VoICE : Search Immunization Evidence

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The VoICE tool is a compendium of the many direct and downstream impacts of vaccine-preventable disease and immunization. The database contains summary explanations of the link between immunization and each impact, as well as sources of evidence for each link. You can browse the VoICE tool by topic, or use the filters to find results based on topic, disease or vaccine, location and published year.

57 Key Concepts, 43 Sources
Key Concept

Key Evidence: A 2019 analysis of survey data from India, Ethiopia and Vietnam found that children vaccinated against measles scored better on cognitive tests of language development, math and reading than children who did not receive measles vaccines.

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Key Concept

Key Evidence: Across many South Asian and sub-Saharan African countries, children of mothers who received no formal education were nearly 3 times as likely to die before reaching age 5 as those born to mothers with some secondary education.

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Key Concept

Key Evidence: A review of gut infections and effects on physical growth and development found that for children living in impoverished areas of the world, episodes of diarrhea during the first two years of life not only negatively affected their physical growth, but could result in a 10 points lower IQ than average by age 7.

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Key Concept

Key Evidence: A comprehensive review of the economics of cholera and cholera prevention concluded that vaccination using oral cholera vaccines can be cost-effective, especially when herd effects are taken into account and when vaccination is administered to populations and age groups with high incidence rates (e.g., children) and to areas with high cholera case fatality rates.

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Key Concept

Key Evidence: Tens of millions of volunteers, social mobilizers, and health workers have participated in the Global Polio Eradication Initiative. The program contributes to efforts to deliver other health benefits, including health systems strengthening. Polio eradication legacy efforts include documenting and applying the lessons learned from polio eradication and transitioning the capacities, assets, and processes of polio to other key health priorities.

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Key Concept

Key Evidence: In a study modeling the economic impact of immunization in 41 low- and middle-income countries, the authors estimate that 24 million cases of medical impoverishment would be averted through the use of vaccines administered from 2016-2030. The largest proportion of poverty cases averted would occur in the poorest 40% of these populations, demonstrating that vaccination can provide financial risk protection to the most economically vulnerable.

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Key Concept

Key Evidence: Children under 5 years of age bear the greatest burden of indirect conflict-associated mortality (indirect mortality results from disruption of health services including immunization, food insecurity, and high risk living conditions such as those found in refugee camps). The leading causes of child death in these circumstances include respiratory infections, diarrhea, measles, malaria, and malnutrition.

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Key Concept

Key Evidence: Mass displacement of people during a complex humanitarian emergency can trigger a “cascade” of risk factors for communicable disease outbreaks, including a breakdown in health services (such as disease surveillance and immunization services); over-crowding (increasing disease transmission rates); inadequate water, sanitation and hygiene; and exposure of displaced population to endemic diseases for which they have no immunity.

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Key Concept

Key Evidence: Researchers estimate that vaccinating against 10 diseases in the world’s 94 poorest countries between 2011-2020 will avert US$586 billion in costs of illness (including treatment costs, transportation costs, lost caretaker wages and productivity losses due to death and disability). The 73 Gavi-supported countries account for US$544 billion of the treatment costs averted.

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Key Concept

Key Evidence: In urban residents in the Democratic Republic of Congo, chronically malnourished children were less likely to have received two doses of measles-containing vaccine compared to healthy children.

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Key Concept

Key Evidence: Missed opportunities for vaccination i.e. percentage of children who failed to attain full immunization coverage (FIC) among those receiving one or more other health interventions were assessed through a study of 14 geographically diverse countries. In children with a vaccination rate below 70%, FIC was observed to be lowest in children born to mothers who failed to attend antenatal care across countries. The largest difference in FIC (54%) was observed in Côte d’Ivoire comparing children born to mothers who attended four or more ANC visits compared to no ANC visits. The presence of skilled birth attendant (SBA) was linked to higher rates of FIC with a 36% lower FIC in children born without a SBA in Nigeria. Post-natal care (PNC) acted as a factor contributing to 31% increase in FIC in the children who received PNC in Ethiopia. Vitamin A supplementation and sleeping under an insecticide treated bed net (ITN) were also positively linked to increase in FIC in the Democratic Republic of Congo and Haiti respectively.

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Key Concept

Key Evidence: The first study of the cost-effectiveness of typhoid conjugate vaccines found that routinely immunizing infants at 9 months of age would actually save costs in 2 settings (Delhi, India and a rural area of Vietnam), due to high incidence or high hospitalization rates, and would be cost-effective in the study’s 3 other sites (in India and Kenya). Adding a one-time catch-up campaign for various older age groups would still save costs in the Delhi and Vietnam, and increase the cost-effectiveness in the others, making it economically justifiable.

From the VoICE Editors: The study incorporated herd effects into its model, looked only at the perspective of healthcare payers and assumed the use of a single dose vaccine at 1 international dollar.

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Key Evidence: In a modeled analysis of the economic impact of vaccine use in the world’s 72 poorest countries, for countries included in the analyses from the African region, scaling up coverage of the Rotavirus (RVV) vaccine to 90% was projected to result in more than US$900 million in treatment costs averted.

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Key Concept

Key Evidence: According to the World Bank, the economic impact of the 2014-15 Ebola epidemic outlasted the epidemiological impact of outbreak, resulting in estimated losses of US$2.8 billion in Guinea, Liberia, and Sierra Leone (or 16% of their combined GDP).

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Key Concept

Key Evidence: An analysis of the association between undernutrition and mortality in young children revealed that in 60% of deaths due to diarrhea, 52% of deaths due to pneumonia, 45% of deaths due to measles and 57% of deaths attributable to malaria, undernutrition was a contributing factor.

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Key Evidence: The  presence of malnourishment correlates with the severity of cholera illness.  Additional factors include the number of V. cholerae bacteria ingested, lack of immunity from prior exposure or vaccination, pregnancy, lack of breast-feeding, immunocompromised state, reduced ability to produce gastric acid, and having blood group O.

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Key Concept

Key Evidence: A meta-analysis of antimicrobial resistance (AMR) in migrant populations in Europe found that 25% of migrants carried or were infected with antibiotic resistant organisms. When considering all migrant types, refugees and asylum seekers had a higher rate (33%) of carrying or being infected with AMR organisms than other migrant groups (7%).

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Key Concept

Key Evidence: The detection of H1N1 influenza virus in Mexico in 2009, and subsequently throughout other countries in the Americas, benefited from the laboratory experience with measles and rubella in the region, leading to the rapid detection of and response to what eventually became a novel pandemic virus.

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Key Concept

Key Evidence: A meta-analysis of antimicrobial resistance (AMR) in migrant populations in Europe found that 25% of migrants carried or were infected with antibiotic resistant organisms. When considering all migrant types, refugees and asylum seekers had a higher rate (33%) of carrying or being infected with AMR organisms than other migrant groups (7%).

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Key Concept

Key Evidence: Although the upfront investment in preparedness is costly – severe influenza pandemic preparedness is US$4.5bn a year – the estimated annual economic benefits would total US$60bn and US$490bn through averted deaths. “Even if only one tenth of these benefits were to materialize, the returns to public investment in preparedness would still be extraordinarily high.”

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Key Concept

Key Evidence: In an analysis of a hypothetical disease outbreak scenario, based on data from the Ebola epidemic in West Africa, researchers estimated that a large-scale disease outbreak spreading to nine Asian countries could cost the US economy $8-41 billion in lost exports and put almost 1.4 million export-related US jobs at risk.

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Key Concept

Key Evidence: Vaccines that can protect against pneumonia – Hib and S. pneumoniae vaccines – can together prevent over 1.25 million cases of poverty over 15 years, found researchers modeling the economic impact of immunization in 41 low- and middle-income countries.

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Key Concept

Key Evidence: A recent study estimated that, during the decade from 2011-2020, every US$1 invested in immunization programs in the world’s 73 poorest countries would yield a US$16 return on investment. Using an approach accounting for additional societal benefits of vaccination (the “full income approach”, which quantifies the value that people place on living longer and healthier lives), researchers estimated the return could be as high as US$44 per US$1 invested.

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Key Concept

Key Evidence: The risk of mortality from tetanus is high for mothers and their newborns, and up to 50% of children who do survive neonatal tetanus may have long-term cognitive impairment, according to a 2007 review.

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Key Concept

Key Evidence: A 2019 analysis of survey data from school aged children in Ethiopia, India and Vietnam shows that children vaccinated against measles achieved 0.2 – 0.3 years of additional schooling compared to children who did not receive the measles vaccine.

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Key Concept

Key Evidence: A study looking at WHO data from member states shows that globally, 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.

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Key Evidence: Researchers looking at vaccination coverage in 45 low- and middle-income countries found that maternal education is a strong predictor of vaccine coverage. Children of the least educated mothers are 55% less likely to have received measles containing vaccine and three doses of DTP vaccine than children of the most educated mothers.

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Key Concept

Key Evidence: Across multiple studies reviewed, the effect of measles vaccine appears to be more beneficial to girls combating all-cause mortality when differences between vaccine effect in boys and girls was assessed.

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Key Concept

Key Evidence: A study looking at DHS data from 67 countries found that, globally, girls and boys had the same likelihood of being vaccinated. In some countries where there is known gender inequity and son preference, girls were more likely to not be vaccinated.

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Key Concept

Key Evidence: An ecological study designed to investigate the association between child mortality rates and gender inequality using the United Nations Development Programme’s Gender Inequality Index (GII), showed that low- and middle-income countries have significantly higher gender inequality and under-5 mortality rates than high-income countries. Greater gender inequality was significantly correlated with lower immunization coverage and higher neonatal, infant, and under-5 mortality.

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Key Evidence: To better understand the drivers of vaccination coverage and equity, a 2017 study examined the country-level factors influencing vaccination coverage in 45 low- and lower-middle income Gavi-supported nations. Countries with the least gender equality – as measured by reproductive health, women-held parliamentary seats, educational attainment, and other factors – also had lower rates of vaccine coverage.

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Key Concept

Key Evidence: In an 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 countries. 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.” The same held true for measles vaccines with a 1.45-fold likelihood of vaccination in children of the most educated mothers.

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Key Concept

Key Evidence: Children in slum settings have higher burdens of vaccine-preventable disease (one study found children in slums in Manila, Philippines were 9 times more likely to have tuberculosis than other urban children) and lower rates of immunization (a study in Niger found 35% coverage in slums vs. 86% in non-slum urban areas).

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Key Concept

Key Evidence: Human Papillomavirus (HPV) infections are more prevalent and persistent in HIV-infected individuals — HPV prevalence rates of 76% in HIV-infected women compared to the 46% prevalence rate in HIV-uninfected women. Cervical prevalence rates are also higher in HIV-infected women — between 48-73% in case compared to 28% in HIV-uninfected women. Additionally, HPV infections and HPV-associated diseases appear to exert a disproportionately higher burden of disease in HIV-infected women as opposed to HIV-uninfected women.

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Key Concept

Key Evidence: An analysis of the association between undernutrition and mortality in young children revealed that in 60% of deaths due to diarrhea, 52% of deaths due to pneumonia, 45% of deaths due to measles and 57% of deaths attributable to malaria, undernutrition was a contributing factor.

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Key Concept

Key Evidence: An analysis of the association between undernutrition and mortality in young children revealed that in 60% of deaths due to diarrhea, 52% of deaths due to pneumonia, 45% of deaths due to measles and 57% of deaths attributable to malaria, undernutrition was a contributing factor.

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Key Concept

Key Evidence: A group of experts evaluated a number of maternal, neonatal, and child health interventions for equity across wealth quintiles using data from 1990-2006. Immunization was found to have the narrowest differences in coverage of services between the poorest and wealthiest children. In other words, of the interventions evaluated, immunization was the most equitable across income groups.

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Key Concept

Key Evidence: Globally, coverage of the third dose of DTP is 15% higher among children in the highest compared to lowest wealth quintile. However, this masks differences of up to 64% in the most inequitable countries (Nigeria).

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Key Concept

Key Evidence: A group of experts evaluated a number of maternal, neonatal, and child health interventions for equity across wealth quintiles using data from 1990-2006. Immunization was found to have the narrowest differences in coverage of services between the poorest and wealthiest children (28% higher coverage in the highest wealth quintile compared to the lowest). By contrast, indicators of treatment coverage for children sick with diarrhea and pneumonia were nearly 60% higher in the highest wealth quintile compared to the poorest. This means that poor children are at a much greater disadvantage with respect to receiving treatment for pneumonia and diarrhea than they are for receiving vaccines to prevent these infections.

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Key Concept

Key Evidence: A study modeling the economic impact of 10 childhood immunizations in 41 low- and middle-income countries found that the bulk of poverty averted through vaccination occurs in poor populations. For most of the vaccines in the study, at least 40% of the poverty averted would occur in the poorest wealth quintile. Particularly for pneumonia, more than half of the two million deaths averted by pneumococcal and Hib vaccines would occur in the poorest 40% of the population.

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Key Concept

Key Evidence: Studies in several countries have shown that, following the introduction of pneumococcal conjugate vaccine, there was a reduction in the number and percent of drug-resistant cases of pneumococcal diseases in children, and in some countries in adults, due to herd effects. In Japan there was a 10-fold decline in the proportion of penicillin-resistance among cases of invasive pneumococcal disease (from 56% to 5%), and in the U.S. there were reductions of 81% and 49% in the proportion of penicillin-resistant cases in children less than two years and in adults more than 65 years old, respectively.

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Key Concept

Key Evidence: Several studies have shown a 13-50% reduction in the use of antibiotics by children who have received influenza vaccine compared with unvaccinated controls. This is due to a decline in febrile illnesses causes by influenza — for which antibiotics are often prescribed inappropriately — as well as a decline in secondary bacterial infections requiring antibiotic treatment, such as pneumonia and middle ear infections, that are triggered by influenza.

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Key Evidence: Vaccines against influenza reduce the use of antibiotics that drive drug resistance in bacteria in two ways. First, they prevent secondary bacterial infections caused by influenza, such as pneumonia and otitis media; in Ontario, Canada, the rate of prescribing for influenza-associated antibiotics declined around 64% after universal introduction of influenza vaccination compared to other Canadian provinces with more limited use of the vaccine. Second, they help prevent inappropriate antibiotic prescriptions for respiratory tract infections caused by influenza and other viruses, which account for half of all respiratory illnesses for which antibiotics are prescribed in the U.S.

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Key Concept

Key Evidence: According to a study in a hypothetical endemic population, vaccination using typhoid conjugate vaccine will reverse the current increase in the percent of chronic carriers of the disease who are antibiotic resistant, if at least 50% of the target population is vaccinated. This would deplete an important “reservoir” of antibiotic resistant typhoid.

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Key Evidence: A systematic review of studies from India found that prior to widespread use of the pneumococcal conjugate vaccine, antibiotic resistance in serious pneumoccocal infections among Indian children has been common. Penicillin resistance was found in 10% of invasive pneumococcal disease (IPD) cases, while trimethoprim/sulfamethoxazole resistance was found in more than 80% of these cases.

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Key Evidence: Shortly after its introduction of Hib vaccine in the United Kingdom, a decrease in resistant (ᵝ-lactamase-positive) strains were documented. In the U.S., following introduction of pneumococcal conjugate vaccines, including PCV13, there was a decrease in both antibiotic use and in the prevalence of pneumococcal strains not susceptible to antibiotics.

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Key Concept

Key Evidence: Researchers investigating the causes of a measles outbreak in Burkina Faso that occurred despite a recent mass vaccination campaign found that migration to and from Cote d’Ivoire was a major risk factor for children. Unvaccinated children who developed measles were 8.5x more likely to have recently traveled to Cote d’Ivoire than unvaccinated children who had not traveled across the border. Children returning to Burkina Faso after a period of time in Cote d’Ivoire were less likely to have been vaccinated due to low routine coverage of measles vaccines in Cote d’Ivoire. Conversely, unvaccinated children from Burkina Faso who traveled to Cote d’Ivoire and returned were more likely to be exposed to measles and thus had a higher rate of disease than children who never visited Cote d’Ivoire.

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Key Evidence: Insecurity resulting from armed conflict, political instability, or social disruption increases the risk of communicable disease outbreaks during complex humanitarian emergencies by inhibiting populations’ access to health services, disrupting activities such as immunization and surveillance that prevent the spread of diseases, and making adequate humanitarian responses more difficult.

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Key Concept

Key Evidence: The latest International Health Regulations (IHR) of the World Health Organization updated in 2005 contained several major changes compared to earlier versions. However, the need to report cases of cholera and yellow fever has remained along with an expansion of the concerned disease list. These diseases continue to be critical threats to national and international health security, making immunization against them a vital disease control approach.

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Key Concept

Key Evidence: In a 2014 review of the non-specific effects of measles vaccines, among others, the WHO Strategic Advisory Group of Experts indicated that some studies of measles vaccine were suggestive (but not conclusive) of a beneficial effect of measles vaccine on overall mortality beyond the expected direct effect of the vaccine against measles. In particular, randomized control trials of children in Guinea- Bissau which looked at mortality up to the age of 9 months showed a low number of deaths post administration of the 3 doses of the measles vaccine over the study follow up period. Another trial in Nigeria also showed similar results.

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Key Concept

Key Evidence: Declining child mortality results in decreased fertility (birth rates), influencing a demographic transition on the national and regional scale. Improvements in public health are at the heart of the this transition due to improved sanitation, immunization programs, antibiotics, and contraceptives.

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Key Concept

Key Evidence: According to a review of nervous system infections, up to 50% of survivors of encephalitis caused by Japanese Encephalitis Virus (JEV) are left with permanent cognitive, psychological or neurological disabilities.

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Key Concept

Key Evidence: Mothers infected with rubella virus during the first trimester of pregnancy can give birth to children with permanent disabilities such as intellectual impairment, autism, blindness, deafness, and cardiac defects. The infection is completely preventable if mothers are vaccinated before pregnancy.

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Key Concept

Key Evidence: Children in slums suffer from higher rates of diarrheal and respiratory illness, malnutrition, and have lower vaccination rates. Mothers residing in slums are more poorly educated and less likely to receive antenatal care and skilled birth assistance.

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Key Concept

Key Evidence: The period following delivery but before an infant acquires immunity to diseases by natural exposure or immunization — is when infant mortality from infections is highest. Vaccinating pregnant women has shown to be effective in protecting young infants against influenza and pertussis.

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Key Evidence: Immunization against tetanus, pertussis and influenza during pregnancy has been shown to have a profound effect on the health of the mother and fetus, and increases survival of infants in their first months of life. Maternal immunizations with tetanus toxoid-containing vaccines has been one of the main contributors to the 94% reduction in global deaths due to tetanus since 1988. Between the 1970s to the early 2000s, maternal immunization against pertussis brought disease incidence down to 5,000 cases per year from the earlier 100,000-250,000 cases per year in the United States. Vaccination of mothers for influenza has brought down confirmed cases of the disease by 63%.

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Key Concept

Key Evidence: Tens of millions of volunteers, social mobilizers, and health workers have participated in the Global Polio Eradication Initiative. The program contributes to efforts to deliver other health benefits, including health systems strengthening. Polio eradication legacy efforts include documenting and applying the lessons learned from polio eradication, and transitioning the capacities, assets, and processes of polio to other key health priorities.

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Key Concept

Key Evidence: In the Americas, a platform built to secure polio eradication has been expanded to help track, control, prevent, and monitor immunization impact for measles and rubella. In India, highly trained polio health workers have become the basis for a trained workforce working towards the elimination of measles and rubella and helping ensure India’s certification by WHO for having eliminated maternal and neonatal tetanus.

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Key Concept

Key Evidence: This study investigated the cost-effectiveness of multiple interventions against childhood pneumonia (including vaccination) and found that different combinations of expanded vaccine coverage with community or facility-based management, nutritional programs, or indoor air pollution measures maximized child health by providing the greatest health yield per dollar spent.

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Key Evidence: A systematic review of studies examining the broader economic impact of vaccination in low-middle income countries (LMICs) found that vaccination programs may improve the financial sustainability and affordability of healthcare programs in LMICs. The use of vaccines as part of a treatment cluster, or in combination with other infrastructure projects (such as water management systems) to maximize community health outcomes, offers opportunities for cost sharing between programs.

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Key Concept

Key Evidence: The American Academy of Pediatrics and the International Pediatric Association were included as partners in the measles and rubella elimination initiative, allowing for more direct collaboration around the interactions of primary health and immunization services and concerns.

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Key Concept

Key Evidence: The detection of H1N1 influenza virus in Mexico in 2009, and subsequently throughout other countries in the Americas, benefited from the laboratory experience with measles and rubella in the region, leading to the rapid detection of, and response to, what eventually became a novel pandemic virus.

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Key Concept

Key Evidence: This paper presents the first cost-benefit comparison of improved water supply investments and cholera vaccination programs. The study results showed that improved water supply interventions combined with targeted cholera vaccination programs are much more likely to yield attractive cost-benefit ratio outcomes than a community-based vaccination program alone.

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Key Evidence: A systematic review of studies examining the broader economic impact of vaccination in low-middle income countries (LMICs) found that vaccination programs may improve the financial sustainability and affordability of healthcare programs in LMICs. The use of vaccines as part of a treatment cluster, or in combination with other infrastructure projects (such as water management systems) to maximize community health outcomes, offers opportunities for cost sharing between programs.

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Key Concept

Key Evidence: Increased uptake of immunization for vaccine-preventable diseases, particularly in low- and middle-income countries, could save the lives of thousands of mothers and children each year. The disease burden of tetanus, influenza, and pertussis has been minimized in many countries through maternal immunization, but wider applications of this strategy are now needed.

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Key Concept

Key Evidence: A review of evaluations of rotavirus vaccine impact on hospitalizations and all-cause acute gastroenteritis (AGE) across multiple countries showed that during the first decade since vaccine licensure, a 32% median reduction in hospitalizations due to AGE were observed in children under a year of age. In children younger than 5 years of age a 38% median reduction was noted. Additionally, laboratory confirmed cases of rotavirus-related hospitalization dropped by 80% and 67% in children under 1 year and 5 years of age respectively. The vaccine introduction also lead to a 46% decrease of AGE in children under 5 years of age in a high mortality setting.

From the VoICE Editors: These observations were evaluated using standardized, evidence- based PRISMA guideline.

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Key Concept

Key Evidence: Globally, coverage of the third dose of DTP is 8% higher among urban dwellers compared to children raised in a rural environment.

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