Equity

The Power of a Single Dose: Evidence for a Single-Dose HPV Vaccine Schedule 

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HPV Vaccination: A Critical Cancer Prevention Tool 

Since 2006, vaccines have been available to protect against human papillomavirus (HPV), an extremely common infection that causes virtually all cases of cervical cancer – the fourth most common cancer in women globally – and is also a known cause of several other types of cancer that impact both men and women [1]. In most instances, the immune system can clear HPV without any need for treatment, but persistent infection with high-risk strains of HPV can lead to several types of cancer [2]. This leads to stark disparities in cancer burden for women living with HIV, whose compromised immune systems may not clear HPV infections as readily; these women are six times more likely to develop cervical cancer [3]. Geographical disparities in cervical cancer burden also persist. In 2020, more than 600,000 women around the world were diagnosed with cervical cancer, with up to 90% of new global cases occurring in low- and middle-income countries (LMICs) and the majority of cancer cases and deaths concentrated in sub-Saharan Africa, Central America, and Southeast Asia [2]. To address these inequities and reduce global disease burden, the World Health Organization (WHO) has committed to a global strategy to accelerate the elimination of cervical cancer as a public health problem. Along with screening and treatment, HPV vaccination is a key cornerstone of this strategy–by 2030, WHO aims to vaccinate 90% of girls against HPV by the age of 15 [4]. 

Although this is an ambitious goal, new evidence-based recommendations from WHO may contribute to increased HPV vaccination coverage, especially where it is needed most. WHO had previously recommended a two-dose schedule for HPV vaccines, but an off-label recommendation for a one-dose schedule was added in December 2022 based on recent efficacy data from single-dose trials [5]. The latest guidance recommends a one or two-dose schedule for girls aged 9–14 as well as those between 15–20-years old, with girls older than 21 and those who are immunocompromised or living with HIV recommended to receive a third dose. This change is expected to have important programmatic and financial implications for HPV vaccination programs, particularly in LMIC settings. Further, a single-dose schedule could be an important tool to improve health equity and reduce disparities in HPV-related cancers, protecting all girls everywhere against this preventable disease.  

Evidence for a Single-Dose HPV Schedule  

A number of rigorous studies have been conducted to determine the efficacy and immunogenicity of a single-dose regimen of HPV vaccines. Researchers have concluded that a single dose of HPV vaccine provides high levels of protection against high-risk strains of HPV, even several years after vaccination, and induces a robust immune response.  

  • In a randomized trial in Kenya (KEN SHE), a single-dose of HPV vaccine was found to be 97.5% effective in preventing cancer-causing strains of HPV among 15–20-year-old girls [6].  Researchers examined the efficacy of single-dose bivalent (a single shot that can protect against two strains of a virus) and nonavalent HPV vaccines (a single shot that can protect against nine strains of a virus) among 15–20-year-old girls. After 18 months of follow-up, both the bivalent and nonavalent vaccines demonstrated 97.5% vaccine efficacy against high-risk strains of HPV. Researchers subsequently published results demonstrating similar vaccine efficacy three years following vaccination: bivalent vaccine efficacy remained at 97.5% (95% CI 90.0–99.4%), while nonavalent vaccine efficacy was 98.8% (CI 91.3–99.8%) [7].  
  • In a Costa Rican study (CVT), a single dose of HPV vaccine was found to provide a similar level of protection (82.1%) against high-risk strains of HPV as two or three doses (83.8% and 80.2%, respectively), even 11 years following vaccination [8]. Researchers examined the dose-specific vaccine efficacy of the bivalent HPV vaccine among 18–25-year-old women and determined that vaccine efficacy against high-risk strains of HPV was high, regardless of the number of doses received. Protection persisted for approximately 11 years following initial vaccination. Vaccine efficacy was 80.2% (95% CI = 70.7% – 87.0%) for three doses, 83.8% (95% CI = 19.5% – 99.2%) for two doses, and 82.1% (95% CI = 40.2% to 97.0%) for a single dose, with no statistically significant differences in either vaccine efficacy or infection rates across the three groups.  
  • A cohort study in India (IARC India) found that the protection provided by a single dose of HPV vaccine was comparable to that provided by two or three doses, even 10 years after vaccination [9]. Researchers compared the vaccine efficacy of a single dose of quadrivalent HPV vaccine to two and three doses in protecting against high-risk HPV strains. After 10 years of following the cohort of women, there were no significant differences in the frequency of incident HPV infection among adolescent women who received one, two, or three doses of HPV vaccine. The vaccine efficacy of a single dose was found to be 95.4% (95% CI 85.0 – 99.0), which did not differ significantly from the efficacy of two or three doses.   
  • In Tanzania, a randomized trial among 9–14-year-old girls (DoRIS) found that two years after vaccination, a single dose of HPV vaccine produced a non-inferior immune response for a high-risk strain of HPV compared to two or three doses [10]. Researchers examined the immune response two years after vaccination with a single dose of HPV vaccine.  Compared to two or three doses, a single dose of either bivalent or nonavalent HPV vaccine produced non-inferior levels of antibodies against HPV 16. Although non-inferiority was not met for HPV 18 antibodies, at least 98% of girls who received a single dose of HPV vaccine were seropositive for these antibodies two years following vaccination.   

Moving to a Single Dose Schedule – Why it Matters  

Compared to many of the routine immunizations given to infants and adolescents, HPV vaccination presents unique programmatic, financial, and logistical challenges, many of which could potentially be addressed by the use of a single-dose vaccination schedule.  

Countries’ limited immunization budgets have put HPV vaccine introduction in direct competition with the introduction of several other life-saving vaccines, including pneumococcal conjugate vaccines and rotavirus vaccines [11]. Compared to a two-dose schedule, a single-dose schedule for HPV vaccines would significantly reduce procurement and delivery costs [11]. For example, an economic study in Tanzania estimated that compared to a two-dose HPV vaccination schedule, a single-dose schedule would reduce the cost per fully vaccinated girl by 51%, accounting for all financial costs including injection supplies, training, and outreach activities [12]. These cost savings could potentially stretch immunization budgets further, allowing countries to protect more girls against HPV and cervical cancer. Additional cost savings may be seen in reduced cold chain requirements, as fewer doses would require countries to purchase fewer refrigerators, for example [13]. 

Although countries are well-versed in delivering vaccines to children under 5, vaccines targeting older children are more difficult to integrate into existing immunization programs. A single dose of HPV vaccine could be delivered once per year during child health weeks or annual vaccination events, eliminating the need for follow-up and simplifying delivery to this hard-to-reach population [11].  

Additional Resources 

The resources below provide additional information about HPV vaccination and the evidence for a single-dose schedule. 

References

1. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660 
2. Cervical Cancer. World Health Organization. Updated 17 November 2023. Accessed 25 January 2024. https://www.who.int/news-room/fact-sheets/detail/cervical-cancer 
3. Stelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV [published correction appears in Lancet Glob Health. 2021 Feb;9(2):e119]. Lancet Glob Health. 2021;9(2):e161-e169. doi:10.1016/S2214-109X(20)30459-9 
4. Global strategy to accelerate the elimination of cervical cancer as a public health problem. Geneva: World Health Organization; 2020 
5. World Health Organization. Human papillomavirus vaccines: WHO position paper (2022 update) Weekly Epidemiological Record. 16 Dec 2022, No 50, 97, 645-672. https://www.who.int/publications/i/item/who-wer9750-645-672 
6. Barnabas RV, Brown ER, Onono M, et al. Single-dose HPV vaccination efficacy among adolescent girls and young women in Kenya (the KEN SHE Study): study protocol for a randomized controlled trial. Trials. 2021;22(1):661. Published 2021 Sep 27. doi:10.1186/s13063-021-05608-8 
7. Barnabas RV, Brown ER, Onono MA, et al. Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results. Nat Med. 2023;29(12):3224-3232. doi:10.1038/s41591-023-02658-0 
8. Kreimer AR, Sampson JN, Porras C, et al. Evaluation of Durability of a Single Dose of the Bivalent HPV Vaccine: The CVT Trial. J Natl Cancer Inst. 2020;112(10):1038-1046. doi:10.1093/jnci/djaa011 
9. Basu P, Malvi SG, Joshi S, et al. Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study [published correction appears in Lancet Oncol. 2022 Jan;23(1):e16]. Lancet Oncol. 2021;22(11):1518-1529. doi:10.1016/S1470-2045(21)00453-8 
10. Watson-Jones D, Changalucha J, Whitworth H, et al. Immunogenicity and safety of one-dose human papillomavirus vaccine compared with two or three doses in Tanzanian girls (DoRIS): an open-label, randomised, non-inferiority trial. Lancet Glob Health. 2022;10(10):e1473-e1484. doi:10.1016/S2214-109X(22)00309-6 
11. Gallagher KE, LaMontagne DS, Watson-Jones D. Status of HPV vaccine introduction and barriers to country uptake. Vaccine. 2018;36(32 Pt A):4761-4767. doi:10.1016/j.vaccine.2018.02.003 
12. Hsiao A, Struckmann V, Stephani V, et al. Costs of delivering human papillomavirus vaccination using a one- or two-dose strategy in Tanzania. Vaccine. 2023;41(2):372-379. doi:10.1016/j.vaccine.2022.11.032 
13. Gallagher KE, Kelly H, Cocks N, et al. Vaccine programme stakeholder perspectives on a hypothetical single-dose human papillomavirus (HPV) vaccine schedule in low and middle-income countries. Papillomavirus Res. 2018;6:33-40. doi:10.1016/j.pvr.2018.10.004 

Breaking the Barriers: How Gender Equity Advances Immunization

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The COVID-19 pandemic has highlighted and exacerbated existing global gender inequities that impact the accessibility of immunizations to women and children worldwide, influencing their access to health services, education, and economic opportunities. Gender-related inequities contribute to barriers to immunization for people of all genders. Although girls and boys in most settings are equally likely to be vaccinated, evidence has found that advancing global gender equity can play an important role in ensuring all children have access to vital health resources such as immunization.

Key Points

  1. Gender inequality can prevent people of either gender from accessing critical health resources such as vaccination for themselves and their children.
  2. Higher levels of gender inequality for women are correlated with higher child mortality and lower childhood immunization rates.
  3. The more empowered women are – i.e. have control over family decision-making, financial resources, and safe travel/transportation – the more likely their children are to be vaccinated.
  4. Maternal education is significantly associated with immunization coverage for children and a child’s immunization status has been found to predict greater educational attainment.
  5. At the national level, higher levels of gender inequality are associated with higher rates of zero-dose status for children (children who received no doses of the DTP vaccine).

Immunization interventions will only succeed in expanding coverage and widening reach when gender roles, norms and relations are understood, analysed and systematically accounted for as part of immunization service planning and delivery.”

Why Gender Matters: Immunization Agenda 2030

Global research has found that gender equality, “the absence of discrimination based on a person’s sex or gender” 1, can be closely linked to health outcomes across populations. Evidence from around the globe finds that “reducing gender inequality could improve health outcomes at a population scale, resulting in increased overall and healthy life expectancy and decreasing years of life lost, years lived with disability, and disease burden, in the general population, and in men as well as women.” 2

What is Gender Equity?

Sex is typically characterized as either male or female and refers to the biological attributes that a person is born with. Gender refers to the socially constructed roles, norms, and behaviors that a given society considers appropriate for individuals based on the sex they were assigned at birth. Gender also shapes the relationships between and within groups of women and men1. Gender inequality can prevent people of either gender from accessing critical health resources such as vaccination for themselves and their children. However, because gender-related barriers are underpinned by power relations that extend across individuals to systemic levels, women and girls are often especially vulnerable to these inequalities.

A recent World Health Organization report on gender and immunization defines gender equity as “The process of being fair to women and men. It recognizes that men and women have different needs, power, and access to resources, which should be identified and addressed in a manner that rectifies the imbalance. Addressing gender equity leads to equality.” 1

The goal of gender equity is for people of all genders to have fair access to critical resources for themselves and their families. While equality means treating everyone exactly the same, equity acknowledges that each person has different circumstances that require resources or opportunities appropriate for their situation. Gender equity involves recognizing and rectifying the gender-based differences that exist, especially those related to needs, access, and control over resources.

The COVID-19 pandemic has highlighted and exacerbated existing global gender inequities that impact the accessibility of immunizations to women and children worldwide, influencing their access to health services, education, and economic opportunities. For example, data collected from 193 countries during the COVID-19 pandemic indicate that women were 1.21 times more likely than men to report ceasing their education for reasons other than school closures.3 Additionally, between March 2020 and September 2021, 26.0% of women reported employment loss compared to 20.4% of their male counterparts.3

Gender Equity and Immunization

Although girls and boys in most low- and middle-income settings are equally likely to be vaccinated, evidence has found that advancing global gender equity can play an important role in ensuring all children have access to vital health resources such as immunization.1

Several global studies have found associations between broad gender inequality and childhood immunization rates. A 2017 study examined the country-level factors influencing vaccination coverage in 45 low- and lower-middle income Gavi-supported countries, finding that countries with the least gender equality–as measured by factors such as reproductive health, women-held parliamentary seats, and educational attainment–also had lower rates of vaccine coverage. 4

How Gender-Related Barriers Impact Immunization Uptake

An increased effort to address existing gender barriers is necessary to achieve universal coverage in child immunization.5 Evidence suggests that increasing gender equality and empowering women have the potential to improve global childhood vaccination rates.

A 2018 discussion paper on immunization and gender barriers from the Equity Reference Group for Immunization identified several key gender-related barriers that limit women’s access to immunization for themselves and their children6. When women have lower status than men within their families or communities, they must rely on men to provide transportation, treatment costs, and permission to obtain immunization services for children.1,6

Several studies have shown that maternal education is significantly associated with immunization coverage for women and their children. Women with limited literacy or those with poor education are less likely to understand vaccination cards and may not know that multiple visits are required for some vaccination4. An analysis of immunization equity in 45 Gavi-eligible countries concluded that “children of the most educated mothers are 1.45 times more likely to have received DTP3 than children of the least educated mothers.” 4

Gender Equity Can Improve Immunization Rates

Evidence indicates that empowering women and increasing gender equality increases the chance that mothers will immunize their children. Across various settings and countries, the association between gender inequality and higher levels of under-immunized children persists.

  • A 2016 systematic review assessed women’s agency and vaccine completion among children under 5 in low-income countries. Largely, decision-making was positively associated with the odds of complete childhood immunization. The review found that in lower-income settings, “specific dimensions of women’s agency may enhance vaccination coverage for children, and that empowering women in such settings shows promise as a means to improve child health.” 7
  • A 2017 review of Gavi-supported countries found that countries with higher levels of gender inequality had lower and less equitable levels of child vaccination coverage.4

Immunization Can Foster Gender Equality

Vaccines provide crucial protection for the most marginalized women and children, particularly those affected by poverty, conflict, and deprivation. The indirect benefits of vaccines reduce gender-based disparities by reducing health gaps and improving healthy life expectancy in women, thus improving their inclusion in the labor market8. This modeling study suggests that by preventing illnesses, childhood vaccination can lead to higher educational attainment and labor participation for women, resulting in reductions in socioeconomic gender disparities8.

  • A 2020 modeling case study8 found that HPV vaccination among girls can narrow socioeconomic gender disparities by reducing the cervical cancer burden of women. One model estimates that HPV vaccination can prevent up to 80% of cervical cancer cases and deaths. A 5% improvement in health from HPV vaccination was estimated to result in a 5.9% increase in female labor force participation.
  • A large study in India9 demonstrated that childhood immunization was associated with improvements in adult schooling attainment in India by as much as 10%. This could lead to a higher income for women, as a woman’s wage in India is estimated to increase by 5-8% for each extra year of schooling.

Gender and Zero-Dose Status

Gender inequity also contributes to “zero-dose” status, which refers to children who have not received a single dose of DTP-containing vaccines10. Countries with higher gender inequity have been found to also have a greater prevalence of zero-dose children than countries with lower gender inequity5. With the spotlight on COVID-19, the 2022 WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) show that 112 countries experienced stagnant or declining DTP3 coverage since 2019, with 62 countries declining by at least 5 percentage points11,12. Globally, an estimated 18 million children have not received a single vaccine12.

The pandemic has not only disrupted routine immunization worldwide, but has also had alarming direct and indirect consequences on progress toward Sustainable Development Goals related to gender equity and child health.

  • Children of mothers with high levels of social independence (a measure of indicators of a woman’s ability to achieve her goals) were found to be 8.3% less likely to be zero-dose than children of women with low independence.13
  • A study representing 165 countries between 2010–2019 found that on average, greater gender equality was associated with markedly better coverage for DTP3 immunization5. Countries with higher gender inequality (as measured by gender-based advantage or disadvantage in health, education, and control over economic resources) had higher zero-dose prevalence (10% vs. 3%) and lower DTP3 immunization coverage (81% vs. 94%) compared to countries with lower measures of gender inequality.
  • An analysis of DHS data from 50 countries14 (representing 74% of low-income, 40% of lower-middle, and 11% of upper-middle-income countries in the world) found that “children born to less empowered women are over three times more likely to belong to the zero-dose category compared to those born to women with a high level of empowerment.”

There is a Strong Association Between Maternal Education and Child Health

Across contexts, research consistently finds that mothers with more education are also more likely to have their children immunized. There is also evidence that women’s education has a “dispersion” or “spillover” effect on child health that can benefit communities more broadly.15

  • A systematic review and meta-analysis found a 31% reduction in under-5 all-cause mortality for children born to mothers with 12 years of education. One additional year of maternal schooling was associated with a 3% reduction in under-5 mortality.16
  • Women who are health literate—irrespective of their education levels—are more likely to vaccinate their children, in both rural and urban settings. A study of 1,170 women from 60 Indian villages found that a mother’s health literacy level was positively associated with children’s receipt of DPT3 vaccination after adjustment for confounding17.
  • An analysis of Nigerian DHS data collected in 2014 revealed that a mother’s education level influences the likelihood of their child being immunized. Furthermore, the average education level of women within a community was found to have a protective effect on children beyond the benefits of their own mother’s schooling that may lead to better opportunities. This dispersion of benefits may be associated with women’s capacity to take advantage of better access to power and resources that having an education can support.18

Solutions: Immunization as an Equity Catalyst

The Immunization Agenda 2030 (IA2030) emphasizes the importance of immunization as a catalyst for advancing gender equality by addressing gender-related barriers. To reach the goal of leaving no one behind, gender-related barriers need to be effectively addressed from both the demand- and supply-side by all stakeholders6,19. Special attention should be paid to setting and context when attempting to implement gender-responsive approaches to immunization.1

Improve the quality, accessibility, and availability of services

  • All people should be treated with dignity and should be provided with the knowledge to make informed decisions.
  • Immunization services should be close to areas where hard-to-reach populations frequently visit and should be bundled together with other health services.

Integrate services and collaborate across sectors while working with change agents

  • To overcome barriers, relationships should be established with organizations beyond the health sector, especially with grassroots organizations and community-based groups.
  • Immunization programs should empower change agents and civil society with the skills to voice their views.

Apply a gender lens to research and innovation by investing in gender data and analysis

  • Action must be informed by data. To best identify and respond to gender inequities, data should be sex-disaggregated and informed by a gender analysis.

Globally, there is a lack of data regarding the needs and experiences of gender-diverse and gender non-conforming people and barriers to immunization. The barriers to health services that gender-diverse people face are important and specific efforts should be made to collect data and include gender-diverse people in research.1,20

References

  1. World Health Organization. Why Gender Matters: Immunization Agenda 2030. World Health Organization; 2021. Accessed December 6, 2022. https://www.who.int/publications/i/item/9789240033948
  2. Veas C, Crispi F, Cuadrado C. Association between gender inequality and population-level health outcomes: Panel data analysis of organization for Economic Co-operation and Development (OECD) countries. EClinicalMedicine. 2021;39:101051. doi:10.1016/j.eclinm.2021.101051
  3. Flor LS, Friedman J, Spencer CN, et al. Quantifying the effects of the COVID-19 pandemic on gender equality on health, social, and economic indicators: a comprehensive review of data from March, 2020, to September, 2021. The Lancet. 2022;399(10344):2381-2397. doi:10.1016/S0140-6736(22)00008-3
  4. Arsenault C, Johri M, Nandi A, Mendoza Rodríguez JM, Hansen PM, Harper S. Country-level predictors of vaccination coverage and inequalities in Gavi-supported countries. Vaccine. 2017;35(18):2479-2488. doi:10.1016/j.vaccine.2017.03.029
  5. Vidal Fuertes C, Johns NE, Goodman TS, Heidari S, Munro J, Hosseinpoor AR. The Association between Childhood Immunization and Gender Inequality: A Multi-Country Ecological Analysis of Zero-Dose DTP Prevalence and DTP3 Immunization Coverage. Vaccines. 2022;10(7):1032. doi:10.3390/vaccines10071032
  6. Feletto M, Sharkey A, Rowley E, Gurley N, Sinha A. A Gender Lens to Advance Equity in Immunization. Equity Reference Group for Immunisation; 2018. https://www.gavi.org/sites/default/files/document/programmatic-policies/ERG_A-gender-lens-to-advance-equity-in-immunization.pdf
  7. Thorpe S, VanderEnde K, Peters C, Bardin L, Yount KM. The Influence of Women’s Empowerment on Child Immunization Coverage in Low, Lower-Middle, and Upper-Middle Income Countries: A Systematic Review of the Literature. Matern Child Health J. 2016;20(1):172-186. doi:10.1007/s10995-015-1817-8
  8. Portnoy A, Clark S, Ozawa S, Jit M. The impact of vaccination on gender equity: conceptual framework and human papillomavirus (HPV) vaccine case study. Int J Equity Health. 2020;19(1):10. doi:10.1186/s12939-019-1090-3
  9. Nandi A, Kumar S, Shet A, Bloom DE, Laxminarayan R. Childhood vaccinations and adult schooling attainment: Long-term evidence from India’s Universal Immunization Programme. Soc Sci Med 1982. 2020;250:112885. doi:10.1016/j.socscimed.2020.112885
  10. Gavi, the Vaccine Alliance. Zero-dose children and missed communities. Published November 4, 2021. Accessed December 13, 2022. https://www.gavi.org/our-alliance/strategy/phase-5-2021-2025/equity-goal/zero-dose-children-missed-communities
  11. UNICEF. Vaccination and Immunization Statistics. UNICEF Data. Published July 2022. Accessed December 6, 2022. https://data.unicef.org/topic/child-health/immunization/
  12. UNICEF. COVID-19 pandemic leads to major backsliding on childhood vaccinations, new WHO, UNICEF data shows. Published July 15, 2021. https://www.unicef.org/press-releases/covid-19-pandemic-leads-major-backsliding-childhood-vaccinations-new-who-unicef-data
  13. Johns NE, Santos TM, Arroyave L, et al. Gender-Related Inequality in Childhood Immunization Coverage: A Cross-Sectional Analysis of DTP3 Coverage and Zero-Dose DTP Prevalence in 52 Countries Using the SWPER Global Index. Vaccines. 2022;10(7):988. doi:10.3390/vaccines10070988
  14. Wendt A, Santos TM, Cata-Preta BO, et al. Children of more empowered women are less likely to be left without vaccination in low- and middle-income countries: A global analysis of 50 DHS surveys. J Glob Health. 12:04022. doi:10.7189/jogh.12.04022
  15. Feletto M, Sharkey A. The influence of gender on immunisation: using an ecological framework to examine intersecting inequities and pathways to change. BMJ Glob Health. 2019;4(5):e001711. doi:10.1136/bmjgh-2019-001711
  16. Balaj M, York HW, Sripada K, et al. Parental education and inequalities in child mortality: a global systematic review and meta-analysis. The Lancet. 2021;398(10300):608-620. doi:10.1016/S0140-6736(21)00534-1
  17. Johri M, Subramanian SV, Sylvestre MP, et al. Association between maternal health literacy and child vaccination in India: a cross-sectional study. J Epidemiol Community Health. 2015;69(9):849-857. doi:10.1136/jech-2014-205436
  18. Burroway R, Hargrove A. Education is the antidote: Individual- and community-level effects of maternal education on child immunizations in Nigeria. Soc Sci Med 1982. 2018;213:63-71. doi:10.1016/j.socscimed.2018.07.036
  19. USAID MOMENTUM. Now Is the Time to Recognize and Reduce Gender-Related Barriers to Immunization. USAID MOMENTUM. Published July 15, 2021. Accessed December 6, 2022. https://usaidmomentum.org/now-is-the-time-to-recognize-and-reduce-gender-related-barriers-to-immunization/
  20. United Nations Office of the High Commissioner for Human Rights. The struggle of trans and gender-diverse persons. OHCHR. Accessed December 6, 2022. https://www.ohchr.org/en/special-procedures/ie-sexual-orientation-and-gender-identity/struggle-trans-and-gender-diverse-persons

Why Rotavirus Vaccine Introduction in Nigeria is a Milestone for Child Health

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In August 2022, Nigeria became the most recent country to introduce the rotavirus vaccine into its national immunization program. The integration of the rotavirus vaccine into Nigeria’s routine immunization schedule is expected to help reduce at least 40% of morbidity and mortality associated with rotavirus infections amongst children.

Key Points

  • Nigeria’s recent introduction of rotavirus vaccine into its immunization schedule has the potential to save the lives of nearly 100,000 children under five over the next decade.
  • Immunization against rotavirus significantly reduces diarrhea-related hospitalizations and can relieve pressure on overburdened health systems.
  • Rotavirus vaccines provide a return on investment and protect families from potentially catastrophic medical expenses.
  • By preventing diarrheal disease and the malnutrition that may be associated with rotavirus infection, rotavirus vaccines can reduce the risk of stunting and promote healthy cognitive development.

Diarrheal diseases are one of the leading killers of children worldwide, claiming the lives of an estimated 484,000 children under five each year.1 Though many bacteria and viruses can cause diarrhea, rotavirus may be responsible for up to 38% of diarrhea-related hospitalizations in children under five in countries where the rotavirus vaccine has not yet been introduced2. The burden of rotavirus is concentrated in low- and middle-income countries, with a 2013 study reporting that nearly half of all global rotavirus deaths occurred in just four countries: India, Nigeria, Pakistan, and Democratic Republic of Congo3. Because rotavirus is so highly transmissible, preventing rotavirus infection with the use of rotavirus vaccines is more effective than treating symptoms after infection.

In August 2022, Nigeria became the most recent country to introduce the rotavirus vaccine into its national immunization program. This measure will protect millions of vulnerable children and significantly lower the global burden of rotavirus disease. “Nigeria’s rotavirus vaccine introduction has been a long-awaited event, making the inaugural rollout a milestone moment for Nigeria as well as the rest of the world united in efforts to reduce the mortality and morbidity of diarrheal diseases caused by rotavirus,” wrote ROTA Council Chair Mathu Santosham. “The implications of this launch event are tremendous.”

Due to the country’s high disease burden, introduction of the vaccine in Nigeria has the potential to avert a significant number of rotavirus hospitalizations and deaths. The mortality rate for rotavirus in children under five in Nigeria is estimated to be 136 per 100,000, accounting for 30% of all global rotavirus deaths in children under five4. Introducing the rotavirus vaccine into Nigeria’s national immunization program has the potential to protect 6.9 million children from this disease each year5, and it could potentially save the lives of nearly 100,000 children over the next decade6.

Relieving Pressure on Health Systems

Like other vaccines, evidence shows that rotavirus vaccines are highly effective in preventing severe illnesses that require children to be hospitalized. Reducing hospitalizations from preventable illnesses like rotavirus infection may be especially important for health system capacity at this time, as delivery of many health services in Nigeria has been disrupted by the COVID-19 pandemic7. Introducing rotavirus vaccine in Nigeria offers great potential to reduce the number of hospitalizations in children under five and alleviate pressure on an overburdened health system.

  • A 2018 study reported that 46% of children under 5 in Nigeria hospitalized for acute gastroenteritis tested positive for rotavirus8.
  • According to a review of 57 articles from 27 countries, hospitalizations due to rotavirus-related acute gastroenteritis (AGE) among children under 5 fell by a median of 67% in the first 10 years after the rotavirus vaccine was licensed9.
  • In Rwanda, hospital admissions due to rotavirus among children under five decreased up to 70% in the two years after the vaccine was introduced10.
  • In Botswana, gastroenteritis-related hospitalizations among children under five decreased by 23% in the two years following rotavirus vaccine introduction, with an even larger decline (43%) during the rotavirus season11.
  • A review of the vaccine’s impact in the United States found that in the first 11 years of its use, rotavirus hospitalizations declined by an average of 80% among children under five12. Rotavirus-related emergency visits declined by a median rate of 57%.

Rotavirus Vaccine is Cost-Effective & Reduces Financial Burdens on Families

Research shows that like other immunizations, the rotavirus vaccine is cost-effective and provides a positive return on investment for both governments and families.

  • In Nigeria, introduction of the rotavirus vaccine is estimated to save the government approximately US$28.5M in healthcare costs over a 10-year period13. These savings translate to a cost per DALY averted of US$116 (95% UI: $69-$169), just five percent of the country’s GDP per capita.
  • A meta-regression analysis of the cost-effectiveness of rotavirus vaccination across 195 countries found that it was cost-effective, particularly in LMICs with the highest disease burden14. Among countries eligible for Gavi support, the mean ICER was $255 per DALY averted (95% UI: $39–$918).
  • Studies from high-income settings have found that introduction of rotavirus vaccines can provide significant short-term returns on investment (ROI). For example, a series of studies in the United States estimated that once rotavirus vaccines were introduced, the average annual savings in direct healthcare costs from rotavirus and acute gastroenteritis were between US$121M and US$231M12. An economic evaluation of rotavirus vaccination in Italy determined that the cost of introducing the vaccine would be more than offset by savings from prevention of disease cases and hospitalizations within as early as two years15.
Economic Costs of Rotavirus Disease and Value of Vaccines

Families of those treated for diarrheal diseases face significant out-of-pocket expenditures, which can be especially burdensome for those already living in poverty. Many of these costs are considered catastrophic, meaning that they exceed 10 percent of the household’s monthly income. In addition to out-of-pocket medical costs for rotavirus-related illnesses, families who miss work to care for a sick child also face indirect costs due to lost wages. By reducing disease burden, the rotavirus vaccine protects vulnerable families from these catastrophic expenditures.

  • In Malaysia, families of those treated for acute gastroenteritis pay an average of US$101 in out-of-pocket costs16. These expenses disproportionately affect families in the lowest income quartile, representing 23% of their monthly household income, compared to less than 6% of monthly household income for families in the highest income quartile.
  • The average direct and indirect costs for rotavirus-related diseases among poor families in Bangladesh are US$105.2, including out-of-pocket expenditures for treatment, non-medical costs like transportation and lodging for caregivers, and the opportunity costs of lost wages17. This accounts for nearly one-third of their total monthly household income.
  • On average, families in Vietnam lose more than nine working days due to caring for a child with rotavirus18.

Reducing Rotavirus Infections Promotes Healthy Development

Enteric infections like rotavirus can have long-term effects on a child’s development. Diarrheal illnesses often lead to malnutrition, which can cause stunting and impact cognitive development—and which also makes children more susceptible to subsequent infections. Rotavirus vaccine can break this vicious cycle by preventing the malnutrition that accompanies diarrheal diseases to promote healthy growth and development. These vaccines are especially beneficial for children living in low-resource and marginalized communities who are more likely to experience undernutrition and stunting.

  • A pooled analysis of studies from five LMICs demonstrated the cumulative effects of repeat diarrheal episodes from 0–24 months20. For every five episodes of diarrhea that a child experiences, they are 13% more likely to be stunted at age two.
  • A study of children in Jamaica found that at age 11 or 12, children who had been stunted by age 2 performed significantly worse than non-stunted children on reading, spelling, and arithmetic tests, even when accounting for socio-economic factors21.
  • An analysis of 8,000 children in five LMICs estimated that children who were stunted by age 2 completed an average of approximately one year less of schooling22. They were also 16% more likely than non-stunted peers to have failed a grade.
  • Children with diarrhea have a greater risk of developing pneumonia or acute lower respiratory infections (ALRI). A study of children in Ghana estimated that more than 1 in 4 cases of ALRI were attributable to recent diarrheal illnesses, and therefore, preventing diarrheal illnesses would also prevent a large number of pneumonia cases23.
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Nigeria’s introduction of rotavirus vaccine is promising, with the potential to protect millions of children from diarrheal diseases caused by rotavirus. Track immunization coverage for rotavirus and other essential vaccines through VIEW-hub, IVAC’s interactive data visualization platform.

References

  1. International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. (2022). Pneumonia and Diarrhea Progress Report 2022.
  2. Lanata CF, Fischer-Walker CL, Olascoaga AC, et al. Global causes of diarrheal disease mortality in children <5 years of age: A systematic review. PLoS One. 2013;8(9):e72788. doi:10.1371/journal.pone.0072788
  3. Tate JE, Burton AH, Boschi-Pinto C, Parashar UD; World Health Organization–Coordinated Global Rotavirus Surveillance Network. Global, Regional, and National Estimates of Rotavirus Mortality in Children <5 Years of Age, 2000-2013. Clin Infect Dis. 2016;62 Suppl 2:S96-S105. doi:10.1093/cid/civ1013
  4. Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2019 (GBD 2019) Results. Institute for Health Metrics and Evaluation (IHME) 2020; Available from: http://ghdx.healthdata.org/ gbd-results-tool.
  5. International Vaccine Access Center. VIEW- hub. [cited 2022 January]; Available from: http://view-hub.org/.
  6. Giwa, Omotayo. Nigeria Writes a New Chapter for Child Health with the Introduction of Rotavirus Vaccine. DefeatDD. Published August 22, 2022. Accessed November 17, 2022. https://www.defeatdd.org/blog/nigeria-writes-new-chapter-child-health-introduction-rotavirus-vaccine
  7. Shapira G, Ahmed T, Drouard SHP, et al. Disruptions in maternal and child health service utilization during COVID-19: analysis from eight sub-Saharan African countries. Health Policy Plan. 2021;36(7):1140-1151. doi:10.1093/heapol/czab064
  8. Tagbo BN, Mwenda JM, Eke CB, et al. Rotavirus diarrhoea hospitalizations among children under 5 years of age in Nigeria, 2011-2016. Vaccine. 2018;36(51):7759-7764. doi:10.1016/j.vaccine.2018.03.084
  9. Burnett E, Jonesteller CL, Tate JE, Yen C, Parashar UD. Global Impact of Rotavirus Vaccination on Childhood Hospitalizations and Mortality From Diarrhea. J Infect Dis. 2017;215(11):1666-1672. doi:10.1093/infdis/jix186
  10. Ngabo, F., Tate, J.E., Gatera, M., et al 2016. Effect of pentavalent rotavirus vaccine introduction on hospital admissions for diarrhea and rotavirus in children in Rwanda: a time-series analysis. Lancet Global Health. 4:e129-36.
  11. Enane LA, Gastanaduy PA, Goldfarb DM, et al. 2016. Impact of rotavirus vaccination on hospitalizations and deaths from childhood gastroenteritis in Botswana. Clinical Infectious Diseases. 2016(2).
  12. Pindyck T, Tate JE, Parashar UD 2018. A decade of experience with rotavirus vaccination in the United States – vaccine uptake, effectiveness, and impact. Expert Review of Vaccines. 17(7).
  13. Debellut, F., Clark, A., Pecenka, C., Tate, J., Baral, R., Sanderson, C., … & Atherly, D. 2019. Re-evaluating the potential impact and cost-effectiveness of rotavirus vaccination in 73 Gavi countries: a modelling study. The Lancet Global Health. 7(12).
  14. Janko MM, Joffe J, Michael D, et al. Cost-effectiveness of rotavirus vaccination in children under five years of age in 195 countries: A meta-regression analysis. Vaccine. 2022;40(28):3903-3917. doi:10.1016/j.vaccine.2022.05.042
  15. Carroll S, Rojas AJ, Glenngård AH, Marin C. Vaccination: short- to long-term benefits from investment. J Mark Access Health Policy. 2015;3:10.3402/jmahp.v3.27279. Published 2015 Aug 12. doi:10.3402/jmahp.v3.27279
  16. Loganathan, T., Lee, W.S., Lee, K.F., et al 2015. Household Catastrophic Healthcare Expenditure and Impoverishment Due to Rotavirus Gastroenteritis Requiring Hospitalization in Malaysia. PLOS One. 10(5).
  17. Ahmed S, Dorin F, Satter SM, et al. The economic burden of rotavirus hospitalization among children < 5 years of age in selected hospitals in Bangladesh. Vaccine. 2021;39(48):7082-7090. doi:10.1016/j.vaccine.2021.10.003
  18. Riewpaiboon A, Shin S, Le TP, et al. Cost of rotavirus diarrhea for programmatic evaluation of vaccination in Vietnam. BMC Public Health. 2016;16(1):777. Published 2016 Aug 11. doi:10.1186/s12889-016-3458-2
  19. Guerrant RL, DeBoer MD, Moore SR, Scharf RJ, Lima AA. The impoverished gut–a triple burden of diarrhoea, stunting and chronic disease. Nat Rev Gastroenterol Hepatol. 2013;10(4):220-229. doi:10.1038/nrgastro.2012.239
  20. Checkley, W., Buckley, G., Gilman, R.H., et al. 2008. Multi-country analysis of the effects of diarrhoea on childhood stunting. International Journal of Epidemiology. 37(4).
  21. Chang SM, Walker SP, Grantham-McGregor S, Powell CA. Early childhood stunting and later behaviour and school achievement. J Child Psychol Psychiatry. 2002;43(6):775-783. doi:10.1111/1469-7610.00088
  22. Martorell R, Horta BL, Adair LS, et al. Weight gain in the first two years of life is an important predictor of schooling outcomes in pooled analyses from five birth cohorts from low- and middle-income countries. J Nutr. 2010;140(2):348-354. doi:10.3945/jn.109.112300
  23. Schmidt WP, Cairncross S, Barreto ML, Clasen T, Genser B. Recent diarrhoeal illness and risk of lower respiratory infections in children under the age of 5 years. Int J Epidemiol. 2009;38(3):766-772. doi:10.1093/ije/dyp159

Leaving No Child Behind: Zero-Dose and UHC

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December 12th is recognized worldwide as Universal Health Coverage (UHC) day. Universal health coverage “ensures all people, everywhere, can get the quality health services they need without financial hardship.” Equity is at the heart of the Sustainable Development Goal target 3.8, which seeks to achieve universal health coverage and financial risk protection for all. Immunization equity helps ensure that all children, regardless of where they live, have the opportunity to live a full, healthy life.

Key Points:

  • As of 2020, 17.1 million children are categorized as zero-dose, defined as never having received a single dose of life-saving DTP vaccine.
  • The number of children at risk due to zero-dose status or under-vaccination has increased according to 2020 reports.
  • Zero-dose children not only lack access to vaccines but lack access to other essential child health services.
  • As the most widely available health intervention in the world, childhood immunization can be leveraged to strengthen primary health care for missed communities, bringing us closer to UHC.

What Does Zero-Dose Mean?

As of 2020, an estimated 17.1 million children did not receive the first dose of Diphtheria-Tetanus-Pertussis vaccine (DTP1) – an increase of 3.5 million children from 20191. An estimated 80% of these zero-dose children live in Gavi-eligible countries1.

The term zero-dose refers to children who have not received a single dose of diphtheria, tetanus, and pertussis vaccine (DTP1). These zero-dose children are often concentrated among the most vulnerable and disadvantaged groups, including the lowest-income households. Zero-dose status can help act as a proxy indicator of access to immunization and health services access more generally: When young children aren’t protected against some of the most lethal infectious diseases it indicates they and their families may be missing out on additional basic services, like antenatal care or schooling2.

  • The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million to 14.5 million3.
  • By 2019, global coverage of the third dose of DTP (DTP3) was estimated at 81.6% globally – more than double from 1980 DTP3 coverage estimates of 39.9%3.
  • Over the past decade, global vaccine coverage has plateaued beneath global coverage goals. Since 2010, 94 countries and territories recorded decreasing DTP3 coverage3.

Where are Zero-Dose Children Located?

Over the last 20 years, national governments and international health organizations have made tremendous progress in ensuring that all children have access to a safe, and healthy start to life. By focusing on zero-dose children, we concentrate resources on the populations who compounded deprivation where access to resources is the most challenging for families:

  • Nearly 50% of zero-dose children live in three key geographic contexts: urban areas, remote communities, and populations in conflict settings4.
  • Six Gavi-supported countries are home to 65% of zero-dose children: Nigeria (20 percent), India (18 percent), Pakistan (9 percent), the DRC (6 percent), Indonesia (6 percent), and Ethiopia (5 percent)4.
  • Communities with many zero-dose children also tend to have girls who are not in school; women with limited agency; high rates of violence against women; and lack of contraceptive, reproductive, maternal, neonatal, and pediatric health services2.
  • These missed communities are often the epicenters of disease outbreaks (e.g., yellow fever, measles, meningitis, cholera, Ebola virus disease) and can thus be valuable targets for prevention efforts2.
Zero Dose Map

Immunization: Investing in Health Systems for All

When children are “zero-dose” this lack of vaccine access often indicates a dire lack of access to other key health services for communities. Unvaccinated children disproportionately live in households with limited access to other primary health care services, and routine vaccination services may provide the opportunity to bring caregivers into contact with the health system5.

  • When a child misses out on basic vaccines, they are also likely to be missing out on other essential health interventions. This also means that their families and communities are most likely to be missing out on basic health services like maternal and neonatal care, access to sexual and reproductive health services nutritional supplements, and malaria prevention6.
  • Mothers of zero dose children are twice as likely to miss out on antenatal care or skilled birth attendance and these families are less likely to have access to clean water or sanitation4.
  • Children from families without access to primary health care services – such as institutional delivery, antenatal care, and maternal vaccination – also tend to be less likely to be vaccinated5.

Deprivation, Missed Communities, and Poverty

A 2021 analysis7 looking at the risk of zero-dose status across 92 LMIC countries found a strong association between deprivation and zero-dose status: The most deprived group represented children who were not born in a health facility, to a mother who did not receive a tetanus vaccine before or during pregnancy and reported no antenatal care visits. The group characterized as the most deprived had the highest prevalence of zero-dose children (42%).

  • Two-thirds of zero-dose children live in households surviving below the international poverty line ($1.90 per day)2,7.
  • Among the highest risk group, 47% were in the poorest wealth quintile, 89% lived in a rural area, and 81% had mothers with no education7.
  • There are large inequalities in drop-out rates, with drop-out being twice as high for children from the poorest households, with a DPT1 to MCV drop-out rate of 18% compared to 9% in wealthier households8.

Gender Equity, Women’s Empowerment, and Zero-Dose Status

In many social contexts, women and mothers are primary caregivers for children and hold an important role in children’s immunization. Women’s empowerment relates to having the autonomy, agency and ability to make informed decisions, including seeking care and health services for children. Several studies have found that women’s empowerment can be associated with higher immunization coverage and better child health for children.

  • A 2022 analysis of standardized national house-hold surveys from 50 countries supports the importance of gender equity and women’s empowerment for child vaccination, especially in countries with weaker routine immunization programs. When data from all 50 countries was pooled, the analysis found that children from mothers in the low levels of social independence had 3.3 times higher prevalence of zero-dose status compared to mothers in the high levels of social independence group9. Assuming that this association is causal, these results show that “there would be 4.7 million fewer no-DPT children in the world if all of them had empowered mothers.”
  • Additionally, research from 2020 has also found routine childhood vaccination is associated with increased educational attainment and earnings for women. Women born after India’s Universal Immunization Program (UIP) rollout attained 0.29 more schooling grades compared to women from the same household born before UIP rollout10. Among unmarried women, the UIP was associated with an increment of 1.2 schooling years, which corresponds to as much as an INR 35 (US $0.60) increase in daily wages. Thus, the researchers concluded that the UIP is also likely to improve the economic status of women in India.
  • In a 2017 analysis of immunization coverage in 45 low- and lower-middle income Gavi-eligible countries, researchers found that overall, maternal and paternal education were two of the most significant drivers of coverage inequities in these countries11. Pooling the data from all countries, the authors found that “children of the most educated mothers are 1.45 times more likely to have received DTP3 than children of the least educated mothers.”
  • In a 2011 study in India, the children of mothers who participated in an empowerment program were significantly more likely to be vaccinated against DTP, measles, and tuberculosis than children of mothers not involved in the program12. This study also spillover effects: In villages where the program occurred, children of mothers not in the program (non-participants) were 9 to 32% more likely to be immunized against measles than in villages where the program did not occur (controls). Overall, measles vaccine coverage was nearly 25% higher in the program villages compared to the control villages.

New Efforts are Needed to Reach Every Child

The COVID-19 pandemic has disrupted health services and preventive interventions, including childhood immunizations, and new efforts are critically needed to ensure no one is left behind. Reaching zero-dose children and missed communities with health services like routine immunization is a key goal of UHC as well as Immunization Agenda 2030 and the Gavi Alliance’s 2021–2025 Strategy.

“Health for all means reaching those left furthest behind with live-saving vaccines as a pathway to providing other health services,” Gavi CEO Seth Berkley said in an International UHC Day video message from leaders around the world. “As countries roll-out COVID-19 vaccines we have a historic opportunity to strengthen routine immunization, to reach zero-dose and missed communities with a full course of vaccines, along with primary healthcare services and build resilience to future shocks.”

References

  1. Muhoza P. Routine Vaccination Coverage — Worldwide, 2020. MMWR Morb Mortal Wkly Rep. 2021;70. doi:10.15585/mmwr.mm7043a1
  2. Forum on Microbial Threats, Board on Global Health, Health and Medicine Division, National Academies of Sciences, Engineering, and Medicine. The Critical Public Health Value of Vaccines: Tackling Issues of Access and Hesitancy: Proceedings of a Workshop. National Academies Press; 2021:26134. doi:10.17226/26134
  3. Galles NC, Liu PY, Updike RL, et al. Measuring routine childhood vaccination coverage in 204 countries and territories, 1980–2019: a systematic analysis for the Global Burden of Disease Study 2020, Release 1. The Lancet. 2021;398(10299):503-521. doi:10.1016/S0140-6736(21)00984-3
  4. Gavi. The Zero-Dose Child: Explained. Published April 26, 2021. Accessed April 13, 2022. https://www.gavi.org/vaccineswork/zero-dose-child-explained
  5. Santos TM, Cata-Preta BO, Mengistu T, Victora CG, Hogan DR, Barros AJD. Assessing the overlap between immunisation and other essential health interventions in 92 low- and middle-income countries using household surveys: opportunities for expanding immunisation and primary health care. EClinicalMedicine. 2021;42:101196. doi:10.1016/j.eclinm.2021.101196
  6. Gupta A. Opinion: Reach “zero-dose” children to build back better. Devex. Published July 6, 2021. Accessed April 13, 2022. https://www.devex.com/news/opinion-reach-zero-dose-children-to-build-back-better-100292
  7. Santos TM, Cata-Preta BO, Victora CG, Barros AJD. Finding children with high risk of non-vaccination in 92 lowand middle-income countries: A decision tree approach. Vaccines. 2021;9(6). doi:10.3390/vaccines9060646
  8. Cata-Preta BO, Santos TM, Mengistu T, Hogan DR, Barros AJD, Victora CG. Zero-dose children and the immunisation cascade: Understanding immunisation pathways in low and middle-income countries. Vaccine. 2021;39(32):4564-4570. doi:10.1016/j.vaccine.2021.02.072
  9. Wendt A, Santos TM, Cata-Preta BO, et al. Children of more empowered women are less likely to be left without vaccination in low- and middle-income countries: A global analysis of 50 DHS surveys. J Glob Health. 2022;12:04022. doi:10.7189/jogh.12.04022
  10. Nandi A, Kumar S, Shet A, Bloom DE, Laxminarayan R. Childhood vaccinations and adult schooling attainment: Long-term evidence from India’s Universal Immunization Programme. Soc Sci Med. 2020;250:112885. doi:10.1016/j.socscimed.2020.112885
  11. Arsenault C, Harper S, Nandi A, Mendoza Rodríguez JM, Hansen PM, Johri M. Monitoring equity in vaccination coverage: A systematic analysis of demographic and health surveys from 45 Gavi-supported countries. Vaccine. 2017;35(6):951-959. doi:10.1016/j.vaccine.2016.12.041
  12. Janssens W. Externalities in Program Evaluation: The Impact of a Women’s Empowerment Program on Immunization. Journal of the European Economic Association. 2011;9(6):1082-1113. doi:10.1111/j.1542-4774.2011.01041.x

Equity and Immunization: Shrinking the Gaps

Posted on by stacy

Although more children than at any point in history are now protected against vaccine-preventable diseases, millions of zero-dose children are still missing out on the life-saving benefits of immunization entirely. These children often live in the world’s most marginalized communities where inequities are clustered and compounded by poverty, geography, gender, and conflict. In order to keep making progress against preventable deaths and illness, leaders will need to integrate equity across global, national, and sub-national immunization strategies.

Key Messages

  • Health inequities are “the unjust differences in health between persons of different social groups, and can be linked to forms of disadvantage such as poverty, discrimination and lack of access to services or goods,” as defined in the WHO Handbook on Health Inequality Monitoring.
  • Both between and within countries, vaccine coverage is often distributed unequally across populations – those in the highest socioeconomic status groups and those with the most education often have the highest immunization rates while marginalized populations, those living in poverty, and those with lower education have the least access to immunization.
  • Improving equitable access to vaccines aligns with achieving the Sustainable Development Goals.
  • Prioritizing equity requires multisectoral strategies designed to reach communities that have previously been excluded from access to health services based on geography, educational status, and sociocultural group.

Compounded Vulnerability

Record numbers of children are protected from preventable illnesses thanks to immunization, yet millions of children, often the poorest and most vulnerable, continue to be left behind. Vaccine-preventable diseases disproportionately affect those who experience both poor overall health and low economic standing; the children who miss out on life-saving vaccines are often those in the poorest households and the most remote locations, and whose families lack access to clean water, education, and adequate nutrition.

Over 13 million ‘zero-dose’ children have never received any vaccines at all, based on a 2019 analysis from UNICEF. These children and their families already experience a disproportionate burden of vaccine-preventable illnesses like measles, diphtheria, and polio. With life-saving immunization services around the world disrupted by the COVID-19 pandemic, these children are at even great risk from disastrous outbreaks of vaccine-preventable illnesses.

On June 4th, 2020 the Global Vaccine Summit will aim to raise at least $7.4 billion for Gavi, the Vaccine Alliance. This funding will help support the mass vaccination campaigns and rebuilding of health systems needed over the coming years to help address the damage done by the COVID-19 pandemic. Gavi’s strategic plan for 2021-2025 prioritizes immunization equity and the need to reach the communities that have missed out on previous immunization efforts, especially those most marginalized by poverty, geography, and conflict.

Combating inequities in health and wealth through immunization

Evidence has shown that vaccines have the greatest health and economic benefit amongst the poor. Globally, the poorest populations often experience the worst impacts of vaccine-preventable diseases, both in terms of health burdens in illness and death as well as carrying potentially crushing costs associated with medical care, missed work, and lasting disability.

Research shows that vaccines are one tool that can help break the pernicious cycle of poverty and ill health, improving equity across both health and wealth. By preventing disease, vaccination also prevents the costs associated with medical treatment and thus helps to reduce the likelihood that households will fall into or remain in poverty.

  • A 2018 modeling study of the economic impact of 10 childhood immunizations in 41 low- and middle-income countries found that with the lowest income households received the greatest financial risk protection from costs of measles, pneumococcal disease, and rotavirus. The authors conclude that: “Including equity components into economic evaluations will allow policy makers to opt for interventions that target specifically the most vulnerable populations.”
  • A 2015 study from Ethiopia looking at the impact of pneumococcal vaccine introduction in Ethiopia found that 30-40% of all deaths averted would be expected to occur in the poorest wealth quintile. The greatest resulting financial risk protection would also be concentrated among the lowest income quintile.
  • A 2018 cost-effectiveness analysis found that expanding rotavirus vaccination coverage among the poorest and most vulnerable populations of children would substantially increase the overall impact of rotavirus immunization in Pakistan; children in the poorest households would experience a three to four times greater mortality reduction benefit compared to children in the richest households.

Empowering and educating women can lead to greater rates of vaccination among children

Although girls and boys are immunized at similar rates globally, barriers that inhibit women’s ability to access healthcare and immunizations for their children may still exist at subnational levels and across different populations. Research in several LMIC contexts has found that access to education, particularly for women and girls, is often strongly associated with higher rates of immunization in children.

Graph
Figure 1. Brinda, E.M., Rajkumar, A.P. & Enemark, U. Association between gender inequality index and child mortality rates: a cross-national study of 138 countries. BMC Public Health 15, 97 (2015). https://doi.org/10.1186/s12889-015-1449-3
  • A 2015 ecological study of 138 countries found that greater gender inequality was significantly correlated with lower immunization coverage and higher neonatal, infant, and under-5 mortality.
  • A 2018 study in Nigeria found a robust association with maternal education and immunization coverage for children at both the individual and at the community levels. The researchers concluded that maternal education had a spillover effect that benefited immunization rates of all community members, not only a mother’s own children. This suggests that even children of uneducated mothers can benefit from the education of women in the community overall.
  • A 2017 systematic analysis of equity in vaccine coverage across 45 low- and middle-income countries found that maternal education is a strong predictor of child vaccine coverage. Children of the least educated mothers were 55% less likely to have received measles vaccine and three doses of DTP vaccine compared to children of the most educated mothers.
  • A 2015 review of health equity and disparities data from Demographic and Health Surveys and Multiple Indicator Cluster Surveys conducted in 70 developing countries found that “with respect to immunization, the greatest disparity exists for children born to women with no education compared with those born to women with secondary (or higher) education.” The global coverage of the third dose of DTP is 26% higher among children born to mothers with some secondary education compared to mothers with no education.

Geography and Sociocultural inequities and the immunization gap

Where a child is born often dictates their access to health resources like vaccines. Despite improvements in vaccination rates at the national level, local level disparities continue to persist. This means that children born in remote, rural, or urban slum settings may have significantly less access to immunization compared to their peers born in urbanized settings near health facilities. Inequities also exist for marginalized populations and minority groups who may have restricted access to health services such as immunizations. Conflict and migration are additional factors that threaten access to immunization for many children and their families.

These inequities in vaccination rates—often concealed in national averages—call for special efforts to improve immunization rates in this rapidly growing sub-population to reduce both health inequities and the risk of infectious disease outbreaks in the wider society.

Restrepo-Méndez, María Clara, Barros, Aluísio JD, Wong, Kerry LM, Johnson, Hope L, Pariyo, George. et al. (‎2016)‎. Inequalities in full immunization coverage: Trends in low- and middle-income countries. Bulletin of the World Health Organization, 94 (‎11)‎, 794 – 805B. World Health Organization. http://dx.doi.org/10.2471/BLT.15.162172
  • A 2015 immunization equity review found that globally, coverage of the third dose of DTP among 1-year-olds is 8% higher among urban dwellers compared to children living in rural environments.
  • Children from families that have migrated from other parts of the country have less access to health services and lower vaccination rates compared to the general population. According to a 2016 systematic review and meta-analysis, children who are rural-urban migrants in China, India, and Nigeria were less likely to be fully immunized by the age of one year than non-migrant urban residents and the general population.
  • A 2019 study in New Zealand found that the use of pneumonia conjugate vaccines (PCV) appears associated with reductions in ethnic and socioeconomic disparities in invasive pneumococcal disease (IPD), all-cause pneumonia (ACP), and otitis media hospitalization among Māori and Pacific children. Following the introduction of conjugate vaccines in the country, Maori and Pacific children’s rates of admission for IPD dropped by 79% and 67%, respectively.
  • A 2019 study examining immunization rates in urban and rural populations in Tanzania found that wealth and mother’s education were significant predictors of vaccination rates in both urban and rural settings. However, low paternal education, lack of antenatal care, and home births were significantly associated with low vaccination rates only in rural settings, suggesting a need for tailored vaccine programs.
  • The results of a 2016 cross-sectional polio serosurvey found that the Jordan Ministry of Health’s proactive campaign to locate and vaccinate high-risk populations has been successful in maintaining high population immunity—even with a recent influx of refugees from Syria. The study included a community sample of 479 children under 5 years old living in areas of Jordan identified as high risk due to being hard-to-reach, having high numbers of refugees, and lower vaccine coverage (under 90%).

World Immunization Week 2020 Social Media Toolkit

VoIce banner for World Immunization Week 2020
Posted on by stacy

World Immunization Week 2020 (April 24-30) is an opportunity for immunization advocates across the world to promote the value of vaccines for protecting people of all ages against preventable diseases. Our VoICE social media toolkit provides messaging on the vital role that vaccines play in global health. Beyond saving millions of lives every year #VaccinesWork For All by strengthening our health care systems, protecting global health security, shrinking equity gaps, and more.

Join us in promoting the message that #VaccinesWork For All by sharing the evidence on the broad benefits of immunization!

VoICE Social Media Toolkit for World Immunization Week 2020

Download the VoICE World Immunization Week 2020 Toolkit for a series of social media messages and shareable images that highlight key evidence on the value of vaccines! Messaging covers the six main topics of the VoICE Compendium: Health, Education, Economics, Equity, Health Systems and Integration, and Global Issues.

The toolkit is also available as a downloadable PDF and all images can be easily copied or saved directly from this page.

Welcome to WIW 2020!

Immunization saves millions of lives every year. Yet, there are still nearly 20 million children worldwide who are not getting the vaccines they need.

We have it in our power to close this gap!

Welcome to World Immunization Week banner

#VACCINESWORK TO PROTECT OUR HEALTH

#DYK those with HIV, cancer, and weakened immune systems benefit from immunization of others through herd immunity?

https://bit.ly/immunization_HerdEffects

Herd Effects Children banner

#VaccinesWork for all by protecting people around us, especially those who are vulnerable like new babies, older adults, and people who are seriously ill.

http://bit.ly/CancerandImmunization

Herd Effects All Ages banner 2

Malnourished kids suffer the most from pneumonia, diarrhea and other vaccine-preventable infections.

It’s time to level the playing field!

Bit.ly/2OqdS7C

Undernutrition cycle

#VACCINESWORK TO IMPROVE EDUCATION

#DYK that immunization is linked to improved education and cognitive outcomes? Immunized children stay healthier so they miss less school and attain higher school grades.

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#VACCINESWORK FOR ECONOMIES

Vaccines don’t just save lives; they keep the world’s most vulnerable people out of poverty. A 2018 @Health_Affairs study found the poorest households receive the most benefit from increased access to vaccines.

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Studies show that vaccines can help stop poverty in addition to saving lives. Read the latest research on the economic benefits of vaccines.

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#VACCINESWORK FOR EQUITY

13.5 million children around the world still can’t access vaccines – these children are often the most vulnerable to disease and health disparities. We have it in our power to close this gap!

Leaving no child behind means ensuring the most marginalized – those touched by conflict or forced from their homes – have access to lifesaving #vaccines.

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Vaccines are a tool for reducing gender, geographic, and sociocultural inequity – find the latest evidence on immunization and equity on VoICE:

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#VACCINESWORK FOR HEALTH SYSTEMS

Immunization can decrease hospital admissions, thus alleviating pressure on overburdened health systems, freeing up needed medical resources.

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In Kenya, rates of pneumonia hospitalizations in children <5 dropped by 27% after 4 years of PCV10. #VaccinesWork for All to reduce hospital admissions and free up more resources to treat and prevent other illnesses.

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#VACCINESWORK FOR HEALTH SECURITY

Between 2005-2014 nearly 400 infectious disease outbreaks (excluding measles) were reported to the @WHO, threatening the health security of the entire world.

View @Voice_Evidence’s feature issue on #outbreaks to learn more: http://bit.ly/voice_outbreaks

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2019 saw a record for measles outbreaks – more than 140,000 lives were lost, mostly children.

Measles is so contagious that the exposure of a single person without immunity to the virus can spark an outbreak that quickly burns through whole communities.

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Universal Health Coverage: What immunization advocates should consider

Posted on by stacy

December 12th is worldwide Universal Health Coverage (UHC) day! Although exceedingly complex in its implementation, the concept behind UHC is simple: All people should benefit from quality health services, medicines and vaccinations, and no one should be put in financial peril to do so. In recognition of UHC Day 2018, the VoICE team brings you a brief look at the interplay between coverage of immunization and other basic health interventions, and the important role of immunization in protecting against financial risk – both within the context of the Sustainable Development Goal Target for UHC.

A selection of VoICE evidence in this issue

Hinman, A.R., and McKinlay, M.A. 2015. Immunization equity. Vaccine. 33(2015).

Chebab, E.T., et al. 2016. Experience of integrating vitamin A supplementation into polio campaigns in the African Region.. Vaccine. 34(43).

Torres-Rueda, S., Rulisa, S., Burchett, H.E., et al. 2016. HPV vaccine introduction in Rwanda: Impacts on the broader health system. Sexual and Reproductive Healthcare. 7.

Niessen, L., ten Hove, A., Hilderink, H., et al 2009. Comparative impact assessment of child pneumonia interventions. Bulletin of the World Health Organization. 87.

Deoganakar, R., Hutubessy, R., van der Putten, I., et al 2012. Systematic review of studies evaluating the broader economic impact of vaccination in low and middle income countries. BMC Public Health. 12(878).

Olusanya, B.O. 2009. Optimising the use of routine immunisation clinics for early childhood development in sub-Saharan Africa. Vaccine. 27.

Restrepo-Mendez, M.C., Barros, A.J., Wong, K.L.M., et al. 2016. Missed opportunities in full immunization coverage: findings from low- and lower-middle-income countries. Global Health Action. 9(1).

Verguet, S., Memirie, S.T., and Norheim, O.F. 2016. Assessing the burden of medical impoverishment by cause: a systematic breakdown by disease in Ethiopia. BMC Medicine. 14(1).

Chang, A.Y., Riumallo-Herl, C., Perales, N.A., et al. 2018. The equity impact vaccines may have on averting deaths and medical impoverishment in developing countries. Health Affairs. 37(2).

Key Points 

  1. Achieving universal coverage of basic health services will require strengthening and expanding current health systems AND new approaches to reaching those who still cannot or do not access health services.
  2. The reach of immunization delivery programs can be leveraged to provide other basic services – and increase financial efficiency of health systems – and the reverse is also true: the delivery of other interventions can help to increase the uptake of vaccines.
  3. Achievement of UHC will positively contribute to at least six of the 17 Sustainable Development Goals.
  4. Immunization can contribute significantly to achieving financial risk protection against health costs.

Universal Health Coverage and the Sustainable Development Goals

December 12th is worldwide Universal Health Coverage (UHC) day!  The aim of drawing attention to this day is to shine the global spotlight on the gaps in achieving health as a human right. Although exceedingly complex in its implementation, the concept behind UHC is simple: All people should benefit from quality health services, medicines and vaccinations, and no one should be put in financial peril to do so.

In 2015, 193 United Nations Member States committed to an ambitious set of 17 “Sustainable Development Goals” (SDGs) by 2030. The right to health not only figures prominently as a goal in and of itself – SDG3 is to “Ensure healthy lives and promote well-being for all at all ages” – but is also fundamentally intertwined with goals related to equity, poverty, economic growth and inclusion. (See Figure 1.)

Figure 1: The interrelatedness of Universal Health Coverage with other Sustainable Development Goals, and the importance of health systems strengthening.

Source: Tracking Universal Health Coverage: 2017 Global Monitoring Report. World Health Organization and International Bank for Reconstruction and Development / The World Bank; 2017. License: CC BY-NC-SA 3.0 IGO. Available here: http://www.who.int/healthinfo/universal_health_coverage/report/2017/en/

Embodied in the 8th Target of  SDG3 (SDG 3.8), the pursuit of UHC is supported by the twin indicators of 1) coverage of essential services (including immunization), and 2) financial risk protection from the incurrence of economically burdensome health costs.  In recognition of UHC Day 2018, the VoICE team brings you a brief look at the interplay between coverage of immunization and other basic health interventions, and the important role of immunization in protecting against financial risk – both within the context of SDG 3.8.

Building on coverage of vaccines gives UHC a head start, but there is more to do

Equity is at the heart of the Sustainable Development Goal target 3.8, which seeks to achieve universal health coverage and financial risk protection for all.  The coverage indicator for the achievement of UHC tracks the coverage of 14 “tracer interventions”, which together serve as a barometer for access to basic health services. Access to immunization is tracked through the coverage of the third dose of DTP3, one of four maternal and child health tracer interventions. Although DTP3 coverage is evidence of the fact that immunization is one of the most widely available and equitably distributed interventions worldwide, several other important vaccines lag behind the 85% coverage of DTP3 worldwide in 2017.

Specific vaccines notwithstanding, high coverage with some vaccines such as DTP make immunization programs a critical backbone of any universal health coverage strategy. Routine and campaign-based immunization programs reach some children in remote or poverty stricken areas whose families have little other connection to the health system, and as such, offer opportunities to provide additional basic health care services to children and their families, especially interventions associated with maternal and child health. See Figure 2 for some highlights from VoICE of the opportunities for mutual reinforcement between immunization and other programs.

Figure 2: Examples of the integration of immunization and other health services.

Vitamin A distribution integrated with polio vaccine campaigns led to increased VitA coverage in several African countries.

Delivery of HPV vaccine to school-age girls in Rwanda provided an opportunity to offer school-age boys a variety of health services at the same time.

Immunization programs provide opportunities for cost-sharing and external funding, when used alongside other health interventions.

The timing of childhood immunizations could be harnessed to deliver a range of early childhood development interventions such as newborn hearing screening, sickle cell screening, treatment and surveillance, maternal education around key newborn care issues such as jaundice, and tracking early signs of poor growth and nutrition.

Despite the relatively high coverage globally of some vaccines, other critical vaccines have reached only a small fraction of the world’s children. Fully 15% of the world’s children are not reached at all by immunization – a gap whose distribution carries significant inequity – so vaccine coverage successes are very much tied to the achievement of UHC goals and targets for other health services.

The achievement of UHC targets will, however, require significant reform and expansion of existing health systems to address challenges such as missed opportunities to integrate services. For example, a recent study in 14 low- and middle-income countries found an exceedingly high rate of missed opportunities to vaccinate in 8 of the 14 countries, despite families coming into contact with the health system. For these countries, children failed to be vaccinated more than 50% of the time, despite they or their mother having received at least one of 5 other basic health interventions provided through the health system. Additionally, for the millions of families not reached at all by current health systems, barriers may include socio-cultural factors, in addition to geography, education, poverty, etc.

For these families and others with inadequate health services, a truly equity-driven approach is needed. That is, governments, partners, health-providers, and systems will need find ways to provide whatever additional support is needed to help them catch up, not just make the same resources available to everyone.

For families, financial barriers to immunization are relatively low, but health and economic returns are high

The second indicator of the universal health coverage target acknowledges that the costs associated with health care – both preventative services and treatment for illness – are a significant barrier for hundreds of millions of people around the world. These costs prevent some people from even trying to access health services, and for those who do seek care they cannot afford, the financial burden of these services can have significant, negative and lasting economic impact. The provision of a basic package of preventative services, including immunization, would thus create a positive, reinforcing cycle of increased health-seeking behavior and improved financial stability for individuals, families and economies.

Immunization is a critical element to success for two reasons. First, thanks to global institutions such as Gavi and UNICEF, immunization is free of charge for a large proportion of families in the world’s middle and low-income nations and financial barriers to access are thus relatively low. However, not all crucial vaccines are yet available through national immunization programs in every country. In some places, lifesaving vaccines against disease such as pneumococcal disease are only available through the private market, carrying a price tag far too high for many families to access. And, as mentioned above, sociocultural factors and other issues are significant drivers of gaps in vaccine coverage and these must be addressed carefully and concertedly.

The second reason immunization is critical to meeting the financial risk protection targets of UHC is much more obvious: the widespread use of vaccines has the power to avert significant costs associated with treatment of infections. The huge economic burden of these infections stems from the costs associated with treating relatively low-cost but frequently occurring infections and complicated infections such as meningitis which are rare but very expensive to treat. These vaccine-preventable episodes of illness are responsible for a large number of families being pushed into poverty each year.

Visit the VoICE tool to find out more about how vaccines can help people avoid economic impoverishment from medical costs. Read our feature on medical impoverishment averted through immunization in 41 low-income nations.

A mother holding her child that is receiving a vaccine.

The hurdles that remain are high, but health for all awaits on the other side

The road to UHC will be fraught with risk and will require creative new ideas for reaching the unreached. For one, we must ensure that whatever systems are put in place to expand access to basic health interventions will not inadvertently damage immunization coverage, but will reinforce progress that has been made in expanding immunization coverage.

It is also clear that the achievement of UHC goals by 2030, or by any time, will require us to not only expand and improve upon the health systems that already exist, but also to change our approach to these imperfect health systems. Those families who receive no basic health services are called “hard to reach” for a reason. The challenge in devising a system flexible and comprehensive enough to reach everyone is very real, and very worthwhile.

The vicious cycle of undernutrition and infectious disease: How does it work and what role do vaccines play?

Posted on by stacy

Undernutrition and infectious diseases are tightly linked in a self-reinforcing cycle. Childhood episodes of diarrhea, pneumonia and measles are exacerbated by undernutrition, which significantly contributes to the death toll from these infections. In this feature, the VoICE team explains the cycle of malnutrition and infectious disease, and brings you evidence of the ways in which vaccines interrupt this cycle and help to protect the overall health, growth and physical development of vulnerable children.

A selection of VoICE evidence in this issue

Kotloff, K.L., Nataro, J.P., Blackwelder, W.C., et al 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 382(9888).

Chisti, M.J., Pietroni, M.A., Smith, J.H., et al. 2011. Predictors of death in under-five children with diarrhoea admitted to a critical care ward in an urban hospital in Bangladesh. Acta Paediatrica. 100(12).

Chisti, M.J., Tebruegge, M., La Vincente, S., et al. 2009. Pneumonia in severely malnourished children in developing countries – mortality risk, aetiology and validity of WHO clinical signs: a systematic review. Tropical Medicine and International Health. 14(10).

Omer, S.B., Goodman, D., Steinhoff, M.C., et al 2011. Maternal influenza immunization and reduced likelihood of prematurity and small for gestational age births: a retrospective cohort study. PLOS Medicine. 8:e1000441.

Steinhoff, M.C., Omer, S.B., Roy, E., et al 2009. Association of infant pneumococcal immunization with infant growth in Asia. Presented at Pediatric Academic Societies meeting, Vancouver, Canada.

Gewa, C.A. and Yandell, N. 2011. Undernutrition among Kenyan children: contribution of child, maternal and household factors. Public Health Nutrition. 15(6).

Anekwe, T.D., Kumar, S. 2012. The effect of a vaccination program on child anthropometry:evidence from India’s Universal Immunization Program.. Journal of Public Health. 34(4).

Paknawin-Mock, J., Jarvis, L., Jahari, A.B., et al 2000. Community-level determinants of child growth in an Indonesian tea plantation. European Journal of Clinical Nutrition. 54(2).

A hidden killer: poor nutrition underlies almost half of all deaths in children under 5

You won’t see nutrition listed as the cause of death in a pie chart of child mortality, but undernutrition is one of the key contributing factors behind child deaths due to infection. Undernutrition is defined as insufficient food intake—including calories and/or nutrients–to sustain growth and health. (Malnutrition, in contrast, is a broader term referring to both undernutrition and overnutrition—the excess intake of food and calories.) The WHO estimates that undernutrition is a factor in 45% of child deaths—contributing to over 3 million deaths in 2004 – including 73% of child deaths due to diarrhea, 44% of pneumonia deaths, 47% of measles deaths, and 45% of deaths due to severe neonatal infections (Figure 1).1, 2, 3 These are the top childhood killers, and they share a recurring theme: undernourished children get sick more often and have worse outcomes—including a higher risk of dying—from every episode of infectious disease.4

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Figure 1: Major causes of death in children under 5 years old with disease-specific contribution of undernutrition, 20041

Source: WHO. Global health risks: mortality and burden of disease attributable to selected major risks. 2009. Click here for full report.

Many children worldwide are still undernourished

Undernutrition is common among children under 5, particularly in the poorest regions of the world, such as South Asia and Sub-Saharan Africa where 1 in every 3 children is undernourished. 5Undernutrition manifests in different ways as stunting, wasting and specific nutritional deficiencies of key vitamins and minerals that children need to grow and develop properly.

Stunting, as defined by a recent report from the WHO, UNICEF and the World Bank, refers to a child who is too short for their age.5 It is a result of chronic or recurrent undernutrition and affects 23% of children globally, or 155 million. Three-quarters of stunted children live in Sub-Saharan Africa and South Asia, where the prevalence of childhood stunting exceeds 33%. A more acute form of undernutrition is wasting, which refers to a child who is too thin for their height. Wasting results from rapid weight loss or a failure to gain weight and affects about 8% of children, or 52 million, under 5 globally. However, in South Asia levels are particularly critical with over 15% of children under 5 experiencing wasting.5 Notably, stunting is more prevalent than wasting as it is cumulative after multiple, shorter episodes of wasting—which in and of themselves can be reversible—but over time leads to stunting which is largely irreversible and has lifelong consequences.6

A vicious cycle: undernutrition and infection

Figure 2: The vicious cycle of undernutrition and infectious disease

Undernutrition Cycle
Undernourished children have less nutritional reserves to grow properly and to fight off infections.

Undernutrition has been called the most common cause of immunodeficiency worldwide.7 With poor nutrition, some parts of a child’s immune system do not function properly. The skin and gut cannot effectively block disease-causing bacteria, viruses and parasites from entering the body. The thymus, a gland in the neck which helps develop the disease-fighting T cells, becomes smaller and other parts of the immune system do not function properly. Thereby undernourished children are put at increased risk of developing diseases to which they are exposed in their environment and against which they otherwise would normally be able to defend themselves.

With each episode of disease, some of the energy and calories a child would otherwise use for growth and development is diverted to fight off the infection. Calories are consumed to mount a fever, one of the body’s protective mechanisms. If the child has pneumonia, breathing requires more work and this will require more calories, too. If the child has diarrhea, less nutrients are absorbed while the gut is inflamed and infected. For these reasons, a sick child needs more energy and calories to fight off the infection and recover, and an undernourished child – who has fewer energy reserves and likely less access to nutrient-rich food to begin with – falls even further behind in fulfilling their nutritional needs and is more susceptible to the next bout of illness.8

Figure 3: Child #1 is Undernourished

Undernourished child cycle
This decreases their immune system function, increases disease risk, duration and severity and significantly increases the risk of death. Infections further negatively impact nutritional status, potentially increasing the severity of undernutrition in this child and pushing them around the vicious circle once more.

A child who is sick also may not eat as much, taking in fewer calories and nutrients for the duration of the illness, putting the child at risk for falling further behind in growth. A prospective case-control study conducted in several developing countries found that children with moderate-to-severe diarrhea grew significantly less in length in the two months following their episode compared to age- and gender-matched controls.

Not only are undernourished children – like child #1 in Figure 3, above – more susceptible to getting sick, but their disease course is more likely to be severe or even fatal. A study of Bangladeshi children found that severely undernourished children had a nearly eight-fold increased risk of death from diarrhea than those who were not severely undernourished. In the case of pneumonia, those who are undernourished are at a 15-times higher risk of death. In this way, undernutrition is a hidden co-killer, masked behind the number of deaths due to diarrhea, pneumonia and other infections such as measles and malaria.

An otherwise healthy child – like child #2 in Figure 4, below – can also become temporarily undernourished because of an infection such as pneumonia, due to the increased energy needs of the infection. This can put the child at increased risk of other infections until a healthy nutritional status is attained once again.

Figure 4: Child #2 was not undernourished, but became undernourished due to an episode of infection.

Undernourished cycle to Infectious Disease
This may set them upon the path of recurrent infection and undernutrition.

Sickness and undernutrition have long-term consequences for children’s growth and development

Recurrent disease, severe disease and undernutrition interact to shape the trajectory of a child’s growth and cognitive development in the critical first 1000 days of life with long-term implications. Certain severe infections such as meningitis leave many children with long-term cognitive impairment and neurological sequelae. In a systematic literature review of studies from Africa, it was found that one quarter of children who survived pneumococcal or Hib meningitis—two vaccine-preventable causes of meningitis–had long-term neuropsychological deficits.

Stunting has been linked with lifelong consequences such as diminished cognitive development and decreased economic productivity for affected individuals.8 Studies have estimated that undernutrition decreases a nation’s economic growth by 8% or more due to the reduced potential of its people to study or work to their full potential.9

Vaccines are an important component of breaking the vicious cycle

The interactions of childhood diarrhea, pneumonia and malnutrition contribute to a vicious cycle of poor health and delayed growth and development. Immunization, as an effective measure to protect against some of the main diseases of childhood, can help to disrupt this cycle.

Vaccines for pregnant women

The pathway to undernutrition often begins early, even as early as pregnancy. In this period of fetal growth and development, a mother’s receipt of influenza vaccine has been associated with improved pregnancy outcomes. In a US study, there was found to be an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity and small for gestational age birth during influenza season. Another review demonstrated that influenza vaccine during pregnancy adds 200 grams to newborn weight and reduces low birth weight by 15%. Reducing prematurity and improving fetal growth translates to a reduced risk of stunting in young children.10

Infant vaccines

Pediatric vaccines recommended by the WHO and UNICEF have been proven safe and effective in reducing children’s risk of disease and death. Vaccines such as pneumococcal conjugate vaccine (PCV) and Hib conjugate vaccine target bacteria that cause pneumonia and meningitis. Live, attenuated rotavirus vaccines target the leading cause of severe, dehydrating diarrhea in young children.11

Even children who are undernourished can respond well to vaccines, though there may be some differences in the amount or type of immunity they can produce depending on the degree of their undernutrition.9 More up-to-date studies are needed on the immune effects of undernutrition as much of the data on this topic is from older studies and using older laboratory tests. However, vaccines given to children on a timely basis have significant benefits for malnourished children and are integral in a multifaceted approach to breaking the vicious cycle of undernutrition and disease. In addition, many vaccines trials have been conducted in populations with high rates of stunting and wasting and have proven that even in these settings vaccines are effective and highly impactful.12, 13, 14, 15

By reducing the frequency of disease in at-risk children, vaccines help undernourished children maintain their nutritional status and use their calories for growth and cognitive development. In a review of recent studies, researchers show that PCV7 given to infants translates into an additional 500 grams of growth in the first 6 months of life. Another study in Kenya found immunization with polio, DPT and measles reduced the proportion of children under 2 years of age with stunting by 27%.

Implementation of a vaccine program has also been linked to improved child nutrition measures at the community level. A study from India found that on average there was a 22-25% reduction in stunting and a 15% reduction in weight-for-age deficit per child after rollout of its Universal Immunization Program. It is important to note that this study evaluated the impact of a vaccination program rather than the effect of vaccination in individual children. The authors describe that the vaccination program may have improved the primary care health infrastructure or resulted in increased maternal education and awareness of child nutrition and disease prevention. These collateral gains of implementing a vaccine program were also observed in an Indonesian study study of 24 communities, which found that children living in communities with higher overall levels of immunization were less likely to be malnourished as measured by how thin they were for their age.

These collateral gains of implementing a vaccine program were also observed in an Indonesian study of 24 communities, which found that children living in communities with higher overall levels of immunization were less likely to be malnourished as measured by how thin they were for their age.

According to a WHO report on global health risks, vaccines are part of a multi-pronged approach to reduce childhood underweight (along with nutritional interventions – such as micronutrient supplementation for children and women of child bearing age, and exclusive breastfeeding in infancy), which is the leading risk factor for death and disability in low income countries.1 By protecting children against common and sometimes deadly diseases, vaccines play a role in breaking the vicious cycle of infection and turning the tide on the hidden epidemic of undernutrition.

FOR ADDITIONAL INFORMATION:

1WHO. Global health risks: mortality and burden of disease attributable to selected major risks. 2009. Available at: http://www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_report_full.pdf.
2Bhutta ZA, et al. Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet 2013; 382: 452-477.
3RE Black, CG Victora, SP Walker, et al., the Maternal and Child Nutrition Study Group. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet (2013) published online June 6.
4WHO Media centre. Children: reducing mortality. 2017. http://www.who.int/mediacentre/factsheets/fs178/en/
5UNICEF, WHO, World Bank. Levels and trends in child malnutrition: UNICEF/ WHO/ World Bank Group joint child malnutrition estimates, key findings of the 2017 edition. 2017. Available at: http://www.who.int/nutgrowthdb/jme_brochoure2017.pdf?ua=1.
6WHO. Stunting. Accessed at http://www.who.int/mediacentre/infographic/nutrition/infographic-stunting.pdf?ua=1.
7Prendergast AJ. Malnutrition and vaccination in developing countries. Phil Trans R Soc B 2015; 370: 20140141.
8Katona P and Katona-Apte J. The interaction between nutrition and infection. CID 2008; 46(10): 1582-1588.
9S Horton, RH Steckel Global economic losses attributable to malnutrition 1990–2000 and projections to 2050. B Lombard (Ed.), appearing in: How much have global problems cost the world? A scorecard from 1900 to 2050, Cambridge University Press, Cambridge (2013)

From the VoICE Editors: This source was a working paper associated with the development think tank, The Copenhagen Consensus Center, which has been published in a 2013 Cambridge University Press book. Additional context and explanation of this paper may be found here: http://www.copenhagenconsensus.com/publication/scorecard-humanity-malnutrition-horton-steckel

10Black RE and the Maternal and Child Nutrition Study Group. Maternal and child nutrition: building momentum for impact. Lancet 2013; 382: 372-375.
11WHO. Rotavirus vaccines: WHO position paper—January 2013. WER 2013; 5(88); 49-64.
12Isanaka S, et al. Efficacy of a low-cost, heat-stable oral rotavirus vaccine in Niger. NEJM 2017; 376: 1121-1130.
13Cutts FT, et al. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: a randomised, double-blind, placebo-controlled trial. Lancet. 2005;365:1139-46.
14Madhi SA, et al. Effect of human rotavirus vaccine on severe diarrhea in African infants. NEJM 2010; 362(4): 289-298.
15Watt JP, et al. Haemophilus influenza type b conjugate vaccine: review of observational data on long term vaccine impact to inform recommendations for vaccine schedules. 2012. Available at: http://www.who.int/immunization/sage/meetings/2012/november/5_Review_observational_data_long_term_vaccine_impact_recommendations_vaccine_schedules_Watt_J_et_al_2012.pdf.

Cancer and Immunization: More than meets the eye

Posted on by stacy

Evidence from several disciplines indicates that immunization has a broader role to play in lessening the impact of cancer than one might expect. While it may be obvious that the widespread and growing use of vaccines against Hepatitis B and human papilloma virus (HPV) is directly responsible for preventing a significant number of related cancers, immunization against a host of other diseases may indirectly help to prevent additional cancers while helping to protect the health of immune-compromised cancer patients considerably. Read on for a brief explanation of how vaccines can prevent cancer, protect cancer patients and more.

A selection of VoICE evidence in this issue

Andrus, J.K., Cochi, S.L., Cooper, L.Z., et al 2016. Combining global elimination of measles and rubella with strengthening of health systems in developing countries. Health Affairs. 35(2).

Ramakrishnan, M., Ulland, A.J., Steinhardt, L.C., et al 2009. Sequelae due to bacterial meningitis among African children: a systematic literature review. BMC Medicine. 7(47).

Goetghebuer, T., West, T.E., Wermenbol, V., et al 2000. Outcome of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae type b in children in The Gambia. Tropical Medicine and International Health. 5(3).

Mina, M.J., Metcalf, C.J. de Swart, R.L., et al 2015. Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Science. 348(6235).

Coles, C.L., Rahmathullah, L., Kanungo, R., et al 2012. Pneumococcal carriage at age 2 months is associated with growth deficits at age 6 months among infants in South India. Journal of Nutrition. 142(6).

Gewa, C.A. and Yandell, N. 2011. Undernutrition among Kenyan children: contribution of child, maternal and household factors. Public Health Nutrition. 15(6).

The direct benefits of preventing cancer-causing infections

HepB and liver cancer

Introduced in 1982, the hepatitis B vaccine was the first widely available vaccine to directly prevent cancer. More than 1 billion doses of HepB vaccine have been delivered, resulting in a significant reduction in the chronic liver infection that leads to cirrhosis or cancer in roughly a quarter of adults. The risk of HepB infection begins at birth – and lasts throughout a person’s life – which is why HepB is the first vaccine most children receive, often within hours of coming in to the world. In fact, 80-90% of children who are infected with HepB during the first year of life will go on to develop chronic liver disease, dramatically increasing their cancer risk.

More from the World Health Organization

HPV and cancer

A leading cause of death among women, cervical cancer took the lives of more than a quarter of a million women in 2012, 85% of whom were from low- or middle-income countries. Cervical cancer is caused by human papillomavirus (HPV), a common infection that can lead to abnormal cell growth and high-mortality cancers. Just two of the more than 100 strains of HPV are responsible for 70% of cervical cancers and precancerous lesions. Each of the three available HPV vaccines has been proven effective in preventing infection with high-risk strains of HPV and could protect against other forms of cancer caused by the virus. The exceedingly high mortality rate for cervical cancer (1 in 2 women will succumb to the disease) is due largely to the lack of access to early detection and treatment for women in much of the world, and reinforces the urgency of prevention through vaccination.

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Additional benefits

HepB, Hib and polio vaccines

Some intriguing new evidence suggests that vaccines against HepB, Hib and polio may indirectly help to prevent the development of childhood cancers. Some scientists have suggested that early and robust stimulation of a child’s immune system – such as that afforded by vaccination – could help the body recognize and neutralize early tumors, thus decreasing the risk of developing certain childhood cancers such as leukemia. A study from the state of Texas in the US tested this idea and found that children born in counties with high coverage of HepB, polio and Hib vaccine were 33-42% less likely to develop a specific kind of leukemia than children born in counties with low vaccine coverage. Although only a small number of studies have demonstrated this indirect benefit of immunization on childhood cancers thus far, it is an exciting new area we will be following closely.

Protecting cancer patients and survivors from other infections

Cancer and cancer treatments can severely diminish the body’s capacity to fight infection, putting cancer patients and survivors at significantly greater risk of vaccine-preventable diseases and death from secondary infections. For example, a study of adults in the US found that invasive pneumococcal disease was more than 20 times more likely to occur in cancer patients than in cancer-naïve people. In a large study that followed survivors of childhood and early adult cancers for more than 5 years, researchers found a significantly higher rate of infections than in the siblings of these patients. Cancer survivors in this study were also 4 times more likely to die of infectious causes than their siblings. Pneumonia, a potentially vaccine-preventable infection, carried some of the highest increased risk to cancer patients, even more than 5 years after cancer diagnosis.

Survivors of pediatric and young-adult cancers must also be concerned about developing other forms of cancer later in life, some of which may be preventable through use of the HPV vaccine. A large study in the US found that longterm cancer survivors – both men and women – appeared to have a significantly increased risk of developing HPV-associated cancers and malignancies later in life. For these reasons, it is critical that cancer patients and survivors be vaccinated, and sometimes re-vaccinated, to ensure the greatest possible protection from additional infection.

Herd immunity in the general population is also an important protective firewall for cancer patients [1] weakened by the disease who may not yet have been vaccinated. Immune-suppressive treatments commonly used to treat some forms of cancer may erase the immunity a patient had already built up through previous vaccination and leave the immune system too weak to tolerate immunization.

The economic benefits of cancer prevention are substantial

Preventing cancer has significant economic implications, and vaccines that help prevent cancer carry a significant return on investment in a variety of settings.

Hep B: Economic benefits

In terms of economic benefits, HepB vaccine carries a high economic return on investment, due in part to the sustained risk of infection across the lifespan. Health economists have estimated that during the decade 2011-2020, the use of this vaccine in the world’s poorest countries will have a return of over nine times its cost, thanks to the widespread use and high effectiveness of HepB Vaccine.

HPV: Health System and economic benefits

HPV vaccine is recommended to be given to girls in early adolescence (as opposed to most other childhood vaccines which are given during the first few years of life), which has resulted in some unique opportunities to expand delivery of other health services to this age group – even those not receiving the vaccine – and to form new collaborations between agencies that may help strengthen health programs overall.

Despite gradual uptake of HPV vaccine among the world’s poorest countries, health economists have estimated a 3-fold return on investment from the use of HPV vaccine in these countries during this decade (2011-2020). Averting the premature death of women through prevention of cervical and other HPV-related cancers increases overall productivity and would prevent destabilization of families and communities.

[1] High vaccine coverage in the general population significantly reduces the chance that an infectious agent is transmitted to others, significantly reducing the risk that an unvaccinated person will be exposed and infected. This phenomenon is called herd immunity.

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