Science
3 April 2015 vol 348, issue 6230, pages 1-150
http://www.sciencemag.org/current.dtl
Special Issue
Cancer Immunology and Immunotherapy

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Infectious Diseases
As Ebola wanes, trials jockey for patients
Kai Kupferschmidt
The Ebola epidemic in West Africa has caused enormous suffering, but scientists also see it as a chance to test experimental therapies that could save lives in the future. With declining case numbers, however, it is becoming less likely that all the drug tests will reach a conclusion. Now, scientists are debating whether some trials should be stopped so that tests of more promising therapies that have only now become available have a better chance of reaching a conclusion. An expert panel at the World Health Organization has given ZMapp and TKM-Ebola highest priority but in a recent meeting did not call for ongoing studies of favipiravir and convalescent blood to be stopped. The experts did convince a group of Italian doctors to test ZMapp instead of the heart drug amiodarone and criticized an interferon trial that has now started in Guinea.

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Policy Forum
Vaccine Testing
Ebola and beyond
Marc Lipsitch1,*, Nir Eyal2, M. Elizabeth Halloran3,4, Miguel A. Hernán5, Ira M. Longini6,
Eli N. Perencevich7,8, Rebecca F. Grais9,*
Author Affiliations
1Center for Communicable Disease Dynamics and Departments of Epidemiology and Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
2Department of Global Health and Population, Harvard T. H. Chan School of Public Health and Center for Bioethics, Harvard Medical School, Boston, MA, USA.
3Center for Inference and Dynamics of Infectious Diseases, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
4Department of Biostatistics, University of Washington, Seattle, WA 98105, USA.
5Center for Communicable Disease Dynamics and Departments of Epidemiology and Biostatistics, Harvard T. H. Chan School of Public Health, and Harvard-MIT Division of Health Sciences and Technology, Boston, MA, USA.
6Center for Inference and Dynamics of Infectious Diseases, Department of Biostatistics, College of Public Health and Health Professions, and College of Medicine, University of Florida, Gainesville, FL, USA.
7Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
8Center for Comprehensive Access and Delivery Research and Evaluation, Iowa Veterans Affairs Health Care System, Iowa City, IA, USA.
9Epicentre, Paris, France.
Many epidemic-prone infectious diseases present challenges that the current West African Ebola outbreak brings into sharp relief. Specifically, the urgency to evaluate vaccines, initially limited vaccine supplies, and large and unpredictable spatial and temporal fluctuations in incidence have presented huge logistical, ethical, and statistical challenges to trial design.

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Report
Mutation rate and genotype variation of Ebola virus from Mali case sequences
T. Hoenen1,*, D. Safronetz1,*, A. Groseth1,*, K. R. Wollenberg2,*, O. A. Koita3, B. Diarra3,
I. S. Fall4, F. C. Haidara5, F. Diallo5, M. Sanogo3, Y. S. Sarro3, A. Kone3, A. C. G. Togo3, A. Traore5, M. Kodio5, A. Dosseh6, K. Rosenke1, E. de Wit1, F. Feldmann7, H. Ebihara1, V. J. Munster1, K. C. Zoon8, H. Feldmann1, S. Sow5,
Author Affiliations
1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Hamilton, MT 59840, USA.
2Bioinformatics and Computational Biosciences Branch, NIAID, NIH, Bethesda, MD 20892, USA.
3Center of Research and Training for HIV and Tuberculosis, University of Science, Technique and Technologies of Bamako, Mali.
4World Health Organization Office, Bamako, Mali.
5Centre des Operations d’Urgence, Centre pour le Développement des Vaccins (CVD-Mali), Centre National d’Appui à la lutte contre la Maladie, Ministère de la Sante et de l’Hygiène Publique, Bamako, Mali.
6World Health Organization Inter-Country Support Team, Ouagadougou, Burkina Faso.
7Rocky Mountain Veterinary Branch, Division of Intramural Research, NIAID, NIH, Hamilton, MT 59840, USA.
8Office of the Scientific Director, NIAID, NIH, Bethesda, MD 20895, USA.
Abstract
Editor’s Summary
The occurrence of Ebola virus (EBOV) in West Africa during 2013–2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 × 10–4 substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns.