Clinical Manifestations and Case Management of

Caused by a Newly Identified Virus Strain, Bundibu

Paul Roddy

, Natasha Howard, Maria D. Van Kerkhove, Julius Lutwama, Joseph Wamala,

Esther Sterk, Benjamin Jes, Michel Van Herp, Matthias Borchert

Aliation: Department of Clinical Scienc
Medicine Antwerp and Department of Ep
Published: December 28, 2012
DOI: 10.1371/journal.pone.0052986
Medicine, University of Antwerp, Antwer

Abstract

A conrmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007
(Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-conrmed cases, and 37
manifestations and case management for 26 hospitalised laboratory-conrmed EHF patients. C
infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), seve
reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains
infection-control procedures required. However, quality data collection is essential to evaluate c
improvement in future epidemics. Organizations usually involved in EHF case management have

Figures

Citation: Roddy P, Howard N, Van Kerkhove MD, Lutwama J, Wamala J, et al. (2012) Clinical
Fever Caused by a Newly Identied Virus Strain, Bundibugyo, Uganda, 20072008. PLoS ON
Editor: Malcolm Gracie Semple, University of Liverpool, United Kingdom

Received: August 31, 2012; Accepted: November 23, 2012; Published: December 28, 2012

Copyright: 2012 Roddy et al. This is an open-access article distributed under the terms o
unrestricted use, distribution, and reproduction in any medium, provided the original autho

Funding: MDVK acknowledges funding from the Medical Research Council UK and the Bill an
design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.

Introduction

Filoviridae family members are characterised by lamentous enveloped particles with a negativ
genera, Ebolavirus and Marburgvirus, respectively causing Ebola and Marburg haemorrhagic fe

haemorrhagic fever (FHF) outbreaks are characterised by secondary transmission and high cas
(CFR) vary considerably: Zaire ebolavirus (ZEBOV; 8090%) [2], [4], [5], Sudan ebolavirus
[6][8], Cte d'Ivoire ebolavirus (CIEBOV; 0%; based on a single patient) [9][11], Reston ebo
[12][16], and Lake Victoria marburgvirus (MARV; 2088%) [17][20]. To date, 35 FHF outbre
MHF), all in or originating from sub-Saharan Africa [2], [21][27].

Suspect and laboratory-conrmed patient categorisation

In sub-Saharan Africa, when a medical professional suspects a lovirus infection, the patient's
(BSL-4) laboratory for diagnostic conrmation. If positive, an outbreak is declared and an inter
contact tracing, with isolation and treatment of suspect and laboratory-conrmed patients in a

Due to delays between outbreak onset, recognition, and response, some individuals potentially
to follow-up before having their blood sampled for disease conrmation. Likewise, if clinical dis
functionality, not all patients are hospitalised and treated on a lovirus ward. Outbreaks therefo
conrmed patient categorisations, with only some patients receiving supportive treatment on a

Once case identication and contact tracing activities commence, individuals matching epidem
lovirus ward for clinical assessment and, when appropriate, categorised as a suspected FHF p
conrmation. Diagnostic results are typically available within four hours from an on-site laborat
week for samples sent abroad [33], [34]. Patients with negative test results are discharged and
re-tested if FHF clinical suspicion remains. Laboratory-conrmed patients remain hospitalised o

Standard case management

In the absence of specic antiloviral therapy, lovirus ward clinicians provide suspect and labo
administered during the 1995 EHF outbreak in Kikwit, Democratic Republic of the Congo and su
rehydration, nutritional supplementation, and psychosocial support [26], [29][31]. Oral medic
as nausea and vomiting (e.g. metoclopramide and promethazine), dyspepsia (e.g. aluminium hy
agitation, or confusion (e.g. diazepam, chlorpromazine), and pain (e.g. paracetamol, tramadol,
oral artemether/lumefantrine for uncomplicated malaria and an oral antibiotic (e.g. amoxicillin,
administered due to the customary absence of an on-site laboratory capable of safely processin
expanded, supportive care may also include prevention and treatment of dehydration via intrav
supplementation, and IV administration of medication for optimum drug delivery when clinicall

Improving knowledge of human clinical manifestations and case ma

Limited quality FHF clinical data from human outbreaks have been collected, analysed, and pub
paper-based clinical records outside the lovirus ward [26]. Records have been destroyed as p
result, most detailed descriptions of clinical manifestation have been from laboratory-based stu
human patients (e.g. ZEBOV [28], [40][52], SEBOV [53][56], CIEBOV [9], and MARV

Substantial uncertainties remain regarding human FHF incubation periods and symptom freque
data are of questionable validity and reliability due to reporting and recall biases [41],
symptom frequency and duration [9], [19], [40], [49], [53], [55], numerous others yielded onl
and period prevalence of symptoms (e.g. at admission to the lovirus ward, during hospital sta
human FHF symptomatology is crucial for advancing outbreak control measures and administe
disease severity [33].

Although anecdotal evidence suggests supportive treatment increases FHF survival, its eectiv
[46]. More data on human clinical manifestations and treatment eectiveness are needed to im

The 20072008 Bundibugyo outbreak

On 29 November 2007, the Uganda Ministry of Health (MoH) and the World Health Organization
western Uganda, and responded in collaboration with Mdecins Sans Frontires (MSF), the Uga
for Disease Control and Prevention (CDC), and others [68]. On 20 February 2008, the outbreak
(30 of whom were hospitalised) and 37 deaths, yielding a 25% CFR [69], [70]. Most cases orig
16,000 and 5,700 inhabitants respectively. Bundibugyo is situated at the base of the Rwenzori
was set up and maintained at each location throughout the outbreak response [70]. Genetic se
the virus causing the Bundibugyo outbreak diered from any known ebolavirus (EBOV) species
proposed as a new EBOV species provisionally named Bundibugyo ebolavirus (BEBOV)

Study rationale and objectives

This outbreak is the rst known observation of human disease caused by this putatively novel E
BEBOV infection furthers knowledge of human FHF symptomatology, while describing the imple
shortcomings, a baseline imperative for improving and assessing the eectiveness of supportiv
this may be the only way for future patients to receive better care. The objectives of this second
demographics and contact histories; (ii) document symptoms from onset to clinical outcome; (i
recommend strategies for improving data collection in future FHF outbreaks.

Methods
Ethics statement

The Uganda National Health Research Organization and the Ethics Review Boards of Mdecins S
Medicine provided ethics approval for a posteriori analyses of the outbreak's anonymous and ro
additional data were collected for research purposes and all data were anonymous before analy
consent.

Study population and data collection

Study subjects were patients hospitalised on Bundibugyo or Kikyo Ebola wards with subsequen
suspected EHF cases in Bundibugyo District were: (i) an epidemiological link to an individual po
(i.e. asthenia, anorexia, myalgia/arthralgia, diarrhoea, abdominal pain, nausea, vomiting, heada
(ii) fever plus at least three of the general symptoms listed above; or (iii) fever plus unexplained
accompanied to an Ebola ward and clinically assessed. Suspected cases further corroborated b
drawn and sent to the UVRI/CDC laboratory in Entebbe, Uganda for biological conrmation by
linked immunosorbent assay (ELISA), or IgM-capture ELISA [69], [71]. Laboratory results were

The makeshift Bundibugyo and Kikyo Ebola wards became fully functional following implementa
[3], [31]. Study subjects were hospitalised on (i) a makeshift ward for the entirety of their stay
stay; or (iii) a fully functional ward for the entirety of their stay. Dierences between fully functi
management as described in the introduction, and standardised data collection [48]. Data were
MSF sta on fully functional wards (Figure 1).

Figure 1. Filovirus ward clinicians administering supportive treatment while concurrently

200708 Ebola haemorrhagic fever outbreak.
Photo by Claude Mahoudeau.
doi:10.1371/journal.pone.0052986.g001

Study variables and data analysis

Data were collected on patient demographics, contact history, symptoms (self-reported from d
healthcare workers from admission until clinical outcome), treatment, patient monitoring, and c

Demographic variables were age, gender, residence, occupation, and Ebola ward. Contact histo
categorized as none, indirect (i.e. via fomite), direct, and direct during funeral practices
Supportive treatment was categorised as EHF-related symptom alleviation, antibiotics, antimala
psychosocial support data were not collected. Patient monitoring data were axillary body temp
Celsius), heart rate (beats per minute), respiratory rate (breaths per minute), and blood pressu
discharge from the Ebola ward.

Data were analysed using Microsoft Excel and Stata 11.0 (StataCorp Texas) to describe symp
associations between demographics, symptoms, or treatment and clinical outcome using exact
regression was used to determine probability of death by number of symptoms. Fisher's exact p

Results

Our study sample included 26 of the 30 hospitalised laboratory-conrmed EHF patients. Four p
outcome data. Self-reported symptoms were recorded for 15 patients, clinically observed symp

Demographics and contact history

Table 1 presents self-reported demographics, days before seeking treatment at an Ebola ward,
outcome. Median age was 37 years (range 2066) and 73% were male. No female patients wer
prior to her Ebola ward admission and another was breastfeeding. Most (73%) were isolated in
occupation recorded were health workers, and ve of these (83%) were male. All 14 patients (1
and/or contact during funeral practices, whereas 12 patients (38%) reported no known contac
associated with clinical outcome (Fisher's exact p-value range: 0.250.69).

Table 1. Self-reported demographics, days before seeking treatment at an Ebola ward, an

Ebola haemorrhagic fever, Bundibugyo District, Uganda (November 2007February 2008
doi:10.1371/journal.pone.0052986.t001

Course of disease and clinical manifestations

Eleven of the 26 patients died (CFR = 42%). The median duration of disease was 9 days (range
patients and 9.9 days (range 2 to 21) from self-reported onset to last recorded symptom prior
Ebola ward after a mean self-reported delay of 3.5 days (range 0 to 8) following symptom onse
increased probability of death (e.g. dierences were not signicant for patients who died after b
three days (4/13; 31%) after symptoms reportedly commenced [Fisher's exact p-value 0.66;

Table 2 presents all recorded patient symptoms. The left side shows frequency, usual day of on
15 patients. The most frequently reported general symptoms were fever, nausea/vomiting and
(9/15; 60%), and conjunctivitis (5/15; 33%). Each self-reported symptom was experienced fo
no individual self-reported symptom was associated with clinical outcome (Fisher's exact p-val
signicantly doubled the odds of death (OR 2.14; 95%CI: 1.028.18).

Table 2. Self-reported symptoms (15 patients), clinically observed symptoms (21 patients
hospitalised laboratory-conrmed EHF patients with known clinical outcome for whom da
2007February 2008).
doi:10.1371/journal.pone.0052986.t002

The centre of Table 2 presents frequency, pattern (continuous versus intermittent), and mean d
patients, from presentation to the Ebola ward until clinical outcome. Frequent symptoms includ
myalgia (16/21; 76%), dysphagia and appetite loss (15/21; 71% each), and non-bloody diarr
3.58 days (range 113). Less frequent clinically observed general symptoms (conjunctivitis, c

protracted duration (mean 47 days). Of ten patients whose body temperature was recorded at
fever for one day.

The right of Table 2 and Figure 2 present symptom frequency from self-reported onset to clinic
study-patients. The most frequently experienced symptoms were non-bloody diarrhoea (81%)
presents their median duration.

Figure 2. Frequency of non-haemorrhagic symptoms from self-reported day of symptom o

percentages, among symptomatic (9 deceased and 12 surviving) laboratory-conrmed E
Uganda, November 2007February 2008.
Note changes in denominator between self-reported and clinically observed sections.
doi:10.1371/journal.pone.0052986.g002

Figure 3. Median duration in days of symptoms from self-reported onset until clinical outc
haemorrhagic fever patients, Bundibugyo District, Uganda (November 2007February 20
Blue and red bars indicate general and haemorrhagic symptoms, respectively. *Day 0 = pres
duration of the self-reported symptoms prior to presentation to the Ebola ward for patient o
clinician-assessed symptoms at presentation to and during hospitalisation on the Ebola war

patients only (n = 9).

doi:10.1371/journal.pone.0052986.g003

No self-reported or clinically observed symptom or combination of symptoms, other than any h

clinical outcome (Fisher's exact p-value range: 0.371.00). However, similarly to self-reported
odds of death increased by approximately 31% (OR 1.31; 95%CI: 1.041.82).

Haemorrhagic symptoms

Seven patients experienced self-reported and/or clinically observed haemorrhagic symptoms, s

times greater odds of dying than those not experiencing any haemorrhagic symptom (86% ver

Three patients self-reported haemorrhagic symptoms prior to admission while ve patients wer
hospitalisation. The one surviving patient self-reported and was clinically observed with epistax
and later died, one reported melaena, while the other reported haematemesis, epistaxis, and po
haemorrhagic symptoms clinically observed during hospitalisation. Of the three patients who s
ward within 24 hours of self-reported bleeding onset, while one tolerated melaena for three day
self-reported median of one day of fever prior to Ebola ward presentation.

Clinically observed haemorrhagic symptoms (Table 2; Figure 4) included melaena and prolonge
haematemesis, bleeding gums, haemoptysis, haematuria, haematoma, and postpartum vaginal
clinically observed with haemorrhagic symptoms, the rst was observed with bleeding gums; th
third with melaena, haematemesis, and prolonged bleeding from an injection site; and the fourt
postpartum bleeding. Petechiae were not observed.

Figure 4. Frequency of haemorrhagic symptoms from self-reported day of symptom onse

among symptomatic (9 deceased and 12 surviving) laboratory-conrmed Ebola haemorrh
November 2007February 2008.
Note changes in denominator between self-reported and clinically observed sections.
doi:10.1371/journal.pone.0052986.g004

Case management

Of the 19 laboratory-conrmed patients with treatment details recorded, 18 (95%) were admin
received cimetidine for dyspepsia (Table 3). No other medication was administered to alleviate
patients (37%) for potential concomitant infections. Antimalarials were administered to 11 pat
borderline signicant positive association between antimalarial administration and fatal outcom
However, two of these patients received quinine, indicating more severe infection. When these t

patients receiving presumptive artemether/lumefantrine, the dierence in clinical outcome was

was administered to 16 patients (84%), while four patients (21%) received IV-uids. Vitamin s
antimalarial treatment, there was no signicant dierence in clinical outcome for any treatment

Table 3. Treatment recorded for 19 hospitalised laboratory-conrmed Ebola haemorrhagi

doi:10.1371/journal.pone.0052986.t003

Of the ten patients whose axillary body temperature was recorded at least once during hospital
daily for 80% of their stay, while seven (70%) had their temperature recorded at least once da
rate, and blood pressure were not recorded for any patients.

Discussion

This study documents clinical manifestations of human BEBOV infection among hospitalised pa
clinical manifestations from a putatively novel EBOV species furthers knowledge of human lovi
for improvement and accentuates the need to assess eectiveness of supportive treatment in fu

Case fatality ratio

To date, the 25% crude CFR of the 20072008 Bundibugyo outbreak is the lowest of recorded
laboratory-conrmed patients the CFR increases to 42%, similar to that found by MacNeil and
and observed consistently in SEBOV [53][55], [72] and occasionally in ZEBOV [41], [73]
among putative cases [8] or more accurate due to inclusion of less severe cases who did not at
species merits caution, as disease recognition often requires a functioning surveillance system
species, including route and dose of infection, genetic susceptibility, and underlying prevalence

Patient demographics and contact histories

Similar to some previous lovirus outbreaks, this study population only comprised adults (206
reported direct contact (11/14) or direct contact with a potentially infected corpse during fune
opportunities for disease transmission in previous lovirus outbreaks [33], [49], [75]
contact history. This may be due to non-rigorous patient interviews during high-workload perio
were missing (e.g. 54%, or 14/26 of study subjects did not have their occupation recorded), in
unnoticed secondary transmission could have occurred. Available data preclude decisive conclu

Regrettably, incubation periods were not measured for this study population. Albeit challenging
with a source case, it is possible to obtain quality contact history and incubation-period data
Contact history data facilitate outbreak control eorts and further understanding of transmissi

understanding of disease course in humans [35], [80]. Without complete and accurate data, in
dicult. Authors are, for example, precluded from explaining why 73% of the study population

Clinical manifestations

Ebola-ward clinicians working on the fully functional ward employed a standardised prospective
prioritised data transfer outside the ward [19], [81], [82]. Subsequent analyses (Tables 2
human disease caused by this putatively novel EBOV species and further knowledge of FHF clin
observed and reported from human ZEBOV [28], [40][52], SEBOV [53][55], CIEBOV
clinical data. A more detailed comparison is not feasible due to substantial variations in FHF rep

As lovirus ward clinicians often use personal discretion to decide whether an individual should
community [33], these documented BEBOV clinical manifestations could potentially assist futur
supposed lovirus disease hallmarks (fever plus haemorrhage) were observed relatively infrequ
prior to hospitalization reported fever plus haemorrhage, no individual whose axillary temperat
and one or more haemorrhagic symptom was observed in only ve hospitalised patients. The m
population (i.e. severe headache, asthenia, myalgia) are subjective and could equally indicate t
settings, authors recommend continued rigorous study of human FHF clinical manifestations to
crucial aspect of outbreak control [28][33]. Further improvements to diagnostic accuracy bey
require the consistent and timely dispatch of eld laboratories to lovirus outbreak settings and
test).

Comprehensive documentation and understanding of FHF clinical manifestations is needed, as

presentation, anticipated symptomatology, and disease severity. Authors recommend that futur
form, further justication of which is delineated below [19].

Case management

Data indicate that components of standard treatment were not comprehensively administered a
should have received antibiotics and antimalarials, but these were recorded for only 27% and 4
this was warranted or rather demonstrate sub-standard treatment, incomplete data recording,
74% increased odds of death, suggesting a possible relationship between data recording and o
1.74; 95%CI: 0.2315.06).

Measurement of axillary body temperature, a basic non-invasive procedure, was recorded spora
temperature recorded at least once per day for 80% of their hospital stay. This indication of su
nding that only one patient developed fever for one day during hospitalisation. It is questiona
infection, which seems likely to have been more frequent than data indicate. Sub-standard pati
respiratory rate, blood pressure and laboratory-based biochemical patient monitoring data. Sin
prevented by safety concerns, it is important to develop a protocol for safe usage of such basic
high-biosafety eld laboratory to be located near-by future outbreak epicentres so that diagnos
desirable if laboratory testing additionally included the monitoring of patient's biochemical par
treatment regimens are to incorporate additional elements of intensive care (e.g. correcting ele
haemodynamics, supplementing oxygen, and mitigating strong inammatory responses and dis
evaluation.

While antibiotics and antimalarial administration and standard patient monitoring are deliverab
as indicated by symptomatology or disease severity. However, as in other data collection initiat
69% of patients experience mild pain and appropriately receive paracetamol for its alleviation,
relief? This diculty in interpretation also applies to administration of cimetidine, IV-uids, and
Organizations responsible for lovirus patient management should, prior to the next outbreak,
collection accordingly.

Study limitations

Data were collected from laboratory-conrmed EBOV hospitalised patients on the two Ebola wa
identied in the community [69]. Individuals receiving hospital care may dier from those not s
less severe disease and survive more frequently, thus explaining the overall lower CFR compare
patients (25% versus 42%). Moreover, limited data were collected from patients hospitalised e

Authors were limited to describing administered treatment rather than assessing its impact on
monitoring data precluded adjusting for potential confounding (e.g. by disease severity) of any
instance, the borderline association of antimalarial treatment with fatal outcome could be expla
with malaria or Ebola than those who did not.

Recommendations for improving data collection in lovirus outbreak

Likely reasons for incomplete patient monitoring and possible sub-standard treatment delivery
collection due to heavy workloads, particularly during the height of the outbreak, (ii) recording
likelihood of data mismanagement or loss, and (iii) lack of sta awareness of the importance an
management during lovirus outbreaks. Organizations responsible for lovirus patient manage
supplies to improve data collection and case management components, similar to those used fo

Those responsible for lovirus case management must ensure that sucient supplies and equip
stethoscope, and sphygmomanometer, as used for previous lovirus patients [9], [19],
available at outbreak response initiation. Together with appropriate training and comprehensive
clinicians' eorts to deliver optimal care to future patients and enhance analyses of accurate ep
outbreak control and treatment eorts for poorly understood lovirus diseases.

Finally, laboratory tests (e.g. haemoglobin, complete and white blood cell counts) performed in
included in routine lovirus patient monitoring. On-site laboratory capacity would greatly facilit
diagnostic and patient status results. The authors recommend on-site diagnostic and biochemi
[29], [33], [34].

Conclusions

Authors did not nd important dierences between the symptomatology of BEBOV and other FH
fatality reported initially [8], but are similar to MacNeil and colleague's ndings among conrm
signicantly increased the probability of patient death. Each additional symptom increased the
factor.

Recordkeeping and data collection were poor in both makeshift and fully functional Ebola ward
recordkeeping on Ebola wards will help address the uncertainties discussed in this paper. Impro
intensifying supportive care in future outbreaks. Safety protocols should be reviewed where the
signicantly improving safety.

Acknowledgments

For their invaluable contributions to outbreak containment, authors thank the Uganda Ministry
Outbreak Alert and Response Network (GOARN), Mdecins Sans Frontires, Uganda Virus Resea
African Field Epidemiology Network, International Federation of Red Cross and Red Crescent So
World Food Programme (WFP).

Author Contributions

Performed the experiments: PR NH MDVK PPP ES BJ JL JW ZY RC MVH MB. Analyzed the data: P

PR NH MDVK PPP ES BJ JL JW ZY RC MVH MB. Wrote the paper: PR NH MDVK PPP ES BJ JL JW ZY

References

1. Feldmann H, Geisbert T, Jahrling P, Klenk H, Netesov S, et al.. (2004) Filoviridae In: C.M
Taxonomy, VIIIth Report of the ICTV. London: Elsevier/Academic Press. pp. 645653.

2. Kuhn J (2008) Filoviruses: a compendium of 40 years of epidemiological, clinical, and la

3. WHO, CDC (1998) Infection Control for Viral Haemorrhagic Fevers in the African Health
/publications/ebola/WHO_EMC_ESR_98_2_EN/en/. Accessed 13 November 2012. Gene

4. Formenty P, Libama F, Epelboin A, Allarangar Y, Leroy E, et al. (2003) [Outbreak of Ebola

strategy?]. Med Trop (Mars) 63: 291295. doi: 10.1086/503836
Google Scholar
View Article
PubMed/NCBI

5. Leroy EM, Rouquet P, Formenty P, Souquiere S, Kilbourne A, et al. (2004) Multiple Ebola
wildlife. Science 303: 387390. doi: 10.1126/science.1092528
Google Scholar
View Article
PubMed/NCBI

6. CDC (2007) Ebola Hemorrhagic Fever Outbreak in Uganda. Available: http://www.cdc.g

November 2012. Outbreak Postings.

7. CDC (2010) Known Cases and Outbreaks of Ebola Hemorrhagic Fever, in Chronological
es/dispages/ebola/ebolatable.htm. [Accessed 13/11/2012]. CDC Special Pathogens B

8. WHO (2008) Ebola outbreak contained in Uganda. Available: http://www.who.int/featur

9. Formenty P, Hatz C, Le Guenno B, Stoll A, Rogenmoser P, et al. (1999) Human infection
presentation. J Infect Dis 179 Suppl 1S4853. doi: 10.1086/514285
Google Scholar
View Article
PubMed/NCBI

10. Le Guenno B, Formenty P, Wyers M, Gounon P, Walker F, et al. (1995) Isolation and parti
12711274. doi: 10.1016/s0140-6736(95)90925-7
Google Scholar
View Article
PubMed/NCBI

11. WHO (1995) Ebola virus Available at: http: whqlibdoc.who.int wer = WHO_WER_1995. [A
Epidemiologique Hebdomadaire 70: 137.
Google Scholar
View Article
PubMed/NCBI

12. Fisher-Hoch SP, Brammer TL, Trappier SG, Hutwagner LC, Farrar BB, et al. (1992) Patho
host and virus strain. J Infect Dis 166: 753763. doi: 10.1093/infdis/166.4.753
Google Scholar
View Article
PubMed/NCBI

13. Becker S, Feldmann H, Will C, Slenczka W (1992) Evidence for occurrence of lovirus an
lovirus infections occur worldwide? Med Microbiol Immunol 181: 4355. doi: 10.1007
Google Scholar
View Article
PubMed/NCBI

14. Rollin PE, Williams RJ, Bressler DS, Pearson S, Cottingham M, et al. (1999) Ebola (subty
imported from the Philippines to the United States. J Infect Dis 179 Suppl 1: S108114
Google Scholar
View Article
PubMed/NCBI

15. Miranda ME, Ksiazek TG, Retuya TJ, Khan AS, Sanchez A, et al. (1999) Epidemiology of E
179 Suppl 1: S115119. doi: 10.1086/514314
Google Scholar
View Article
PubMed/NCBI

16. Bausch DG, Feldmann H, Geisbert TW, Bray M, Sprecher AG, et al. (2007) Outbreaks of
Infect Dis 196 Suppl 2: S136141. doi: 10.1086/520542
Google Scholar
View Article
PubMed/NCBI

17. WHO (2005) Marburg haemorrhagic fever in Angola - update 25 (August 24, 2005). Ava
Accessed 13 November 2012. Geneva.

18. Bausch DG, Borchert M, Grein T, Roth C, Swanepoel R, et al. (2003) Risk factors for Mar
Emerg Infect Dis 9: 15311537. doi: 10.3201/eid0912.030355
Google Scholar
View Article
PubMed/NCBI

19. Colebunders R, Tshomba A, Van Kerkhove MD, Bausch DG, Campbell P, et al. (2007) Ma
Republic of the Congo: clinical documentation, features of illness, and treatment. J Infec
Google Scholar
View Article
PubMed/NCBI

20. Bausch DG, Nichol ST, Muyembe-Tamfum JJ, Borchert M, Rollin PE, et al. (2006) Marburg
virus. N Engl J Med 355: 909919. doi: 10.1056/nejmoa051465
Google Scholar
View Article
PubMed/NCBI

21. Bausch DG, Sprecher AG, Jes B, Boumandouki P (2008) Treatment of Marburg and Ebo
vaccines under outbreak conditions. Antiviral Res 78: 150161. doi: 10.1016/j.antivira
Google Scholar
View Article
PubMed/NCBI
22. WHO (2008) Case of Marburg Haemorrhagic Fever imported into the Netherlands from
/index.html. Accessed 13 November 2012. Geneva.

23. WHO (2008) Ebola haemorrhagic fever in the Democratic Republic of the Congo. Availab
Accessed 13 November 2012. Geneva.

24. CDC (2009) Imported case of Marburg hemorrhagic fever Colorado 2008. Morbidity a
View Article
PubMed/NCBI
Google Scholar

25. Tus A (2009) Experimental vaccine may have saved Hamburg scientist from Ebola feve
View Article
PubMed/NCBI
Google Scholar

26. Roddy P, Colebunders R, Lim M (in preparation) Filovirus hemorrhagic fever outbreak ca
options. Journal of Infectious Disease doi: 10.1093/infdis/jir297
Google Scholar
View Article
PubMed/NCBI

27. WHO (2011) Ebola in Uganda. Available: http://www.who.int/csr/don/2011_05_18/en

28. Ndambi R, Akamituna P, Bonnet MJ, Tukadila AM, Muyembe-Tamfum JJ, et al. (1999) Epi
Mosango, Democratic Republic of the Congo, 1995. J Infect Dis 179 Suppl 1: S810. do
Google Scholar
View Article
PubMed/NCBI

29. Jes B, Roddy P, Weatherill D, de la Rosa O, Dorion C, et al. (2007) The Medecins Sans F
epidemic, Uige, Angola, 2005. I. Lessons learned in the hospital. J Infect Dis 196 Suppl
Google Scholar
View Article
PubMed/NCBI

30. Baert B (2001) Ebola outbreak preparedness and management. Brussels: Mdecins San

31. Sterk E (2008) Filovirus haemorrhagic fever guidelines. Barcelona: Mdecins Sans Fron

32. Casillas AM, Nyamathi AM, Sosa A, Wilder CL, Sands H (2003) A current review of Ebola
assessment. Biol Res Nurs 4: 268275. doi: 10.1177/1099800403252603
Google Scholar
View Article
PubMed/NCBI

33. Roddy P, Thomas SL, Jes B, Nascimento Folo P, Pablo Palma P, et al. (2010) Factors as
from Uige, Angola. J Infect Dis 201: 19091918. doi: 10.1086/652748
Google Scholar
View Article
PubMed/NCBI

34. Grolla A, Jones SM, Fernando L, Strong JE, Stroher U, et al. (2011) The Use of a Mobile
Epidemiological Surveillance during the 2005 Marburg Outbreak in Angola. PLoS Negl T
Google Scholar
View Article
PubMed/NCBI

35. Bray M, Mahanty S (2003) Ebola hemorrhagic fever and septic shock. J Infect Dis 188: 1
View Article
PubMed/NCBI
Google Scholar

36. Stroher U, Feldmann H (2006) Progress towards the treatment of Ebola haemorrhagic f
10.1517/13543784.15.12.1523
Google Scholar
View Article
PubMed/NCBI

37. Zaki SR, Goldsmith CS (1999) Pathologic features of lovirus infections in humans. Curr
10.1007/978-3-642-59949-1_7
Google Scholar
View Article
PubMed/NCBI

38. Davis KJ, Anderson AO, Geisbert TW, Steele KE, Geisbert JB, et al. (1997) Pathology of e
Involvement of broblastic reticular cells. Arch Pathol Lab Med 121: 805819.
Google Scholar
View Article
PubMed/NCBI

39. Jaax NK, Davis KJ, Geisbert TJ, Vogel P, Jaax GP, et al. (1996) Lethal experimental infect
oral and conjunctival route of exposure. Arch Pathol Lab Med 120: 140155.
Google Scholar
View Article
PubMed/NCBI

40. Sureau PH (1989) Firsthand clinical observations of hemorrhagic manifestations in Ebo

S790793. doi: 10.1093/clinids/11.supplement_4.s790
Google Scholar
View Article
PubMed/NCBI

41. Georges AJ, Leroy EM, Renaut AA, Benissan CT, Nabias RJ, et al. (1999) Ebola hemorrha
health control issues. J Infect Dis 179 Suppl 1: S6575. doi: 10.1086/514290
Google Scholar
View Article
PubMed/NCBI

42. Leroy EM, Souquiere S, Rouquet P, Drevet D (2002) Re-emergence of ebola haemorrhag
10.1016/s0140-6736(02)07796-6
Google Scholar
View Article
PubMed/NCBI

43. Kalongi Y, Mwanza K, Tshisuaka M, Lusiama N, Ntando E, et al. (1999) Isolated case of E
Kinshasa, Democratic Republic of the Congo. J Infect Dis 179 Suppl 1: S1517. doi: 10.
Google Scholar
View Article
PubMed/NCBI

44. Kibadi K, Mupapa K, Kuvula K, Massamba M, Ndaberey D, et al. (1999) Late ophthalmolo
in Kikwit, Democratic Republic of the Congo. J Infect Dis 179 Suppl 1: S1314. doi: 10.1
Google Scholar
View Article
PubMed/NCBI

45. Mupapa K, Mukundu W, Bwaka MA, Kipasa M, De Roo A, et al. (1999) Ebola hemorrhagic

10.1086/514289
View Article
PubMed/NCBI

Google Scholar

46. Mupapa K, Massamba M, Kibadi K, Kuvula K, Bwaka A, et al. (1999) Treatment of Ebola h
patients. International Scientic and Technical Committee. J Infect Dis 179 Suppl 1: S1
Google Scholar
View Article
PubMed/NCBI

47. Bonnet MJ, Akamituna P, Mazaya A (1998) Unrecognized Ebola hemorrhagic fever at Mo
Republic of the Congo. Emerg Infect Dis 4: 508510. doi: 10.3201/eid0403.980349
Google Scholar
View Article
PubMed/NCBI

48. Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, et al. (1999) Ebola hemorrha
observations in 103 patients. J Infect Dis 179 Suppl 1: S17. doi: 10.1086/514308
Google Scholar
View Article
PubMed/NCBI

49. WHO (1978) Ebola haemorrhagic fever in Zaire, 1976. Bull World Health Organ 56: 271
View Article
PubMed/NCBI
Google Scholar

50. Isaacson M, Sureau P, Courteille G, Pattyn S (1978) Clinical aspects of Ebola virus disea
editor. Ebola virus hemorrhagic fever. Amsterdam: Elsevier/North Holland. pp. 1520.

51. Piot P, Sureau P, Breman G (1978) Clinical aspects of Ebola virus infection in Yambuku a
fever: Elsevier/North-Holland. pp. 714.

52. Heymann DL, Weisfeld JS, Webb PA, Johnson KM, Cairns T, et al. (1980) Ebola hemorrha
doi: 10.1093/infdis/142.3.372
View Article
PubMed/NCBI
Google Scholar
53. WHO (1978) Ebola haemorrhagic fever in Sudan, 1976. Report of a WHO/International
View Article
PubMed/NCBI
Google Scholar

54. Baron RC, McCormick JB, Zubeir OA (1983) Ebola virus disease in southern Sudan: hosp
Organ 61: 9971003.
Google Scholar
View Article
PubMed/NCBI
55. Emond RT, Evans B, Bowen ET, Lloyd G (1977) A case of Ebola virus infection. Br Med J
View Article
PubMed/NCBI
Google Scholar

56. Mupere E, Kaducu OF, Yoti Z (2001) Ebola haemorrhagic fever among hospitalised child
clinical observations. Afr Health Sci 1: 6065.
Google Scholar
View Article
PubMed/NCBI

57. Siegert R, Shu HL, Slenczka W, Peters D, Muller G (1967) [On the etiology of an unknow
Wochenschr 92: 23412343. doi: 10.1055/s-0028-1106144
Google Scholar
View Article
PubMed/NCBI

58. Martini GA (1969) Marburg agent disease: in man. Trans R Soc Trop Med Hyg 63: 2953
View Article
PubMed/NCBI
Google Scholar

59. Martini GA, Knau HG, Schmidt HA, Mayer G, Baltzer G (1968) A hitherto unknown infec
disease. Ger Med Mon 13: 457470.
Google Scholar
View Article
PubMed/NCBI

60. Martini G (1971) Marburg virus disease. Clinical syndrome. Marburg Virus Disease. New

61. Egbring R, Slenczka W, Baltzer G (1971) Clinical manifestations and mechanism of the h
Disease. Berlin: Springer-Verlag. pp. 4249.

62. Stille W, Bohle E (1971) Clinical course and prognosis of Marburg virus (Green Monkey
1018.

63. Todorovitch K, Mocitch M, Klasnja R (1971) Clinical picture of two patients infected by t
Verlag. pp. 1923.

64. Nikiforov VV, Turovskii Iu I, Kalinin PP, Akinfeeva LA, Katkova LR, et al.. (1994) [A case o
Epidemiol Immunobiol: 104106.

65. Johnson ED, Johnson BK, Silverstein D, Tukei P, Geisbert TW, et al. (1996) Characterizat
Kenya. Arch Virol Suppl 11: 101114. doi: 10.1007/978-3-7091-7482-1_10
View Article
PubMed/NCBI
Google Scholar

66. Smith DH, Johnson BK, Isaacson M, Swanapoel R, Johnson KM, et al. (1982) Marburg-vi
10.1016/s0140-6736(82)91871-2
Google Scholar
View Article
PubMed/NCBI

67. Gear JS, Cassel GA, Gear AJ, Trappler B, Clausen L, et al. (1975) Outbreak of Marburg v
10.1136/bmj.4.5995.489
Google Scholar
View Article
PubMed/NCBI

68. WHO (2007) Ebola haemorrhagic fever in Uganda. Available: http://www.who.int/csr/d

Geneva.

69. MacNeil A, Farnon EC, Wamala J, Okware S, Cannon DL, et al. (2010) Proportion of deat
Uganda. Emerg Infect Dis 16: 19691972. doi: 10.3201/eid1612.100627
Google Scholar
View Article
PubMed/NCBI

70. WHO (2007) End of Ebola outbreak in Uganda. Available: http://www.who.int/csr/don/

Geneva.

71. Towner JS, Sealy TK, Khristova ML, Albarino CG, Conlan S, et al. (2008) Newly discovere
Uganda. PLoS Pathog 4: e1000212. doi: 10.1371/journal.ppat.1000212
Google Scholar
View Article
PubMed/NCBI
72. WHO (2004) WHO announces end of Ebola outbreak in southern Sudan. Available:
13 November 2012. Geneva.
73. WHO (2008) End of Ebola outbreak in the Democratic Republic of the Congo. Available:
Accessed 13 November 2012. Geneva.
74. Borchert M, Muyembe-Tamfum JJ, Colebunders R, Libande M, Sabue M, et al. (2002) Sh
an infant. Trop Med Int Health 7: 902906. doi: 10.1046/j.1365-3156.2002.00945.x
View Article
PubMed/NCBI
Google Scholar

75. Dowell SF (1996) Ebola hemorrhagic fever: why were children spared? Pediatr Infect Di
View Article
PubMed/NCBI
Google Scholar

76. Roels TH, Bloom AS, Bungton J, Muhungu GL, Mac Kenzie WR, et al. (1999) Ebola hem
risk factors for patients without a reported exposure. J Infect Dis 179 Suppl 1: S9297.
Google Scholar
View Article
PubMed/NCBI

77. Francesconi P, Yoti Z, Declich S, Onek PA, Fabiani M, et al. (2003) Ebola hemorrhagic fev
Infect Dis 9: 14301437. doi: 10.3201/eid0911.030339
Google Scholar
View Article
PubMed/NCBI

78. Hewlett BS, Amola RP (2003) Cultural contexts of Ebola in northern Uganda. Emerg Infe
View Article
PubMed/NCBI
Google Scholar

79. Conrad JL, Isaacson M, Smith EB, Wul H, Crees M, et al. (1978) Epidemiologic investig
Med Hyg 27: 12101215.
Google Scholar
View Article
PubMed/NCBI

80. Bray M, Murphy FA (2007) Filovirus research: knowledge expands to meet a growing th
View Article
PubMed/NCBI
Google Scholar

81. Bausch DG, Towner JS, Dowell SF, Kaducu F, Lukwiya M, et al. (2007) Assessment of the
Infect Dis 196 Suppl 2: S142147. doi: 10.1086/520545
Google Scholar
View Article
PubMed/NCBI

82. Buhler S (2008) Health care workers' experiences and preferences regarding document
Marburg wards (MSc thesis). London: London School of Hygiene & Tropical Medicine.