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.

48 Key Concepts, 70 Sources
Key Concept

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: 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: An study using GIS to quantify the percent of pregnant women in Mozambique without access to tetanus toxoid (TT) vaccine at varying distances from health facilities estimated that if women cannot travel more than 5 km to a TT immunization site there will be almost 18,000 neonatal tetanus cases each year that could be prevented, costing the country more than US$362 million in treatment costs and lost productivity. Covering 99% of women with TT will currently require people to travel up to 35 km to obtain an immunization.

From the VoICE Editors: GIS, a geospatial information system, is a computer system capable of capturing, storing, analyzing, and displaying geographically referenced information.

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Key Concept

Key Evidence: Seizures are the most common non-gastrointestinal symptom associated with rotavirus infection. Studies have found that during the year following rotavirus vaccination the risk of childhood seizures were reduced by 18-21% for seizures requiring emergency care or hospitalization in the U.S. and by 16-34% for childhood seizures requiring hospitalization in Spain.

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Key Concept

Key Evidence: In a study of school-based influenza vaccination in Los Angeles County, California, children who were vaccinated missed significantly fewer days of school than children who were not (2.8 vs. 4.3 per 100 school days).

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Key Concept

Key Evidence: Findings of a systematic review evaluating the relationship between pneumonia and malnourishment found that severely malnourished children in developing countries had 2.5 to 15 times the risk of death. For children with moderate malnutrition, the risk of death ranged from 1.2 to 36.

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Key Concept

Key Evidence: In a study of invasive pneumococcal disease in neonates in New Zealand following the introduction of pneumococcal conjugate vaccine (PCV) for infants, 67% of the cases in children <7 days old were of Maori ethnicity, while Maoris make up only 27% of New Zealand’s population. This over-representation of Maoris may be due to poverty and crowded living conditions and suggests that crowded households may be slower to experience the benefits of population-wide pneumococcal vaccination.

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Key Concept

Key Evidence: A pooled analysis of nine studies assessing the effects of diarrhea on stunting prior to the age of 24 months showed that the odds of stunting were significantly increased with each diarrheal episode. Each day of diarrhea prior to attaining 24 months of age also contributed to the risk of stunting. For each five episodes of diarrhea, the odds of stunting increased by 13%. In addition, once a child becomes stunted, only 6% of those stunted at 6 months of age recovered by 24 months of age.

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Key Concept

Key Evidence: The introduction of PCV-10, along with a “catch-up” campaign for 1-4 year olds, led to dramatic reductions in the rates of pneumococcal pneumonia in adults (≥18 years old) in a rural area of Kenya with high rates of both adult pneumococcal pneumonia and HIV. Over five years following the vaccine introduction, the incidence rates among adults were 47-94% lower each year than in the pre-vaccine period, with similar declines for HIV-infected and HIV-uninfected adults.

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Key Evidence: Children with cancer often rely on herd immunity as protection from vaccine-preventable diseases, so vaccinating family members and health workers is critical. Herd effects may be the only source of protection against diseases for which the vaccines are not recommended for immunosuppressed children, such as measles.

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Key Concept

Key Evidence: Through use of local Maternal Child Health (MCH) incentives, along with the use of locally appointed Health Activists, India’s National Rural Health Mission (NRHM) multiple-strategy community intervention program was able to achieve household level improvements in all of the following indicators for women and children over the 7 year program:
– the proportion of pregnant women having 3 or more ante-natal check-ups (from 43% to 74.5%)
– receiving at least one Tetanus Toxoid injection (from 83.5% to 93.6%)
– institutional deliveries (from 35.7% to 77%)
– post-natal check-ups within 2 weeks of delivery (from 49% to 67.2%) and,
– children who received ORS for diarrhea from (32.3% to 44.8%).

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Key Concept

Key Evidence: In India, a multi-strategy community intervention, the National Rural Health Mission (NRHM) was successful in reducing disparities between pregnant women who had an institutional delivery in urban and rural areas. Geographic inequities reduced from 22% to 7.6% and socioeconomic disparities declined from 48.2% to 13%. Post the NRHM period, the difference between the number of children with full vaccination i.e., Bacillus Calmette Guerin (BCG) vaccine for tuberculosis, 3 doses of Diphtheria Pertussis and Tetanus vaccine (DTP), 3 doses of Oral Polio Vaccine (OPV), and measles vaccine, in urban and rural areas was observed to be non-significant.

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Key Concept

Key Evidence: Those who experienced more frequent or longer episodes of diarrhea as an infant were more likely to have metabolic syndrome as adults. A longitudinal study in Guatemala found that diarrhea episodes in early infancy are associated with chronic health issues later in life. Each 1% increase in diarrhea burden in children 0-6 months was associated with a 3% increased prevalence in high blood pressure in adulthood. Similarly, a 1% increase in diarrhea burden in older infants 6-12 months was associated with a 4% increased prevalence in elevated waist circumference in adulthood.

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Key Evidence: In a study of data from England & Wales, Denmark and the US, it was shown that measles infection suppresses the immune system for up to 3 years after infection, increasing the risk of death due to other childhood infections during that time. This means that prevention of measles significantly impacts overall health during critical childhood years.

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Key Concept

Key Evidence: An analysis conducted in areas of Ethiopia with high proportions of refugees found that high measles vaccination coverage was linked to lower rates of acute malnutrition (wasting) in children under five. For each percentage point increase in measles vaccination coverage, there was a 0.65% decrease in the rate of acute malnutrition in these areas.

From the VoICE Editors: The analysis was conducted on data from more than 150 nutrition surveys.

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Key Concept

Key Evidence: A study of insurance claims in the U.S. for children under five estimated that, from 2007 to 2011, rotavirus vaccination prevented more than 176,000 hospitalizations, 242,000 emergency room visits and more than 1.1 million outpatient visits due to diarrhea — saving an estimated $924 million in direct health care costs over four years.

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Key Evidence: In a study using actual data on hospitalizations and costs before and after PCV-10 vaccine was introduced in Brazil, an estimated 463,000 hospitalizations from all causes of pneumonia were prevented in persons less than 65 years of age over 5 years following introduction of the vaccine — saving an estimated US$147 million in hospitalization costs. Half of the costs averted were due to fewer hospitalizations in children under five, who were targeted for the vaccine, while the remaining half were due to fewer hospitalizations in persons 5-49 years of age, as a result of herd protection.

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Key Concept

Key Evidence: An analysis conducted in areas of Ethiopia with high proportions of refugees found that high measles vaccination coverage was linked to lower rates of acute malnutrition (wasting) in children under five. For each percentage point increase in measles vaccination coverage, there was a 0.65% decrease in the rate of acute malnutrition in these areas.

From the VoICE Editors: The analysis was conducted on data from more than 150 nutrition surveys.

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Key Concept

Key Evidence: A series of studies in the U.S. estimated that the average savings in direct healthcare costs from rotavirus and acute gastroenteritis were between $121 million and $231 million per year once rotavirus vaccines were introduced.

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Key Concept

Key Evidence: In Japan, which has experienced a re-emergence of pertussis among adolescents and adults, vaccinating pregnant women with the Tdap vaccine would be cost effective in preventing the illness in young infants (<3 months of age) and in mothers, according to the WHO definition of cost effectiveness. This is true even if only 50% of pregnant women receive the vaccine.

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Key Evidence: Pertussis causes nearly 200,000 deaths in children worldwide, nearly all in infants too young to be vaccinated. Vaccinating pregnant women against pertussis with a single dose of Tdap vaccine would be 89% effective in protecting infants against the disease over their first 2 months of life and would reduce pertussis incidence in newborns in the U.S. by 68% (assuming 75% of mothers are vaccinated). This strategy is cost-effective, whereas vaccinating the father before the birth or vaccinating parents and/or other family members after the child is born would not be.

From the VoICE Editors: The analysis assumes a vaccination cost of ≈$44 per dose.

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Key Evidence: The cost-effectiveness of vaccinating infants with PCV-13 in China was estimated to be 21 times greater when the indirect effects of vaccination in reducing invasive pneumococcal disease and hospitalized cases of pneumonia in older (unvaccinated) individuals was taken into account — with costs per quality of life-year gained (QALY) of around US$564 (Y3,777) vs. $11,836 (Y79,204) when only the direct impact on vaccinated children is considered.

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Key Concept

Key Evidence:A study assessing the cost-effectiveness of Pneumococcal Conjugate Vaccine (PCV) demonstrated that nealy 38,000 cases of invasive pneumococcal disease were averted in the first five years post introduction of PCV in the US. These results, based on active surveillance data also revealed that the costs averted translated to US $112,000 per life year saved.

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Key Evidence: Assuming 90% coverage, a 9-valent PCV (PCV9) program in The Gambia would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, for the birth cohort over the first 5 years of life. The estimated cost would be $670 per DALY averted in The Gambia.

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Key Evidence: A study in Australia estimated that adding dTpa vaccination for pregnant women to the current pertussis immunization program for children would prevent an additional 8,800 symptomatic pertussis cases (mostly unreported) and 146 hospitalizations each year in all ages, including infants and their mothers, as well as one death every 22 months. The study found maternal pertussis vaccination to be cost-effective.

From the VoICE Editors: Note: The formulation used in this study is abbreviated dTpa.

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Key Concept

Key Evidence: A large longitudinal study in the Philippines found that children suffering bouts of diarrhea and respiratory infections were at a significantly increased risk of physical stunting which is associated with “poor functional outcomes such as impaired cognitive development.”

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Key Concept

Key Evidence: In The Gambia, 58% of children who survived pneumococcal meningitis had long lasting negative health outcomes. Half had major disabilities such as mental retardation, hearing loss, motor abnormalities, and seizures.

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Key Evidence: In a systematic literature review of studies in Africa, it was found that 25% of children who survived pneumococcal or Hib meningitis had neuropsychological deficits.

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Key Concept

Key Evidence: Children in the U.S. whose mothers were not educated beyond high school have significantly lower vaccination rates for rotavirus than children of mothers with advanced degrees (68% vs. 84%).

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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: 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: Prior to the introduction of PCV, adults with HIV in a rural area of Kenya were nearly five times more likely to have pneumococcal pneumonia than non-infected adults, and the majority of cases with bacteremia (blood infection) occurred in HIV positive individuals.

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Key Concept

Key Evidence: Even though the incidence of invasive pneumococcal disease declined in all groups, including individuals on immunosuppressive drugs, following the introduction of pneumococcal conjugate vaccines for infants in Norway, people on chemotherapy were still 20 times more likely to get IPD than individuals not on any immunosuppressants, while individuals on long-term corticosteroids or other immunosuppressive drugs were around 6 times more likely to get the disease.

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Key Evidence: Among children and young adults being treated for certain cancers, immunosuppressive therapies can erase immunity previously acquired through vaccination, dramatically increasing the risk of vaccine-preventable infections. The authors assert that vaccination during and after immunosuppressive treatment is necessary to rebuild immunity and protect the most at-risk children.

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Key Concept

Key Evidence: Over a five-year period following the introduction of PCV for infants in Kenya, the incidence of pneumococcal pneumonia in adults with HIV in a rural area fell sharply — narrowing the gap in incidence rates between HIV-infected and non-infected adults — as a result of both the herd effects of the vaccine and improved access to HIV care during this period.

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Key Concept

Key Evidence: A study of Kenyan children under 5 years of age found that immunization with polio, BCG, DPT, and measles to be protective against stunting in young children (27% less likely to be stunted than unimmunized children under age 2 years). In addition, children with diarrhea and cough in the 2 weeks prior to the survey were 80-90% more likely to be underweight or to suffer from wasting.

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Key Concept

Key Evidence: Children in U.S. families living below the poverty line have significantly lower rotavirus vaccination rates than children at or above the poverty line (67% vs. 77%).

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Key Concept

Key Evidence: A large U.S. study of surveillance data examining the impact of switching from PCV7 to PCV13 for infants demonstrated how important vaccination is in combating antimicrobial resistance. While the incidence of antibiotic-resistant invasive pneumococcal disease (IPD) was increasing before the introduction of PCV13, drug resistant IPD declined 78-96% in children under five after the vaccine introduction.

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Key Concept

Key Evidence: In a study of data from England & Wales, Denmark, and the US, it was shown that measles infection suppresses the immune system for up to 3 years after infection, increasing the risk of death due to other childhood infections during that time. This means that prevention of measles significantly impacts overall health during critical childhood years.

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Key Evidence: An analysis of children aged 12-59 months in rural India showed that children who were not vaccinated against measles vaccine in infancy had a three times higher likelihood of death, with unvaccinated children from lower caste households having the highest risk of mortality (odds ratio, 8.9). However, the results also revealed a nonspecific reducing effect of the vaccine on the overall child mortality in this region. This indicates that vaccination against measles can benefit the overall population, especially those in lower castes who have not received the vaccine in infancy. Thus, making them the group that would receive the highest benefit.

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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: A study including thousands of children from the U.S. state of Texas found that children born in counties with high coverage of HepB, Polio, and Hib vaccines were 33%, 37%, and 42% less likely to develop a specific type of leukemia than children born in counties with lower coverage of each vaccine.

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Key Concept

Key Evidence:A study from South Africa shows that reduction in birth rate (fertility) can yield certain socioeconomic benefits. These include 1) a decrease in ratio of economically dependent people 2) increased per capita labor force and 3) increased savings. These savings can be invested in physical human capital which aids in economic growth. As average family sizes decrease, parents are likely to invest more on their child’s health and education. This in turn offers potential benefits to long term productivity in adulthood.

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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: Respiratory infections during pregnancy may exert indirect effects on the developing fetus through placental function and maternal immune responses. This in turn may lead to pre term births and reduced growth of the fetus. However, a review of recent studies, researchers show that administration of influenza vaccine during pregnancy adds 200 grams to newborn weight and that PCV7 vaccine given to infants translates into an additional 500 grams of growth in the first 6 months of life. In addition, maternal influenza vaccine led to a 15% reduction in low birth-weight. This indicates that immunization can improve intrauterine growth.

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Key Evidence: In a study of families living on 24 plantations in Indonesia, the community immunization rate was found to be protective against thinness for age in children. In other words, children in communities with higher overall levels of immunization had better nutritional status.

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Key Evidence: Modeling of data from India’s National Family Health Survey-3 indicated that vaccinations against DPT, polio and measles were significant positive predictors of a child’s height, weight and hemoglobin concentration. This was ascertained post modeling of data obtained from over 25,000 children.

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Key Evidence: This study, conducted in the United States, demonstrates an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods. Moreover, during the period of widespread influenza activity there was an association between maternal receipt of influenza vaccine and reduced likelihood of small for gestational age (SGA) birth.

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Key Evidence: Children enrolled in Universal Immunization Programs observe improvements in terms of age-appropriate height and weight as per results of a study focused on 4 year old children in India. On an average height and weight deficits were reduced by 22-25% and 15% respectively.

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Key Evidence: A study in Kenya revealed that immunization with polio, BCG, DPT and measles had protective effects with respect to stunting in children under 5 years of age. In children under the age of 2 years, immunized children were 27% less likely to experience stunting when compared to unimmunized children. Additionally, children who suffered from cough or diarrhea in the 2 weeks prior to the study showed an 80-90% higher probability of being underweight or experiencing wasting.

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Key Concept

Key Evidence: Several studies in the U.S. have shown that hospitalizations due to rotavirus fell sharply in children too old to be vaccinated as well as in adults after rotavirus vaccines were introduced, indicating herd protection. In one large study, rotavirus hospitalizations in 2008 — two years after the first vaccine was introduced — declined by 71% in 5-14 year old children and by 65% in 15-24 year olds compared to the pre-vaccine period.

From the VoICE Editors: For more information also see Lopman 2011. https://academic.oup.com/jid/article/204/7/980/810889

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Key Evidence: Several countries have seen a significant decrease in the number of rotavirus-related hospital admissions in rotavirus unvaccinated children ages 2-5 years who were not age eligible to receive the vaccine post introduction. The US had a 41-92% decrease, Australia had a 30-70% decrease, Belgium had a 20-64% decrease, Austria had a 35% reduction and El Salvador had a 41-81% decrease. In addition, there was a reduction in hospitalizations due to gastroenteritis of any cause by 17-51% in the US and 40% in Australia.

From the VoICE Editors: This data is from a review article of multiple studies that evaluated the benefits of rotavirus vaccine following vaccine introduction.

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Key Evidence: While there have been concerns that vaccinating infants against varicella (chicken pox) would shift the disease to older age groups, numerous studies in countries that have introduced the vaccine have shown a decrease in varicella incidence or in hospitalizations in older age groups of 80% or greater. Indirect protection from vaccination has been reported in individuals not eligible for live vaccines and those who may be at higher risk of complications from chicken pox, such as children <1 year of age, pregnant women and immuno-compromised individuals.

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Key Evidence: HPV vaccine given to young women may also protect similarly-aged men against oropharyngeal cancers, which have been rising in incidence in the U.S. and Western Europe. In a small study in the UK, rates of oral HPV infections caused by HPV-16 were similar for males 12-24 years of age and vaccinated females (0% vs. 0.5%). This was considerably lower than the rates for unvaccinated females (5.6%) and men ≥25 years old (7.1%).

From the VoICE Editors: HPV-16 is the main HPV type linked to oropharyngeal cancers

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Key Evidence: There is evidence that the 4-strain HPV vaccine protects people who haven’t been vaccinated from getting HPV infection. A study in the U.S. of sexually active 13-26 year old women found that, as the vaccination rate of these women climbed from 0% to 84% over an 11-year period, the rate of infection with any of the four vaccine strains fell 40% among those who had not been vaccinated.

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Key Evidence: A study in rural Kenya, over a 4-year period following the introduction of the 10-strain pneumococcal conjugate vaccine for infants, that included a catch-up vaccination campaign for children 12-59 months of age, suggests that the catch-up vaccination for older birth cohorts may have been a key factor in protecting unvaccinated individuals and speeding up the reduction of the disease in the community. In contrast, a study in The Gambia, where no catch-up campaign took place, found no herd effects during the first three years following the introduction of PCV-13 for infants.

From the VoICE Editors: The Gambia study publication referenced can be found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909992/ 

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Key Evidence: According to some studies, hospitalizations from all causes of pneumonia declined in 18-39 year old adults in the U.S. by 26% 4 years after PCV7 vaccine was included in the infant vaccination schedule and by a further 12% with the first 2 years after PCV13 replaced PCV7. Though reductions in older age groups were not statistically significant, other U.S. studies showed significant reductions in pneumonia hospitalization rates in all adult age groups, including the elderly.

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Key Evidence: In Nagoya, Japan, hospitalizations due to rotavirus (RV) decreased sharply in children 2-4 years of age once the percent of infants vaccinated against RV climbed to around 80%. Few of these older children had likely received the vaccine, suggesting that they were protected as a result of herd immunity.

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Key Evidence: In a major children’s hospital in the Indian state of Tamil Nadu, meningitis cases caused by Haemophilus influenzae type b (Hib) in children under two years declined by 79% within two years of the introduction of Hib vaccine. This decline was greater than expected given a vaccination coverage of ~70% for one dose of the vaccine and much greater than expected with a 53% coverage rate for three doses. This suggests that the vaccine protected unvaccinated children through herd immunity.

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Key Evidence: Hospitalization rates for pneumococcal pneumonia in adults 65 and older in Portugal — which had been increasing on average by 16% per year before pneumococcal conjugate vaccines became available — began to reverse once PCVs became available for infants. The reduction in the elderly, over expected rates, was greatest after the introduction of PCV13.

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Key Evidence: The rate of invasive pneumococcal disease (IPD) in children too old to be vaccinated (≈1.5 – 10 years old) fell by 33% over a five-year period following the introduction of PCV-10 vaccines in Finland. The rate of IPD caused by serotypes in the vaccine fell by 58% in these children.

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Key Evidence: School-aged children (5-18 years old) experience the highest attack rates of influenza of any age group and are thus the most important means of spread of infection in the community, making them crucial targets for influenza vaccination. In a study of school-based influenza vaccination in Los Angeles County, California, schools that offered flu vaccine to their students reduced the risk of any child getting the flu by 30% (regardless of vaccination status) compared to schools that did not offer flu vaccine to students.

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Key Concept

Key Evidence: Multiple studies show that

  1. Diarrhea and pneumonia impair children’s growth and that underlying malnutrition is a major risk factor for these conditions.
  2. “Episodes of diarrhea may predispose to pneumonia in undernourished children” and
  3. Immunization against influenza (in mothers) and Streptococcus pneumoniae may improve infant growth. In addition, new studies from Bangladesh, Colombia, Ghana, and Israel further support the paradigm that malnutrition is a key risk factor for diarrhea and pneumonia.

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Key Concept

Key Evidence: A large longitudinal study in the Philippines found that children suffering bouts of diarrhea and respiratory infections were at a significantly increased risk of physical stunting which is associated with “poor functional outcomes such as impaired cognitive development.”

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Key Evidence: 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.

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Key Evidence: In a study conducted in Southern India, pneumococcal carriage at age 2 months was associated with a 3-fold risk of stunting and decreased weight, length, and length-for-age by 6 months of age. Pneumococcal carriage at 4 months of age did not affect growth.

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Key Evidence: A study of Kenyan children under 5 years of age found that children with diarrhea and cough in the 2 weeks prior to the survey were 80-90% more likely to be underweight or to suffer from wasting.

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Key Concept

Key Evidence: In a recent review of data from developing countries, researchers found that episodes of diarrhea may predispose undernourished children to pneumonia.

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Key Concept

Key Evidence: Data obtained through active surveillance pre and post introduction of PCV in the US showed that the vaccine averted an estimated 38,000 cases of invasive pneumococcal disease within its first five years of use. Additionally, 71,000 cases of disease were estimated to be prevented by herd effects.

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Key Evidence: Following the introduction of PCV-10 for infants in Brazil, which included catch-up vaccination for children 7-23 months old and achieved high coverage (82% increasing to 94% within 5 years), hospitalization rates for pneumonia from any cause declined over the next five years by 11-27% in persons 5-49 years of age, after adjusting for trends with other causes of hospitalization.

From the VoICE Editors: Note that the rate for the elderly (65+) increased by 15% over this period —  a trend that preceded the introduction of the vaccine. 

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Key Evidence: Assuming 90% coverage, a program in The Gambia using a 9-valent PCV (PCV9) would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs over the first 5 years of life of a birth cohort. The estimated cost would be $670 per DALY averted in The Gambia.

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Key Evidence: In one of the first studies of real-world use of pneumococcal conjugate vaccine (PCV) in Africa, the 10-strain vaccine introduced in Kenya for infants and provided to all children under five in “catch-up” campaigns reduced the incidence of any cause of pneumonia confirmed by a chest X-ray by nearly half (48%) in children 2-59 months of age over a five-year period. This sharp reduction in radiological-confirmed pneumonia is more than twice the reduction seen in several clinical trials of PCV in Africa and Latin America which was around 20-23%.

From the VoICE Editors: The sharp reduction in radiological-confirmed pneumonia as a result of immunization in this study is likely because – unlike in some clinical trials – the herd effects of the vaccine on unvaccinated children were prospectively captured in the study.

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Key Evidence: In Rwanda, the number of hospital admissions for diarrhea and rotavirus fell substantially after rotavirus vaccine (RVV) introduction, including among older children age-ineligible for vaccination. This suggests indirect protection through reduced transmission of rotavirus. Two years after RVV introduction, the country had nearly 400 fewer hospital admissions for diarrhea among young children.

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Key Evidence: After PCV13 replaced PCV7 in the U.S. infant immunization program in 2010, the incidence of invasive pneumococcal disease (IPD) caused by the 6 additional serotypes in the new vaccine declined by 75% in children too old to be vaccinated (5-17 years) by the third year following the switch, and by 58-72% in adults, compared to the expected incidence if PCV7 alone had been continued. This led to overall reductions in IPD incidence of 53% in 5-17 year olds and of 12-32% in adults within three years of the switch from PCV7 to PCV13.

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Key Evidence: According to a study using local epidemiological data in China, vaccinating infants with pneumococcal conjugate vaccine (PCV-13), using a 3+1 schedule, would prevent more than 10 times as many deaths from invasive pneumococcal disease and pneumonia in unvaccinated individuals (147,500 per year) than it would prevent directly in those vaccinated (12,800 per year). This would be due mainly to a reduction in hospitalizations for pneumonia.

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Key Evidence: A meta-analysis of studies measuring the impact of rotavirus vaccine (RVV) on severe gastroenteritis morbidity and mortality, found a 22% herd immunity effect for severe rotavirus gastroenteritis in children less than one year of age in US and El Salvador.  In Latin America, severe gastroenteritis due to any cause was reduced by 25%.

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Key Evidence: A large study in Norway found that the overall incidence of invasive pneumococcal disease (IPD) declined significantly in individuals on immunosuppressive drugs following the introduction of PCVs for infants — and most significantly in people undergoing chemotherapy. These findings underscore the benefits that childhood vaccination with PCVs affords the entire population.

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Key Evidence: According to a modeled data study on cholera transmission in Bangladesh, a cholera vaccination program for 1-14 year olds in the slums of Dhaka, Bangladesh involving periodic (every 3 years) campaigns would reduce cholera incidence in adults living in these areas by 40% due to the herd effects of oral cholera vaccines.

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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 Evidence: In Gambia, 58% of children who survived a bout of pneumococcal meningitis “had clinical sequelae; half of them had major disability preventing normal adaptation to social life” (mental retardation, hearing loss, motor abnormalities, seizures).

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Key Evidence: A systematic literature review analyzing data from 21 African countries revealed that bacterial meningitis is associated with high case fatality and frequent neurophysiological sequelae. Pneumococcal and Hib meningitis contribute to one third of disease related mortality. They also cause clinically evident sequalae in 25% of survivors prior to hospital discharge. The three main causes of bacterial meningitis- Haemophilus influenzae type B; Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are vaccine preventable, routine use of conjugate vaccines have potential for significant health and economic benefits.

From the VoICE Editors: Neuropsychological sequelae includes hearing loss, vision loss, cognitive delay, speech/language disorder, behavioural problems, motor delays/impairment, and seizures. 

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Key Evidence: A systematic literature review of studies of the long-term effects of invasive meningococcal disease in high-income countries found that children who survived the disease had a greater incidence of hearing loss and psychological problems, including attention-deficit/hyperactivity disorder (ADHD) than control groups or the general population. In addition, they had increased odds of death – one study showed more than a 25% greater mortality rate in this population than did the general public up to 30 years after having the disease.

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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 Evidence: Pregnant women are at particularly high risk of serious illness and death from a variety of bacterial and viral diseases, such as influenza, pneumococcal pneumonia, and Group B strep, for which vaccines exist or are in development. Vaccine-preventable diseases in pregnancy are associated with adverse pregnancy outcomes such as spontaneous abortion, congenital anomalies, preterm birth, and low birth weight.

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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: In Brazil, where pertussis cases have climbed, mainly in infants <4 months of age, vaccinating pregnant women with Tdap vaccine at the same coverage rate as influenza vaccination in pregnant women (57%) would reduce pertussis cases in children under 1 year of age by 41%, deaths by 43%, and would be cost-effective, according to the WHO thresholds.

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Key Evidence: In Japan, which has experienced a re-emergence of pertussis among adolescents and adults, vaccinating pregnant women with the Tdap vaccine would be cost effective in preventing the illness in young infants (<3 months of age) and in mothers, according to the WHO definition of cost effectiveness. This is true even if only 50% of pregnant women receive the vaccine.

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Key Evidence: Pertussis causes nearly 200,000 deaths in children worldwide, nearly all in infants too young to be vaccinated. Vaccinating pregnant women against pertussis with a single dose of Tdap vaccine would be 89% effective in protecting infants against the disease over their first 2 months of life and would reduce pertussis incidence in newborns in the U.S. by 68% (assuming 75% of mothers are vaccinated).

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Key Evidence: A study in Australia estimated that adding dTpa vaccination for pregnant women to the current pertussis immunization program for children would prevent an additional 8,800 symptomatic pertussis cases (mostly unreported) and 146 hospitalizations each year in all ages, including infants and their mothers, as well as one death every 22 months. The study found maternal pertussis vaccination to be cost-effective.

From the VoICE Editors: Note: The formulation used in this study is abbreviated dTpa.

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Key Evidence: A large study in California involving nearly 150,000 newborns found that vaccinating pregnant women with the Tdap vaccine provided 91% protection against pertussis infection among infants under 2 months of age and 88% protection before the infants had any vaccinations. The study also showed that vaccinating mothers during their pregnancy did not reduce the effectiveness of infant vaccination but that maternal Tdap vaccination provided additional protection to the infants through their first year of life.

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Key Evidence: In Argentina, more than 50% of deaths due to pertussis occurred in infants younger than 2 months of age — too young to be vaccinated in the country. The impact of maternal pertussis vaccination in protecting their infants against the disease reduced the incidence of pertussis in infants less than 2 months old by half, when comparing states with high and low maternal vaccination rates.

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Key Evidence: Infants born to mothers who reported receiving influenza vaccination during pregnancy had a 64% lower risk of getting influenza-like illness in their first 6 months of life, a 70% lower risk of laboratory-confirmed influenza, and an 81% lower chance of being hospitalized with influenza than infants whose mothers did not report getting the influenza vaccine during pregnancy. Since influenza vaccines are not effective in children less than 6 months old, immunizing pregnant women against influenza is a public health priority.

From the VoICE Editors: Data is from a study spanning more than 8 years at a large healthcare organization in the Western U.S.

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Key Evidence: An analysis of data from three studies showed that the rates of severe pneumonia in infants in their first six months of life was 20% lower overall in infants whose mothers received the influenza vaccination during pregnancy than in infants whose mothers had not, and the rates of severe pneumonia was 56% lower during periods when influenza circulation was highest. These findings correspond with evidence that influenza infection predisposes individuals to pneumococcal infection.

From the VoICE Editors: The incidence rate of severe pneumonia in the vaccine group compared to the control group was 43% lower in South Africa, 31% lower in Nepal, but not significantly different in Mali.

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Key Evidence: Vaccinating women during their second or third trimester of pregnancy with the Tdap vaccine was 81% effective in preventing pertussis in their infants in the first two months of life, according to a case-control study in Argentina.

From the VoICE Editors: This is one of the first studies to measure the effectiveness of maternal pertussis vaccination in a middle-income country and its findings support Argentina’s decision to introduce the vaccine.

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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: Despite the introduction of pneumococcal conjugate vaccine (PCV) in the childhood immunization program in New Zealand, the incidence of invasive pneumococcal disease in neonates (<30 days old) remains relatively high at 6 per 100,000 (versus 2/100,000 in the U.S.). Out of 19 cases in infants <30 days old in this study, 9 (47%) occurred during the first 7 days of life and 6 within the first 48 hours. If proven effective, maternal vaccination would cover 74% to 84% of the serotypes that infected these infants, depending on the vaccine.

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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 Evidence: Vaccinating pregnant women against pertussis at least one week before delivery was found to be 91% effective in preventing the disease in infants <3 months old and 95% effective in preventing infant deaths in a study conducted in England over a 3-year period following the introduction of dTap-IPV vaccine for pregnant women. Of the 37 deaths from pertussis in infants that occurred in England from 2009 to 2015, 32 (86%) were in infants <2 months of age, highlighting the vulnerability of very young infants to severe pertussis. All but 2 of the deaths in <2 month olds were in children whose mothers hadn’t been vaccinated against pertussis during their pregnancy, while in the 2 other cases, the vaccination occurred too late in the pregnancy (<10 days before the birth).

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Key Evidence: An study using GIS to quantify the percent of pregnant women in Mozambique without access to tetanus toxoid (TT) vaccine at varying distances from health facilities estimated that if women cannot travel more than 5 km to a TT immunization site there will be almost 18,000 neonatal tetanus cases each year that could be prevented, costing the country more than US$362 million in treatment costs and lost productivity. Covering 99% of women with TT will currently require people to travel up to 35 km to obtain an immunization.

From the VoICE Editors: GIS, a geospatial information system, is a computer system capable of capturing, storing, analyzing, and displaying geographically referenced information.

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Key Evidence: In a case-control study in the state of São Paulo, Brazil, vaccination of pregnant women with Tdap vaccine was 83% effective in preventing pertussis in their infants less than 2 months of age — before their first dose of DPT — and 81% effective after controlling for household income and mother’s age.

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Key Evidence: Infants less than 2 months old are too young to be vaccinated against pertussis yet are at highest risk of severe disease – – a 75% hospitalization rate and a 1% case fatality rate. A case-control study in six U.S. states found that vaccinating women during the third trimester of pregnancy with Tdap vaccine provided 81% protection against pertussis to infants <2 months and 91% protection against hospitalized cases of pertussis.

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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: 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: 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: Prior to the introduction of rotavirus vaccines in the U.S., there were an estimated 205,000 – 272,000 emergency department visits and 55,000 – 70,000 hospitalizations due to rotavirus in children each year. A series of studies found that hospitalizations in children under five due to rotavirus declined, on average by 80% from the pre-vaccine to the post-vaccine era, while both outpatient visits and emergency department visits due to rotavirus declined 57%.

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Key Evidence: Two years after rotavirus vaccine introduction in Rwanda, the country saw nearly 400 fewer hospital admissions for diarrhea among young children at 24 district hospitals.

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Key Evidence: A study based on population- and lab-based surveillance of bacterial infections in the U.S. estimated that, of the estimated 400,000 cases and 30,000 deaths from invasive pneumococcal disease (IPD) that were likely prevented from 2001 to 2012 with the introduction of PCV7 (in 2000) and PCV13 (in 2010) in the infant immunization schedule, more than half of cases prevented and nearly 90% of prevented deaths were among people older than 5 years of age.

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Key Evidence: A study in Australia estimated that adding dTpa vaccination for pregnant women to the current pertussis immunization program for children would prevent an additional 8,800 symptomatic pertussis cases (mostly unreported) and 146 hospitalizations each year in all ages, including infants and their mothers, as well as one death every 22 months. The study found maternal pertussis vaccination to be cost-effective.

From the VoICE Editors: Note: The formulation used in this study is abbreviated dTpa.

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