The cost-effectiveness of alternative vaccination strategies for polyvalent meningococcal vaccines in Burkina Faso: A transmission dynamic modeling study.

BACKGROUND: The introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with several alternative vaccination policies in Burkina Faso. METHODS AND FINDINGS: We developed and calibrated a mathematical model of meningococcal transmission to project the disability-adjusted life years (DALYs) averted and costs associated with the current Base policy (serogroup A conjugate vaccination at 9 months, as part of the Expanded Program on Immunization [EPI], plus district-specific reactive vaccination campaigns using polyvalent meningococcal polysaccharide [PMP] vaccine in response to outbreaks) and three alternative policies: (1) Base Prime: novel polyvalent meningococcal conjugate (PMC) vaccine replaces the serogroup A conjugate in EPI and is also used in reactive campaigns; (2) Prevention 1: PMC used in EPI and in a nationwide catch-up campaign for 1-18-year-olds; and (3) Prevention 2: Prevention 1, except the nationwide campaign includes individuals up to 29 years old. Over a 30-year simulation period, Prevention 2 would avert 78% of the meningococcal cases (95% prediction interval: 63%-90%) expected under the Base policy if serogroup A is not replaced by remaining serogroups after elimination, and would avert 87% (77%-93%) of meningococcal cases if complete strain replacement occurs. Compared to the Base policy and at the PMC vaccine price of US$4 per dose, strategies that use PMC vaccine (i.e., Base Prime and Preventions 1 and 2) are expected to be cost saving if strain replacement occurs, and would cost US$51 (-US$236, US$490), US$188 (-US$97, US$626), and US$246 (-US$53, US$703) per DALY averted, respectively, if strain replacement does not occur. An important potential limitation of our study is the simplifying assumption that all circulating meningococcal serogroups can be aggregated into a single group; while this assumption is critical for model tractability, it would compromise the insights derived from our model if the effectiveness of the vaccine differs markedly between serogroups or if there are complex between-serogroup interactions that influence the frequency and magnitude of future meningitis epidemics. CONCLUSIONS: Our results suggest that a vaccination strategy that includes a catch-up nationwide immunization campaign in young adults with a PMC vaccine and the addition of this new vaccine into EPI is cost-effective and would avert a substantial portion of meningococcal cases expected under the current World Health Organization-recommended strategy of reactive vaccination. This analysis is limited to Burkina Faso and assumes that polyvalent vaccines offer equal protection against all meningococcal serogroups; further studies are needed to evaluate the robustness of this assumption and applicability for other countries in the meningitis belt.

Costs of Neisseria meningitidis Group A Disease and Economic Impact of Vaccination in Burkina Faso.

BACKGROUND: Five years since the successful introduction of MenAfriVac in a mass vaccination campaign targeting 1- to 29-year-olds in Burkina Faso, consideration must be given to the optimal strategies for sustaining population protection. This study aims to estimate the economic impact of a range of vaccination strategies in Burkina Faso. METHODS: We performed a cost-of-illness study, comparing different vaccination scenarios in terms of costs to both households and health systems over a 26-year time horizon. These scenarios are (1) reactive vaccination campaign (baseline comparator); (2) preventive vaccination campaign; (3) routine immunization at 9 months; and (4) a combination of routine and an initial catchup campaign of children under 5. Costs were estimated from a literature review, which included unpublished programmatic documents and peer-reviewed publications. The future disease burden for each vaccination strategy was predicted using a dynamic transmission model of group A Neisseria meningitidis. RESULTS: From 2010 to 2014, the total costs associated with the preventive campaign targeting 1- to 29-year-olds with MenAfriVac were similar to the estimated costs of the reactive vaccination strategy (approximately 10 million US dollars [USD]). Between 2015 and 2035, routine immunization with or without a catch-up campaign of 1- to 4-year-olds is cost saving compared with the reactive strategy, both with and without discounting costs and cases. Most of the savings are accrued from lower costs of case management and household costs resulting from a lower burden of disease. After the initial investment in the preventive strategy, 1 USD invested in the routine strategy saves an additional 1.3 USD compared to the reactive strategy. CONCLUSIONS: Prevention strategies using MenAfriVac will be significantly cost saving in Burkina Faso, both for the health system and for households, compared with the reactive strategy. This will protect households from catastrophic expenditures and increase the development capacity of the population.

Costs for households and community perception of meningitis epidemics in burkina faso.

Bacterial meningitis in the African meningitis belt remains 1 of the most serious threats to health. The perceptions regarding meningitis in local populations and the cost of illness for households are not well described. We conducted an anthropologic and economic study in Burkina Faso, in the heart of the meningitis belt. Respondents reported combining traditional and modern beliefs regarding disease etiology, which in turn influenced therapeutic care-seeking behavior. Households spent US $90 per meningitis case, or 34% of the annual gross domestic product per capita, and up to US $154 more when meningitis sequelae occurred. Much of this cost was attributable to direct medical expenses, which in theory are paid by the government. Preventive immunization against meningitis will overcome limitations imposed by traditional beliefs and contribute to poverty reduction goals.

Cost-Effectiveness of Alternative Uses of Polyvalent Meningococcal Vaccines in Niger: An Agent-Based Transmission Modeling Study.

Background. Despite the introduction of an effective serogroup A conjugate vaccine (MenAfriVac™), sporadic epidemics of other Neisseria meningitidis serogroups remain a concern in Africa. Polyvalent meningococcal conjugate (PMC) vaccines may offer alternatives to current strategies that rely on routine infant vaccination with MenAfriVac plus, in the event of an epidemic, district-specific reactive campaigns using polyvalent meningococcal polysaccharide (PMP) vaccines. Methods. We developed an agent-based transmission model of N. meningitidis in Niger to compare the health effects and costs of current vaccination practice and 3 alternatives. Each alternative replaces MenAfriVac in the infant vaccination series with PMC and either replaces PMP with PMC for reactive campaigns or implements a one-time catch up campaign with PMC for children and young adults. Results. Over a 28-year period, replacement of MenAfriVac with PMC in the infant immunization series and of PMP in reactive campaigns would avert 63% of expected cases (95% prediction interval 49%-75%) if elimination of serogroup A is not followed by serogroup replacement. At a PMC price of $4/dose, this would cost $1412 ($81-$3510) per disability-adjusted life-year (DALY) averted. If serogroup replacement occurs, the cost-effectiveness of this strategy improves to $662 (cost-saving, $2473) per DALY averted. Sensitivity analyses accounting for incomplete laboratory confirmation suggest that a catch-up PMC campaign would also meet standard cost-effectiveness thresholds. Limitations. The assumption that polyvalent vaccines offer similar protection against all serogroups is simplifying. Conclusions. The use of PMC vaccines to replace MenAfriVac in routine infant immunization and in district-specific reactive campaigns would have important health benefits and is likely to be cost-effective in Niger. An additional PMC catch-up campaign would also be cost-effective if we account for incomplete laboratory reporting.

The actual and potential costs of meningitis surveillance in the African meningitis belt: Results from Chad and Niger.

BACKGROUND: The introduction of serogroup A meningococcal conjugate vaccine in the African meningitis belt required strengthened surveillance to assess long-term vaccine impact. The costs of implementing this strengthening had not been assessed. METHODOLOGY: The ingredients approach was used to retrospectively determine bacterial meningitis surveillance costs in Chad and Niger in 2012. Resource use and unit cost data were collected through interviews with staff at health facilities, laboratories, government offices and international partners, and by reviewing financial reports. Sample costs were extrapolated to national level and costs of upgrading to desired standards were estimated. RESULTS: Case-based surveillance had been implemented in all 12 surveyed hospitals and 29 of 33 surveyed clinics in Niger, compared to six out of 21 clinics surveyed in Chad. Lumbar punctures were performed in 100% of hospitals and clinics in Niger, compared to 52% of the clinics in Chad. The total costs of meningitis surveillance were US$ 1,951,562 in Niger and US$ 338,056 in Chad, with costs per capita of US$ 0.12 and US$ 0.03, respectively. Laboratory investigation was the largest cost component per surveillance functions, comprising 51% of the total costs in Niger and 40% in Chad. Personnel resources comprised the biggest expense type: 37% of total costs in Niger and 26% in Chad. The estimated annual, incremental costs of upgrading current systems to desired standards were US$ 183,299 in Niger and US$ 605,912 in Chad, which are 9% and 143% of present costs, respectively. CONCLUSIONS: Niger's more robust meningitis surveillance system costs four times more per capita than the system in Chad. Since Chad spends less per capita, fewer activities are performed, which weakens detection and analysis of cases. Countries in the meningitis belt are diverse, and can use these results to assess local costs for adapting surveillance systems to monitor vaccine impact.

Costs of routine immunization and the introduction of new and underutilized vaccines in Ghana.

BACKGROUND: Limited knowledge exists on the full cost of routine immunization in Africa. Ghana was the first African country to simultaneously introduce rotavirus, pneumococcal and measles second-dose vaccines. Given their high price, it would be beneficial to Ghanaian health authorities to know the true cost of their introduction. METHODS: The economic costs of routine immunization for 2011 and the incremental costs of new vaccines were assessed as part of a multi-country study on costing and financing of routine immunization known as the Expanded Program on Immunization Costing (EPIC). Immunization delivery costs were evaluated at the local facility, district, regional, and central levels. Stratified random sampling was used for district and facility selection. We calculated the allocation of nationwide costs to the four health-system levels. RESULTS: The total aggregated national costs for routine immunization - including vaccine costs - equaled US$ 53.5 million during 2011 (including central, regional, and district costs); this equated to US$ 60.3 per fully immunized child (FIC) when counting vaccine costs, or US$ 48.1 without. National immunization program delivery costs were allocated as follows: local facility level, 85% of total national cost; district, 11%; central, 2% and regional, 2%. Salaried labor represented 61% of total costs, and vaccines represented 17%. For new vaccine introduction, programmatic start-up costs amounted to US$ 3.9 million, primarily due to salaried labor (66%). The mean facility-level cost per vaccine dose administered in a routine immunization program was US$ 5.1 (with a range of US$ 2.4-7.8 depending on facility characteristics) and US$ 3.7 for delivery costs. DISCUSSION: We identified a high cost per fully immunized child, mostly due to non-vaccine costs at the facility level, which indicates that immunization program financing - whether national or donor-driven - must take a broad viewpoint. This substantial variation in overall costs emphasizes the additional effort associated with reaching children in various settings.

Determinants of routine immunization costing in Benin and Ghana in 2011.

BACKGROUND: Existing tools to evaluate costs do not always capture the heterogeneity of costs at the facility level. This study seeks to address this issue through an analysis of determinants of health facility immunization costs. METHODS: A statistical analysis on facility routine delivery and vaccine costs was conducted using ordinary least squares regression. Explanatory variables included the number of doses administered; proportion of time spent by facility staff on immunization; average staff wage; whether the health facility had enough staff; presence of cold chain equipment; distance to a vaccine collection point; and, facility ownership. Data were drawn from representative samples of primary care facilities in Benin and Ghana (46 and 50 facilities, respectively) collected as part of the EPIC studies. RESULTS: Weighted average RI immunization facility cost was US$ 16,459 in Ghana and US$ 14,994 in Benin. The regression found total doses administered to be positively and significantly associated with facility cost in both countries. A 10% increase in doses resulted in a 4% increase in cost in Ghana, and a 7.5% increase in Benin. In Ghana, the proportion of immunization time, presence of cold chain, and sufficiency of staff were positively and significantly associated with total cost. In Benin, facility cost was negatively and significantly related to distance to the vaccine collection point. In the pooled sample, facilities in capital cities were associated with significantly higher costs. CONCLUSIONS: This study provides evidence on the importance of the level of scale in determining facility immunization cost, as well as the role of availability of health workers and time they spend on immunization in Ghana and Benin. This type of analysis can provide insights into the costs of scaling up immunization services, and can assist with development of more efficient immunization strategies.

Acceptability and Feasibility of Delivering Pentavalent Vaccines in a Compact, Prefilled, Autodisable Device in Vietnam and Senegal.

BACKGROUND: Prefilled syringes are the standard in developed countries but logistic and financial barriers prevent their widespread use in developing countries. The current study evaluated use of a compact, prefilled, autodisable device (CPAD) to deliver pentavalent vaccine by field actors in Senegal and Vietnam. METHODS: We conducted a logistic, programmatic, and anthropological study that included a) interviews of immunization staff at different health system levels and parents attending immunization sessions; b) observation of immunization sessions including CPAD use on oranges; and c) document review. RESULTS: Respondents perceived that the CPAD would improve safety by being non-reusable and preventing needle and vaccine exposure during preparation. Preparation was considered simple and may reduce immunization time for staff and caretakers. CPAD impact on cold storage requirements depended on the current pentavalent vaccine being used; in both countries, CPAD would reduce the weight and volume of materials and safety boxes thereby potentially improving outreach strategies and waste disposal. CPAD also would reduce stock outages by bundling vaccine and syringes and reduce wastage by using a non-breakable plastic presentation. Respondents also cited potential challenges including ability to distinguish between CPAD and other pharmaceuticals delivered via a similar mechanism (such as contraceptives), safety, and concerns related to design and ease of administration (such as activation, ease of delivery, and needle diameter and length). CONCLUSIONS: Compared to current pentavalent vaccine presentations in Vietnam and Senegal, CPAD technology will address some of the main barriers to vaccination, such as supply chain issues and safety concerns among health workers and families. Most of the challenges we identified can be addressed with health worker training, minor design modifications, and health messaging targeting parents and communities. Potentially the largest remaining barrier is the marginal increase in pentavalent cost--if any--from CPAD use, which we did not assess in our study.

A systematic literature review of missed opportunities for immunization in low- and middle-income countries.

BACKGROUND: Missed opportunities for immunization (MOIs) may contribute to low coverage in diverse settings, including developing countries. METHODS: We conducted a systematic literature review on MOIs among children and women of childbearing age from 1991 to the present in low- and middle-income countries. We searched multiple databases and the references of retrieved articles. Meta-analysis provided a pooled prevalence estimate and both univariate and multivariate meta-regression analysis was done to explore heterogeneity of results across studies. RESULTS: We found 61 data points from 45 studies involving 41,310 participants. Of the 45 studies, 41 involved children and 10 involved women. The pooled MOI prevalence was 32.2% (95% CI: 26.8-37.7) among children - with no change during the study period - and 46.9% (95% CI: 29.7-64.0%) among women of child-bearing age. The prevalence varied by region and study methodology but these two variables together accounted for only 12% of study heterogeneity. Among 352 identified reasons for MOIs, the most common categories were health care practices, false contraindications, logistic issues related to vaccines, and organizational limitations, which did not vary by time or geographic region. CONCLUSIONS: MOI prevalence was high in low- and middle-income settings but the large number of identified reasons precludes standardized solutions.

Budget process bottlenecks for immunization financing in the Democratic Republic of the Congo (DRC).

BACKGROUND: In Democratic Republic of the Congo (DRC), the availability of domestic resources for the immunization program is limited and relies mostly on external donor support. DRC has introduced a series of reforms to move the country toward performance-based management and program budgets. METHODS: The objectives of the study were to: (i) describe the budget process norm, (ii) analyze the budget process in practice and associated bottlenecks at each of its phases, and (iii) collect suggestions made by the actors involved to improve the situation. Quantitative and qualitative data were collected through: a review of published and gray literature, and individual interviews. RESULTS: Bottlenecks in the budget process and disbursement of funds for immunization are one of the causes of limited domestic resources for the program. Critical bottlenecks include: excessive use of off-budget procedures; limited human resources and capacity; lack of motivation; interference from ministries with the standard budget process; dependency toward the development partner's disbursements schedule; and lack of budget implementation tracking. Results show that the health sector's mobilization rate was 59% in 2011. For the credit line specific to immunization program activities, the mobilization rate for the national Expanded Program for Immunization (EPI) was 26% in 2011 and 43% for vaccines (2010). The main bottleneck for the EPI budget line (2011) and vaccine budget line (2011) occurs at the authorization phase. DISCUSSION: Budget process bottlenecks identified in the analysis lead to a low mobilization rate for the immunization program. The bottlenecks identified show that a poor flow of funds causes an insufficient percentage of already allocated resources to reach various health system levels.

EPIVAC International Conference on Financial Sustainability of Immunization Programs in sub-Saharan Africa, February 16-18, 2012, Ouidah, Benin.

The introduction of new vaccines with much higher prices than traditional vaccines results in increasing budgetary pressure on immunization programs in GAVI-eligible countries, increasing the need to ensure their financial sustainability. In this context, the third EPIVAC (Epidemiology and Vaccinology) technical conference was held from February 16 to 18, 2012 at the Regional Institute of Public Health in Ouidah, Benin. Managers of ministries of health and finance from 11 West African countries (GAVI eligible countries), as well as former EPIVAC students and European experts, shared their knowledge and best practices on immunization financing at district and country level. The conference concluded by stressing five major priorities for the financial sustainability of national immunization programs (NIPs) in GAVI-eligible countries. - Strengthen public financing by increasing resources and fiscal space, improving budget processes, increasing contribution of local governments and strengthen efficiency of budget spending. - Promote equitable community financing which was recognized as a significant and essential contribution to the continuity of EPI operations. - Widen private funding by exploring prospects offered by sponsorship through foundations dedicated to immunization and by corporate social responsibility programs. - Contain the potential crowding-out effect of GAVI co-financing and ensure that decisions on new vaccine introductions are evidence-based. - Seek out innovative financing mechanisms such as taxes on food products or a national solidarity fund.

Sustainability of National Immunization Programme (NIP) performance and financing following Global Alliance for Vaccines and Immunization (GAVI) support to the Democratic Republic of the Congo (DRC).

BACKGROUND: The Global Alliance for Vaccines and Immunization (GAVI) is a public-private global health partnership aiming to increase access to immunisation in poor countries. The Democratic Republic of the Congo (DRC) is the third largest recipient of GAVI funds in terms of cumulative disbursed support. We provided a comprehensive assessment of GAVI support and analysed trends in immunisation performance and financing in the DRC from 2002 to 2010. METHODS: The scope of the analysis includes GAVI's total financial support and the value of vaccines and syringes purchased by GAVI for the DRC from 2002 to 2010. Data were collected through a review of published and grey literature and interviews with key stakeholders in the DRC. We assessed the allocation and use of GAVI funds for each of GAVI's support areas, as well as trends in immunisation performance and financing. FINDINGS: DTP3 coverage increased from 2002 (38%) to 2007 (72%) but had decreased to a level below 70% in 2008 (68%) and 2010 (63%). The overall funding for vaccines increased from US$5.4 million in 2006 to US$30.5 million in 2010 (mostly from GAVI support for new vaccines). However, during the same period, the funding from national (government) and international (GAVI and other donors) sources for routine immunisation services (except vaccines) decreased from US$36.4 million to US$24.4 million. This drop in overall funding (33%) primarily affected surveillance, transport, and cold chain equipment. INTERPRETATION: GAVI support to DRC has enhanced significant progress in routine immunisation performance and financing during 2002-2010. Although progress has been partly sustained, the initial observed increase in DTP3 coverage and available funding for routine immunisation halted towards the end of the analysis period, coinciding with tetravalent and pentavalent vaccine introduction. These findings highlight the need for additional efforts to ensure the sustainability of routine immunization program performance and financing.

Costs and impact of meningitis epidemics for the public health system in Burkina Faso.

BACKGROUND: Epidemic meningococcal meningitis remains a serious health threat in the African meningitis belt. New meningococcal conjugate vaccines are relatively costly and their efficiency will depend on cost savings realized from no longer having to respond to epidemics. METHODS: We evaluated the cost and impacts to the public health system of the 2007 epidemic bacterial meningitis season in Burkina Faso through a survey at the different level of the health system. A micro-economic approach was used to evaluate direct medical and non medical costs for both the public health system and households, as well as indirect costs for households. RESULTS: The total national cost was 9.4 million US$ (0.69 US$ per capita). Health system costs were 7.1 million US$ (1.97% of annual national health spending), with 85.6% for reactive vaccination campaigns. The remaining 2.3 million US$ was borne by households of meningitis cases. The mean cost per person vaccinated was 1.45 US$; the mean cost of case management per meningitis case was 116.3 US$ when including household costs and 26.4 US$ when including only health sector costs. Meningitis epidemics disrupted all health services from national to operational levels with the main contributor being a large increase in medical consultations. CONCLUSIONS: Preventive meningococcal conjugate vaccines should contribute to more efficient use of funds dedicated to meningitis epidemics and limit the disruption of routine health services.