factors play a much more important role in
cholera dynamics in Africa than climatic and
environmental factors (6, 7). Our data do not
suggest that aquatic environmental reservoirs
are the primary source of epidemic cholera in
Africa, as has been suggested (30). Instead, these
results highlight the role that humans play in
the long-term spread and maintenance of the
pathogen, whether by direct (human-to-human)
or indirect (pollution of the environment with feces
from cholera patients) transmission. Undoubtedly,
the factors influencing the epidemiology and
transmission of cholera are complex, but these
data provide a detailed genetic context against
which we can gauge the impact of interventions
on future patterns of disease in this region.
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This study was supported by the Institut Pasteur and the Institut
Pasteur International Network, the Institut de Veille Sanitaire, the
French government’s Investissement d’Avenir program,
Laboratoire d’Excellence “Integrative Biology of Emerging
Infectious Diseases” (grant no. ANR-10-LABX-62-IBEID), the
Fondation Le Roch-Les Mousquetaires, the Wellcome Trust through
grant 098051 to the Sanger Institute, and the Indian Council of
Medical Research, New Delhi, India. The findings and conclusions in
this report are those of the authors and do not necessarily
represent the official position of the Centers for Disease Control
and Prevention. We thank C. Bréchot and H.-F. Thiéfaine for their
support; O. Vandenberg, Y. Germani, and M.-C. Fonkoua for
providing isolates; D. Nedelec and E. E. Hansen for helpful
discussions; S. Dupke and A. Smith for technical assistance; L. Ma,
M. Santovenia, J. Winkjer, M. Aslett, A. J. Page, J. Keane, and
the sequencing teams at the Institut Pasteur, the Wellcome Trust
Sanger Institute, and the Centers for Disease Control and
Prevention for sequencing the samples. F.J.L. and M.-L.Q. are
members of the WHO Global Task Force on Cholera Control.
F.J.L. is a past member of the WHO Strategic Advisory Group of
Experts working group for cholera vaccines. J.P. is a member
of the Institut Pasteur Scientific Council. J.P. has received
consulting fees from Specific Technologies, Mountain View,
California. Short-read sequences have been deposited in the
European Nucleotide Archive (ENA) ( www.ebi.ac.uk/ena) under
study accession numbers PRJEB8764, PRJEB2215, and
PRJEB19893. The whole-genome alignment for the 1070 genomes
and other files have been deposited in FigShare: https://figshare.
com/s/d6c1c6f02eac0c9c871e. Phylogeny and metadata can be
viewed interactively at https://microreact.org/project/
Materials and Methods
Figs. S1 to S12
Tables S1 to S9
26 June 2017; accepted 10 October 2017
Integrated view of Vibrio cholerae in
Daryl Domman,1 Marie-Laure Quilici,2 Matthew J. Dorman,1 Elisabeth Njamkepo,2
Ankur Mutreja,1,3 Alison E. Mather,1,4 Gabriella Delgado,5 Rosario Morales-Espinosa,5
Patrick A. D. Grimont,6 Marcial Leonardo Lizárraga-Partida,7 Christiane Bouchier,8
David M. Aanensen,9 Pablo Kuri-Morales,10 Cheryl L. Tarr,11 Gordon Dougan,1,3
Julian Parkhill,1 Josefina Campos,12 Alejandro Cravioto,13
François-Xavier Weill,1,2† Nicholas R. Thomson1,14*†
Latin America has experienced two of the largest cholera epidemics in modern history; one in
1991 and the other in 2010. However, confusion still surrounds the relationships between
globally circulating pandemic Vibrio cholerae clones and local bacterial populations. We used
whole-genome sequencing to characterize cholera across the Americas over a 40-year time
span. We found that both epidemics were the result of intercontinental introductions of
seventh pandemic El Tor V. cholerae and that at least seven lineages local to the Americas are
associated with disease that differs epidemiologically from epidemic cholera. Our results
consolidate historical accounts of pandemic cholera with data to show the importance of local
lineages, presenting an integrated view of cholera that is important to the design of future
disease control strategies.
Cholera is an acute intestinal infection that leads to a rapid and severe dehydrating diarrhea, and is caused by serogroup O1 and O139 Vibrio cholerae. The global disease burden of cholera is estimated to bebetween
1.3 and 4 million cases a year with 21,000 to
143,000 deaths (1). The current seventh pandemic
(7P) of cholera began in 1961 and is attributed to
a V. cholerae O1 biotype El Tor lineage, which is
different from the Classical biotype V. cholerae O1
thought to be responsible for previous pandemics.
Aside from being a prominent human pathogen,
exploratory analyses have demonstrated since
the 1970s that V. cholerae is an integral member
of many coastal, estuarine, and brackish water
ecosystems, as are other Vibrio species, in which
it is often associated with copepods and zoo-
plankton (2). Accordingly, a view of V. cholerae
epidemiology emerged in the following decades,
which posits that locally evolving, but globally
distributed, V. cholerae populations are respon-
sible for cholera outbreaks, which occur when
climatic or environmental stimuli provide favor-
able bacterial growth conditions in these environs
(3, 4). This perception has had profound effects
on all levels of global public health; cholera is
now considered to be ineradicable because its
etiological agent is ubiquitous in aquatic eco-
systems (3, 5).
Despite advances in our understanding of the
global epidemiology of cholera, we still face un-answered fundamental questions about the relationships between local and global V. cholerae
populations. Latin America presents a notable
opportunity to investigate these relationships.
Although this region has local foci of endemic
V. cholerae, such as on the Gulf Coast of the
United States and Mexico (6), pandemic cholera was absent from Latin America for nearly
100 years. In January 1991, a cholera outbreak
occurred along the coast of Peru and spread
rapidly to nearly every country in Latin America,
causing 1.2 million disease cases and 12,000 deaths
by 1997 (7 ). More recently, pandemic cholera was
introduced into Haiti (8), where the resultant
epidemic has affected more than 797,000 people
and caused over 9400 deaths (9). In response to
these two large-scale epidemics, regional and