Boosting understanding of Lassa Fever virus epidemiology: Field testing a novel assay to identify past Lassa Fever virus infection in blood and oral fluids of survivors and unexposed controls in Sierra Leone.

BACKGROUND: Despite identification 50 years ago, the true burden of Lassa Fever (LF) across Africa remains undefined for reasons including research focus on hospitalised patients, lack of validated field-feasible tools which reliably identify past infection, and the fact that all assays require blood samples making large-scale surveys difficult. Designated a priority pathogen of epidemic potential requiring urgent research by the World Health Organisation, a better understanding of LF sero-epidemiology is essential to developing and evaluating new interventions including vaccines. We describe the first field testing of a novel species-neutral Double Antigen Binding Assay (DABA) designed to detect antibodies to LF in plasma and oral fluid. METHODOLOGY/PRINCIPAL FINDINGS: Paired plasma and oral fluid were collected in Sierra Leone from survivors discharged from Kenema Government Hospital Lassa Fever Unit between 1980 and 2018, and from controls recruited in Freetown in 2019. Epidemiological sensitivity and specificity of the DABA measured against historical diagnosis in survivors and self-declared non-exposed controls was 81.7% (95% CI 70.7%- 89.9%) and 83.3% (72.7%- 91.1%) respectively in plasma, and 71.8% (60.0%- 81.9%) and 83.3% (72.7%- 91.1%) respectively in oral fluid. Antibodies were identified in people infected up to 15 years and, in one case, 40 years previously. Participants found oral fluid collection easy and painless with 80% happy to give an oral fluid sample regularly. CONCLUSIONS/SIGNIFICANCE: Given the difficulties of assay validation in a resource-limited setting, including unexpected exposures and diagnostics of varying accuracy, the new assay performed well in both plasma and oral fluid. Sensitivity and specificity are expected to be higher when case/control ascertainment is more definitive and further work is planned to investigate this. Even at the performance levels achieved, the species-neutral DABA has the potential to facilitate the large-scale seroprevalence surveys needed to underpin essential developments in LF control, as well as support zoonotic investigations.

Utilizing Nurses to Staff an Ebola Vaccine Clinical Trial in Sierra Leone during the Ebola Outbreak.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Implementing a Multisite Clinical Trial in the Midst of an Ebola Outbreak: Lessons Learned From the Sierra Leone Trial to Introduce a Vaccine Against Ebola.

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV∆G-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18-24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at ≤-60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow-up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Changes in catastrophic health expenditure in post-conflict Sierra Leone: an Oaxaca-blinder decomposition analysis.

BACKGROUND: At the end of the eleven-year conflict in Sierra Leone, a wide range of policies were implemented to address both demand- and supply-side constraints within the healthcare system, which had collapsed during the conflict. This study examines the extent to which households' exposure to financial risks associated with seeking healthcare evolved in post-conflict Sierra Leone. METHOD: This study uses the 2003 and 2011 cross-sections of the Sierra Leone Integrated Household Survey to examine changes in catastrophic health expenditure between 2003 and 2011. An Oaxaca-Blinder decomposition approach is used to quantify the extent to which changes in catastrophic health expenditure are attributable to changes in the distribution of determinants (distributional effect) and to changes in the impact of these determinants on the probability of incurring catastrophic health expenditure (coefficient effect). RESULTS: The incidence of catastrophic health expenditure decreased significantly by 18% from approximately 50% in 2003 t0 32% in 2011. The decomposition analysis shows that this decrease represents net effects attributable to the distributional and coefficient effects of three determinants of catastrophic health expenditure - ill-health, the region in which households reside and the type of health facility used. A decrease in the incidence of ill-health and changes in the regional location of households contributed to a decrease in catastrophic health expenditure. The distributional effect of health facility types observed as an increase in the use of public health facilities, and a decrease in the use of services in facilities owned by non-governmental organizations (NGOs) also contributed to a decrease in the incidence of catastrophic health expenditure. However, the coefficient effect of public health facilities and NGO-owned facilities suggests that substantial exposure to financial risk remained for households utilizing both types of health facilities in 2011. CONCLUSION: The findings support the need to continue expanding current demand-side policies in Sierra Leone to reduce the financial risk of exposure to ill health.

Free health care for under-fives, expectant and recent mothers? Evaluating the impact of Sierra Leone's free health care initiative.

This study evaluates the impact of Sierra Leone's 2010 Free Health Care Initiative (FHCI). It uses two nationally representative surveys to identify the impact of the policy on utilisation of maternal care services by pregnant women and recent mothers as well as the impact on curative health care services and out-of-pocket payments for consultation and prescription in children under the age of 5 years. A Regression Discontinuity Design (RDD) is applied in the case of young children and a before-after estimation approach, adjusted for time trends in the case of expectant and recent mothers. Our results suggest that children affected by the FHCI have a lower probability of incurring any health expenditure in public, non-governmental and missionary health facilities. However, a proportion of eligible children are observed to incur some health expenditure in participating facilities with no impact of the policy on the level of out-of-pocket health expenditure. Similarly, no impact is observed with the utilisation of services in these facilities. Utilisation of informal care is observed to be higher among non-eligible children while in expectant and recent mothers, we find substantial but possibly transient increases in the use of key maternal health care services in public facilities following the implementation of the FHCI. The diminishing impact on utilisation mirrors experience in other countries that have implemented free health care initiatives and demonstrates the need for greater domestic and international efforts to ensure that resources are sufficient to meet increasing demand and monitor the long run impact of these policies.

A window of opportunity for reform in post-conflict settings? The case of Human Resources for Health policies in Sierra Leone, 2002-2012.

BACKGROUND: It is recognized that decisions taken in the early recovery period may affect the development of health systems. Additionally, some suggest that the immediate post-conflict period may allow for the opening of a political 'window of opportunity' for reform. For these reasons, it is useful to reflect on the policy space that exists in this period, by what it is shaped, how decisions are made, and what are their long-term implications. Examining the policy trajectory and its determinants can be helpful to explore the specific features of the post-conflict policy-making environment. With this aim, the study looks at the development of policies on human resources for health (HRH) in Sierra Leone over the decade after the conflict (2002-2012). METHODS: Multiple sources were used to collect qualitative data on the period between 2002 and 2012: a stakeholder mapping workshop, a document review and a series of key informant interviews. The analysis draws from political economy and policy analysis tools, focusing on the drivers of reform, the processes, the contextual features, and the actors and agendas. FINDINGS: Our findings identify three stages of policy-making. At first characterized by political uncertainty, incremental policies and stop-gap measures, the context substantially changed in 2009. The launch of the Free Health Care Initiative provided to be an instrumental event and catalyst for health system, and HRH, reform. However, after the launch of the initiative, the pace of HRH decision-making again slowed down. CONCLUSIONS: OUR STUDY IDENTIFIES THE KEY DRIVERS OF HRH POLICY TRAJECTORY IN SIERRA LEONE: (i) the political situation, at first uncertain and later on more defined; (ii) the availability of funding and the stances of agencies providing such funds; (iii) the sense of need for radical change - which is perhaps the only element related to the post-conflict setting. It also emerges that a 'windows of opportunity' for reform did not open in the immediate post-conflict, but rather 8 years later when the Free Health Care Initiative was announced, thus making it difficult to link it directly to the features of the post-conflict policy-making environment.