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Filovirus Outbreak Detection and Surveillance: Lessons From Bundibugyo

Article · November 2011with59 Reads
DOI: 10.1093/infdis/jir294 · Source: PubMed
Abstract
The first outbreak of Ebola hemorrhagic fever (EHF) due to Bundibugyo ebolavirus occurred in Uganda from August to December 2007. During outbreak response and assessment, we identified 131 EHF cases (44 suspect, 31 probable, and 56 confirmed). Consistent with previous large filovirus outbreaks, a long temporal lag (approximately 3 months) occurred between initial EHF cases and the subsequent identification of Ebola virus and outbreak response, which allowed for prolonged person-to-person transmission of the virus. Although effective control measures for filovirus outbreaks, such as patient isolation and contact tracing, are well established, our observations from the Bundibugyo EHF outbreak demonstrate the need for improved filovirus surveillance, reporting, and diagnostics, in endemic locations in Africa.
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SUPPLEMENT ARTICLE
Filovirus Outbreak Detection and Surveillance:
Lessons From Bundibugyo
Adam MacNeil,
1,2
Eileen C. Farnon,
1
Oliver W. Morgan,
2
Philip Gould,
2
Tegan K. Boehmer,
2
David D. Blaney,
2
Petra Wiersma,
2
Jordan W. Tappero,
3
Stuart T. Nichol,
1
Thomas G. Ksiazek,
1,4
and Pierre E. Rollin
1
1
Viral Special Pathogens Branch,
2
Epidemic Intelligence Service Program, and
3
Global Aids Program, The Centers for Disease Control and Prevention,
Atlanta, Georgia; and
4
Galveston National Laboratory, Department of Pathology, UTMB, Galveston, Texas
The first outbreak of Ebola hemorrhagic fever (EHF) due to Bundibugyo ebolavirus occurred in Uganda from
August to December 2007. During outbreak response and assessment, we identified 131 EHF cases (44 suspect,
31 probable, and 56 confirmed). Consistent with previous large filovirus outbreaks, a long temporal lag
(approximately 3 months) occurred between initial EHF cases and the subsequent identification of Ebola virus
and outbreak response, which allowed for prolonged person-to-person transmission of the virus. Although
effective control measures for filovirus outbreaks, such as patient isolation and contact tracing, are well
established, our observations from the Bundibugyo EHF outbreak demonstrate the need for improved filovirus
surveillance, reporting, and diagnostics, in endemic locations in Africa.
The family Filoviridae has two genera of viruses, Ebo-
lavirus and Marburgvirus, which are associated with
similar clinical syndromes: Ebola hemorrhagic fever
(EHF) and Marburg hemorrhagic fever (MHF). Inves-
tigators have identified 4 species of Ebola virus—Zaire
ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV),
Reston ebolavirus (REBOV), Cote d’Ivoire ebolavirus
(CIEBOV)—and 1 proposed species, Bundibugyo
ebolavirus (BEBOV) [1], whereas a single species of
Marburg virus, Lake Victoria marburgvirus (MARV) is
known. EHF and MHF are notable for the overall se-
verity of disease in humans, often with hemorrhagic
characteristics and high case fatality. Considerable dif-
ferences in the mortality of various Ebola viruses and
strains of Marburg virus have been noted, ranging from
a low of approximately 40% for Bundibugyo ebolavirus
[2] to nearly 90% for Zaire ebolavirus [3, 4], and simi-
larly, mortality among Marburg viruses have ranged
from 25% to 90% [5]. Typical early symptoms of EHF
and MHF, such as fever, fatigue, headache, muscle
aches, vomiting, and diarrhea, are nonspecific [3, 6–11],
making initial syndromic-based identification of these
diseases a challenge. Serologic, molecular, and virologic
data suggest that fruit bats are the zoonotic reservoir of
filoviruses [12–16]; however, filovirus outbreaks are
characterized by prolonged chains of familial and nos-
ocomial person-to-person transmission, which occurs
through direct contact, contact with bodily fluids, or
contact with contaminated clothes or linens of an in-
fected person [17–21].
In November 2007, EHF was confirmed by Viral
Special Pathogens Branch, Centers for Disease Control
and Prevention (CDC), Atlanta, GA, in diagnostic
samples associated with an outbreak of illnesses with
unknown etiology in Bundibugyo District, Uganda.
Genetic sequencing demonstrated that infections were
caused by a novel fifth Ebolavirus species, BEBOV [22],
marking the first time a new filovirus species had been
identified since 1994 [23]. In the following days, a large
national and international outbreak response was star-
ted to contain the outbreak. Organizations involved in
outbreak response included the Uganda Ministry of
Health, Me
´decins Sans Frontie
`res, the World Health
Organization, the African Field Epidemiology Training
Network, the Uganda Virus Research Institute, and the
Potential conflicts of interest: none reported.
Correspondence: Adam MacNeil, PhD, MPH, Viral Special Pathogens Branch,
Centers for Disease Control and Prevention, 1600 Clifton Rd NE, MS G-14, Atlanta,
GA 30333 (aho3@cdc.gov).
The Journal of Infectious Diseases 2011;204:S761–S767
Published by Oxford University Press on behalf of the Infectious Diseases Society of
America 2011.
0022-1899 (print)/1537-6613 (online)/2011/204S3-0002$14.00
DOI: 10.1093/infdis/jir294
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International Federation of Red Cross. Previous reports on this
outbreak have focused on identification and the clinical and
epidemiologic characteristics associated with EHF in Bundibu-
gyo District [2, 22, 24]. The goal of this article is to discuss
challenges and contrast characteristics of surveillance, case
classification, and epidemiology of the 2007 Bundibugyo EHF
outbreak with those from previous large filovirus outbreaks.
METHODS
Data Collection
Epidemiologic data collection and laboratory testing (poly-
merase chain reaction [PCR], antigen detection enzyme-
linked immunosorbent assay [ELISA], immunoglobulin
M ELISA, immunoglobulin G ELISA) was performed, using
standardized procedures, as described previously [2]. Case
reportformswerefilledoutinthefieldatthetimeofthe
patient’s initial presentation. In some cases, information re-
garding signs, symptoms, dates, and contacts were retro-
spectively collected by follow-up interview or by hospital
chart review. Data collection and management was performed
by and shared daily with multiple organizations involved in
the acute outbreak response. Laboratory testing was per-
formed at the Uganda Virus Research Institute, Entebbe,
Uganda. In addition, sample aliquots were shipped to Atlanta,
to the CDC for confirmatory laboratory testing. All data for
this report was collected as part of public health surveillance
and outbreak response. Whereas other reports have described
slightly different aggregate case numbers [24], for this article,
patient classification was based on confirmatory laboratory
testing, combined with epidemiologic data, at CDC; finalized
data was provided to the Uganda Ministry of Health.
Case Classification
Final case classification was based on signs and symptoms,
history of contact, and laboratory testing. The assignment of
history of contact was based on the question, ‘‘Did the patient
have a contact with a known suspect case anytime in the 3 weeks
before becoming ill?’’ along with the name of the contact pro-
vided on the case investigation form at the time of presentation.
Information regarding history of contact, on the case in-
vestigation form, was limited to a single contact per case. Cases
of disease were classified as suspect, probable, or confirmed
cases; or characterized as not a case of EHF. A suspect EHF case
was defined as the occurrence of 1 of the following in a resident
of or visitor to Bundibugyo District after 1 August 2007:
(1) sudden onset of fever, plus at least 4 of the following signs or
symptoms: vomiting, diarrhea, abdominal pain, conjunctivitis,
skin rash, unexplained bleeding from any site, muscle pain, in-
tense fatigue, difficulty swallowing, difficulty breathing, hiccups,
headache; or (2) sudden onset of fever, plus history of contact
with a suspect, probable, or confirmed EHF case; or (3) any
sudden, unexplained death. A probable EHF case was defined as
an individual meeting the suspect case definition, with a history
of contact with a probable or confirmed EHF case in the 3 weeks
prior to development of signs and symptoms, plus at least 3 of
the following signs or symptoms: vomiting, diarrhea, un-
explained bleeding, conjunctivitis, or skin rash. A confirmed
case was defined as a suspect or probable case with laboratory
confirmation of infection. An individual was defined as not
being a case of EHF if within 3 days or more following the onset
of symptoms, the individual demonstrated the absence of Ebola
virus infection by laboratory testing, or the individual did not
meet the clinical definition of a suspect EHF case.
During the acute stage of the outbreak response, the above
suspect case definition was liberally applied as a surveillance and
prevention tool for the identification and isolation of potential
EHF cases within Bundibugyo district. As such, a number of ill
persons were investigated during the outbreak response who did
not meet the final criteria for a suspect EHF case. In this report,
all potential EHF cases for which surveillance information was
collected (including those whose symptoms did not meet the
final criteria as a suspect case) during the outbreak response are
considered investigated cases.
RESULTS
Case Classification
In total, 192 cases of illness in Bundibugyo District were
investigated during the EHF outbreak response (Figure 1).
Of these, a definitive laboratory outcome was obtained for
101 cases: 56 individuals were identified as confirmed cases of
EHF, and 45 individuals were classified as not cases of EHF.
Among the remaining 91 individuals, for whom a laboratory
outcome was not available, 16 individuals were classified as not
a case, on the basis ofnot having the clinical signs and symptoms
congruent with the suspect case definition. For the remaining
cases, 75 met the suspect EHF case definition, and 31 of those
individuals met the probable EHF case definition (44 remained
classified as suspect cases).
In summary, 131 total cases of suspect (n544), probable
(n531), or confirmed (n556) EHF were identified in Bun-
dibugyo District. Of the 131 cases, 42 had fatal outcomes (32%).
In contrast, only 7% of investigated illnesses that were classified
as not a case of EHF had fatal outcomes (Table 1). Among all
suspect, probable, and confirmed EHF cases, no trend for in-
creasing or decreasing case fatality was noted over the course of
the outbreak, when cases were classified on the basis of the
month of symptom onset (P5.5827; Cochran–Armitage trend
test).
Outbreak Dynamics
The first suspect EHF case identified in Bundibugyo District
developed a fever on 20 August (Figure 2) and subsequently died
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on 4 September 2007. No cases meeting the suspect EHF case
definition with symptom onset prior to this date were identified;
however, owing to the delayed investigation (full outbreak re-
sponse occurred in early December 2007), whether this in-
dividual is the actual index case of the outbreak remains unclear.
The first laboratory-confirmed case developed symptoms on 14
September and later recovered.
Case counts remained relatively low through most of Sep-
tember and October. A peak in case detections occurred in late
November and early December. This peak was largely associated
with secondary transmission from a single individual who de-
veloped signs and symptoms of illness in early November, was
hospitalized on 16 November, and died with severe hemorrhagic
disease on 23 November. This individual had prominent status
in the community, and numerous members of the local pop-
ulation had contact with this individual, either shortly before his
death, or at his funeral. In total, 27 people developed EHF fol-
lowing contact with this individual (including 22 laboratory-
confirmed cases); 11 of these cases died. Secondary transmission
from this individual accounted for 21% of the case total in the
Bundibugyo District outbreak. In contrast, only 2 instances of
tertiary transmission (transmission from a secondary case) were
identified. Of the 27 secondary cases, we note there is a single
secondary EHF case with an exceptionally long incubation pe-
riod (25 d). It remains possible that whereas this case did have
contact with the index EHF case in this cluster, transmission
occurred following contact with a different individual infected
with BEBOV.
DISCUSSION
Challenges in Case Identification and Classification
Although the use of structured of case investigation forms (in-
cluding use during retrospective follow-up investigations) al-
lowed us to standardize clinical information on cases, there are
clear limitations with this approach.For instance, a large portion
of information was collected during triage, and may not capture
the whole range of signs and symptoms subsequently experi-
enced by EHF cases. Similarly, whereas chart reviews were per-
formed for those case patients who had developed disease prior
to recognition of the outbreak, the clinical information extracted
from the written record was often limited. In addition, although
follow-up interviews were performed on some surviving cases,
actual signs and symptoms reported during follow-up interview
may have been subject to recall bias. Regardless of these limi-
tations, we do note strong concordance between severity of
disease and classification as a case of BEBOV infection. As de-
scribed, among all cases meeting the final suspect, probable, or
confirmed case definition, case fatality was 32% (and case fa-
tality was 40% among laboratory confirmed cases diagnosed on
the basis of an acute diagnostic sample [2]), whereas only 7% of
identified illnesses that were classified as not a case of EHF had
a fatal outcome.
Review of epidemiologic data from the 2007 Bundibugyo
investigation underscores the difficulty in assigning case defi-
nitions when investigating filovirus outbreaks. As with any
pathogen that has not been well characterized, there is a circular
logic in prospectively using cases definitions based on signs and
symptoms to identify cases, which will subsequently be used to
describe the signs and symptoms of the disease. Furthermore,
although predefined case definitions represent a valuable activity
in outbreak planning and response, the reality is often more
complex. Investigators developing case definitions may not be
the same personnel attempting to determine whether an ill
person should be characterized as a case of EHF for purposes of
isolation. As would be expected, medical personal attempting to
Table 1. Case Fatality Rates Among Ebola Hemorrhagic Fever
(Suspect, Probable, or Confirmed) and Illnesses Ruled as Not
a Case of Ebola Hemorrhagic Fever Among Illnesses Investigated
During the Bundibugyo Outbreak Response
Fatal Cases/Total
Number of Cases
Case Fatality
Rate
Suspect, probable, and
confirmed EHF cases
42/131 32.0%
Not a case of EHF 4/61 6.6%
NOTE. EHF, Ebola hemorrhagic fever.
Figure 1. Classification of cases investigated during the Ebola
hemorrhagic fever outbreak response, Bundibugyo District, Uganda, 2007.
EHF, Ebola hemorrhagic fever.
1
Includes investigated cases that had no
laboratory testing and investigated cases with an inconclusive laboratory
result.
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triage sick individuals during a filovirus outbreak may rely on
clinical judgment in addition to epidemiologically assigned
criteria in assessing patients.
In some filovirus outbreaks with extremely high case fatality
(for instance, outbreaks due to ZEBOV and the MARV out-
breaks in the Democratic Republic of Congo [DRC] and Angola,
in which 80%–90% of cases have a fatal outcome [3, 7, 8, 10,
25–27]), severe illness, death, or both are expected to be strongly
predictive of filovirus infection. In the case of BEBOV infection,
fewer than half of cases had a fatal outcome. Common signs
and symptoms of EHF are largely nonspecific and may mimic
other tropical infections. For instance, common signs and
symptoms of laboratory-confirmed cases of BEBOV infection
included fever, fatigue, headache, nausea, vomiting, abdominal
pain, muscle pain, joint pain, and diarrhea, and among those
with a well-documented contact history, the average time from
last contact to symptom onset was 6.3 days [2].
As previously described, many illnesses investigated in Bun-
dibugyo District were classified as not a case of EHF on the basis
of laboratory testing or signs and symptoms. Because filovirus
outbreak control is reliant on identifying cases and minimizing
person-to-person transmission, it remains important to identify
all potentially infectious individuals. In 2004, during the con-
comitant Ebola virus and measles virus outbreaks in Yambio,
Sudan, both viruses spread within families and within groups of
contacts, with similar signs and symptoms of illness during the
early stages of infection [28]. In that setting, it was difficult to
clinically and epidemiologically differentiate severe measles from
EHF, leading to isolation of patients with measles and EHF
together. Only retrospective testing was able to differentiate the
diseases. We believe the combination of broad (highly sensitive)
surveillance criteria and rapid laboratory diagnostic capacity
(highly specific) to correctly classify ill persons as having or not
having EHF will maximize the ability to identify the virus,
provide medical care, and prevent further spread of the virus
from infectious individuals. Such a system will also allow those
who do not have a filovirus infection to be released back into the
community or triaged to receive appropriate medical care.
Adding to challenges faced in syndromic-based case identi-
fication and classification, at times during the EHF outbreak in
Bundibugyo District there was a reluctance to collect diagnostic
samples due to the perception that specimens were being
collected for reasons other than diagnostic testing. This was
particularly the case for retrospective investigation and classifi-
cation of individuals who had an illness consistent with EHF
prior to the outbreak response. At times we noted a similar
hesitancy in sharing clinical records among partner organ-
izations, the result of the lack of communication between groups
due to being overwhelmed by urgent patient care and outbreak
response issues. We believe it remains a crucial responsibility of
every group involved in outbreak response to scientifically
characterize clinical, laboratory, and epidemiologic aspects of
filovirus outbreaks (particularly in the case of a novel virus, such
as BEBOV) to develop improved prevention measures and
Figure 2. Distribution of suspect, probable, and confirmed Ebola hemorrhagic fever cases, based on the date of onset of symptoms, Bundibugyo
District, Uganda, 2007. EHF, Ebola hemorrhagic fever. Date of onset of symptoms of the individual associated with a large cluster of transmission events
is shown in red. Date of onset of secondary cases and tertiary cases from this individual are shown in green and blue, respectively.
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outbreak response guidelines for future human outbreaks. We
additionally believe that efforts to increase dialog and collabo-
rative activities between partner organizations, both prior and
during outbreak response, will help alleviate these issues in
future outbreak responses.
Common Characteristics of Filovirus Outbreaks
There are common, recurrent themes that characterize most
large (100 or more cases) filovirus outbreaks. For example,
filovirus outbreaks often involve long temporal lags between
initial cases and subsequent outbreak identification and
response. In the instance of Bundibugyo District, .2 months
elapsed between initial EHF cases and preliminary investigation,
and .3 months elapsed before filovirus-specific outbreak
control measures were fully implemented. Similar lag periods
have also been associated with many previous filovirus outbreaks
(Table 2). As shown, in large filovirus outbreaks, the time from
initial spill-over events to recognition and implementation of
a full-scale outbreak response has consistently been .1 month,
and often much longer. Although outbreak response following
etiologic identification tends to occur rapidly, the long temporal
lag between early cases and subsequent outbreak recognition
fosters the perpetuation of person-to-person transmission in
community and hospital settings. We believe this observation
demonstrates the importance of improving surveillance for
filovirus infections in endemic areas of sub-Saharan Africa. With
improved surveillance and rapid outbreak detection, it is possi-
ble to quickly intervene and limit person-to-person transmission
and geographic dissemination in outbreak settings, thus mini-
mizing the time and overall size of future filovirus outbreaks.
Large outbreaks tend to occur in remote locations, where
proper medical, public health, transportation, and communi-
cation infrastructure are limited. The transmission (and often
amplification) of filovirus infections in hospital settings has been
well described [3, 4, 6, 10, 17]. Whereas the use of personal
protective equipment is recommended for medical personnel in
outbreaks, transmission of filoviruses in health care settings can
be largely prevented by basic infection control precautions and
proper disposal of potentially infectious items [33, 34]. Wide-
spread filovirus transmission events typically involve hospital
settings where available protective equipment is limited or un-
available, and these events underscore the need for improved
infection control measures in areas that have potential for filo-
virus infections.
Although the index case is often not identified, most filovirus
outbreaks are typically the result of a single or small number
of initial zoonotic transmission events that lead to subsequent
prolonged chains of person-to-person transmission. Most hu-
man filovirus infections associated with large outbreaks in the
previous 30 years have been the result of person-to-person
transmission (with the notable exceptionof an outbreak of MHF
in northern DRC from 1998 to 2000, which involved multiple
Table 2. Timeliness of Outbreak Detection and Response for Large (>100 Cases) Filovirus Outbreaks
Location, year (disease)
1
Onset of first
identified case
Date of preliminary
assessment or report
Date of international
outbreak response
Time between onset
and outbreak response
Total number of
cases identified Reference
Zaire, 1976 (EHF) 1 September 1976 21 September 1976 19 October 1976 .1.5 months 318 [3]
Sudan, 1976 (EHF) 27 June 1976 4 October 1976 29 October 1976 .4 months 284 [6]
Democratic Republic of
Congo, 1995 (EHF)
6 January 1995 1 May 1995 11 May 1995 .4 months 315 [4]
Democratic Republic of
Congo, 1998–2000
2
(MHF)
October 1998 23 April 1999 8 May 1999 7 months 154 [10]
Uganda, 2000 (EHF) 30 August 2000 8 October 2000 21 October 2000 .1.5 months 425 [9, 29, 30]
Congo/Gabon, 2001 (EHF) 25 October 2001 24 November 2001 16 December 2001 .1.5 months 124 [25]
Congo, 2003
3
(EHF) 25 December 2002 28 January 2003 19 February 2003 .1.5 months 143 [26]
Angola, 2005 (MHF) October 2004 (presumed) 9 March 2005 27 March 2005 .5 months 374 [27, 31]
Democratic Republic of
Congo, 2007 (EHF)
Late May 2007 21 August 2007 17 September 2007 .3.5 months 264 [32]
Uganda, 2007 (EHF) 20 August 2007 5 November 2007 3 December 2007 .3 months 131 [24], current
manuscript
NOTE.
1
Ebola hemorrhagic fever (EHF) or Marburg hemorrhagic fever (MHF).
2
Numerous introductions occurred over the course of 2 years within a gold-mining village.
3
At least 3 independent introductions.
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zoonotic introductions associated with mining activities [10]).
Although the infectious nature of person-to-person trans-
mission of filoviruses is limited to direct contact, contact with
bodily fluids, or contact with contaminated objects (and so is
less efficient than aerosol or food- or waterborne transmission),
large filovirus outbreaks continue to occur, demonstrating the
potentially explosive nature of filoviruses in resource-challenged
parts of Africa.
We identified a large cluster of secondary EHF cases associ-
ated with transmission from a single individual in Bundibugyo
District. This is not the first occurrence of a focus of secondary
infections from a single individual accounting for a large portion
of overall infections in a filovirus outbreak. For instance, Khan
et al described 2 individuals who accounted for 20% of all in-
fections during the outbreak of EHF in Kikwit, DRC [4]. Despite
the large number of secondary cases associated with this single
individual in Bundibugyo District, we documented only 2 ter-
tiary cases of EHF in this chain of transmission. Importantly, the
onset of symptoms in secondary cases occurred approximately
at the same time as the implementation of the international
outbreak response. Others have previously described the im-
portance of surveillance and patient isolation in filovirus out-
break control [31, 35]. We believe the absence of a tertiary wave
of infections in this instance demonstrates the efficacy of es-
tablished outbreak control measures in controlling filovirus
outbreaks.
CONCLUSION
The outbreak associated with BEBOV resulted in over 100 cases
of EHF in Uganda in 2007. Although it was due to a novel Ebola
virus, this outbreak had characteristics that were similar to those
of other large filovirus outbreaks. Importantly, the long delay
between initial cases and filovirus detection and response al-
lowed for chains of person-to-person transmission. Although
filovirus outbreaks often occur in remote, underdeveloped, re-
source-limited settings, outbreak detection and management is
largely reliant on basic case identification and infection control
practices. Based on lessons from previous outbreaks, we note the
following as surveillance measures for ministries of health and
international public health organizations working in endemic
areas to consider:
1. Education to rural medical personnel on the signs and
symptoms of filovirus infections, such that early chains of
transmission can be identified by local populations. For
instance, in response to numerous outbreaks of EHF that
occurred in the Republic of Congo and Gabon from 1994 to
2003, educational activities were provided to medical staff and
individuals in rural areas on EHF disease and risk factors for
Ebola virus infection. These activities may have contributed to
the absence of documented EHF in this area since 2005.
2. Implementation of basic infection control procedures,
including patient isolation, disinfection of contaminated
materials, and contact precautions (including gowns and
gloves), in rural hospitals, such that individual or small clusters
of filovirus cases can be contained without transmission
amplification in the health care setting.
3. Improve the capacity for local medical staff and public
health personnel to identify, collect standardized information,
and report suspect filovirus infections to the ministry of health
or national public health authorities.
4. Pre-establish an effective network to collect and transport
diagnostic specimens, including preplacement of sample
collection materials and secure packaging and shipping
containers at rural health centers, and identifying the most
appropriate transportation mechanisms (personal transport,
public transport, air transport) to rapidly delivery diagnostic
specimens to the national (or other appropriate) laboratory.
5. Improve the capacity to do filovirus diagnostic testing in-
country to avoid the temporal lag associated with shipping
diagnostic specimens internationally, such that outbreak
measures can be implemented as rapidly as possible in the
event of an actual filovirus infection.
Funding
This work was supported by the Centers for Disease Control and Pre-
vention.
Acknowledgments
The findings and conclusions of this report are those of the authors and
do not necessarily represent the views of the Centers for Disease Control
and Prevention.
We acknowledge the numerous organizations that were involved in
outbreak investigation and response in Uganda in 2007, including the
Uganda Ministry of Health, the Uganda Virus Research Institute, the
World Health Organization, Me
´decins Sans Frontie
`res, the African Field
Epidemiology Network, the Centers for Disease Control and Prevention,
Atlanta, and the government of Uganda.
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EHF Surveillance in Bundibugyo dJID 2011:204 (Suppl 3) dS767
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Article
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