Vaccine 38 (2020) A4–A6

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Vaccine
journal homepage: www.elsevier.com/locate/vaccine

Contrasts, contradictions and control of cholera

Sophia Lonappan a, Ria Golecha a, G. Balakrish Nair b,⇑
a
Global Health Strategies, New Delhi, India
b
Microbiome Laboratory, Rajiv Gandhi Centre for Biotechnology, Kerala, India

a r t i c l e i n f o a b s t r a c t

Article history: Cholera has been extremely pervasive during the past four decades and continues to remain a significant
Available online 23 August 2019 public health concern. The disease has plagued humankind in the form of seven pandemics since the last
two centuries. There is considerable scientific evidence based on research on cholera and its etiologic
Keywords: agent Vibrio cholerae, however we are still unable to accurately forecast and pre-empt the occurrence
Oral cholera vaccine of cholera outbreaks. The commentary discusses the contrasts and contradictions of cholera, its control
Cholera and its unpredictable nature. Through a multi-sectoral approach and broad stakeholder collaboration
Outbreak
cholera control is possible with meticulous country-level planning for early detection and response to
Forecast
Global Task Force on Cholera Control
outbreaks. The commentary reiterates that every potential death on account of cholera is preventable
because of the available knowledge and tools to effectively prevent and treat cholera.
Ó 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://
creativecommons.org/licenses/by/4.0/).

Cholera, also known to the world as the ‘disease of poverty’, is a
bacterial gut infection producing watery diarrhea that can quickly
lead to severe dehydration and prove fatal within hours if
untreated. It thrives in regions lacking adequate access to clean
water or sanitation and spreads with an unmatched swiftness.
Even though cholera is presently a preventable and treatable dis-
ease, the occurrence of cholera outbreaks has been difficult to pre-
dict. As per current World Health Organization (WHO) estimates,
1.3–4 million cholera cases are reported globally every year and
an estimated 21,000–143,000 deaths occur [1]. Even though great
progress has been made in mathematical models to understand
cholera transmission, prevention, and control strategies, these
models are yet to make significant impact on public health
decision-making owing to several challenges.
Cholera has been extremely pervasive during the past four dec-
ades and continues to remain a significant public health concern.
Even though there have been fluctuations in the number of
reported cholera cases every year, the overall incidence and the
geographic spread of the disease does not seem to be declining.
Fig. 1 shows the differing incidence of cholera as reported to the
WHO from 1989 to 2016 in four continents. One also suspects
underestimation of cholera in a few cholera-endemic countries.
Some studies have indicated that the annual number of cholera
cases reported to the WHO by the Indian government was several
⇑ Corresponding author at: Microbiome Laboratory, Rajiv Gandhi Centre for
Biotechnology, Poojappura, Thycaud, P.O., Thiruvananthapuram 695014, Kerala,
India.
E-mail address: gbnair_2000@yahoo.com (G. Balakrish Nair).
times lower than the numbers recorded by the national phage typ-
ing facility housed at the National Institute of Cholera and Enteric
Diseases [2]. The numbers of hospital admissions of cholera cases
in hospitals like the Infectious Disease Hospital in Kolkata is also
higher than that reported by the government to the WHO [3].
Cholera has terrified humankind in the form of seven pan-
demics since the last two centuries, impacting most continents
and taking thousands of lives in countries like the Dominican
Republic, Haiti, Afghanistan, Iraq, Mozambique, Kenya, Malawi,
and the Democratic Republic of the Congo (DRC), among others
[4]. This commentary discusses the contrasts and contradictions
of cholera, its control and its unpredictable nature.
There is considerable scientific evidence available based on
research on the disease and its etiologic agent Vibrio cholerae—a
bacterium autochthonous to aquatic environments—but we are
still unable to accurately forecast and pre-empt the occurrence of
cholera outbreaks. Globally, scientists have thoroughly investi-
gated and analyzed the complete genome sequence of more than
1526 strains of Vibrio cholerae, studied the epidemiology of the dis-
ease, the impact of climate change, and the ecology of the patho-
gen. However, science is yet to unravel the reason behind the
rapid spread of cholera to certain geographical areas and of the
pathogen’s behaviour during outbreaks. Why is it that in some
instances, cholera breaks out into a fulminant outbreak, while in
other instances there is sporadic cholera which tends to remain
endemic to that area?
In January 1991, Peru reported hundreds of cases of severe
watery diarrhea identified as cholera. In no time the disease spread
to every other country in Central and South America, except Uru-

https://doi.org/10.1016/j.vaccine.2019.08.022
0264-410X/Ó 2019 The Authors. Published by Elsevier Ltd.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
 S. Lonappan et al. / Vaccine 38 (2020) A4–A6
Fig. 1. Cholera cases reported to the WHO by year and by continent 1989–2016.
guay and the Caribbean islands. Between 1991 and 1997, the Latin
American epidemic resulted in 1.2 million cases and claimed
around 12,000 human lives [5]. While a few experts believe that
the release of ballast water from a ship sailing from Asia or Africa
very close to the South American landmass caused the cholera epi-
demic, others suggest the import of cholera from Angola (in West
Africa), whereas another group of experts believes that the epi-
demic occurred due to climatic factors, particularly due to El Nino
wind patterns causing a spurt in plankton blooms. The precise ori-
gin of the outbreak in Peru still remains a mystery. Using high res-
olution markers (single-nucleotide polymorphisms) the South
American isolates may have traveled via Angola. However, the ori-
gin of the cholera outbreak in Angola (December 1971) is also
unclear as it occurred more than 1000 km away from Camer-
oon—the closest country with a cholera outbreak at that time [6].
Even Haiti’s epidemic, which took a toll of 9000 lives (and pos-
sibly more), cannot be ruled out without contradictions [7]. Some
hypotheses point out that the cholera outbreak was the result of
an earthquake in Haiti in 2010 leading to disruptions in the aquatic
environment, causing the bacteria to enter into the drinking water
supply, while others argue that it is due to untreated sewage from
United Nations peacekeeping camps. From Angola and Peru to
Haiti and recently in Yemen—the worst epidemic till date with
over 5000 cases each day—there have been uncertainties associ-
ated with the manifestation of cholera outbreaks [8].
Even in the 21st century, what is well known to us is that pop-
ulations dwelling in insalubrious conditions with minimal access
to clean drinking water, proper sanitation, and lack of environmen-
tal safety are much more prone to cholera. Yemen is testimony to
this fact as the aforementioned factors created favorable condi-
tions for a large cholera outbreak. The Rohingya refugee crisis in
Bangladesh presented a similar condition—paucity of food, medici-
nes, clean drinking water, and extremely poor hygiene—an ideal
A5
breeding ground for diseases such as cholera, diarrhea, measles,
and diphtheria. In September 2017, an Oral Cholera Vaccine
(OCV) campaign was undertaken which appears to have prevented
a cholera outbreak or epidemic, and this model of pre-emptive
delivery of OCVs from stockpiles has proven to be an effective mea-
sure so far [9].
What has been stopping us from pre-empting cholera in places
where it recurs frequently, especially in known endemic countries
in Asia and Africa? Many argue it is more to do with the stigma
attached to it and the fear of loss of economic opportunities. As a
result, national and regional governments often do not want to
admit that there have been cholera outbreaks in their territory. It
is observed that many countries not only curtail travel to and from
cholera-stricken countries, but also place restrictions on imports
and produce from such countries. In the long term, this could affect
macro-economic parameters such as exports, private consumption,
consumer prices, employment, and even GDP due to pandemic
shock. So, many nations, instead of reporting, seeking help and
controlling cholera, have pushed it under the carpet in many
instances. For example, in 1993, even though thousands of
Venezuelan citizens reported cholera-related symptoms and suf-
fered deaths, in poor rural regions like the Amacuro Delta, the gov-
ernment declared an end to the epidemic [5].
While there is no debate about the fact that providing safe
drinking, water is crucial for preventing cholera, the infrastructure
and maintenance required for setting up mechanisms for this tend
to be resource-intensive and time-consuming to implement. We
need to be aware that developing countries struggle to find the
requisite resources and even substantial investments do not ensure
adequate protection. One in ten people across the globe still do not
have access to clean water, while 2.1 billion people—one in three—
do not have access to proper toilets [10]. Point-of-use solutions for
microbial purification of drinking water at household level feasible
A6 S. Lonappan et al. / Vaccine 38 (2020) A4–A6
for use by communities have been observed to be a practical and
effective solution for providing sustained access to safe drinking
water [11].
Within the scientific community, the cholera control debates
are manifold. Despite the proven safety and efficacy of vaccines,
there are deliberations on including vaccines as part of an inte-
grated strategy. In February 2018, the end of the longest cholera
outbreak in South Sudan depicted that even in the context of
instability, it is viable to halt persistent cholera outbreaks in
endemic settings through the use of OCVs [12]. During the
Yemen and Haiti cholera outbreaks, cholera vaccination plans
were annulled owing to reasons like equity, inadequate supply
of vaccines, and myths relating to their impact once an outbreak
had commenced [13].
Experts from strong Water, Sanitation and Hygiene (WASH)
groups as well as those promoting cholera vaccinations have
acknowledged that the disagreement has harmed the fight against
cholera. Therefore, the WHO has supported both approaches and
recommended an integrated solution. The world today celebrates
the advent of the Global Roadmap to End Cholera, prepared by
the Global Task Force on Cholera Control (GTFCC), highlighting
the need for a multi-sectoral approach and broader stakeholder
collaboration to cholera control with country-level planning for
early detection and response to outbreaks [14]. Every potential
death on account of this disease is preventable because of the
available knowledge and the tools to effectively prevent and treat
cholera. The National Aeronautics and Space Administration
(NASA) for the first-time ever, in August 2018, detected triggers
of cholera outbreak in Yemen through a model observed from
space which forecasted high-risk regions based on environmental
conditions [15]. However, a lot more needs to be done to ensure
that forecast models provide accurate predictions everywhere,
the outcomes of the NASA-supported model validate the belief that
regardless of the challenges faced today, science will one day
decode the enigma around cholera.
One must remember that bringing an end to cholera will
require a change in mindsets—of people, countries and global orga-
nizations—to fully implement the existing wealth of knowledge
and research on cholera. The world needs to fight the disease not
only with science but also with stronger communication and
awareness campaigns led by credible champions who cut across
race and class to stamp out the stigma and fear attached to cholera.
Only then can we succeed in our battle against cholera.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
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