Identify the Reservoir

Predicting EBOV epizootics requires increased understanding of virus ecology. Epidemiology, serologic data, and detection of viral RNA support a role of bats and nonhuman primates in EBOV maintenance and spillover transmission from animal reservoirs to humans. However, EBOV has yet to be isolated in nature from any bat species or nonhuman primates. In contrast to EBOV, ecologic and experimental evidence confirms fruit bats (Rousettus aegyptiacus) as a reservoir for MBGV, and MBGV spillover events from bats to humans have been documented (4,17,29). Ecologic investigations of R. aegyptiacus fruit bats showed seasonal pulses of MBGV spillover events (30). MBGV has been isolated from naturally infected R. aegyptiacus fruit bats 20 times (15,17,31), and virus replication and oral shedding in the absence of clinical disease was observed in experimentally infected R. aegyptiacus fruit bats (15).

Although EBOV exhibits ecologic patterns similar to those of MBGV, confirming EBOV reservoir hosts by virus isolation in nature remains elusive. One difficulty in obtaining EBOV isolates from bats, despite many attempts, appears to be identifying and sampling the appropriate bat species. Only 1, or a limited number of, bat species most likely can serve as hosts for each of the filovirus species, a phenomenon also seen with rodentborne hantaviruses and arenaviruses (32). In contrast to MBGV, no detectable viremia develops in R. aegyptiacus fruit bats experimentally infected with ebolaviruses (Sudan, Ebola, Bundibugyo, Taï Forest, and Reston viruses), and viral RNA detection was localized to the injection site (33), suggesting that R. aegyptiacus fruit bats are not a competent reservoir species for EBOVs. MBGV ecologic studies support the theory of 1, or a limited number of, host species because infection was found consistently in R. aegyptiacus fruit bats but not in Hipposideros spp. bats, despite their close interaction (17).

Figure 2

Figure 2. Relationship between location of index case in Ebola virus (Zaire ebolavirus) outbreaks and putative reservoir distribution. Ebola virus outbreaks (red dots) and distribution of Eidolon helvum, Mops condylurus, Myonycteris torquata, Epomops...

Although bat species involved in EBOV maintenance have yet to be discovered, limited detection of EBOV RNA and EBOV antibodies has implicated some frugivorous and insectivorous bat species distributed in areas of previous outbreaks, including the little collared fruit bat (Myonycteris torquata), hammer-headed bat (Hypsignathus monstrosus), Franquet's epauletted fruit bat (Epomops franqueti), straw-colored fruit bat (Eidolon helvum), and Angolan free-tailed bat (Mops condylurus) (12,34–36). Further investigation of these species as putative EBOV reservoirs is warranted; identifying EBOV reservoir species would enable predictive modeling based on distribution (Figure 2) and population dynamics (population size, reproduction, proximity to human populations). Tracking fruit bat migrations across their distribution ranges (Figure 2) including riverine highways and conducting reservoir population surveillance could identify high-risk disease foci before human population exposure, potentially mitigating another spillover and outbreak. In the case of MBGV, understanding the bat reservoir has led to risk reduction measures, such as identifying seasons at high risk for spillover, restricting access of miners or ecotourists to mines and caves with circulating MBGV, and constructing a safe viewing platform at a national park in Uganda.

Increase In-Country Surveillance, Diagnostic Capacity, and Epidemiologic Support

Curbing disease spread requires rapid identification of the initial human case or cluster after a spillover event to permit patient isolation and timely contact tracing. The payoff for investment in surveillance systems and diagnostic capacity to rapidly identify and respond to outbreaks is illustrated by efforts in Uganda and Democratic Republic of Congo, where the past several EVD and MVD outbreaks were quickly identified and restricted to a few cases. Effective contact tracing to interrupt disease transmission is personnel intensive and requires rapid organization and deployment after notification of suspected cases. In all EVD outbreaks to date, most transmission events involve close-contact human-to-human transmission. Because resources are often limited, case investigations should thoroughly rule out known sources of EBOV transmission before investigating speculated or new (e.g., airborne, environmental, dogs, or asymptomatic human) sources that have never been reported to be associated with disease in previous filovirus outbreaks. Accomplishing the aforementioned recommendations requires increased awareness at the community clinic level, improved quality of central laboratories and capacity for specimen transport (rapid collection and delivery, proper packaging, appropriate storage conditions), and more epidemiologists throughout the region. Finally, laboratorians and epidemiologists must work closely with well-trained clinical and infection control personnel to effectively identify and isolate infectious persons (37).

Test Appropriate Samples and Interpret Evidence-Based Data

Accurate diagnosis requires including EBOV in the differential diagnoses for febrile tropical illness and considering the possibility of co-infection with other frequent tropical diseases (e.g., malaria, typhoid). If appropriate diagnostic samples are not collected, cases might be missed at critical points in the response. Blood is the most sensitive diagnostic specimen early in EVD; oral swabbing, although less invasive, does not offer adequate sensitivity until late in the course of disease, but it is a sensitive and appropriate modality for testing postmortem specimens (13,14). Diagnostic data are critical in patient management and development of clinical recommendations and discharge policies. Interpretation of diagnostics should consider the sensitivity and specificity of the test and specimen type and what the test is detecting. For instance, qPCR is widely used, but a common mistake in interpreting results is that RNA detection is synonymous with the presence of infectious virus or viral shedding, which is not always the case (38). Although detectable viral RNA might indicate shedding, it does not equate with shedding, and this fact must be considered when transmission risk is evaluated on the basis of qPCR.

Investigate Viral Persistence and Physical and Psychological Sequelae in Survivors

The ≈17,000 survivors from the 2013–2016 EBOV outbreak might face major medical and social challenges after recovering from acute disease. Semen samples from EVD survivors in Kikwit, Democratic Republic of Congo, were positive for EBOV by RT-PCR up to 101 days after illness onset, and 1 sample obtained 82 days after disease onset yielded infectious virus (19,39). In addition, MBGV was isolated from semen of a convalescent patient and was the source of infection of a contact (40; reference 41 [Technical Appendix]). Sexual transmission was also implicated in EBOV transmission recently in Liberia (references 42,43 [Technical Appendix]). This outbreak confirmed that EBOV can persist in immune-privileged sites and has highlighted the implications of these findings. EBOV has now been isolated from aqueous humor of the eye (reference 44 [Technical Appendix]), semen (references 17,45 [Technical Appendix]), and cerebrospinal fluid (reference 46 [Technical Appendix]) of patients in whom the initial viremia cleared. The details and dynamics of EBOV shedding in body fluids after convalescence remain unclear and need to be investigated further, especially in fluids with higher potential for involvement in transmission events (e.g., semen and amniotic fluid) to clearly define specimens and behaviors with transmission risk.

Although understanding putative disease transmission from convalescent patients is essential to prevent EVD, clinicians and public health professionals also must investigate and address disease sequelae and social stigma associated with EVD in affected populations. Convalescent EVD patients reported arthralgia and myalgia more significantly than control patients during the 1995 Kikwit outbreak (39). In addition, 15% of the Kikwit survivors interviewed reported ocular sequelae, including ocular pain, photophobia, hyperlacrimation, and loss of visual acuity; all 4 patients reporting ocular sequelae had uveitis that responded to topical treatment (reference 47 [Technical Appendix]). EVD survivors of the Bundibugyo virus outbreak in Uganda in 2007 also had arthralgia and ocular deficits; hearing loss, neurologic abnormalities, sleep disturbance, memory loss, and various other constitutional symptoms. Chronic health problems also were reported (references 48,49 [Technical Appendix]).

In addition to medical burdens associated with recovery, survivors are concurrently dealing with considerable psychological issues of fear, denial, and shame. In severe instances, the social stigma associated with disease can be profound, resulting in abandonment by family and friends (reference 50 [Technical Appendix]).

Increase Public Education and Risk Communication

The response to an EVD outbreak requires rapid, effective, widespread public education. In addition to increased potential for transmission, a lack of public education and knowledge can contribute to panic, anxiety, and psychosocial trauma; fear and distrust of treatment units and responders, sometimes to the point of violence; and isolation, stigmatization, and community ostracism of survivors and family members of patients (references 51,52 [Technical Appendix]). Despite extensive communication efforts during the current EVD outbreak, knowledge and understanding of EVD symptoms remained low, and fear of ill and recovered EVD patients and treatment units persists (reference 52 [Technical Appendix]). To be effective, public education must recognize community-specific risks and concerns. This education must balance culturally appropriate messaging in the context of scientifically founded risk reduction messages to minimize human exposure (references 52–54 [Technical Appendix]). Risky behavior must be identified, and messages about risky behavior, prevention strategies, and feasible alternatives must be communicated. Establishing in-country community partners should be integrated to health communication; these partners are often most effective at providing behavioral health education and overcoming language and cultural barriers (reference 54 [Technical Appendix]).

Risk communication can prevent or greatly reduce transmission. EBOV transmission occurs through close contact with symptomatic EVD patients. Familial and social networks play a major role in transmission, particularly through caregivers’ contact with infectious fluids from ill persons at home and in healthcare facilities and through contact with deceased persons during funeral rites. Viral transmission is relatively inefficient compared with other highly infectious agents (reference 55 [Technical Appendix]). An exception is the proposed contribution of EBOV superspreaders (reference 56 [Technical Appendix]): persons who infect disproportionally more secondary contacts. For EBOV, superspreaders fall into 2 categories: biologic superspreaders, who shed more virus, and situational superspreaders, who solely because of circumstances or behavior potentially expose more persons, for example, persons who travel extensively, have occupations that interact closely with many persons (e.g., traditional healers), or deceased patients who had a highly attended funeral. Although biologic superspreaders appear to occur in EVD outbreaks (references 57,58 [Technical Appendix]), situational superspreaders more notably elicit transmission events, which successful community education on EVD can greatly reduce.

Promote Productive Interagency Relationships

Overall outbreak prevention and response will benefit greatly from continuing efforts to develop relationships with nongovernment organizations operating in the region and encouragement of constructive reform of national and international response agencies. We believe the very large and complex nature of the outbreak made communication within and among agencies exceptionally difficult during the outbreak. Frequently, well-intended centralized decision-making did not translate into appropriate application in the field. During the outbreak, partnering among agencies evolved in an effort to improve communication and the outcome of collaborative efforts, but further improvements are possible. Delegating roles among agencies in accordance with their strengths and abilities to acquire the necessary resources for epidemiologic investigations, diagnostics, clinical care, media relations, public education, and logistics might improve efficiency.

Continue Support for Basic Research

Pathogenesis studies and development of diagnostic tests, therapeutic drugs, and vaccines are the foundation of the public heath response. The international scientific community must continue to prioritize research on EBOV and viral pathogens that have yet to manifest into large outbreaks but have the fundamental characteristics to do so: viruses causing high rates of illness and death that are capable of person-to-person transmission and lack therapeutic drugs, vaccines, and other interventions (e.g., Nipah virus and Crimean-Congo hemorrhagic fever virus). The development and study of new tools toward the end of an outbreak is more likely to be hampered by a lack of patients, as we observed with the EBOV vaccine trials and new diagnostic test evaluations. Thus, future vital research projects should be poised to deploy at the start of new outbreaks, which will require prioritization and substantial regulatory forethought and preparation. However, research projects should not detract from outbreak response. The benefits of research investigations and fundamental response efforts must be balanced appropriately. In response to the outbreak, EBOV researchers worked together in a remarkable effort to advance research and address questions from the field in real time. Interagency collaborations and the open communication of data should continue after the outbreak to develop vaccines and therapeutic drugs and to address key questions on EBOV and other high-consequence, high-containment hemorrhagic fever viruses.