The Journal of Infectious Diseases SUPPLEMENT ARTICLE

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1 The Journal of Infectious Diseases SUPPLEMENT ARTICLE The Epi Info Viral Hemorrhagic Fever (VHF) Application: A Resource for Outbreak Data Management and Contact Tracing in the West Africa Ebola Epidemic Ilana J. Schafer, 1,2,a Erik Knudsen, 1,a Lucy A. McNamara, 3 Sachin Agnihotri, 1 Pierre E. Rollin, 2 and Asad Islam 1 1 Epi Info Team, Division of Health Informatics and Surveillance, 2 Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, and 3 Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia The Epi Info Viral Hemorrhagic Fever application (Epi Info VHF) was developed in response to challenges managing outbreak data during four 2012 filovirus outbreaks. Development goals included combining case and contact data in a relational database, facilitating data-driven contact tracing, and improving outbreak data consistency and use. The application was first deployed in Guinea, when the West Africa Ebola epidemic was detected, in March 2014, and has been used in 7 African countries and 2 US states. Epi Info VHF enabled reporting of compatible data from multiple countries, contributing to international Ebola knowledge. However, challenges were encountered in accommodating the epidemic s unexpectedly large magnitude, addressing country-specific needs within 1 software product, and using the application in settings with limited Internet access and information technology support. Use of Epi Info VHF in the West Africa Ebola epidemic highlighted the fundamental importance of good data management for effective outbreak response, regardless of the software used. Keywords. Ebola; viral hemorrhagic fever; outbreak; contact tracing; data management; software. Between July and November 2012, 4 filovirus outbreaks 3 of Ebola virus disease (EVD) and 1 of Marburg virus disease (MVD) were identified in Uganda and the Democratic Republic of the Congo, demonstrating unprecedented frequency [1]. Despite previous filovirus outbreaks in those countries, the outbreaks back-to-back occurrence, and overlapping response partners, avoidable and repeated data-management challenges occurred in each response. Filovirus outbreak responses comprise many components, each generating and relying on different but interrelated data sets. Case investigation involves completing a case investigation form (CIF) on every person meeting the case definition, with data collected on patient demographic characteristics, clinical signs and symptoms, hospitalization, possible sources of virus exposure, and final outcome. Laboratory diagnostic testing either confirms or rules out filovirus infection, and results must be used to update case classifications assigned during initial case investigation, from suspected or probable to either confirmed (for positive test results) or not a case (for negative results), and to inform management of patients and their contacts. Case management teams, providing clinical care to Presented in part: 2015 International Symposium on Filoviruses, Washington D.C., March 2015; 2015 International Conference on Emerging Infectious Diseases, Atlanta, Georgia, August a Present affiliations: Bacterial Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia (I. J. S.) and Office of the Associate Director for Communication, Division of Communication Services, Centers for Disease Control and Prevention, Atlanta, Georgia (E. K.). Correspondence: I. J. Schafer, 1600 Clifton Rd NE, MS A-30, Atlanta, GA (wii3@cdc.gov). The Journal of Infectious Diseases 2016;214(S3):S Published by Oxford University Press for the Infectious Diseases Society of America This work is written by (a) US Government employee(s) and is in the public domain in the US. DOI: /infdis/jiw272 patients, record clinical information and final outcome. Contact tracing, which helps rapidly identify and isolate new cases and interrupt virus transmission, requires listing all persons exposed to cases and then following them and recording their health status on a daily basis for the duration of the virus smaximumincubation period.high-qualityandreliablecase,contact,andlaboratorydata are required to drive, evaluate, and maximize the effectiveness of the outbreak response. These data must be efficiently communicated among all response components and also be compiled in a centralized database for analysis and situational reporting (Figure 1). As each response component depends on information from the others, data-communication gaps can lead to serious response lapses, such as insufficient contact listing and tracing, leading to delayed identification and isolation of new cases and avoidable virus transmission. Three of the 2012 filovirus outbreaks were confined to 1 location, with each response including 1 Ebola treatment unit (ETU), 1 main laboratory, and a colocated surveillance team. However, in all 4 outbreaks, case, laboratory, and contact-tracing data were maintained in separate databases with overlapping data content, often managed by different response organizations. Case and laboratory databases were usually maintained in Microsoft Excel, with laboratory results entered separately into both. The contact-tracing database, also containing basic case data, was managed either on paper or in the Field Information Management System (FIMS) [2]. Diagrams of virus transmission between cases were maintained in Microsoft PowerPoint. Having 4 unconnected data sets resulted in decreased efficiency due to duplicate data entry, occasional conflicting data, difficulties compiling daily situation reports, and inefficient communication among outbreak response components. S122 JID 2016:214 (Suppl 3) Schafer et al

2 Figure 1. Ideal data flow during a viral hemorrhagic fever (VHF) outbreak. During a VHF outbreak response, it is essential that data are shared between response components to maximize outbreak response effectiveness. The Epi Info Viral Hemorrhagic Fever application (Epi Info VHF) helps to streamline some of this data-sharing process by integrating case and contact data into the same relational database, which enables case data (such as laboratory results and epidemiology case classifications) to influence daily contact-tracing activities and contact-tracing data to inform case counts (such as by automatically creating case records for contacts that have become sick). Ideally, new case investigation form, laboratory, and patient outcome data are entered every day to maintain a real-time case database. Laboratory data influences the classification of cases, which in turn informs contact-tracing needs. Laboratory data must also be shared directly with patient-care facilities to inform patient management. In addition to case information, newly listed contacts and daily contact status information must be entered every day to maintain a real-time contact database that can be used to drive daily contacttracing activities. Contact-tracing teams must immediately notify case investigation and management teams of any contacts who have fallen ill, to ensure timely investigation and isolation. The data-management tools used in 2012 have certain limitations. Excel allows free-form data entry that leads to data inconsistency and errors, and it cannot accommodate the relational database structure needed to most efficiently manage case, contact, and laboratory data. Paper-based contact-tracing systems are prone to error, inefficient, and difficult to analyze, especially as the number of contacts increases. Data on contacts, initially listed by the case they were exposed to, must then be transcribed by hand into contact-tracing follow-up sheets (with each contact s data recorded on a separate sheet or data for all contacts in a given location grouped together in the same sheet[s]). Transcription errors and loss of paper sheets can lead to unintentionally dropped contacts, and updating paper records when new exposures extend a contact s follow-up period is difficult and inefficient. FIMS was created by the World Health Organization (WHO) in 2006 to manage both case and contact outbreak data but was only used to organize contact-tracing data in select outbreaks because of its complexity, need for customization for each outbreak (since it is not etiology specific), and lack of sufficient support staff to provide updates. Contact-tracing lists produced by FIMS automatically dropped contacts after their last day of follow-up even if they were never seen by the contact-tracing team. In each 2012 outbreak, a data-management plan (including standardized data-collection forms and databases, a unique case identifier system, and data-communication protocols) had to be generated anew at the beginning of each outbreak, leading to multiweek delays in establishing a data-driven outbreak response (which was never attained in some outbreaks). Even after databases were established, poor data-management practices resulted in less efficient outbreak responses. The Epi Info Viral Hemorrhagic Fever application (Epi Info VHF) was initially developed as a solution to the challenges experienced managing case, contact, and laboratory outbreak data during the 2012 filovirus outbreaks, and it was eventually used and adapted during the West Africa Ebola epidemic. METHODS Application Goals and Development Development of Epi Info VHF began in February 2013 with the goal of preparing for data-management needs in future VHF outbreaks by developing a user-friendly, comprehensive database for case, contact, and laboratory data, built around standardized datacollection forms that would (1) allow management of complex relationship data; (2) reduce data-entry errors; (3) automate the generation of daily contact-tracing lists to ensure appropriate contact follow-up windows and prevent inadvertent loss or premature discharge of contacts from follow-up; (4) operate in locations with no Internet connectivity, sometimes for the entire duration of an outbreak; (5) automate the generation of epidemiologic transmission chains; (6) automate and simplify the analysis of data needed for outbreak situation reports; and (7) improve the overall consistency, communication, and effective use of outbreak data. A standardized CIF (Supplementary Appendix 1) andcontactlisting form (Supplementary Appendix 2) were created by the Epi Info VHF and the West Africa Ebola Epidemic JID 2016:214 (Suppl 3) S123

3 Table 1. Epi Info Viral Hemorrhagic Fever (VHF) Application Functions That Promote Best Practices in VHF Outbreak Responses Function Automatically sets correct contact follow-up window, based on VHF outbreak type Contact follow-up lists and individual contact status and follow-up windows automatically updated as source cases are added, removed, or reclassified and as daily contact status data are entered Contacts are not removed from follow-up lists until the user verifies they were seen and healthy on their last day of follow-up (or until they are marked as sick) Case and contact records linked for contacts converted to cases Automatic case and contact-tracing data analysis generated including case counts, fatality rates, and descriptive epidemiologic statistics; epidemic curve; number of contacts under follow-up and proportion followed each day; and number of contacts who have become cases Preformatted reports produced on confirmed and probable cases without listed contacts, currently isolated cases, and live cases classified as suspected or probable Microsoft.SQL server database use enables multiuser data entry, with records being edited locked to other users Data entered into individual databases can be merged into a central database, updating already existing information; the merge process occurs offline Effect Ensures that correct follow-up period is used Ensures that contacts are followed for the appropriate period (even if additional exposures occur), helping prevent transmission by ensuring adequate followup duration and conserving resources by avoiding unnecessary contact tracing Prevents contacts who have gone missing and could potentially be sick from being overlooked because their follow-up period is over Enables tracking of how many contacts were converted to cases and the proportion of cases who were previously identified as contacts, which is important for evaluating effectiveness of contact tracing Promotes evaluation of outbreak response effectiveness and gaps Promotes outbreak response actions, including contact listing, inquiries on hospitalized case status and outcome, and diagnostic sample acquisition Provides a mechanism to keep up with a high volume of data entry, while preventing the simultaneous entry of conflicting data values into the same record by multiple users Enables multiple databases to be actively maintained at a local level, where the data are collected, and then to be merged at a central level for outbreak analysis and reporting; offline merging accommodates areas with limited Internet connectivity Centers for Disease Control and Prevention s (CDC s) Viral Special Pathogens Branch on the basis of forms used and lessons learned in the 2012 outbreaks, with input from the Uganda Ministry of Health (MoH), Médecins Sans Frontières, and the WHO. Application requirements were written by the Viral Special Pathogens Branch on the basis of previous outbreak experiences and discussions with the same response partners, including staff involved in the development and use of FIMS. Epi Info VHF was originally designed for VHF outbreak data management in Uganda, where outbreaks were usually isolated to 1 geographic location. Options accommodating additional countries, languages, and outbreak scenarios were planned for after the application was finalized for Uganda. Epi Info 7 (available at: selected as the base upon which to build the VHF data-management application because of its wide international use, customizable and user-friendly data-entry forms with data-validation features, point-and-click data analysis requiring minimal training to use effectively, free availability online, and existence of a software support and development team enthusiastic to provide an informatics solution to the data-management problems of VHF outbreaks. Epi Info 7 lacked preexisting contact tracing, transmission-chain mapping, or interactive line-list features. Epi Info 7 and the Epi Info VHF application were designed to execute on the Microsoft.NET Framework and were written in the C# programming language. Leveraging.NET allowed the application to remain compact, facilitating installation in areas with slow and unreliable Internet connectivity and allowing the software to be installed without administrative rights. Microsoft Access was used as the back-end database format. In September 2013, a week-long workshop was held in Uganda to provide training on a beta version of Epi Info VHF and obtain feedback on the application from response partners. Attendees included representatives from the Uganda MoH, the Uganda Central Public Health Laboratories, the Uganda Virus Research Institute, the Uganda People s Defense Force, the CDC (Uganda and Atlanta), Médecins Sans Frontières (Belgium and Spain), and the WHO (Uganda and Geneva). Application development continued after the meeting, based on the feedback obtained. Subsequent beta versions of Epi Info VHF were used during the West Africa Ebola epidemic, during which firsthand field experiences of the Epi Info VHF team and feedback from users informed continuous application development. RESULTS Features of the Epi Info VHF Application Extensive subject matter expertise regarding the science and outbreak response needs of EVD and other VHFs is built into Epi Info VHF (Table 1). The most recent version as of August 2016 ( ), is outlined below and can be freely downloaded from the Epi Info VHF website (available at: com) along with its user guide, which provides a more detailed review of the application s features. It contains many improvements and added functionalities (including a US-specific mode), compared with the last version publicly released for use in the West Africa epidemic ( , also available on the Epi Info VHF website). Importantly, version is not backward compatible with version or earlier versions these older versions are incapable of importing data from the new version. Operational Requirements and Data-Storage Options Epi Info VHF requires Windows (Vista, 7, 8, or 10) and Microsoft.NET Framework, version 4.5. Epi Info 7 is included with the Epi Info VHF application download. When creating a new S124 JID 2016:214 (Suppl 3) Schafer et al

4 Figure 2. Case line list. Screenshot of a case line list in the Epi Info Viral Hemorrhagic Fever application (Epi Info VHF). For the selected case (highlighted in blue), either all contacts linked to that case (displayed here) or the source case(s) who that case is linked to can be viewed at the bottom of the screen. A!! towards the left of a case record alerts the user that both a case and contact record exist for that patient in the database. database in Epi Info VHF, the default data-storage format is Microsoft Access. For multiuser data entry, the application can be configured to instead connect to a Microsoft SQL Server database. Database-Setup Options Databases can be created in international or US mode and in French or English these settings cannot be adjusted after database creation. Epi Info VHF can accommodate outbreaks of EVD, MVD, Lassa fever, Crimean-Congo hemorrhagic fever (CCHF), and Rift Valley fever (RVF), and will use the appropriate contact-tracing follow-up period, based on which virus is selected (21 days for EVD, MVD, and Lassa fever; 14 days for CCHF; and none for RVF). Administrative location labels can be customized for the affected country. Case Database/Data Management Case data, including CIF and outcome information, are entered into an electronic form, with both a long form and short form (containing a subset of long-form variables) available for interchangeable use, which are based on the corresponding paper CIFs. Each case is assigned an epidemiology case classification. Detailed laboratory diagnostic results can be entered for an unlimited number of samples per patient. Extensive data-validation logic is included in the entry forms to reduce data-entry errors. All case records are displayed in a searchable, sortable line list comprising an abbreviated set of essential variables (Figure 2). Virus transmission information can be included by entering a relationship link between a case and its source case(s), defined as an upstream case that may have been the source of infection, based on a known exposure event (Figure 3). Contact Database/Data Management and Contact Tracing Contact records are created by entering information collected on the contact-listing form (Figure 4) and then linking the contact to1ormoresourcecases(thecase[s]theywerelistedfor;figure3) by entering information on the relationship between the entered contact and each source case (Figure 4). By having only 1 record per contact that can be linked to multiple source cases, contact duplication is avoided while allowing contact follow-up periods to be automatically updated when multiple exposures occur. An overall date of last contact is automatically calculated for each contact, corresponding to the most recent exposure to any source case who is not classified as not a case. The date of last contact is used to calculate the contact s follow-up window and is updated accordingly when the contact is linked to or unlinked from an additional source case or if the epidemiologic classification of a source case changes, to ensure that the contact is followed for the appropriate period. All Figure 3. Source case, case, contact relationships. In the Epi Info Viral Hemorrhagic Fever application (Epi Info VHF), source case can refer to either the case who another case-patient was exposed to or the case who a contact was exposed to. Anyone designated as a case is/was sick and meets the case definition, whereas anyone designated as a contact is an asymptomatic person who had exposure to a case while the case was sick. Epi Info VHF and the West Africa Ebola Epidemic JID 2016:214 (Suppl 3) S125

5 Figure 4. Contact data entry form and relationship box in the Epi Info Viral Hemorrhagic Fever application (Epi Info VHF). A, Each line from the contact-listing form (Supplementary Appendix 2) is entered as an individual contact record into the contact data-entry form. The contact s final outcome at the bottom of the form is not editable by the user but is instead automatically assigned by the application, based on data entered for the contact (Figure 6) or the contact s source cases. Discharged from follow-up : contact successfully completes follow-up without developing Ebola virus disease (marked as healthy on their last day of follow-up); developed symptoms and isolated OR died : contact becomes sick and is converted to a case (marked as sick and isolated); dropped from follow-up : all source cases the contact is linked to are classified as not a case, and therefore the contact does not need to be followed any longer. B, Every time a link between a contact and their source case or between a case and their source case (Figure 3) is entered into the application, the relationship information between those 2 people (including the date of last contact, the type of relationship, and types of contact) are entered into a relationship information pop-up box. This enables each individual case or contact to maintain 1 case or contact record but, at the same time, an unlimited number of relationships to their source case(s). contact records are displayed in a searchable, sortable contact line listthatisviewedseparatelyfromthecaselinelist(figure5). Epi Info VHF generates printable contact-tracing follow-up sheets (with contacts grouped by location) in daily or 21- day formats (Figure 6), with an option to export the follow-up list to Microsoft Excel for user customization. Each contact s daily status recorded by contact tracers can be entered into the application through data entry involving 1-click per contact, with the option to record body temperatures and notes (Figure 6). The application automatically inactivates contacts (ie, removes them from follow-up lists and assigns them a final outcome) if the contact is (1) marked as seen and healthy on their 21st day of followup (ie, discharged from follow-up), (2) marked as sick and isolated (ie, converted to a case) at any point during follow-up, or (3) dropped from follow-up because all source cases for the contact were reclassified as not a case (Figure 4). If, on a contact s 21st day of follow-up, nothing is recorded or the contact was noted as not seen, the contact remains active and continues to appear on daily follow-up lists until their health status is verified and entered for their 21st day of follow-up. This ensures that contacts are only removed from follow-up if they are actively verified to not have Ebola-like illness, instead of automatically dropping them at the end of their follow-up window irrespective of follow-up status, which could result in overlooking a sick contact who has not been seen by the contact-tracing teams. When the user indicates that a contact has become ill and been isolated, the application converts that contact to a case, creating a new, linked case record containing applicable information from their contact record. Linkage of the case and contact records for the same person allows the contact record to be automatically S126 JID 2016:214 (Suppl 3) Schafer et al

6 Figure 5. Contact line list. Screenshot of the contact line list in the Epi Info Viral Hemorrhagic Fever application (Epi Info VHF). Gray shading indicates that a contact is inactive or no longer under follow-up. For the selected contact (highlighted in blue), either a list of that contact s source case(s) or a 21-day individual follow-up report for that contact (as displayed at the bottom of the screen) can be viewed. The contact individual report is color-coded on the basis of the status entered for each day of follow-up. Green indicates the contact was seen and healthy, red indicates the contact was sick and isolated/met the case definition, yellow indicates the contact was sick but not isolated/didn t meet the case definition, gray indicates the contact was not seen or no information was recorded by the contact tracers, and blank/white indicates that the user did not enter follow-up information for that day. A!! listed to the left of the contact record indicates that both a case and contact record exist in the database for that patient. reactivated for continued follow-up if the patient tests negative (as indicated by reclassification to not a case ) while still inside his/ her follow-up window, and it allows investigators to track how many cases were originally followed as contacts. Alternatively, a person entered first as a case and eventually classified as not a case can be converted to a contact (creating a new, linked contact record) if they need to be followed after exposure to a confirmed case (eg, during hospitalization). The automated contact-tracing features of Epi Info VHF, including determination of which contacts need follow-up, calculating and updating each contact s follow-up window, and generation of daily follow-up lists, reduce errors and omissions in contacttracing data management and save response staff time and effort (Table 1), and they are major advantages as compared to Excel or paper contact-tracing systems. In addition, the daily submission of contact follow-up status data intended with Epi Info VHF (as compared to submission at completion of the follow-up period, with paper systems) increases the accountability of contact tracers and enables multiple checks (by supervisors and data managers) for raising alerts about sick or missing contacts. Data Analysis and Reporting Epi Info VHF provides an automatically generated analysis of statistics on cases and contact tracing that is continuously updated as new data are entered into the application, as well as preformatted reports intended to drive specific outbreak response actions (Table 1). The user can also conduct a free-form analysis by loading the case and/or contact record data into Epi Info 7 s Dashboard Analysis tool directly from the application, with optional preset data filters. These custom analyses can be saved within Epi Info VHF and run again at any time with a single button click to update the analysis with the current data. Case and contact data exported into a comma-separated value file or in the back-end Access database (both containing the daily contact-tracing data) can be analyzed in the user s choiceofsoftware. Transmission-Chain Mapping A transmission-chain diagram (still in beta) is automatically generated for confirmed and probable cases. The transmission chain is displayed on a time line based on each patient s dateof symptom onset (Figure 7); therefore, any patient with a missing date of onset, as well as cases downstream of that patient, will not be displayed. Importing and Exporting Data An Epi Info VHF database can be exported as a data-sync file, and during export data can be filtered by multiple criteria and/or deidentified. The data-sync file can be imported into a blank Epi Info Epi Info VHF and the West Africa Ebola Epidemic JID 2016:214 (Suppl 3) S127

7 Figure 6. Daily contact-tracing data collection and entry into the Epi Info Viral Hemorrhagic Fever application (Epi Info VHF). A, Automated lists of contacts who need to be followed each day, grouped by location, are compiled by the application and can be printed to give to contact tracers. The daily status of each contact is recorded in the Status column, using 1 of 3 predefined symbols defined at the top of the form (corresponding to either healthy, sick, or not seen). The completed form can then be turned into contacttracing supervisors and, subsequently, data managers. B, Contact-tracing sheets can also be printed in a 21-day format (instead of the daily format). Each time the 21-day follow-up sheet format is printed, it will be prefilled with the symbols corresponding to each contact s daily status that have already been entered into Epi Info VHF. C, Once the day s completed contact follow-up sheets have been submitted, the data manager can enter each contact s daily status in the displayed Epi Info VHF data-entry screen, using 1 click per contact to select a box matching the symbol recorded by the contact tracers. There is also room to record up to 2 temperatures per day for each contact, as well as free-form notes. S128 JID 2016:214 (Suppl 3) Schafer et al

8 Figure 7. Transmission chain. A transmission-chain diagram, displayed on a time line, is automatically generated in the Epi Info Viral Hemorrhagic Fever application (Epi Info VHF), based on relationship information entered between cases. Solid arrows denote an established exposure event, and dotted lines denote a presumed exposure event. Boxes with solid lines denote confirmed cases, and boxes with dotted lines denote probable cases. The width of the box represents the amount of time a case was in the community while infectious. The left side of the box shows the date of symptom onset, and the right side of the box shows either the date of isolation or the date of death. Symbols: H, healthcare worker; +, fatal case. VHF database, for data viewing, analysis, or seeding a new database, or into an existing database, to merge with and update that database. In the latter scenario, the information in any matching records (based on a global unique identifier assigned by Epi Info) in the sending database will overwrite the information in the receiving database, while any nonmatching records from the sending database will be added as new records to the receiving database. These import/export rules are built upon the requirement that, in a multilocation outbreak where multiple databases are maintained, data will be actively managed at regional or local levels and merged at a higher central level, with unidirectional data flow (Figure 8). Administrative Functions Features are built into Epi Info VHF for administrative-level control over data quality. For example, an administrative code must be entered any time a case or contact is deleted from the database. In addition, a database can be opened in super user mode by providing a separate code, which enables the user to access tools for administrative tasks such as creating drop-down lists for data-entry variables or editing variable values automatically assigned by the application. US Mode Differences Modifications in the US mode of Epi Info VHF (compared with the international mode) include (1) US-oriented and customizable case and contact data-entry forms to accommodate differing data-collection between states and entry of more-detailed contact data than collected in Africa and (2) US-specific labels and data-entry drop-down lists throughout the application, including case and contact classifications used in the United States during the West Africa EVD epidemic. These changes reflect a fundamental difference between EVD responses in Africa, where only enough contact data are collected to facilitate contact tracing in the face of numerous cases and contacts and ongoing community transmission, and the US response, which focused on preventing any community transmission from the few imported cases through more-intense contact monitoring and, therefore, moredetailed data collection, especially for healthcare workers caring for patients in isolation facilities, who were considered contacts in the United States but not Africa. A beta version of the application containing the US mode was available upon request starting in December 2014, with a more updated version available in May Epi Info VHF and the West Africa Ebola Epidemic JID 2016:214 (Suppl 3) S129

9 Figure 8. Central and satellite databases. When using the Epi Info Viral Hemorrhagic Fever application (Epi Info VHF) for data management in multiple locations involved in the same outbreak, 1 central database should be established (such as a national database), as well as multiple satellite databases (such as districtlevel databases), with data for nonoverlapping regions entered into each satellite database. Exported data-sync files from each satellite database can be imported into the central database on a regular basis. Since, during the import process, records are matched and merged on the basis of each record s global unique identifier assigned by Epi Info, a satellite database for a particular region should be started with a seed database exported from any database that already contains information for that region, if any such database exists. UseDuringthe West Africa Ebola Epidemic During the West Africa Ebola epidemic, the Epi Info VHF application was used in 7 African countries (Guinea, Sierra Leone, Liberia, Nigeria, Senegal, Mali, and, for a concurrent unrelated outbreak, Uganda) and at least 2 US states (Texas and Virginia). In each country, the application was implemented in varying fashions and over different time lines, used with varying database network structures (centralized vs diffuse) and for different purposes, and affected by shared and country-specific challenges. The primary CIF and contact-listing forms used throughout the affected African countries were the forms developed and standardized for use in conjunction with Epi Info VHF or shortened forms derived from them. Initial Implementation and Modification for Use in the West Africa EVD Epidemic An EVD outbreak was identified in Guinea in March 2014 [3], with cases initially localized in 2 distinct areas [4], individually resembling the type of small, localized outbreak for which Epi Info VHF was designed. In preparation for potential use, the entire application and all associated data-collection forms were translated into French within 1 week of the outbreak s identification, and a few days later, on 31 March 2014, a CDC response team, including the software developer and epidemiologist who created Epi Info VHF, arrived in Guinea. CDC and WHO response staff agreed that the nascent Epi Info VHF application, although unfinished, was the best option for management of the outbreak data, and it was thus adopted for use. Within 2 days, all contacts listed in Conakry had been entered into an Epi Info VHF database, and the application was being used to drive Conakry s contact-tracing activities. Within 1 week, all available case data for the entire country had been entered into the Epi Info VHF database, which was then maintained in real time and shortly thereafter used to produce the daily outbreak situation report. The CDC provided on-site application support and continuous development to make needed modifications and additions, establishing a stable version of the software that accommodated Guinea s existing data-management needs by the end of April. Unlike previous EVD outbreaks, however, the 2014 outbreak continued to grow, spreading both within Guinea and to neighboring Sierra Leone and Liberia by May 2014, and, by June 2014, had more cases recorded than any previous EVD outbreak [4]. By July 2014, weekly case counts in Sierra Leone and Liberia far exceeded the more-stable case counts in Guinea [5]. The sheer number of cases, large geographic area affected, and resulting proliferation of ETUs, laboratories, and surveillance teams that were managed by varying response partners between regions led to unique data-management challenges. Although Epi Info VHF had not been designed for such a widespread outbreak, its use spread quickly because it was being successfully used in Guinea, it was the only software designed specifically for VHF outbreaks, and the CIF and contact-listing forms the application wasdesignedaroundhadbeenrapidly adopted for data collection in all 3 countries. To accommodate the unique data-management needs of the West Africa EVD epidemic, vigorous development of Epi Info VHF resumed in July 2014 and continued through May The application, originally developed for single-user data entry in 1 location, had 2 major modifications implemented in August Microsoft SQL Server support was added to enable multiuser data entry to accommodate the volume of data generated by the high case incidence. In addition, database import, export, and merge functions were created to allow separate Epi Info VHF databases to be maintained at the local and regional level and then merged into a national database, which could then be merged into an international database. The merge functions were designed to work without continuous Internet connectivity, owing to the poor communications infrastructure in many areas. Another key modification was the introduction of a shortened version of the case data-entry form (in fall 2014) with an improved user interface and a subset of variables from the original CIF (Supplementary Appendix 3). This addition was made in concert with the development of shorter hard copy CIFs in each country and enabled faster data entry, with the option to switch back to the long, more detailed form when needed. In addition, a US mode was added to the application to support its use for contact data entry and contact tracing in the United States, based on requests from multiple state health departments. Throughout the outbreak, user support and training were provided by the Epi Info VHF team, both remotely and in-country over repeated deployments to Guinea, Liberia, and Sierra Leone, and training sessions were conducted for US S130 JID 2016:214 (Suppl 3) Schafer et al

10 responders deploying to West Africa and for state and local health department staff. Guinea Continued Use The centralized Epi Info VHF database established in Conakry at the beginning of the epidemic included data for cases reported throughout the country. Based on a system implemented at the outbreak s start, data managers in other affected prefectures compiled and transmitted epidemiologic data (from a CIF or alternate abbreviated data), laboratory data, and outcome data to Conakry on a daily basis via Excel spreadsheets for entry into the national Epi Info VHF database, where Conakry case data were entered directly. Starting April 2014 and continuing until 16 March 2016 (greater than 2 months after Guinea was first declared Ebola free by WHO), the Epi Info VHF database was maintained in this way in real time and was the main source of information for daily situation reports (M. Worrell, personal communication). On 17 March 2016, a new cluster of EVD cases was detected in N'Zerekore prefecture, for which a new Epi Info VHF case database was created, which remains in use as of 28 July 2016 (M. Worrell, personal communication). Epi Info VHF use in Conakry to organize and drive contacttracing activities continued between April and September of 2014, with contact-tracing lists printed every morning and daily status information entered each evening. Originally maintained in the same Epi Info VHF database as the national case data, the Conakry contact-tracing data was split into a separate Epi Info VHF database in May 2014, in part because of difficulties entering both case and contact data during the day multiuser data-entry functionality had not yet been developed, and CDC staff conducting evening contact data entry had departed. The benefits of managing real-time case and contact data in the same database, such as reduced data entry and automatically updated contact follow-up status, were therefore removed. In September 2014, Conakry contact-tracing data management was switched to Excel. Guinea was the only country where (1) the Epi Info VHF team was deployed to directly facilitate the set-up and use of the application from the beginning of both the outbreak response and the application s use in-country, (2) the centralized case database and the associated data management and communication structure established at the start of the outbreak successfully persisted throughout the outbreak response, and (3) the centralized case database was maintained in real time and used to create daily situation reports. Sierra Leone The first confirmed EVD case in Sierra Leone was identified in Kenema District on 24 May 2014 [4], with most cases located in Kailahun and Kenema districts until July or August. Use of the CIF created for use with Epi Info VHF was instituted in June. In August 2014, when the first CDC team arrived in Sierra Leone, the existing Excel case and contact databases in Kenema and Kailahun, containing data for the entire country, were imported into Epi Info VHF to create a new centralized database. This database was initially maintained in Kenema, with CIF data from Kailahun transmitted for entry via an Excel spreadsheet (J. Bangura, personal communication). By 14 September, Epi Info VHF case databases were operational in 6 districts (Kailahun, Kenema, Bo, Bombali, Port Loko, and Western). Using the newly developed data export, import, and merge functionalities in Epi Info VHF, these districts regularly transmitted sync files for import into the national database, then located at the Sierra Leone Ministry of Health and Sanitation in Freetown, where data for the remaining affected districts were entered directly. Eventually, all 13 districts in Sierra Leone entered case data into their own local Epi Info VHF databases, with most transmitting a sync file to Freetown on a weekly basis for merging into the national case database (A. Kamara, personal communication). Data for all investigated cases continued to be entered into Epi Info VHF until the end of the outbreak (A. Kamara, personal communication). Sierra Leone was the only country affected by the West Africa Ebola epidemic that deployed the Epi Info VHF application so diffusely, with databases maintained on a district level and merged at a central level. The national Epi Info VHF database, designated as Sierra Leone s official outbreak database, was the only place in which the country s comprehensive outbreak case data were maintained (J. Redd, personal communication). Both the CDC and the WHO conducted ongoing analyses on these data to evaluate outbreak progression, make decisions about resource deployment, and plan for personnel movement. The data quality of the district Epi Info VHF databases varied widely due to differences in completeness of initial data entry, how well case records were updated, the quality of data management, and the level of training provided on the use of Epi Info VHF. Therefore, unlike in Guinea, Sierra Leone s national Epi Info VHF database was not maintained in real time and, thus, was not used to produce daily outbreak situation reports, which were instead compiled from daily laboratory results and ETU data. However, some districts, such as Bombali and Port Loko, operated their Epi Info VHF case databases in real time and used them to conduct analyses for district situational meetings and assessment of outbreak control measures (B. Gleason, personal communication) [6]. Although almost all districts entered their contact lists into their Epi Info VHF databases, most used Excel or paper-based datamanagement systems to organize and drive contact-tracing activities. A notable exception was that, in January 2015, Kambia began using Epi Info VHF to drive daily contact-tracing activities for up to a few hundred contacts each day, with data managers and contact-tracing supervisors communicating contacts who needed follow-up and their daily status by phone [7]. Kambia continued using Epi Info VHF for contact tracing through the end of widespread community transmission, in July 2015 (R. Levine, personal communication). Epi Info VHF and the West Africa Ebola Epidemic JID 2016:214 (Suppl 3) S131

11 Liberia During the first wave of the Ebola outbreak in Liberia (late March early April 2014) Epi Info VHF was used by CDC and WHO response staff to create a central case and contact database (B. Petersen, personal communication), eventually located in the capital, Monrovia. Contact lists entered into the database were exported to Excel to create county-specific contact-tracing lists and guide creation of paper 21-day contact follow-up sheets (WHO April 2014 Liberia team, personal communication). When the second wave of EVD cases was detected in Liberia, in May, the MoH surveillance staff in Monrovia used the existing Epi Info VHF database to add CIF and other data on newly reported cases. By the time a CDC team arrived, in July 2014, the rapid increase in case incidence and spread around the country, difficulties consistently transmitting data from affected counties to Monrovia (hampered by unreliable internet), and the initial restriction of single-user data entry into the Epi Info VHF database had led to a large backlog of unentered data. Therefore, the database could not be used to produce daily situation reports, which were instead based on aggregate county reports. In August, the newly developed SQL server based multiuser data-entry system was implemented in Monrovia, and a countylevel Epi Info VHF case database was established in Lofa, transitioning all data entry for that county to the local level, with data-sync files sent for incorporation into the central Monrovia database as often as Internet connectivity would allow. As the outbreak continued to spread within Liberia during summer and fall 2014, additional counties established local Epi Info VHF case databases, including Margibi and Grand Cape Mount. Although many contact lists and some contact-tracing outcomes were entered into Epi Info VHF in select locations, such as Montserrado County, the application was not used to actively drive daily contact-tracing activities; if used, contact lists were first exported to Excel. Unfortunately, difficulties involving data flow and transmission remained, and despite the new multiuser data entry, data influx still outpaced data-entry capacity in Monrovia. As the number of records in the Epi Info VHF databases grew into the thousands, application response times slowed and data-import times increased as a result of the software s initial design for use in small, localized outbreaks. Capacity to handle larger record numbers was eventually added to the application but not until after the large surge in Liberia s case numbers. With the goal of improving database timeliness and completeness by instituting an online database for real-time data entry of minimal essential case and contact data at the county level, the MoH switched to using a system developed specifically for their needs in DHIS2 software ( in December 2014 [8]. All historically entered data were maintained in the central Epi Info VHF database, with limited data migrated to DHIS2. However, in the end, continued fragmentation of the data-management system, case and contact data submission to the national level in a variety of formats (including in Epi Info VHF, in DHIS2, in Excel, and on paper) and without consistent adherence to a standardized case ID system, and the varying strengths and weaknesses of the different software resulted in outbreak data maintenance and analysis using a combination of Excel, DHIS2, and Epi Info VHF for the rest of the outbreak (M. Mulbah, personal communication). Nigeria, Senegal, and Mali An EVD case from Liberia travelled to Nigeria on 20 July 2014, triggering an EVD outbreak there [9]. Epi Info VHF was initially used in Lagos as the central case database, until the end of August 2014 (D. Tom-Aba, personal communication), at which time a datamanagement system customized for the needs of Nigeria had been developed [10]. All case and contact data in Lagos were entered retrospectively into the Epi Info VHF database toward the end of the outbreak, for backup data storage (D. Tom-Aba, personal communication). At the end of August 2014, an EVD case travelled to Senegal from Guinea [11], and at the end of October, the first EVD case in Mali was imported from Guinea. Epi Info VHF was used by some response partners to create one of the multiple parallel databases containing case and contact information in each country. Uganda Concurrent with but not related to the EVD epidemic in West Africa, a case of MVD was detected in Uganda in October 2014 [12], and Epi Info VHF was successfully used to organize and drive contact tracing for the 197 contacts. Each day, contact follow-up sheets were printed and distributed to contact-tracing teams, and data on contact status from the completed sheets were entered into the database (T. Shoemaker, personal communication) [13]. Texas and Virginia On 30 September 2014, EVD was diagnosed in a patient who had travelled to Texas from Liberia [14]. Epi Info VHF was initially used for contact data management, including generating lists for contact tracing and monitoring and recording symptom data. However, because the US mode of the application had not yet been created at the time this case was diagnosed, the application could not accommodate some of the US-specific contact data-management needs, such as the ability to add or modify the data variables entered for contacts. As a result, the response team transitioned to using other software for contact data management [15]. The challenges identified with the use of Epi Info VHF in Texas helped inform the development of the application s US mode. Once the US mode of the application was made available, Virginia used Epi Info VHF to enter follow-up information, mostly retrospectively, on 12 healthcare workers who cared for a patient with EVD being treated in Maryland during March April Virginia also conducted a pilot of the application for 3 weeks, in June and July 2015, for monitoring travelers returning from West Africa but continued using their already existing system in Excel S132 JID 2016:214 (Suppl 3) Schafer et al