BACKGROUND: Following the West African Ebola virus disease (EVD) outbreak of 2013-2016 and more recent EVD outbreaks in the Democratic Republic of Congo, thousands of EVD survivors are at-risk for sequelae including uveitis, which can lead to unremitting inflammation and vision loss from cataract. Because of the known risk of Ebola virus persistence in ocular fluid and the need to provide vision-restorative, safe cataract surgery, the Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study was implemented in Sierra Leone. During implementation of this multi-national study, challenges included regulatory approvals, mobilization, community engagement, infection prevention and control, and collaboration between multiple disciplines. In this report, we address the multifacted approach to address these challenges and the impact of implementation science research to address an urgent clinical subspecialty need in an outbreak setting. METHODOLOGY/PRINCIPAL FINDINGS: Given the patient care need to develop a protocol to evaluate ocular fluid for Ebola virus RNA persistence prior to cataract surgery, as well as protocols to provide reassurance to ophthalmologists caring for EVD survivors with cataracts, the EVICT study was designed and implemented through the work of the Ministry of Health, Sierra Leone National Eye Programme, and international partnerships. The EVICT study showed that all 50 patients who underwent ocular fluid sampling at 19 and 34 months, respectively, tested negative for Ebola virus RNA. Thirty-four patients underwent successful cataract surgery with visual acuity improvement. Here we describe the methodology for study implementation, challenges encountered, and key issues that impacted EVD vision care in the immediate aftermath of the EVD outbreak. Key aspects of the EVICT study included defining the pertinent questions and clinical need, partnership alignment with key stakeholders, community engagement with EVD survivor associations, in-country and international regulatory approvals, study site design for infection prevention and control, and thorough plans for EVD survivor follow-up care and monitoring. Challenges encountered included patient mobilization owing to transportation routes and distance of patients in rural districts. Strong in-country partnerships and multiple international organizations overcame these challenges so that lessons learned could be applied for future EVD outbreaks in West and Central Africa including EVD outbreaks that are ongoing in Guinea and Democratic Republic of Congo. CONCLUSIONS/SIGNIFICANCE: The EVICT Study showed that cataract surgery with a protocol-driven approach was safe and vision-restorative for EVD survivors, which provided guidance for EVD ophthalmic surgical care. Ophthalmologic care remains a key aspect of the public health response for EVD outbreaks but requires a meticulous, yet partnered approach with international and local in-country partners. Future efforts may build on this framework for clinical care and to improve our understanding of ophthalmic sequelae, develop treatment paradigms for EVD survivors, and strengthen vision health systems in resource-limited settings.

BACKGROUND: Ebola virus disease (EVD) survivors are at risk for uveitis during convalescence. Vision loss has been observed following uveitis due to cataracts. Since Ebola virus (EBOV) may persist in the ocular fluid of EVD survivors for an unknown duration, there are questions about the safety and feasibility of vision restorative cataract surgery in EVD survivors. METHODS: We conducted a cross-sectional study of EVD survivors anticipating cataract surgery and patients with active uveitis to evaluate EBOV RNA persistence in ocular fluid, as well as vision outcomes post cataract surgery. Patients with aqueous humor that tested negative for EBOV RNA were eligible to proceed with manual small incision cataract surgery (MSICS). FINDINGS: We screened 137 EVD survivors from June 2016 - August 2017 for enrolment. We enrolled 50 EVD survivors; 46 with visually significant cataract, 1 with a subluxated lens, 2 with active uveitis and 1 with a blind painful eye due to uveitis. The median age was 24.0years (IQR 17-35) and 35 patients (70%) were female. The median logMAR visual acuity (VA) was 3.0 (Snellen VA Hand motions; Interquartile Range, IQR: 1.2-3.0, Snellen VA 20/320 - Hand motions). All patients tested negative for EBOV RNA by RT-PCR in aqueous humor/vitreous fluid and conjunctiva at a median of 19months (IQR 18-20) from EVD diagnosis in Phase 1 of ocular fluid sampling and 34months (IQR 32-36) from EVD diagnosis in Phase 2 of ocular fluid sampling. Thirty-four patients underwent MSICS, with a preoperative median VA improvement from hand motions to 20/30 at three-month postoperative follow-up (P<0.001). INTERPRETATION: EBOV persistence by RT-PCR was not identified in ocular fluid or conjunctivae of fifty EVD survivors with ocular disease. Cataract surgery can be performed safely with vision restorative outcomes in patients who test negative for EBOV RNA in ocular fluid specimens. These findings impact the thousands of West African EVD survivors at-risk for ocular complications who may also require eye surgery during EVD convalescence.

Partnership for Health (PfH) is an evidence-based, clinician-delivered HIV prevention program conducted in the United States for HIV-positive patients. This intervention strives to reduce risky sexual behaviors through provider-patient discussions on safer sex and HIV status disclosure. A cross-sectional, mixed-methods design was used to evaluate the dissemination and implementation of PfH, including training evaluations, an online trainee survey, and interviews with national trainers for PfH. Descriptive statistics were calculated with the categorical data, whereas thematic analysis was completed with the qualitative data. Between 2007 and 2013, PfH was disseminated to 776 individuals from 104 different organizations in 21 states/territories. The smallest proportion of trainees was physicians (6.9%). More than three-fourths of survey respondents (78.6%) reported using PfH, but less than one-third (31.8%) used the intervention with every patient. The PfH training supports the implementation of the intervention; however, challenges were experienced in clinician engagement. Tailored strategies to recruit and train clinicians providing care to HIV-positive patients are required.

HIV prevalence and socio-demographic data were analyzed to assess the alignment of CDC-funded HIV testing activity in 2012 with its high-impact prevention approach. CDC-funded HIV-testing was conducted in counties with high HIV prevalence and in places potentially more affected by HIV as measured by urbanicity, percent black, percent poverty, and percent uninsured. The percent Hispanic/Latino was associated with a lower probability of HIV testing activity. Higher percentages of black and Hispanic/Latino in the population was positively associated with new HIV diagnoses. Analyzing county-level data confirmed the appropriateness of CDC-funded HIV testing activities under a high-impact prevention approach but also suggested areas for possible improvement.

OBJECTIVES: To assess the association between state per capita allocations of Centers for Disease Control and Prevention (CDC) funding for HIV testing and the percentage of persons tested for HIV. SETTING AND PARTICIPANTS: We examined data from 2 sources: 2011 Behavioral Risk Factor Surveillance System and 2010-2011 State HIV Budget Allocations Reports. Behavioral Risk Factor Surveillance System data were used to estimate the percentage of persons aged 18 to 64 years who had reported testing for HIV in the last 2 years in the United States by state. State HIV Budget Allocations Reports were used to calculate the state mean annual per capita allocations for CDC-funded HIV testing reported by state and local health departments in the United States. DESIGN: The association between the state fixed-effect per capita allocations for CDC-funded HIV testing and self-reported HIV testing in the last 2 years among persons aged 18 to 64 years was assessed with a hierarchical logistic regression model adjusting for individual-level characteristics. MAIN OUTCOME: The percentage of persons tested for HIV in the last 2 years. RESULTS: In 2011, 18.7% (95% confidence interval = 18.4-19.0) of persons reported being tested for HIV in last 2 years (state range, 9.7%-28.2%). During 2010-2011, the state mean annual per capita allocation for CDC-funded HIV testing was $0.34 (state range, $0.04-$1.04). A $0.30 increase in per capita allocation for CDC-funded HIV testing was associated with an increase of 2.4 percentage points (14.0% vs 16.4%) in the percentage of persons tested for HIV per state. CONCLUSIONS: Providing HIV testing resources to health departments was associated with an increased percentage of state residents tested for HIV.

AIMS: Bradykinin (BK) stimulates tissue plasminogen activator (t-PA) release from human endothelium. Although BK stimulates both nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) release, the role of EDHF in t-PA release remains unexplored. This study sought to determine the mechanisms of BK-stimulated t-PA release in the forearm vasculature of healthy human subjects. METHODS: In 33 healthy subjects (age 40.3 +/- 1.9 years), forearm blood flow (FBF) and t-PA release were measured at rest and after intra-arterial infusions of BK (400 ng/min) and sodium nitroprusside (3.2 mg/min). Measurements were repeated after intra-arterial infusion of tetraethylammonium chloride (TEA; 1 micromol/min), fluconazole (0.4 micromol.min(-1).l(-1)), and N(G)-monomethyl-L-arginine (L-NMMA, 8 micromol/min) to block nitric oxide, and their combination in separate studies. RESULTS: BK significantly increased net t-PA release across the forearm (p < 0.0001). Fluconazole attenuated both BK-mediated vasodilation (-23.3 +/- 2.7% FBF, p < 0.0001) and t-PA release (from 50.9 +/- 9.0 to 21.3 +/- 8.9 ng/min/100 ml, p = 0.02). TEA attenuated FBF (-14.7 +/- 3.2%, p = 0.002) and abolished BK-stimulated t-PA release (from 22.9 +/- 5.7 to -0.8 +/- 3.6 ng/min/100 ml, p = 0.0002). L-NMMA attenuated FBF (p < 0.0001), but did not inhibit BK-induced t-PA release (nonsignificant). CONCLUSION: BK-stimulated t-PA release is partly due to cytochrome P450-derived epoxides and is inhibited by K(+)Ca channel blockade. Thus, BK stimulates both EDHF-dependent vasodilation and t-PA release.