Perspectives on West Africa Ebola Virus Disease Outbreak, 2013

The variety of factors that contributed to the initial unde-

tectedspreadofEbolavirusdiseaseinWestAfricaduring

2013–2016andthedifcultycontrollingtheoutbreakonce

the etiology was identied highlight priorities for disease

prevention,detection,andresponse.Thesefactorsinclude

occurrenceinaregionrecoveringfromcivilinstabilityand

lackingexperiencewithEbolaresponse;inadequatesurveil-

lance,recognitionofsuspectedcases,andEboladiagnosis;

mobilepopulationsandextensiveurbantransmission;and

the community’s insufcient general understanding about

thedisease.Themagnitudeoftheoutbreakwasnotattrib-

utabletoasubstantialchangeofthevirus.Continuedefforts

duringtheoutbreakandinpreparationforfutureoutbreak

responseshouldinvolveidentifyingthereservoir,improving

in-countrydetectionandresponsecapacity,conductingsur-

vivorstudiesandsupportingsurvivors,engagingincultur-

allyappropriatepubliceducationandriskcommunication,

buildingproductiveinteragencyrelationships,andcontinu-

ingsupportforbasicresearch.

n 1976, the investigation of concurrent outbreaks of

a hemorrhagic fever syndrome (Ebola virus disease

[EVD]) in Zaire (currently Democratic Republic of Con-

go) and Sudan (currently Republic of South Sudan) (1,2)

led to isolation of 2 viruses now referred to as Ebola virus

(EBOV) and Sudan virus, respectively, and to identica-

tion of a newly recognized viral hemorrhagic fever genus,

Ebolavirus (family Filoviridae). Ebolaviruses now include

EBOV, Sudan virus, Reston virus, Taï Forest virus and Bun-

dibugyo virus. The other genus in the family Filoviridae is

Marburgvirus, consisting of Marburg virus and Ravn virus

(termed marburgviruses; MBGV), both of which are asso-

ciated with severe disease (Marburg virus disease [MVD])

in humans (3,4). Before 2013, the largest Ebola outbreak

was associated with Sudan virus in Gulu, Uganda, in 2000

that caused 425 cases (224 fatal) (5). The largest EVD out-

break associated with EBOV (the same virus responsible

for the 2013–2016 outbreak in West Africa) was in Zaire

(1976) and caused 318 cases and an associated case-fatality

rate of 88% (2).

The EVD outbreak in Guinea, Liberia, and Sierra Leone

was unprecedented in its sheer magnitude and the emergence

of EBOV outside the Congo basin. The effect of the outbreak

is profound; as of March 27, 2016, a total of 28,646 EVD

cases and 11,323 deaths had been documented (6). Further-

more, this outbreak prompted an unparalleled international

response: 7 US agencies operated 9 laboratories, and 11

international agencies operated 13 laboratories performing

in-country diagnostic tests (Figure 1). The Centers for Dis-

ease Control and Prevention (CDC) supported ≈2,300 inter-

national deployments of ≈1,600 total personnel (both CDC

and non-CDC staff) (7); and thousands of personnel from

international aid agencies, e.g., World Health Organization,

Médecins Sans Frontières, International Rescue Committee,

International Finance Corporation, and Public Health Eng-

land provided in-country support.

The EVD outbreak was not restricted to the 3 heav-

ily affected West African countries; cases also occurred in

Senegal, Nigeria, and Mali. In addition, EBOV-infected

foreign aid workers were transported for treatment to Eu-

rope and the United States, and naturally imported cases

(United States, Italy, United Kingdom) and domestic trans-

mission (Spain, United States) were reported for the rst

time in several countries (6). The US EVD response includ-

ed establishment of EBOV testing in the US Laboratory

Response Network. As a result, 57 state, county, and local

public health laboratories in 44 states currently are quali-

ed to perform presumptive EBOV real-time quantitative

PCR (qPCR).

This EVD outbreak highlights globalization, interna-

tional social responsibility, and the importance of global

health security. As the response to the outbreak progresses,

the international research community must continue to ad-

dress questions of EBOV emergence, pathogenesis, and

transmission and advance therapeutic and vaccine develop-

ment. National and international organizations must criti-

cally assess the details of this outbreak and the correspond-

ing response to enable improved response and control of

emerging viral outbreaks.

Perspectives on West Africa

Ebola Virus Disease Outbreak,

2013–2016

Jessica R. Spengler, Elizabeth D. Ervin, Jonathan S. Towner, Pierre E. Rollin, Stuart T. Nichol

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PERSPECTIVE

Authorafliation:CentersforDiseaseControlandPrevention,

Atlanta,Georgia,USA

DOI:http://dx.doi.org/10.32032/eid2206.160021

WestAfricaEbolaOutbreak

Why Here? Why Now?

We lack precise answers to these questions. A spillover

event is an exceedingly rare but high-consequence event

that is likely the most critical initiating factor for an out-

break. Features of the virus phylogenetic analyses and pu-

tative reservoir species, and what we know about prior ebo-

lavirus and MBGV spillover events, offer possible insight

into “Why here? Why now?” All currently recognized EB-

OVs appear to share a recent common ancestor ≈50 years

ago, probably because of a recent genetic bottleneck (8).

Current EBOV lineages, rst detected in northern Demo-

cratic Republic of Congo in 1976, appear to have spread

across the Congo basin during this relatively short period

and arrived to West Africa only in the past few years. Be-

fore the 2013–2016 outbreak, the only denitive evidence

of ebolaviruses or the diseases they cause in West Afri-

ca was 1 nonfatal human case associated with Taï Forest

virus, which caused illness and death in chimpanzees in

Côte d’Ivoire in 1994 (9).

How EBOV spread across the Congo basin and wheth-

er this spread involved movement through bat, nonhuman

primate, or other animal populations are unclear. EVD in

humans has been linked to preparing and eating nonhuman

primate (chimpanzee, gorilla, monkey) or duiker bushmeat

(10). Contact with bats also has been identied as a puta-

tive source of EBOV spillover (11). However, the role of

bats in virus maintenance and initiation of human disease

outbreaks remains unclear. Evidence of bats involvement in

the spillover event initiating the 2013–2016 outbreak is lim-

ited to anecdotal reports of interactions between bats and vil-

lagers in Guinea; no epidemiologic or genetic data associate

a putative reservoir species with the current outbreak (12).

Unlike MBGV, EBOV has yet to be isolated from bats, and

no direct evidence links bats to EBOV infection in humans.

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Figure 1.Geographicdistribution

ofdiagnosticlaboratories

currentlyorpreviously

operationalinWestAfrica

duringthe2014–2015Ebola

virusresponse,asofDecember

9,2015.DataarefromWorld

HealthOrganizationEbolavirus

diseasesituationreports.

PERSPECTIVE

Regardless, epizootic spillover remains the most widely ac-

cepted theory for how the outbreak began.

Experimental infection studies with loviruses in-

dicate that the viral load in the carcass of an animal that

died of EVD would be high (13,14), but the viral load in

the carcass of a healthy reservoir species is probably much

lower (15,16). However, the virus inoculum required to

infect animal models of EVD by traditional experimental

routes is very low. Thus, viral shedding through excreta

or viral load in tissue (eaten or handled raw) of reservoir

species might provide sufcient inoculum to initiate virus

spillover. In spillover events involving MBGV, sequences

from human isolates were ≈99% identical to virus isolates

obtained directly from infected bats (17); thus, the EBOV

spillover event most likely involved little or no virus ad-

aptation. Most EBOV outbreaks appear to involve a single

initiating spillover event followed by human-to-human

transmission (18,19), whereas several MVD outbreaks

have been associated with multiple spillover events (4,17).

This dissimilarity might reect a difference in the nature

of human interactions with the different primary reservoir

species of EBOV and MBGV.

Why So Big?

Some early speculation about the differences in magnitude

between the 2013–2016 EVD outbreak and previous lo-

virus outbreaks was focused on the presence of a rapidly

mutating, highly transmissible or highly virulent EBOV

strain. Gire et al. reported a rapid accumulation of interhost

and intrahost genetic variation in 99 EBOV genomes from

78 patients in Sierra Leone (20). However, later analysis

of more EBOV full-length sequences indicated that the

overall virus nucleotide substitution rate was consistent

with rates observed in previous outbreaks in Central Africa

(8,21). Pathogenesis studies also support that the size of

the outbreak and characteristics of EVD in West Africa are

not related to change in the virus but instead appear to be a

result of factors extrinsic to the virus (22–25).

Although differences in the outbreak strain do not ex-

plain the magnitude of the outbreak, the situation in these

West African countries in 2013 made them particularly

vulnerable to a large outbreak in the event of the arrival

of EBOV or spillover from wildlife. The West African

outbreak occurred in an extremely resource-poor area that

lacked basic infrastructure and was recovering from the

effects of decades of civil war. The consequences of civil

instability included the collapse of government institutions

and schools, disruption of traditional societal values and

structures, poor education standards, and struggling basic

healthcare infrastructures (26–28). Unlike several other

African countries, Guinea, Liberia, and Sierra Leone had

no past experience in recognizing and managing lovirus

outbreaks, and the outbreak occurred in a region with very

high endemic levels of malaria that has a similar clinical

presentation to EVD. Although these countries had experi-

ence with Lassa hemorrhagic fever, that experience most

likely negatively affected the initial response: suspecting

Lassa might have delayed identifying EBOV and enabled

early EBOV transmission. Based on limited chains of hu-

man-to-human transmission Lassa virus appears to be less

transmissible and requires less stringent use of personal

protective equipment and containment to prevent health-

care worker infections.

Slow recognition of suspected cases, inability to accu-

rately diagnose disease, and absence of appropriate surveil-

lance for critical decision-making early in the outbreak se-

verely hampered interruption of EVD spread at key points

during the response. Distrust of government and outsiders

hindered response efforts, and the spread of conspiracy

theories among residents resulted in fear, superstition, and

secrecy (27). In contrast to prior lovirus outbreak where

treatment of cases and transmission occurred in major ur-

ban areas (e.g., Kinshasa, Zaire, in 1976; Nairobi, Kenya,

in 1980; Kinshasa in 1995; Johannesburg, South Africa, in

1995; Luanda, Angola, in 2005; Kampala, Uganda, 2007;

Kampala, Uganda, in 2014 [http://www.cdc.gov/vhf/ebola/

outbreaks/history/chronology.html; http://www.cdc.gov/

vhf/marburg/resources/outbreak-table.html]); the West Af-

rican outbreak was the rst to include multiple reintroduc-

tions to urban areas (such as Conakry) from human cases

and extensive urban transmission. Porous borders and high

population mobility within each country and into neighbor-

ing countries exacerbated widespread dissemination of dis-

ease from urban and rural transmission (27).

Future Priorities and Considerations

Identify the Reservoir

Predicting EBOV epizootics requires increased understand-

ing of virus ecology. Epidemiology, serologic data, and de-

tection 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 experimen-

tal evidence conrms 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 experimen-

tally infected R. aegyptiacus fruit bats (15).

Although EBOV exhibits ecologic patterns similar

to those of MBGV, conrming EBOV reservoir hosts by

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WestAfricaEbolaOutbreak

virus isolation in nature remains elusive. One difculty

in obtaining EBOV isolates from bats, despite many at-

tempts, appears to be identifying and sampling the ap-

propriate bat species. Only 1, or a limited number of, bat

species most likely can serve as hosts for each of the lo-

virus 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 compe-

tent reservoir species for EBOVs. MBGV ecologic studies

support the theory of 1, or a limited number of, host spe-

cies because infection was found consistently in R. aegyp-

tiacus fruit bats but not in Hipposideros spp. bats, despite

their close interaction (17).

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 (Myonycte-

ris torquata), hammer-headed bat (Hypsignathus monstro-

sus), Franquet’s epauletted fruit bat (Epomops franqueti),

straw-colored fruit bat (Eidolon helvum), and Angolan

free-tailed bat (Mops condylurus) (12,34–36). Further in-

vestigation 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 migra-

tions across their distribution ranges (Figure 2) including

riverine highways and conducting reservoir population sur-

veillance could identify high-risk disease foci before hu-

man population exposure, potentially mitigating another

spillover and outbreak. In the case of MBGV, understand-

ing the bat reservoir has led to risk reduction measures,

such as identifying seasons at high risk for spillover, re-

stricting 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 identication of the

initial human case or cluster after a spillover event to per-

mit patient isolation and timely contact tracing. The payoff

for investment in surveillance systems and diagnostic ca-

pacity to rapidly identify and respond to outbreaks is il-

lustrated by efforts in Uganda and Democratic Republic of

Congo, where the past several EVD and MVD outbreaks

were quickly identied and restricted to a few cases. Ef-

fective contact tracing to interrupt disease transmission is

personnel intensive and requires rapid organization and de-

ployment after notication 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 in-

vestigating speculated or new (e.g., airborne, environmen-

tal, dogs, or asymptomatic human) sources that have never

been reported to be associated with disease in previous

lovirus outbreaks. Accomplishing the aforementioned

recommendations requires increased awareness at the com-

munity clinic level, improved quality of central laborato-

ries and capacity for specimen transport (rapid collection

and delivery, proper packaging, appropriate storage condi-

tions), and more epidemiologists throughout the region. Fi-

nally, 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 differ-

ential 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 diagnos-

tic 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). Diag-

nostic data are critical in patient management and develop-

ment of clinical recommendations and discharge policies.

Interpretation of diagnostics should consider the sensitivity

and specicity 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 detec-

tion 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 recov-

ering from acute disease. Semen samples from EVD survi-

vors in Kikwit, Democratic Republic of Congo, were posi-

tive 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

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PERSPECTIVE

infection of a contact (40; reference 41 in online Techni-

cal Appendix, http://wwwnc.cdc.gov/EID/article/22/6/16-

0021-Techapp1.pdf). Sexual transmission was also impli-

cated in EBOV transmission recently in Liberia (references

42,43 in online Technical Appendix). This outbreak con-

rmed that EBOV can persist in immune-privileged sites

and has highlighted the implications of these ndings.

EBOV has now been isolated from aqueous humor of the

eye (reference 44 in online Technical Appendix), semen

(17, reference 45 in online Technical Appendix), and cere-

brospinal uid (reference 46 in online Technical Appendix)

of patients in whom the initial viremia cleared. The details

and dynamics of EBOV shedding in body uids after con-

valescence remain unclear and need to be investigated fur-

ther, especially in uids with higher potential for involve-

ment in transmission events (e.g., semen and amniotic

uid) to clearly dene specimens and behaviors with trans-

mission risk.

Although understanding putative disease transmis-

sion 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. Convales-

cent EVD patients reported arthralgia and myalgia more

signicantly 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 in online

Technical Appendix). EVD survivors of the Bundibugyo

virus outbreak in Uganda in 2007 also had arthralgia and

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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 franqueti,and

Hypsignathus monstrosusbats(insets)areshown.DataarefromtheCentersforDiseaseControlandPreventionandtheInternational

UnionfortheConservationofNature.

WestAfricaEbolaOutbreak

ocular decits; hearing loss, neurologic abnormalities,

sleep disturbance, memory loss, and various other con-

stitutional symptoms. Chronic health problems also were

reported (references 48,49 in online Technical Appendix).

In addition to medical burdens associated with recov-

ery, 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 in online Technical Appendix).

Increase Public Education and Risk Communication

The response to an EVD outbreak requires rapid, effective,

widespread public education. In addition to increased poten-

tial for transmission, a lack of public education and knowl-

edge can contribute to panic, anxiety, and psychosocial

trauma; fear and distrust of treatment units and responders,

sometimes to the point of violence; and isolation, stigma-

tization, and community ostracism of survivors and family

members of patients (references 51,52 in online 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 in

online Technical Appendix). To be effective, public educa-

tion must recognize community-specic risks and concerns.

This education must balance culturally appropriate messag-

ing in the context of scientically founded risk reduction

messages to minimize human exposure (references 52–54

in online Technical Appendix). Risky behavior must be

identied, and messages about risky behavior, prevention

strategies, and feasible alternatives must be communicated.

Establishing in-country community partners should be in-

tegrated to health communication; these partners are often

most effective at providing behavioral health education and

overcoming language and cultural barriers (reference 54 in

online Technical Appendix).

Risk communication can prevent or greatly reduce

transmission. EBOV transmission occurs through close

contact with symptomatic EVD patients. Familial and so-

cial networks play a major role in transmission, particular-

ly through caregivers’ contact with infectious uids from

ill persons at home and in healthcare facilities and through

contact with deceased persons during funeral rites. Viral

transmission is relatively inefcient compared with other

highly infectious agents (reference 55 in online Technical

Appendix). An exception is the proposed contribution of

EBOV superspreaders (reference 56 in online Technical

Appendix): persons who infect disproportionally more

secondary contacts. For EBOV, superspreaders fall into

2 categories: biologic superspreaders, who shed more vi-

rus, 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 superspread-

ers appear to occur in EVD outbreaks (references 57,58

in online 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 benet

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 difcult during

the outbreak. Frequently, well-intended centralized deci-

sion-making did not translate into appropriate application

in the eld. During the outbreak, partnering among agen-

cies evolved in an effort to improve communication and

the outcome of collaborative efforts, but further improve-

ments are possible. Delegating roles among agencies in ac-

cordance with their strengths and abilities to acquire the

necessary resources for epidemiologic investigations, diag-

nostics, clinical care, media relations, public education, and

logistics might improve efciency.

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 scientic commu-

nity 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 develop-

ment 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 diagnos-

tic 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 benets of

research investigations and fundamental response efforts

must be balanced appropriately. In response to the out-

break, EBOV researchers worked together in a remarkable

effort to advance research and address questions from the

eld in real time. Interagency collaborations and the open

communication of data should continue after the outbreak

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PERSPECTIVE

to develop vaccines and therapeutic drugs and to address

key questions on EBOV and other high-consequence, high-

containment hemorrhagic fever viruses.

Conclusions

The large size and long duration of the West Africa EVD

outbreak and the resulting enormous national and interna-

tional response efforts yielded many lessons for improved

prevention and control efforts for emerging viral diseases.

Although the current outbreak comes to a close and other

health crises emerge in the news headlines, we must not

forget that many features of this tragic outbreak strongly re-

inforce the benet of continued investment in global health

security efforts.

Acknowledgments

We thank Tatyana Klimova for critical editing of the manuscript.

We also acknowledge and commend the international response

to the EVD outbreak in West Africa and thank the other

members of CDC’s Viral Special Pathogens Branch, Division of

High-Consequence Pathogens and Pathology, National Center

for Emerging and Zoonotic Infectious Diseases, for important

discussions and continued response efforts.

This work was supported in part by an appointment to the

Research Participation Program at CDC by the Oak Ridge

Institute for Science and Education through an interagency

agreement between the US Department of Energy and CDC (to

J.R.S.) and by the National Institutes of Health Loan Repayment

Award (to J.R.S.).

Dr. Spengler is a postdoctoral research fellow with the Viral

Special Pathogens Branch, National Center for Emerging and

Zoonotic Infectious Diseases, CDC. During the EVD outbreak

in West Africa, she assisted response efforts by providing

laboratory support domestically and by serving in the

Emergency Operations Center as a subject-matter expert for the

Laboratory Task Force and the Animal–Human Interface Team.

Her research interests include the pathogenesis, transmission,

and species barriers of viral hemorrhagic fevers.

References

1. World Health Organization. Ebola haemorrhagic fever in Sudan,

1976. Report of a WHO/International Study Team. Bull World

Health Organ. 1978;56:247–70.

2. World Health Organization. Ebola haemorrhagic fever in Zaire,

1976. Report of an international commission. Bull World Health

Organ. 1978;56:27193.

3. Johnson ED, Johnson BK, Silverstein D, Tukei P, Geisbert TW,

Sanchez AN, et al. Characterization of a new Marburg virus

isolated from a 1987 fatal case in Kenya. Arch Virol Suppl.

1996;11:101–14.

4. Bausch DG, Nichol ST, Muyembe-Tamfum JJ, Borchert M,

Rollin PE, Sleurs H, et al.; International Scientic and

Technical Committee for Marburg Hemorrhagic Fever Control in

the Democratic Republic of the Congo. Marburg hemorrhagic fever

associated with multiple genetic lineages of virus. N Engl J Med.

2006;355:909–19 http://dx.doi.org/10.1056/NEJMoa051465.

5. Towner JS, Rollin PE, Bausch DG, Sanchez A, Crary SM,

Vincent M, et al. Rapid diagnosis of Ebola hemorrhagic fever by

reverse transcription-PCR in an outbreak setting and assessment of

patient viral load as a predictor of outcome. J Virol. 2004;78:

4330–41 http://dx.doi.org/10.1128/JVI.78.8.4330-4341.2004.

6. World Health Organization. Ebola situation report. 2016 [cited

2016 Apr 25]. http://apps.who.int/ebola/ebola-situation-reports

7. Frieden TR, Damon IK. Ebola in West Africa—CDC’s role in

epidemic detection, control, and prevention. Emerg Infect Dis.

2015;21:1897–905 http://dx.doi.org/10.3201/eid2111.150949.

8. Carroll SA, Towner JS, Sealy TK, McMullan LK, Khristova ML,

Burt FJ, et al. Molecular evolution of viruses of the family

Filoviridae based on 97 whole-genome sequences. J Virol. 2013;

87:2608–16 http://dx.doi.org/10.1128/JVI.03118-12.

9. Formenty P, Hatz C, Le Guenno B, Stoll A, Rogenmoser P,

Widmer A. Human infection due to Ebola virus, subtype

Côte d’Ivoire: clinical and biologic presentation. J Infect Dis.

1999;179(Suppl 1):S48–53 http://dx.doi.org/10.1086/514285.

10. Leroy EM, Rouquet P, Formenty P, Souquière S, Kilbourne A,

Froment J-M, et al. Multiple Ebola virus transmission events and

rapid decline of central African wildlife. Science. 2004;303:387–90

http://dx.doi.org/10.1126/science.1092528.

11. Leroy EM, Epelboin A, Mondonge V, Pourrut X, Gonzalez J-P,

Muyembe-Tamfum J-J, et al. Human Ebola outbreak resulting

from direct exposure to fruit bats in Luebo, Democratic Republic

of Congo, 2007. Vector Borne Zoonotic Dis. 2009;9:723–8

http://dx.doi.org/10.1089/vbz.2008.0167.

12. Marí Saéz A, Weiss S, Nowak K, Lapeyre V, Zimmermann F,

Düx A, et al. Investigating the zoonotic origin of the West African

Ebola epidemic. EMBO Mol Med. 2014;7:17–23 http://dx.doi.org/

10.15252/emmm.201404792.

13. Prescott J, Bushmaker T, Fischer R, Miazgowicz K, Judson S,

Munster VJ. Postmortem stability of Ebola virus. Emerg Infect Dis.

2015;21:856–9 http://dx.doi.org/10.3201/eid2105.150041.

14. Spengler JR, Chakrabarti AK, Coleman-McCray JD, Martin BE,

Nichol ST, Spiropoulou CF, et al. Utility of oral swab sampling

for Ebola virus detection in guinea pig model. Emerg Infect Dis.

2015;21:1816–9 http://dx.doi.org/10.3201/eid2110.150840.

15. Amman BR, Jones MEB, Sealy TK, Uebelhoer LS, Schuh AJ,

Bird BH, et al. Oral shedding of Marburg virus in experimentally

infected Egyptian fruit bats (Rousettus aegyptiacus). J Wildl Dis.

2015;51:113–24 http://dx.doi.org/10.7589/2014-08-198.

16. Paweska JT, Jansen van Vuren P, Masumu J, Leman PA,

Grobbelaar AA, Birkhead M, et al. Virological and serological

ndings in Rousettus aegyptiacus experimentally inoculated with

vero cells-adapted hogan strain of Marburg virus. PLoS One.

2012;7:e45479 http://dx.doi.org/10.1371/journal.pone.0045479.

17. Towner JS, Amman BR, Sealy TK, Carroll SA, Comer JA,

Kemp A, et al. Isolation of genetically diverse Marburg viruses

from Egyptian fruit bats. PLoS Pathog. 2009;5:e1000536

http://dx.doi.org/10.1371/journal.ppat.1000536.

18. Ladner JT, Wiley MR, Mate S, Dudas G, Prieto K, Lovett S,

et al. Evolution and spread of Ebola virus in Liberia, 2014–2015.

Cell Host Microbe. 2015;18:659–69 http://dx.doi.org/10.1016/

j.chom.2015.11.008.

19. Rodriguez LL, De Roo A, Guimard Y, Trappier SG, Sanchez A,

Bressler D, et al. Persistence and genetic stability of Ebola virus

during the outbreak in Kikwit, Democratic Republic of the Congo,

1995. J Infect Dis. 1999;179(Suppl 1):S170–6 http://dx.doi.org/

10.1086/514291.

20. Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L,

et al. Genomic surveillance elucidates Ebola virus origin and

transmission during the 2014 outbreak. Science. 2014;345:1369–72

http://dx.doi.org/10.1126/science.1259657.

962 EmergingInfectiousDiseases•www.cdc.gov/eid•Vol.22,No.6,June2016

WestAfricaEbolaOutbreak

21. Hoenen T, Safronetz D, Groseth A, Wollenberg KR, Koita OA,

Diarra B, et al. Virology. Mutation rate and genotype variation of

Ebola virus from Mali case sequences. Science. 2015;348:117–9

http://dx.doi.org/10.1126/science.aaa5646.

22. Albariño CG, Wiggleton Guerrero L, Lo MK, Nichol ST,

Towner JS. Development of a reverse genetics system to generate

a recombinant Ebola virus Makona expressing a green uorescent

protein. Virology. 2015;484:259–64 http://dx.doi.org/10.1016/

j.virol.2015.06.013.

23. Dunham EC, Banadyga L, Groseth A, Chiramel AI, Best SM,

Ebihara H, et al. Assessing the contribution of interferon

antagonism to the virulence of West African Ebola viruses.

Nat Commun. 2015;6:8000 http://dx.doi.org/10.1038/ncomms9000.

24. Marzi A, Feldmann F, Hanley PW, Scott DP, Günther S,

Feldmann H. Delayed disease progression in cynomolgus

macaques infected with Ebola virus Makona strain. Emerg Infect

Dis. 2015;21:1777–83 http://dx.doi.org/10.3201/eid2110.150259.

25. Bird BH, Spengler JR, Chakrabarti AK, Khristova ML,

Sealy TK, Coleman-McCray JD, et al. Humanized mouse model of

Ebola virus disease mimics immune responses in human disease.

J Infect Dis. 2016;213:703–11 http://dx.doi.org/10.1093/infdis/

jiv538.

26. McPake B, Witter S, Ssali S, Wurie H, Namakula J, Ssengooba F.

Ebola in the context of conict affected states and health systems:

case studies of Northern Uganda and Sierra Leone. Con Health.

2015;9:23 http://dx.doi.org/10.1186/s13031-015-0052-7.

27. World Health Organization. One year into the Ebola epidemic:

a deadly, tenacious and unforgiving virus [cited 2016 Jan 4].

http://www.who.int/csr/disease/ebola/one-year-report/

introduction/en/

28. Bausch DG, Schwarz L. Outbreak of ebola virus disease in Guinea:

where ecology meets economy. PLoS Negl Trop Dis. 2014;8:e3056

http://dx.doi.org/10.1371/journal.pntd.0003056.

29. Adjemian J, Farnon EC, Tschioko F, Wamala JF, Byaruhanga E,

Bwire GS, et al. Outbreak of Marburg hemorrhagic fever among

miners in Kamwenge and Ibanda Districts, Uganda, 2007.

J Infect Dis. 2011;204(Suppl 3):S796–9 http://dx.doi.org/10.1093/

infdis/jir312.

30. Amman BR, Carroll SA, Reed ZD, Sealy TK, Balinandi S,

Swanepoel R, et al. Seasonal pulses of Marburg virus circulation

in juvenile Rousettus aegyptiacus bats coincide with periods of

increased risk of human infection. PLoS Pathog. 2012;8:e1002877

http://dx.doi.org/10.1371/journal.ppat.1002877.

31. Amman BR, Nyakarahuka L, McElroy AK, Dodd KA, Sealy TK,

Schuh AJ, et al. Marburgvirus resurgence in Kitaka Mine bat

population after extermination attempts, Uganda. Emerg Infect Dis.

2014;20:1761–4 http://dx.doi.org/10.3201/eid2010.140696.

32. Mills JN, Childs JE. Ecologic studies of rodent reservoirs: their

relevance for human health. Emerg Infect Dis. 1998;4:529–37

http://dx.doi.org/10.3201/eid0404.980403.

33. Jones ME, Schuh AJ, Amman BR, Sealy TK, Zaki SR, Nichol ST,

et al. Experimental inoculation of Egyptian rousette bats (Rousettus

aegyptiacus) with viruses of the Ebolavirus and Marburgvirus

genera. Viruses. 2015;7:3420–42 http://dx.doi.org/10.3390/v7072779.

34. Leroy EM, Kumulungui B, Pourrut X, Rouquet P, Hassanin A,

Yaba P, et al. Fruit bats as reservoirs of Ebola virus. Nature.

2005;438:575–6 http://dx.doi.org/10.1038/438575a.

35. Pourrut X, Délicat A, Rollin PE, Ksiazek TG, Gonzalez JP,

Leroy EM. Spatial and temporal patterns of Zaire ebolavirus anti-

body prevalence in the possible reservoir bat species. J Infect Dis.

2007;196(Suppl 2):S176–83 http://dx.doi.org/10.1086/520541.

36. Ogawa H, Miyamoto H, Nakayama E, Yoshida R, Nakamura I,

Sawa H, et al. Seroepidemiological prevalence of multiple species

of loviruses in fruit bats (Eidolon helvum) migrating in Africa.

J Infect Dis. 2015;212(Suppl 2):S101–8 http://dx.doi.org/10.1093/

infdis/jiv063.

37. Chowell D, Castillo-Chavez C, Krishna S, Qiu X, Anderson KS.

Modelling the effect of early detection of Ebola. Lancet Infect Dis.

2015;15:148–9 http://dx.doi.org/10.1016/S1473-3099(14)71084-9.

38. Spengler JR, McElroy AK, Harmon JR, Ströher U, Nichol ST,

Spiropoulou CF. Relationship between Ebola virus real-time

quantitative polymerase chain reaction–based threshold cycle

value and virus isolation from human plasma. J Infect Dis.

2015;212(Suppl 2):S346–9 http://dx.doi.org/10.1093/infdis/

jiv187.

39. Rowe AK, Bertolli J, Khan AS, Mukunu R, Muyembe-Tamfum JJ,

Bressler D, et al. Clinical, virologic, and immunologic follow-

up of convalescent Ebola hemorrhagic fever patients and their

household contacts, Kikwit, Democratic Republic of the Congo.

Commission de Lutte contre les Epidémies à Kikwit. J Infect Dis.

1999;179(Suppl 1):S28–35 http://dx.doi.org/10.1086/514318.

40. Martini GA, Schmidt HA. Spermatogenic transmission of the

“Marburg virus”. (Causes of “Marburg simian disease”) [in

German]. Klin Wochenschr. 1968;46:398–400 http://dx.doi.

org/10.1007/BF01734141.

Address for correspondence: Stuart T. Nichol, Centers for Disease

Control and Prevention, 1600 Clifton Rd NE, Mailstop G14, Atlanta, GA

30329-4027, USA; email: [email protected]

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The incidence of severe Haemophilus influenza infections,

such as sepsis and meningitis, has declined substantially

since the introduction of the H. influenzae serotype b

vaccine. However, the H. influenzae type b vaccine

fails to protect against nontypeable H. influenzae

strains, which have become increasingly frequent causes of

invasive disease, especially among children and the elderly.

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