Correspondence
Ebola: the real lessons
This online publication
has been corrected.
The corrected version rst
appeared at thelancet.com/
infection on May 19, 2015
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guide programming at the national,
from HIV scale-up
In his Correspondence,1 Paul Drain
suggests that lessons from the HIV
epidemic can be applied to the Ebola
outbreak in parts of west Africa,
stressing the importance of point-of-
care testing, interventions to reduce
stigma, widespread screening of
individuals exposed to Ebola virus,
and infection prevention and control.
Although we agree that these are
crucial components of an effective
Ebola response, we believe that some
of the most important lessons learned
from the scale-up of HIV services in
low-resource settings lie elsewhere.
One lesson is the importance of
engaging aected communities. People
living with HIV are central to the HIV
response, linking their communities
to prevention, care and treatment
services, fighting stigma, supporting
service delivery, and catalysing the
development of innovative and eective
programmes. To enable individuals
and communities affected by Ebola
virus diseaseincluding survivorsto
meaningfully participate in programme
design and delivery will be essential to
successful and sustained interventions.
A second key lesson is the need for
innovative approaches to the dire
shortage of health workers in low-
resource settings. Supportive and
enabling systems, including effective
health workforce management,
policies and licensure adjustments to
permit task-shifting, and attention
to health worker satisfaction, career
development, and remuneration will be
as important to the long-term control
of Ebola outbreaks as they are for HIV.
A third lesson is the importance
of investing in data for decision
making. Despite the challenges of data
collection and analysis in low-resource
settings where documentation is
often scarce and paper-based, the
experience of HIV scale-up shows the
power of standardised indicators,
harmonised ledgers, forms, and ow
sheets, and the eect of use of data to
another zoonotic transmission event
subnational, and health facility levels.
Finally, the HIV response underlines
a lesson about the effect of vertical
programming on health systems.
Although vertical programmes
have some advantagesincluding
speed of implementationthey
might undermine existing health
programmes and their governance
if not appropriately designed and
implemented. The Ebola response has
rightly prioritised getting to zero new
cases and disease-specic interventions
supported by the international
community. But the reservoir of Ebola
virus has not been eradicated, and
mitigation of the effect of the next
outbreak will need robust health
systems. Strengthening of health
systems will also be needed to address
other health threats faced by west
African populations. Careful attention
to the eects of vertical programming,
and efforts to integrate the Ebola
response into national health systems
are a high priority.
We declare no competing interests.
bodies (eg, ZMapp). Though currently
*Miriam Rabkin, Wafaa M El-Sadr
mr84@columbia.edu
Columbia University Mailman School of Public
Health, New York, NY 10032, USA
1 Drain PK. Ebola: lessons learned from HIV and
tuberculosis epidemics. Lancet Inf Dis 2015;
15: 14647.
Long-term vaccine
strategies for Ebola
We agree with the Claire Tully and
colleagues1 excellent summary of
therapeutic and preventive strategies
for Ebola. For long-term strategies,
multipathogen (multivalent) vaccines
or therapeutic vaccines should be
considered. With the implementation
of vaccines and public health
measures, this outbreak will probably
be contained, but the social and
economic burden for west Africa will
persist long after this epidemic. A
substantial risk of Ebola virus disease
becoming endemic or re-emerging for
exists. Implementation of a routine
Ebola vaccine into existing vaccination
schedules would address these issues.
To help with this undertaking, we
suggest substituting a routinely
used vaccine with a multipathogen
(multivalent) filovirus vaccine and
use of already established structures
for distribution. Poxviruses, such as
modified vaccinia Ankara, exhibit
suitable characteristics for such a
vaccine. A combination of several
filovirus strains together with other
endemic pathogens such as rabies virus
or yellow fever virus in one vaccination
could crucially allow marginal health
services to deliver sucient means of
protection against local pathogens.
In survivors of Ebola virus disease,
recovery is associated with early,
vigorous, and longlasting antibody
response, compared with the poor
anti body responses evident in
lethal infections. This finding has
led to experimental therapies with
convalescent serum or cocktails of
dierent neutralising monoclonal anti-
unproven, these treatments are likely
to be ecacious. However, drawbacks
such as limited supply, adventitious
biohazards, and the need for repeated
administration should be considered. In
future, delivery of human or humanised
neutralising monoclonal antibodies
in vivo by lentiviral gene therapy, in
combination with a vaccine to elicit
cellular immune responses, might be
possible. Data from studies25 identied
that antibody responses alone are
insufficient to protect against Ebola
virus infection and that the degree of
protection is associated with antibody
titre and antigen-specific T-cell
responses.6 Such direct immunotherapy
might be useable for prevention and a
long-term scalable solution to this
deadly viral epidemic.
TJB is coinventor of a prime-boost patent employing
recombinant modied vaccinia Ankara. KBL and
LF declare no competing interests.
*Katharina B Lauer, Layla Faqih,
Thomas J Blanchard
www.thelancet.com/infection Vol 15 May 2015

katharina.lauer@postgrad.manchester.
ac.uk
University of Manchester, Manchester M13 9PT, UK
(KBL, LF, TJB); and North Manchester General
Hospital, Manchester, UK (TJB)
1 Tully CM, Lambe T, Gilbert SC, Hill AVS.
Emergency Ebola response: a new approach to
the rapid design and development of vaccines
against emerging diseases. Lancet Infect Dis
2015; 15: 3599.
2 Sullivan N, Yang Z, Nabel GJ. Ebola virus
pathogenesis: implications for vaccines and
therapies. J Virol 2003; 77: 973337.
3 Wong G, Kobinger GP, Qiu X. Characterization of
host immune responses in Ebola virus infections.
Expert Rev Clin Immunol 2014; 10: 78190.
4 Baize S, Leroy EM, Georges-Courbot MC, et al.
Defective humoral responses and extensive
intravascular apoptosis are associated with
fatal outcome in Ebola virus-infected patients.
Nat Med 1999; 5: 42326.
5 Parren PW, Geisbert TW, Maruyama T,
Jahrling PB, Burton DR. Pre- and postexposure
prophylaxis of Ebola virus infection in an animal
model by passive transfer of a neutralizing
human antibody. J Virol 2002; 76: 640812.
6 Shedlock DJ, Aviles J, Talbott KT, et al. Induction
of broad cytotoxic T cells by protective DNA
vaccination against Marburg and Ebola.
Mol Ther 2013; 21: 143244.
Ebola superspreading
Ousmane Faye and colleagues recently 1
described the chains of transmission
for 152 individuals infected with
Ebola virus diseases in Guinea. The
resulting transmission trees provide
unique insights into the individual
variation in the number of secondary
cases generated by an infected index
case. A better understanding of this
variation provides crucial information
about epidemic spread, the expected
number of superspreading events, and
the eects of control measures.2
The number of secondary cases
in the transmission trees is highly
skewed, with 72% of individuals not
generating further cases (gure). Fitting
a negative binomial distribution to the
data (appendix) provides maximum-
likelihood estimates of the mean (095,
95% CI 057134) and the dispersion
parameter (k=018, 95% CI 010026).
The mean corresponds to the basic
reproduction number (R0) of the overall
population. The estimated value of k,
which is substantially smaller than 1,
suggests that the distribution of the
www.thelancet.com/infection Vol 15 May 2015
Correspondence
individual reproduction number is A
highly overdispersed.2 The value for
Ebola virus disease is similar to that
estimated for severe acute respiratory
06
syndrome (k=016). 2 This finding
suggests that superspreading events
for Ebola virus disease are an expected
feature of the individual variation in
Frequency
infectiousness.3 04
I simulated stochastic trajectories of
Ebola virus disease outbreaks starting
from one infected index case (gure).
To this end, I drew the number of 02
secondary cases for each case from the
fitted negative binomial distribution
(appendix). The time from disease
onset in one case to disease onset in the 0
next case was drawn from the reported 0 5 10 15 20
Number of secondary cases
gamma-distributed serial interval with
a mean duration of 153 days.4 Although B
100
most outbreaks rapidly become extinct,
some epidemic trajectories can reach
to more than 100 infected cases. This
80
finding is particularly remarkable
Cumulative number of EVD cases
because R0 is less than 1, and shows the
potential for explosive outbreaks of
60
Ebola virus disease.
R0 during the early phase of the Ebola
virus disease epidemic in Guinea has
40
been estimated to be roughly 15.5
The transmission trees from Faye
and colleagues were generated from
20
data obtained between February and
August, 2014, when the reproduction
number was uctuating around unity.1,4
0
That scenario is similar to the present 0 20 40 60 80 100
situation in parts of west Africa where Time (days)
the incidence is declining but new
Figure: Distribution of the number of secondary cases and outbreak trajectories
outbreaks still occur. The observed for Ebola virus disease
variation in individual infectiousness for (A) The histogram represents the observed frequencies in the number of secondary cases
Ebola virus disease means that although as given by the transmission trees in Faye and colleagues study.1 The line and dots
correspond to the tted negative binomial distribution. (B) Each line represents one of
the probability of extinction is high, new
200 stochastic realisations of epidemic trajectories. Dots show when the outbreak
index cases also have the potential for becomes extinct. A detailed analysis is reported in the appendix. EVD=Ebola virus disease.
explosive regrowth of the epidemic.
I received funding through an Ambizione grant 2 Lloyd-Smith JO, Schreiber SJ, Kopp ME,
Getz WM. Superspreading and the eect of
from the Swiss National Science Foundation
individual variation on disease emergence.
(project 136737). I declare no competing interests.
Nature 2005; 438: 35559.
See Online for appendix
Christian L Althaus 3 Volz EM, Pond SL. Phylodynamic analysis of
Ebola virus in the 2014 Sierra Leone epidemic.
christian.althaus@alumni.ethz.ch PLoS Curr 2014; published online Oct 24. This online publication
Institute of Social and Preventive Medicine, DOI:10.1371/currents.outbreaks.6f7025f1271 has been corrected.
821d4c815385b08f5f80e.
University of Bern, 3012 Bern, Switzerland The corrected version rst
4 WHO Ebola Response Team. Ebola virus appeared at thelancet.com/
1 Faye O, Bolle P-Y, Heleze E, et al. Chains of disease in West Africathe rst 9 months of infection on May 19, 2015
transmission and control of Ebola virus disease the epidemic and forward projections.
in Conakry, Guinea, in 2014: an observational N Engl J Med 2014; 317: 148195.
study. Lancet Infect Dis 2015; 15: 32026.
507