especially if no medical care was sought [11]
Intra household   In Argentina, households have reported negative changes in behaviours when a member in the household has cervical cancer. This resulted in negative impact on educational attainment which could have been prevented with the HPV vaccination [12]
Supply-side   Outside health systems Yearly influenza immunization reduces infection and related complications in the elderly and therefore result in reduced use of social support services outside the health care sector, such as social care services [13]
Provider   Previously influenza vaccinated healthcare providers demonstrated positive behavioural changes in their willingness to be vaccinated in forthcoming seasons [14]
  1. Italic = internal person (host); bolditalic = external person (host)
  2. PCV Pneumococcal conjugate vaccine, BCG Bacillus Calmette–Guérin, Hib Haemophilus influenzae type b, HPV Human papillomavirus vaccine, RCT Randomized Control Trial
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