49 Key Concepts

Key Evidence: Malnutrition is a leading contributor to morbidity and mortality during humanitarian emergencies, and a cyclical relationship exists between malnutrition and infectious diseases. Universal immunization programs have been shown to improve the height and weight measurement markers associated with malnutrition.

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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 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 Evidence: Respiratory infections and diarrhea are the leading causes of death during humanitarian emergencies according to a 2016 review of vaccine-preventable diseases and the use of immunizations during complex humanitarian emergencies.

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Key Evidence: Children living in the Yida refugee camp in South Sudan in 2013 were found to have an elevated rate of pneumonia infections likely due to malnutrition, overcrowding, and inadequate shelter. Using these data, the CDC estimated that the use of Hib and pneumococcal vaccines in children under 2 years of age in the camp would be cost-effective under all dosing scenarios evaluated. Medecines Sans Frontiers (MSF) provided medical services to this refugee camp and found delivery of these vaccines to be feasible and effective in this setting.

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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 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 Evidence: In New Zealand, Maori and Pacific children have historically suffered high hospitalization rates for invasive pneumococcal disease (IPD), all cause pneumonia (ACP), and otitis media. 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, while significant reductions in ACP and otitis media admissions were also noted, resulting in reductions in disparities for these populations.

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Key Evidence: Population-based surveillance data collected in the state of Tennessee from 1998 – 2016 found that the introduction of PCV13 was associated with reductions in socioeconomic and racial disparities in PCV13-serotype invasive pneumococcal disease (IPD). PCV13 introduction was associated with the prevention of IPD in the overall population as well as substantial decreases in racial disparities in IPD over time between Black and White populations. Before PCV13 was introduced, Black people in the study had an IPD incidence 1.5 times higher than White people – 24.7 and 16.4, respectively. After PCV13 introduction, Black people had an IPD incidence 1.15 times the incidence among Whites: 15 and 13.1, respectively.

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Key Evidence: A study looking at the impact of pneumococcal vaccine introduction and scaling up pneumonia treatment in Ethiopia found that 30-40% of all deaths averted by these interventions would be expected to occur in the poorest wealth quintile. The greatest resulting financial risk protection would also be concentrated among the bottom income quintile.

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Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. Vaccination programs for ten selected pathogens will have averted an estimated 69 million deaths in 98 low- and middle-income countries between 2000 and 2030. Most of this impact has been concentrated in a reduction in mortality among children younger than 5 years (57% reduction), most notably from measles. These public health gains are predicted to increase in coming decades if progress in increasing vaccine coverage is sustained.

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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: A study modeling the relationship between disease and poverty in Ethiopia found that among the top 20 causes of death in Ethiopia, diarrhea and lower respiratory infections (LRIs) are the top two drivers of medical impoverishment. It is estimated that in 2013, out-of-pocket direct medical costs for diarrheal disease drove an estimated 164,000 households below the poverty line (representing 47% of all the diarrhea cases), and LRIs led to an estimated 59,000 cases of poverty (17% of LRI cases). Of the top 10 health-associated drivers of poverty, four are at least partially vaccine-preventable (1. Diarrhea, 2. LRI, 4. TB. 10. Pertussis).

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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 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 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: PCV7 use in Argentina resulted in an estimated cost of US$5,599 per life year gained. The purchase of the 4 doses of vaccine for the entire cohort at a cost of US$26.5 per dose would required an investment of US$73,823,806.00. This investment would significantly reduce the number of deaths brought about by cases of meningitis, bacteremia, pneumonia, otitis media and meningitis sequelae. The resultant decrease in morbidity and mortality coupled with herd immunity offered by immunization would contribute substantially to national productivity making PCV immunization a highly cost effective strategy.

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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: An analysis in Kenya found that, although the government will need to more than double its current vaccine budget to continue using PCV after GAVI support ends, continuing the vaccination will prevent more than 101,000 cases of invasive pneumoccocal disease and pneumonia, more than 14,000 deaths over an 11-year period, and would be cost-effective (cost per DALY of $153 by 2032), even at the full GAVI price of US$3.05 per dose.

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Key Evidence: A study looking at the impact of pneumococcal vaccine introduction and scaling up pneumonia treatment in Ethiopia found that 30-40% of all deaths averted by these interventions would be expected to occur in the poorest wealth quintile. The greatest resulting financial risk protection would also be concentrated among the bottom income quintile.

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Key Evidence: An analysis of the potential impact of pneumococcal conjugate vaccine (PCV) in India found that introducing PCV vaccine will protect the population from potentially catastrophic health expenditures due to treatment and hospitalizations for pneumococcal disease – saving an estimated $49-63 million in out-of-pocket expenditures each year, depending on the assumed vaccination coverage rate. Financial protection will be greatest for the poorest households, with the poorest quintile is estimated to have the greatest savings in out-of-pocket expenditures of all wealth quintiles.

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Key Evidence: A study in Bangladesh found that families are heavily borrowing or losing assets to be able to bear the cost of pneumonia in their children <5 years of age.

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Key Evidence: Three studies in Bangladesh and India found that the direct medical costs for children hospitalized with pneumonia were 27% to 116% of the average monthly income of households. And, while these costs represent a major portion of a family’s monthly income, they don’t include non-medical costs, such as transport and food costs, nor the lost wages of family members who miss work to care for the child.

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Key Evidence: In a global review of the costs of treating childhood pneumonia, the average costs of a hospitalized case of pneumonia in children under five years of age was US$243 in primary or secondary hospitals in low- and middle-income countries (ranging from US$40 – US$563) and US$559 in tertiary hospitals (ranging from US$20 – US$1,474). In high-income countries, the cost of hospitalized cases averaged US$2,800 in primary or secondary hospitals and more than US$7,000 in tertiary hospitals. Note that in most of these studies, only direct medical costs were included and thus total costs – including non-medical costs and lost wages – would be considerably higher.

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Key Evidence: In a study in The Gambia – a setting where healthcare is free of charge to patients – pneumococcal disease nonetheless placed a heavy financial burden on families seeking treatment before arrival at the hospital, with families paying for transportation costs, drugs, diagnostic tests and even burial in the case of death. 50-80% of the cost of treating an episode of pneumococcal disease was born by the health system, which still left families to cover a cost up to 10 times their average daily household budget. In addition the estimated treatment cost for inpatient pneumonia of US$109 is nearly 4 times the annual per capita expenditure for health in The Gambia.

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Key Evidence: A modeled analysis of the potential impact of pneumococcal conjugate vaccine (PCV) in India estimated that the greatest reductions in deaths due to PCV vaccination would be among the poorest segments of the population. Assuming a vaccination coverage rate of 77% (the current DTP3 coverage rate), PCV would prevent nearly 2.5 times as many deaths per 100,000 children under five in the 2 poorest income quintiles than in the 2 wealthiest groups (313 vs. 134), and nearly 3 times as many deaths per 100,000 if coverage reaches 90% (446 vs. 167).

From the VoICE Editors: The model used was specific to the epidemiology, health system situation, and population characteristics of India. 

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By preventing illness, disability, premature death, lost wages, and other costs, this modeling study found that vaccines against ten pathogens averted $828.5 billion of economic burden in 94 low- and middle-income countries between 2021 and 2030. Immunization programs provided a high return on investment (ROI), with projections for net benefits of vaccine programs estimated at $1,445.3 billion (using a cost-of-illness approach) and $3,371.5 billion (using a value-of-a-statistical-life approach) from 2011 to 2030. For every $1 invested in immunization, there was a return on investment of $20 using cost-of-illness and $52 using a value-of-a-statistical-life approach.

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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 Evidence: Among both HIV positive and HIV negative parents in a study in Kenya, 99% of pneumococcal strains found and tested were resistant to one or more antibiotics. HIV positive parents carried 16% more strains that were resistant to penicillin than those carried by HIV negative parents.

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Key Evidence: In a study of national surveillance records in South Africa, HIV positive people over 5 years of age were found to have a 43-fold risk of invasive pneumococcal disease compared to HIV negative person. This risk was highest among children age 5-19 who were found have a more than 120-fold risk of invasive pneumococcal disease compared to HIV negative uninfected children of the same age. 90% of South Africa’s invasive pneumococcal disease cases during the 5 year period occurred in the 18% of the population who are HIV positive.

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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 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: In survivors of pediatric and young adult cancers in the US, the risk of mortality from infectious complications is 4 times higher than in their cancer-naïve siblings. Within the first five years after cancer diagnosis, the risk of some vaccine-preventable infections such as pneumonia and hepatitis is more than 9-fold and 6-fold higher, respectively. More than 5 years after cancer diagnosis, the risk of these two infections remains high at 3.7 and 2.5 times higher than siblings.

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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 Evidence: A review of evidence for the use of pneumococcal conjugate vaccine in South Africa showed that children who are HIV positive are at significantly increased risk of pneumococcal disease, and so will benefit the most from vaccination, despite decreased vaccine efficacy in this group compared to healthy children.

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Key Evidence: A large randomized controlled trial of a pneumococcal conjugate vaccine in South Africa found that use of the vaccine prevented 10 times as many cases of pneumococcal pneumonia in HIV positive children than in HIV negative children.

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Key Evidence: In a long-term study of Canadian surveillance data researchers found that immunocompromised people were at a 12-fold risk of invasive pneumococcal disease (IPD) compared to healthy people. In addition, the risk of death from IPD in immunocompromised people was found to be 30-80% higher than healthy individuals who had contracted IPD. 10 years after introduction of PCV7 in Canada, the incidence of IPD due to serotypes included in the vaccine had decreased by 90%.

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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: In a long-term study of Canadian surveillance data researchers found that immunocompromised people were at a 12-fold risk of invasive pneumococcal disease (IPD) compared to healthy people. In addition, the risk of death from IPD in immunocompromised people was found to be 30-80% higher than healthy individuals who had contracted IPD.

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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: A publicly funded 23vPPV (23 valent pneumococcal polysaccharide vaccine) program in Victoria, Australia not only dramatically increased vaccination coverage among the elderly in the public purchase program, but in other Australian states and territories that did not have a public program, the number of prescriptions issued for 23vPPV actually increased over the same period.

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Key Evidence: A study looking at the impact of pneumococcal vaccine introduction and scaling up pneumonia treatment in Ethiopia found that 30-40% of all deaths averted by these interventions would be expected to occur in the poorest wealth quintile. Scaling up PCV13 to levels achieved with DTP3 in Ethiopia would be expected to avert nearly 3000 child deaths and 60,000 episodes of pneumococcal pneumonia annually, not including any potential herd benefit. A publicly financed program to scale up pneumococcal vaccines would cost about US$40 per year of healthy life gained.

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Key Evidence: A modeled analysis of the potential impact of pneumococcal conjugate vaccine (PCV) in India estimated that the greatest reduction in deaths due to PCV vaccination would be among the poorest segments of the population. Assuming a vaccination coverage rate of 77% (the current DTP3 coverage rate), PCV would prevent nearly 2.5 times as many deaths per 100,000 children under five in the 2 poorest income quintiles than in the 2 wealthiest groups (313 vs. 134), and nearly 3 times as many deaths per 100,000 if coverage reaches 90% (446 vs. 167).

From the VoICE Editors: The model used was specific to the epidemiology, health system situation, and population characteristics of India. 

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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 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 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 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 Evidence: This study from South Africa demonstrates significant declines in invasive pneumococcal disease cases caused by bacteria that are resistant to one or more antibiotics. In fact, the rate of infections resistant to two different antibiotics declined nearly twice as much as infections that could be treated with antibiotics.

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Key Evidence: A retrospective observational register-based study found that the 2010 introduction of PCV10 for infants in Finland led to an estimated 15% reduction among unvaccinated children in purchases of antimicrobials recommended for acute otitis media (AOM), the most common reason for antimicrobial use in many countries. The indirect effects of PCV10 introduction contribute to health care savings and may also help to combat antimicrobial resistance.

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Key Evidence: Evaluation of the ability of pneumococcal conjugate vaccine to reduce the occurrence of respiratory infections and the resultant antibiotic drug use was conducted among day care attendees in Israel. It was observed that children who had received the 9-valent conjugate vaccine showed a 17% overall reduction in antibiotic usage. In particular, a 10% reduction in days of antibiotic usage for upper respiratory tract infections, 47% fewer days of antibiotic usage for lower respiratory tract infections, and 20% fewer days of antibiotic usage for otitis media (ear infections) when compared to children who did not receive PCV.

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Key Evidence: In Iceland, a study of all children born over an 11-year period, before and after the introduction of pneumococcal conjugate vaccine (PCV) into the national immunization program, found a 6% decrease in all antibiotic prescriptions for children during their first four years of life and a 22% reduction in prescriptions for otitis media after the vaccine was introduced. Thus, in addition to reducing the burden of pneumococcal disease, PCV may also slow the spread of antibiotic resistance.

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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: In a study modeling the cost-effectiveness of vaccination campaigns in Somalia – the country with the second largest number of refugees in 2012 – the use of Hib vaccine, PCV10, or both Hib and PCV10 were all found to be cost effective means to prevent excess morbidity and mortality from pneumonia in young Somali children. Such a vaccination campaign could conservatively reduce pneumonia cases and deaths by nearly 20%.

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Key Evidence: Children living in the Yida refugee camp in South Sudan in 2013 were found to have an elevated rate of pneumonia infections likely due to malnutrition, overcrowding, and inadequate shelter. Using these data, the CDC estimated that the use of Hib and pneumococcal vaccines in children under 2 years of age in the camp would be cost-effective under all dosing scenarios evaluated. Medecines Sans Frontiers (MSF) provided medical services to this refugee camp and found delivery of these vaccines to be feasible and effective in this setting.

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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: 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: 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: 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 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: 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 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: 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: 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: 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 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: Following introduction of PCV in New Zealand, hospitalizations of children under 6 years of age due to invasive pneumococcal disease decreased by 73%, due to all-cause pneumonia decreased by 8%, and due to otitis media decreased by 25%.

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Key Evidence: In a Bangladeshi study, pneumonia and acute diarrhea were the first and third most common reasons for childhood hospital admission with over half (54%) of the acute diarrhea admissions caused by rotavirus. One in four children taken to this large pediatric hospital were refused admission because all beds were occupied. Vaccination could have prevented children with rotavirus from requiring essential hospital resources when one in four children refused admission had symptoms of pneumonia.

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