The clinical and economic burden of varicella in the Middle East: a systematic literature review.

This systematic literature review was conducted to better understand the epidemiology and burden of varicella across the Middle East, gain insight into the evidence to support using universal varicella vaccination (UVV), and identify potential data gaps. Both epidemiology and economic data on the burden of varicella were limited and varied significantly. Most of the data focussed on varicella burden in the absence of a UVV program. In the absence of UVV, varicella incidence is increasing across this region with varicella infection associated with substantial morbidity. Although limited, data on the impact of vaccination at a population level indicated UVV programs reduce varicella incidence and hospitalizations, in line with global experience. Further research and action are needed to better understand varicella epidemiology in the Middle East, increase awareness and understanding in the region, and provide local data to support national public-health decisions regarding the implementation of UVV programs.

The Impact of Varicella Vaccination on the Incidence of Varicella and Herpes Zoster in the United States: Updated Evidence From Observational Databases, 1991-2016.

BACKGROUND: Universal childhood vaccination against varicella began in the United States as a 1-dose schedule in 1996, changing to a 2-dose schedule in 2006. The exogenous boosting hypothesis, which postulates that reexposure to circulating wild-type varicella delays the onset of herpes zoster, predicts a transient increase in the incidence of herpes zoster, peaking in adults 15-35 years after the start of varicella vaccination. METHODS: This was a retrospective study of administrative claims data from the MarketScan Commercial and Medicare databases between 1991-2016. Outcome measures were the incidences of herpes zoster per 100 000 person-years, by calendar year and age category, and the annual rates of change in herpes zoster by age category, in an interrupted time series regression analysis, for the periods of 1991-1995 (prevaccine), 1996-2006 (1-dose vaccination period), and 2007-2016 (2-dose vaccination period). RESULTS: The annual incidences of herpes zoster increased throughout the period of 1991-2012 in all adult age categories, with a plateau in 2013-2016 that was most evident in the ≥65 age group. In 1991-1995, the herpes zoster incidences increased at annual rates of 4-6% in age categories 18-34, 35-44, 45-54, and 55-64 years. In the same age categories during 1996-2006 and 2007-2016, the herpes zoster incidences increased at annual rates of 1-5%. CONCLUSIONS: Although the annual incidence of herpes zoster in adults has continued to increase, the rates of change decreased during both the 1- and 2-dose vaccination periods. The hypothesized increase in herpes zoster predicted from modelling of the exogenous boosting hypothesis was not observed.

Budget impact analysis of multiple varicella vaccination strategies: a Mexico perspective.

A number of live-attenuated varicella vaccines are produced globally that provide protection against the varicella zoster virus. In Mexico, varicella vaccination is not included in the national immunization program and is recommended for use only in high-risk subgroups. We developed a budget impact model to estimate the impact of universal childhood immunization against varicella on the national payer system in Mexico. A scenario of no varicella vaccination was compared to scenarios with vaccination with a single dose at 13 months of age, in alignment with the existing program of immunization with the measles-mumps-rubella vaccine. Nine different vaccination scenarios were envisioned, differing by vaccine type and by coverage. Varicella cases and treatment costs of each scenario were computed in a dynamic transmission model of varicella epidemiology, calibrated to the population of Mexico. Unit costs were based on Mexico sources or were from the literature. The results indicated that each of the three vaccine types increased vaccine acquisition and administration expenditures but produced overall cost savings in each of the first 10 years of the program, due to fewer cases and reduced varicella treatment costs. A highly effective vaccine at 95% coverage produced the greatest cost savings.

Cost-effectiveness analysis of universal varicella vaccination in Turkey using a dynamic transmission model.

BACKGROUND: In 2013, Turkey introduced one-dose universal varicella vaccination (UVV) at 12 months of age. Inclusion of a second dose is being considered. METHODS: We developed a dynamic transmission model to evaluate three vaccination strategies: single dose at 12 months (1D) or second dose at either 18 months (2D-short) or 6 years of age (2D-long). Costs and utilization were age-stratified and separated into inpatient and outpatient costs for varicella and herpes zoster (HZ). We ran the model including and excluding HZ-related costs and impact of exogenous boosting. RESULTS: Five years post-introduction of UVV (1D), the projected varicella incidence rate decreases from 1,674 cases pre-vaccine to 80 cases/100,000 person-years. By 25 years, varicella incidence equilibrates at 39, 12, and 16 cases/100,000 person-years for 1D, 2D-short, and 2D-long strategies, respectively, using a highly effective vaccine. With or without including exogenous boosting impact and/or HZ-related costs and health benefits, the 1D strategy is least costly, but 2-dose strategies are cost-effective considering a willingness-to-pay threshold equivalent to the gross domestic product. The model predicted a modest increase in HZ burden during the first 20-30 years, after which time HZ incidence equilibrates at a lower rate than pre-vaccine. CONCLUSIONS: Our findings support adding a second varicella vaccine dose in Turkey, as doing so is highly cost-effective across a wide range of assumptions regarding the burden associated with varicella and HZ disease.

Burden of varicella in Latin America and the Caribbean: findings from a systematic literature review.

BACKGROUND: Varicella is typically mild and self-limiting, but can be associated with complications and even death. The limited data available on varicella in Latin America and the Caribbean (LAC) indicate substantial burden in countries where varicella vaccine is not part of publicly funded childhood national immunization programs. METHODS: A systematic literature review of published studies was complemented by "gray" literature on varicella incidence, complications, mortality, and economic consequences, in the absence and presence of universal varicella vaccination (UVV) in LAC. RESULTS: Seroprevalence data indicate that varicella is usually a disease of childhood in LAC. Varicella incidence rates, while unreliable in the absence of mandatory reporting, show a trend to increased incidence due to greater urbanization and population density. The introduction of UVV in national immunization programs has led to significant reductions in varicella incidence in these areas. CONCLUSIONS: Varicella continues to pose a substantial healthcare burden in LAC. The future introduction of UVV in additional countries is predicted to provide substantial reductions in cases, with important economic benefits. For countries that have already implemented UVV, the challenge is to maintain high rates of coverage and, where relevant, consider inclusion of a second dose to reduce breakthrough cases. Given the significant proportion of the region now implementing UVV, a regional recommendation in order to prevent any potential for age-shifts in varicella infection might be considered.

Carga económica de la varicela en niños en Perú, entre 2011 y 2016 / Economic Burden of Varicella in Children in Peru from 2011 to 2016

Objetivo: Describir las complicaciones más frecuentes y la carga económica asociada con la varicela en el Perú. Material y métodos: Estudio multicéntrico de revisión de historias clínicas de pacientes de 1 a 14 años con diagnóstico de varicela entre 2011 y 2016. El uso de recursos de atención médica (URAM) asociados con la varicela, los costos unitarios y la pérdida de trabajo se utilizaron para estimar los costos directos e indirectos, presentados en USD ($). Los datos de costos y URAM se combinaron con estimaciones de carga de enfermedad para calcular el costo total anual de la varicela en el Perú. Resultados: Se incluyeron un total de 179 niños con varicela (101 ambulatorios, 78 hospitalizados). Entre los pacientes ambulatorios, el 5,9 % presentó una o más complicaciones, en comparación con 96,2 % de pacientes hospitalizados. El URAM incluyó el uso de medicamentos de venta libre (72,3 % frente a 89,7 % de pacientes ambulatorios y hospitalizados, respectivamente), medicamentos con receta (30,7 % frente a 94,9 %) y análisis y procedimientos (0,0 % frente a 80,8 %). Los costos directos e indirectos por caso ambulatorio fueron $36 y $62 respectivamente y por caso hospitalizado fueron $548 y $222. El costo anual total asociado con la varicela se estimó en $13 907 146. Conclusión: La varicela está asociada con complicaciones clínicas importantes y elevado URAM en Perú, lo que respalda la necesidad de implementación de un plan de vacunación universal. (AU)

Objective: The purpose of this study was to evaluate the clinical and economic burden associated with varicella in Peru. Methods: This was a multicenter, retrospective chart review study of patients aged 1-14 years with a varicella diagnosis between 2011 and 2016. Healthcare resource utilization (HCRU) associated with varicella, unit costs, and work loss were used to estimate direct and indirect costs, presented in USD ($). The cost and HCRU data was combined with estimates of varicella disease burden to estimate the overall annual costs of management of varicella in Peru. Results: A total of 179 children with varicella (101 outpatients, 78 inpatients) were included. Among outpatients, 5.9% experienced ≥1 complication, compared with 96.2% of inpatients. HCRU estimates included use of over-the-counter (OTC) medications (72.3% vs. 89.7% of outpatient and inpatients, respectively), prescription medications (30.7% vs. 94.9%), tests/procedures (0.0% vs. 80.8%). Among outpatients, direct and indirect costs per case were $36 and $62, respectively; among inpatients, respective costs were $548 and $222. The total annual cost associated with varicella was estimated at $ 13 907 146. Conclusion: Varicella is associated with substantial clinical complications and high HCRU in Peru, supporting the need for implementation of a routine childhood varicella vaccination plan. (AU)

Burden of varicella in the Asia-Pacific region: a systematic literature review.

INTRODUCTION: Varicella is a highly contagious infection that can lead to serious complications, particularly in high-risk groups; however, it is vaccine preventable. Disease awareness and understanding of the disease burden can strongly influence vaccine coverage. This review provides insight into the current epidemiology and the importance of varicella from both public health and economic perspectives across the Asia-Pacific (APAC) region. Areas covered: A systematic literature review was conducted to identify studies on the incidence, seroprevalence, fatality rate and complication rate of varicella. Economic burden studies were also captured. Altogether, 125 studies were identified across the region; these were supplemented by government reports (gray data). Reported vaccine coverage varied from 2.8% to 97%; a key influencing factor was inclusion of the varicella vaccine in national immunization programs. In general, varicella incidence in the unvaccinated population was highest in children ≤5 years old and seroprevalence increased with age. Economic analyses highlighted the cost-saving potential of vaccination programs, especially from a societal perspective. Expert opinion: Varicella-related data varied greatly across the APAC region, highlighting the need to better understand the burden of varicella in this area, and particularly identified the need for better surveillance and reporting.

Burden of varicella in Central and Eastern Europe: findings from a systematic literature review.

INTRODUCTION: Vaccination against varicella rapidly reduces disease incidence, resulting in reductions in both individual burden and societal costs. Despite these benefits, there is no standardization of varicella immunization policies in Europe, including countries in Central and Eastern Europe (CEE). AREAS COVERED: This systematic literature review identified publications on the epidemiology of varicella, its associated health and economic burden, and vaccination strategies within the CEE region, defined as Albania, Bosnia-Herzegovina, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Serbia, Slovakia, and Slovenia. Twenty-six studies were identified from a search of PubMed, Embase®, and MEDLINE® biomedical literature databases, supplemented by gray literature and country-specific/global websites. EXPERT COMMENTARY: Limited information exists in published studies on the burden of varicella in CEE. The wide variability in incidence rates between countries is likely explained by a lack of consistency in reporting systems. Funded universal varicella vaccination (UVV) in CEE is currently available only in Latvia as a one-dose schedule, but Hungary together with Latvia are introducing a two-dose strategy in 2019. For countries that do not provide UVV, introduction of vaccination is predicted to provide substantial reductions in cases and rates of associated complications, with important economic benefits.

Varicella healthcare resource utilization in middle income countries: a pooled analysis of the multi-country MARVEL study in Latin America & Europe.

Varicella is a mild and self-limited illness in children, but can result in significant healthcare resource utilization (HCRU). To quantify/contrast varicella-associated HCRU in five middle-income countries (Hungary, Poland, Argentina, Mexico, and Peru) where universal varicella vaccination was unimplemented, charts were retrospectively reviewed among 1-14 year-olds. Data were obtained on management of primary varicella between 2009-2016, including outpatient/inpatient visits, allied healthcare contacts, tests/procedures, and medications. These results are contrasted across countries, and a regression model is fit to extrapolated country-level costs as a function of gross domestic product (GDP). A total of 401 outpatients and 386 inpatients were included. Significant differences between countries were observed in the number of skin lesions among outpatients, ranging from 5.3% to 25.4% of patients with ≥250 lesions. Among inpatients, results were less variable. Average ambulatory medical visits ranged from 1.1 to 2.2. Average hospital stay ranged from 3.6 to 6.8 days. Use of tests/procedures was infrequent in outpatients, except in Argentina (13.3%); among inpatients, a test/procedure was ordered for 81.3% of patients, without regional variation. Prescription medications were administered in 44.4% of outpatients (range 9.3%-80.0%), and in 86% of inpatients (range 70.4%-94.9%). Total estimated spending on varicella treatment in the absence of vaccination was predicted from income levels (GDP) with an exponential function (R2 = 0.89). This study demonstrates that substantial HCRU is associated with varicella resulting in significant public health burden that could be alleviated through the use of varicella vaccination. Differences observed between countries possibly reflect treatment guidelines, healthcare resource availabilities and physician practices.

Varicella in Poland: economic burden in children 1-12 years of age in Poland, 2010-2015.

BACKGROUND: The safety and efficacy of live-attenuated varicella zoster virus (VZV) vaccines in preventing varicella and reducing associated morbidity and mortality in real-world have been previously shown. In Poland, VZV vaccination is only mandatory for certain high-risk individuals. Here, we have conducted an evaluation of the clinical and economic burden of varicella in Poland. METHODS: Multicenter, retrospective chart review of varicella inpatients and outpatients aged 1-12 years with a primary diagnosis between 2010 and 2015. Varicella-related outcomes included the incidence of complications, the proportion of patients reporting healthcare resource utilization (HCRU), and frequency of HCRU. Direct costs were derived from per patient resource use multiplied by unit costs, and indirect costs were calculated as loss of revenue of caregivers reporting work days missed. The overall annual cost of varicella in Poland was estimated based on the calculated direct and indirect costs per case and the estimated number of varicella cases. All costs are presented in 2015 Polish zloty (PLN) / Euros (€). RESULTS: A total of 150 children with varicella were included, of which 75 were outpatients and 75 were inpatients with a mean (± SD) age of 3.9 (±2.6) and 4.2 (±2.3) years, respectively. Complications were experienced by 14.7% of outpatients and 82.7% of inpatients, of which the most common were skin and soft tissue infections and dehydration. The rate of HCRU was as follows: over-the-counter medications (80.0% outpatients, 81.3% inpatients), prescription medications (80.0% outpatients, 93.3% inpatients), tests/procedures (0.0% outpatients, 69.3% inpatients), and allied health professional consults (0.0% outpatients, 24.0% inpatients). Total (direct and indirect) cost per varicella case was 5013.3 PLN (€ 1198.1) for inpatients and 1027.2 PLN (€ 245.5) for outpatients, resulting in an estimated overall annual (2015) cost of varicella in Poland of 178,198,320 PLN (€ 42,588,385) among children aged 1-15 years. CONCLUSIONS: Significant clinical and economic burden is associated with varicella in Poland. These results may be used to foster discussion related to the implications of implementing routine VZV vaccination in Poland.

Economic burden of varicella in children 1-12 years of age in Argentina, 2009-2014.

BACKGROUND: In Argentina, varicella vaccination was included in the national schedule for mandatory immunizations in 2015. The vaccine has been shown to substantially reduce the morbidity and mortality associated with the virus. The purpose of this study was to evaluate the clinical and economic burden associated with varicella in Argentina prior to vaccine introduction. METHODS: This was a multi-center, retrospective chart review study among patients aged 1-12 years with a primary varicella diagnosis in 2009-2014 in Argentina. Healthcare resource utilization (HCRU) associated with varicella and its complications, unit costs, and work loss were used to estimate direct and indirect costs. All costs are presented in 2015 United States dollars (USD). RESULTS: One hundred and fifty children with varicella were included (75 outpatients, 75 inpatients), with a mean age of 3.8 (SD = 2.4) and 2.9 (SD = 2.2) years, respectively. One or more complications were experienced by 28.0% of outpatients and 98.7% of inpatients, the most common being skin and soft tissue infections, pneumonia, sepsis, cerebellitis, and febrile seizure. HCRU estimates included use of over-the-counter (OTC) medications (58.7% outpatients, 94.7% inpatients), prescription medications (26.7% outpatients, 77.3% inpatients), tests/procedures (13.3% outpatients, 70.7% inpatients), and consultation with allied health professionals (1.3% outpatients, 32.0% inpatients). The average duration of hospital stay was 4.9 (95% CI = 4.2-5.7) days, and the average duration of ICU stay was 4.8 (95% CI = 1.6-14.1) days. The total combined direct and indirect cost per varicella case was 2947.7 USD (inpatients) and 322.7 USD (outpatients). The overall annual cost of varicella in Argentina for children aged ≤14 years in 2015 was estimated at 40,054,378.0 USD. CONCLUSION: The clinical burden of varicella in Argentina was associated with utilization of significant amounts of healthcare resources, resulting in substantial economic costs. These costs should be reduced with the recent implementation of routine vaccination of children.

Economic burden of varicella in children 1-12 Years of age in Hungary, 2011-2015.

BACKGROUND: Although live-attenuated varicella-zoster virus (VZV) vaccines have been proven to be safe and effective in preventing varicella and real-word evidence shows routine childhood immunization programs are effective in dramatically reducing varicella associated morbidity and mortality, varicella vaccine is not included in the National Immunization Program (NIP) in Hungary. The purpose of this study was to evaluate the clinical and economic burden associated with varicella in Hungary. METHODS: This was a multicenter, retrospective, chart review study of patients aged 1-12 years with a primary varicella diagnosis between 2011 and 2015. Healthcare resource utilization (HCRU) associated with varicella, unit costs, and work loss were used to estimate direct and indirect costs. All costs are presented in 2015 HUF / Euros (€). RESULTS: 156 children with varicella were included (75 outpatients, 81 inpatients), with a mean age of 4.4 (SD: 2.0) and 3.7 (SD: 2.1) years, respectively. One or more complications were reported by 12.0% of outpatients and 92.6% of inpatients, the most common being dehydration, skin and soft tissue infections, pneumonia, keratoconjunctivitis, and cerebellitis. HCRU estimates included use of over-the-counter (OTC) medications (96.0% outpatients, 53.1% inpatients), prescription medications (9.3% outpatients, 70.4% inpatients), tests/procedures (4.0% outpatients, 97.5% inpatients), and consultation with allied health professionals (2.7% outpatients, 30.9% inpatients). The average duration of hospital stay (inpatients) was 3.6 (95% CI: 3.2, 4.1) days. The total combined direct and indirect cost per varicella case was 228,146.7 Hungarian Forint (HUF)/€ 736.0 for inpatients and 49,790.6 HUF/€ 106.6 for outpatients. The overall annual cost of varicella in Hungary for children aged <15 years in 2015 was estimated at 1,903,332,524.3 HUF/ € 6,139,980.4. CONCLUSION: Varicella is associated with substantial clinical burden in Hungary, resulting in the utilization of a significant amount of healthcare resources. These results support the need for routine vaccination of all healthy children to reduce the varicella-associated disease burden.

Health outcomes of bedaquiline in the treatment of multidrug-resistant tuberculosis in selected high burden countries.

BACKGROUND: Less than one-third of patients who are estimated to be infected with multidrug-resistant tuberculosis (MDR-TB) receive MDR-TB treatment regimens, and only 48% of those who received treatment have successful outcomes. Despite current regimens, newer, more effective and cost-effective approaches to treatment are needed. The aim of the study was to project health outcomes and impact on healthcare resources of adding bedaquiline to the treatment regimen of MDR-TB in selected high burden countries: Estonia, Russia, South Africa, Peru, China, the Philippines, and India. METHODS: This study adapted an existing Markov model to estimate the health outcomes and impact on total healthcare costs of adding bedaquiline to current MDR-TB treatment regimens. A price threshold analysis was conducted to determine the price range at which bedaquiline would be cost-effective. RESULTS: Adding bedaquiline to the background regimen (BR) resulted in increased disability-adjusted life years (DALYs) averted, and reduced total healthcare costs (excluding treatment acquisition costs) compared with BR alone in all countries analyzed. Addition of bedaquiline to BR resulted in savings to healthcare costs compared with BR alone in all countries analyzed, with the highest impact expected in Russia (US$194 million) and South Africa (US$43 million). The price per regimen at which bedaquiline would be cost-effective ranged between US$23,904-US$203,492 in Estonia, Russia, Peru, South Africa, and China (high and upper middle-income countries) and between US$6,996-US$20,323 in the Philippines and India (lower middle-income countries); however, these cost-effective prices do not necessarily address concerns about affordability. CONCLUSIONS: Adding bedaquiline to BR provides improvements in health outcomes and reductions in healthcare costs in high MDR-TB burden countries. The range of prices per regimen for which bedaquiline would be cost-effective varied between countries.

Cost-effectiveness of adding bedaquiline to drug regimens for the treatment of multidrug-resistant tuberculosis in the UK.

OBJECTIVE: To evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR) of drugs for multidrug-resistant tuberculosis (MDR-TB) in the United Kingdom (UK). METHODS: A cohort-based Markov model was developed to estimate the incremental cost-effectiveness ratio of bedaquiline plus BR (BBR) versus BR alone (BR) in the treatment of MDR-TB, over a 10-year time horizon. A National Health Service (NHS) and personal social services perspective was considered. Cost-effectiveness was evaluated in terms of Quality-Adjusted Life Years (QALYs) and Disability-Adjusted Life Years (DALYs). Data were sourced from a phase II, placebo-controlled trial, NHS reference costs, and the literature; the US list price of bedaquiline was used and converted to pounds (£18,800). Costs and effectiveness were discounted at a rate of 3.5% per annum. Probabilistic and deterministic sensitivity analysis was conducted. RESULTS: The total discounted cost per patient (pp) on BBR was £106,487, compared with £117,922 for BR. The total discounted QALYs pp were 5.16 for BBR and 4.01 for BR. The addition of bedaquiline to a BR resulted in a cost-saving of £11,434 and an additional 1.14 QALYs pp over a 10-year period, and is therefore considered to be the dominant (less costly and more effective) strategy over BR. BBR remained dominant in the majority of sensitivity analyses, with a 81% probability of being dominant versus BR in the probabilistic analysis. CONCLUSIONS: In the UK, bedaquiline is likely to be cost-effective and cost-saving, compared with the current MDR-TB standard of care under a range of scenarios. Cost-savings over a 10-year period were realized from reductions in length of hospitalization, which offset the bedaquiline drug costs. The cost-benefit conclusions held after several sensitivity analyses, thus validating assumptions made, and suggesting that the results would hold even if the actual price of bedaquiline in the UK were higher than in the US.

Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates.

BACKGROUND: Haemophilus influenzae type b (Hib) is a leading cause of childhood bacterial meningitis, pneumonia, and other serious infections. Hib disease can be almost completely eliminated through routine vaccination. We assessed the global burden of disease to help national policy makers and international donors set priorities. METHODS: We did a comprehensive literature search of studies of Hib disease incidence, case-fatality ratios, age distribution, syndrome distribution, and effect of Hib vaccine. We used vaccine trial data to estimate the proportion of pneumonia cases and pneumonia deaths caused by Hib. We applied these proportions to WHO country-specific estimates of pneumonia cases and deaths to estimate Hib pneumonia burden. We used data from surveillance studies to develop estimates of incidence and mortality of Hib meningitis and serious non-pneumonia, non-meningitis disease. If available, high-quality data were used for national estimates of Hib meningitis and non-pneumonia, non-meningitis disease burden. Otherwise, estimates were based on data from other countries matched as closely as possible for geographic region and child mortality. Estimates were adjusted for HIV prevalence and access to care. Disease burden was estimated for the year 2000 in children younger than 5 years. FINDINGS: We calculated that Hib caused about 8.13 million serious illnesses worldwide in 2000 (uncertainty range 7.33-13.2 million). We estimated that Hib caused 371,000 deaths (247,000-527,000) in children aged 1-59 months, of which 8100 (5600-10,000) were in HIV-positive and 363,000 (242,000-517,000) in HIV-negative children. INTERPRETATION: Global burden of Hib disease is substantial and almost entirely vaccine preventable. Expanded use of Hib vaccine could reduce childhood pneumonia and meningitis, and decrease child mortality. FUNDING: GAVI Alliance and the Vaccine Fund.

Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates.

BACKGROUND: Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide. However, many countries lack national estimates of disease burden. Effective interventions are available, including pneumococcal conjugate vaccine and case management. To support local and global policy decisions on pneumococcal disease prevention and treatment, we estimated country-specific incidence of serious cases and deaths in children younger than 5 years. METHODS: We measured the burden of pneumococcal pneumonia by applying the proportion of pneumonia cases caused by S pneumoniae derived from efficacy estimates from vaccine trials to WHO country-specific estimates of all-cause pneumonia cases and deaths. We also estimated burden of meningitis and non-pneumonia, non-meningitis invasive disease using disease incidence and case-fatality data from a systematic literature review. When high-quality data were available from a country, these were used for national estimates. Otherwise, estimates were based on data from neighbouring countries with similar child mortality. Estimates were adjusted for HIV prevalence and access to care and, when applicable, use of vaccine against Haemophilus influenzae type b. FINDINGS: In 2000, about 14.5 million episodes of serious pneumococcal disease (uncertainty range 11.1-18.0 million) were estimated to occur. Pneumococcal disease caused about 826,000 deaths (582,000-926,000) in children aged 1-59 months, of which 91,000 (63,000-102,000) were in HIV-positive and 735,000 (519,000-825,000) in HIV-negative children. Of the deaths in HIV-negative children, over 61% (449,000 [316,000-501,000]) occurred in ten African and Asian countries. INTERPRETATION: S pneumoniae causes around 11% (8-12%) of all deaths in children aged 1-59 months (excluding pneumococcal deaths in HIV-positive children). Achievement of the UN Millennium Development Goal 4 for child mortality reduction can be accelerated by prevention and treatment of pneumococcal disease, especially in regions of the world with the greatest burden. FUNDING: GAVI Alliance and the Vaccine Fund.

Estimating the costs of achieving the WHO-UNICEF Global Immunization Vision and Strategy, 2006-2015.

OBJECTIVE: To estimate the cost of scaling up childhood immunization services required to reach the WHO-UNICEF Global Immunization Vision and Strategy (GIVS) goal of reducing mortality due to vaccine-preventable diseases by two-thirds by 2015. METHODS: A model was developed to estimate the total cost of reaching GIVS goals by 2015 in 117 low- and lower-middle- income countries. Current spending was estimated by analysing data from country planning documents, and scale-up costs were estimated using a bottom-up, ingredients-based approach. Financial costs were estimated by country and year for reaching 90% coverage with all existing vaccines; introducing a discrete set of new vaccines (rotavirus, conjugate pneumococcal, conjugate meningococcal A and Japanese encephalitis); and conducting immunization campaigns to protect at-risk populations against polio, tetanus, measles, yellow fever and meningococcal meningitis. FINDINGS: The 72 poorest countries of the world spent US$ 2.5 (range: US$ 1.8-4.2) billion on immunization in 2005, an increase from US$ 1.1 (range: US$ 0.9-1.6) billion in 2000. By 2015 annual immunization costs will on average increase to about US$ 4.0 (range US$ 2.9-6.7) billion. Total immunization costs for 2006-2015 are estimated at US$ 35 (range US$ 13-40) billion; of this, US$ 16.2 billion are incremental costs, comprised of US$ 5.6 billion for system scale-up and US$ 8.7 billion for vaccines; US$ 19.3 billion is required to maintain immunization programmes at 2005 levels. In all 117 low- and lower-middle-income countries, total costs for 2006-2015 are estimated at US$ 76 (range: US$ 23-110) billion, with US$ 49 billion for maintaining current systems and $27 billion for scaling-up. CONCLUSION: In the 72 poorest countries, US$ 11-15 billion (30%-40%) of the overall resource needs are unmet if the GIVS goals are to be reached. The methods developed in this paper are approximate estimates with limitations, but provide a roadmap of financing gaps that need to be filled to scale up immunization by 2015.

Has the 2005 measles mortality reduction goal been achieved? A natural history modelling study.

BACKGROUND: In 2002, the UN General Assembly Special Session on Children adopted a goal to reduce deaths owing to measles by half by the end of 2005, compared with 1999 estimates. We describe efforts and progress made towards this goal. METHODS: We assessed trends in immunisation against measles on the basis of national implementation of the WHO/UNICEF comprehensive strategy for measles mortality reduction, and the provision of a second opportunity for measles immunisation. We used a natural history model to evaluate trends in mortality due to measles. RESULTS: Between 1999 and 2005, according to our model mortality owing to measles was reduced by 60%, from an estimated 873,000 deaths (uncertainty bounds 634,000-1,140,000) in 1999 to 345,000 deaths (247,000-458,000) in 2005. The largest percentage reduction in estimated measles mortality during this period was in the western Pacific region (81%), followed by Africa (75%) and the eastern Mediterranean region (62%). Africa achieved the largest total reduction, contributing 72% of the global reduction in measles mortality. Nearly 7.5 million deaths from measles were prevented through immunisation between 1999 and 2005, with supplemental immunisation activities and improved routine immunisation accounting for 2.3 million of these prevented deaths. INTERPRETATION: The achievement of the 2005 global measles mortality reduction goal is evidence of what can be accomplished for child survival in countries with high childhood mortality when safe, cost-effective, and affordable interventions are backed by country-level political commitment and an effective international partnership.