End-user acceptability study of the nanopatch™; a microarray patch (MAP) for child immunization in low and middle-income countries.

A promising new delivery technology, the microarray patch (MAPs) consists of an array of small solid-coated or dissolvable needles, up to one mm in length, that administers a dry formulation of a vaccine or pharmaceutical. This study is not a real-life evaluation study but determines the anticipated acceptability of the Nanopatch™, a solid microarray patch device, in Benin, Nepal and Vietnam for vaccine delivery, and identifies factors that could improve the acceptability of the technology to increase measles immunization coverage. This study combined several evaluation methods, including simulation of vaccine administration on children and in-depth interviews with key stakeholders, healthcare workers, community health volunteers, caretakers, and community representatives. A total of 314 people participated in the study. The overall rate of total acceptability of the patch for child immunization was 92.7%. General opinions were very positive, providing clinical studies confirm that MAP administration is demonstrated to be painless, safe and effective for infectious disease prevention. The study participants were asked to consider the best strategy to introduce such vaccine delivery innovation. Firstly, delivery by skilled healthcare workers at the healthcare facilities will be preferred to establish the technology. Following this, administration by selected volunteers and outreach delivery may be possible, though under the supervision of skilled healthcare workers. This study's protocol received approval from the World Health Organization (WHO) Ethical Research Committee (ERC0002813) and the national IRB in Benin, Nepal and Vietnam.

Vaccine vial monitor availability and use in low- and middle-income countries: A systematic review.

INTRODUCTION: The vaccine vial monitor (VVM) registers cumulative heat exposure on vaccines over time. As low- and lower-middle-income countries transition beyond support from the Global Alliance for Vaccines and Immunization (Gavi), they will assume full responsibility for vaccine financing and procurement. It is unclear to what extent countries transitioning out of Gavi support will continue to include VVMs on their vaccines. This paper aims to systematically review evidence on VVM availability and use in low- and middle-income countries to document factors behind global access to and country demand for VVMs. Such results could help identify actions needed to ensure continued use of VVMs in countries that transition out of Gavi support. METHODS: We performed a systematic review of electronic databases, reference lists, and grey literature in English and French languages with publication dates from 2005 onwards. The studies included were analyzed for the following outcomes: (1) availability and deployment of VVM-labeled vaccines; (2) VVM practices and perceptions in the immunization system; (3) vaccine introduction and decision-making processes; (4) Gavi graduation and vaccine program sustainability. RESULTS: The study found that VVM availability and use was affected by multiple sourcing of vaccines and the extent to which VVM was included in the vaccine specification in the tendering documents when procuring vaccines. Knowledge about VVM and its impact on the EPI program was found to be high among health workers as well as decision-makers. However, the study also found that weak capacity in key national institutions such as NRA and NPA might impact on demand for VVM. As countries take decisions regarding the adoption of new vaccines, factors such as disease burden and vaccine price may assume greater importance than vaccine characteristics and presentation. Finally, the study found that countries rely largely on the advice and recommendations from technical partners such as WHO and PAHO. CONCLUSION: The study concludes that global access to and country demand for VVM are dependent on policy statements and recommendations about VVM by key policy institutions such as WHO and UNICEF. The study also concludes that despite Gavi-eligible countries having access to VVM-labeled vaccines, inclusion is often below 100%. Weak institutional capacity in key national agencies such as NRA and NPA seems to be a contributing factor, while other factors include the procurement of clear national policies on the inclusion of VVM on vaccines, along with the capacity to enforce the policy. Finally, the study concludes that knowledge about VVM and its impact on vaccine program efficiency, safety, and cost is critical for transitioning countries' continuous demand for VVM.

System redesign of the immunization supply chain: Experiences from Benin and Mozambique.

INTRODUCTION: Evidence suggests that immunization supply chains are becoming outdated and unable to deliver needed vaccines due to growing populations and new vaccine introductions. Redesigning a supply chain could result in meeting current demands. METHODS: The Ministries of Health in Benin in Mozambique recognized known barriers to the immunization supply chain and undertook a system redesign to address those barriers. Changes were made to introduce an informed push system while consolidating storage points, introducing transport loops, and increasing human resource capacity for distribution. Evaluations were completed in each country. RESULTS: Evaluation in each country indicated improved performance of the supply chain. The Effective Vaccine Management (EVM) assessment in Benin documented notable improvements in the distribution criteria of the tool, increasing from 40% to 100% at the district level. In Mozambique, results showed reduced stockouts at health facility level from 79% at baseline to less than 1% at endline. Coverage rates of DTP3 also increased from 68.9% to 92.8%. DISCUSSION: Benin and Mozambique are undertaking system redesign in order to respond to constraints identified in the vaccine supply chain. Results and learnings show improvements in supply chain performance and make a strong case for system redesign. These countries demonstrate the feasibility of system redesign for other countries considering how to address outdated supply chains.

Professional changes induced by a redesigned immunization supply chain in the Comé Health Zone, Benin.

At the end of 2013, the Government of Benin and Agence de Médecine Préventive (AMP) launched a demonstration project in Comé Health Zone (HZ) to optimize the vaccine supply chain. A key part of the demonstration project was the creation of an "informed push model" of vaccine distribution supported by a new logistician position at the health zone (district) level. At the conclusion of the demonstration project in 2015, the authors conducted an anthropological study consisting of semi-structured interviews with 62 participants to assess how the new model changed the professional identities, roles, responsibilities, and practices of personnel involved in vaccine management during and just after the demonstration project end in Comé HZ. The study found that health workers considered the logistician as a key player in enabling them to perform their public health mission, notably by improving knowledge and practices in vaccine management, providing supportive supervision, and improving the availability of vaccines and other supplies so that immunization sessions could occur more reliably and professionally within the communities they served. The demonstration project was widely accepted among study participants. The study was approved by the Cotonou Ethics Committee (CER-ISBA No. 56 dated 09/04/2015).

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.

The Benin experience: How computational modeling can assist major vaccine policy changes in low and middle income countries.

While scientific studies can show the need for vaccine policy or operations changes, translating scientific findings to action is a complex process that needs to be executed appropriately for change to occur. Our Benin experience provided key steps and lessons learned to help computational modeling inform and lead to major policy change. The key steps are: engagement of Ministry of Health, identifying in-country "champions," directed and efficient data collection, defining a finite set of realistic scenarios, making the study methodology transparent, presenting the results in a clear manner, and facilitating decision-making and advocacy. Generating scientific evidence is one component of policy change. Enabling change requires orchestration of a coordinated set of steps that heavily involve key stakeholders, earn their confidence, and provide them with relevant information. Our Benin EVM+CCEM+HERMES Process led to a decision to enact major changes and could serve as a template for similar approaches in other countries.

One size does not fit all: The impact of primary vaccine container size on vaccine distribution and delivery.

BACKGROUND: While the size and type of a vaccine container (i.e., primary container) can have many implications on the safety and convenience of a vaccination session, another important but potentially overlooked consideration is how the design of the primary container may affect the distribution of the vaccine, its resulting cost, and whether the vial is ultimately opened. METHODS: Using our HERMES software platform, we developed a simulation model of the World Health Organization Expanded Program on Immunization supply chain for the Republic of Benin and used the model to explore the effects of different primary containers for various vaccine antigens. RESULTS: Replacing vaccines with presentations containing fewer doses per vial reduced vaccine availability (proportion of people arriving for vaccines who are successfully immunized) by as much as 13% (from 73% at baseline) and raised logistics costs by up to $0.06 per dose administered (from $0.25 at baseline) due to increased bottlenecks, while reducing total costs by as much as $0.15 per dose administered (from $2.52 at baseline) due to lower open vial wastage. Primary containers with a greater number of doses per vial each improved vaccine availability by 19% and reduced logistics costs by $0.05 per dose administered, while reducing the total costs by up to $0.25 per dose administered. Changes in supply chain performance were more extreme in departments with greater constraints. Implementing a vial opening threshold reversed the direction of many of these effects. CONCLUSIONS: Our results show that one size may not fit all when choosing a primary vaccine container. Rather, the choice depends on characteristics of the vaccine, the vaccine supply chain, immunization session size, and goals of decision makers. In fact, the optimal vial size may vary among locations within a country. Simulation modeling can help identify tailored approaches to improve availability and efficiency.

The benefits of redesigning Benin's vaccine supply chain.

INTRODUCTION: New vaccine introductions have put strains on vaccine supply chains around the world. While increasing storage and transportation may be the most straightforward options, it is also important to consider what financial and operational benefits can be incurred. In 2012, suboptimal vaccine coverage and impending vaccine introductions prompted the Republic of Benin's Ministry of Health (MOH) to explore ways to improve their vaccine supply chain. METHODS: Working alongside the Beninese MOH, we utilized our computational model, HERMES, to explore the impact on cost and vaccine availability of three possible options: (1) consolidating the Commune level to a Health Zone level, (2) removing the Commune level completely, and (3) removing the Commune level and expanding to 12 Department Stores. We also analyzed the impact of adding shipping loops during delivery. RESULTS: At baseline, new vaccine introductions without any changes to the current system increased the logistics cost per dose ($0.23 to $0.26) and dropped the vaccine availability to 71%. While implementing the Commune level removal scenario had the same capital costs as implementing the Health Zone scenario, the Health Zone scenario had lower operating costs. This increased to an overall cost savings of $504,255 when implementing shipping loops. DISCUSSION: The best redesign option proved to be the synergistic approach of converting to the Health Zone design and using shipping loops (serving ten Health Posts/loop). While a transition to either redesign or only adding shipping loops was beneficial, implementing a redesign option and shipping loops can yield both lower capital expenditures and operating costs.

A field based evaluation of adverse events following MenAfriVac® vaccine delivered in a controlled temperature chain (CTC) approach in Benin.

INTRODUCTION: An estimated one hundred million African meningitis belt residents have received MenAfriVac(®)meningococcal serogroup A conjugate vaccine. Since October 2012 the vaccine has been licensed for use in a controlled temperature chain (CTC) approach, at temperatures of up to 40°C for up to four days. The Benin Ministry of Health conducted a pilot evaluation in one of its 34 health districts to assess whether the CTC approach was associated with increased adverse events following immunisation (AEFIs). METHODES: We compared the occurrence of AEFIs during the 5 days following immunisation for 4 villages in the district using the CTC approach to 4 villages in another district using the traditional approach (vaccine kept at +2 to +8°C). Severe events resulting in hospitalisation or death of non-interviewed household members also were recorded. RESULTS: We included 1000 persons in the CTC and 999 in the non-CTC group. Only mild and transient AEFIs were noted in both groups, such as pain at injection site or fever. Compared to the non-CTC group, the CTC group had similar or lower rates of AEFIs and the occurrence of AEFIs in both groups was similar to that indicated in the vaccine package insert. No case of hospitalisation or death occurred among interviewed and non-interviewed household members. CONCLUSION: The CTC approach, as implemented in Benin, was not associated with an increased rate of adverse events in the five days following immunisation, either when compared to a concurrent non-CTC population or to previous studies.

Emergence of epidemic Neisseria meningitidis serogroup X meningitis in Togo and Burkina Faso.

Serogroup X meningococci (NmX) historically have caused sporadic and clustered meningitis cases in sub-Saharan Africa. To study recent NmX epidemiology, we analyzed data from population-based, sentinel and passive surveillance, and outbreak investigations of bacterial meningitis in Togo and Burkina Faso during 2006-2010. Cerebrospinal fluid specimens were analyzed by PCR. In Togo during 2006-2009, NmX accounted for 16% of the 702 confirmed bacterial meningitis cases. Kozah district experienced an NmX outbreak in March 2007 with an NmX seasonal cumulative incidence of 33/100,000. In Burkina Faso during 2007-2010, NmX accounted for 7% of the 778 confirmed bacterial meningitis cases, with an increase from 2009 to 2010 (4% to 35% of all confirmed cases, respectively). In 2010, NmX epidemics occurred in northern and central regions of Burkina Faso; the highest district cumulative incidence of NmX was estimated as 130/100,000 during March-April. Although limited to a few districts, we have documented NmX meningitis epidemics occurring with a seasonal incidence previously only reported in the meningitis belt for NmW135 and NmA, which argues for development of an NmX vaccine.

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.

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.