Cost-effectiveness analysis of pertussis booster vaccination for adolescents in Japan.

INTRODUCTION: In Japan, the introduction of a fifth diphtheria-tetanus-acellular pertussis (DTaP) vaccination has been considered, and adolescents aged 11-12 years old who are currently receiving the diphtheria-tetanus (DT) vaccine are one candidate group. We analyze the cost-effectiveness of replacing the DT vaccine with the DTaP vaccine for 11-year-old adolescents and investigate the indirect effect of vaccinated adolescents on unvaccinated infant siblings. We undertake two analyses using high- and low-morbidity pertussis cases, and based on the results, present suggestions for pertussis prevention in the post-COVID-19 pandemic era. METHOD: We used the number of pertussis cases in 2019 as the high-morbidity case and the average number of cases in 2020-2021 as the low-morbidity case, and evaluated the incremental cost-effectiveness ratio (ICER) of the DTaP strategy to the DT strategy based on quality-adjusted life years (QALYs). The economic model contained adolescent and infant sub-models. The indirect effect for infants was considered as the probability of unvaccinated infants avoiding pertussis infection from their vaccinated siblings. RESULTS: The ICER from the payers' perspective was Japanese yen (JPY) 4,254,515 per QALY gained in the high-morbidity case and JPY 62,546,776 per QALY gained in the low-morbidity case. The sensitivity analysis showed that the utility of pertussis had the greatest impact on the ICER, with a 60.58% and 0% probability that the ICER was less than JPY 5 million per QALY gained in the high-morbidity case and low-morbidity case, respectively. CONCLUSION: The cost-effectiveness of replacing the DT vaccine with the DTaP vaccine is affected by the level of pertussis morbidity, with the ICER becoming more favorable in the high-morbidity case. The indirect effect has little impact on the ICER. Thus, policy-makers should continue to monitor the pertussis epidemic in the post-COVID-19 era, and determine the need to introduce a booster based on perceived trends.

Influenza and Tetanus, Diphtheria, and Acellular Pertussis Vaccination Coverage During Pregnancy: Pregnancy Risk Assessment Monitoring System, 2020.

OBJECTIVES: Estimates of vaccination coverage during pregnancy and identification of disparities in vaccination coverage can inform vaccination campaigns and programs. We reported the prevalence of being offered or told to get the influenza vaccine by a health care provider (hereinafter, provider); influenza vaccination coverage during the 12 months before delivery; and tetanus, diphtheria, and acellular pertussis (Tdap) vaccination coverage during pregnancy among women with a recent live birth in the United States. METHODS: We analyzed 2020 data from the Pregnancy Risk Assessment Monitoring System from 42 US jurisdictions (n = 41 673). We estimated the overall prevalence of being offered or told to get the influenza vaccine by a provider and influenza vaccination coverage during the 12 months before delivery. We estimated Tdap vaccination coverage during pregnancy from 21 jurisdictions with available data (n = 22 020) by jurisdiction and select characteristics. RESULTS: In 2020, 84.9% of women reported being offered or told to get the influenza vaccine, and 60.9% received it, ranging from 35.0% in Puerto Rico to 79.7% in Massachusetts. Influenza vaccination coverage was lower among women who were not offered or told to get the influenza vaccine (21.4%) than among women who were offered or told to get the vaccine (68.1%). Overall, 72.7% of women received the Tdap vaccine, ranging from 52.8% in Mississippi to 86.7% in New Hampshire. Influenza and Tdap vaccination coverage varied by all characteristics examined. CONCLUSIONS: These results can inform vaccination programs and strategies to address disparities in vaccination coverage during pregnancy and may inform vaccination efforts for other infectious diseases among pregnant women.

Universal Tetanus-Diphtheria-Pertussis Vaccination During Pregnancy: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess the cost effectiveness of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination in pregnant patients in the United States. METHODS: A decision-analytic model in TreeAge was developed to compare universal Tdap vaccination in pregnancy with no Tdap vaccination in pregnancy using a theoretical cohort of 3.66 million pregnant individuals, the approximate number of deliveries per year in the United States. Outcomes included infant pertussis infections, infant hospitalizations, infant encephalopathy cases, infant deaths, and maternal pertussis infections. All probabilities and costs were derived from the literature. Utilities were applied to discounted life expectancies at a rate of 3% to generate quality-adjusted life-years (QALYs). A strategy was considered cost effective if it had an incremental cost-effectiveness ratio of less than $100,000 per QALY. Univariable and multivariable sensitivity analyses were performed to assess the robustness of the model to changes in the baseline assumptions. RESULTS: With a baseline assumption of vaccine cost at $47.75, Tdap vaccination was cost effective at $7,601 per QALY. The vaccination strategy was associated with a decrease of 22 infant deaths, 11 infant encephalopathy cases, 2,018 infant hospitalizations, 6,164 infant pertussis infections, and 8,585 maternal pertussis infections, with an increase of 19,489 QALYs. In sensitivity analyses, the strategy was cost effective until the incidence of maternal pertussis became lower than 1.6 cases per 10,000 individuals, the cost of the Tdap vaccine was greater than $540, or previous pertussis immunity was present in more than 92.1% of pregnant individuals. CONCLUSION: In a theoretical U.S. cohort of 3.66 million pregnant individuals, Tdap vaccination during pregnancy is cost effective and reduces infant morbidity and mortality compared with no vaccination during pregnancy. These findings are especially relevant given that approximately half of individuals are not vaccinated during pregnancy and recent data have shown that postpartum maternal vaccination and cocooning strategies are ineffective. Public health strategies to encourage greater uptake of Tdap vaccination should be used to reduce the morbidity and mortality of pertussis infection.

Development of a cell line-based in vitro assay for assessment of Diphtheria, Tetanus and acellular Pertussis (DTaP)-induced inflammasome activation.

Safety and potency assessment for batch release testing of established vaccines still relies partly on animal tests. An important avenue to move to batch release without animal testing is the consistency approach. This approach is based on thorough characterization of the vaccine to identify critical quality attributes that inform the use of a comprehensive set of non-animal tests to release the vaccine, together with the principle that the quality of subsequent batches follows from their consistent production. Many vaccine antigens are by themselves not able to induce a protective immune response. The antigens are therefore administered together with adjuvant, most often by adsorption to aluminium salts. Adjuvant function is an important component of vaccine potency, and an important quality attribute of the final product. Aluminium adjuvants are capable of inducing NLRP3 inflammasome activation. The aim of this study was to develop and evaluate an in vitro assay for NLRP3 inflammasome activation by aluminium-adjuvanted vaccines. We evaluated the effects of Diphtheria-Tetanus-acellular Pertussis combination vaccines from two manufacturers and their respective adjuvants, aluminium phosphate (AP) and aluminium hydroxide (AH), in an in vitro assay for NLRP3 inflammasome activation. All vaccines and adjuvants tested showed a dose-dependent increase in IL-1ß production and a concomitant decrease in cell viability, suggesting NLRP3 inflammasome activation. The results were analysed by benchmark dose modelling, showing a similar 50% effective dose (ED50) for the two vaccine batches and corresponding adjuvant of manufacturer A (AP), and a similar ED50 for the two vaccine batches and corresponding adjuvant of manufacturer B (AH). This suggests that NLRP3 inflammasome activation is determined by the adjuvant only. Repeated freeze-thaw cycles reduced the adjuvant biological activity of AH, but not AP. Inflammasome activation may be used to measure adjuvant biological activity as an important quality attribute for control or characterization of the adjuvant.

Cost of Delivering Tetanus Toxoid and Tetanus-Diphtheria Vaccination in Vietnam and the Budget Impact of Proposed Changes to the Schedule.

INTRODUCTION: In 2017, aligned with global World Health Organization tetanus guidelines, Vietnam prepared evidence to support a recommendation to introduce the tetanus-diphtheria (Td) vaccine into routine immunization. This study aimed to provide evidence on the costs and budgetary impact of the potential replacement of the tetanus-toxoid (TT) vaccine with the Td vaccine, considering different possible delivery strategies. METHOD: We used an activity-based ingredients costing approach to estimate the 2017 program costs of providing TT vaccination to girls aged 15-16 years and conducting Td campaigns in outbreak areas. We performed a budget impact analysis for 2018-2025 using the cost per dose estimates based on the current delivery of these vaccines. We assumed complete cessation of TT vaccination of girls aged 15-16 years and a transition period where Td outbreak control campaigns would still occur. Td vaccine was assumed to be provided to children aged 7 years using either facility- or school-based delivery or combined facility- and school-based delivery. RESULTS: The delivery cost per dose for current TT vaccination for girls aged 15-16 years was US$1.49 for school-based delivery, US$1.76 for facility-based delivery, and US$3.86 for delivery via outreach. Td vaccination through campaigns was estimated to cost US$3.56/dose. During 2018-2025, replacing the TT vaccine for girls aged 15-16 years with the Td vaccine for children aged 7 years is estimated to save US$4.61 million in immunization delivery costs if a school-based delivery strategy is used or US$1.04 million if facility-based delivery is used. CONCLUSION: Compared to the current plan, delivery of Td routine vaccination via a school-based strategy was the most cost saving. These results were used in late 2019 to support the delivery of Td vaccination using a school-based delivery strategy for children aged 7 years in 30 Northern provinces in Vietnam.

The need for pertussis vaccination among older adults and high-risk groups: a perspective from advanced economies of the Asia Pacific region.

Introduction: Influenza and pneumococcal vaccines are the most regularly prescribed vaccines amongst adults <65 years of age. Pertussis booster vaccines (available as combined diphtheria-tetanus-acellular pertussis, Tdap) uptake is relatively low in many countries in the Asia-Pacific region. Increasing Tdap vaccination is a strategy that may aid healthy aging.Areas Covered: Epidemiology data, including notification reports from 6 advanced economies in Asia (Australia, Hong Kong, New Zealand, Singapore, South Korea, and Taiwan) were reviewed to assess the pertussis disease burden and identify high-risk groups. Existing Tdap vaccination recommendations were reviewed. Current vaccination practices were discussed to benchmark and identify barriers and success factors for Tdap booster vaccination in older adults.Expert Opinion: The available evidence supports Tdap vaccination at an individual level for the prevention of pertussis, along with tetanus and diphtheria in those aged 65+ years, together with influenza and pneumococcal vaccination. Data gaps need to be filled to support the development of national/supranational recommendations for pertussis booster vaccination. Groups at higher risk of pertussis infection and its complications, including those with chronic obstructive pulmonary disease and asthma, could be considered as priority groups. Increasing disease awareness and establishing adult vaccination registries could improve vaccine coverage and promote healthy aging.

PLAIN LANGUAGE SUMMARYPertussis, also called whooping cough, is a common disease in adults. However, how it affects adults in some countries in the Asia-Pacific region is not well understood. In 2019, a panel of experts met to review the available information on adult cases of pertussis in Australia, Hong Kong, New Zealand, Singapore, South Korea, and Taiwan. Here, we present the outcomes of the meeting. Pertussis is increasingly reported in the Asia-Pacific region, including cases diagnosed in adults. The diagnosis may be missed in countries where awareness is still low and/or it is not tested routinely. The experts concluded that physicians should consider recommending pertussis vaccination to older adults (aged 65 or older) on an individual basis, as well as people with asthma or chronic obstructive pulmonary disease, who appear to be at higher risk of severe pertussis. Uptake of pertussis vaccination in adults could be improved by increasing awareness of the vaccines available and vaccination infrastructure for this age-group. Some of the measures proposed were as follows: improved access to vaccination; personalized reminders when vaccines are due; and more education about pertussis in adults for doctors, nursesnurses, and patients. The experts also proposed setting up adult vaccination registries for tracking and evaluation of vaccine uptake. This expert opinion might help the healthcare community build action plans to recognise the burden of the disease and increase rates of vaccination among adults. In addition, better data on the disease burden would help to generate awareness.

Subnational inequalities in diphtheria-tetanus-pertussis immunization in 24 countries in the African Region.

OBJECTIVE: To analyse subnational inequality in diphtheria-tetanus-pertussis (DTP) immunization dropout in 24 African countries using administrative data on receipt of the first and third vaccine doses (DTP1 and DTP3, respectively) collected by the Joint Reporting Process of the World Health Organization and the United Nations Children's Fund. METHODS: Districts in each country were grouped into quintiles according to the proportion of children who dropped out between DTP1 and DTP3 (i.e. the dropout rate). We used six summary measures to quantify inequalities in dropout rates between districts and compared rates with national dropout rates and DTP1 and DTP3 immunization coverage. FINDINGS: The median dropout rate across countries was 2.4% in quintiles with the lowest rate and 14.6% in quintiles with the highest rate. In eight countries, the difference between the highest and lowest quintiles was 14.9 percentage points or more. In most countries, underperforming districts in the quintile with the highest rate tended to lag disproportionately behind the others. This divergence was not evident from looking only at national dropout rates. Countries with the largest inequalities in absolute subnational dropout rate tended to have lower estimated national DTP1 and DTP3 immunization coverage. CONCLUSION: There were marked inequalities in DTP immunization dropout rates between districts in most countries studied. Monitoring dropout at the subnational level could help guide immunization interventions that address inequalities in underserved areas, thereby improving overall DTP3 coverage. The quality of administrative data should be improved to ensure accurate and timely assessment of geographical inequalities in immunization.

Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Pertussis in the Newborn in Publicly and Privately Insured Mother-infant Pairs in the United States.

BACKGROUND: In the United States, pertussis circulation persists and primarily infects infants and children, despite routine vaccinations. To minimize infant morbidity and mortality from the disease before the first DTaP dose, the Advisory Committee on Immunization Practices recommends maternal Tdap vaccination in weeks 27-36 of pregnancy. METHODS: Cohorts of mother-infant pairs in the Medicaid Analytic eXtract (MAX) (2010-2014) and IBM MarketScan (2011-2015) databases were analyzed to estimate the effectiveness of prenatal Tdap vaccination compared with no vaccination to prevent infant pertussis in the first 6 months. Hazard ratios were estimated with Cox proportional hazards models and adjusted for potential confounders via inverse probability weights. The impact of preterm delivery on the risk of pertussis was analyzed. Results from the 2 databases were pooled. RESULTS: In MarketScan, women received Tdap vaccination before delivery in 114,067 (25.6%) of 445,638 pregnancies and in MAX, 33,286 (4.8%) of 695,262 pregnancies. Among pregnancies with preterm delivery, only 21.2% and 3.8% in MarketScan and MAX had been vaccinated. The risk of pertussis in unvaccinated term infants was 3.5 (MarketScan) and 17 (MAX) per 10,000; and in preterm infants, it was 8.4 (MarketScan) and 19.8 (MAX) per 10,000. The pooled hazard ratio for Tdap vaccination any time before delivery versus no vaccination was 0.64 [95% confidence interval (CI): 0.41-1.00]. The hazard ratio was 0.11 (95% CI: 0.03-0.36) for preterm and 0.78 (95% CI: 0.48-1.29) for term infants vaccinated before 37 weeks. The incidence of pertussis was higher and the protective hazard ratio stronger during pertussis outbreaks. CONCLUSIONS: Prenatal Tdap vaccination reduces the risk of pertussis infections in the infants' first 6 months by 36%. Vaccination soon after 27 weeks of pregnancy, before when deliveries began, ensures vaccination includes those born preterm, who are at highest risk for pertussis and benefit particularly from this vaccination.

Timeliness of immunisation with the pentavalent vaccine at different levels of the health care system in the Lao People's Democratic Republic: A cross-sectional study.

BACKGROUND: The timely administration of vaccines is considered to be important for both individual and herd immunity. In this study, we investigated the timeliness of the diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (pentavalent) vaccine, scheduled at 6, 10 and 14 weeks of age in the Lao People's Democratic Republic. We also investigated factors associated with delayed immunization. METHODS: 1162 children aged 8-28 months who had received the full course of the pentavalent vaccine at different levels of the health care system were enrolled. Vaccination dates documented in hospital records and/or immunisation cards were recorded. Age at vaccination and time intervals between doses were calculated. Predictors for timely completion with the pentavalent vaccine at 24 weeks were assessed by bivariate and multivariable analyses. RESULTS: Several discrepancies in dates between vaccination documents were observed. In general, vaccination with the pentavalent vaccine was found to be delayed, especially in health care settings below the provincial hospital level. Compared to the central hospital level, less participants who were vaccinated at the district/health center level received the third dose by 16 (48% at the central hospital level vs. 7.1% at the district and 12.4% at the health center level) and 24 weeks of age (94.4% at the central hospital level vs 64.6% at the district-outreach and 57.4% at the health center level) respectively. In logistic regression analyses, lower education level of the mother as well as vaccination by outreach service, were independently associated with delayed completion of vaccination. CONCLUSION: We observed a general delay of vaccination, especially at lower ranked facilities, which correlated with indicators of poor access to health services. This highlights the need for further improving health equity in rural areas. Age-appropriate vaccination should become a quality indicator for the national immunization programme. In addition, we recommend further training of the health care staff regarding the importance of reliable documentation of dates.

Economic impact of implementing decennial tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccination in adults in the United States.

BACKGROUND: In the United States, persons ≥11 years are recommended to receive one dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, followed by decennial tetanus- and diphtheria-toxoid (Td) boosters. Many providers use Tdap instead of Td. We evaluated epidemiologic and economic impacts of replacing Td boosters with Tdap. METHODS: We used a static cohort model to examine replacing Td with Tdap over the lifetime of 4,386,854 adults ≥21 years. Because pertussis is underdiagnosed and true incidence is unknown, we varied incidence from 2.5 cases/100,000 person-years to 500 cases/100,000 person-years. We calculated vaccine and medical costs from claims data. We estimated cost per case prevented and per quality-adjusted life year (QALY) saved; sensitivity analyses were conducted on vaccine effectiveness (VE), protection duration, vaccine cost, disease duration, hospitalization rates, productivity loss and missed work. We did not include programmatic advantages resulting from use of a single tetanus-toxoid containing vaccine. RESULTS: At lowest incidence estimates, administering Tdap resulted in high costs per averted case ($111,540) and QALY saved ($8,972,848). As incidence increased, cases averted increased and cost per QALY saved decreased rapidly. With incidence estimates of 250 cases/100,000 person-years, cost per averted case and QALY saved were $984 and $81,678 respectively; at 500 cases/100,000 person-years, these values were $427 and $35,474. In multivariate sensitivity analyses, assuming 250 cases/100,000 person-years, estimated cost per QALY saved ranged from $971 (most favorable) to $217,370 (least favorable). CONCLUSIONS: Our findings suggest that replacing Td with Tdap for the decennial booster would result in high cost per QALY saved based on reported cases. However, programmatic considerations were not accounted for, and if pertussis incidence, which is incompletely measured, is assumed to be higher than reported through national surveillance, substituting Tdap for Td may lead to moderate decreases in pertussis cases and cost per QALY.

Factors influencing basic vaccination coverage in Myanmar: secondary analysis of 2015 Myanmar demographic and health survey data.

BACKGROUND: Immunization is one of the most effective measures for preventing disease when vaccination coverage is sufficient. Although vaccination coverage is known to be influenced by social and cultural barriers, the determinants of childhood immunization in Myanmar remain poorly understood. This study analyzed factors that influenced complete vaccination status (one dose each for Bacillus Calmette-Guérin and measles and three doses each for diphtheria-pertussis and polio) using 2015 data from the Myanmar Demographic Health and Survey. METHODS: Data from 12 to 23-month-old children and their mothers were extracted from the nationally representative survey results. Bivariate and multivariate analyses with survey-weighted logistic regression were performed to examine the relationships between vaccination status and various sociodemographic and medical factors. The independent variables for the analyses included area of residence, economic status, maternal age, marital status, education, literacy, employment status, antenatal care attendance, tetanus vaccination, place of delivery, postnatal evaluations, child's sex, number of children, previous child death, decision maker(s) regarding child's health, frequency of healthcare visits, paternal education, and paternal occupation. RESULTS: A representative sample of 904 cases were extracted for the analysis. The overall complete vaccination rate was 55.4%. In the multivariate analysis with backward step-wise selection, complete vaccination was independently associated with middle or high economic status (adjusted odds ratio [AOR]: 2.64, 95% confidence interval [CI]: 1.85-3.78), older maternal age (AOR: 2.87, 95% CI: 1.62-5.10), ≥4 antenatal care visits (AOR: 1.87, 95% CI: 1.28-2.73), and maternal tetanus vaccination before delivery (AOR: 3.26, 95% CI: 1.82-5.85). CONCLUSION: The first Demographic and Health Survey in Myanmar revealed that only approximately one-half of 12-23-year-old children had received complete vaccination, which was lower than the estimated rate from routine administrative coverage. Our results indicate that incomplete immunization status was associated with low economic status, younger maternal age, fewer antenatal care visits, and no maternal tetanus vaccination. These findings may help improve the targeting and strategic implementation of the Expanded Programme on Immunization.

Cost-effectiveness of adult vaccinations: A systematic review.

BACKGROUND: Coverage levels for many recommended adult vaccinations are low. The cost-effectiveness research literature on adult vaccinations has not been synthesized in recent years, which may contribute to low awareness of the value of adult vaccinations and to their under-utilization. We assessed research literature since 1980 to summarize economic evidence for adult vaccinations included on the adult immunization schedule. METHODS: We searched PubMed, EMBASE, EconLit, and Cochrane Library from 1980 to 2016 and identified economic evaluation or cost-effectiveness analysis for vaccinations targeting persons aged ≥18 years in the U.S. or Canada. After excluding records based on title and abstract reviews, the remaining publications had a full-text review from two independent reviewers, who extracted economic values that compared vaccination to "no vaccination" scenarios. RESULTS: The systematic searches yielded 1688 publications. After removing duplicates, off-topic publications, and publications without a "no vaccination" comparison, 78 publications were included in the final analysis (influenza = 25, pneumococcal = 18, human papillomavirus = 9, herpes zoster = 7, tetanus-diphtheria-pertussis = 9, hepatitis B = 9, and multiple vaccines = 1). Among outcomes assessing age-based vaccinations, the percent indicating cost-savings was 56% for influenza, 31% for pneumococcal, and 23% for tetanus-diphtheria-pertussis vaccinations. Among age-based vaccination outcomes reporting $/QALY, the percent of outcomes indicating a cost per QALY of ≤$100,000 was 100% for influenza, 100% for pneumococcal, 69% for human papillomavirus, 71% for herpes zoster, and 50% for tetanus-diphtheria-pertussis vaccinations. CONCLUSIONS: The majority of published studies report favorable cost-effectiveness profiles for adult vaccinations, which supports efforts to improve the implementation of adult vaccination recommendations.

Protocolo del Sistema Nacional de Vigilancia Epidemiológica de enfermedades inmunoprevenibles. No. 06 / Protocol of the National Epidemiological Surveillance System of immunoprevenible diseases. No. 06

Estos protocolos están dirigido a personal médico, paramédico y otros profesionales que realizan acciones gerenciales y operativas de vigilancia epidemiológica en los servicios de salud del país, y están divididos en varios tomos para dar a conocer y actualizar la identificación y medidas de control para diversos padecimientos a fin de continuar con el mejoramiento de las capacidades técnicas de los trabajadores de salud, que permita planificar la prestación de servicios con decisiones partiendo de un enfoque epidemiológico comprobado, para responder a los cambios de tendencias epidemiológicas y con ello contribuir al fortalecimiento de prácticas asertivas de la salud pública de nuestro país. La vigilancia epidemiológica de las enfermedades prevenibles con vacuna, busca reducir la mortalidad y morbilidad por infecciones inmunoprevenibles. La vigilancia epidemiológica, es fundamental para evaluar el impacto de las intervenciones y la toma de decisiones de acuerdo al análisis permanente de la situación de salud.

Validación de un ensayo inmunoenzimático tipo ELISA para cuantificar niveles de antitoxina diftérica en suero humano / Validation of an ELISA-type immune-enzymatic test to quantify levels of diphtheria antitoxin in human serum

Introducción: La difteria aún persiste en numerosos países. En Cuba, estudios realizados en diferentes grupos etarios han demostrado que existen niveles no protectores de antitoxina diftérica en la población, por lo que es necesario contar con métodos que permitan la estimación serológica de la inmunidad poblacional. La cuantificación de anticuerpos contra antígenos vacunales como la toxina diftérica es además un método útil, rápido y económico para evaluar la respuesta inmune. Objetivo: Validar un ensayo inmunoenzimático tipo ELISA para cuantificar los niveles de antitoxina diftérica en suero humano. Material y Método: Se realizó un estudio experimental de desarrollo tecnológico, en el cual se determinaron los valores óptimos de las variables que influyen en el resultado de un ensayo inmunoenzimático heterogéneo indirecto para la cuantificación de antitoxina diftérica, desarrollado en el laboratorio de Inmunología del Centro Nacional de Genética Médica de Cuba. La curva de calibración se evaluó contra el estándar de la OMS (Diphtheria Antitoxin Human Serum 00/496). Se realizó la validación analítica del método estandarizado. Resultados: Los coeficientes de variación intraensayo e interensayo fueron inferiores a 10 por ciento y 20 por ciento, respectivamente. En la exactitud y selectividad se encontraron valores de recobrado entre 90 y 110 por ciento. El paralelismo entre la curva estándar y las muestras estudiadas presentó un coeficiente de variación menor o igual a 10 por ciento. El límite de cuantificación fue 0,015 UI/mL y el de detección 0,0039 UI/mL. Conclusiones: El resultado obtenido en la precisión, exactitud y selectividad del ensayo inmunoenzimático tipo ELISA desarrollado demostró que puede ser utilizado en la práctica clínica para cuantificar los valores de antitoxina diftérica en suero humano(AU)

Introduction: Diphtheria still persists in many countries. In Cuba, studies conducted in different age groups have demonstrated that there are non-protective levels of diphtheria antitoxin in the population, so it is necessary to have methods that allow the serologic survey of population immunity. The quantification of antibodies against vaccine antigens such as diphtheria toxin is also a useful, rapid and economic method to evaluate the immune response. Objective: To validate an ELISA-type immune-enzymatic test to quantify the levels of diphtheria antitoxin in human serum. Material and Method: An experimental study of technological development was carried out in the Immunology Laboratory of the National Medical Genetics Center, Havana, Cuba. The optimal values ​​of the variables that influence on the result of the indirect heterogeneous immune-enzymatic test for the quantification of diphtheria antitoxin were determined. The calibration curve obtained was evaluated against the WHO standard (Diphtheria Antitoxin Human Serum 00/496). The analytical validation of the standardized method was performed. Results: The intra-assay and inter-assay coefficients of variation were less than 10 percent and 20 percent, respectively. Recovery values ​​between 90 and 110% were found in accuracy and selectivity. The parallelism between the standard curve and the samples studied showed a coefficient of variation lower or equal to 10 percent. The limit of quantification was 0,015 IU/mL and the one of detection was 0,0039 IU/mL. Conclusions: The result obtained in the precision, accuracy and selectivity of the ELISA-type immune-enzymatic test developed and validated in the National Medical Genetics Center demonstrated that it can be used in the clinical practice to quantify the values ​​of diphtheria antitoxin in human serum(AU)

The public health value of vaccination for seniors in Europe.

Longer life expectancy and decreasing fertility rates mean that the proportion of older people is continually increasing worldwide, and particularly in Europe. Ageing is associated with an increase in the risk and severity of infectious diseases. These diseases are also more difficult to diagnose and manage in seniors who often have at least one comorbid condition (60% of seniors have two or more conditions). Infectious diseases increase the risk of hospitalization, loss of autonomy and death in seniors. Effective vaccines are available in Europe for infectious diseases such as influenza, pneumococcal diseases, herpes zoster, diphtheria, tetanus and pertussis. Their effectiveness has been demonstrated in terms of reducing the rates of hospitalization, disability, dependency and death. The prevention of diseases in seniors also results in savings in healthcare and societal costs each year in Europe. Despite the availability of vaccines, vaccine-preventable diseases affect millions of European citizens annually, with the greatest burden of disease occurring in seniors, and the medical and economic benefits associated with are not being achieved. Vaccination coverage rates must be improved to achieve the full benefits of vaccination of seniors in Europe.

A decision analytic model for prevention of hepatitis B virus infection in Sub-Saharan Africa using birth-dose vaccination.

OBJECTIVE: To compare prenatal maternal hepatitis B virus (HBV) screening and infant vaccination strategies to inform policy on HBV prevention in Sub-Saharan Africa. METHODS: A decision analytic model was created using previously published data to assess the ability of three intervention strategies to prevent HBV infection by age 10 years. Strategy 1 comprised of universal vaccination with a pentavalent vaccine (HBV, diphtheria, tetanus, pertussis, and Haemophilus influenzae) at age 6 weeks. Strategy 2 comprised of universal HBV vaccine at birth plus pentavalent vaccine. Strategy 3 comprised of maternal prenatal HBV screening and targeted HBV vaccine at birth for all exposed infants plus pentavalent vaccine. The reference strategy provided neither maternal screening nor infant vaccination. Rates of HBV infection and costs were compared. RESULTS: The reference strategy had an HBV infection rate of 2360 per 10 000 children. The HBV infection rate for strategy 1 was 813 per 10 000 children vaccinated (1547 cases prevented). Strategies 2 and 3 prevented an additional 384 cases and 362 cases, respectively. Inclusion of HBV vaccination at birth was the preferred approach at a willingness-to-pay threshold of US$150. CONCLUSION: Including a birth-dose HBV vaccine in the standard schedule was both cost-effective and prevented additional infections.

Immunization Practices of U.S. Obstetrician/Gynecologists for Pregnant Patients.

INTRODUCTION: U.S. obstetrician/gynecologists play a critical role as vaccinators of pregnant women. However, little is known about their current immunization practices. Thus, study objectives were to determine (1) practices related to assessment of vaccination status and vaccine delivery for pregnant patients; (2) barriers to stocking and administering vaccines; and (3) factors associated with administering both influenza and tetanus, diphtheria, and acellular pertussis (Tdap) vaccines. METHODS: An e-mail and mail survey among a national sample of obstetrician/gynecologists conducted July-October 2015 (analysis August 2016-August 2017). RESULTS: The response rate was 73.2% (353/482). Among obstetrician/gynecologists caring for pregnant women (n=324), vaccination status was most commonly assessed for influenza (97%), Tdap (92%), and measles, mumps, and rubella vaccines (88%). Vaccines most commonly administered included influenza (85%) and Tdap (76%). Few respondents reported administering other vaccines to pregnant patients. More physicians reported using standing orders for influenza (66%) than Tdap (39%). Other evidence-based strategies for increasing vaccine uptake were less frequently used (electronic decision support, 42%; immunization information system to record [13%] or assess vaccination status [11%]; reminder/recall, 7%). Barriers most commonly reported were provider financial barriers, yet provider attitudinal barriers were rare. Providers who administered both influenza and Tdap vaccines were more likely to be female, perceive fewer financial and practice barriers, less likely to be in private practice, and perceive more patient barriers. CONCLUSIONS: Although most obstetrician/gynecologists administer some vaccines to pregnant women, the focus remains on influenza and Tdap. Financial barriers and infrequent use of evidence-based strategies for increasing vaccination uptake may be hindering delivery of a broader complement of adult vaccines in obstetrician/gynecologist offices.

Achievements of healthcare services vis a vis the MDG targets: Evidence from Pakistan.

OBJECTIVE: To investigate the impact of public healthcare facilities and socio-economic circumstances on the status of child health. METHODS: The study was conducted at the School of Social Sciences and Humanities of the National University of Sciences and Technology, Islamabad, Pakistan. The human opportunity index framework was used to measure the trends in health inequalities and coverage using Pakistan Social and Living Standards Measurement dataset from year 2001-02 to 2012-13 at national and provincial levels. The health goals considered in this study were: reducing infant and child mortality rates and immunisation against measles and other major diseases such as diphtheria, polio, Bacillus Calmette-Guerin, and hepatitis. Socio-economic variables such as age, household income, gender, mother's education, housing conditions, water and sanitation facilities, awareness of health services and provision of public hospitals, distance to and cost of immunisation were used to generate quantitative estimates.. RESULTS: The human opportunity index for reduction in child mortality rates improved for 6879(50.4%) mothers in 2001-02 to 8763(64.1%) in 2011-12. Similarly, immunisation against measles and other diseases also registered an improvement from 8430(51.6%) to 9495(69.9%) children during the period at national level. CONCLUSIONS: Health indicators vis-à-vis the Millennium Development Goals targets showed improvement.

Cost effectiveness of a practice-based intervention to improve vaccination rates in adults less than 65-years-old.

The cost-effectiveness of the 4 Pillars™ Practice Transformation Program to improve vaccination rates in adults <65-years-old is unknown. Two vaccines, influenza and Tdap (tetanus, diphtheria, acellular pertussis), were targeted for this age group. Cost-effectiveness of the intervention compared with control, with a primary outcome of cost per quality adjusted life year (QALY) gained, was estimated from societal and third party payer perspectives over a 10-year time horizon using a decision analysis model. Vaccination rates and intervention costs were derived from an intervention trial, and vaccine effectiveness, illness rates, and costs with/without vaccination were obtained from US databases and literature data. Future costs and effectiveness were discounted at 3%/year. The intervention cost was $1.78 per eligible patient/year. From the societal perspective, per patient total vaccination and illness costs with the intervention were $27.43 higher than control while gaining 0.00087 QALYs, costing $31,700/QALY gained. The intervention, extrapolated to the US population, could prevent 4.2 million cases, 87,489 hospitalizations, and 5,680 deaths due to influenza over 10 y in adults <65-years-old. In a probabilistic sensitivity analysis, the intervention was favored in 68.2% of model runs at a $50,000/QALY level and in 94.3% at $100,000/QALY. In a separate scenario analysis, the intervention became cost saving if influenza economic burden was >$2,099 per case (societal base case $846). Thus, the 4 Pillars Practice Transformation Program is an economically reasonable intervention to improve vaccination rates in adults <65-years-old, and could have a substantial public health impact.

Health Maintenance Deficits in a Fully Insured Population of Adolescents With Chronic Medical Conditions.

The current national monitoring of routine wellness care and vaccine uptake does not provide data on health maintenance among pediatric populations with chronic medical conditions. In this case-control study that analyzes wellness visits and vaccine uptake among adolescents, ages 16 to 18 years, we identified 938 without (controls) and 74 with (cases) 1 of 12 specific chronic medical conditions. The PPSV23 (23-valent pneumococcal polysaccharide vaccine) is recommended by the Advisory Committee on Immunization Practices for these 12 conditions and served as a measure of uptake for medically indicated vaccines. Our controls were twice as likely as cases to have a documented well visit in the past year, and there was a significantly higher proportion of controls than cases vaccinated with Tdap (tetanus toxoid, reduced diphtheria toxoid, acellular pertussis), MCV-4 (quadrivalent meningococcal conjugate), and HPV (human papillomavirus), all P < .05. More than 60% of cases failed to receive PPSV23. Adolescents with chronic medical conditions are at high risk of neglecting routine health maintenance.