Ebola control: effect of asymptomatic infection and acquired immunity.

Evidence suggests that many Ebola infections are asymptomatic, a factor overlooked by recent outbreak summaries and projections. Particularly, results from one post-Ebola outbreak serosurvey showed that 71% of seropositive individuals did not have the disease; another study reported that 46% of asymptomatic close contacts of patients with Ebola were seropositive. Although asymptomatic infections are unlikely to be infectious, they might confer protective immunity and thus have important epidemiological consequences. Although a forceful response is needed, forecasts that ignore natural ly acquired immunity from asymptomatic infections overestimate incidence late in epidemics. We illustrate this point by comparing the projections of two simple models based on the Ebola epidemic in Liberia, a model that does not account for asymptomatic infections, and another that assumes 50% of infections are asymptomatic and induce protective immunity. In both models, the basic reproduction number (R0) is identical and based on published estimates. The figure shows the projected cumulative incidence through time. Although the initial outbreaks are almost identical, by Jan 10, the model without asymptomatic infections projects 50% more cumulative symptomatic cases than the model that accounts for asymptomatic infection. This difference arises because asymptomatic infection contributes to herd immunity and thereby dampens epidemic spread. W i d e s p r e a d a s y m p t o m a t i c immunity would likewise have implications for Ebola control measures and should be considered when planning intervention strategies. For instance, should a safe and effective vaccine become available, the vaccination coverage needed for elimination will depend on pre-existing immunity in the population (appendix). Immunity resulting from asymptomatic infections should reduce the intervention effort needed to interrupt transmission but might also complicate the design and interpretation of vaccine trials. Trials and interventions are likely to target exactly those high-risk populations most likely to have been asymptomatically immunised. Thus, for assessment of vaccines and other countermeasures, baseline serum should be collected to improve both estimates of intervention effectiveness and our understanding of asymptomatic immunity. Additionally, assessment of intervention measures should account for the contribution of asymptomatic immunity in curbing epidemic spread. Asymptomatic infection could also potentially be directly harnessed to mitigate transmission. If individuals who have cleared asymptomatic infections could be identifi ed reliably, and if they are indeed immune to symptomatic re-infection, they could potentially be recruited to serve as caregivers or to undertake other high-risk disease control tasks, providing a buff er akin to that of ring vaccination. Recruitment of such individuals might be preferable to enlistment of survivors of symptomatic Ebola disease because survivors might experience psychological trauma or stigmatisation and be fewer in number—in view of the asymptomatic proportions suggested in previous studies and the low survival rate of symptomatic cases. Health-care workers with natural immunity acquired from asymptomatic infection, if identifi ed, could be allocated to care for acutely ill and infectious patients, minimising disease spread to susceptible health-care workers. The conclusions above depend on whether asymptomatic infections are common, and protective against future infection. Further, strategies to leverage protective immunity will depend on the development and validation of assays that can reliably identify individuals who are eff ectively protected against re-infection. Previous studies have identified many asymptomatic infections using IgM and IgG antibody assays and PCR, which, although indicative of infection, do not necessarily imply protective immunity. Evidence for long-term protective immunity reported in (symptomatic) Ebola survivors is suggestive, but the extent of protective immunity after asymptomatic infection and the identifi cation of serological markers for protective immunity can only be defi nitively addressed in settings with ongoing transmission risk. As has been proposed for vaccination, the epidemic therefore provides a unique opportunity to investigate asymptomatically acquired protective immunity to Ebola virus. Although resources are scarce, now is the time for interventions protecting people at risk of contracting Ebola (ie, health-care workers and household caregivers) to incorporate Published Online October 14, 2014 http://dx.doi.org/10.1016/ S0140-6736(14)61839-0