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

BackgroundThis 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.MethodsWe 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.ResultsThe 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.ConclusionsStatic 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 registryClinical Trial registry name and registration number: Not applicable.     

Modeling the cost-effectiveness of maternal acellular pertussis immunization (aP) in different socioeconomic settings: A dynamic transmission model of pertussis in three Brazilian states

ObjectivesUsing dynamic transmission models we evaluated the health and cost outcomes of adding acellular pertussis (aP) vaccination of pregnant women to infant vaccination in three Brazilian states that represent different socioeconomic conditions. The primary objective was to determine whether the same model structure could be used to represent pertussis disease dynamics in differing socioeconomic conditions.MethodsWe tested three model structures (SIR, SIRS, SIRSIs) to represent population-level transmission in three socio-demographically distinct Brazilian states: São Paulo, Paraná and Bahia. Two strategies were evaluated: infant wP vaccination alone versus maternal aP immunization plus infant wP vaccination. Model projections for 2014–2029 include outpatient and inpatient pertussis cases, pertussis deaths, years of life lost, disability-adjusted life-years (DALYs) lost, and costs (in 2014 USD) of maternal aP vaccination, infant vaccination, and pertussis medical treatment. Incremental cost per DALY averted is presented from the perspective of the Brazilian National Health System.ResultsBased on goodness-of-fit statistics, the SIRSIs model fit best, although it had only a modest improvement in statistical quantitative assessments relative to the SIRS model. For all three Brazilian states, maternal aP immunization led to higher costs but also saved infant lives and averted DALYs. The 2014 USD cost/DALY averted was $3068 in Sao Paulo, $2962 in Parana, and $2022 in Bahia. These results were robust in sensitivity analyses with the incremental cost-effectiveness ratios exceeding per capita gross regional product only when the probability that a pertussis case is reported was assumed higher than base case implying more overt cases and deaths and therefore more medical costs.ConclusionsThe same model structure fit all three states best, supporting the idea that the disease behaves similarly across different socioeconomic conditions. We also found that immunization of pregnant women with aP is cost-effective in diverse Brazilian states.     

Evaluating the cost-effectiveness of maternal pertussis immunization in low- and middle-income countries: A review of lessons learnt

This issue of Vaccine is devoted to papers from a research project that developed two types of simulation models, static and dynamic transmission, to evaluate the cost-effectiveness of maternal immunization to prevent pertussis in infants in low- and middle-income countries (LMICs). The research was conducted by a multinational team of investigators and funded by the Bill & Melinda Gates Foundation to gain an understanding of when and where maternal immunization might be a good public health investment for LMICs. Here we review the project’s central lessons for vaccine policy and research. Models require a lot of data. As most LMICs lack good data, the models were built using pertussis disease burden data from Brazil, a middle-income country with three long-established, independent information systems (disease surveillance, hospitalization, and mortality), on the hypothesis that the disease process is similar across countries. Values for key parameters, particularly infant mortality, infant vaccine coverage, and costs of vaccination and treatment, were then varied to represent other LMICs. The results show that coverage levels of infant whole cell pertussis (wP) vaccine are key to the cost-effectiveness of maternal pertussis immunization. In settings where infant wP coverage is below the threshold thought necessary to eliminate pertussis in the population, 90–95%, maternal immunization is cost-effective, even cost-saving. By contrast, it is very expensive in countries capable of maintaining infant vaccination in or above the threshold range. The research also suggests that, while static models may serve to explore an intervention’s cost-effectiveness initially, dynamic transmission models are essential for more accurate estimates. These findings can help guide policies toward maternal pertussis immunization, but also show that developing better data on neonatal pertussis mortality burden and infant vaccine coverage in LMICs, and on the duration of immunity of currently available pertussis vaccines, are key priorities to support better vaccine policy.     

Cost-effectiveness analysis of universal adult immunization with tetanus-diphtheria-acellular pertussis vaccine (Tdap) versus current practice in Brazil

BackgroundA pertussis outbreak occurred in Brazil from 2011 to 2014, despite high coverage of whole-cell pertussis containing vaccines in early childhood. Infants were the most affected. This study aimed to evaluate the cost-effectiveness of introducing universal adult vaccination with Tdap into the National Immunization Program in Brazil.MethodsEconomic evaluation using a dynamic model to compare two strategies: (1) universal vaccination with single dose of Tdap at 20 years of age and (2) current practice (only pregnant women pertussis vaccination). The health system perspective was adopted. Temporal horizon was 10 years. Discount rate of 5% was applied to costs and benefits. Vaccine effectiveness (VE) was obtained from a population-based observational study. Epidemiological, resource utilization and cost estimates were obtained from the Brazilian Health Information Systems. The primary outcome was cost per life year saved (LYS), based on life expectancy at birth in Brazil in 2015. Univariate and multivariate sensitivity analysis were performed.ResultsAdult vaccination with VE of 82.6% and coverage of 40%, at price of US$7.01 per dose, and assuming herd protection would avoid 167 infant deaths by pertussis, saving 12,325 years of life and costing a total of US$105495891.61, from the health system perspective. The universal immunization would result in ICER of US$8459.13. The results were highly sensitive to disease incidence.ConclusionsThe results suggest that universal adult vaccination with Tdap would not be a cost-effective intervention for preventing pertussis cases and deaths in infants in Brazil.     

Cost-effectiveness analysis of typhoid conjugate vaccines in five endemic low- and middle-income settings

BackgroundTyphoid fever remains endemic in low- and middle-income countries. Programmatic use of existing vaccines is limited, but upcoming typhoid conjugate vaccines (TCVs) could warrant wider use. We evaluated the cost-effectiveness of five TCV delivery strategies in three urban areas (Delhi and Kolkata, India and Nairobi, Kenya) and two rural settings (Lwak, Kenya and Dong Thap, Vietnam) with varying incidence.Methods and findingsWe evaluated routine infant vaccination with and without catch-up campaigns among older individuals. We used a dynamic model of typhoid transmission to simulate cases, hospitalizations, deaths, disability-adjusted life-years (DALY) lost, treatment and intervention costs. We estimated cost-effectiveness (in terms of cost in international dollars (I$) per DALY averted) from the healthcare payer perspective, and assessed how it was influenced by uncertain model parameters. Compared to no vaccination, routine infant vaccination at I$1/dose was cost-saving in Delhi and Dong Thap, “very cost-effective” in Kolkata and Nairobi, and “cost-effective” in Lwak according to World Health Organization thresholds. However, routine vaccination was not the optimal strategy compared to strategies that included a catch-up campaign, which yielded the highest probability of being cost-saving in Delhi and Dong Thap and were most likely to provide a return on investment above a willingness-to-pay threshold of I$1440 in Kolkata, I$2300 in Nairobi, and I$5360 in Lwak. Vaccine price impacted the optimal strategy, and the number of doses required and rate of hospitalization were the primary sources of uncertainty.ConclusionRoutine vaccination with TCV would be cost-effective in most settings, and additional one-time catch-up campaigns would also be economically justified.     

Cost-effectiveness analysis of universal maternal immunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in Brazil

BackgroundPertussis incidence has increased significantly in Brazil since 2011, despite high coverage of whole-cell pertussis containing vaccines in childhood. Infants <4 months are most affected. This study aimed to evaluate the cost-effectiveness of introducing universal maternal vaccination with tetanus-diphtheria-acellular pertussis vaccine (Tdap) into the National Immunization Program in Brazil.MethodsEconomic evaluation using a decision tree model comparing two strategies: (1) universal vaccination with one dose of Tdap in the third trimester of pregnancy and (2) current practice (no pertussis maternal vaccination), from the perspective of the health system and society. An annual cohort of newborns representing the number of vaccinated pregnant women were followed for one year. Vaccine efficacy were based on literature review. Epidemiological, healthcare resource utilization and cost estimates were based on local data retrieved from Brazilian Health Information Systems. Costs of epidemiological investigation and treatment of contacts of cases were included in the analysis. No discount rate was applied to costs and benefits, as the temporal horizon was one year. Primary outcome was cost per life year saved (LYS). Univariate and best- and worst-case scenarios sensitivity analysis were performed.ResultsMaternal vaccination of one annual cohort, with vaccine effectiveness of 78%, and vaccine cost of USD$12.39 per dose, would avoid 661 cases and 24 infant deaths of pertussis, save 1800 years of life and cost USD$28,942,808 and USD$29,002,947, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$15,608 and USD$15,590 per LYS, from the health system and societal perspective, respectively. In sensitivity analysis, the ICER was most sensitive to discounting of life years saved, variation in case-fatality, disease incidence, vaccine cost, and vaccine effectiveness.ConclusionThe results indicate that universal maternal immunization with Tdap is a cost-effective intervention for preventing pertussis cases and deaths in infants in Brazil.     

Economic modelling assessment of the HPV quadrivalent vaccine in Brazil: a dynamic individual-based approach

We examined the cost-effectiveness of the quadrivalent HPV vaccine for the pre-adolescent female population of Brazil. Using demographic, epidemiological and cancer data, we developed a dynamic individual-based model representing the natural history of HPV/cervical cancer as well as the impact of screening and vaccination programmes. Assuming the current screening strategies, we calculated the incremental cost-effectiveness ratio (ICER) for cohorts with and without vaccination taking into account different combinations of vaccination coverage (50%, 70%, 90%) and cost per vaccinated woman (US$25, US$55, US$125, US$556). The results varied from cost-saving (coverage 50% or 70% and cost per vaccinated woman US$25) to 5950 US$/QALY (coverage 90% and cost per vaccinated 556 US$). In a scenario in which a booster shot was needed after 10 years in order to secure lifelong protection, the ICER resulted in 13,576 US$/QALY. Considering the very cost-effective and cost-effective thresholds based on Brazil's GDP per capita, apart from the booster scenario which would be deemed cost-effective, all the other scenarios would be deemed very cost-effective. Both the cost per dose of vaccine and discount rate (5%) had an important impact on the results. Vaccination in addition to the current screening programme is likely to save years of life and, depending on the cost of vaccination, may even save resources. Price negotiations between governments and manufacturers will be paramount in determining that the vaccine not only represents good value for money, but is also affordable in middle-income countries like Brazil.     

Cost-effectiveness of a potential group B streptococcal vaccine program for pregnant women in South Africa

Background

In low- and middle-income countries neonatal infections are important causes of infant mortality. Group B streptococcus (GBS) is a major pathogen. A GBS polysaccharide–protein conjugate vaccine, the only option that has the potential to prevent both early- and late-onset GBS disease, has completed Phase II trials. Screening-based intrapartum antibiotic prophylaxis (IAP) for pregnant women, an effective strategy in high-income countries, is often not practical in these settings. Risk factor-based IAP (RFB-IAP) for women with risk factors at delivery has had limited success in preventing neonatal infection. We evaluated the cost and health impacts of maternal GBS vaccination in South Africa.

Methods and findings

We developed a decision-analytic model for an annual cohort of pregnant women that simulates the natural history of GBS disease in their infants. We compared four strategies: doing nothing, maternal GBS vaccination, RFB-IAP, and vaccination plus RFB-IAP. Assuming vaccine efficacy varies from 50% to 90% against covered serotypes and 75% of pregnant women are vaccinated, GBS vaccination alone prevents 30–54% of infant GBS cases compared to doing nothing. For vaccine prices between $10 and $30, and mid-range efficacy, its cost ranges from $676 to $2390 per disability-adjusted life-year (DALY) averted ($US 2010), compared to doing nothing. RFB-IAP alone, compared to doing nothing, prevents 10% of infant GBS cases at a cost of $240/DALY. Vaccine plus RFB-IAP prevents 48% of cases at a cost of $664–2128/DALY.

Conclusions

Vaccination would substantially reduce the burden of infant GBS disease in South Africa and would be very cost-effective by WHO guidelines. RFB-IAP is also very cost-effective, but prevents only 10% of cases. Vaccination plus RFB-IAP is more effective and more costly than vaccination alone, and consistently very cost-effective.     

Global routine vaccination coverage, 2010

The Expanded Program on Immunization was established by the World Health Organization (WHO) in 1974 to ensure universal access to routinely recommended childhood vaccines. Six vaccine-preventable diseases initially were targeted: tuberculosis, poliomyelitis, diphtheria, tetanus, pertussis, and measles. In 1974, fewer than 5% of the world's infants were fully immunized; by 2005, global coverage with the third dose of diphtheria-tetanus-pertussis (DTP) vaccine (DTP3) was 79%, but many children, especially those living in poorer countries, still were not being reached. That year, WHO and the United Nations Children's Fund (UNICEF) developed the Global Immunization Vision and Strategy (GIVS), with the aim of decreasing vaccine-preventable disease--related morbidity and mortality by improving national immunization programs. One goal of GIVS was for all countries to achieve 90% national DTP3 coverage by 2010. This report summarizes the status of vaccination coverage globally and regionally in 2010 and progress toward meeting the GIVS goal. In 2010, 130 (67%) countries had achieved 90% DTP3 coverage, and an estimated 85% of infants worldwide had received at least 3 doses of DTP vaccine. However, 19.3 million children were not fully vaccinated and remained at risk for diphtheria, tetanus, and pertussis and other vaccine-preventable causes of morbidity and mortality; approximately 50% of these children live in India, Nigeria, and the Democratic Republic of Congo. Despite the overall improvement in vaccination coverage during the past 37 years, routine vaccination programs need to be strengthened globally, especially in countries with the greatest numbers of unvaccinated children.     

Impact and cost-effectiveness of rotavirus vaccination in Bangladesh

IntroductionDiarrheal disease is a leading cause of child mortality globally, and rotavirus is responsible for more than a third of those deaths. Despite substantial decreases, the number of rotavirus deaths in children under five was 215,000 per year in 2013. Of these deaths, approximately 41% occurred in Asia and 3% of those in Bangladesh. While Bangladesh has yet to introduce rotavirus vaccination, the country applied for Gavi support and plans to introduce it in 2018. This analysis evaluates the impact and cost-effectiveness of rotavirus vaccination in Bangladesh and provides estimates of the costs of the vaccination program to help inform decision-makers and international partners.MethodsThis analysis used Pan American Health Organization’s TRIVAC model (version 2.0) to examine nationwide introduction of two-dose rotavirus vaccination in 2017, compared to no vaccination. Three mortality scenarios (low, high, and midpoint) were assessed. Benefits and costs were examined from the societal perspective over ten successive birth cohorts with a 3% discount rate. Model inputs were locally acquired and complemented by internationally validated estimates.ResultsOver ten years, rotavirus vaccination would prevent 4000 deaths, nearly 500,000 hospitalizations and 3 million outpatient visits in the base scenario. With a Gavi subsidy, cost/disability adjusted life year (DALY) ratios ranged from $58/DALY to $142/DALY averted. Without a Gavi subsidy and a vaccine price of $2.19 per dose, cost/DALY ratios ranged from $615/DALY to $1514/DALY averted.ConclusionThe discounted cost per DALY averted was less than the GDP per capita for nearly all scenarios considered, indicating that a routine rotavirus vaccination program is highly likely to be cost-effective. Even in a low mortality setting with no Gavi subsidy, rotavirus vaccination would be cost-effective. These estimates exclude the herd immunity benefits of vaccination, so represent a conservative estimate of the cost-effectiveness of rotavirus vaccination in Bangladesh.     

Pertussis in Latin America: Recent epidemiological data presented at the 2017 Global Pertussis Initiative meeting

The Global Pertussis Initiative (GPI) is an expert scientific forum that publishes consensus recommendations for pertussis monitoring, prevention, and treatment across many regions of the world. Here, we report on the regional 2017 GPI meeting on the Americas, focusing on Latin America. Information on current pertussis epidemiology, surveillance, vaccine strategies, diagnostic capabilities, disease awareness, and major local obstacles was presented by researchers from Argentina, Brazil, Colombia, Costa Rica, El Salvador, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela. Pertussis outbreaks have occurred during the last decade in the majority of participant countries and have been followed by improvements in surveillance. In the countries that introduced maternal immunization during pregnancy, a reduction in the infant case fatality rate has been detected. All countries need to maintain and improve pertussis surveillance to reach primary vaccination coverage >90%. Moreover, countries without maternal immunization programs should strongly consider them.     

Contribution of polio eradication initiative to strengthening routine immunization: Lessons learnt in the WHO African region

BackgroundImportant investments were made in countries for the polio eradication initiative. On 25 September 2015, a major milestone was achieved when Nigeria was removed from the list of polio-endemic countries. Routine Immunization, being a key pillar of polio eradication initiative needs to be strengthened to sustain the gains made in countries. For this, there is a huge potential on building on the use of polio infrastructure to contribute to RI strengthening.MethodsWe reviewed estimates of immunization coverage as reported by the countries to WHO and UNICEF for three vaccines: BCG, DTP3 (third dose of diphtheria-tetanus toxoid- pertussis), and the first dose of measles-containing vaccine (MCV1).We conducted a systematic review of best practices documents from eight countries which had significant polio eradication activities.ResultsImmunization programmes have improved significantly in the African Region. Regional coverage for DTP3 vaccine increased from 51% in 1996 to 77% in 2014. DTP3 coverage increased >3 folds in DRC (18–80%) and Nigeria from 21% to 66%; and >2 folds in Angola (41–87%), Chad (24–46%), and Togo (42–87%). Coverage for BCG and MCV1 increased in all countries. Of the 47 countries in the region, 18 (38%) achieved a national coverage for DTP3 ⩾90% for 2 years meeting the Global Vaccine Action (GVAP) target. A decrease was noted in the Ebola-affected countries i.e., Guinea, Liberia and Sierra Leone.ConclusionsPEI has been associated with increased spending on immunization and the related improvements, especially in the areas of micro planning, service delivery, program management and capacity building. Continued efforts are needed to mobilize international and domestic support to strengthen and sustain high-quality immunization services in African countries. Strengthening RI will in turn sustain the gains made to eradicate poliovirus in the region.     

Evaluation of the effectiveness of maternal immunization against pertussis in Alberta using agent-based modeling: A Canadian immunization research network study

IntroductionThe re-emergence of pertussis has occurred in the past two decades in developed countries. The highest morbidity and mortality is seen among infants. Vaccination in pregnancy is recommended to reduce the pertussis burden in infants.MethodsWe developed and validated an agent-based model to characterize pertussis epidemiology in Alberta. We computed programmatic effectiveness of pertussis vaccination during pregnancy (PVE) in relation to maternal vaccine coverage and pertussis disease reporting thresholds. We estimated the population preventable fraction (PFP) of different levels of maternal vaccine coverage against counterfactual ”no-vaccination” scenario. We modeled the effect of immunological blunting and measured protection through interruption of exposure pathways.ResultsPVE was inversely related to duration of passive immunity from maternal immunization across most simulations. In the scenario of 50% maternal vaccine coverage, PVE was 87% (95% quantiles 82–91%), with PFP of 44% (95% quantiles 41–45%). For monthly age intervals of 0–2, 2–4, 4–6 and 6–12, PVE ranged between 82 and 99%, and PFP ranged between 41 and 49%. At 75% maternal vaccine coverage, PVE and PFP were 90% (95% quantiles 86–92%) and 68% (95% quantiles 65–69%), respectively. At 50% maternal vaccine coverage and 10% blunting, PVE and PFP were 86% (95% quantiles 77–87%) and 43% (95% quantiles 39–44%), respectively, while at 50% blunting, the corresponding values of PVE and PFP were 76% (95% quantiles 70–81%) and 38% (95% quantiles 35–40%). PVE attributable to interruption of exposure pathways was 54–57%.ConclusionsOur model predicts significant reduction in future pertussis cases in infants due to maternal vaccination, with immunological blunting slightly moderating its effectiveness. The model is most sensitive to maternal vaccination coverage. The interruption of exposure pathways plays a role in the reduction of pertussis burden in infants due to maternal immunization. The effect of maternal immunization on population other than infants remains to be elucidated.     

Evaluating the impact of a continued maternal pertussis immunisation programme in England: A modelling study and cost-effectiveness analysis

IntroductionAn unexpected resurgence of pertussis cases and infant deaths was observed in some countries that had switched to acellular pertussis vaccines in the primary immunisation schedule. In response to the outbreaks, maternal pertussis vaccination programmes in pregnant women have been adopted worldwide, including the USA in 2011 and the UK in 2012. Following the success of the programme in England, we evaluated the health and economic impact of stopping versus continuing the maternal pertussis immunisation to inform public health policy making.MethodsWe used a mathematical model to estimate the number of infant hospitalisations and deaths related to pertussis in England over 2019–2038. Losses in quality-adjusted life years, QALYs, were considered for infants (aged 0–2 months) who survived or died from pertussis, bereaved parents (of infants who died from pertussis), and women with pertussis (aged 20–44 years). Direct medical costs to the National Health Service included infant hospitalisations, maternal vaccinations, and disease in women. Costs and QALYs were discounted at 3.5%. Changes in the incremental cost-effectiveness ratio, ICER, were explored in sensitivity analyses.ResultsThe model supports continuing the maternal pertussis immunisation programme as a cost-effective intervention at an ICER of £14,500/QALY (2.5% and 97.5%-quantile: £7,300/QALY to £32,400/QALY). Stopping versus continuing the maternal programme results in an estimated mean of 972 (range 582 to 1489) versus 308 (184 to 471) infant hospitalisations annually. Results were most sensitive to the number of hospitalisations and deaths when stopping the maternal programme. At a cost-effectiveness threshold of £30,000/QALY, the probability of the maternal programme being cost-effective was 96.2%.ConclusionOur findings support continuing the maternal pertussis vaccination programme as otherwise higher levels of disease activity and infant mortality are expected to return. These results have led policy makers to decide to continue the maternal programme in the UK routine immunisation schedule.     

Global economic evaluations of rotavirus vaccines: A systematic review

Introduction: World Health Organization (WHO) recommends Rotavirus vaccines to prevent and control rotavirus infections. Economic evaluations (EE) have been considered to support decision making of national policy. Summarizing global experience of the economic value of rotavirus vaccines is crucial in order to encourage global WHO recommendations for vaccine uptake. Therefore, a systematic review of economic evaluations of rotavirus vaccine was conducted.Methods: We searched Medline, Embase, NHS EED, EconLit, CEA Registry, SciELO, LILACS, CABI-Global Health Database, Popline, World Bank - e-Library, and WHOLIS. Full economic evaluations studies, published from inception to November 2015, evaluating Rotavirus vaccines preventing Rotavirus infections were included. The methods, assumptions, results and conclusions of the included studies were extracted and appraised using WHO guide for standardization of EE of immunization programs.Results: 104 relevant studies were included. The majority of studies were conducted in high-income countries. Cost-utility analysis was mostly reported in many studies using incremental cost-effectiveness ratio per DALY averted or QALY gained. Incremental cost per QALY gained was used in many studies from high-income countries. Mass routine vaccination against rotavirus provided the ICERs ranging from cost-saving to highly cost-effective in comparison to no vaccination among low-income countries. Among middle-income countries, vaccination offered the ICERs ranging from cost-saving to cost-effective. Due to low- or no subsidized price of rotavirus vaccines from external funders, being not cost-effective was reported in some high-income settings.Conclusion: Mass vaccination against rotavirus was generally found to be cost-effective, particularly in low- and middle-income settings according to the external subsidization of vaccine price. On the other hand, it may not be a cost-effective intervention at market price in some high-income settings. This systematic review provides supporting information to health policy-makers and health professionals when considering rotavirus vaccination as a national program.     

Reciprocal interference of maternal and infant immunization in protection against pertussis

BackgroundBecause of the current re-emergence of pertussis, vaccination during the 3rd trimester of pregnancy is recommended in several countries in order to protect neonates by placental transfer of maternal antibodies. Here, we examined the potential reciprocal interference of mother and infant vaccination in protection against pertussis in mice.MethodsFemale mice were vaccinated with acellular pertussis vaccines and protection against Bordetella pertussis challenge, as well as functional antibodies were measured in their offspring with or without re-vaccination.ResultsMaternal immunization protected the offspring against B. pertussis challenge, but protection waned quickly and was lost after vaccination of the infant mice with the same vaccine. Without affecting antibody titers, infant vaccination reduced the protective functions of maternally-derived antibodies, evidenced both in vitro and in vivo. Protection induced by infant vaccination was also affected by maternal antibodies. However, when mothers and infants were immunized with two different vaccines, no interference of infant vaccination on the protective effects of maternal antibodies was noted.ConclusionIt may be important to determine the functionality of antibodies to evaluate potential interference of maternal and infant vaccination in protection against pertussis.     

National vaccine coverage trends and funding in Latin America and the Caribbean

BackgroundFrom 2006 to 2011 nearly 174,000 deaths were prevented in Latin America and the Caribbean through vaccination of children under five, which is widely attributed to the Expanded Program on Immunization (EPI). Despite near global adoption of EPI recommendations, vaccination coverage shows substantial variation across world regions. Causes for low immunizations within regions are multifaceted and include vaccination program costs. To date, publications regarding vaccine coverage across Latin America and the Caribbean are not readily available. This study aimed to: (1) compare vaccine coverage trends across nations within the region; and (2) assess whether national immunization program expenditures are correlated with vaccine coverage.MethodsCoverage for nine vaccines were collected by nation using publicly available data from WHO. National immunization program expenditures for each country were collected from the World Bank Index. The proportion of countries achieving 90% coverage in the years 2013 and 2017 for each vaccine were compared. Pearson correlation coefficients were calculated to measure the relationship between financing variables and DTP3 coverage for 2017.ResultsIn 2017, fewer Latin American and Caribbean nations were able to achieve 90% vaccine coverage for five vaccines compared to 2013. Mostly weak to moderate positive relationships were found between national immunization program expenditures and DTP3 coverage for 2017. Excluding Haiti, a weak negative relationship was found between total government expenditure on vaccines per infant and DTP3 coverage for 2017. Countries across Latin America and the Caribbean were largely self-reliant in funding vaccine expenditures.ConclusionsFewer countries across Latin America and the Caribbean are currently achieving optimum national vaccine coverage and weak to moderate relationships between routine immunization and vaccine expenditures and coverage were observed. Additional factors contributing to national vaccine coverage should be concomitantly examined to implement strategies which optimize delivery of childhood immunizations.     

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

ObjectiveTo 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.MethodsDistricts 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.FindingsThe 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.ConclusionThere 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.     

The cost-effectiveness of introducing hepatitis B vaccine into infant immunization services in Mozambique

OBJECTIVE: To estimate the cost-effectiveness of introducing hepatitis B vaccine into routine infant immunization services in Mozambique, which took place in the year 2001. METHODS: A decision analytic model was used to estimate the impact of hepatitis B vaccination. This model was developed for the WHO to estimate the global burden of disease from hepatitis B. Cost data of vaccine delivery and medical treatment related to hepatitis B infection were collected for the analysis. FINDINGS: The introduction of hepatitis B vaccine has increased the annual budget for immunization services by approximately 56%. It is predicted that more than 4000 future deaths are averted annually by the intervention. In the base case scenario, the incremental costs per undiscounted deaths averted amount to US$436, and the costs per undiscounted DALY averted amount to US$36. Since the major impact of hepatitis B vaccination will not start to be evident for at least another 40 years (deaths from hepatitis B mainly occur between 40-60 years of age), the cost per DALY averted rises to US$47, when using a discount rate of 3% on health effects. We found that the monovalent hepatitis B vaccine was considerably more cost-effective than the hepatitis B vaccine in combination with DTP. INTERPRETATION: If policy makers value future health benefits equal to current benefits, the cost-effectiveness of infant hepatitis B vaccination is in the range of other primary health care interventions for which similar analysis has been undertaken.     

Health and economic outcomes of HPV 16,18 vaccination in 72 GAVI-eligible countries

The risk of dying from cervical cancer is disproportionately borne by women in developing countries. Two new vaccines are highly effective in preventing HPV 16,18 infection, responsible for approximately 70% of cervical cancer, in girls not previously infected. The GAVI Alliance (GAVI) provides technical assistance and financial support for immunization in the world's poorest countries. Using population-based and epidemiologic data for 72 GAVI-eligible countries we estimate averted cervical cancer cases and deaths, disability-adjusted years of life (DALYs) averted and incremental cost-effectiveness ratios (I$/DALY averted) associated with HPV 16,18 vaccination of young adolescent girls. In addition to vaccine coverage and efficacy, relative and absolute cancer reduction depended on underlying incidence, proportion attributable to HPV types 16 and 18, population age-structure and competing mortality. With 70% coverage, mean reduction in the lifetime risk of cancer is below 40% in some countries (e.g., Nigeria, Ghana) and above 50% in others (e.g., India, Uganda, Kenya). At I$10 per vaccinated girl (approximately $2.00 per dose assuming three doses, plus wastage, administration, program support) vaccination was cost-effective in all countries using a per capita GDP threshold; for 49 of 72 countries, the cost per DALY averted was less than I$100 and for 59 countries, it was less than I$200. Taking into account country-specific assumptions (per capita GNI, DPT3 coverage, percentage of girls who are enrolled in fifth grade) for the year of introduction, percent coverage achieved in the first year, and years to maximum coverage, a 10-year modeled scenario prevented the future deaths of approximately 2 million women vaccinated as adolescents. Despite favorable cost-effectiveness, assessment of financial costs raised concerns about affordability; as the cost per vaccinated girl was increased from I$10 to I$25 (approximately $2 to $5 per dose), the financial costs for the 10-year scenario increased from >US$ 900 million to US$ 2.25 billion. Provided high coverage of young adolescent girls is feasible, and vaccine costs are lowered, HPV 16,18 vaccination could be very cost-effective even in the poorest countries, and provide comparable value for resources to other new vaccines such as rotavirus.