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.

45 Key Concepts, 50 Sources
Key Concept

Key Evidence: Over a four-year period following the introduction of PCV-10 in Finland, purchases of antimicrobials that are recommended for the treatment of acute otitis media (middle-ear infection) for children born during these years fell by nearly 18%, compared to pre-vaccine years, and the rate of surgeries to place ear tubes for severe cases fell 15%. Although it is considered a mild disease, acute otitis media caused by pneumococcus is 1,000 times more common in young children than invasive pneumococcal disease, such as pneumonia or meningitis, and thus the public health impact of the vaccine in reducing otitis media cases and in saving health care costs is considerable.

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Key Evidence: In a study of nearly 40,000 recipients of PCV7 and control subjects in northern California, there was a 5.4% reduction in the number of antibiotic prescriptions and a 12.6% reduction in the use of “second-line antibiotics” among children who received the pneumococcal conjugate vaccine. Between the time the first dose was administered and the age of 3.5 years, use of the vaccine prevented 35 antibiotic prescriptions per 100 fully vaccinated children.

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Key Concept

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 Concept

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

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Key Concept

Key Evidence: It is estimated that under current vaccine coverage trends in 41 Gavi-eligible countries, enhanced Gavi funding would help to avoid out-of-pocket health expenditures in an amount that surpasses US$4.5 billion attributable to measles, US$168 million attributable to severe pneumococcal disease, and US$200 million attributable to severe rotavirus.

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Key Concept

Key Evidence: In 41 Gavi-eligible countries it is estimated that, in the absence of measles vaccination, the occurrence of Medical Impoverishment (MI) or households falling below the poverty line due to medical expenditures to manage measles disease would be 5.3 million. With current coverage rates, 700 thousand households would suffer MI. If Gavi support afforded enhanced coverage, the estimate of households suffering MI would decrease to 500 thousand.

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Key Concept

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: In 41 Gavi-eligible countries, it is estimated that without any rotavirus vaccine (RVV) coverage, an estimated 2.2 million Catastrophic Health Costs (CHC) cases and 600,000 Medical Impoverishment (MI) cases would occur due to rotavirus gastroenteritis. Unfortunately these figures would not significantly decrease under the current immunization forecasts because very few countries have introduced the RVV. However, with the introduction of RVV the number of CHC cases would drop to 1.3 million and MI cases to 400,000, representing a 40% reduction.

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Key Concept

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 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 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 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 Concept

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: 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 Concept

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: In a financial risk model analysis of 41 Gavi-eligible countries, the burden of Catastrophic Health Costs (CHC) and Medical Impoverishment (MI) would be greatest in the lowest income populations. With expanded vaccine coverage, the share of prevented cases of measles, pneumococcal disease, and rotavirus, in relation to the total number of cases prevented, would be larger in the lowest income populations thereby providing a larger financial risk protection (FRP) to these populations.

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Key Concept

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 41 Gavi-eligible countries it is estimated that, in the absence of any measles vaccine use, approximately 18.9 million households would have Catastrophic Health Costs (CHC) attributable to measles. The number of CHC decreases to 3.4 million households in these countries if the current vaccine coverage forecasts is unchanged and decreases to 2.6 million cases if coverage was enhanced with Gavi support. Overall, optimizing vaccine coverage for measles can reduce by approximately 90% the incidence of CHC due to measles disease.

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Key Concept

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 Concept

Key Evidence: It is estimated that in 41 Gavi-eligible countries, approximately 6.6 million households would suffer Catastrophic Health Costs (CHC) in the absence of pneumococcal vaccine coverage. Due to the current absence of a pneumococcal immunization plan in many of these countries, the number of CHC cases would only decrease slightly to 6.4 million with current immunization programs. If pneumococcal vaccine programs would be implemented or expanded with Gavi support, the number of households experiencing CHC would decrease to 4.6 million – a decrease of approximately 30%.
Similarly, the estimates of medical impoverishment without vaccine coverage in this model showed that pneumococcal disease would cause 800,000 households to fall under the poverty line.

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

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Key Concept

Key Evidence: A study analyzing the long-term consequences of middle ear disease in children in an urban health center and a private practice in the United States found that time spent with middle ear effusion during the first 3 years of life was significantly associated with lower school performance and lower scores in cognitive ability, speech, and language.

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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: 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 Concept

Key Evidence: Two years after the introduction of 10-strain pneumococcal conjugate vaccine (PCV-10) in Kenya, the percent of HIV-positive adults who carried pneumococcal bacteria declined significantly (from 43% to 28%), but did not decline in HIV-negative adults. However, the reduction in carriage of pneumococcal strains that are in PCV10 declined significantly in both HIV-positive and HIV-negative adults. This reduction was still four times higher in HI- positive vs. HIV-negative adults (2.8% vs. 0.7%), indicating that HIV positive adults continue to be at considerably higher risk of invasive pneumococcal disease than HIV-uninfected adults.

From the VoICE Editors: Nasopharyngeal carriage is an indicator of the risk for invasive pneumococcal disease and pneumonia. 

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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 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 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 Concept

Key Evidence: Nearly a quarter of a million children are born with sickle cell disease in Africa each year. SCD was found to increase the risk of Hib infections by 13-fold and pneumococcal infections by 36 fold. This means that children with SCD stand to benefit enormously from PCV and Hib immunization.

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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 Concept

Key Evidence: A study in the US found that the incidence of invasive pneumococcal disease was 22 to 38 times higher in adults with cancer than in healthy adults.

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Key Concept

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 Concept

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 Concept

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 Concept

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

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Key Concept

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

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Key Concept

Key Evidence: A study of sickle cell disease patients in Ghana found that pneumoccocus bacteria found in their noses and throats had high rates of drug resistance with 37% of positive samples resistant to penicillin and 34% resistant to multiple drugs (typically penicillin + tetracycline + cotrimoxazole).

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Key Concept

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: Two years after the introduction of 10-strain pneumococcal conjugate vaccine (PCV-10) in Kenya, the percent of HIV-positive adults who carried pneumococcal bacteria declined significantly (from 43% to 28%), but did not decline in HIV-negative adults. However, the reduction in carriage of pneumococcal strains that are in PCV10 declined significantly in both HIV-positive and HIV-negative adults. This reduction was still four times higher in HI- positive vs. HIV-negative adults (2.8% vs. 0.7%), indicating that HIV positive adults continue to be at considerably higher risk of invasive pneumococcal disease than HIV-uninfected adults.

From the VoICE Editors: Nasopharyngeal carriage is an indicator of the risk for invasive pneumococcal disease and pneumonia. 

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Key Concept

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

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Key Evidence: In a study evaluating the impact of PCV7 on 40,000 recipients and control subjects in northern California revealed that the vaccine could significantly decrease the need for antibiotics to treat the disease. The children who had received the vaccine displayed a 5.4% reduction in the number of antibiotic prescriptions and a 12.6% reduction in the use of “second-line antibiotics” compared to the controls. Additionally, when looking at children in the time period between their first dose and attainment of the age of 3.5 years, receiving the vaccine had prevented 35 antibiotic prescriptions per 100 fully vaccinated children.

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

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Key Concept

Key Evidence: A community-based study in Vietnam found a high percent of children under five years of age were carrying pneumococcal bacteria in their noses and throats that were non-susceptible to commonly-used antibiotics. Of the strains tested, 18% were not susceptible to penicillin, 26% weren’t susceptible to cefotaxime, 76% were not susceptible to meropenem and 14% were not susceptible to all three nor to any of the “macrolide” drugs (e.g., erthromycin and azithromycin). However, 90% of the multi-drug resistant strains are serotypes that are in the 13-strain pneumococcal conjugate vaccine (PCV-13) and thus the introduction of a vaccine is expected to increase the susceptibility of circulating strains of the bacteria.

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Key Evidence: The US CDC identifies the use of vaccines as one of the 4 critical steps for controlling 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: Shortly after its introduction of Hib vaccine in the United Kingdom, a decrease in resistant (ᵝ-lactamase-positive) strains were documented. In the U.S., following introduction of pneumococcal conjugate vaccines, including PCV13, there was a decrease in both antibiotic use and in the prevalence of pneumococcal strains not susceptible to antibiotics.

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Key Concept

Key Evidence: 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 Concept

Key Evidence: TB and pneumococcal infections are two of 18 drug-resistant threats to US health security identified by the CDC in 2013 and are potentially vaccine-preventable. Most antibiotic resistant TB infections in the US occur in people born outside the US.

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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 Concept

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 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: 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 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: 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 Concept

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 Concept

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: 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 Concept

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 Concept

Key Evidence: The US CDC estimates that antibiotic resistant pneumococcal infections in the US add $96 million to the costs of treatment each year.

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