The 2013–2016 epidemic of Ebola virus disease was of unprecedented magnitude, duration and impact. Analysing 1610 Ebola virus genomes, representing over 5% of known cases, we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic ‘gravity’ model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already set the seeds for an international epidemic, rendering these measures ineffective in curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing they were susceptible to significant outbreaks but at lower risk of introductions. Finally, we reveal this large epidemic to be a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help inform interventions in future epidemics.

Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%.

Analysis of 179 new Ebola virus sequences from patient samples collected in Guinea between March 2014 and January 2015 shows how different lineages evolved and spread in West Africa. Supplementary information The online version of this article (doi:10.1038/nature14594) contains supplementary material, which is available to authorized users.

Background An Ebola Virus Disease (EVD) epidemic of unprecedented magnitude is ongoing in West Africa, affecting for the first time large urban centers like Conakry, the capital of Guinea. Methods Interviews of EVD patients, relatives and neighbors and laboratory databases were used to reconstruct EVD chains of transmission in Conakry, from March to August 2014. Findings Out of 193 confirmed and probable EVD cases reported in Conakry, Boffa and Télimélé, 152 (79%) were positioned in the chains of transmission. In March, non-Health Care Workers cases infected on average 2.3 (95% CI: 1.6, 3.2) persons, breaking down into 1.4 (95% CI: 0.9, 2.2) persons in the community, 0.4 (95% CI: 0.1, 0.9) in the hospital and 0.5 (95% CI: 0.2, 1.0) at funerals. Following implementation of infection control in April, the reproduction number in the hospital and at funerals reduced below 0.1. In the community, the reproduction number, which was positively correlated with patients viremia, dropped by 50% for hospitalized cases but remained unchanged for those not hospitalized. Hospital and funeral transmission represented 35% (7/20) and 15% (3/20) of all transmissions in March; but only 9% (11/128) and 4% (5/128) from April onward. Overall, 82% (119/145) of transmission occurred in the community and 72% (105/145) between family members. Simulations showed that a 10% increase in hospitalizations could have reduced the length of chains by 26% (95% CI: 4%, 45%). Interpretation Monitoring chains of transmission is critical to evaluate and optimize local control strategies for EVD. In Conakry, interventions had the potential to stop the epidemic but reintroductions of the disease and lack of cooperation of a small number of families led to prolonged low-level spread, highlighting challenges of EVD control in large urban centers. Funding Labex IBEID, Reacting, PREDEMICS, NIGMS MIDAS initiative, Institut Pasteur de Dakar.

Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus (EBOV)2,3. Here, we have for the first time evaluated the physiology of the human T cell immune response in EVD patients at the time of admission at the Ebola Treatment Center (ETC) in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we have identified an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by high percentage of CD4 and CD8 T cells expressing the inhibitory molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1), which was correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation despite comparable overall T cell activation. Concommittant with virus clearance, survivors mounted a robust EBOV-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.