pubs.acs.

org/journal/aidcbc Review

Update on Environmental and Host Factors Impacting the Risk of

Vibrio cholerae Infection
Denise Chac, Chelsea N. Dunmire, Jasneet Singh, and Ana A. Weil*

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ABSTRACT: Vibrio cholerae is the causative agent of cholera, a diarrheal disease that kills
tens of thousands of people each year. Cholera is transmitted primarily by the ingestion of
Downloaded via UNIV OF NEW MEXICO on May 16, 2021 at 12:38:27 (UTC).

drinking water contaminated with fecal matter, and a safe water supply remains out of reach
in many areas of the world. In this Review, we discuss host and environmental factors that
impact the susceptibility to V. cholerae infection and the severity of disease.

KEYWORDS: Vibrio cholerae, cholera, microbiota, immune response, diarrhea

Vibrio cholerae infection can cause severe diarrhea and is most
commonly transmitted by fecal contamination of drinking
water. The World Health Organization aims to diminish the
public health threat posed by cholera in a campaign to achieve
a reduction of cholera deaths by 90% by 2030.1 The estimated
burden of cholera ranges from 1.3 to 4 million cases with a
range of 21,000 to 143,000 deaths per year, and most disease
occurs in 51 cholera-endemic countries.2 In nonendemic
countries, cholera occurs in outbreaks with an annual case and
death estimate of 87,000 and 2500, respectively.2 Outbreaks
can occur due to human movement from endemic to
nonendemic areas and in the time periods after natural
disasters where floods and a displacement of large populations
occur.3,4
Clinical Manifestations and Treatment. Characterized
by acute, severe watery diarrhea, V. cholerae infections can be
deadly if not treated promptly. Vomiting, if it occurs, is
typically an early symptom, and severe dehydration is the most
frequent cause of death in fatal cases.5 Fever is typically absent,
and the incubation period for V. cholerae infections can range
from a few hours to 4 days.6 The cornerstone of cholera
treatment is an oral rehydration solution or salts (ORS)
containing sugar, salt, and clean water. For patients who are
able to drink on their own, timely treatment with ORS can
reduce fatalities to far less than 1%. Prior to the advent of ORS
and other rehydration therapies, case-fatality rates of up to 50%
were observed.7 For dehydrated persons who cannot drink due
to a decreased level of consciousness, young age, vomiting, or
other reasons, intravenous fluids are required for treatment.
Additional treatments that reduce the duration and severity of
symptoms include antibiotics and, in children, zinc supple-
mentation.8−10
Microbiology. V. cholerae is a Gram-negative, facultative
anaerobe in the Proteobacteria phylum. Although there are
over 200 serogroups of V. cholerae, the O1 serogroup is
responsible for nearly all pandemic cholera. In 2021, V. cholerae
infections around the world are caused by the serogroup O1 El
Tor biotype. This biotype appears to have emerged in 1961 in
Indonesia;11 the strain then spread globally, replacing the
previous classical biotype and causing the current seventh
pandemic of cholera.12,13 Epidemics that have occurred in
recent decades are clonal in nature and can be traced to South
Asian origins.13 The O1 El Tor biotype can be further
classified into two main serotypes, Ogawa and Inaba, that differ
in the methylation of a terminal perosamine in the O-side
chain of lipopolysaccharide (LPS).14−16 Either the Ogawa or
Inaba serotype tends to dominate at a specific time in a
particular geographic location, while the rarer Hikojima
serotype that can produce both the unmethylated (Inaba)
and methylated (Ogawa) LPS is rarely observed.17,18 In recent
Special Issue: Gut Pathogens
Received: December 30, 2020
Published: April 12, 2021

© 2021 American Chemical Society https://doi.org/10.1021/acsinfecdis.0c00914

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ACS Infectious Diseases pubs.acs.org/journal/aidcbc Review

Figure 1. V. cholerae life cycle and pathogenesis. V. cholerae is a waterborne disease that causes cholera and is a human-restricted pathogen. (1)
V. cholerae is introduced to the human host through contaminated water. (2) In the stomach, V. cholerae encounters a low pH environment. (3) To
induce disease, V. cholerae colonizes the small intestine. (4) V. cholerae uses a single flagellum to propel through the mucus and reaches the
epithelial surface. V. cholerae responds to host signals including bile, mucins, pH, and oxygen availability to induce virulence factors such as toxin
coregulated pilus (TCP) and cholera toxin (CT). (5) TCP facilitates the colonization of the epithelial surface, and CT is produced, binding GM1
on the host cells. (6) CT is then endocytosed and induces cyclic AMP (cAMP). High cAMP levels cause the efflux of electrolytes and water,
resulting in the characteristic watery diarrhea of cholera. (7) Microcolonies form, and V. cholerae produces extracellular matrix components
including Vibrio polysaccharides, biofilm proteins, and extracellular DNA. At high cell density, V. cholerae represses virulence genes through quorum
sensing. (8) At this high density, V. cholerae detaches from the epithelial surface and migrates to the lumen. Genes required for transitioning into
the aquatic environment are upregulated. (9) V. cholerae is excreted from the host in diarrheal stool and in vomitus. (10) V. cholerae returns to the
environment, where contamination of drinking water may infect another host.

years, hybrid strains have circulated widely; these are biotype
El Tor strains with classical cholera toxin (CT) genes.19
V. cholerae strains causing human disease are characterized by
the presence of virulence genes including cholera toxin and
toxin-coregulated pilus (TCP) in comparison to environmental
strains, which typically lack these genes.20
Pathogenesis. The successful infection with V. cholerae
typically requires a large inoculum (108−1011 organisms) due
to the significant killing of the organism in the low pH
environment of the stomach21,22 (Figure 1). Surviving
V. cholerae then enter the small intestine and sense environ-
mental cues including temperature, bile, and low oxygen,
triggering the activation of the ToxR regulon on the Vibrio
pathogenicity island 1, which encodes for transcriptional
activators ToxR, ToxT, and TcpP.23−30 Once in the small
intestine, V. cholerae uses a single polar flagellum for motility
and mucin-degrading proteins to penetrate the mucus
overlying the small intestinal epithelium.31−33 In this process,
ToxT activates the transcription of the CT and TCP
genes.34,35 TCP facilitates the adherence of V. cholerae to the
epithelial surface, and CT is expressed, which results in
diarrhea, the hallmark of clinical cholera.36,37 CT consists of
two subunits, A and B, and the five B subunits form a pentamer
around the A subunit. The CT B subunit (CTB) binds the
ganglioside receptor GM1 on intestinal epithelial cells, and the
toxigenic A subunit triggers cAMP production that induces the
expulsion of water and other ions (e.g., chloride, sodium, and
other electrolytes) into the intestinal lumen.21,38 The resulting
diarrhea contains large quantities of V. cholerae (up to 1012 per
liter). Even without diarrhea, asymptomatically infected
persons can shed 103 organisms per gram of stool.39
1011
Immune Responses to V. cholerae Infection. Natural
V. cholerae infection results in protection from reinfection for
up to 3 years in North American volunteers,40 and surveillance
studies in cholera endemic areas demonstrate that even longer
periods of protection may occur.41−43 The most commonly
used measure of immune responses to V. cholerae infection is
the vibriocidal titer that primarily targets the O-specific antigen
of the V. cholerae lipopolysaccharide (OSP).44,45 An elevated
vibriocidal titer is correlated with protection from V. cholerae
infection in adults and children, but there is no vibriocidal titer
that provides complete immunity.46−49 Household contacts of
patients with cholera are known to be at high risk of infection,
and in this group, serum IgA specific for CT, V. cholerae LPS,
and TcpA has been associated with a short-term decreased risk
of infection.46 However, V. cholerae-specific memory B cell
(MBC) responses to OSP measured in household contacts has
correlated with a 44−68% decreased risk of infection.50,51 The
mechanism of this protection was recently studied by Charles
et al. who demonstrated that OSP-specific antibodies of all
isotypes from cholera patients in Bangladesh limit V. cholerae
motility in vitro, reduce V. cholerae colonization in vivo, and
prolong the survival of neonatal mice.52 The OSP-specific
antibody mediated inhibition of V. cholerae motility appears to
be at least partially responsible for the long-term protection
from cholera.52
T cells are another cell type that may participate in initiating
and sustaining long-term immunity after cholera, although
OSP is a T-cell independent antigen. After V. cholerae
infection, the early induction of V. cholerae-specific T follicular
helper cells (Tfh) has been correlated with later memory B cell
responses to the same V. cholerae antigens. In vitro, Tfh cells
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isolated from cholera patients induced class-switching in a B
cell−Tfh coculture.53 Overall, it seems that T cell-mediated
V. cholerae responses may contribute to V. cholerae protective
immunity, potentially through T cell help or other mechanisms
that are not yet understood.53
■ HOST RISK FACTORS
Age, nutritional, and genetic factors are known to impact
susceptibility to V. cholerae infection; a summary of character-
istics that may contribute to susceptibility is shown in Figure 2.
Studies in this area have sought to identify modifiable factors
such as micronutrient levels and potentially, in the future, the
gut microbiota.
Figure 2. Factors that impact the susceptibility to V. cholerae. *Blood
group O is associated with an increased severity of disease.
Blood Group and Other Genes. A relationship between
the severity of cholera and blood type was first observed in
1977.54 Individuals with blood type O are not more susceptible
to infection but more likely to develop severe disease if
infected, a finding most pronounced with biotype El Tor
V. cholerae infection.46,55−58 As a possible consequence of this,
geographic regions known to be cholera endemic for centuries
have a lower prevalence of blood O group individuals,
presumably due to a higher likelihood of these individuals
dying of cholera prior to reproductive age.56 To understand
the mechanism of the interaction between blood type and the
severity of disease, Kuhlmann et al. used a human intestinal
organoid model to study the differential binding of CT on
epithelial cells.59 The study demonstrated greater cAMP
activity when CT was applied to blood type O cells, which
could explain why patients with blood type O have more
severe diarrheal disease. Another group furthered this work by
studying the crystal structure of CT and blood group glycans
and found that CT, and particularly El Tor CT, could bind
cells with blood type O glycans with greater affinity than other
blood types, thereby proposing a mechanism for why
individuals with blood group O have greater mortality
compared to non-blood group O individuals.60 It is not
known how the hybrid El Tor strains with a classical toxin
sequence will impact the relationship between blood group and
the severity of disease.
Other studies have explored the results of selective pressure
in populations where cholera is prevalent and has been a
pubs.acs.org/journal/aidcbc Review
potentially fatal disease for centuries. A genetic factor found to
impact the susceptibility to V. cholerae infection is an innate
immunity protein called the long palate, lung, and nasal
epithelium clone 1 (LPLUNC1), which is enriched in
duodenal biopsies during acute cholera.61 In a candidate
gene association study, a single-nucleotide variant within the
promoter region of LPLUNC1 was significantly associated
with severe cholera.62 To explore the mechanism of this
finding, Shin et al. used HEK293 cells to show that LPLUNC1
blocks proinflammatory responses to V. cholerae LPS. The
addition of LPLUNC1 to in vitro cultures with V. cholerae LPS
decreased nuclear factor kappa B (NF-kB) activation and
interleukin-8 production in a dose-dependent manner.63
Additionally, using a genome-wide approach to identify
genes impacted by cholera over generations, Karlsson et al.
identified 305 genomic regions under natural selection in
Bengali persons living in a cholera-endemic area, when
compared to East Asian, North/West European, and Yoruba
populations.64 Enriched genes included the NF-kB activating
kinase protein NEMO and inflammasome-activating genes
including PYCARD. The identification of genes in the innate
immunity that have been shaped by cholera over centuries has
generated a new interest in the role of innate immune
responses in protective immunity to V. cholerae infection.
Age. Individuals younger than five are known to have an
elevated risk of infection based on studies conducted in
Bangladesh, India, Indonesia, and Mozambique.65,66 One study
of household contacts in Bangladesh demonstrated an inverse
relationship between age and the likelihood of infection.46
Children under the age of 5 years were 2.7 times more likely to
develop an infection and were also more likely to develop a
symptomatic illness. This increased susceptibility is independ-
ent of the lack of pre-existing immunity in children and may be
due to increased susceptibility to bacterial infections in
children and a tendency toward less hygienic behavior in this
age group compared to adults.67,68 In cholera nonendemic
areas (such as Haiti in 2010−2011), older individuals (over 60
years old) were also observed to have an increased risk of
death compared to younger adults and children.69
Nutrition. The susceptibility to V. cholerae may be
impacted by specific micronutrient deficiencies. In the 1970s,
a study of patients aged 2 to 50 in Bangladesh demonstrated
that diarrhea was prolonged in persons with severe
malnutrition.70 A more recent study found that height- and
weight-for-age in children were not correlated with suscepti-
bility to V. cholerae infection, but individuals with retinol
deficiency were at a higher risk of infection and more likely to
have symptomatic disease.46 In additional studies of household
contacts of patients with cholera, the severity of disease and the
duration of bacterial shedding has been associated with
malnutrition.71,72 A more recent study in children hospitalized
with cholera revealed that micronutrient deficiencies were
common.73 In Bangladesh, zinc deficiency has been noted in
both adults and children hospitalized with cholera (30%), and
children age 2−12 years hospitalized with cholera were more
likely to have retinol deficiency (47%) compared to older
adults hospitalized with cholera (16%).73 The mechanisms of
these relationships remain under study.
Gut Microbiome. A multitude of microbes inhabit the
human gastrointestinal tract, providing essential functions
including the maintenance of intestinal integrity and protection
from pathogens.74 To identify gut microbe associated differ-
ences in susceptibility, Midani et al. prospectively analyzed the
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microbiota of household contacts of persons with cholera in
Bangladesh.75 Using a machine learning analysis of the baseline
gut microbiota paired with the clinical outcomes of household
contacts of patients with cholera, the baseline gut microbiota
was found to predict susceptibility to V. cholerae infection as
well as or better than known clinical risk factors including age,
vibriocidal titer, and blood group O status. By comparing the
baseline microbiota of individuals who became infected versus
those who did not, the authors found increased Prevotella,
Blautia, Lactobacillus, and Bacteroides species among individ-
uals who remained uninfected. Conversely, Streptococcus,
Enterobacteriaceae, and some Prevotella species were more
highly correlated with the stool of individuals who became
infected. These results were further confirmed using a
metagenomics analysis of an expanded version of this cohort.76
In this study, the abundance of genes that function in iron
metabolism and regulation in the baseline microbiota samples
correlated with remaining uninfected after the exposure to
V. cholerae. Although further details about this correlation
cannot be derived from this study (i.e., the direction of effect
and the amount of gene transcription), this finding is plausible
since iron is required for bacterial growth. V. cholerae possesses
several known mechanisms of scavenging iron in the intestinal
lumen, both from the host and from other gut bacteria.77 Prior
studies have described that V. cholerae strains with defects in
the Fur−iron complex, a master regulator of iron, are
outcompeted by wild-type V. cholerae strains in infant mouse
studies.78,79 Another mechanism of the gut microbe and
V. cholerae interaction is through bile acid enzymes. Using
germ-free mouse models and bacterial consortia constructed
from human microbiome studies, Hsiao and colleagues found
that Blautia obeum impacts V. cholerae colonization by
degrading taurocholate, a conjugated bile acid.80 Taurocholate
is sensed by V. cholerae to perceive the small intestinal
environment, and this signal induces the genes necessary for
causing disease; in the presence of B. obeum, virulence was
reduced in this model.80,81 The presence of specific commensal
microbes in the human gut has the potential to impact the
susceptibility to V. cholerae infection by modifying the
availability of nutrients and modifying signaling molecules. A
limitation of this work is that nearly all studies of the gut
microbiota and V. cholerae have examined microbes found in
stool, rather than microbes present in the small intestine,
where V. cholerae colonizes the gut and interacts with the
intestinal mucosa. As the connection between the gut
microbiota and V. cholerae infection is increasingly examined,
it will ideally become possible to design preventative
interventions for use within a household or setting where a
cholera outbreak is rapidly spreading. At this time, the nature
and extent of a causal relationship between the gut microbiota
and V. cholerae susceptibility are not yet well understood.
■
ENVIRONMENTAL RISK FACTORS
In 1854, the founder of modern epidemiology, John Snow,
painstakingly traced the spread of cholera in London at a time
when cholera was attributed to miasma or “bad air”.82 Snow’s
investigation revealed a link between cholera and a drinking
water source (i.e., the famous Broad Street pump), ultimately
dismissing the predominant hypothesis of miasma.82 Snow was
successful in identifying that disease risk is linked to sanitation
practices, and this remains the most critical risk factor for
cholera today, more than 150 years later.
pubs.acs.org/journal/aidcbc Review
Socioeconomic Status. Cholera is a “disease of the
world’s poorest people” and “a disease of poverty”.83,84 While
cholera has been eradicated in regions of the world where safe
water is accessible, overcrowding, poverty, and insufficient
sanitation are primary risk factors for infection.85 In Matlab,
Bangladesh, a cholera endemic area, socioeconomic status
(SES) was studied during cholera outbreaks between 1993 and
2007.86 The SES index in households correlated with cholera
cases better than sanitation variables alone, and the reduced
risk of cholera among high SES households was thought to be
attributable to higher education, better hygiene practices,
improved housing, and access to clean drinking water.86
Symptomatic infections requiring hospitalization have also
been linked to education and income. Among children under 5
in Bangladesh, having a mother who read newspapers and a
higher household income reduced the risk of hospitalization
due to cholera.87 Education also corresponded with a
decreased risk of hospitalization due to cholera among adults
in Bangladesh; individuals with over 9 years of education had a
40% lower risk of hospitalization compared to those with no
education.88 A recent systematic review found the risk of
symptomatic cholera was 2.6 times more likely with less than a
secondary level of education.89 Cholera outbreaks are also
more likely to occur in areas of civil unrest, usually due to
reduced access to safe water sources.90 In a recent systematic
literature review of individuals in transition during forcible
displacement, 27 out of 88 studies (31%) reported V. cholerae
as a source of disease, followed by malaria (20%) and measles
(13%).91
Close Contact with Persons Who Have Cholera.
Prospective studies of household contacts of persons
hospitalized with cholera demonstrate that household contacts
are at high risk for infection.5,46,66,92 Among 399 households
and 944 contacts of persons with cholera studied in Dhaka,
Bangladesh, 21% of contacts had confirmed V. cholerae
infection during the three week follow up period with most
infections occurring in the first several days after the household
case infection.5 The increased risk of V. cholerae in this group is
likely due to multiple factors, and shared contaminated
drinking water sources is probably the most important. In
urban Bangladesh, investigators followed household contacts of
persons with recent cholera and observed that contacts who
drank stored household drinking water that contained
V. cholerae had an 8.6-fold increase risk of cholera.93 Another
study in Zambia during a cholera outbreak in 2017 found that
sharing a pit latrine with a patient with cholera increased the
odds of becoming infected by 4-fold.94 Fecal shedding of
V. cholerae in the household may also contribute to an
increased risk of infection. Infected household contacts in
Bangladesh were found to shed for an average of 2 days, and in
households where a person shed V. cholerae for 4 days or more,
a higher likelihood of infection in other household members
was observed.5,66 The exact proportion of V. cholerae that is
transmitted human-to-human, without cycling through an
aquatic reservoir, is not known. Current studies of close
contacts of persons with cholera indicate that the increased risk
of infection in this group is partly attributable to shared water
sources, and fecal−oral transmission through other contact
also contributes to spread.66
Geography. V. cholerae can inhabit a range of environ-
mental conditions, including temperatures ranging from 12 to
30 °C, a salinity of 1.9 to 30 practical salinity units, and a pH of
6.5 to 9.95−98 This flexibility in aquatic niches enables
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V. cholerae to re-enter the human population from the
environment and contributes to the spread of V. cholerae
within communities. People who consume water from rivers
and lakes are at risk of exposure to V. cholerae if sewage
contaminates water sources. This is well documented in
cholera outbreaks linked to drinking water from the Zamani
river in Nigeria and the Cheptui River in East Uganda.99,100
River flow and water availability have also been linked to
cholera spread in Bangladesh.101,102 Outbreaks along coastlines
in which a source of V. cholerae cannot be found are suspected
to be due to the destruction or alteration of the sanitation
infrastructure that allows mixing of sewage with flood
waters.101 Cross-contamination due to adulterated piped
water infrastructure and pipe leakage due to the lack of
maintenance are known contributors to cholera spread, as
described in Uganda, Bangladesh, and India.103−105
V. cholerae can also be transmitted by marine and freshwater
animal vectors. Outbreaks in China have been linked to the
consumption of soft-shell turtles where V. cholerae colonizes
the shell as well as the intestines.106 The consumption of
contaminated bivalve shellfish (i.e., oysters and muscles)
regularly causes solitary cholera cases in areas where endemic
and epidemic cholera is absent.107−110 V. cholerae can also
colonize the surface and intestines of fish, including freshwater
species, with transmission to humans via consumption of raw
meat.111−115 In addition to the spread of cholera by animals
that inhabit aquatic environments, fecal contamination of any
food can also spread V. cholerae. Infections have been linked to
contaminated commercial frozen foods, cooked rice, and even
peanut sauce.116−121
Climate Change. The rise and fall of cholera cases in some
areas have been linked to climate patterns that impact the
world’s oceans. Lipp et al. proposed a hierarchy of environ-
mental conditions that affect the transmission of V. cholerae.122
They describe abiotic features including sunlight, salinity,
temperature, and pH that influence V. cholerae reservoirs. In
the aquatic environment, V. cholerae naturally inhabit the gut
and shell of zooplankton (i.e., copepods), using the chitinous
surface as a nutrient source.123−125 V. cholerae also attach and
survive on phytoplankton, including green algae and
cyanobacteria.122,125,126 The abundance of specific zooplank-
ton species carrying V. cholerae has been correlated with
cholera cases and outbreaks.127,128 Sea water monitoring of
conditions that encourage V. cholerae growth has been
employed to understand how warming oceans may expand
the V. cholerae niche. By investigating the geographic
distribution of V. cholerae in oceans between 1950 and 2014,
Escobar et al. identified sea-surface temperature (SST),
chlorophyll a (a measure of phytoplankton abundance), and
pH as the most important variables to predict the presence of
V. cholerae.129 In this study, V. cholerae suitability (determined
by chlorophyll a, oxygen, temperature, and pH) was mapped to
areas including the Gulf of California, the north and south
Atlantic coast of Africa, the southern coast of Australia, the Bay
of Biscay and North Sea in Europe, and the Yellow Sea off of
the coast of China.129 The model was then applied to climate
data and future climate scenarios demonstrated that by 2100
there would be an expanded ecological niche for V. cholerae
with the potential for spread latitudinally across the globe into
the ocean waters of North America and New Zealand.129
Additionally, a study of formalin-fixed plankton samples from
the North Atlantic Ocean during the 1958−2011 time period
revealed a correlation between SST and nontoxigenic Vibrio
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species in ocean water.130 As SST continues to rise, it is
possible that toxigenic Vibrio cholerae species will also find
new areas that are suitable to inhabit, and this could impact
human populations.
Climate change is also associated with extreme weather
events that are linked to cholera outbreaks. An increased risk of
cholera can be found after heatwaves during high rainfall in
Bangladesh with a further increased risk in households with
less tree coverage.131 Seasons of excess water (wherein
overflowing sewage contaminates drinking water) or a shortage
of water (increased stagnant water and reduced clean water
sources) can both contribute to the contamination of drinking
water.132−136 For example, flooding in Bangladesh was found
to significantly increase the risk of cholera up to 5- to 7-fold.137
Similarly, in sub-Saharan Africa, Rieckmann et al. reported
droughts and floods to be strongly associated with cholera
outbreaks between 1990 and 2010.138 During drought, cholera
incidence rates were 4.3 times higher than in drought- or flood-
free periods.138 The impact of climate change on cholera
incidence is not isolated to low resource areas. Sweden and
Finland experienced extremely warm summers that corre-
sponded with high SST and an increase in human Vibrio
infections in 2014.139 Volcanic activity has even been
associated with increased V. cholerae in freshwater lakes and
with corresponding fluctuations in nearby cholera cases due to
changes in water temperature and other chemical factors.140
Overall, climate change has the potential to expand the
ecological niche of V. cholerae, and an increase in natural
disasters can increase the risk of waterborne diseases.141
Models of global climate change can help predict where
V. cholerae outbreaks could become more common.3
■ CONCLUSION
Cholera continues to cause significant morbidity and mortality
in areas where safe drinking water is not readily available. In
recent decades, an increase in human travel has contributed to
the ongoing seventh cholera pandemic. In the future, climate
change and natural disasters may have an increasing impact on
the spread of disease. In addition to traditionally recognized
host factors that influence the susceptibility to V. cholerae
infection, such as age and prior infection, additional studies
have shed light on possible genetic, nutritional, and even gut
microbiota-related impacts on the likelihood of infection.
Defining risk factors for infection that can be intervened upon
to avoid disease is of high importance, in addition to the use of
cholera vaccines, for the prevention of the ongoing spread of
cholera.
■ AUTHOR INFORMATION
Corresponding Author
Ana A. Weil − Department of Medicine, Division of Allergy
and Infectious Diseases, University of Washington, Seattle,
Washington 98109, United States; orcid.org/0000-0002-
6170-4306; Phone: 206-616-0779; Email: anaweil@
uw.edu
Authors
Denise Chac − Department of Medicine, Division of Allergy
and Infectious Diseases, University of Washington, Seattle,
Washington 98109, United States
Chelsea N. Dunmire − Department of Medicine, Division of
Allergy and Infectious Diseases, University of Washington,
Seattle, Washington 98109, United States
https://doi.org/10.1021/acsinfecdis.0c00914
ACS Infect. Dis. 2021, 7, 1010−1019
ACS Infectious Diseases
Jasneet Singh − Department of Medicine, Division of Allergy
and Infectious Diseases, University of Washington, Seattle,
Washington 98109, United States
Complete contact information is available at:
https://pubs.acs.org/10.1021/acsinfecdis.0c00914
Notes
The authors declare no competing financial interest.
■
ABBREVIATIONS
ORS, oral rehydration solution; LPS, lipopolysaccharide; CT,
cholera toxin; CTB, CT B subunit; TCP, toxin-coregulated
pilus; cAMP, cyclic AMP; SST, sea-surface temperature; SES,
socioeconomic status; LPLUNC1, lung and nasal epithelium
clone 1; NF-κB, nuclear factor kappa B; OSP, O-specific
polysaccharide; Ig, immunoglobulin; MBC, memory B cell;
Tfh, T follicular helper cells; SNP, single-nucleotide poly-
morphic
■
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