Characteristics and Outcomes of Pediatric Patients With Ebola Virus Disease Admitted to Treatment Units in Liberia and Sierra Leone: A Retrospective Cohort Study
Characteristics and Outcomes of Pediatric Patients With Ebola Virus Disease Admitted to Treatment Units in Liberia and Sierra Leone: A Retrospective Cohort Study
Michael A. Smit 1 2 3
Ian C. Michelow 1 2 3
Justin Glavis-Bloom 2 3
Vanessa Wolfman 0 3
Adam C. Levine 0 2 3
0 International Medical Corps , Los Angeles, California
1 Department of Pediatrics, Division of Infectious Diseases, Brown University , Providence, Rhode Island
2 Warren Alpert Medical School
3 Table 2. Comparison of Demographic and Clinical Characteristics in Children Who Survived Vs Those Who Died
Background. The clinical and virologic characteristics of Ebola virus disease (EVD) in children have not been thoroughly documented. Methods. Consecutive children aged <18 years with real-time polymerase chain reaction (RT-PCR)-confirmed EVD were enrolled retrospectively in 5 Ebola treatment units in Liberia and Sierra Leone in 2014/2015. Data collection and medical management were based on standardized International Medical Corps protocols. We performed descriptive statistics, multivariate logistic regression, and Kaplan-Meier survival analyses. Results. Of 122 children enrolled, the median age was 7 years and one-third were aged <5 years. The female-to-male ratio was 1.3. The most common clinical features at triage and during hospitalization were fever, weakness, anorexia, and diarrhea, although 21% of patients were initially afebrile and 6 patients remained afebrile. Bleeding was rare at presentation (5%) and manifested subsequently in fewer than 50%. The overall case fatality rate was 57%. Factors associated with death in bivariate analyses were age <5 years, bleeding at any time during hospitalization, and high viral load. After adjustment with logistic regression modeling, the odds of death were 14.8-fold higher if patients were aged <5 years, 5-fold higher if the patient had any evidence of bleeding, and 5.2-fold higher if EVD RT-PCR cycle threshold value was ≤20. Plasmodium parasitemia had no impact on EVD outcomes. Conclusions. Age <5 years, bleeding, and high viral loads were poor prognostic indicators of children with EVD. Research to understand mechanisms of these risk factors and the impact of dehydration and electrolyte imbalance will improve health outcomes.
The Ebola virus disease (EVD) outbreak in West Africa from
2014 to 2016 was the largest and deadliest in history, with 28
616 EVD cases and 11 310 deaths, including a significant
number of children . Prior to this epidemic, there was a paucity
of data describing children with EVD. However, the recent
outbreak presented unique opportunities to characterize pediatric
EVD patients systematically in order to understand the natural
history of disease and to identify clinical and virologic
prognostic indicators and predictors of mortality .
Consistent with sparse information from previous smaller
epidemics, the limited pediatric data from the recent outbreak show
that the youngest children had the highest case fatality ratios,
which approximated those of adults aged >45 years . The data
also show that the overall incidence of EVD among children was
significantly lower than that among adults, possibly because of
traditional burial practices [4–9]. Detailed descriptions of the
natural history of EVD largely have been limited to adult, ex-patriot
healthcare workers returning for treatment in the United States
and Europe [10–14]. These cases highlight the favorable
prognoses of adult patients treated in advanced intensive care units
with meticulous fluid resuscitation, electrolyte replacement, and
certain experimental therapies. Not surprisingly, prognosis is
significantly worse in regions with poor healthcare resources where
sophisticated supportive care is unavailable. Therefore, more
detailed studies of highly vulnerable populations, such as
children, are critical to maximize efficient use of limited resources.
Caring for proven or suspected Ebola virus–infected
children presents unique challenges in resource-limited countries.
Socioeconomic and cultural factors frequently contribute to
worse outcomes, especially when this devastating disease has
led to infected children being orphaned. Many children may
have been treated in Ebola treatment units (ETUs) without
dedicated caregivers, given the risks associated with having an
uninfected family member in the ETU. In addition, EVD may affect
children’s immunologic responses and endothelial function
differently compared with adults, which could adversely affect
their survival [15, 16].
Although there are some studies of Ebola virus–infected adults
from low-resource settings [17–21], there remain significant
gaps in our knowledge about the determinants and evolution
of adverse outcomes in children with EVD [15, 16, 22, 23]. Our
aim in this study was to characterize systematically a large cohort
of retrospectively enrolled children with EVD during the West
African epidemic in 2014 to 2015 in order to identify clinical
and virologic risk factors for mortality. Knowledge of potentially
modifiable risk factors may be useful to guide effective social and
medical interventions in future EVD outbreaks.
This retrospective, cohort study includes patient data collected
at 5 ETUs operated by International Medical Corps (IMC)
in Liberia and Sierra Leone from 15 September 2014 to 15
September 2015 as part of its comprehensive response to the
West African EVD epidemic.
All patients who presented to the study ETUs with symptoms
concerning for EVD were triaged to ensure that they met the
suspect case definition, which was created based on World Health
Organization (WHO)  and Ministry of Health guidelines
from each country (Supplementary Appendix 1). After triage,
patients who met the suspect case definition were admitted to the
ETU suspect ward and had a blood sample drawn within 24 hours
for EVD and malaria diagnostic testing. Patients with an initial
negative EVD test remained as inpatients for repeated testing
after 2 days. Patients with a second negative EVD result were
discharged or transferred to another healthcare facility. Patients with
positive EVD test results were moved to the ETU confirmed ward.
All patients aged <18 years who were admitted at any of IMC’s 5
ETUs with a positive EVD test and outcome data were included
All patients were treated according to standard treatment
protocols based on guidelines developed by the WHO , Médecins
Sans Frontières , and local ministries of health, as
permitted by local resources. Empiric treatment included antimalarial
medications, broad-spectrum antibiotics, and nutritional
supplementation, as well as focused supportive treatment (Appendix
1). Patients were cared for by trained medical staff who recorded
clinical data on paper forms. These data were digitized at each
ETU and unified into a database, as described previously .
Laboratory data, including EVD real-time polymerase chain
reaction (RT-PCR) and malaria testing, were linked to clinical data for
analyses. RT-PCR testing was performed by the US Naval Medical
Research Center for ETUs in Liberia, by Public Health England
laboratories for Lunsar and Makeni ETUs in Sierra Leone, and
by the Nigerian laboratory for the Kambia ETU in Sierra Leone.
Cycle threshold (Ct) values, which are based on RT-PCR of the
same Ebola virus (EBOV) Zaire locus, are presented in this study
as surrogates of viral load. A Ct >40 was considered negative in
all cases, though RNA extraction procedures differed slightly
between laboratories. Malaria testing (conducted in Sierra Leone
only) was performed at each laboratory site using the
commercially available BinaxNow rapid diagnostic test, which identifies 4
Plasmodium species: falciparum, malariae, vivax, and ovale.
Throughout hospitalization, patients were cared for by trained
local or international nurses, physician assistants, or physicians,
who rounded at least daily and recorded vital signs, clinical data,
and laboratory results on paper forms. Patient temperatures were
measured with infrared or oral thermometers. For children who
were unable to communicate history and who had no
accompanying guardians, only objective signs were recorded. These data
were transferred to separate electronic databases at each ETU
and later combined. A random sampling audit concluded that
>99% of the data in IMC’s unified database was accurate .
The variables of interest included demographic and clinical
characteristics, malaria status, initial EVD RT-PCR Ct values,
and mortality. Length of stay was calculated as the number
of days from date of admission to date of discharge. Age was
categorized into the following groups: <2 years, 2–4 years, 5–9
years, 10–14 years, and 15–17 years. For descriptive statistics,
median values with interquartile ranges (IQRs) were calculated
for nonnormally distributed continuous data, and proportions
were calculated for categorical data. Bivariate analyses were
performed to determine the associations between mortality,
the primary outcome of interest, and independent covariates
using the Mann-Whitney U test for continuous variables and
χ2 or Fisher exact test for categorical variables where
appropriate. Covariates that had a P value <0.1 from bivariate analyses
were entered in a backward stepwise logistic regression model
to determine which variables independently predicted
mortality. Goodness of fit was determined using the Hosmer and
Lemeshow test. We used Kaplan-Meier curves and the log-rank
test to compare survival among children by age group,
hemorrhagic features, and viral loads estimated by Ct values. A 2-tailed
P < .05 was considered to be statistically significant. Statistical
analyses were performed with SPSS Statistics, version 22.0.
The Sierra Leone Ethics and Scientific Review Committee, the
University of Liberia–Pacific Institute for Research & Evaluation Institutional Review Board, and the Lifespan (Rhode Island
Hospital) Institutional Review Board provided ethics approval
for this study and exemption from informed consent.
Among the 547 pediatric cases admitted to IMC ETUs in
Liberia and Sierra Leone during the study period, 123 had
PCR-confirmed EVD. One patient, whose outcome was
unknown, was transferred to another facility, leaving 122
patients available for analysis. Included in this number were 7
patients who were previously admitted briefly with suspected
EVD but whose diagnosis was confirmed during second
Incidence in females (56%) and males (44%) was similar.
Median age was 7 years (IQR, 3–13). Children were divided into
5 age categories: younger than 2 years (15%), 2–4 years (21%),
5–9 years (25%), 10–14 years (26%), and 15–17 years (13%).
The median length of stay was 9 days (IQR, 6–15; range, 1–31).
Almost all children (94%) had a history of contact with
documented cases of EVD.
At triage, more than 50% of children had fever, anorexia, and
weakness (Table 1). The most commonly observed signs and
symptoms during hospitalization were weakness, fever,
diarrhea, and anorexia (Table 1). Hemorrhagic features were
present in 5% at triage and 45% any time during admission.
Malaria testing was available at the Sierra Leone sites only; 68 of
84 (81%) children were tested, of whom 27 (40%) were positive for
Plasmodium parasitemia. The differences in incidence by age group
were significant (P = .024), with the most cases reported among
children aged <5 years (56%) compared with 5–9 years (50%),
10–14 years (25%), and 15–17 years (9%). There was no difference
in rates of Plasmodium parasitemia in children with or without
fever (38% vs 43%, respectively; P = 1.0).
The overall case fatality rate (CFR) was 57%. As shown in
Table 2, median length of stay was significantly longer for those
who survived compared with those who died (16 vs 6 days;
P < .001). The median age of patients who died was significantly
younger than of patients who survived (4 vs 11 years; P < .001).
Stratified by age, the CFR was highest (89%) for children aged
<5 years compared with other age groups (5–9 years, 43%;
10–14 years, 41%; 15–17 years, 25%; P < .001; Figure 1). In
addition to age, other significant predictors of mortality included
evidence of bleeding at any time during hospitalization (58% in
children who died vs 27% in survivors; P = .003; Figure 2) and
median initial PCR Ct values (19.2 in children who died vs 25.0
in survivors; P < .001). Overall, a PCR Ct cutoff value of 20
predicted mortality across age groups better than a cutoff value of
25, except for children aged <2 years (Figure 3, Supplementary
Figure 1). A diagnosis of Plasmodium parasitemia did not
influence mortality in aggregate (P = .76) or by age stratified analyses
(data not shown). No other characteristics differed between the
Approximately one-fifth of children (26/121) presented
without fever. Of these children, 73% developed fever but 6
remained afebrile throughout their hospitalization. The
difference in death rates among afebrile hospitalized children
stratified by age (<5 years, 2; 5–9 years, 2; 10–14 years, 2) was not
significant (P = .6). Fifty percent of the afebrile children died,
but no distinguishing clinical features or RT-PCR Ct values
predicted these deaths.
Significant variables from the bivariate analyses (Table 2)
were entered in backward stepwise logistic regression models.
Table 1. Clinical Characteristics of Ebola Virus Disease Patients Observed at Triage and During Hospitalization at Ebola Treatment Units in Liberia and
Number at Triage (%)
Number of Inpatients (%)
All Ages <5 5–9 10–14 15–17
95/121 (79) 35/43 (81) 23/30 (77) 25/32 (78) 12/16 (75)
26/38 (68) 5/9 (56) 7/11 (64) 11/13 (85) 3/5 (60)
77/121 (64) 21/43 (49) 15/30 (50) 27/32 (84) 14/16 (88)
53/121 (44) 11/43 (26) 11/30 (37) 20/32 (63) 11/16 (69)
45/106 (43) 12/34 (35) 14/27 (52) 11/29 (38) 8/16 (50)
44/121 (36) 11/43 (26) 6/30 (20) 14/32 (44) 13/16 (81)
P Value All Ages <5 5–9 10–14 15–17
.94 99/108 (92) 36/39 (92) 22/25 (88) 26/29 (90) 14/15 (93)
.47 90/112 (80) 27/40 (68) 24/27 (89) 27/30 (90) 12/15 (80)
.001 103/112 (92) 34/40 (85) 25/27 (93) 29/30 (97) 15/15 (100)
.002 72/112 (64) 15/40 (38) 19/27 (70) 24/30 (80) 14/15 (93)
.51 89/112 (80) 31/40 (78) 22/27 (82) 25/30 (83) 11/15 (73)
<.001 53/112 (47) 9/40 (23) 14/27 (52) 18/30 (60) 12/15 (80)
5/43 (12) 11/30 (37) 10/32 (31) 8/16 (50)
2/43 (5) 7/30 (23) 11/32 (34) 10/16 (63)
1/43 (2) 7/30 (23) 5/32 (16) 6/16 (38)
75/112 (67) 21/40 (53) 19/27 (70) 26/30 (87) 9/15 (60)
64/112 (57) 12/40 (30) 16/27 (59) 25/30 (83) 11/15 (73)
33/111 (30) 6/40 (15) 8/27 (30) 12/29 (41) 7/15 (47)
31/112 (28) 14/40 (35) 2/27 (7) 8/30 (27)
50/112 (45) 18/40 (45) 13/27 (48) 14/30 (47)
22/112 (20) 7/40 (18) 4/27 (15) 5/30 (17)
Abbreviation: ND, no data available.
a Self-reported at triage; measured during hospitalization at least daily (range 1–6 times per person per day).
In the first model that excluded PCR tests (n = 112; goodness
of fit, 0.68), the odds of mortality were 20.1-fold higher for
patients aged <5 years compared with older children (95%
confidence interval [CI], 5.9–69.0) and 5.9-fold higher if there was
evidence of bleeding at any time during hospitalization (95%
CI, 2.2–15.6). When EVD RT-PCR Ct values were added to the
model (n = 86; goodness of fit, 0.53), the odds of mortality were
14.8-fold higher for patients aged <5 years compared with older
children (95% CI, 3.5–62.1), 5.2-fold higher if the RT-PCR Ct
value was ≤20 (95% CI, 1.5–18.3), and 5.0-fold higher if there
Figure 1. Kaplan-Meier curve for overall survival among 122 Ebola virus disease
patients stratified by age. Children aged <5 years had significantly greater mortality
than older children (log rank test, P < .001).
was evidence of bleeding at any time during hospitalization
(95% CI, 1.6–15.8).
This is one of the largest cohort studies of children and
adolescents with EVD published to date. The odds of death were
20-fold higher in EVD patients aged <5 years compared with
older children. This finding is consistent with other data
reported from the West African EVD epidemic [4, 21, 27, 28].
Days of hospitalization before death for half of those aged <2
years ranged from 6 to 12 days. This range is comparable to that
reported by Shah et al [21, 28]. Hemorrhagic features developed
in fewer than half of pediatric patients; when present, they were
associated with a 5-fold higher odds of mortality. This
observation is in line with other reports that bleeding was not a
prominent finding among all EVD patients during this epidemic [19,
21, 22, 29]. It is also noteworthy that 1 in 5 children presented
without fever and, of these, 27% never developed fever, which is
similar to findings from one study  but not another . Our
findings support the mounting evidence that fever is not a
sensitive screening tool for EVD [17, 28]. In fact, the low frequency
of hemorrhagic features and the conspicuous absence of fever at
presentation in up to 20% of patients during the West African
epidemic questions the utility of referring to EVD as a disease
characterized primarily as “viral hemorrhagic fever,” which may
mislead clinicians .
Figure 2. Kaplan-Meier curve for overall survival among 112 Ebola virus disease
patients stratified by bleeding status. Children with evidence of bleeding at any
time during their hospitalization had significantly greater mortality (log rank test,
P = .003).
We confirmed that a high viral load estimated by a low
RT-PCR Ct value (<20) at the time of presentation
reliably predicted mortality in infected children who had 5-fold
higher odds of mortality . We also confirmed that
mortality was highest in children aged <2 years . The fact that
PCR Ct values did not differ between survivors and fatal cases
in those aged <2 years (unlike the older age groups) suggests
that factors other than viral load, such as immunological
or physiological dysregulation, contributed to death in the
youngest age group . Therefore, semiquantitative
molecular diagnostic testing at the time of initial evaluation is a
simple and effective method for screening for EVD as well
as for prognosticating outcomes (especially in children aged
>2 years) if Ct values are below a predefined threshold and
should be used routinely.
A diagnosis of Plasmodium parasitemia did not impact the
risk of mortality or presence of fever in a subpopulation of
children who had testing performed, which differs from a recent
report in which a diagnosis of malaria reduced the risk of EVD
Prominent features of EVD in children included
constitutional and gastrointestinal signs and symptoms. Considering
that children’s body surface area to volume ratio is higher than
that of adults and some children are malnourished, children
are particularly susceptible to life-threatening dehydration and
nutritional decompensation. Chertow et al made the
observation that large volumes of diarrhea caused by EVD were “not
unlike that of cholera” . Treatment protocols for future
EVD outbreaks could potentially improve outcomes by
instituting early and aggressive rehydration strategies. This along
with serum electrolyte balance and nutrition could be the most
important treatments to reduce mortality in those aged <5 years
in a low-resource setting. Furthermore, prompt, accurate
diagnosis and isolation precautions are critically important to
reduce transmission both in the community and in healthcare
It is likely that death of children from EVD results from 3 main
causes. The first and historically most often associated reason is
multiorgan failure secondary to coagulopathy associated with
a cytokine storm and immune dysregulation . The odds of
mortality in our cohort were significantly higher in children with
the “classic” presentation of viral hemorrhagic fever. Bleeding,
however, was not a feature in most of our patients. The second
In conclusion, we found that 3 clinical and virologic factors,
reason for death is cumulative dehydration. The large volumes
after adjustment, were significant poor prognostic factors for
of diarrhea often accompanied by vomiting and exacerbated
children with EVD: aged <5 years, bleeding at any time during
by weakness and inability to drink fluids quickly depletes the
hospitalization, and high viral loads as estimated by RT-PCR Ct
younger children. In the low-resource settings of West Africa,
values. There is an urgent need to investigate the mechanisms
the scarcity of healthcare providers to administer oral fluids
freof disease to understand how these risk factors as well as
malquently or appropriate continuous intravenous (IV) fluids
probnutrition, dehydration, and electrolyte imbalance contribute to
ably resulted in numerous deaths that could have been prevented
severe outcomes. The goal is to identify simple, scalable, and
relwith more resources. The third reason for death is cardiac arrest
atively inexpensive measures that can improve health outcomes
from electrolyte disturbances. In patients treated in high-resource
substantially in children in resource-limited settings. These
settings, abnormal serum levels of potassium and magnesium
fundamental interventions will effectively complement vaccines
were observed, along with cardiac arrhythmias; similar
electroand antiviral agents that are currently undergoing human trials.
lyte findings were noted in children in West Africa [34–36]. The
abnormal electrolyte levels may result from profuse diarrhea,
renal kidney dysfunction from dehydration, or direct acute kidney
injury (AKI) from EVD. Beyond the direct effects of the virus on
the kidney, EVD has been associated with rhabdomyolysis, which
can cause AKI and subsequent electrolyte abnormalities .
This study had limitations in common with others conducted
during the West African EVD epidemic. Environmental
conditions made it challenging for clinicians to collect patient data, given
that they were working in full EVD personal protective equipment
in extreme heat, which limited the time with each patient. Patients’
temperatures were measured with an infrared digital thermometer
gun or oral thermometer, which may be less accurate than the gold
standard rectal thermometer. Frequently, clinicians were unable to
collect dependable medical histories because of patients’ severity
of illness, absence of accompanying guardians, varying skills of
clinicians, or language and cultural barriers. Because accurate
nutritional assessments were not performed, the additional impact of
malnutrition was not taken into account. Without clinicians’ ability
to confirm the length of illness prior to arrival at ETUs, we were
limited in determining the total duration of illness and in assessing
accurately patients’ clinical courses. A few of the patients included
in this analysis received an experimental antiviral treatment as part
of a separate trial, which may have impacted their outcomes. In
addition, it is quite likely many patients either died or recovered
from EVD without seeking medical attention, thereby potentially
introducing ascertainment bias.
Two important interventions that were not accounted for
in the analyses could have impacted mortality rates. First was
whether or not patients received IV fluids, which typically was
inconsistent among ETUs because of varying practices relating
to the use of IV catheters. The second intervention that was not
taken into consideration was whether young children had
conworkers, who administered and encouraged oral rehydration
and nutrition and provided critical emotional support. Practices
varied among ETUs because some parents were incapacitated
or did not want to assume the risk of nosocomial infection and
caregivers were not always continuously available.
stant bedside caregivers, either family members or healthcare
Supplementary materials are available at Clinical Infectious Diseases online.
Consisting of data provided by the author to benefit the reader, the posted
materials are not copyedited and are the sole responsibility of the author, so
questions or comments should be addressed to the author.
Acknowledgements. The authors thank the governments of Liberia,
Sierra Leone, and Guinea for contributing to International Medical
Corps(ICM)’ humanitarian response. We also thank all of our generous
institutional, corporate, foundation, and individual donors who placed
their confidence and trust in International Medical Corps (ICM) and
made our work during the Ebola epidemic possible. We thank the US
Naval Medical Research Center, Public Health England, the European
Union Mobile Laboratory, and the Nigerian Laboratory for providing
laboratory data to our Ebola treatment units (ETUs). We further
acknowledge the many contributions made by all members of our research review
committee and other technical teams that contributed to this research,
including Rabih Torbay, Ann Canavan, Dennis Walto, Dan Rodman, Yoav
Rappaport, Samuel Grindley, Syed Hassan, Erin Shedd, Ryan Burbach,
Saikrishna Madhireddy, Benedict Adjogah, Melody Xie, Nadezda
Sekularac, Inka Weissbecker, Sean Casey, Farrah Zughni, Natalie Sarles,
and August Felix. We also thank medical directors Vanessa Wolfman
and Kassahun Gebrehiwot and monitoring and evaluation staff including
Annie Abbate, Razia Laghari, Allison Stewart, Alex Tran, Matthew Siakor,
David Mansaray, Lamin Bangura, Sorie Sesay, and Joseph Fangawa as well
as all other data collection officers at our ETUs. Finally, we thank the
medical and support staff, both local and ex-patriot, who set up and operated
International Medical Corps (ICM)’ ETUs and cared for the patients
during the Ebola epidemic in West Africa.
Financial support. The International Medical Corps provided all
funding for this research study. ICM was supported by grants from the National
Institutes of Health, National Institute of Allergy and Infectious Diseases
(K08 AI100997) and National Institute of General Medical Sciences
Potential conflicts of interest. All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
1. World Health Organization. Ebola Situation Report-10 June 2016 . Available at: http://apps.who.int/iris/bitstream/10665/208883/1/ebolasitrep_10Jun2016_eng. pdf?ua=1. Accessed 31 August 2016 .
2. Remy KE , Chertow DS. A place at the table for children in the Ebola virus disease discussion . Pediatr Crit Care Med 2015 ; 16 : 184 - 5 .
3. Qin E , Bi J , Zhao M , et al. Clinical features of patients with Ebola virus disease in Sierra Leone . Clin Infect Dis 2015 ; 61 : 491 - 5 .
4. World Health Organization Ebola Response Team . Ebola virus disease among children in West Africa . N Engl J Med 2015 ; 372 : 1274 - 7 .
5. McElroy AK , Erickson BR , Flietstra TD , et al. Biomarker correlates of survival in pediatric patients with Ebola virus disease . Emerg Infect Dis 2014 ; 20 : 1683 - 90 .
6. Dowell SF . Ebola hemorrhagic fever: why were children spared? Pediatr Infect Dis J 1996 ; 15 : 189 - 91 .
7. World Health Organization/International Study Team. Ebola haemorrhagic fever in Sudan , 1976 . Report of a WHO/International Study Team. Bull World Health Organ 1978 ; 56 : 247 - 70 .
8. Baron RC , McCormick JB , Zubeir OA . Ebola virus disease in southern Sudan: hospital dissemination and intrafamilial spread . Bull World Health Organ 1983 ; 61 : 997 - 1003 .
9. Alexander KA , Sanderson CE , Marathe M , et al. What factors might have led to the emergence of Ebola in West Africa? PLoS Negl Trop Dis 2015; 9:e0003652 .
10. Wolf T , Kann G , Becker S , et al. Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care . Lancet 2015 ; 385 : 1428 - 35 .
11. Schibler M , Vetter P , Cherpillod P , et al. Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report . Lancet Infect Dis 2015 ; 15 : 1034 - 40 .
12. Petrosillo N , Nicastri E , Lanini S , et al; INMI EBOV Team. Ebola virus disease complicated with viral interstitial pneumonia: a case report . BMC Infect Dis 2015 ; 15 : 432 .
13. Liddell AM , Davey RT Jr, Mehta AK , et al. Characteristics and clinical management of a cluster of 3 patients with Ebola virus disease, including the first domestically acquired cases in the United States . Ann Intern Med 2015 ; 163 : 81 - 90 .
14. Mora-Rillo M , Arsuaga M , Ramírez-Olivencia G , et al; La Paz-Carlos III University Hospital Isolation Unit . Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with Ebola virus disease contracted in Madrid , Spain. Lancet Respir Med 2015 ; 3 : 554 - 62 .
15. Eriksson CO , Uyeki TM , Christian MD , et al. Care of the child with Ebola virus disease . Pediatr Crit Care Med 2015 ; 16 : 97 - 103 .
16. Trehan I , Kelly T , Marsh RH , George PM , Callahan CW . Moving towards a more aggressive and comprehensive model of care for children with Ebola . J Pediatr 2016 ; 170 : 28 - 33 .e1-7.
17. Levine AC , Shetty PP , Burbach R , et al. Derivation and internal validation of the Ebola prediction score for risk stratification of patients with suspected Ebola virus disease . Ann Emerg Med 2015 ; 66 : 285 - 93 e1.
18. Lado M , Walker NF , Baker P , et al. Clinical features of patients isolated for suspected Ebola virus disease at Connaught Hospital, Freetown, Sierra Leone: a retrospective cohort study . Lancet Infect Dis 2015 ; 15 : 1024 - 33 .
19. Yan T , Mu J , Qin E , et al. Clinical characteristics of 154 patients suspected of having Ebola virus disease in the Ebola holding center of Jui Government Hospital in Sierra Leone during the 2014 Ebola outbreak . Eur J Clin Microbiol Infect Dis 2015 ; 34 : 2089 - 95 .
20. Cournac JM , Karkowski L , Bordes J , et al. Rhabdomyolysis in Ebola virus disease. Results of an observational study in a treatment center in Guinea . Clin Infect Dis 2016 ; 62 : 19 - 23 .
21. Fitzgerald F , Naveed A , Wing K , et al. Ebola virus disease in children , Sierra Leone , 2014 - 2015 . Emerg Infect Dis 2016 ; 22 : 1769 - 77 .
22. World Health Organization Ebola Response Team . Ebola virus disease in West Africa-the first 9 months of the epidemic and forward projections . N Engl J Med 2014 ; 371 : 1481 - 95 .
23. Schieffelin JS , Shaffer JG , Goba A , et al; KGH Lassa Fever Program; Viral Hemorrhagic Fever Consortium; WHO Clinical Response Team . Clinical illness and outcomes in patients with Ebola in Sierra Leone . N Engl J Med 2014 ; 371 : 2092 - 100 .
24. World Health Organization. Clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker . World Health Organization: Geneva, Switzerland , 2014 .
25. Médecins Sans Frontières. Filovirus haemorrhagic fever guideline . Barcelona, Spain, 2008 : 1 - 136 . http://www.slamviweb.org/es/ebola/FHFfinal.pdf. Accessed 31 August 2016 .
26. Roshania R , Mallow M , Dunbar N , et al. Successful implementation of a multicountry clinical surveillance and data collection system for Ebola virus disease in West Africa: findings and lessons learned . Glob Health Sci Pract 2016 ; 4 : 394 - 409 .
27. Bower H , Smout E , Bangura MS , et al. Deaths, late deaths, and role of infecting dose in Ebola virus disease in Sierra Leone: retrospective cohort study . BMJ 2016 ; 353 :i2403.
28. Shah T , Greig J , van der Plas LM , et al. Inpatient signs and symptoms and factors associated with death in children aged 5 years and younger admitted to two Ebola management centres in Sierra Leone, 2014: a retrospective cohort study . Lancet Glob Health 2016 ; 4 : e495 - 501 .
29. McElroy AK , Erickson BR , Flietstra TD , et al. Ebola hemorrhagic fever: novel biomarker correlates of clinical outcome . J Infect Dis 2014 ; 210 : 558 - 66 .
30. Mupere E , Kaducu OF , Yoti Z. Ebola haemorrhagic fever among hospitalised children and adolescents in northern Uganda: epidemiologic and clinical observations . Afr Health Sci 2001 ; 1 : 60 - 5 .
31. Chertow DS , Kleine C , Edwards JK , Scaini R , Giuliani R , Sprecher A. Ebola virus disease in West Africa-clinical manifestations and management . N Engl J Med 2014 ; 371 : 2054 - 7 .
32. Rosenke K , Adjemian J , Munster VJ , et al. Plasmodium parasitemia associated with increased survival in Ebola virus-infected patients . Clin Infect Dis 2016 ; 63 : 1026 - 33 .
33. McElroy AK , Harmon JR , Flietstra TD , et al. Kinetic analysis of biomarkers in a cohort of US patients with Ebola virus disease . Clin Infect Dis 2016 ; 63 : 460 - 7 .
34. Palich R , Gala JL , Petitjean F , et al; ALIMA N'zérékoré Ebola Treatment Center Medical Group. A 6-year-old child with severe Ebola virus disease: laboratory-guided clinical care in an Ebola treatment center in Guinea . PLoS Negl Trop Dis 2016 ; 10 :e0004393.
35. Uyeki TM , Mehta AK , Davey RT Jr, et al; Working Group of the U.S.- European Clinical Network on Clinical Management of Ebola Virus Disease Patients in the U .S. and Europe . Clinical management of Ebola virus disease in the United States and Europe . N Engl J Med 2016 ; 374 : 636 - 46 .
36. Sissoko D , Laouenan C , Folkesson E , et al; JIKI Study Group. Experimental treatment with Favipiravir for Ebola virus disease (the JIKI trial): a historically controlled, single-arm proof-of-concept trial in Guinea . PLoS Med 2016 ; 13 :e1001967.