Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT).

INTRODUCTION: A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1ß has been developed as a point-of-care test-called the Genital InFlammation Test (GIFT)-for detecting genital inflammation associated with sexually transmitted infections (STIs) and/or bacterial vaginosis (BV) in women. In this paper, we describe the rationale and design for studies that will be conducted in South Africa, Zimbabwe and Madagascar to evaluate the performance of GIFT and how it could be integrated into routine care. METHODS AND ANALYSIS: We will conduct a prospective, multidisciplinary, multicentre, cross-sectional and observational clinical study comprising two distinct components: a biomedical ('diagnostic study') and a qualitative, modelling and economic ('an integration into care study') part. The diagnostic study aims to evaluate GIFT's performance in identifying asymptomatic women with discharge-causing STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG)) and BV. Study participants will be recruited from women attending research sites and family planning services. Several vaginal swabs will be collected for the evaluation of cytokine concentrations (ELISA), STIs (nucleic acid amplification tests), BV (Nugent score) and vaginal microbiome characteristics (16S rRNA gene sequencing). The first collected vaginal swab will be used for the GIFT assay which will be performed in parallel by a healthcare worker in the clinic near the participant, and by a technician in the laboratory. The integration into care study aims to explore how GIFT could be integrated into routine care. Four activities will be conducted: user experiences and/or perceptions of the GIFT device involving qualitative focus group discussions and in-depth interviews with key stakeholders; discrete choice experiments; development of a decision tree classification algorithm; and economic evaluation of defined management algorithms. ETHICS AND DISSEMINATION: Findings will be reported to participants, collaborators and local government for the three sites, presented at national and international conferences, and disseminated in peer-reviewed publications.The protocol and all study documents such as informed consent forms were reviewed and approved by the University of Cape Town Human Research Ethics Committee (HREC reference 366/2022), Medical Research Council of Zimbabwe (MRCZ/A/2966), Comité d'Ethique pour la Recherche Biomédicale de Madagascar (N° 143 MNSAP/SG/AMM/CERBM) and the London School of Hygiene and Tropical Medicine ethics committee (LSHTM reference 28046).Before the start, this study was submitted to the Clinicaltrials.gov public registry (NCT05723484). TRIAL REGISTRATION NUMBER: NCT05723484.

Examining multiple funding flows to public healthcare providers in low- and middle-income countries - results from case studies in Burkina Faso, Kenya, Morocco, Nigeria, Tunisia and Vietnam.

Provider payment methods are traditionally examined by appraising the incentive signals inherent in individual payment mechanisms. However, mixed payment arrangements, which result in multiple funding flows from purchasers to providers, could be better understood by applying a systems approach that assesses the combined effects of multiple payment streams on healthcare providers. Guided by the framework developed by Barasa et al. (2021) (Barasa E, Mathauer I, Kabia E et al. 2021. How do healthcare providers respond to multiple funding flows? A conceptual framework and options to align them. Health Policy and Planning  36: 861-8.), this paper synthesizes the findings from six country case studies that examined multiple funding flows and describes the potential effect of multiple payment streams on healthcare provider behaviour in low- and middle-income countries. The qualitative findings from this study reveal the extent of undesirable provider behaviour occurring due to the receipt of multiple funding flows and explain how certain characteristics of funding flows can drive the occurrence of undesirable behaviours. Service and resource shifting occurred in most of the study countries; however, the occurrence of cost shifting was less evident. The perceived adequacy of payment rates was found to be the strongest driver of provider behaviour in the countries examined. The study results indicate that undesirable provider behaviours can have negative impacts on efficiency, equity and quality in healthcare service provision. Further empirical studies are required to add to the evidence on this link. In addition, future research could explore how governance arrangements can be used to coordinate multiple funding flows, mitigate unfavourable consequences and identify issues associated with the implementation of relevant governance measures.

Financial issues in times of a COVID-19 pandemic in a tertiary hospital in Mali.

BACKGROUND: This study examines how the functioning of healthcare providers during the COVID-19 pandemic was affected by the government financing response, which was shaped by existing healthcare financing systems. METHODS: The study applied a single case study design at a tertiary hospital in Bamako during the 1st and 2nd waves of the COVID-19 pandemic. Data were gathered through 51 in-depth interviews with hospital staff, participatory observation, and reviewing media articles and hospital financial records. RESULTS: The study revealed the disruptions experienced by hospital managers, human resources for health and patients in Mali during the early stages of the pandemic. While the government aimed to support universal access to COVID-19-related services, efforts were undermined by issues associated with complex public financing management procedures. The hospital experienced long delays in transferring government funds. The hospital suffered a decrease in revenue during the early stages of the pandemic. Government budgets were not effectively used because of complex, non-agile procedures that could not adapt to the emergency. The challenges faced by the hospitals led to the delays in the staff payments of salaries and promised bonuses, which created potential for unfair treatment of patients. Excluding some COVID-19 related items from the government funded benefit package created a financial burden on people receiving services. The managerial challenges experienced in the study hospital during the first wave continued in the second wave. CONCLUSIONS: Pre-existent issues in healthcare financing and governance constrained the effective management of COVID-19-related services and created confusion at the front line of healthcare service delivery.

Factors for Consideration When Setting Prices for Private Healthcare Providers Operating in Public Systems: A Comparison of France and Japan.

Background: Most publicly-funded health systems purchase healthcare from private providers, but the optimal purchasing arrangements between public purchasers and private healthcare providers are yet to be determined. Objective: This study compares the healthcare purchasing arrangements made with private providers in 2 social health insurance (SHI)-based systems to identify factors that influence the prices paid for private healthcare service provision. Results: France and Japan use different approaches to determine the payment arrangements with public and private providers. The presence of for-profit healthcare providers in the French health system explains the different payment rates for public and private healthcare providers in that country. In both France and Japan, in addition to payment rates, several policy tools are used to assure the provision of public good services and the availability of necessary healthcare for all, which public providers are required to deliver but private providers can choose to deliver. Conclusion: This study highlights the importance of considering the profit-making status of the private healthcare providers operating in the healthcare market, and clarity in the roles and responsibilities of the public, for-profit and not-for-profit providers when determining healthcare purchasing arrangements. Regulatory policy instruments, used alongside payment rates, are essential to influence efficiency, equity, and quality in mixed (public-private) health systems.

How do healthcare providers respond to multiple funding flows? A conceptual framework and options to align them.

Provider payment methods are a key health policy lever because they influence healthcare provider behaviour and affect health system objectives, such as efficiency, equity, financial protection and quality. Previous research focused on analysing individual provider payment methods in isolation, or on the actions of individual purchasers. However, purchasers typically use a mix of provider payment methods to pay healthcare providers and most health systems are fragmented with multiple purchasers. From a health provider perspective, these different payments are experienced as multiple funding flows which together send a complex set of signals about where they should focus their effort. In this article, we argue that there is a need to expand the analysis of provider payment methods to include an analysis of the interactions of multiple funding flows and the combined effect of their incentives on the provision of healthcare services. The purpose of the article is to highlight the importance of multiple funding flows to health facilities and present a conceptual framework to guide their analysis. The framework hypothesizes that when healthcare providers receive multiple funding flows, they may find certain funding flows more favourable than others based on how these funding flows compare to each other on a range of attributes. This creates a set of incentives, and consequently, healthcare providers may alter their behaviour in three ways: resource shifting, service shifting and cost shifting. We describe these behaviours and how they may affect health system objectives. Our analysis underlines the need to align the incentives generated by multiple funding flows. To achieve this, we propose three policy strategies that relate to the governance of healthcare purchasing: reducing the fragmentation of health financing arrangements to decrease the number of multiple purchaser arrangements and funding flows; harmonizing signals from multiple funding flows; and constraining providers from responding to undesirable incentives.

Examining purchasing reforms towards universal health coverage by the National Hospital Insurance Fund in Kenya.

BACKGROUND: Kenya has prioritized the attainment of universal health coverage (UHC) through the expansion of health insurance coverage by the National Hospital Insurance Fund (NHIF). In 2015, the NHIF introduced reforms in premium contribution rates, benefit packages, and provider payment methods. We examined the influence of these reforms on NHIF's purchasing practices and their implications for strategic purchasing and health system goals of equity, efficiency and quality. METHODS: We conducted an embedded case study with the NHIF as the case and the reforms as embedded units of analysis. We collected data at the national level and in two purposively selected counties through 41 in-depth interviews with health financing stakeholders, facility managers and frontline providers; 4 focus group discussions with 51 NHIF members; and, document reviews. We analysed the data using a Framework approach. RESULTS: The new NHIF reforms were characterized by weak purchasing actions. Firstly, the new premium contribution rates were inadequately communicated and unaffordable for certain citizen groups. Secondly, while the new benefit packages were reported to be based on service needs, preferences and values of the population, they were inadequately communicated and unequally distributed across different citizen groups. In addition, the presence of service delivery infrastructure gaps in public healthcare facilities and the pro-urban and pro-private distribution of contracted health facilities compromised delivery of, and access to, these new services. Lastly, the new provider payment methods and rates were considered inadequate, with delayed payments and weak links to financial accountability mechanisms which compromised their ability to incentivize equity, efficiency and quality of healthcare delivery. CONCLUSION: While NHIF sought to expand population and service coverage and reduce out-of-pocket payments with the new reforms, weaknesses in the reforms' design and implementation limited NHIF's purchasing actions with negative implications for the health system goals of equity, efficiency and quality. For the reforms to accelerate the country's progress towards UHC, policy makers at the NHIF and, national and county government should make deliberate efforts to align the design and implementation of such reforms with strategic purchasing actions that are aimed at improving health system goals.

Payment Arrangements for Private Healthcare Purchasing Under Publicly Funded Systems in Low- and Middle-Income Countries: Issues and Implications.

This paper examines private healthcare purchasing under publicly financed health systems in low- and middle-income countries (LMICs) to argue that the payment methods and rates applied to private and public health providers need careful attention to ensure equity, efficiency and quality in healthcare service provision. Specifically, public purchasers should develop a clear mechanism to establish justifiable payment rates for the purchase of private health services under publicly funded systems, using cost information and appropriate engagement with private health providers. In order to determine the validity of payment arrangements with private providers, clarification of the shared roles and responsibilities of public and private healthcare providers is required, including specification of types of services to be delivered by public and private providers, and the services for which public providers receive government budget and salaries above payments for other publicly funded services. In addition, carefully designed payment methods should include incentives to encourage healthcare providers to deliver efficient, equitable and quality health services, which requires consideration of how the healthcare purchasing market is structured. Furthermore, governments should establish sound legal frameworks to ensure that public purchasers establish 'strategic' payment arrangements with healthcare providers and that healthcare providers are able to respond to the incentives sent by the payment arrangements. To deepen understanding of public purchasing of private healthcare services and gain further insight in the LMIC context, in-depth empirical studies are necessary on the payment methods and rates used by public purchasers in a range of settings and the implications of payment arrangements on efficiency, equity and quality in healthcare service provision.

Strategic Purchasing: The Neglected Health Financing Function for Pursuing Universal Health Coverage in Low-and Middle-Income Countries Comment on "What's Needed to Develop Strategic Purchasing in Healthcare? Policy Lessons from a Realist Review".

Sanderson et al's realist review of strategic purchasing identifies insights from two strands of theory: the economics of organisation and inter-organisational relationships. Our findings from a programme of research conducted by the RESYST (Resilient and Responsive Health Systems) consortium in seven countries echo these results, and add to them the crucial area of organisational capacity to implement complex reforms. We identify key areas for policy development. These are the need for: (1) a policy design with clearly delineated responsibilities; (2) a task network of organisations to engage in the broad set of functions needed; (3) more effective means of engaging with populations; (4) a range of technical and management capacities; and (5) an awareness of the multiple agency relationships that are created by the broader financing environment and the provider incentives generated by multiple financing flows.

For more than money: willingness of health professionals to stay in remote Senegal.

BACKGROUND: Poor distribution of already inadequate numbers of health professionals seriously constrains equitable access to health services in low- and middle-income countries. The Senegalese Government is currently developing policy to encourage health professionals to remain in areas defined as 'difficult'. Understanding health professional's preferences is crucial for this policy development. METHODS: Working with the Senegalese Government, a choice experiment (CE) was developed to elicit the job preferences of physicians and non-physicians. Attributes were defined using a novel mixed-methods approach, combining interviews and best-worst scaling (Case 1). Six attributes were categorised as 'individual (extrinsic) incentive' attributes ('type of contract', 'provision of training opportunities', 'provision of an allowance' and 'provision of accommodation') or 'functioning health system' attributes ('availability of basic equipment in health facilities' and 'provision of supportive supervision by health administrators'). Using face-to-face interviews, the CE was administered to 55 physicians (3909 observations) and 246 non-physicians (17 961 observations) randomly selected from those working in eight 'difficult' regions in Senegal. Conditional logit was used to analyse responses. This is the first CE to both explore the impact of contract type on rural retention and to estimate value of attributes in terms of willingness to stay (WTS) in current rural post. RESULTS: For both physicians and non-physicians, a permanent contract is the most important determinant of rural job retention, followed by availability of equipment and provision of training opportunities. Retention probabilities suggest that policy reform affecting only a single attribute is unlikely to encourage health professionals to remain in 'difficult' regions. The relative importance of an allowance is low; however, the level of such financial incentives requires further investigation. CONCLUSION: Contract type is a key factor impacting on retention. This has led the Senegalese Health Ministry to introduce a new rural assignment policy that recruits permanent staff from the pool of annually contracted healthcare professionals on the condition that they take up rural posts. While this is a useful policy development, further efforts to retain rural health workers, considering both personal incentives and the functioning of health systems, are necessary to ensure health worker numbers are adequate to meet the needs of rural communities.

Do beneficiaries' views matter in healthcare purchasing decisions? Experiences from the Nigerian tax-funded health system and the formal sector social health insurance program of the National Health Insurance Scheme.

BACKGROUND: Purchasing is a health financing function that involves the transfer of pooled resources to providers on behalf of a covered population. Little attention has been paid to the extent to which the views of that population  are reflected in purchasing decisions. This article explores how purchasers in two financing mechanisms: the Formal Sector Social Health Insurance Programme (FSSHIP) operating under the Nigerian National Health Insurance Scheme (NHIS), and the tax-funded health system perform their roles in light of their responsibilities to the populations. METHODS: A case study approach was adopted in which each financing mechanism is a case. Sixteen (16) in-depth interviews with purchasers and eight (8) focus group discussions with beneficiaries were held. Agency and organizational behavioural theories were used to characterise the purchaser-citizen relationships. A deductive framework approach was used to assess whether actions identified in a model of 'ideal' strategic purchasing actions were undertaken in each case. RESULTS: For both cases, mechanisms exist to reflect people's health needs in purchasing decisions, including quantitative and qualitative needs assessment, mechanisms to raise awareness of benefit entitlements and allow choice. However, purchasers do not use the mechanisms to effectively engage with and hold themselves accountable to the people. In the tax-funded system, weak information systems and unclear communication channels between the purchaser and citizens constrain assessment of needs; while timeliness of health information and poor engagement practices of Health Maintenance Organisations (HMOs) are the main constraints in FSSHIP. Inadequate information sharing in both mechanisms limits beneficiaries' awareness of entitlements. Although beneficiaries of FSSHIP can choose providers, lack of information on the quality of services offered by providers constrains rational decision-making and the inability to change HMOs reduces HMO responsiveness to beneficiary needs. CONCLUSIONS: Responsiveness and accountability to beneficiaries are undervalued by purchasers in both financing mechanisms. In the tax-funded system, civil society organisations can facilitate engagement and accountability of purchasers and the people. In FSSHIP, NHIS needs to provide stronger stewardship of HMOs to promote effective engagement with members. Furthermore, the NHIS should introduce mechanisms that allow FSSHIP members to choose their own HMO, which could encourage HMOs to be more responsive to members.

Analysis of agency relationships in the design and implementation process of the equity fund in Madagascar.

BACKGROUND: There are large gaps in the literature relating to the implementation of user fee policy and fee exemption measures for the poor, particularly on how such schemes are implemented and why many have not produced expected outcomes. In October 2003, Madagascar instituted a user fee exemption policy which established "equity funds" at public health centres, and used medicine sales revenue to subsidise the cost of medicine for the poor. This study examines the policy design and implementation process of the equity fund in Madagascar in an attempt to explore factors influencing the poor equity outcomes of the scheme. METHODS: This study applied an agency-incentive framework to investigate the equity fund policy design and implementation practices. It analysed agency relationships established during implementation; examined incentive structures given to the agency relationships in the policy design; and considered how incentive structures were shaped and how agents responded in practice. The study employed a case-study approach with in-depth analysis of three equity fund cases in Madagascar's Boeny region. RESULTS: Policy design problems, triggering implementation problems, caused poor equity performance. These problems were compounded by the re-direction of policy objectives by health administrators and strong involvement of the administrators in the implementation of policy. The source of the policy design and implementation failure was identified as a set of principal-agent problems concerning: monitoring mechanisms; facility-based fund management; and the nature and level of community participation. These factors all contributed to the financial performance of the fund receiving greater attention than its ability to financially protect the poor. CONCLUSION: The ability of exemption policies to protect the poor from user fees can be found in the details of the policy design and implementation; and implications of the policy design and implementation in a specific context determine whether a policy can realise its objectives. The equity fund experience in Madagascar, which illustrates the challenges of beneficiary identification, casts doubts on the application of the 'targeting' approach in health financing and raises issues to be considered in universal health policy formulation. The agency framework provides a useful lens through which to examine policy process issues.

Improving the public health sector in South Africa: eliciting public preferences using a discrete choice experiment.

BACKGROUND: The introduction of national health insurance (NHI), aimed at achieving universal coverage, is the most important issue currently on the South African health policy agenda. Improvement in public sector health-care provision is crucial for the successful implementation of NHI as, regardless of whether health-care services become more affordable and available, if the quality of the services provided is not acceptable, people will not use the services. Although there has been criticism of the quality of public sector health services, limited research is available to identify what communities regard as the greatest problems with the services. METHODS: A discrete choice experiment (DCE) was undertaken to elicit public preferences on key dimensions of quality of care when selecting public health facilities in South Africa. Qualitative methods were applied to establish attributes and levels for the DCE. To elicit preferences, interviews with community members were held in two South African provinces: 491 in Western Cape and 499 in Eastern Cape. RESULTS: The availability of necessary medicine at health facilities has the greatest impact on the probability of attending public health facilities. Other clinical quality attributes (i.e. provision of expert advice and provision of a thorough examination) are more valued than non-clinical quality of care attributes (i.e. staff attitude, treatment by doctors or nurses, and waiting time). Treatment by a doctor was less valued than all other attributes. CONCLUSION: Communities are prepared to tolerate public sector health service characteristics such as a long waiting time, poor staff attitudes and lack of direct access to doctors if they receive the medicine they need, a thorough examination and a clear explanation of the diagnosis and prescribed treatment from health professionals. These findings prioritize issues that the South African government must address in order to meet their commitment to improve public sector health-care service provision.

Promoting universal financial protection: evidence from seven low- and middle-income countries on factors facilitating or hindering progress.

Although universal health coverage (UHC) is a global health policy priority, there remains limited evidence on UHC reforms in low- and middle-income countries (LMICs). This paper provides an overview of key insights from case studies in this thematic series, undertaken in seven LMICs (Costa Rica, Georgia, India, Malawi, Nigeria, Tanzania, and Thailand) at very different stages in the transition to UHC.These studies highlight the importance of increasing pre-payment funding through tax funding and sometimes mandatory insurance contributions when trying to improve financial protection by reducing out-of-pocket payments. Increased tax funding is particularly important if efforts are being made to extend financial protection to those outside formal-sector employment, raising questions about the value of pursuing contributory insurance schemes for this group. The prioritisation of insurance scheme coverage for civil servants in the first instance in some LMICs also raises questions about the most appropriate use of limited government funds.The diverse reforms in these countries provide some insights into experiences with policies targeted at the poor compared with universalist reform approaches. Countries that have made the greatest progress to UHC, such as Costa Rica and Thailand, made an explicit commitment to ensuring financial protection and access to needed care for the entire population as soon as possible, while this was not necessarily the case in countries adopting targeted reforms. There also tends to be less fragmentation in funding pools in countries adopting a universalist rather than targeting approach. Apart from limiting cross-subsidies, fragmentation of pools has contributed to differential benefit packages, leading to inequities in access to needed care and financial protection across population groups; once such differentials are entrenched, they are difficult to overcome. Capacity constraints, particularly in purchasing organisations, are a pervasive problem in LMICs. The case studies also highlighted the critical role of high-level political leadership in pursuing UHC policies and citizen support in sustaining these policies.This series demonstrates the value of promoting greater sharing of experiences on UHC reforms across LMICs. It also identifies key areas of future research on health care financing in LMICs that would support progress towards UHC.

Do equity funds protect the poor? Case studies from north-western Madagascar.

BACKGROUND: User fees, if applied indiscriminately, have the potential to impose catastrophic costs on poor households at a time when a family member is sick and the household vulnerable. This can drive households into, or further into, poverty. In October 2003, Madagascar instituted a user fee policy that created 'equity funds' at public health centres to subsidize free medicine for the poor. OBJECTIVE: This study aims to assess the outcomes of the equity funds in Madagascar from three perspectives: accuracy of targeting; improvement in health care access for the poor; and reduction in financial burden on the poor. METHODS: Data collection took place in the Boeny region, Madagascar, between March and October 2006. Structured questionnaires asking about health-seeking behaviour and health expenditures were administered to all equity fund member households and two of their neighbouring, non-member households in each study site. RESULTS: The mean socio-economic status of equity fund members was lower than that of non-members. However, both leakage and under-coverage occurred under the equity fund scheme, the degree of which varied between sites. Equity fund members were more likely to seek care at public health centres than non-members, although variation existed among study sites, with particularly negative results at one site. Equity fund members who were aware of their member status were more likely to seek care at public health centres. Although out-of-pocket payments for outpatient consultation were significantly lower for members than for non-members, no significant difference was found for medicine payments at public health centres. CONCLUSION: The effectiveness outcomes varied across case studies and the ability of the Madagascan equity funds to protect households against financial risk was ambiguous. To some extent, contextual factors explain these outcome variations. Consequently, nationwide policy should be designed with consideration of the broader health system context and incorporate measures to manage contextual factors to achieve benefit for the entire population.

Affordability of emergency obstetric and neonatal care at public hospitals in Madagascar.

Timely access to emergency obstetric care is necessary to save the lives of women experiencing complications at delivery, and for newborn babies. Out-of-pocket costs are one of the critical factors hindering access to such services in low- and middle-income countries. This study measured out-of-pocket costs for caesarean section and neonatal care at an urban tertiary public hospital in Madagascar, assessed affordability in relation to household expenditure and investigated where families found the money to cover these costs. Data were collected for 103 women and 73 newborns at the Centre Hospitalier Universitaire de Mahajanga in the Boeny region of Madagascar between September 2007 and January 2008. Out-of-pocket costs for caesarean section were catastrophic for middle and lower socio-economic households, and treatment for neonatal complications also created a big financial burden, with geographical and other financial barriers further limiting access to hospital care. This study identified 12 possible cases where the mother required an emergency caesarean section and her newborn required emergency care, placing a double burden on the household. In an effort to make emergency obstetric and neonatal care affordable and available to all, including those living in rural areas and those of medium and lower socio-economic status, well-designed financial risk protection mechanisms and a strong commitment by the government to mobilise resources to finance the country's health system are necessary.

Identification of broad-spectrum antiviral compounds and assessment of the druggability of their target for efficacy against respiratory syncytial virus (RSV).

The search for novel therapeutic interventions for viral disease is a challenging pursuit, hallmarked by the paucity of antiviral agents currently prescribed. Targeting of viral proteins has the inextricable challenge of rise of resistance. Safe and effective vaccines are not possible for many viral pathogens. New approaches are required to address the unmet medical need in this area. We undertook a cell-based high-throughput screen to identify leads for development of drugs to treat respiratory syncytial virus (RSV), a serious pediatric pathogen. We identified compounds that are potent (nanomolar) inhibitors of RSV in vitro in HEp-2 cells and in primary human bronchial epithelial cells and were shown to act postentry. Interestingly, two scaffolds exhibited broad-spectrum activity among multiple RNA viruses. Using the chemical matter as a probe, we identified the targets and identified a common cellular pathway: the de novo pyrimidine biosynthesis pathway. Both targets were validated in vitro and showed no significant cell cytotoxicity except for activity against proliferative B- and T-type lymphoid cells. Corollary to this finding was to understand the consequences of inhibition of the target to the host. An in vivo assessment for antiviral efficacy failed to demonstrate reduced viral load, but revealed microscopic changes and a trend toward reduced pyrimidine pools and findings in histopathology. We present here a discovery program that includes screen, target identification, validation, and druggability that can be broadly applied to identify and interrogate other host factors for antiviral effect starting from chemical matter of unknown target/mechanism of action.