Comment: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE)

Comment: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) We think of this Supplement of the Journal of Infectious Diseases as a figurative manual of operations for how to build an airplane while flying it through a storm. The human toll of the Ebola virus disease (Ebola) epidemic of 2014–2016 was worse than that experienced in all previously recognized Ebola epidemics put together. The idea of testing experimental vaccines that were just entering Phase 1 studies in humans felt both essential and incredibly daunting, given the chaos of this epidemic and the setting of an ongoing epidemic where medical management and monitoring capacity were already strained and most commercial air carriers had cancelled routes. Nonetheless, our team of figurative airplane designers built the airplane, flew it, and landed it safely. Our airplane, the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) (Figure 1), forged strong partnerships between institutions in Sierra Leone and the broader public health and research community. With the successful collection of safety data on approximately 8000 vaccinated persons, the study findings also bring the world closer to having a safe and effective vaccine for preventing Ebola. (Clinical Trial Registration. ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].) Unlike previous Ebola outbreaks, which had generally been small and limited to remote, rural communities, this epidemic was huge and threatened an entire region. Ebola emerged in Guinea in March 2014 and then spread widely within Guinea and across borders into Liberia and Sierra Leone [1]. Early in the epidemic, cases occurred in Conakry, the capital of Guinea, the first time Ebola transmission had ever been reported in a major city. This was an ominous development given the size and density of the population; it meant that Ebola could spread more rapidly and extensively than it ever had before, and it also had profound repercussions for travel and trade [2]. By August 2014, Ebola was spreading rapidly in rural areas and had reached urban areas in all 3 highly affected West African countries. Case counts were increasing exponentially. Estimates of the future death toll were dire, highlighting the urgent need to rapidly scale up the ongoing control activities and to develop new tools for control and prevention [3]. The spread of Ebola to other countries in Africa, Europe, and the United States heightened fears and complicated humanitarian assistance. Despite aggressive efforts that were launched across West Africa during the last quarter of 2014 and continuing into 2016, approximately 29000 cases and more than 11000 deaths were reported throughout the region. These figures are likely a significant underestimate of the epidemic’s true mortality and morbidity. Many survivors continue to contend with the substantial long-term health effects of Ebola [4]. The Centers for Disease Control and Prevention (CDC) first sent staff to assist in Guinea in March 2014. In July, the agency activated its Emergency Operations Center and launched a large-scale response that would stretch into 2016 [5]. Many CDC staff who deployed to West Africa in 2014 had extensive global public health experience including in natural disasters, epidemics, and famine, but they still returned home stunned by what they had seen and the challenges that affected countries faced with controlling the epidemic. In the fall of 2014, the CDC began plans to expand its Ebola response to include sponsoring a vaccine trial. In late October 2014, CDC staff traveled to Sierra Leone to meet with the Ministry of Health and Sanitation (MOHS) and the College of Medicine and Allied Health Sciences (COMAHS), University of Sierra Leone, to discuss whether implementing an investigational vaccine trial would be possible in the midst of the epidemic. The higher risk of Ebola for healthcare workers had been recognized early in the Sierra Leone epidemic as these dedicated workers responded to the crisis. The CDC worked intensively with MOHS, COMAHS, and other key collaborators to begin planning a Phase 2/3 vaccine trial among healthcare and frontline Ebola response workers. This Phase 2/3 trial would test 1 of the 2 experimental Ebola vaccines selected after the Phase 1 trial data became available. The overarching goal of STRIVE was to accelerate the introduction of an Ebola vaccine among at-risk people in Sierra Leone while concurrently evaluating vaccine efficacy and safety. Guiding principles included starting the trial as soon as possible in the most-affected districts of Sierra Leone to provide as many people as possible the opportunity for protection. The study design and data-monitoring plan had to allow the flexibility to add study sites if the epidemiology of the epidemic changed and immediate recognition if the risk from the vaccine exceeded potential benefit to participants. It was also essential to extend the offer of vaccine to every participant by the end of the trial. Planning for the safety of participants who were volunteering to receive a product that had thus far been given to very few people was paramount [6]. Rapidly planning and implementing STRIVE in the midst of the Ebola epidemic presented enormous challenges. One was making a final decision on which vaccine to test. The STRIVE researchers ultimately chose the recombinant vesicular stomatitis virus vaccine (rVSVΔG-ZEBOV-GP) (acquired by Newlink Genetics from Public Health Agency of Canada and later licensed to Merck & Co., Inc., Kenilworth, NJ); a major factor in this decision was that, because the vaccine was replication-competent, a single dose might provide both immediate and more durable protection. The limited healthcare infrastructure and clinical trial experience in Sierra Leone posed additional challenges. A cold chain to store and transport this vaccine at ≤−60°C had to be created and maintained. Facilities to enroll, vaccinate, and follow participants in 7 locations across 5 districts had to be built or renovated. An especially challenging but ultimately very successful and rewarding task was hiring and training more than 350 local staff while ensuring that such hiring did not interfere with Sierra Leone’s Ebola response. Finally, given that the local population had limited understanding of Ebola disease and its prevention, communicating effectively and transparently was critical for gaining the trust of local communities. The STRIVE researchers had to ensure that potential participants understood that participation was voluntary and that the consent of those who decided to enroll was truly informed. The study was staffed by locally hired personnel who were supervised by the COMAHS Principal Investigator. They worked alongside CDC staff in Sierra Leone, the majority rotating on short-term assignments; CDC staff in Atlanta provided scientific, administrative, and logistical support. The US Biomedical Advanced Research and Development Authority, the National Institutes of Health, the US Embassy in Sierra Leone, the CDC Ebola Response Team in Sierra Leone and Atlanta, the CDC Foundation, eHealth Africa, The Emmes Corporation, FHI 360, Technical Resources, Inc., the World Health Organization, Global Good/Intellectual Ventures, and Modality Solutions all contributed critical skills and experience vital to STRIVE’s success. As trial planning proceeded, Ebola response efforts in Sierra Leone were already bringing the epidemic under control. The epidemic peaked in December 2014 and, by the time STRIVE was launched, Ebola incidence had declined to low levels. The first STRIVE participant was vaccinated on April 9, 2015, less than 6 months after the CDC’s first exploratory trip to Sierra Leone. By December 2015, when vaccination was completed, STRIVE had vaccinated approximately 8000 healthcare and frontline workers. Safety follow-up was completed in 2016. No confirmed Ebola cases occurred among STRIVE participants, so we were unable to assess efficacy. The Sierra Leone epidemic was officially declared over in November 2015 with 14112 reported cases and 4806 deaths, although new cases or small clusters emerged in the 3 highly affected countries as late as the spring of 2016. In this Journal of Infectious Diseases supplement, we present STRIVE safety data from 6 months of postvaccination follow-up on approximately 8000 vaccinated persons. These data will support application for vaccine licensure. The additional 9 articles in this supplement summarize many of the experiences and lessons learned during STRIVE. Although the precise circumstances surrounding implementation of STRIVE are unlikely to recur, these reports may be informative for trial researchers and public health personnel facing research challenges amidst other epidemics. Topics include the following: overall study implementation; development and monitoring of a ≤−60°C cold chain for vaccine storage; communications strategies; development of a regulatory infrastructure in Sierra Leone to support a clinical trial of an investigational vaccine; systems put into place to monitor study participants for Ebola, vaccine safety, and participant retention; analysis of basic health data collected from participants during screening, enrollment, and follow-up; and the role of nurses in STRIVE. CONCLUSIONS One important objective of STRIVE was to build Sierra Leone’s institutional capacity to lead clinical research of global importance. One of STRIVE’s most important legacies is its contribution to the professional development of its talented Sierra Leonean research staff, some of whom have continued to work on other vaccine trials in Sierra Leone and others who are pursuing postgraduate education in public health and associated fields. The STRIVE infrastructure also provided permanent facilities for conducting trials and storing investigational vaccines. These staff and facilities can facilitate rapid emergency vaccination response efforts if Ebola re-emerges in Sierra Leone as it did in the Democratic Republic of the Congo in 2017. More broadly, the capacity built through the Ebola response and STRIVE supports the global health security agenda, which aims to strengthen each country’s ability to prevent, detect, and respond to epidemics. In 2017, Sierra Leone was again struck by a catastrophe when heavy rains led to massive mudslides that wiped out entire neighborhoods. The emergency response capacity built during the Ebola epidemic facilitated the national authorities’ incident response, which included a large-scale preventive cholera vaccination effort. Maintaining this enhanced preparedness capacity, through ongoing investments by the government of Sierra Leone and its partners, will reduce the chance that another public health crisis will cause nationwide repercussions as devastating and long-lasting as those that occurred as a result of the Ebola epidemic. Figure 1. View largeDownload slide A Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) participant being vaccinated. Reprinted with permission. Figure 1. View largeDownload slide A Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) participant being vaccinated. Reprinted with permission. Notes Acknowledgments. We are grateful to the staff members of all the organizations in Sierra Leone and the United States that made the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) possible. We acknowledge the College of Medicine and Allied Health Sciences and Ministry of Health and Sanitation staff in Sierra Leone who worked so hard to implement STRIVE, as well as the Centers for Disease Control and Prevention (CDC) staff who contributed to STRIVE in Atlanta and Sierra Leone. Disclaimer. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Financial support. The trial was funded by the Centers for Disease Control and Prevention, the Biomedical Advanced Research and Development Authority, and the National Institutes of Health, with additional support from the CDC Foundation. Supplement sponsorship. This work is part of a supplement sponsored by the Centers for Disease Control and Prevention. Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Sierra Leone College of Medicine and Allied Health Sciences (COMAHS) and Ministry of Health and Sanitation (MOHS) Team: Janet S. J. Abu, John Karimu Abu, Elizabeth Adeyinka, Sao K. Amara, Abibatu S. Bah, Adama Bah, Aminata Bah, Binta Bah, Fatmata Bah, Fatmata W. J. Bah, Haja Yeroh Bah, Hawa Bah, Mariama Bah, Mohamed Bah, Nuhu Bah, Patricia Matu Bah, Daniel Solomon Bangura, Isatu S. Bangura, N’tumah Bangura, Ramatulai K. Bangura, Rosaline Dissa Bangura, Susan F. Bangura, Umu Bangura, Zainab Esther Bangura, Zainab Y. Bangura, Melvina Banya, Sam Sama Banya, Donald Bash-Taqi, Isata Bawoh, Mohamed Bawoh, Alex Bayoh, Mohamed Bayoh, Merilyn C. Bendu,Yeama Ben-Rogers, Alex A. Bindi, Sandy Blango, Ronilia Donna Bobb-Williams, Jeneba Bockarie, Betty Feimata Boima, Sonia Boyle, Michael Tanu Brima, Sesay Brima, Betty F. Bull, Dolcie J. Bultman, Rashidatu Bundu, Solomon Bureh, Egertina D. Campbell, Elsa Carew, Amanda F. Y. Caulker, Isata Charm, Modupeh Coker, Alrine Cheryl Cole, Lucinda D. O. Cole, Alhaji Mohamed Conteh, David Conteh, Edward Conteh, Fatmata Assiatu Conteh, Lansana Conteh, Maada M. Conteh, Mariama Conteh, Marie Francess Conteh, Mohamed Conteh, Saidu Conteh, Salamatu Conteh, Sorie Bundu Conteh, Muhammad-Abbas Conteh, Fatmata J. Dabo, Albert Davies, David G. M. Davies, Doris Tewoh Davies, Ophelia Eva Davies, Gibrilla Fadlu Deen, Sandratu Dumbuya, Joseph Edem-Hotah, Laura Ezue-Deen, Zainab Fadika, Prince Fatoma, Philip Fatorma, Seibatu Ayo Fatorma, Lansana Feika, Zainab Babah V. Fofana, Mameh Fofanah, Osman Sheku Fofanah, Doris Sia Fomba, Augustine E. Fombah, Foray Mohamed Foray, Amara K. Fornah, Francess Fornah, Sahid Nixon Fornah, Dusu Foryoh, Anthony Freeman, Rexmonda Helen Freeman, Hannah Gandi, Joseph Gandi, Ahmed Tejan Garber, Ibrahim Gassama, Francis Gbando, Mohamed Osman Gbessay, Winstona P. Gbondo, Michael Faada George, Peter M. George, Ruby Gilpin Macfoy, Isata T. Golfa, Rosaline Hanson, Marie Hassan, Joseph S. Hotah, Konah Lucia Humpah, Ayesha Idriss, Mariama, Priscilla Jabati, Ibrahim Mustapha Jabbie, Abdul Malik Jalloh, Hassan Jalloh, Hawa Umu Jalloh, Ibrahim Tupeh Jalloh, Isata K. Jalloh, Isatu R. Jalloh, Mohamed I. Jalloh, Mohamed Samba Jalloh, Ramatulai Jalloh, Rugiatu Jalloh, Unisa Jalloh, Faustine Oswald James, Lucinda B. James, Francess Jarett, Umaru Jaward, Augustine S. Jimissa, Samuel R. John, Bernadette Johnny, Magdalene Johnny, Ernest Jusu, Kakpama Jusu, Matilda Nglanda Jusu, Morrisson Oliver Jusu, Alpha Kabba, Foday Kabba, Adbdul Kabia, Karim Kabineh, Angella Kaikai, Josephine Kai-Tongie, Kenneth Kallay, Ahamed Kallon, Hawa Kallon, Hawa Kallon, Joyce M. Kallon, Feima Kamanoh, Abdul Kamara, Abdul Aziz M. Kamara, Abu Bakaar Kamara, Adikalie Kamara, Albert Kamara, Alhaji M. Kamara, Aruna Kamara, Brima Osaio Kamara, Delris Kamara, Doris T. Kamara, Francess Jatu Kamara, Frederica Theresa Kamara, Haja Abibatu Kamara, Halimatu Kamara, Halimatu Kamara, Hannah Kamara, Hellen Kamara, Ibrahim Kamara, Isatu V. Kamara, Junior Lamin Kamara, Mariama Kabba Kamara, Maseray Kamara, Mohamed M. Kamara, Osman Kamara, Patrick Kamara, Sallieu Kamara, Theresa B. V. I. Kamara, Umu Kamara, Victoria Sally Kamara, Ramata Bernadette Kanneh, Aminata P. Kanu, David Kanu, Idrissa Kanu, Lamin Kanu, Sulaiman Kanu, Alpha J. Kargbo, Dora S. Kargbo, Fatmata Bintu Kargbo, Kadiatu Kargbo, Samuel A. S. Kargbo, Alice Karim, John Karimu, Diane Kawa, Andrew Keddy, Charles Keimbe, Anthony Kenneh, Mohamed S. Khan, Abraham I. Khanu, Allie Koedoyoma, Kumba L. S. Koedoyoma, Darlinda Boima Kogba, Idrissa Momoh Kondorvoh, Alhaji F. Konneh, Musa J. Konneh, Francis Konteh, Abdulah Sam Koroma, Aminata Koroma, Bockarie Koroma, Fatmata Isha Koroma, Hawa A. Koroma, Henrietta G. Koroma, Ibrahim F. Koroma, Joan Mabinty Koroma, Maada Musa Koroma, Mary Koroma, Mohamed Ishmael Koroma, Mohamed S. Koroma, Rukiatu Koroma, Salamatu Koroma, Victoria Koroma, Cecilia Kortu, Yatta Jennifer Kosia, Fatmata Kpukumu, Sahr Sansie Kwigba, Francis Lahai, Kumba Lahai, Michael Lahai, Sahr Lamin, Josephine B. I. Lamina, Konah Lansana, Joan B. Lavally, Munis Jeneba Grace Lebbie, Bailah Leigh, Elizabeth Kathleen Lemor, Susan Mary Lewis, Radcliff D. Lisk, Agatha M. Luseni, Martha Luseni, Laurel Macarthy, Manjia Yvonne Magbity, John T. Mammie, Francis Mansaray, Lansana S. Mansaray, Marian Mansaray, Sandy Mansaray, Ignatius Gabriel Margai, Marjoe Margai, Suba M’bayo, Tenema M’bayo, Beatrice Minah, Patrick Moinina, Roselyn Momoh, Shembe Momoh, Osman Ansumana Morie, Joya Musa, Sia Ndomaina, Marina Nelson, Jennifer Nicol, Abdul Jibril Njai, Josephine T. Nyuma, Ann-Marie Parker, Richmonda M. L. Pearce, Henrietta Pessima, Wuyata Pokawa, Dudley Pratt, Keddy Pratt, Rebecca Randall, Chemford Renner-Lisk, Mohamed Hasim Rogers, James B. W. Russell, Foday Sahr, Rebecca Saidu, Raymond M. Sallu, Aiah Sam, Ibrahim Sam, Alfred Jinnah Samai, Mohamed Samai, Sydney Samai, Thomas T. Samba, Jiabo D. Sandy, Mimie K. Sanganya, Abdulai Sangla, Sidney Sankoh, Fadiru Sannoh, Ishmail Sannoh, Lansana Sannoh, Mustapha Sannoh, Tamba Saquee, Ramata Savage, Rebecca Scott, Thelma Scott, Bondo Sebba, Komba Senesie, Samuel Hassan Serry, Abdul Karim Sesay, Abibatu Sesay, Amara Bangali Sesay, Daniel Sesay, Ezekiel B. Sesay, Haja Fatmata Sesay, Jattu Rahman Sesay, Mohamed Sesay, Mohamed A. Sesay, Olaimatu D. Sesay, Ramatu Sesay, Samba Sesay, Samuel Sesay, Tom Sesay, Juliet Sevalie, Diana Shehab, Marie Sheriff, Massah M. Sheriff, Halimatu Shyllon, Isatu S. Sillah, Yeali Princess Sillah, Dominga A. Sogie-Thomas, Kadie B. Soloku, Paul Samuel Sondai, Miatta Songa, Peter Songu, Isata Sowa, Maada Joe Steven, Massah J. Stevens, Amadu Sumaila, Angella Sumaila, Hawa Swaray, Lexina Taidy-Leigh, Samuel Lansana Tarawally, Edward Taylor, Richard Taylor, Jane Tejan, Sumaila M. Tejan, Jacob Sahr Tengbeh, Sahr Tengbeh, Shirley V. Terry, Daphne Thomas, George Thomas, Alfred Coleson Thompson, Melvina Thompson, Moses Thompson, Beatrice Yatta Tommy, Samuel Tommy, Fanta Musa Turay, Feremusu Turay, Ibrahim Sorie Turay, Jane Turay, Juliana T. Turay, Patrick Turay, Philip Turay, Prince Turay, Saiduba Turay, Saio Turay, Sukaina Hamida Turay, Isata Vallie, Aruna Vandy, Lucinda Vincent, Willietta Vincent, Jude N. Williams, Alicia Wilson-Taylor, Edmond Wilson-Taylor, Andrew Wonnie, Marie P. M. Wright, Victoria Wright, Abass Wurie, Abdulai I. Wurie, Haja Ramatulai Wurie, Ian A. O. Wurie, Nabieu Yambasu, John Fallah Yillia. Centers for Disease Control and Prevention (CDC) Team (Atlanta and Sierra Leone): Winston Abara, Anna Acosta, Ann Aikin, Alison Albert, Joseph Alcober, Hammad Ali, Robert Allison, Abhijeet Anand, Gabe Anaya, Lauren Andersen, Sara Anderson, Linette Anthony, Melissa Arvay, Ralph Aviles, Jacqueline Bagby, Brian Baker, Arunmozhi Balajee, Kira Barbre, Michelle Basket, Holly Biggs, Heather Bradley, Joseph Bresee, Karen Broder, Richard Brooks, Deron Burton, Chassydi Butts, Amy Callis, Scott Campbell, Wendy Carr, Victoria Carter, Rosalind Carter, Lawrence Carter, Kathy Cavallaro, Teneale Chapton, Dawn Childs, Ana Choban, Terrence Chorba, Kenja Christian, Kathleen Clark, Tom Clark, Joshua Clayton, Nakia Clemmons, Kelli Clifton, Amanda Cohn, Laura Conklin, Michelle Conner, Margaret Cortese, Emily Cramer, Kathryn Curran, Rebecca Dahl, Dave Daigle, Carolynn DeByle, Sharon Dedreu, Malini DeSilva, Maureen Diaz, Kasey Diebold, Michelle Dittrich, Sandra Dos Santos Chaves, Jillian Doss-Walker, Detrice Dumas, Halima Dumas, Michelle Dynes, Paul Eke, Lorna English, Stefanie Erskine, Matthew Esona, Concepcion Estivariz, Gerry Fajardo, Nicholas Farrell, Daniel Feikin, Marc Fischer, Leah Fischer, Tom Fitzgerald, Nicole Flowers, Temi Folaranmi, John Francis, Meghan Frey, Sirena Gandy, Yvonne Garcia, Paul Gargiullo, Julianne Gee, Kathy Gensheimer, Halle Getachew, Jane Gidudu, Kandi Givner, Rebecca Gold, Susan Goldstein, Stacie Greby, Lisa Grohskopf, Michael Gronostaj, Amy Groom, Steve Hadler, Rana Hajjeh, Craig Hales, Eric Halsey, Mary Hamel, Lee Hampton, Ercilla Harrison, Alexia Harrist, Kira Harvey, Chad Heilig, Margaret Hercules, Beth Hibbs, Susan Hiers, Stephanie Hillard, Christine Ho, Walter Holt, James Hudgens, Tiffany Humbet-Rico, Debby Hurlburt, Arthur Hurst, Mary Huynh, John Iskander, Olamide Jarrett, Jennifer Johnson, Valerie Johnson, Anjella Johnson-Hooker, John Jordan, Yocasta Julio-Irizarry, Susan Kaydos-Daniels, Erin Kennedy, Lindsay Kim, Jeff Kingsbury, Martin Klingbeil, Andrew Kroger, Judy Kruger, Preeta Kutty, James Lange, Maribeth Larzelere, Ellen Lee, Jennifer Legardy-Williams, Billie Lester, Thijuanie Lockhart, Benjamin Lopman, Paul Lucas, Nicole Lukovsky Akhsanov, Elizabeth Luman, Nora Macklin, Inas Mahdi, Barbara Mahon, Allison Maiuri, Mark Mandelbaum, Karen Mason, Wendi McDonald, Mike McDonough, Jody McLean, Patricia Lynn Mercer, Nancy Messionnier, Sarah Meyer, Lara Misegades, Benjamin Monroe, Debby Moore, Michele Morales, Mahnaz Motevalli-Oliner, Noele Nelson, Cameron Nobilt, Kristen Nordlund, Chloe Oram, Julie Orta, Ana Maria Osario, Christina Ottis, Ishani Pathmanathan, Daniel Payne, Kate Pearson, Chandra Pendragraft, Tamara Pilishvili, Robert Pinner, Kelsey Pistotnik, Kara Polen, Brad Prescott, Kimberly Pringle, Carolynn Rao, Todd Raziano, Sarah Reagan-Steiner, Carrie Reed, Valerie Robison, Denise Rogers, Charles Rose, Laura Rose, Melanie Ross, Kate Russell, Stephanie Rutledge, Angela Salazar, Joseph Sarcone, Rebekah Schicker, Kristine Schmit, Ann Schmitz, David Schnabel, Stephanie Schrag, Anne Schuchat, Robin Senior, Jane Seward, Dave Sharma, April Shaw, Kris Sheedy, Nadine Shehab, Jessica Simpson, Stephanie Sincock, Erin Sizemore, Laurence Slutsker, Sarah (Lizzie) Smith, Andrew Stein, Elaine Stevens-Emilien, John Stevenson, Patricia Tanifum, Vasavi Thomas, Brittani Thomas, Patricia Thompson-Reid, Kathleen Thurman, Tejpratap Tiwani, Sara Tomczyk, Wen-Pin Tzeng, Jennifer Verani, John Visser, David Wang, Margaret Watkins, Leo Weakland, Douglas Weigelt, Cindy Weinbaum, Hope White, Marc-Alain Widdowson, Karen Wilkins, Kondra Williams, Maria Wright, Patty Yu, Yon Yu, Christina Zackery, Jane Zucker. References 1. World Health Organization . Ebola Response Roadmap Situation Report 1, 29 August 2014. http://www.who.int/csr/disease/ebola/evd-sitrep1-20140828.pdf. Accessed 6 December 2017. 2. Dixon MG, Schafer IJ; Centers for Disease Control and Prevention (CDC). Ebola viral disease outbreak–West Africa, 2014. MMWR Morb Mortal Wkly Rep 2014; 63:548–51 . 3. Meltzer MI , Atkins CY , Santibanez S ; Centers for Disease Control and Prevention (CDC) et al. Estimating the future number of cases in the Ebola epidemic—Liberia and Sierra Leone, 2014–2015 . MMWR Suppl 2014 ; 63 : 1 – 14 . Google Scholar PubMed 4. Tiffany A , Vetter P , Mattia J , et al. Ebola virus disease complications as experienced by survivors in Sierra Leone . Clin Infect Dis 2016 ; 62 : 1360 – 6 . Google Scholar CrossRef Search ADS PubMed 5. Dahl BA , Kinzer MH , Raghunathan PL , et al. CDC’s response to the 2014–2016 Ebola epidemic—Guinea, Liberia, and Sierra Leone . MMWR Suppl 2016 ; 65 : 12 – 20 . Google Scholar CrossRef Search ADS PubMed 6. Agnandji ST , Huttner A , Zinser ME , et al. Phase 1 trials of rVSV Ebola vaccine in Africa and Europe . N Engl J Med 2016 ; 374 : 1647 – 60 . Google Scholar CrossRef Search ADS PubMed Published by Oxford University Press for the Infectious Diseases Society of America 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Infectious Diseases Oxford University Press

Comment: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE)

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Abstract

We think of this Supplement of the Journal of Infectious Diseases as a figurative manual of operations for how to build an airplane while flying it through a storm. The human toll of the Ebola virus disease (Ebola) epidemic of 2014–2016 was worse than that experienced in all previously recognized Ebola epidemics put together. The idea of testing experimental vaccines that were just entering Phase 1 studies in humans felt both essential and incredibly daunting, given the chaos of this epidemic and the setting of an ongoing epidemic where medical management and monitoring capacity were already strained and most commercial air carriers had cancelled routes. Nonetheless, our team of figurative airplane designers built the airplane, flew it, and landed it safely. Our airplane, the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) (Figure 1), forged strong partnerships between institutions in Sierra Leone and the broader public health and research community. With the successful collection of safety data on approximately 8000 vaccinated persons, the study findings also bring the world closer to having a safe and effective vaccine for preventing Ebola. (Clinical Trial Registration. ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].) Unlike previous Ebola outbreaks, which had generally been small and limited to remote, rural communities, this epidemic was huge and threatened an entire region. Ebola emerged in Guinea in March 2014 and then spread widely within Guinea and across borders into Liberia and Sierra Leone [1]. Early in the epidemic, cases occurred in Conakry, the capital of Guinea, the first time Ebola transmission had ever been reported in a major city. This was an ominous development given the size and density of the population; it meant that Ebola could spread more rapidly and extensively than it ever had before, and it also had profound repercussions for travel and trade [2]. By August 2014, Ebola was spreading rapidly in rural areas and had reached urban areas in all 3 highly affected West African countries. Case counts were increasing exponentially. Estimates of the future death toll were dire, highlighting the urgent need to rapidly scale up the ongoing control activities and to develop new tools for control and prevention [3]. The spread of Ebola to other countries in Africa, Europe, and the United States heightened fears and complicated humanitarian assistance. Despite aggressive efforts that were launched across West Africa during the last quarter of 2014 and continuing into 2016, approximately 29000 cases and more than 11000 deaths were reported throughout the region. These figures are likely a significant underestimate of the epidemic’s true mortality and morbidity. Many survivors continue to contend with the substantial long-term health effects of Ebola [4]. The Centers for Disease Control and Prevention (CDC) first sent staff to assist in Guinea in March 2014. In July, the agency activated its Emergency Operations Center and launched a large-scale response that would stretch into 2016 [5]. Many CDC staff who deployed to West Africa in 2014 had extensive global public health experience including in natural disasters, epidemics, and famine, but they still returned home stunned by what they had seen and the challenges that affected countries faced with controlling the epidemic. In the fall of 2014, the CDC began plans to expand its Ebola response to include sponsoring a vaccine trial. In late October 2014, CDC staff traveled to Sierra Leone to meet with the Ministry of Health and Sanitation (MOHS) and the College of Medicine and Allied Health Sciences (COMAHS), University of Sierra Leone, to discuss whether implementing an investigational vaccine trial would be possible in the midst of the epidemic. The higher risk of Ebola for healthcare workers had been recognized early in the Sierra Leone epidemic as these dedicated workers responded to the crisis. The CDC worked intensively with MOHS, COMAHS, and other key collaborators to begin planning a Phase 2/3 vaccine trial among healthcare and frontline Ebola response workers. This Phase 2/3 trial would test 1 of the 2 experimental Ebola vaccines selected after the Phase 1 trial data became available. The overarching goal of STRIVE was to accelerate the introduction of an Ebola vaccine among at-risk people in Sierra Leone while concurrently evaluating vaccine efficacy and safety. Guiding principles included starting the trial as soon as possible in the most-affected districts of Sierra Leone to provide as many people as possible the opportunity for protection. The study design and data-monitoring plan had to allow the flexibility to add study sites if the epidemiology of the epidemic changed and immediate recognition if the risk from the vaccine exceeded potential benefit to participants. It was also essential to extend the offer of vaccine to every participant by the end of the trial. Planning for the safety of participants who were volunteering to receive a product that had thus far been given to very few people was paramount [6]. Rapidly planning and implementing STRIVE in the midst of the Ebola epidemic presented enormous challenges. One was making a final decision on which vaccine to test. The STRIVE researchers ultimately chose the recombinant vesicular stomatitis virus vaccine (rVSVΔG-ZEBOV-GP) (acquired by Newlink Genetics from Public Health Agency of Canada and later licensed to Merck & Co., Inc., Kenilworth, NJ); a major factor in this decision was that, because the vaccine was replication-competent, a single dose might provide both immediate and more durable protection. The limited healthcare infrastructure and clinical trial experience in Sierra Leone posed additional challenges. A cold chain to store and transport this vaccine at ≤−60°C had to be created and maintained. Facilities to enroll, vaccinate, and follow participants in 7 locations across 5 districts had to be built or renovated. An especially challenging but ultimately very successful and rewarding task was hiring and training more than 350 local staff while ensuring that such hiring did not interfere with Sierra Leone’s Ebola response. Finally, given that the local population had limited understanding of Ebola disease and its prevention, communicating effectively and transparently was critical for gaining the trust of local communities. The STRIVE researchers had to ensure that potential participants understood that participation was voluntary and that the consent of those who decided to enroll was truly informed. The study was staffed by locally hired personnel who were supervised by the COMAHS Principal Investigator. They worked alongside CDC staff in Sierra Leone, the majority rotating on short-term assignments; CDC staff in Atlanta provided scientific, administrative, and logistical support. The US Biomedical Advanced Research and Development Authority, the National Institutes of Health, the US Embassy in Sierra Leone, the CDC Ebola Response Team in Sierra Leone and Atlanta, the CDC Foundation, eHealth Africa, The Emmes Corporation, FHI 360, Technical Resources, Inc., the World Health Organization, Global Good/Intellectual Ventures, and Modality Solutions all contributed critical skills and experience vital to STRIVE’s success. As trial planning proceeded, Ebola response efforts in Sierra Leone were already bringing the epidemic under control. The epidemic peaked in December 2014 and, by the time STRIVE was launched, Ebola incidence had declined to low levels. The first STRIVE participant was vaccinated on April 9, 2015, less than 6 months after the CDC’s first exploratory trip to Sierra Leone. By December 2015, when vaccination was completed, STRIVE had vaccinated approximately 8000 healthcare and frontline workers. Safety follow-up was completed in 2016. No confirmed Ebola cases occurred among STRIVE participants, so we were unable to assess efficacy. The Sierra Leone epidemic was officially declared over in November 2015 with 14112 reported cases and 4806 deaths, although new cases or small clusters emerged in the 3 highly affected countries as late as the spring of 2016. In this Journal of Infectious Diseases supplement, we present STRIVE safety data from 6 months of postvaccination follow-up on approximately 8000 vaccinated persons. These data will support application for vaccine licensure. The additional 9 articles in this supplement summarize many of the experiences and lessons learned during STRIVE. Although the precise circumstances surrounding implementation of STRIVE are unlikely to recur, these reports may be informative for trial researchers and public health personnel facing research challenges amidst other epidemics. Topics include the following: overall study implementation; development and monitoring of a ≤−60°C cold chain for vaccine storage; communications strategies; development of a regulatory infrastructure in Sierra Leone to support a clinical trial of an investigational vaccine; systems put into place to monitor study participants for Ebola, vaccine safety, and participant retention; analysis of basic health data collected from participants during screening, enrollment, and follow-up; and the role of nurses in STRIVE. CONCLUSIONS One important objective of STRIVE was to build Sierra Leone’s institutional capacity to lead clinical research of global importance. One of STRIVE’s most important legacies is its contribution to the professional development of its talented Sierra Leonean research staff, some of whom have continued to work on other vaccine trials in Sierra Leone and others who are pursuing postgraduate education in public health and associated fields. The STRIVE infrastructure also provided permanent facilities for conducting trials and storing investigational vaccines. These staff and facilities can facilitate rapid emergency vaccination response efforts if Ebola re-emerges in Sierra Leone as it did in the Democratic Republic of the Congo in 2017. More broadly, the capacity built through the Ebola response and STRIVE supports the global health security agenda, which aims to strengthen each country’s ability to prevent, detect, and respond to epidemics. In 2017, Sierra Leone was again struck by a catastrophe when heavy rains led to massive mudslides that wiped out entire neighborhoods. The emergency response capacity built during the Ebola epidemic facilitated the national authorities’ incident response, which included a large-scale preventive cholera vaccination effort. Maintaining this enhanced preparedness capacity, through ongoing investments by the government of Sierra Leone and its partners, will reduce the chance that another public health crisis will cause nationwide repercussions as devastating and long-lasting as those that occurred as a result of the Ebola epidemic. Figure 1. View largeDownload slide A Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) participant being vaccinated. Reprinted with permission. Figure 1. View largeDownload slide A Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) participant being vaccinated. Reprinted with permission. Notes Acknowledgments. We are grateful to the staff members of all the organizations in Sierra Leone and the United States that made the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) possible. We acknowledge the College of Medicine and Allied Health Sciences and Ministry of Health and Sanitation staff in Sierra Leone who worked so hard to implement STRIVE, as well as the Centers for Disease Control and Prevention (CDC) staff who contributed to STRIVE in Atlanta and Sierra Leone. Disclaimer. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Financial support. The trial was funded by the Centers for Disease Control and Prevention, the Biomedical Advanced Research and Development Authority, and the National Institutes of Health, with additional support from the CDC Foundation. Supplement sponsorship. This work is part of a supplement sponsored by the Centers for Disease Control and Prevention. Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Sierra Leone College of Medicine and Allied Health Sciences (COMAHS) and Ministry of Health and Sanitation (MOHS) Team: Janet S. J. Abu, John Karimu Abu, Elizabeth Adeyinka, Sao K. Amara, Abibatu S. Bah, Adama Bah, Aminata Bah, Binta Bah, Fatmata Bah, Fatmata W. J. Bah, Haja Yeroh Bah, Hawa Bah, Mariama Bah, Mohamed Bah, Nuhu Bah, Patricia Matu Bah, Daniel Solomon Bangura, Isatu S. Bangura, N’tumah Bangura, Ramatulai K. Bangura, Rosaline Dissa Bangura, Susan F. Bangura, Umu Bangura, Zainab Esther Bangura, Zainab Y. Bangura, Melvina Banya, Sam Sama Banya, Donald Bash-Taqi, Isata Bawoh, Mohamed Bawoh, Alex Bayoh, Mohamed Bayoh, Merilyn C. Bendu,Yeama Ben-Rogers, Alex A. Bindi, Sandy Blango, Ronilia Donna Bobb-Williams, Jeneba Bockarie, Betty Feimata Boima, Sonia Boyle, Michael Tanu Brima, Sesay Brima, Betty F. Bull, Dolcie J. Bultman, Rashidatu Bundu, Solomon Bureh, Egertina D. Campbell, Elsa Carew, Amanda F. Y. Caulker, Isata Charm, Modupeh Coker, Alrine Cheryl Cole, Lucinda D. O. Cole, Alhaji Mohamed Conteh, David Conteh, Edward Conteh, Fatmata Assiatu Conteh, Lansana Conteh, Maada M. Conteh, Mariama Conteh, Marie Francess Conteh, Mohamed Conteh, Saidu Conteh, Salamatu Conteh, Sorie Bundu Conteh, Muhammad-Abbas Conteh, Fatmata J. Dabo, Albert Davies, David G. M. Davies, Doris Tewoh Davies, Ophelia Eva Davies, Gibrilla Fadlu Deen, Sandratu Dumbuya, Joseph Edem-Hotah, Laura Ezue-Deen, Zainab Fadika, Prince Fatoma, Philip Fatorma, Seibatu Ayo Fatorma, Lansana Feika, Zainab Babah V. Fofana, Mameh Fofanah, Osman Sheku Fofanah, Doris Sia Fomba, Augustine E. Fombah, Foray Mohamed Foray, Amara K. Fornah, Francess Fornah, Sahid Nixon Fornah, Dusu Foryoh, Anthony Freeman, Rexmonda Helen Freeman, Hannah Gandi, Joseph Gandi, Ahmed Tejan Garber, Ibrahim Gassama, Francis Gbando, Mohamed Osman Gbessay, Winstona P. Gbondo, Michael Faada George, Peter M. George, Ruby Gilpin Macfoy, Isata T. Golfa, Rosaline Hanson, Marie Hassan, Joseph S. Hotah, Konah Lucia Humpah, Ayesha Idriss, Mariama, Priscilla Jabati, Ibrahim Mustapha Jabbie, Abdul Malik Jalloh, Hassan Jalloh, Hawa Umu Jalloh, Ibrahim Tupeh Jalloh, Isata K. Jalloh, Isatu R. Jalloh, Mohamed I. Jalloh, Mohamed Samba Jalloh, Ramatulai Jalloh, Rugiatu Jalloh, Unisa Jalloh, Faustine Oswald James, Lucinda B. James, Francess Jarett, Umaru Jaward, Augustine S. Jimissa, Samuel R. John, Bernadette Johnny, Magdalene Johnny, Ernest Jusu, Kakpama Jusu, Matilda Nglanda Jusu, Morrisson Oliver Jusu, Alpha Kabba, Foday Kabba, Adbdul Kabia, Karim Kabineh, Angella Kaikai, Josephine Kai-Tongie, Kenneth Kallay, Ahamed Kallon, Hawa Kallon, Hawa Kallon, Joyce M. Kallon, Feima Kamanoh, Abdul Kamara, Abdul Aziz M. Kamara, Abu Bakaar Kamara, Adikalie Kamara, Albert Kamara, Alhaji M. Kamara, Aruna Kamara, Brima Osaio Kamara, Delris Kamara, Doris T. Kamara, Francess Jatu Kamara, Frederica Theresa Kamara, Haja Abibatu Kamara, Halimatu Kamara, Halimatu Kamara, Hannah Kamara, Hellen Kamara, Ibrahim Kamara, Isatu V. Kamara, Junior Lamin Kamara, Mariama Kabba Kamara, Maseray Kamara, Mohamed M. Kamara, Osman Kamara, Patrick Kamara, Sallieu Kamara, Theresa B. V. I. Kamara, Umu Kamara, Victoria Sally Kamara, Ramata Bernadette Kanneh, Aminata P. Kanu, David Kanu, Idrissa Kanu, Lamin Kanu, Sulaiman Kanu, Alpha J. Kargbo, Dora S. Kargbo, Fatmata Bintu Kargbo, Kadiatu Kargbo, Samuel A. S. Kargbo, Alice Karim, John Karimu, Diane Kawa, Andrew Keddy, Charles Keimbe, Anthony Kenneh, Mohamed S. Khan, Abraham I. Khanu, Allie Koedoyoma, Kumba L. S. Koedoyoma, Darlinda Boima Kogba, Idrissa Momoh Kondorvoh, Alhaji F. Konneh, Musa J. Konneh, Francis Konteh, Abdulah Sam Koroma, Aminata Koroma, Bockarie Koroma, Fatmata Isha Koroma, Hawa A. Koroma, Henrietta G. Koroma, Ibrahim F. Koroma, Joan Mabinty Koroma, Maada Musa Koroma, Mary Koroma, Mohamed Ishmael Koroma, Mohamed S. Koroma, Rukiatu Koroma, Salamatu Koroma, Victoria Koroma, Cecilia Kortu, Yatta Jennifer Kosia, Fatmata Kpukumu, Sahr Sansie Kwigba, Francis Lahai, Kumba Lahai, Michael Lahai, Sahr Lamin, Josephine B. I. Lamina, Konah Lansana, Joan B. Lavally, Munis Jeneba Grace Lebbie, Bailah Leigh, Elizabeth Kathleen Lemor, Susan Mary Lewis, Radcliff D. Lisk, Agatha M. Luseni, Martha Luseni, Laurel Macarthy, Manjia Yvonne Magbity, John T. Mammie, Francis Mansaray, Lansana S. Mansaray, Marian Mansaray, Sandy Mansaray, Ignatius Gabriel Margai, Marjoe Margai, Suba M’bayo, Tenema M’bayo, Beatrice Minah, Patrick Moinina, Roselyn Momoh, Shembe Momoh, Osman Ansumana Morie, Joya Musa, Sia Ndomaina, Marina Nelson, Jennifer Nicol, Abdul Jibril Njai, Josephine T. Nyuma, Ann-Marie Parker, Richmonda M. L. Pearce, Henrietta Pessima, Wuyata Pokawa, Dudley Pratt, Keddy Pratt, Rebecca Randall, Chemford Renner-Lisk, Mohamed Hasim Rogers, James B. W. Russell, Foday Sahr, Rebecca Saidu, Raymond M. Sallu, Aiah Sam, Ibrahim Sam, Alfred Jinnah Samai, Mohamed Samai, Sydney Samai, Thomas T. Samba, Jiabo D. Sandy, Mimie K. Sanganya, Abdulai Sangla, Sidney Sankoh, Fadiru Sannoh, Ishmail Sannoh, Lansana Sannoh, Mustapha Sannoh, Tamba Saquee, Ramata Savage, Rebecca Scott, Thelma Scott, Bondo Sebba, Komba Senesie, Samuel Hassan Serry, Abdul Karim Sesay, Abibatu Sesay, Amara Bangali Sesay, Daniel Sesay, Ezekiel B. Sesay, Haja Fatmata Sesay, Jattu Rahman Sesay, Mohamed Sesay, Mohamed A. Sesay, Olaimatu D. Sesay, Ramatu Sesay, Samba Sesay, Samuel Sesay, Tom Sesay, Juliet Sevalie, Diana Shehab, Marie Sheriff, Massah M. Sheriff, Halimatu Shyllon, Isatu S. Sillah, Yeali Princess Sillah, Dominga A. Sogie-Thomas, Kadie B. Soloku, Paul Samuel Sondai, Miatta Songa, Peter Songu, Isata Sowa, Maada Joe Steven, Massah J. Stevens, Amadu Sumaila, Angella Sumaila, Hawa Swaray, Lexina Taidy-Leigh, Samuel Lansana Tarawally, Edward Taylor, Richard Taylor, Jane Tejan, Sumaila M. Tejan, Jacob Sahr Tengbeh, Sahr Tengbeh, Shirley V. Terry, Daphne Thomas, George Thomas, Alfred Coleson Thompson, Melvina Thompson, Moses Thompson, Beatrice Yatta Tommy, Samuel Tommy, Fanta Musa Turay, Feremusu Turay, Ibrahim Sorie Turay, Jane Turay, Juliana T. Turay, Patrick Turay, Philip Turay, Prince Turay, Saiduba Turay, Saio Turay, Sukaina Hamida Turay, Isata Vallie, Aruna Vandy, Lucinda Vincent, Willietta Vincent, Jude N. Williams, Alicia Wilson-Taylor, Edmond Wilson-Taylor, Andrew Wonnie, Marie P. M. Wright, Victoria Wright, Abass Wurie, Abdulai I. Wurie, Haja Ramatulai Wurie, Ian A. O. Wurie, Nabieu Yambasu, John Fallah Yillia. Centers for Disease Control and Prevention (CDC) Team (Atlanta and Sierra Leone): Winston Abara, Anna Acosta, Ann Aikin, Alison Albert, Joseph Alcober, Hammad Ali, Robert Allison, Abhijeet Anand, Gabe Anaya, Lauren Andersen, Sara Anderson, Linette Anthony, Melissa Arvay, Ralph Aviles, Jacqueline Bagby, Brian Baker, Arunmozhi Balajee, Kira Barbre, Michelle Basket, Holly Biggs, Heather Bradley, Joseph Bresee, Karen Broder, Richard Brooks, Deron Burton, Chassydi Butts, Amy Callis, Scott Campbell, Wendy Carr, Victoria Carter, Rosalind Carter, Lawrence Carter, Kathy Cavallaro, Teneale Chapton, Dawn Childs, Ana Choban, Terrence Chorba, Kenja Christian, Kathleen Clark, Tom Clark, Joshua Clayton, Nakia Clemmons, Kelli Clifton, Amanda Cohn, Laura Conklin, Michelle Conner, Margaret Cortese, Emily Cramer, Kathryn Curran, Rebecca Dahl, Dave Daigle, Carolynn DeByle, Sharon Dedreu, Malini DeSilva, Maureen Diaz, Kasey Diebold, Michelle Dittrich, Sandra Dos Santos Chaves, Jillian Doss-Walker, Detrice Dumas, Halima Dumas, Michelle Dynes, Paul Eke, Lorna English, Stefanie Erskine, Matthew Esona, Concepcion Estivariz, Gerry Fajardo, Nicholas Farrell, Daniel Feikin, Marc Fischer, Leah Fischer, Tom Fitzgerald, Nicole Flowers, Temi Folaranmi, John Francis, Meghan Frey, Sirena Gandy, Yvonne Garcia, Paul Gargiullo, Julianne Gee, Kathy Gensheimer, Halle Getachew, Jane Gidudu, Kandi Givner, Rebecca Gold, Susan Goldstein, Stacie Greby, Lisa Grohskopf, Michael Gronostaj, Amy Groom, Steve Hadler, Rana Hajjeh, Craig Hales, Eric Halsey, Mary Hamel, Lee Hampton, Ercilla Harrison, Alexia Harrist, Kira Harvey, Chad Heilig, Margaret Hercules, Beth Hibbs, Susan Hiers, Stephanie Hillard, Christine Ho, Walter Holt, James Hudgens, Tiffany Humbet-Rico, Debby Hurlburt, Arthur Hurst, Mary Huynh, John Iskander, Olamide Jarrett, Jennifer Johnson, Valerie Johnson, Anjella Johnson-Hooker, John Jordan, Yocasta Julio-Irizarry, Susan Kaydos-Daniels, Erin Kennedy, Lindsay Kim, Jeff Kingsbury, Martin Klingbeil, Andrew Kroger, Judy Kruger, Preeta Kutty, James Lange, Maribeth Larzelere, Ellen Lee, Jennifer Legardy-Williams, Billie Lester, Thijuanie Lockhart, Benjamin Lopman, Paul Lucas, Nicole Lukovsky Akhsanov, Elizabeth Luman, Nora Macklin, Inas Mahdi, Barbara Mahon, Allison Maiuri, Mark Mandelbaum, Karen Mason, Wendi McDonald, Mike McDonough, Jody McLean, Patricia Lynn Mercer, Nancy Messionnier, Sarah Meyer, Lara Misegades, Benjamin Monroe, Debby Moore, Michele Morales, Mahnaz Motevalli-Oliner, Noele Nelson, Cameron Nobilt, Kristen Nordlund, Chloe Oram, Julie Orta, Ana Maria Osario, Christina Ottis, Ishani Pathmanathan, Daniel Payne, Kate Pearson, Chandra Pendragraft, Tamara Pilishvili, Robert Pinner, Kelsey Pistotnik, Kara Polen, Brad Prescott, Kimberly Pringle, Carolynn Rao, Todd Raziano, Sarah Reagan-Steiner, Carrie Reed, Valerie Robison, Denise Rogers, Charles Rose, Laura Rose, Melanie Ross, Kate Russell, Stephanie Rutledge, Angela Salazar, Joseph Sarcone, Rebekah Schicker, Kristine Schmit, Ann Schmitz, David Schnabel, Stephanie Schrag, Anne Schuchat, Robin Senior, Jane Seward, Dave Sharma, April Shaw, Kris Sheedy, Nadine Shehab, Jessica Simpson, Stephanie Sincock, Erin Sizemore, Laurence Slutsker, Sarah (Lizzie) Smith, Andrew Stein, Elaine Stevens-Emilien, John Stevenson, Patricia Tanifum, Vasavi Thomas, Brittani Thomas, Patricia Thompson-Reid, Kathleen Thurman, Tejpratap Tiwani, Sara Tomczyk, Wen-Pin Tzeng, Jennifer Verani, John Visser, David Wang, Margaret Watkins, Leo Weakland, Douglas Weigelt, Cindy Weinbaum, Hope White, Marc-Alain Widdowson, Karen Wilkins, Kondra Williams, Maria Wright, Patty Yu, Yon Yu, Christina Zackery, Jane Zucker. References 1. World Health Organization . Ebola Response Roadmap Situation Report 1, 29 August 2014. http://www.who.int/csr/disease/ebola/evd-sitrep1-20140828.pdf. Accessed 6 December 2017. 2. Dixon MG, Schafer IJ; Centers for Disease Control and Prevention (CDC). Ebola viral disease outbreak–West Africa, 2014. MMWR Morb Mortal Wkly Rep 2014; 63:548–51 . 3. Meltzer MI , Atkins CY , Santibanez S ; Centers for Disease Control and Prevention (CDC) et al. Estimating the future number of cases in the Ebola epidemic—Liberia and Sierra Leone, 2014–2015 . MMWR Suppl 2014 ; 63 : 1 – 14 . Google Scholar PubMed 4. Tiffany A , Vetter P , Mattia J , et al. Ebola virus disease complications as experienced by survivors in Sierra Leone . Clin Infect Dis 2016 ; 62 : 1360 – 6 . Google Scholar CrossRef Search ADS PubMed 5. Dahl BA , Kinzer MH , Raghunathan PL , et al. CDC’s response to the 2014–2016 Ebola epidemic—Guinea, Liberia, and Sierra Leone . MMWR Suppl 2016 ; 65 : 12 – 20 . Google Scholar CrossRef Search ADS PubMed 6. Agnandji ST , Huttner A , Zinser ME , et al. Phase 1 trials of rVSV Ebola vaccine in Africa and Europe . N Engl J Med 2016 ; 374 : 1647 – 60 . Google Scholar CrossRef Search ADS PubMed Published by Oxford University Press for the Infectious Diseases Society of America 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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Published: May 18, 2018

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