Cervical cancer screening guidelines and screening practices in 11 countries: A systematic literature review.

The World Health Organization (WHO) advocates population-based screening programs to reduce the global incidence of cervical cancer. However, screening guidelines and practice continually change to reflect scientific developments. Here we describe and compare cervical cancer screening guidelines and clinical practice in 11 countries across North America, Europe, and Asia-Pacific. We conducted a systematic literature review (SLR) complemented by a targeted literature review (TLR) to identify relevant peer-reviewed publications and policy documents, which include 120 publications, of which 86 were identified from the SLR and 34 from the TLR. Only six of 11 countries assessed have population-based screening programs in place. Considerable differences persist across countries' screening guidelines, even among comparable systems. Moreover, methods of data collection are also heterogenous, and systematic data collection is often not established. As future changes in screening guidelines and clinical practice occur (e.g., when the first cohorts of women vaccinated against HPV reach screening age), systematic collection of screening data is essential to monitor and improve screening performance.

Health Care Resource Utilization and Economic Burden Associated With Congenital Cytomegalovirus Infection: A Longitudinal Analysis of Data From Clinical Practice at a Large Health Care Provider in Israel.

PURPOSE: Congenital cytomegalovirus infection (cCMVi) is the leading cause of nonhereditary sensorineural hearing loss and can cause other long-term neurodevelopmental disabilities; however, data on the economic burden of cCMVi during early childhood are scarce. The primary objective of the study was to describe longitudinal patterns of health care resource utilization (HCRU) and direct medical costs among infants with cCMVi compared to infants unexposed to cCMVi. METHODS: A retrospective cohort study was performed using data on infants born between 2013 and 2017, as captured in the database of Maccabi Healthcare Services, a 2.5 million-member health care organization in Israel. cCMVi cases were identified by physician diagnosis and/or dispensed valganciclovir within 90 days after birth. Infants born to mothers CMV-seronegative throughout pregnancy were selected for comparison (unexposed controls). Infants were retrospectively followed up through December 31, 2018, or 4 years of age (Y4). HCRU included physician visits, hospital admissions, audiology tests/procedures, imaging, and valganciclovir treatment. Direct medical costs, in US dollars per person per year (USD PPPY) were calculated from the health-system perspective. To compare costs of cCMVi cases and controls, direct medical costs were estimated using a generalized linear model with a log link function and γ distribution after adjustment for patient characteristics. FINDINGS: A total of 351 cCMVi cases and 11,733 control infants with continuous follow-up during their first year of life (Y1) were included in the study. In Y1, cases were more likely to have a hospital admission (8.5% cases vs 4.5% control; P < 0.001) and higher numbers of pediatrician visits (median, 18 vs 15), audiology visits and tests, and cranial ultrasounds (all, P < 0.05). Longitudinally, incremental costs associated with cases were highest in Y1 (1686.7 USD PPPY; cost ratio = 2.6; P < 0.001) and remained elevated through Y4. IMPLICATIONS: cCMVi was associated with substantial increases in HCRU and economic burden during early childhood, and particularly during the first year of life.

Epidemiology of cytomegalovirus infection in pregnancy in Israel: Real-world data from a large healthcare organization.

Congenital cytomegalovirus infection (cCMVi) is the leading cause of nonhereditary sensorineural hearing loss among newborns. Women newly acquiring cytomegalovirus infection (CMVi) during pregnancy have the highest risk of vertical transmission. This study aimed to describe the epidemiology of CMVi in pregnancy in a large healthcare database. A retrospective cohort study was performed using the Maccabi Healthcare Services database (Israel). Women aged 18-44 years old on July 1, 2013 with no record of pregnancy in the prior 6 months were followed through December 31, 2017 for first pregnancy occurrence. Pregnancy outcomes (live birth, spontaneous/therapeutic abortions, stillbirth, and uncertain outcomes) were captured. CMV test results were obtained to assess serostatus at the start of pregnancy (SoP) and primary CMV infection (CMVi) during pregnancy. Associations of demographic and reproductive factors with pCMVi were investigated (multivariable logistic regression). The study included 84 699 pregnant women (median age = 31 years; interquartile range = 28-35). Live birth, fetal loss, and uncertain pregnancy outcomes accounted for 76.8%, 18.2%, and 5.0%, respectively. The seroprevalence of CMV at the start of pregnancy in this cohort was 63.4% (95% confidence interval [CI]: 63.1-63.7). Among seronegative women with available test results (n = 10 657), CMVi incidence was 14.5 per 1000 (95% CI = 12.2-16.7). In multivariate logistic regression models adjusting for maternal age, CMVi was significantly associated with having one or more prior live births (odds ratio [OR]: 3.8 [95% CI: 2.6-5.4]) and having a child less than 6 years of age (OR: 4.3 [95%CI: 3.0-6.1]). One in three pregnant women in Israel is at risk for primary CMVi. This study demonstrates that real-world electronic healthcare data can be leveraged to support clinical management and development of interventions for congenital CMV by identifying women at high risk for CMVi during pregnancy.

Real-world impact and effectiveness assessment of the quadrivalent HPV vaccine: a systematic review of study designs and data sources.

INTRODUCTION: Vaccine effectiveness and impact studies are typically observational, generating evidence after vaccine launch in a real-world setting. For human papillomavirus (HPV) vaccination studies, the variety of data sources and methods used is pronounced. Careful selection of study design, data capture and analytical methods can mitigate potential bias in such studies. AREAS COVERED: We systematically reviewed the different study designs, methods, and data sources in published evidence (1/2007-3/2020), which assessed the quadrivalent HPV vaccine effectiveness and impact on cervical/cervicovaginal, anal, and oral HPV infections, anogenital warts, lesions in anus, cervix, oropharynx, penis, vagina or vulva, and recurrent respiratory papillomatosis. EXPERT OPINION: The rapid growth in access to real-world data allows global monitoring of effects of different public health interventions, including HPV vaccination programs. But the use of data which are not collected or organized to support research also underscore a need to develop robust methodology that provides insight of vaccine effects and consequences of different health policy decisions. To achieve the WHO elimination goal, we foresee a growing need to evaluate HPV vaccination programs globally. A critical appraisal summary of methodology used will provide timely guidance to researchers who want to initiate research activities in various settings.

Frequency and impact of the inclusion of broader measures of value in economic evaluations of vaccines.

BACKGROUND: The health and economic benefits of immunization may extend beyond the elements traditionally included in cost-effectiveness analyses (CEAs). This review investigated how broader impacts are considered in economic evaluations of vaccines and whether their inclusion would substantially change CEA findings. METHODS: We reviewed CEAs of vaccines associated with the largest global health burden, published from 2014 to 2019 using the Tufts CEA Registry and Tufts Global Health CEA Registry. We supplemented this with a systematic review of published and grey literature. We conducted descriptive analyses to examine the frequency of inclusion of specific social factors and study characteristics associated with their inclusion. We also conducted a case study of the human papilloma virus (HPV) vaccine to illustrate the potential change in CEA findings from selected social impacts. RESULTS: We identified 475 relevant health economic assessments. Overall, 40% of studies included at least one category of social impact. The most commonly included non-healthcare cost among cost-per-QALY studies was productivity (25%), while cost-per-DALY studies reported transportation costs most frequently (24%). Few studies examined the impact of vaccination on other sectors such as education and housing (<3%). Middle-income and North American settings were positively associated with social impact inclusion, while sub-Saharan African location was negatively associated. In the HPV case study, the addition of nonhealth costs improved cost-effectiveness by up to 90% or made the vaccine cost-saving, depending on geographic setting. The cost-saving scenario saved up to $30,000 in costs per case of cervical cancer averted. CONCLUSIONS: A minority of vaccine CEAs include social impacts, particularly for nonhealth sectors. The omission of these impacts may result in a systematic undervaluation of vaccines from a societal perspective. Further efforts are required to document the full benefits of vaccination for policymaker consideration.

The data used to build the models: Pertussis morbidity and mortality burden considering various Brazilian data sources.

BACKGROUND: Pertussis is associated with significant disease burden in children worldwide. In addition to its cyclical nature, resurgences of pertussis cases, hospitalizations and deaths have been reported by many countries. We describe the dynamics of pertussis in Brazil, a middle-income country that has experienced a resurgence and that provides good quality data to allow building a dynamic transmission disease model. METHODS: We conducted a descriptive analysis of pertussis burden considering data from the national disease surveillance system, national hospitalization information system and national mortality registry. Study period was 2000-2016. Absolute numbers and rates per 100,000 inhabitants over time, by age sub-groups and geographical regions are presented. RESULTS: From 2000 to 2016, a total of 37,299 reported pertussis cases, 25,240 hospitalizations, and 601 deaths due to pertussis were reported. Although the outcomes - pertussis cases, hospitalizations, and deaths - come from independent information systems, our results document low disease burden with periodic increases every 3-4 years during the years 2000-2010, followed by a sharp increase which peaked in 2014. In both periods, disease burden is concentrated in young children, while its more serious outcomes - hospitalizations and deaths, are concentrated in infants. Pre-outbreak and outbreak disease burden as well as timing of peak during the outbreak period vary by states and within geographical regions, representing valuable resources of data for modelling purposes. CONCLUSION: Consistent disease burden patterns were observed over time in Brazil using a variety of data sources. Given the scarcity of good epidemiological data on pertussis available from low- and middle-income countries, our reported data provide valuable information for the assessment of the public health impact and cost-effectiveness modelling studies of newer strategies to prevent and control pertussis. These data were used to build and calibrate a national dynamic transmission model, which was used to evaluate the cost-effectiveness of maternal immunization. Clinical Trial registry name and registration number: Not applicable.

Cost-effectiveness of maternal pertussis immunization: Implications of a dynamic transmission model for low- and middle-income countries.

OBJECTIVE: This study evaluates the cost-effectiveness of maternal acellular pertussis (aP) immunization in low- and middle-income countries using a dynamic transmission model. METHODS: We developed a dynamic transmission model to simulate the impact of infant vaccination with whole-cell pertussis (wP) vaccine with and without maternal aP immunization. The model was calibrated to Brazilian surveillance data and then used to project health outcomes and costs under alternative strategies in Brazil, and, after adjusting model parameter values to reflect their conditions, in Nigeria and Bangladesh. The primary measure of cost-effectiveness is incremental cost (2014 USD) per disability-adjusted life-year (DALY). RESULTS: The dynamic model shows that maternal aP immunization would be cost-effective in Brazil, a middle-income country, under the base-case assumptions, but would be very expensive at infant vaccination coverage in and above the threshold range necessary to eliminate the disease (90-95%). At 2007 infant coverage (DTP1 90%, DTP3 61% at 1 year of age), maternal immunization would cost < $4,000 per DALY averted. At high infant coverage, such as Brazil in 1996 (DTP1 94%, DTP3 74% at 1 year), cost/DALY increases to $1.27 million. When the model's time horizon was extended from 2030 to 2100, cost/DALY increased under both infant coverage levels, but more steeply with high coverage. The results were moderately sensitive to discount rate, maternal vaccine price, and maternal aP coverage and were robust using the 100 best-fitting parameter sets. Scenarios representing low-income countries showed that maternal aP immunization could be cost-saving in countries with low infant coverage, such as Nigeria, but very expensive in countries, such as Bangladesh, with high infant coverage. CONCLUSION: A dynamic model, which captures the herd immunity benefits of pertussis vaccination, shows that, in low- and middle-income countries, maternal aP immunization is cost-effective when infant vaccination coverage is moderate, even cost-saving when it is low, but not cost-effective when coverage levels pass 90-95%.

Comparison of static and dynamic models of maternal immunization to prevent infant pertussis in Brazil.

BACKGROUND: This paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile. METHODS: We defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models' different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated. RESULTS: The dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90-95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models' estimates over their different time horizons are compared at infant coverage < 90-95%, their projections fall in the same range. CONCLUSIONS: Static models may serve to explore an intervention's cost-effectiveness against infectious disease: the direction and principal drivers of change were the same in both models. When, however, an intervention too small to have significant herd immunity effects itself, such as maternal aP immunization, takes place against a background of vaccination in the rest of the population, a dynamic model is crucial to accurate estimates of cost-effectiveness. This finding is particularly important in the context of widely varying routine infant vaccination rates globally. CLINICAL TRIAL REGISTRY: Clinical Trial registry name and registration number: Not applicable.

The Role of Congenital Cytomegalovirus Infection in Adverse Birth Outcomes: A Review of the Potential Mechanisms.

Human cytomegalovirus (CMV) is a major cause of nonhereditary adverse birth outcomes, including hearing and visual loss, neurologic deficits, and intrauterine growth retardation (IUGR), and may contribute to outcomes such as stillbirth and preterm delivery. However, the mechanisms by which CMV could cause adverse birth outcomes are not fully understood. This study reviewed proposed mechanisms underlying the role of CMV in stillbirth, preterm birth, and IUGR. Targeted literature searches were performed in PubMed and Embase to identify relevant articles. Several potential mechanisms were identified from in vitro studies in which laboratory-adapted and low-passage strains of CMV and various human placental models were used. Potential mechanisms identified included impairment of trophoblast progenitor stem cell differentiation and function, impairment of extravillous trophoblast invasiveness, dysregulation of Wnt signaling pathways in cytotrophoblasts, tumor necrosis factor-α mediated apoptosis of trophoblasts, CMV-induced cytokine changes in the placenta, inhibition of indoleamine 2,3-dioxygenase activity, and downregulation of trophoblast class I major histocompatibility complex molecules. Inherent challenges for the field remain in the identification of suitable in vivo animal models. Nonetheless, we believe that our review provides useful insights into the mechanisms by which CMV impairs placental development and function and how these changes could result in adverse birth outcomes.

A framework for assessing the lifetime economic burden of congenital cytomegalovirus in the United States.

BACKGROUND: In the United States (US), congenital cytomegalovirus infection (cCMVi) is a major cause of permanent disabilities and the most common etiology of non-genetic sensorineural hearing loss. Evaluations of prevention strategies will require estimates of the economic implications of cCMVi. We aimed to develop a conceptual framework to characterize the lifetime economic burden of cCMVi in the US and to use that framework to identify data gaps. METHODS: Direct health care, direct non-health care, indirect, and intangible costs associated with cCMVi were considered. An initial framework was constructed based on a targeted literature review, then validated and refined after consultation with experts. Published costs were identified and used to populate the framework. Data gaps were identified. RESULTS: The framework was constructed as a chance tree, categorizing clinical event occurrence to form patient profiles associated with distinct economic trajectories. The distribution and magnitude of costs varied by patient life stage, cCMVi diagnosis, severity of impairment, and developmental delays/disabilities. Published studies could not fully populate the framework. The literature best characterized direct health care costs associated with the birth period. Gaps existed for direct non-health care, indirect, and intangible costs, as well as health care costs associated with adult patients and those severely impaired. CONCLUSIONS: Data gaps exist concerning the lifetime economic burden of cCMVi in the US. The conceptual framework provides the basis for a research agenda to address these gaps. Understanding the full lifetime economic burden of cCMVi would inform clinicians, researchers, and policymakers, when assessing the value of cCMVi interventions.

The Economic Burden of Congenital Cytomegalovirus Disease in the First Year of Life: A Retrospective Analysis of Health Insurance Claims Data in the United States.

PURPOSE: Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in the United States; however, limited data exist regarding the economic burden of cCMV disease (cCMVd) among newborns and infants. The purpose of this study was to compare health care resource utilization and costs between infants with cCMVd at birth and during the first year of life versus matched infants without diagnosed cCMVd. METHODS: Retrospective analyses of health insurance claims data from the MarketScan Commercial Claims and Encounters and Multi-State Medicaid databases (January 1, 2011-December 31, 2016) were conducted. Infants with cCMV diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 771.1 or 078.5; International Classification of Diseases, Tenth Revision, Clinical Modification code P35.1 or B25) were included. Two mutually exclusive periods were examined: initial hospital stay at birth ("birth" analysis) and subsequent 12 months ("postbirth" analysis). Infants with cCMVd in both periods were matched 1:1 to infants without cCMVd based on demographic and clinical characteristics. All-cause costs for cCMVd in infants versus matched control infants were reported in 2016 US dollars. Multivariable regression analyses controlled for additional confounding factors. FINDINGS: In the birth analysis, 397 of 404 newborns with cCMVd (167 vaginal deliveries, 230 cesarean deliveries) were matched to control infants; newborns with cCMVd had an additional mean (95% CI) of 9.1 (5.8-12.3) and 9.0 (4.6-13.5) inpatient days and $24,274 (10,082-38,466) and $31,770 (9911-53,630) more unadjusted inpatient costs versus control infants for vaginal and cesarean deliveries, respectively. In the postbirth analysis, 678 of 679 infants with cCMVd were matched with control infants; infants with cCMVd had an additional $58,806 (95% CI, 41,247-76,365) in unadjusted costs versus control infants, with inpatient visits accounting for 85% of the difference. Newborns with cCMVd accrued costs at birth averaging 1.5 to 2.1 times greater than control infants for cesarean and vaginal deliveries. During the first year of life, infants with cCMVd had costs averaging 7 times greater than control infants. IMPLICATIONS: cCMVd is associated with substantial economic burden from birth and during the first year of life. Our findings support the notion that developing effective prevention of cCMVd and increasing awareness of the disease among women should be a public health priority, given the economic burden of cCMVd.

Using Cluster Analysis to Group Countries for Cost-effectiveness Analysis: An Application to Sub-Saharan Africa.

OBJECTIVE: To explore the use of cluster analysis to define groups of similar countries for the purpose of evaluating the cost-effectiveness of a public health intervention-maternal immunization-within the constraints of a project budget originally meant for an overall regional analysis. METHODS: We used the most common cluster analysis algorithm, K-means, and the most common measure of distance, Euclidean distance, to group 37 low-income, sub-Saharan African countries on the basis of 24 measures of economic development, general health resources, and past success in public health programs. The groups were tested for robustness and reviewed by regional disease experts. RESULTS: We explored 2-, 3- and 4-group clustering. Public health performance was consistently important in determining the groups. For the 2-group clustering, for example, infant mortality in Group 1 was 81 per 1,000 live births compared with 51 per 1,000 in Group 2, and 67% of children in Group 1 received DPT immunization compared with 87% in Group 2. The experts preferred four groups to fewer, on the ground that national decision makers would more readily recognize their country among four groups. CONCLUSIONS: Clusters defined by K-means clustering made sense to subject experts and allowed a more detailed evaluation of the cost-effectiveness of maternal immunization within the constraint of the project budget. The method may be useful for other evaluations that, without having the resources to conduct separate analyses for each unit, seek to inform decision makers in numerous countries or subdivisions within countries, such as states or counties.

Cost-effectiveness of maternal GBS immunization in low-income sub-Saharan Africa.

BACKGROUND: A maternal group B streptococcal (GBS) vaccine could prevent neonatal sepsis and meningitis. Its cost-effectiveness in low-income sub-Saharan Africa, a high burden region, is unknown. METHODS: We used a decision tree model, with Markov nodes to project infants' lifetimes, to compare maternal immunization delivered through routine antenatal care with no immunization. 37 countries were clustered on the basis of economic and health resources and past public health performance. Vaccine efficacy for covered serotypes was ranged from 50% to 90%. The model projected EOGBS (early-onset) and LOGBS (late-onset) cases and deaths, disability-adjusted life years (DALYs), healthcare costs (2014 US$), and cost-effectiveness for a representative country in each of the four clusters: Guinea-Bissau, Uganda, Nigeria, and Ghana. Maximum vaccination costs/dose were estimated to meet two cost-effectiveness benchmarks, 0.5 GDP and GDP per capita/DALY, for ranges of disease incidence (reported and adjusted for under-reporting) and vaccine efficacy. RESULTS: At coverage equal to the proportion of pregnant women with≥4 antenatal visits (ANC4) and serotype-specific vaccine efficacy of 70%, maternal GBS immunization would prevent one-third of GBS cases and deaths in Uganda and Nigeria, where ANC4 is 50%, 42-43% in Guinea-Bissau (ANC4=65%), and 55-57% in Ghana (ANC4=87%). At a vaccination cost of $7/dose, maternal immunization would cost $320-$350/DALY averted in Guinea-Bissau, Nigeria, and Ghana, less than half these countries' GDP per capita. In Uganda, which has the lowest case fatality ratios, the cost would be $573/DALY. If the vaccine prevents a small proportion of stillbirths, it would be even more cost-effective. Vaccination cost/dose, disease incidence, and case fatality were key drivers of cost/DALY in sensitivity analyses. CONCLUSION: Maternal GBS immunization could be a cost-effective intervention in low-income sub-Saharan Africa, with cost-effectiveness ratios similar to other recently introduced vaccines. The vaccination cost at which introduction is cost-effective depends on disease incidence and vaccine efficacy. Clinical Trial registry name and registration number: Not applicable.

Cost-effectiveness of a potential group B streptococcal vaccine for pregnant women in the United States.

BACKGROUND: In the U.S., intrapartum antibiotic prophylaxis (IAP) for pregnant women colonized with group B streptococcus (GBS) has reduced GBS disease in the first week of life (early-onset/EOGBS). Nonetheless, GBS remains a leading cause of neonatal sepsis, including 1000 late-onset (LOGBS) cases annually. A maternal vaccine under development could prevent EOGBS and LOGBS. METHODS: Using a decision-analytic model, we compared the public health impact, costs, and cost-effectiveness of five strategies to prevent GBS disease in infants: (1) no prevention; (2) currently recommended screening/IAP; (3) maternal GBS immunization; (4) maternal immunization with IAP when indicated for unimmunized women; (5) maternal immunization plus screening/IAP for all women. We modeled a pentavalent vaccine covering serotypes 1a, 1b, II, III, and V, which cause almost all GBS disease. RESULTS: In the base case, screening/IAP alone prevents 46% of EOGBS compared to no prevention, at a cost of $70,275 per quality-adjusted life-year (QALY) from a healthcare and $51,249/QALY from a societal perspective (2013 US$). At coverage rates typical of maternal vaccines in the U.S., a pentavalent vaccine alone would not prevent as much disease as screening/IAP until its efficacy approached 90%, but would cost less per QALY. At vaccine efficacy of ≥70%, maternal immunization together with IAP for unimmunized women would prevent more disease than screening/IAP, at a similar cost/QALY. CONCLUSIONS: GBS maternal immunization, with IAP as indicated for unvaccinated women, could be an attractive alternative to screening/IAP if a pentavalent vaccine is sufficiently effective. Coverage, typically low for maternal vaccines, is key to the vaccine's public health impact.

Estimated economic impact of vaccinations in 73 low- and middle-income countries, 2001-2020.

OBJECTIVE: To estimate the economic impact likely to be achieved by efforts to vaccinate against 10 vaccine-preventable diseases between 2001 and 2020 in 73 low- and middle-income countries largely supported by Gavi, the Vaccine Alliance. METHODS: We used health impact models to estimate the economic impact of achieving forecasted coverages for vaccination against Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae and yellow fever. In comparison with no vaccination, we modelled the costs - expressed in 2010 United States dollars (US$) - of averted treatment, transportation costs, productivity losses of caregivers and productivity losses due to disability and death. We used the value-of-a-life-year method to estimate the broader economic and social value of living longer, in better health, as a result of immunization. FINDINGS: We estimated that, in the 73 countries, vaccinations given between 2001 and 2020 will avert over 20 million deaths and save US$ 350 billion in cost of illness. The deaths and disability prevented by vaccinations given during the two decades will result in estimated lifelong productivity gains totalling US$ 330 billion and US$ 9 billion, respectively. Over the lifetimes of the vaccinated cohorts, the same vaccinations will save an estimated US$ 5 billion in treatment costs. The broader economic and social value of these vaccinations is estimated at US$ 820 billion. CONCLUSION: By preventing significant costs and potentially increasing economic productivity among some of the world's poorest countries, the impact of immunization goes well beyond health.

Decision-Tree Model for Support of Health Policy Choices Based on Pneumococcal Conjugate Vaccine (PCV) Program Outcomes.

Pneumococcal Conjugate Vaccine (PCV) has the potential to save lives in low-income countries. We have developed a computational model and web-based decision support software for comparing cost-benefit tradeoffs from alternative PCV program designs, considering their direct and indirect effects on early childhood populations in resource-poor settings. This supports policy-makers in estimating potential health outcomes and cost-effectiveness of different vaccination program strategies for a wide range of population coverage and vaccine effectiveness assumptions.

Funding gap for immunization across 94 low- and middle-income countries.

Novel vaccine development and production has given rise to a growing number of vaccines that can prevent disease and save lives. In order to realize these health benefits, it is essential to ensure adequate immunization financing to enable equitable access to vaccines for people in all communities. This analysis estimates the full immunization program costs, projected available financing, and resulting funding gap for 94 low- and middle-income countries over five years (2016-2020). Vaccine program financing by country governments, Gavi, and other development partners was forecasted for vaccine, supply chain, and service delivery, based on an analysis of comprehensive multi-year plans together with a series of scenario and sensitivity analyses. Findings indicate that delivery of full vaccination programs across 94 countries would result in a total funding gap of $7.6 billion (95% uncertainty range: $4.6-$11.8 billion) over 2016-2020, with the bulk (98%) of the resources required for routine immunization programs. More than half (65%) of the resources to meet this funding gap are required for service delivery at $5.0 billion ($2.7-$8.4 billion) with an additional $1.1 billion ($0.9-$2.7 billion) needed for vaccines and $1.5 billion ($1.1-$2.0 billion) for supply chain. When viewed as a percentage of total projected costs, the funding gap represents 66% of projected supply chain costs, 30% of service delivery costs, and 9% of vaccine costs. On average, this funding gap corresponds to 0.2% of general government expenditures and 2.3% of government health expenditures. These results suggest greater need for country and donor resource mobilization and funding allocation for immunizations. Both service delivery and supply chain are important areas for further resource mobilization. Further research on the impact of advances in service delivery technology and reductions in vaccine prices beyond this decade would be important for efficient investment decisions for immunization.

What Pertussis Mortality Rates Make Maternal Acellular Pertussis Immunization Cost-Effective in Low- and Middle-Income Countries? A Decision Analysis.

BACKGROUND: Despite longstanding infant vaccination programs in low- and middle-income countries (LMICs), pertussis continues to cause deaths in the youngest infants. A maternal monovalent acellular pertussis (aP) vaccine, in development, could prevent many of these deaths. We estimated infant pertussis mortality rates at which maternal vaccination would be a cost-effective use of public health resources in LMICs. METHODS: We developed a decision model to evaluate the cost-effectiveness of maternal aP immunization plus routine infant vaccination vs routine infant vaccination alone in Bangladesh, Nigeria, and Brazil. For a range of maternal aP vaccine prices, one-way sensitivity analyses identified the infant pertussis mortality rates required to make maternal immunization cost-effective by alternative benchmarks ($100, 0.5 gross domestic product [GDP] per capita, and GDP per capita per disability-adjusted life-year [DALY]). Probabilistic sensitivity analysis provided uncertainty intervals for these mortality rates. RESULTS: Infant pertussis mortality rates necessary to make maternal aP immunization cost-effective exceed the rates suggested by current evidence except at low vaccine prices and/or cost-effectiveness benchmarks at the high end of those considered in this report. For example, at a vaccine price of $0.50/dose, pertussis mortality would need to be 0.051 per 1000 infants in Bangladesh, and 0.018 per 1000 in Nigeria, to cost 0.5 per capita GDP per DALY. In Brazil, a middle-income country, at a vaccine price of $4/dose, infant pertussis mortality would need to be 0.043 per 1000 to cost 0.5 per capita GDP per DALY. CONCLUSIONS: For commonly used cost-effectiveness benchmarks, maternal aP immunization would be cost-effective in many LMICs only if the vaccine were offered at less than $1-$2/dose.

Cost of management of severe pneumonia in young children: systematic analysis.

BACKGROUND: Childhood pneumonia is a major cause of childhood illness and the second leading cause of child death globally. Understanding the costs associated with the management of childhood pneumonia is essential for resource allocation and priority setting for child health. METHODS: We conducted a systematic review to identify studies reporting data on the cost of management of pneumonia in children younger than 5 years old. We collected unpublished cost data on non-severe, severe and very severe pneumonia through collaboration with an international working group. We extracted data on cost per episode, duration of hospital stay and unit cost of interventions for the management of pneumonia. The mean (95% confidence interval, CI) and median (interquartile range, IQR) treatment costs were estimated and reported where appropriate. RESULTS: We identified 24 published studies eligible for inclusion and supplemented these with data from 10 unpublished studies. The 34 studies included in the cost analysis contained data on more than 95 000 children with pneumonia from both low- and-middle income countries (LMIC) and high-income countries (HIC) covering all 6 WHO regions. The total cost (per episode) for management of severe pneumonia was US$ 4.3 (95% CI 1.5-8.7), US$ 51.7 (95% CI 17.4-91.0) and US$ 242.7 (95% CI 153.6-341.4)-559.4 (95% CI 268.9-886.3) in community, out-patient facilities and different levels of hospital in-patient settings in LMIC. Direct medical cost for severe pneumonia in hospital inpatient settings was estimated to be 26.6%-115.8% of patients' monthly household income in LMIC. The mean direct non-medical cost and indirect cost for severe pneumonia management accounted for 0.5-31% of weekly household income. The mean length of stay (LOS) in hospital for children with severe pneumonia was 5.8 (IQR 5.3-6.4) and 7.7 (IQR 5.5-9.9) days in LMIC and HIC respectively for these children. CONCLUSION: This is the most comprehensive review to date of cost data from studies on the management of childhood pneumonia and these data should be helpful for health services planning and priority setting by national programmes and international agencies.