Leveraging natural history biorepositories as a global, decentralized, pathogen surveillance network

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic reveals a major gap in global biosecurity infrastructure: a lack of publicly available biological samples representative across space, time, and taxonomic diversity. The shortfall, in this case for vertebrates, prevents accurate and rapid identification and monitoring of emerging pathogens and their reservoir host(s) and precludes extended investigation of ecological, evolutionary, and environmental associations that lead to human infection or spillover. Natural history museum biorepositories form the backbone of a critically needed, decentralized, global network for zoonotic pathogen surveillance, yet this infrastructure remains marginally developed, underutilized, underfunded, and disconnected from public health initiatives. Proactive detection and mitigation for emerging infectious diseases (EIDs) requires expanded biodiversity infrastructure and training (particularly in biodiverse and lower income countries) and new communication pipelines that connect biorepositories and biomedical communities. To this end, we highlight a novel adaptation of Project ECHO’s virtual community of practice model: Museums and Emerging Pathogens in the Americas (MEPA). MEPA is a virtual network aimed at fostering communication, coordination, and collaborative problem-solving among pathogen researchers, public health officials, and biorepositories in the Americas. MEPA now acts as a model of effective international, interdisciplinary collaboration that can and should be replicated in other biodiversity hotspots. We encourage deposition of wildlife specimens and associated data with public biorepositories, regardless of original collection purpose, and urge biorepositories to embrace new specimen sources, types, and uses to maximize strategic growth and utility for EID research. Taxonomically, geographically, and temporally deep biorepository archives serve as the foundation of a proactive and increasingly predictive approach to zoonotic spillover, risk assessment, and threat mitigation

Implementation and evaluation of a Project ECHO telementoring program for the Namibian HIV workforce.

BACKGROUND: The Namibian Ministry of Health and Social Services (MoHSS) piloted the first HIV Project ECHO (Extension for Community Health Outcomes) in Africa at 10 clinical sites between 2015 and 2016. Goals of Project ECHO implementation included strengthening clinical capacity, improving professional satisfaction, and reducing isolation while addressing HIV service challenges during decentralization of antiretroviral therapy. METHODS: MoHSS conducted a mixed-methods evaluation to assess the pilot. Methods included pre/post program assessments of healthcare worker knowledge, self-efficacy, and professional satisfaction; assessment of continuing professional development (CPD) credit acquisition; and focus group discussions and in-depth interviews. Analysis compared the differences between pre/post scores descriptively. Qualitative transcripts were analyzed to extract themes and representative quotes. RESULTS: Knowledge of clinical HIV improved 17.8% overall (95% confidence interval 12.2-23.5%) and 22.3% (95% confidence interval 13.2-31.5%) for nurses. Professional satisfaction increased 30 percentage points. Most participants experienced reduced professional isolation (66%) and improved CPD credit access (57%). Qualitative findings reinforced quantitative results. Following the pilot, the Namibia MoHSS Project ECHO expanded to over 40 clinical sites by May 2019 serving more than 140 000 people living with HIV. CONCLUSIONS: Similar to other Project ECHO evaluation results in the United States of America, Namibia's Project ECHO led to the development of ongoing virtual communities of practice. The evaluation demonstrated the ability of the Namibia HIV Project ECHO to improve healthcare worker knowledge and satisfaction and decrease professional isolation

Afternoon Plenary Session

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Outcomes of Antiretroviral Therapy in Vietnam: Results from a National Evaluation

<div><h3>Objectives</h3><p>Vietnam has significantly scaled up its national antiretroviral therapy (ART) program since 2005. With the aim of improving Vietnam’s national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID). The results of this evaluation may have relevance for other national ART programs with significant PWID populations.</p> <h3>Design</h3><p>Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART.</p> <h3>Methods</h3><p>Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data.</p> <h3>Results</h3><p>Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4–76.5, median age 30, interquartile range [IQR]: 26–34, 62.0% reported a history of intravenous drug use, CI: 58.6–65.3). Median baseline CD4 cell count was 78 cells/mm³ (IQR: 30–162) and 30.4% (CI: 25.8–35.1) of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3%) or d4T/3TC/EFV (18.6%). Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8–89.9), 84.0% (CI: 81.8–86.0), 78.8% (CI: 75.7–81.6), and 74.6% (CI: 69.6–79.0). Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45–153), 142 (IQR: 78–217), 213 (IQR: 120–329), and 254 (IQR: 135–391) cells/mm³. Patients who were PWID showed significantly poorer retention.</p> <h3>Conclusions</h3><p>The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.</p> </div

A technology-enabled multi-disciplinary team-based care model for the management of Long COVID and other fatiguing illnesses within a federally qualified health center: protocol for a two-arm, single-blind, pragmatic, quality improvement professional cluster randomized controlled trial.

BACKGROUND: The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions. METHODS: We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&amp;FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&amp;FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts. DISCUSSION: We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021

Prevalence of cryptococcal antigenemia and cost-effectiveness of a cryptococcal antigen screening program--Vietnam.

An estimated 120,000 HIV-associated cryptococcal meningitis (CM) cases occur each year in South and Southeast Asia; early treatment may improve outcomes. The World Health Organization (WHO) recently recommended screening HIV-infected adults with CD4<100 cells/mm(3) for serum cryptococcal antigen (CrAg), a marker of early cryptococcal infection, in areas of high CrAg prevalence. We evaluated CrAg prevalence and cost-effectiveness of this screening strategy in HIV-infected adults in northern and southern Vietnam.Serum samples were collected and stored during 2009-2012 in Hanoi and Ho Chi Minh City, Vietnam, from HIV-infected, ART-naïve patients presenting to care in 12 clinics. All specimens from patients with CD4<100 cells/mm(3) were tested using the CrAg lateral flow assay. We obtained cost estimates from laboratory staff, clinicians and hospital administrators in Vietnam, and evaluated cost-effectiveness using WHO guidelines.Sera from 226 patients [104 (46%) from North Vietnam and 122 (54%) from the South] with CD4<100 cells/mm(3) were available for CrAg testing. Median CD4 count was 40 (range 0-99) cells/mm(3). Nine (4%; 95% CI 2-7%) specimens were CrAg-positive. CrAg prevalence was higher in South Vietnam (6%; 95% CI 3-11%) than in North Vietnam (2%; 95% CI 0-6%) (p = 0.18). Cost per life-year gained under a screening scenario was $190,$137, and $119 at CrAg prevalences of 2%, 4% and 6%, respectively.CrAg prevalence was higher in southern compared with northern Vietnam; however, CrAg screening would be considered cost-effective by WHO criteria in both regions. Public health officials in Vietnam should consider adding cryptococcal screening to existing national guidelines for HIV/AIDS care

Cost-effectiveness of cryptococcal screening at a range of prevalences and cost scenarios.

<p>This graph has prevalence of asymptomatic cryptococcal antigenemia on the x-axis and incremental cost-effectiveness ratio (ICER) (increased cost per life-year gained [LYG] in US dollars) on the y-axis. The blue line represents the cost curve of full-cost fluconazole for one year of treatment. The red line represents the cost curve of full-cost fluconazole for ten weeks of treatment; the green line represents the cost curve of if fluconazole is obtained at no-cost. For Vietnam, the World Health Organization considers any intervention with an ICER under $6,948 to be ‘highly cost-effective’. This graph shows that cryptococcal screening, at any prevalence and under each of the three cost scenarios, should be considered a highly cost-effective intervention in Vietnam.</p

Costs associated with cryptococcal meningitis diagnosis, treatment and a cryptococcal screening program in Vietnam, in US dollars.

*<p>Inclusive of: CSF culture, cell count, glucose, protein, India Ink, and LFA.</p

Number Needed to Screen (NNS), by prevalence of serum CrAg-positive persons in Vietnam.

<p>Number Needed to Screen (NNS), by prevalence of serum CrAg-positive persons in Vietnam.</p

Sensitivity analysis: variation in cost/LYG through screening by varied testing and drug costs, positive symptoms screen, LP rate, CM mortality rate and discount rate.

<p>Sensitivity analysis: variation in cost/LYG through screening by varied testing and drug costs, positive symptoms screen, LP rate, CM mortality rate and discount rate.</p