Although the current epidemic of EVD in West Africa is unprecedented in scale, the clinical course of infection and the transmissibility of the virus are similar to those in previous EVD outbreaks. The incubation period, duration of illness, case fatality rate, and R 0 are all within the ranges reported for previous EVD epidemics.7,13-18 Our estimates of R 0 are similar to other recent estimates for this West Africa epidemic.19-23 The combination of signs and symptoms recorded between symptom onset and clinical presentation is also similar to that in other reports.14,17,24-26 We infer that the present epidemic is exceptionally large, not principally because of the biologic characteristics of the virus, but rather because of the attributes of the affected populations and because control efforts have been insufficient to halt the spread of infection.

Certain characteristics of the affected populations may have led to the rapid geographic dissemination of infection. The populations of Guinea, Liberia, and Sierra Leone are highly interconnected, with much cross-border traffic at the epicenter and relatively easy connections by road between rural towns and villages and between densely populated national capitals. The large intermixing population has facilitated the spread of infection, but a large epidemic was not inevitable. In Nigeria, the number of cases has so far been limited, despite the introduction of infection into the large cities of Lagos (approximately 20 million people) and Port Harcourt (>1 million people). The critical determinant of epidemic size appears to be the speed of implementation of rigorous control measures.

Previous experience with EVD outbreaks, though they have been limited in size and geographic spread, suggests that transmission can be interrupted, and case incidence reduced, within 2 to 3 weeks after the introduction of control measures.1,5,7,14-17,24,27-31 This view is reinforced by the estimates of case reproduction number presented in this analysis. We estimate the R 0 to have varied between 1.71 (upper boundary of the 95% confidence interval, 2.01) in Guinea to 2.02 (upper boundary of the 95% confidence interval, 2.26) in Sierra Leone. This means that transmission has to be a little more than halved to achieve control of the epidemic and eventually to eliminate the virus from the human population. Considering the prospects for a novel Ebola vaccine, an immunization coverage exceeding 50% would have the same effect. Greater reductions in transmission would, of course, be desirable, but minimum requirements for the containment of EVD are far less severe than for the containment of more contagious diseases, such as measles. Between March and July 2014, the reproduction number in Guinea fluctuated around the threshold value of 1, suggesting that modest further intervention efforts at that point could have achieved control.

The analyses in this paper can be used to inform recommendations regarding control measures. The measured duration of the incubation period, and its variation, imply that the advice to follow case contacts for 21 days1 is appropriate. To curtail transmission in the community, the period from symptom onset to hospitalization (a mean of 5 days but a maximum of >40 days) clearly needs to be reduced. Surprisingly, the mean was not shorter among health care workers, who are at risk both of acquiring and transmitting the infection to others. The average length of hospital stay of about 1 week (6.4 days) means that the number of beds required to treat EVD patients is roughly equal to the rising weekly case incidence. Even without allowing for underreporting, 995 patients with confirmed, probable, or suspected infection were known to need clinical care in the week of September 8 through 14 alone, which far exceeds the present bed capacity in Guinea, Liberia, and Sierra Leone (approximately 610 beds in total).

The data used in these analyses were collected in the field by various field teams across Guinea, Liberia, Nigeria, and Sierra Leone. Although they provide an excellent opportunity to better understand the current EVD epidemic in Africa, they understate the magnitude of the problem. It is likely that many cases have not been detected, and for those cases that have been reported, case records are often incomplete. Therefore, interpretation of the available case data requires care. We recognize, however, that data are being collected under extreme conditions, and the top priorities are patient care, contact tracing, and limiting transmission in the community, rather than epidemiologic investigations. In addition, in this initial assessment it was not possible to consider all the sources of heterogeneity (e.g., geographic and health care-related) affecting the development of this epidemic. Thus the future projections provided here should be regarded as indicative of likely future trends more than precise predictions. Despite these limitations and the resulting uncertainties, the results presented here help us to understand the spread of infection and the potential for control.

Some details of the current analysis remain to be confirmed by further investigation. For example, our estimate of 15.3 days for the serial interval is slightly longer than past estimates.32,33 This may reflect the difficulties of collecting temporally unbiased data on exposure through contact tracing, either in the current outbreak or during previous outbreaks. Alternatively, a longer serial interval may indicate that case isolation has been less effective in the current epidemic, resulting in a higher proportion of transmission events occurring late in the course of illness.

Case fatality is among the most important topics for further investigation. Our estimates of case fatality are consistent in Guinea (70.7%), Liberia (72.3%), and Sierra Leone (69.0%) when estimates are derived with data only for patients with recorded definitive clinical outcomes (1737 patients). Estimates for hospitalized patients with recorded definitive clinical outcomes are also consistent across countries but are lower than those for all patients with definitive clinical outcomes. In contrast, simply taking the ratio of reported deaths to reported cases gives estimates that differ among countries (Table 2). These discrepancies perhaps reflect the challenges of clinical follow-up and data capture. The lower case fatality rate among hospitalized patients than among all persons with EVD could indicate that hospitalization increased survival, that cases of EVD in nonhospitalized persons were more likely to be detected if they were fatal, or that some persons died before they could be admitted to the hospital. In each of the countries studied, the case fatality rate is lowest among persons 15 to 44 year of age, and highest among persons 45 years of age or older, and some limited variation in the case fatality rate among health care workers was observed among countries. The reasons for this variation are not yet known. Moreover, the case fatality rate among hospitalized patients may differ from that among patients who are never seen by a physician. Liberia has reported an unusually high proportion of deaths among patients with suspected (but not probable or confirmed) EVD cases (58% [440 of 754 patients]), as compared with Guinea (13% [4 of 30 patients]) and Sierra Leone (35% [74 of 213 patients]). The implication is that many true EVD case patients in Liberia may have died before receiving a definitive diagnosis.

Notwithstanding the geographic variation in case incidence within and among Guinea, Liberia, and Sierra Leone, the current epidemiologic outlook is bleak. Forward projections suggest that unless control measures — including improvements in contact tracing, adequate case isolation, increased capacity for clinical management, safe burials, greater community engagement, and support from international partners — improve quickly, these three countries will soon be reporting thousands of cases and deaths each week, projections that are similar to those of the Centers for Disease Control and Prevention. Experimental therapeutics and vaccines offer promise for the future but are unlikely to be available in the quantities needed to make a substantial difference in control efforts for many months, even if they are proved to be safe and effective. Furthermore, careful assessment of the most effective means of utilizing such interventions (e.g., vaccination or treatment of contacts versus health care workers) will be required while stocks remain limited. For the medium term, at least, we must therefore face the possibility that EVD will become endemic among the human population of West Africa, a prospect that has never previously been contemplated. The risk of continued epidemic expansion and the prospect of endemic EVD in West Africa call for the most forceful implementation of present control measures and for the rapid development and deployment of new drugs and vaccines.