Using EpiCore to Enable Rapid Verification of Potential Health Threats: Illustrated Use Cases and Summary Statistics.

BACKGROUND: The proliferation of digital disease-detection systems has led to an increase in earlier warning signals, which subsequently have resulted in swifter responses to emerging threats. Such highly sensitive systems can also produce weak signals needing additional information for action. The delays in the response to a genuine health threat are often due to the time it takes to verify a health event. It was the delay in outbreak verification that was the main impetus for creating EpiCore. OBJECTIVE: This paper describes the potential of crowdsourcing information through EpiCore, a network of voluntary human, animal, and environmental health professionals supporting the verification of early warning signals of potential outbreaks and informing risk assessments by monitoring ongoing threats. METHODS: This paper uses summary statistics to assess whether EpiCore is meeting its goal to accelerate the time to verification of identified potential health events for epidemic and pandemic intelligence purposes from around the world. Data from the EpiCore platform from January 2018 to December 2022 were analyzed to capture request for information response rates and verification rates. Illustrated use cases are provided to describe how EpiCore members provide information to facilitate the verification of early warning signals of potential outbreaks and for the monitoring and risk assessment of ongoing threats through EpiCore and its utilities. RESULTS: Since its launch in 2016, EpiCore network membership grew to over 3300 individuals during the first 2 years, consisting of professionals in human, animal, and environmental health, spanning 161 countries. The overall EpiCore response rate to requests for information increased by year between 2018 and 2022 from 65.4% to 68.8% with an initial response typically received within 24 hours (in 2022, 94% of responded requests received a first contribution within 24 h). Five illustrated use cases highlight the various uses of EpiCore. CONCLUSIONS: As the global demand for data to facilitate disease prevention and control continues to grow, it will be crucial for traditional and nontraditional methods of disease surveillance to work together to ensure health threats are captured earlier. EpiCore is an innovative approach that can support health authorities in decision-making when used complementarily with official early detection and verification systems. EpiCore can shorten the time to verification by confirming early detection signals, informing risk-assessment activities, and monitoring ongoing events.

Uganda's experience in establishing an electronic compendium for public health emergencies.

Uganda has implemented several interventions that have contributed to prevention, early detection, and effective response to Public Health Emergencies (PHEs). However, there are gaps in collecting and documenting data on the overall response to these PHEs. We set out to establish a comprehensive electronic database of PHEs that occurred in Uganda since 2000. We constituted a core development team, developed a data dictionary, and worked with Health Information Systems Program (HISP)-Uganda to develop and customize a compendium of PHEs using the electronic Integrated Disease Surveillance and Response (eIDSR) module on the District Health Information Software version 2 (DHIS2) platform. We reviewed literature for retrospective data on PHEs for the compendium. Working with the Uganda Public Health Emergency Operations Center (PHEOC), we prospectively updated the compendium with real-time data on reported PHEs. We developed a user's guide to support future data entry teams. An operational compendium was developed within the eIDSR module of the DHIS2 platform. The variables for PHEs data collection include those that identify the type, location, nature and time to response of each PHE. The compendium has been updated with retrospective PHE data and real-time prospective data collection is ongoing. Data within this compendium is being used to generate information that can guide future outbreak response and management. The compendium development highlights the importance of documenting outbreak detection and response data in a central location for future reference. This data provides an opportunity to evaluate and inform improvements in PHEs response.

Looking Ahead in the Rearview Mirror: During Action Review and Tabletop (DART) to Strengthen Health Emergency Readiness and Resiliency.

During health emergencies, such as the COVID-19 pandemic, systematic evaluation of capabilities, and multisector coordination are challenging while operating in triage mode. During Action Review and Tabletop (DART) identifies recommendations for strengthening readiness and resiliency by creating a single methodology integrating retrospective analysis of the response to date with a prospective analysis of future scenarios. DART utilizes a role-based questionnaire and participant-led discussion for retrospective response review and identification of future scenarios of concern. Tabletop exercises exploring those future scenarios are conducted in a multi-role format to assess readiness and resiliency. Participants evaluate findings to determine recommended actions to improve response capabilities. 3 COVID-19 focused DARTs demonstrated the ability of this participant-led approach to systematically assess, not only readiness for today, but also resiliency to future complications. While demonstrating its usefulness during COVID-19, DART's flexible and modular design promises to be an effective for any ongoing health emergency.

The Landscape of Participatory Surveillance Systems Across the One Health Spectrum: Systematic Review.

BACKGROUND: Participatory surveillance systems augment traditional surveillance systems through bidirectional community engagement. The digital platform evolution has enabled the expansion of participatory surveillance systems, globally, for the detection of health events impacting people, animals, plants, and the environment, in other words, across the entire One Health spectrum. OBJECTIVE: The aim of this landscape was to identify and provide descriptive information regarding system focus, geography, users, technology, information shared, and perceived impact of ongoing participatory surveillance systems across the One Health spectrum. METHODS: This landscape began with a systematic literature review to identify potential ongoing participatory surveillance systems. A survey was sent to collect standardized data from the contacts of systems identified in the literature review and through direct outreach to stakeholders, experts, and professional organizations. Descriptive analyses of survey and literature review results were conducted across the programs. RESULTS: The landscape identified 60 ongoing single-sector and multisector participatory surveillance systems spanning five continents. Of these, 29 (48%) include data on human health, 26 (43%) include data on environmental health, and 24 (40%) include data on animal health. In total, 16 (27%) systems are multisectoral; of these, 9 (56%) collect animal and environmental health data; 3 (19%) collect human, animal, and environmental health data; 2 (13%) collect human and environmental health data; and 2 (13%) collect human and animal health data. Out of 60 systems, 31 (52%) are designed to cover a national scale, compared to those with a subnational (n=19, 32%) or multinational (n=10, 17%) focus. All systems use some form of digital technology. Email communication or websites (n=40, 67%) and smartphones (n=29, 48%) are the most common technologies used, with some using both. Systems have capabilities to download geolocation data (n=31, 52%), photographs (n=29, 48%), and videos (n=6, 10%), and can incorporate lab data or sample collection (n=15, 25%). In sharing information back with users, most use visualization, such as maps (n=43, 72%); training and educational materials (n=37, 62%); newsletters, blogs, and emails (n=34, 57%); and disease prevention information (n=32, 53%). Out of the 46 systems responding to the survey regarding perceived impacts of their systems, 36 (78%) noted "improved community knowledge and understanding" and 31 (67%) noted "earlier detection." CONCLUSIONS: The landscape demonstrated the breadth of applicability of participatory surveillance around the world to collect data from community members and trained volunteers in order to inform the detection of events, from invasive plant pests to weekly influenza symptoms. Acknowledging the importance of bidirectionality of information, these systems simultaneously share findings back with the users. Such directly engaged community detection systems capture events early and provide opportunities to stop outbreaks quickly.

EpiHacks, a Process for Technologists and Health Experts to Cocreate Optimal Solutions for Disease Prevention and Control: User-Centered Design Approach.

BACKGROUND: Technology-based innovations that are created collaboratively by local technology specialists and health experts can optimize the addressing of priority needs for disease prevention and control. An EpiHack is a distinct, collaborative approach to developing solutions that combines the science of epidemiology with the format of a hackathon. Since 2013, a total of 12 EpiHacks have collectively brought together over 500 technology and health professionals from 29 countries. OBJECTIVE: We aimed to define the EpiHack process and summarize the impacts of the technology-based innovations that have been created through this approach. METHODS: The key components and timeline of an EpiHack were described in detail. The focus areas, outputs, and impacts of the twelve EpiHacks that were conducted between 2013 and 2021 were summarized. RESULTS: EpiHack solutions have served to improve surveillance for influenza, dengue, and mass gatherings, as well as laboratory sample tracking and One Health surveillance, in rural and urban communities. Several EpiHack tools were scaled during the COVID-19 pandemic to support local governments in conducting active surveillance. All tools were designed to be open source to allow for easy replication and adaptation by other governments or parties. CONCLUSIONS: EpiHacks provide an efficient, flexible, and replicable new approach to generating relevant and timely innovations that are locally developed and owned, are scalable, and are sustainable.

Using Timeliness Metrics to Track Progress and Identify Gaps in Disease Surveillance.

Timely outbreak detection and response can translate into illnesses averted and lives saved. As such, timeliness is an important criterion for evaluating performance of infectious disease surveillance systems. Through the use of clearly defined outbreak milestones, timeliness metrics can capture the speed of outbreak detection, verification, response, and other key actions across the timeline of an outbreak and evaluate progress over time. In this article, we describe a series of country-level pilot studies designed to assess the feasibility and utility of tracking timeliness metrics and highlight key findings. We then discuss subsequent efforts to develop a timeliness metrics measurement framework through expert consultation and provide recommendations for implementation. National surveillance programs, international agencies, and donor organizations can use timeliness metrics to identify gaps in surveillance performance and track progress toward improved global health security.

Evaluation of the EpiCore outbreak verification system.

OBJECTIVE: To describe a crowdsourced disease surveillance project (EpiCore) and evaluate its usefulness in obtaining information regarding potential disease outbreaks. METHODS: Volunteer human, animal and environmental health professionals from around the world were recruited to EpiCore and trained to provide early verification of health threat alerts in their geographical region via a secure, easy-to-use, online platform. Experts in the area of emerging infectious diseases sent requests for information on unverified health threats to these volunteers, who used local knowledge and expertise to respond to requests. Experts reviewed and summarized the responses and rapidly disseminated important information to the global health community through the existing event-based disease surveillance network, ProMED. FINDINGS: From March 2016 to September 2017, 2068 EpiCore volunteers from 142 countries were trained in methods of informal disease surveillance and use of the EpiCore online platform. These volunteers provided 790 individual responses to 759 requests for information addressing unverified health threats in 112 countries; 361 (45%) responses were considered to be useful. Most responses were received within hours of the requests. The responses led to 194 ProMED posts, of which 99 (51%) supported verification of an outbreak, were published on ProMED and sent to over 87 000 subscribers. CONCLUSION: There is widespread willingness among health professionals around the world to voluntarily assist efforts to verify and provide supporting information on unconfirmed health threats in their region. By linking this member network of health experts through a secure online reporting platform, EpiCore enables faster global outbreak detection and reporting.

Ambulance Service Associated With Reduced Probabilities Of Neonatal And Infant Mortality In Two Indian States.

India had no large-scale, centralized emergency medical system or ambulance service until 2005. Since then, the GVK Emergency Management and Research Institute (GVK EMRI) has emerged as India's largest ambulance service provider, covering more than 630 million people. This study provides the first quantitative evidence of GVK EMRI's early impact on population-level infant and maternal health outcomes in Andhra Pradesh and Gujarat, two Indian states with a combined population of about 145 million people. We found that GVK EMRI coverage is associated with reductions in the probability of neonatal and infant mortality as well as delivery complications (statewide in Andhra Pradesh and in high-mortality districts in Gujarat). However, we found little change in the probability of institutional delivery or skilled birth attendance. Taken together, our findings suggest that population-level health gains were achieved through improvements in the quality (rather than quantity) of maternal and neonatal health services-an interpretation consistent with qualitative reports. More research on this topic is needed.

Scaling up antiretroviral therapy in South Africa: the impact of speed on survival.

BACKGROUND: Only 33% of eligible human immunodeficiency virus (HIV)-infected patients in South Africa receive antiretroviral therapy (ART). We sought to estimate the impact of alternative ART scale-up scenarios on patient outcomes from 2007-2012. METHODS: Using a simulation model of HIV infection with South African data, we projected HIV-associated mortality with and without effective ART for an adult cohort in need of therapy (2007) and for adults who became eligible for treatment (2008-2012). We compared 5 scale-up scenarios: (1) zero growth, with a total of 100,000 new treatment slots; (2) constant growth, with 600,000; (3) moderate growth, with 2.1 million; (4) rapid growth, with 2.4 million); and (5) full capacity, with 3.2 million. RESULTS: Our projections showed that by 2011, the rapid growth scenario fully met the South African need for ART; by 2012, the moderate scenario met 97% of the need, but the zero and constant growth scenarios met only 28% and 52% of the need, respectively. The latter scenarios resulted in 364,000 and 831,000 people alive and on ART in 2012. From 2007 to 2012, cumulative deaths in South Africa ranged from 2.5 million under the zero growth scenario to 1.2 million under the rapid growth scenario. CONCLUSIONS: Alternative ART scale-up scenarios in South Africa will lead to differences in the death rate that amount to more than 1.2 million deaths by 2012. More rapid scale-up remains critically important.

HIV morbidity and mortality in Jamaica: analysis of national surveillance data, 1993--2005.

OBJECTIVES: Pre-antiretroviral therapy (ART) HIV-related survival and timing of HIV identification have not been reported from the Caribbean. Using Jamaican national surveillance data, we estimated overall, AIDS-free, and AIDS survival, identified factors influencing HIV-related mortality, and examined factors associated with late HIV/AIDS identification. METHODS: The Jamaican HIV/AIDS tracking system (HATS) national surveillance data included timing of first positive HIV test, stage at identification, date of AIDS diagnosis, and death. We estimated overall and AIDS-free survival by initial stage, using a proportional hazard model to identify factors associated with worse survival, and logistic regression to examine factors related to later case identification. RESULTS: Of 10674 reported HIV cases, 48% were asymptomatic, 14% symptomatic, and 38% first reported with AIDS. Five-year AIDS-free survival was 77% for asymptomatic persons and 63% for symptomatic. Median survival after AIDS diagnosis was 1.02 years. Age, number of opportunistic diseases, and initial stage were strongly associated with mortality. Older age, drug use, and sex with a commercial sex worker were associated with later identification. CONCLUSIONS: In the pre-ART era, over one-third of HIV-infected persons in Jamaica were first identified with advanced disease. This highlights the need for earlier diagnosis as ART programs roll out in the Caribbean.

The cost-effectiveness of antiretroviral therapy for treating HIV disease in the Caribbean.

BACKGROUND: Antiretroviral therapy (ART) recently became available in the Organization of Eastern Caribbean States (OECS). Survival benefits and budgetary implications associated with universal access to ART have not been examined in the Caribbean. METHODS: Using a state-transition simulation model of HIV with regional data, we projected survival, cost, and cost-effectiveness of treating an HIV-infected cohort. We examined 1 or 2 ART regimens and cotrimoxazole. In sensitivity analysis, we varied HIV natural history and ART efficacy, cost, and switching criteria. RESULTS: Without treatment, mean survival was 2.30 years (mean baseline CD4 count = 288 cells/microL). One ART regimen with cotrimoxazole when the CD4 count was <350 cells/microL provided an additional 5.86 years of survival benefit compared with no treatment; the incremental cost-effectiveness ratio was $690 per year of life saved (YLS). A second regimen added 1.04 years of survival benefit; the incremental cost-effectiveness ratio was $10,960 per YLS compared with 1 regimen. Results were highly dependent on second-line ART costs. Per-person lifetime costs decreased from $17,020 to $9290 if second-line ART costs decreased to those available internationally, yielding approximately $8 million total savings. CONCLUSIONS: In the OECS, ART is cost-effective by international standards. Reducing second-line ART costs increases cost-effectiveness and affordability. Current funding supports implementing universal access regionally over the next year, but additional funding is required to sustain lifetime care for currently infected persons.

Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy.

BACKGROUND: India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. OBJECTIVE: To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. METHODS: We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/microl (SD 291 cells/microl). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-based regimen. Cost-effectiveness in US dollars per year of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. RESULTS: Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 <350 cells/microl, to 88.9 (106.5) months with two lines of therapy initiated at CD4 <350 cells/microl. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430/YLS to US$550/YLS as the CD4 starting criterion was increased from CD4 <250 cells/microl to <350 cells/microl. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. CONCLUSIONS: In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival, but their cost-effectiveness depends on their relative cost compared with first-line regimens.

Estimates of opportunistic infection incidence or death within specific CD4 strata in HIV-infected patients in Abidjan, Côte d'Ivoire: impact of alternative methods of CD4 count modelling.

CD4 lymphocyte count is an important surrogate marker of HIV disease progression, but it is often unavailable at the time of clinical events. We analysed data from the Cotrame cohort (1999-2004) and the Trivacan Structured Treatment Interruption trial (2002-2005) to estimate the incidence of opportunistic infections and death within specific CD4 strata in HIV-infected patients receiving highly active antiretroviral therapy (HAART) in sub-Saharan Africa. We used three methods of CD4 modelling: the first assumed that CD4 cell count remained constant until the next measurement; the second assumed that it changed immediately to the level of the subsequent measurement; and the third assumed that it followed a linear function between two consecutive CD4 measurements. The cohort used in this analysis consisted of 981 patients. The incidence rates of opportunistic infections were highest in the lower CD4 strata and decreased in the higher CD4 count strata. The incidence rates of mild opportunistic infections and severe bacterial infections, however, remained high in the highest CD4 stratum. Although all confidence intervals overlapped among the three methods, the incidence rate estimates showed differences of up to 74% in the lowest CD4 stratum. Different methods of estimating CD4 counts at the time of clinical events led to minor differences in incidence rates, except in the CD4 stratum <50 cells/mm(3), where the follow-up time was shorter. All of the models indicate that the overall incidence of opportunistic infections under HAART in sub-Saharan Africa is high. This suggests that prophylaxis against opportunistic infections may be needed even for patients receiving HAART.

HIV drug resistance surveillance for prioritizing treatment in resource-limited settings.

BACKGROUND: Sentinel testing programs for HIV drug resistance in resource-limited settings can inform policy on antiretroviral therapy (ART) and drug sequencing. OBJECTIVE: : To examine the value of resistance surveillance in influencing recommendations toward effective and cost-effective sequencing of ART regimens. METHODS: A state-transition model of HIV infection was adapted to simulate clinical care in Côte d'Ivoire and evaluate the incremental cost-effectiveness of (1) no ART; (2) ART beginning with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen followed by a boosted protease inhibitor (PI)-based regimen; and (3) ART beginning with a boosted PI-based regimen followed by an NNRTI-based regimen. RESULTS: At a 5% prevalence of NNRTI resistance, a strategy that started with a PI-based regimen had a smaller health benefit and higher cost-effectiveness ratio than a strategy that started with an NNRTI-based regimen (cost-effectiveness ratio $910/year of life saved). Results consistently favored initiation with an NNRTI-based regimen, regardless of the population prevalence of NNRTI resistance (up to 76%) and the efficacy of an NNRTI-based regimen in the setting of resistance. The most influential parameters on the cost-effectiveness of sequencing strategies were boosted PI-based regimen costs and the efficacy of this regimen when used as second-line therapy. CONCLUSIONS: Drug costs and treatment efficacies, but not NNRTI resistance levels, were most influential in determining optimal HIV drug sequencing in Côte d'Ivoire. Results of surveillance for NNRTI resistance should not be used as a major guide to treatment policy in resource-limited settings.

Medicare's national coverage decisions, 1999-2003: quality of evidence and review times.

In 1998 Medicare amended its procedures for making national coverage decisions for new technologies in an attempt to make the process more transparent and evidence based. We examined the quality of evidence for sixty-nine technologies reviewed by Medicare since then. Determinations by the Centers for Medicare and Medicaid Services (CMS) have generally been consistent with the strength of evidence. Good clinical evidence from rigorous studies is usually lacking for the technologies Medicare considers, although in most cases the CMS covers with conditions if there is at least fair evidence that benefits outweigh harms. Decisions referred to the external Medicare Coverage Advisory Committee (MCAC) have averaged eight months longer than non-MCAC decisions.