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Paul K Drain
[email protected]
Medical Practice Evaluation Center, Department of
Medicine, Massachusetts General Hospital and
Harvard Medical School, Boston, MA 02114, USA
Westcott L. CDC Director draws parallels
between Ebola outbreak and HIV/AIDS
epidemic. Newsweek (USA), Oct 9, 2014.
http://www.newsweek.com/cdc-directordraws-parallels-between-ebola-outbreak-andhivaids-epidemic-276466 (accessed Nov 14,
Drain PK, Hyle EP, Noubary F, et al. Diagnostic
point-of-care tests in resource-limited
settings. Lancet Infect Dis 2014; 14: 239–49.
Vogel G. Testing new Ebola tests. Science 2014;
345: 1549.
WHO. UNAIDS report shows that 19 million of
the 35 million people living with HIV today do
not know that they have the virus (press
release). Geneva: World Health Organization.
July 16, 2014. http://www.unaids.org/en/
july/20140716prgapreport/ (accessed Nov 14,
WHO 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.
Ebola: between
mathematics and reality
Ebola needs to be contained. Despite
this basic epidemiological truth, we
have difficulty understanding the
intelligence, money, and institutional
efforts dedicated to this disease.
In their Article on the control of Ebola
virus transmission, Joseph Lewnard
and colleagues1 conclude that 4800
additional beds could save many
lives in Montserrado, Liberia. They
estimated that expanding treatment
centres on Oct 15 could have prevented
137 432 cases by Dec 15. By contrast,
they predicted 170 996 cases over
the same period if treatment was not
expanded. During that time (106 days),
therefore, their projections argue that
an additional 4800 beds would have
treated 33 564 patients. In fact, this
was a ten times overprojection.
www.thelancet.com/infection Vol 15 February 2015
In our resource-depleted hospital,
we treat up to 95 000 inpatients per
year2 with 1300 beds; equivalent to
27 500 patients per 106 days. This
care includes some quite complex
treatments such as ventilation,
dialysis, paediatric surgery, neurosurgery, and chemotherapy. 40%
of our patients are HIV positive and
need complicated schemes to deal
with tuberculosis, cryptococcosis,
and Kaposi´s sarcoma. Many of these
patients stay in hospital longer than
do Ebola patients.
We cannot see why we would need
369% of our present number of beds
to treat almost the same number of
patients for a disease that is relatively
easy to treat (even when the protective
gear can be unpleasant to wear).
Working daily with existing pandemic conditions such as malaria,
sepsis, and road traffic accidents—
which have killed more patients in the
past 2 weeks than Ebola, severe acute
respiratory syndrome, Middle East
respiratory syndrome, bird flu, and
swine flu combined in human history—
we find it difficult to explain the
reasoning behind resource allocation
to our non-physician collaborators
or to a patient who succumbs to a
ketoacidotic coma because his cheap
insulin was not available.
Considering the level of care used
and accepted for patients with Ebola
in Africa (no intensive care units
needed, no very costly procedures,
beds can be set up in tents, no
expensive drugs), the low prices for
protective clothing, the assumed
full cooperation of African states,
and almost negligible local salaries
we do not understand the reasoning
ourselves. The World Bank alone
wants to spend more on Ebola than
the entire health budget of Malawi—a
budget that covers the cost of all
the health challenges of 15 million
Is the fear of the spread of Ebola
really enough of an ethical reason
to withhold efforts and money from
people suffering and dying not in
projection, but in reality, from other
diseases in Africa? We dare to doubt.
We declare no competing interests.
*Gregor Pollach, Christian Pietruck
[email protected]
Department of Anaesthesia and Intensive Care,
University of Malawi, Blantyre, Malawi
Lewnard JA, Ndeffo Mbah ML,
Alfaro-Murillo JA, et al. Dynamics and control
of Ebola virus transmission in Montserrado,
Liberia: a mathematical modelling analysis.
Lancet Infect Dis 2014; 14: 1189–95.
Queen Elizabeth Central Hospital. Annual
reviews 2011–2014. Blantyre: Queen Elizabeth
Central Hospital.
Malawi Nyasa Times. Malawi budget
statement 2013/2014.
(accessed Aug 22, 2014).
Ebola control: rapid
diagnostic testing
In their analysis of Ebola transmission,1
Joseph Lewnard and colleagues
emphasise the need for an
“acceleration of case ascertainment”,
which so far has been a major
challenge. Most patients with Ebola
in west Africa remain undiagnosed
in their communities, 2 and the
average delay from symptom onset
to diagnosis is about 5 days.3 For a
PCR-based diagnosis, patients need to
attend a laboratory, or visit a transit
centre where blood can be drawn
and transported to a laboratory. This
process introduces delays during which
Published Online
November 19, 2014
Time to diagnosis
5 days
3 days
2 days
1 day
Attack rate (%)
Harvard University Center for AIDS Research (P30
AI060354), and the Massachusetts General Hospital
Executive Committee on Research. The content is
solely my responsibility and does not represent the
official views of the National Institutes of Health or
other funding agencies. I declare no competing
Effectiveness of isolation strategy (%)
Figure: Proportion of the population eventually infected with Ebola according to
effectiveness of isolation strategy, by time to diagnosis
See Online for appendix
transmission can occur. Accurate,
point-of-care, rapid tests could
minimise this window of transmission.
If Ebola is diagnosed at home when
symptoms first appear, household
members could use protective kits
until the infected person is securely
transported to a treatment centre.
To investigate the effect of reducing
the time between symptom onset and
diagnosis with rapid testing, we used
a standardised epidemic simulator4
for a population of 10 million and
basic reproduction rate of 2·0. The
proportion of the population eventually
infected (attack rate) is shown as a
function of the proportion of patients
infected with Ebola who are diagnosed
and then isolated (effectiveness of
the isolation strategy; figure). If 60%
of patients infected with Ebola are
diagnosed rapidly and isolated, the
attack rate drops from 80% to nearly
0% because the delay is reduced from
5 days to 1 day.
Rapid point-of-care testing
provides other advantages. Because
Ebola causes common, non-specific
symptoms, large numbers of people
need to be tested in areas where most
cases are unreported, such as Sierra
Leone and Liberia. Establishing PCR
capacity to meet this need remains
a challenge. At the same time,
transporting blood samples collected
at remote sites is logistically difficult
and introduces contamination risks.
Many patients are also reluctant to
wait in so-called holding areas with
others who might have Ebola for
the several hours to days it takes
for results, discouraging people
from coming forward. Rapid testing
could also prove useful for screening
travellers at border crossings.
Rapid diagnostic tests (RDTs) similar
to those used for influenza and malaria
are under development and might
offer a solution. In preliminary results
from the Viral Hemorrhagic Fever
Consortium, Ebola RDTs achieve
greater than 90% sensitivity and
nearly 100% specificity, similar to
PCR. RDTs need only small quantities
of blood obtainable by fingerstick,
and could be applied safely by trained
paramedical cadres.
The large-scale introduction of rapid
testing could reduce time to diagnosis
and have a major effect on Ebola
RFG has received grants from the National Institutes
of Health, and is affiliated with the Viral
Hemorrhagic Fever Consortium, which has
developed diagnostic tests for Ebola, Lassa fever,
and other viral diseases. All other authors declare no
competing interests.
*Ranu S Dhillon,
Devabhaktuni Srikrishna,
Robert F Garry, Gerardo Chowell
[email protected]
Brigham and Women’s Hospital, Boston, MA 02115,
USA (RSD); Earth Institute, Columbia University,
New York, NY, USA (RSD); Patient Knowhow, San
Mateo, CA, USA (DS); Viral Hemorrhagic Fever
Consortium and Tulane University, New Orleans, LA,
USA (RFG); and Arizona State University, Tempe, AZ,
Lewnard JA, Ndeffo Mbah ML,
Alfaro-Murillo JA, et al. Dynamics and control
of Ebola virus transmission in Montserrado,
Liberia: a mathematical modeling analysis.
Lancet Infect Dis 2014; published online
Oct 24. http://dx.doi.org/10.1016/S14733099(14)70995-8.
Meltzer MI, Atkins CY, Santibanez S, et al.
Estimating the future number of cases in the
Ebola epidemic—Liberia and Sierra Leone,
2014–2015. MMWR Surveill Summ 2014;
63: 1–14.
WHO 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.
Chowell G, Nishiura H. Transmission dynamics
and control of Ebola virus disease (EVD):
a review. BMC Med 2014; 12: 196.
Modelling the effect of
early detection of Ebola
Almost 20 000 cases of Ebola virus
disease have been reported in west
Africa.1 Estimates of the reproductive
ratio of the outbreak2–5 suggest that
about half of infectious contacts
need to be prevented to control the
epidemic. The international response
in the affected regions has focused
mainly on establishing infrastructure
that enhances local capabilities
to improve contact surveillance,
people, educate people on mode of
transmission and risk, and provision
of supportive treament.6
PCR can detect Ebola virus in both
human beings and non-human
primates in the pre-symptomatic
stage,7,8 and consequently, the effect
of timely diagnosis of pre-symptomatic individuals should be
assessed. We evaluated the potential
effect of early diagnosis of presymptomatic individuals in west
Africa. We used a simple mathematical
model calibrated to the transmission
dynamics of Ebola virus in west Africa.
The baseline model includes the
effects of contact tracing and effective
isolation of infectious individuals in
health-care settings (appendix).
In the absence of vaccines or effective
antiviral drugs for Ebola, controlling
the outbreak relies on identification
of infectious people quickly enough to
break chains of transmission. Several
organisations have developed pointof-care Ebola diagnostic tests, which
have been proposed for door-to-door
screening campaigns and in contact
tracing in west Africa.9 Nevertheless,
tracing contacts has been hampered
by the difficulty of keeping track of the
many ongoing chains of infection.
We found that the effect of early
diagnosis of pre-symptomatic infections is strongly dependent on the
effectiveness of isolation of infectious
individuals in health-care settings.
For instance, with an isolation
effectiveness of 50% and with an
average time of 3 days from the onset
of symptoms to isolation, the attack
rate (total number of Ebola cases per
population size) remains essentially
unchanged as the rate of detection
of pre-symptomatic cases increases
(figure). By contrast, early detection of
pre-symptomatic individuals can have
a striking effect on the transmission
dynamics of Ebola if the effectiveness
of isolating infectious people is at least
60%. Even at this level of isolation,
at least 50% of pre-symptomatic
patients would need to be detected
in the community, which is difficult
to achieve with limited resources.
www.thelancet.com/infection Vol 15 February 2015