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.     

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

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

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.     

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.     

Using pneumococcal carriage studies to monitor vaccine impact in low- and middle-income countries

Pneumococcal disease is a leading cause of childhood mortality, globally. The pneumococcal conjugate vaccine (PCV) has been introduced to many countries worldwide. However there are few studies evaluating PCV impacts in low- and middle-income countries (LMIC) because measuring the impact of PCV on pneumococcal disease in LMICs is challenging. We review the role of pneumococcal carriage studies for the evaluation of PCVs in LMICs and discuss optimal methods for conducting these studies. Fifteen carriage studies from 13 LMICs quantified the effects of PCV on carriage, and identified replacement carriage serotypes in the post-PCV era. Ten studies reported on the indirect effects of PCV on carriage. Results can be used to inform cost-effectiveness evaluations, guide policy decisions on dosing and product, and monitor equity in program implementation. Critically, we highlight gaps in our understanding of serotype replacement disease in LMICs and identify priorities for research to address this gap.     

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.     

Effect of oral contraception on anemia in 12 low- and middle-income countries

Context

In low- and middle-income countries, anemia is a major public health issue in women of reproductive age for a series of factors including iron deficiency.

Enablers and inhibitors: A review of the situation regarding mHealth adoption in low- and middle-income countries

Objective

The objective of this review is to identify enabling and inhibiting factors for mHealth adoption in low resource settings, by giving emphasis on the stakeholders representing the caregiving side. Another objective of this study is to support implementation agencies (governmental and non-governmental) in designing scalable mHealth interventions.

Regulating health care in low- and middle-income countries: Broadening the policy response in resource constrained environments

Regulation is traditionally seen as the use of bureaucratic and administrative controls by government to correct market failure. Yet traditional methods such as licensing and certification frequently fail to control behaviour because of the limited resources available to government in low- and middle-income countries, and because of the powerful countervailing incentives that encourage deviant behaviour to continue. It is increasingly being realised, therefore, that goals of policy can sometimes be achieved more efficiently by involving other actors in the regulatory mechanism. In addition, a more flexible view of regulatory tools and strategies may enable governments, particularly in resource constrained environments, to utilise a much wider range of administrative controls and market enhancing incentives. The review suggests a wide range of tools that may be utilised to encourage better behaviour. These require that governments become aware of the need to reinforce controls with enabling incentives, utilise external standards where local measures are deemed inadequate and promote greater access to information on standards and services to consumers and providers.     

Cost-effectiveness and economic benefits of vaccines in low- and middle-income countries: A systematic review

Background

Public health interventions that prevent mortality and morbidity have greatly increased over the past decade. Immunization is one of these preventive interventions, with a potential to bring economic benefits beyond just health benefits. While vaccines are considered to be a cost-effective public health intervention, implementation has become increasingly challenging. As vaccine costs rise and competing priorities increase, economic evidence is likely to play an increasingly important role in vaccination decisions.

Methods

To assist policy decisions today and potential investments in the future, we provide a systematic review of the literature on the cost-effectiveness and economic benefits of vaccines in low- and middle-income countries from 2000 to 2010. The review identified 108 relevant articles from 51 countries spanning 23 vaccines from three major electronic databases (Pubmed, Embase and Econlit).

Results

Among the 44 articles that reported costs per disability-adjusted life year (DALY) averted, vaccines cost less than or equal to $100 per DALY averted in 23 articles (52%). Vaccines cost less than $500 per DALY averted in 34 articles (77%), and less than $1000 per DALY averted in 38 articles (86%) in one of the scenarios. 24 articles (22%) examined broad level economic benefits of vaccines such as greater future wage-earning capacity and cost savings from averting disease outbreaks. 60 articles (56%) gathered data from a primary source. There were little data on long-term and societal economic benefits such as morbidity-related productivity gains, averting catastrophic health expenditures, growth in gross domestic product (GDP), and economic implications of demographic changes resulting from vaccination.

Conclusions

This review documents the available evidence and shows that vaccination in low- and middle-income countries brings important economic benefits. The cost-effectiveness studies reviewed suggest to policy makers that vaccines are an efficient investment. This review further highlights key gaps in the available literature that would benefit from additional research, especially in the area of evaluating the broader economic benefits of vaccination in the developing world.     

Misunderstandings and ambiguities in strategic purchasing in low- and middle-income countries

Strategic purchasing is branded as an approach that is necessary for progress towards universal health coverage. While we agree that publicly purchased health services should respond to society's needs and patient expectations, and thus generally endorse strategic purchasing, here we would like to explore two emerging concerns within current discussions in low- and middle-income countries. First, there exists a great deal of misunderstanding and conceptual unclarity, within practitioner groups, around the concept of strategic purchasing and what instruments it incorporates. Second, there is a growing trend to regularly fuse strategic purchasing into a performance-based financing (PBF) discourse in ways that increasingly blur their distinctive properties and policy orientations, while perhaps too easily obfuscating potential tensions. We believe the discourse on strategic purchasing would benefit from better conceptual clarity by dissociating and prioritising its two objectives, namely: priority should be given to needs-based allocation of resources, while rewarding performance is a subsequent concern. We argue there is a need for a more thoroughgoing conceptual and empirical re-examination of strategic purchasing's priorities, its link with PBF, as well as for a wider evidence-base on what strategic purchasing tools exist and which are most appropriate for diverse contexts.     

Cost-effectiveness of next-generation vaccines: The case of pertussis

Despite steady vaccination coverage rates, pertussis incidence in the United States has continued to rise. This public health challenge has motivated calls for the development of a new vaccine with greater efficacy and duration of protection. Any next-generation vaccine would likely come at a higher cost, and must provide sufficient health benefits beyond those provided by the current vaccine in order to be deemed cost-effective. Using an age-structured transmission model of pertussis, we quantified the health and economic benefits of a next-generation vaccine that would enhance either the efficacy or duration of protection of the childhood series, the duration of the adult booster, or a combination. We developed a metric, the maximum cost-effective price increase (MCPI), to compare the potential value of such improvements. The MCPI estimates the per-dose price increase that would maintain the cost-effectiveness of pertussis vaccination. We evaluated the MCPI across a range of potential single and combined improvements to the pertussis vaccine. As an upper bound, we found that a next-generation vaccine which could achieve perfect efficacy for the childhood series would permit an MCPI of $18 per dose (95% CI: $12–$31). Pertussis vaccine improvements that extend the duration of protection to an average of 75 years would allow for an MCPI of $22 per dose for the childhood series (CI: $10–$33) or $12 for the adult booster (CI: $4–$18). Despite the short duration of the adult booster, improvements to the childhood series could be more valuable than improvements to the adult booster. Combining improvements in both efficacy and duration, a childhood series with perfect efficacy and average duration of 75 years would permit an MCPI of $39 per dose, the highest of any scenario evaluated. Our results highlight the utility of the MCPI metric in evaluating potential vaccines or other interventions when prices are unknown.     

Review of the epidemiological evidence for physical activity and health from low- and middle-income countries

Almost 80% of deaths from non-communicable diseases (NCDs) occur in low- and middle-income countries. Physical inactivity is a key risk factor for NCDs. Enhancing understanding of the scientific evidence linking physical activity and health in low- and middle-income countries is important for supporting national efforts to promote physical activity and reduce NCDs in these countries. A systematic review of three electronic databases was conducted in July 2013, including large population-based epidemiological studies with adult participants, conducted in low- and middle-income countries, and published in the past 30 years. Physical activity was consistently associated with a reduced risk of all-cause mortality, cardiovascular disease (CVD), diabetes and several types of cancer. Positive associations were also found between physical activity and body composition (including overweight and obesity), blood pressure, cholesterol, metabolic indices and bone mineral density. Overall, the results confirm that the epidemiological research into the health benefits of physical activity in low- and middle-income countries is consistent with previous research conducted in high-income countries. This summary of the available research can be used as an advocacy tool in low- and middle-income countries to support greater prominence of physical activity in NCD policies.     

Adolescent demand for contraception and family planning services in low- and middle-income countries: A systematic review

ABSTRACT

An estimated 23 million adolescent girls age 15–19 in low- and middle-income countries (LMICs) have an unmet need for contraception. Despite the recognised importance of expanding access to appropriate methods of contraceptives for adolescents in LMICs, the evidence base on their total demand for contraception is limited, and there is no consensus on how to measure this important phenomenon. The aim of this study was to review the published literature in order to better understand the level of adolescent demand for contraception in LMICs and to explore what demand-related indicators are being measured. A total of 1375 articles were identified and 18 met the inclusion criteria. Included studies reported findings from 29 LMICs, revealing high adolescent demand for contraception. The demand for contraception among adolescents and young women ranged from 22% among married adolescents in Azerbaijan to 98% in Peru. However, measures of this phenomenon were limited, with most studies only reporting current contraceptive use or unmet need. Most studies relied on cross-sectional data, and young, unmarried, and male adolescents were largely excluded. We make several recommendations for alternative approaches for a more comprehensive understanding of adolescent demand for contraception in LMICs.     

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.     

Sexual and reproductive health and rights of adolescent girls: Evidence from low- and middle-income countries

This paper reviews the evidence on sexual and reproductive health and rights (SRHR) of adolescent girls in low-income and middle-income countries (LMIC) in light of the policy and programme commitments made at the International Conference on Population and Development (ICPD), analyses progress since 1994, and maps challenges in and opportunities for protecting their health and human rights. Findings indicate that many countries have yet to make significant progress in delaying marriage and childbearing, reducing unintended childbearing, narrowing gender disparities that put girls at risk of poor SRH outcomes, expanding health awareness or enabling access to SRH services. While governments have reaffirmed many commitments, policy development and programme implementation fall far short of realising these commitments. Future success requires increased political will and engagement of young people in the formulation and implementation of policies and programmes, along with increased investments to deliver at scale comprehensive sexuality education, health services that are approachable and not judgemental, safe spaces programmes, especially for vulnerable girls, and programmes that engage families and communities. Stronger policy-making and programming also require expanding the evidence on adolescent health and rights in LMICs for both younger and older adolescents, boys and girls, and relating to a range of key health matters affecting adolescents.     

Impact of a maternal immunization program against pertussis in a developing country

BackgroundPertussis disease is a growing concern for developing countries. In Argentina, rates of illness and death peaked in 2011. More than 50% of fatalities due to pertussis occurred in infants younger than two months of age, too young for vaccination. In 2012, the government offered immunization with a vaccine containing Tdap to all pregnant women after 20 weeks of gestation with the intent of reducing morbidity and mortality in young infants.MethodsMaternal acellular pertussis vaccine impact on reducing infant disease burden was estimated based on data from the Argentinean Health Surveillance System. We divided Argentinean states in two groups experiencing high (>50) and low (⩽50) Tdap vaccine coverage and compared these two groups using a Bayesian structural time-series model. Low coverage regions were used as a control group, and the time series were compared before and after the implementation of the Tdap program.FindingsWe observed a relative reduction of 51% (95% CI [−67%, −35%]; p = 0.001) in pertussis cases in high coverage states in comparison with the low coverage areas. Analysis of infants between two and six months showed a 44% (95% CI [−66%, −24%]; p = 0.001) reduction in illness. Number of deaths was highest in 2011 with 76 fatalities, for an incidence rate of 2.9 per 100,000. Comparing with 2011, rates decreased by 87% to 10 subjects, or 0.9 per 100,000 in 2013.InterpretationWe show an age-dependent protective effect of maternal Tdap immunization in a developing country for infants younger than six months.     

Agriculture and musculoskeletal disorders in low- and middle-income countries

Objectives: To systematically explore and summarize the risk factors of work-related musculoskeletal disorders (WMSDs) among the agricultural workers in low- and middle-income countries (LMIC). In addition, to identify and analyze the methodological flaws in the reviewed studies.

Methods: A comprehensive electronic literature search was conducted using PubMed, Medline, SCOPUS, CINAHL, Science Direct, Embase, Wiley Online Library, Google Scholar, and Web of Science databases. Three-phased screening process was undertaken to eliminate irrelevant publications. Assessment of methodological quality was done using a standardized assessment tool.

Results: Eighteen cross-sectional studies were included in the narrative synthesis. Based on the median score of 38%, nine publications were classified as having higher methodological quality. Eight countries were represented in this review, mainly the South East Asia countries. Majority of the participants were rice farmers. Most common risk factors associated with WMSDs were physical factors (n = 10), followed by individual (n = 6) and psychosocial (n = 5) risk factors. A majority of the studies investigated the risk factors for spinal region. Several methodological weaknesses were noticed in the studies concerning outcome definition, assessment of potential confounders, generalizability, selection bias, information bias, and statistical analysis. Extensive heterogeneity across the studies prevented statistical pooling.

Conclusions: The common anatomical region evaluated was the spine and the most reported risk factors were physical risk factors. Future researches in the LMIC should focus on conducting longitudinal studies that could infer temporality. Researchers should give more attention in defining the study population, evaluating the exposure and outcome in an unbiased way, and in executing reliable statistical analysis.     

Application of a cost-effectiveness analysis of pathogen-specific vaccines against gastroenteritis to a military population in a developing country setting

Vaccine implementation planning in low- and middle-income countries (LMIC) often focuses on children without considering special adult populations. We adapted an economic model developed by the United States Department of Defense (DoD) to evaluate the cost-effectiveness of vaccine acquisition strategies for Campylobacter-, ETEC-, Shigella-, and norovirus-associated gastroenteritis. We compared implementation costs with current medical management in the Peruvian armed forces, a special population of low- and middle-income (LMIC) adults with a high incidence of infectious gastroenteritis. Pathogen-specific vaccine implementation resulted in calculated cost-effectiveness ratio (CER) per duty day lost averted (CER_DDL) of $13,741; $1,272; $301; and $803, and a CER per diarrhea day averted of $2,130; $215; $51; and $199 for Campylobacter, ETEC, Shigella, and norovirus, respectively. These estimates compare favorably to CER_DDL estimates from high-income military population and suggest that implementing vaccines gastroenteritis may be cost-effective in the Peruvian military population.