Interventions to increase the distribution of vaccines in Sub-Saharan Africa: a scoping review

Achieving universal access to immunization, as envisioned in the global vaccine action plan continues to be a challenge for many countries in Sub-Saharan Africa. Weak immunization supply chain (iSC) has widely been recognized as a key barrier, hindering progress towards vaccination targets in this region. These iSCs, which were designed in the 1980s, have become increasing fragile and are now considered outdated. The objective of this review was to assess the effectiveness of system redesign and outsourcing to improve outdated iSC systems in sub-Saharan Africa. We searched the following electronic databases from January 2007 to December 2017: Medline, EMBASE (Excerpta Medica Database), the Cochrane Library, Google Scholar, CINAHL (Cumulative Index to Nursing and Allied Health Literature), WHOLIS (World Health Organization Library Database), LILACS (Latin American and Caribbean Literature on Health Sciences) and contacted experts in the field. Our search strategy yielded 80 records and after assessment for eligibility, seven papers met the inclusion criteria. Five studies evaluated the experiences of system redesign in three countries (Nigeria, Benin and Mozambique), two assessed outsourcing vaccine logistics to the private sector in Nigeria and South Africa. According to these studies, system redesign improved vaccine availability at service delivery points and reduce the cost of distributing vaccines. Similarly, outsourcing vaccine logistics to the private sector reduced the cost of vaccines distribution and improve vaccine availability at service delivery points.


Introduction
Vaccination coverage in Africa has improved dramatically since the Expanded Program on Immunization (EPI) was established in 1976.
However, achieving universal access to immunization in this region, as envisioned in the global vaccine action plan (GVAP) continues to be a challenge for many countries [1]. In 2015, only 13% of countries in the region achieved the GVAP target of 80% coverage in every district or administrative equivalent with all EPI vaccines in their national programs, suggesting that the continent's progress toward global immunization goals is largely off-track [1]. Although several factors have been advanced for this failing, there is a growing recognition of the contribution of outdated immunization supply chain systems on missed opportunities for vaccination [2]. Indeed, these systems, which were designed in the late 1970s to manage fewer, less expensive and less bulky vaccines, are being confronted with several new realities [3]. Amongst these are the needs to handle a widening variety of new vaccines and immunization schedules, a greater diversity of service delivery strategies, an ever-expanding target population to vaccinate, and an increased cold chain infrastructure requirement [3]. Taken together, these factors have created significant storage and transport shortfalls at all levels, which ultimately hinder progress towards coverage and equity goals in the continent [4]. In 2016, only 19% of Gavi-supported countries in the region met with the 80% minimum threshold for the World Health Organization (WHO) recommendations for effective vaccine management (EVM) [2], representing a marginal improvement from 2010, where no country met the 80% bench mark across all nine EVM categories [5]. This marginal progress seems to indicate that adherence to many EVM policies, standards and quality management continues to be problematic in the region. Indeed, an earlier report has shown that over three in four African countries lacked adequate systems for proper vaccine handling, leading to recurrent stock outs, expired products, and stock damage during storage and transit, all of which contribute to missed opportunities for vaccination [2].
In 2014, for instance, 22% of African countries experienced district level stockouts, which interrupted immunization service delivery at facility level, leading to missed opportunities to vaccinate children [4].
Today, with few exceptions, immunization supply chains in this region faces chronic difficulties in providing uninterrupted availability of potent vaccines up to service delivery levels, and many governmentmanaged systems remain crippled by inefficiencies in vaccine storage, distribution, vaccine management and stock control [3]. The global vaccine community has long recognized that, overcoming these challenges will require a radical shift in the way immunization supply chain systems are designed, managed, resourced and supported [2].
In 2013 a task force, involving four core Alliance partners, namely the Gavi secretariat, WHO, UNICEF and the Bill & Melinda Gates Foundation, was established to lead the development of an immunization supply chain strategy that leverages core capabilities and strengths of each organization to support and influence meaningful and measurable improvements in national immunization supply chains [6]. Key focus areas included developing strategies, which can improve vaccine adequacy and availability at the last mile.
Many of these innovative strategies have been piloted in several countries, but little is known about their impact on various immunization outcomes. In this paper, we assessed the effectiveness of system redesign and outsourcing of vaccine logistics to the private to improve immunization outcomes in Sub-Saharan Africa.

Methods
Type of studies: all study designs, which provided information on routine iSC and vaccine logistics in Sub Saharan Africa, were eligible for inclusion. This included randomized controlled trials, controlled/uncontrolled before and after trials, interrupted time series, cross-sectional studies, cohorts, and case control studies.  Excel as a systematic tool to collect the relevant data for our study ( Table 2). Critical appraisal of all identified citations was done independently by two authors (MZV and CMAM) to establish the possible relevance of the articles for inclusion in the review.
Disagreements were resolved by consensus or by arbitration of a third review author (JME). We retrieved full text copies of the articles identified as potentially relevant either by one or both review authors.
Where appropriate, we contacted study authors for further information and clarification.

Current status of knowledge
Description of studies: out of the 81 papers (of which, 21 duplicates were removed), we pre-selected 60 based on their title and abstract. After reading full text, we excluded 53 papers because their content did not match our review goals. As shown in Figure 1, just seven studies met our inclusion criteria, two of which were conducted in Benin [7,8], two in Nigeria [9,10], one in Mozambique [11], one in both Benin and Mozambique [12] and one in South Africa [13].

Effects of interventions
System redesigned followed by Informed Push Model: the effects of system redesign was measured differently in different settings. In Benin, outcomes were assessed by comparing scores from EVM assessment conducted at baseline and endline [12]. Overall, EVM scores significantly improved between baseline and endline across all 9 criteria in Come district but improvements were more marked with focus criteria of the pilot [12]. Indeed, EVM scores for distribution rose from 40% to 100%, vaccine management practices increased from 58% to 98% and infrastructure from 55% to 94% [7]. Furthermore, the scores observed in Come district were significantly higher than those in the control district in all criteria, with unmatched differences in distribution (100% versus 32%), vaccine management (94% versus 63%) and maintenance (79% versus 6%). In addition, improved EVM scores were observed at the health facility level, and scores exceeded the recommended 80% for five of the eight criteria as opposed by none in the baseline study. Finally, facilities in Comé district significantly outperformed the control districts in all EVM criteria [12].
In Mozambique, outcomes other than EVM were used to measure the impact of the iSC redesign [12]. In the pilot province, DTP-3 coverage in children aged 12-23 months increased by nearly 24 points, rising from 68.9% at baseline to 92.8% at endline (OR 5.8, 95% CI 3.2-10.5) [12]. Drop-out rates between DTP-1 and DTP-3 plummeted by 8.2 points, falling from 12% at baseline to 3.8% at endline.
Furthermore, stockouts rates reduced from 79% at baseline to less than 1% at endline [12]. Over 96% of intervention facilities had a functional refrigerator one year after the pilot had ended. Overall, the improvements observed in the pilot provinces were superior to those in the control provinces [12].
In Nigeria, stock adequacy and stock-outs were the primary outcome measured during the pilot [10]. Overall, stock adequacy improved by 14 points, rising from 54% at baseline to 68% at endline [10]. In contrast, stock-out rates plummeted by 31 points, falling from 41% at baseline to 10% at endline [10]. Similar trends were observed in analysis restricted only to facilities that had cold chain equipment at the start of the intervention, with stock-outs decreasing from 40% to 13%, and stock adequacy increasing from 46% to 70% over the period [10]. In addition to the above improvements, the reviewed studies-including an anthropological study-unveiled other important benefits of redesigning outdate and failing iSC [8]. In pilot facilities, a dramatic improvement in the frequency of immunization services was observed across all sides [8]. This improvement was attributed to improved vaccine availability and staff time to care for patients. The latter has been linked to the relieve of facility staff from the burden of vaccine collection as well as the elimination of other risks that staff faced during vaccine collection-notably the risk of injuries from road traffic accidents [8]. Improvements in staff motivation and professional awareness emanating from trainings, supportive supervision, and improved work conditions were also noted [8].
Outsourcing vaccine logistics to the private sector: scores from EVM assessments were used to measure the outcome of the outsourcing arrangement in South Africa [13]. According to the authors, the overall EVM scores for the outsourced iSC segments covered exceeded the 80% as opposed to 63% in the segment managed "in-house" [13]. Although, the private provider outperformed the government run supply chain in 6 EVM dimension, the difference was mostly marked on the criteria for temperature monitoring, vaccine distribution, and vaccine logistics information systems. However, it is worth indicating that the government-run segment outperformed the private sector in two EVM dimensionssufficient cold chain storage capacity and compliance with vaccine management policies [13]. In Nigeria, stock-out rates and immunization coverage were used to measure impact of outsourcing in pilot health facilities [9]. In the pilot areas, the percentage of Page number not for citation purposes 5 facilities with vaccine stock-outs dropped from 43% to 0%. At the same time, immunization coverage in these facilities rose from 57% to 88% [9]. suggesting that iSC redesign was 17% more cost-effective than the program [12]. In addition, the cost per dose delivered was US$1.18

Cost of implementing the interventions
in the pilot province compared to US$1.50 in the control province, indicating that the pilot was 21% less expensive [12]. In Benin, the cost per dose administered decreased from US$0.14 at baseline to US$0.13 after eliminating the regional ISC tier. In Nigeria, the overall weighted average cost per delivery was US$29.8 [12]. The cost of outsourcing the vaccine delivery services following system redesign was initially US$15.1 (N5,462) per facility per month but this reduced by 15% to US$12.7 (N4,600) per facility per month as more health facilities were added [10]. The cost-efficiencies found in these pilots suggest that system redesign can improve supply chain performance while reducing overall logistic costs. However, it is noteworthy these may not reflect precise cost incurred in the pilots as several variables (e.g. variables in local salaries, operating cost and cost of goods) appeared not to have been included in the analysis [10]. This limitation highlights the need for further research into this area.

Conclusion
Although there is little published evidence on successful interventions to increase vaccines distribution in sub Saharan Africa, our review has identified success stories in few countries in the continent. Pilots in these countries suggest that system redesign and outsourcing vaccine logistics to a third party can improve vaccine availability, decrease stock outs and contribute to improvements in vaccination coverage.
These interventions were also associated with other indirect benefits such as improved staff motivation and professional awareness, emanating from trainings, supportive supervision, and improved working conditions. Furthermore, the cost-efficiencies found in these pilots suggest that these interventions can improve supply chain performance while reducing overall logistic costs. Despite these promises, there are apparently clear knowledge gaps, highlighting the need for more research in this important area that has been undermining progress towards universal vaccine coverage and equity goals.
What is known about this topic  Interventions to improve the availability of vaccines are commonly grouped into those targeting health services for delivery or supply; Page number not for citation purposes 6  The most recent review considered showed that much has to be done to improve availability of vaccines in Sub-Saharan Africa.

What this study adds
 There is insuficient evidence to support or refute the use of informed push model approach in improving vaccine availability at delivery points in Sub-Saharan Africa;  There is insuficient evidence to support or refute the use of outsourcing vaccine logistics to the private sector in Sub-Saharan Africa.

Competing interests
The authors declare no competing interests.

Authors' contributions
Marius