Cholera

Brijesh Singh Yadav

brijeshbioinfo@gmail.com

Common Name: Asiatic cholera, epidemic cholera

Causative agent: Vibrio cholerae
Disease Type: Bacterial

Disease description:
Cholera, sometimes known as Asiatic cholera or epidemic cholera, is a serious infection,
involving the lower part of the small bowel. It is one of the most severe diseases of the
intestines. It is a waterborne disease and is common during monsoon. The disease is
predominant in children in endemic areas like India and other countries of South East and
Mid East Asia. Its incidence is much higher in the age group between one and five years
than in other age groups of children. Cholera strikes suddenly and fills the intestinal
canal with bacilli, which die rapidly and leave the person alive or dead. It is an acute,
diarrheal illness caused by infection of the intestine with the bacterium Vibrio cholerae.
The infection is often mild or without symptoms, but sometimes it can be severe.
Approximately one in 20 infected persons have severe disease characterized by profuse
watery diarrhea, vomiting, and leg cramps. In these persons, rapid loss of body fluids
leads to dehydration and shock. Without treatment, death can occur within hours.

Fig. 1 Pictures showing people suffering from cholera

Disease Host: Humans

Causes of Cholera:
Contaminated water supplies are the main source of cholera infection, Uncooked
shellfish, milk, cooked rice, lentils, potatoes, beans, eggs, chicken and coconut milk all
can become sources of the disease, but potable water remains the most important source.

The most common sources of cholera infection include:

 Surface or well water. Cholera bacteria can lie dormant in water for long
periods, and contaminated public wells are frequent sources of large-scale cholera
outbreaks. Cholera epidemics are most likely to occur in communities without
adequate sanitation and in areas affected by natural disasters or war. People living in
crowded refugee camps are especially at risk of cholera.
 Seafood. Eating raw or undercooked seafood, especially shellfish that originate
from certain locations can expose you to cholera bacteria.
  Raw fruits and vegetables. Raw, unpeeled fruits and vegetables are a frequent
source of cholera infection in areas where cholera is endemic. In developing nations,
uncomposted manure fertilizers or irrigation water containing raw sewage can
contaminate produce in the field.
 Grains. In regions where cholera is widespread, grains such as rice and millet
that are contaminated after cooking and allowed to remain at room temperature for
several hours become a medium for the growth of cholera bacteria.

Causal Organism: Vibrio cholerae

Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae

Details of Vibrio Cholerae

Vibrio bacteria are gram-negative, a motile, aerobic organism and largely halophilic
bacterium with a curved-rod shape. However, a few species are nonhalophilic, depending
on their sodium chloride requirements. Most species are also oxidase-positive. Most
species are sensitive to acid pH, but tolerant of alkaline pH. V. cholerae and other species
of the genus Vibrio belong to the gamma subdivision of the Proteobacteria. There are
two major strains of V. cholerae, classic and El Tor, and numerous other serogroups.

V. cholerae occurs naturally in the plankton of fresh, brackish, and salt water, attached
primarily to copepods in the zooplankton. Coastal cholera outbreaks typically follow
zooplankton blooms. This makes cholera a typical zoonosis

Vibrio cholerae produces cholera toxin, an enterotoxin, whose action on the mucosal
epithelium lining of the small intestine is responsible for the characteristic massive
diarrhoea of the disease.

There are two general types of Vibrio cholerae:

Vibrio cholerae Serogroup O1

• Vibrio cholerae Serogroup non-O1. Vibrio cholerae Serogroup O1 is the type of

Vibrio cholerae that is most often the cause of cholera.
• Vibrio cholerae Serogroup O139, a Vibrio cholerae Serogroup non-O1 bacterium,
is the other cause of cholera. There are about 70 other
species of Vibrio cholerae Serogroup non-O1; these
other species rarely cause diarrhea.
Morphological features:
A novel filamentous bacteriophage, fs-2, was isolated from Vibrio cholerae O139 strain
MDO14. The fs-2 phage was a long filamentous particle 1200 nm long and 7 nm wide.
The purified phage formed a turbid plaque when spotted on a lawn of the host organisms.
The plaque-formation activity was stable following heating to 70 °C but was inhibited by
treatment with chloroform. fs-2 had a single-stranded DNA genome and was converted to
a double-stranded replicative form in the host cell. Almost all V. cholerae O139 and O1
El Torbiotype strains tested were sensitive to the phage, but most O1 classical strains and
non-O1 non-O139 strains were resistant. The fs-2 genome comprised 8651 nucleotides
containing nine open reading frames, five of which had predicted protein products
partially homologous to the reported protein products of other filamentous phages.
Although the extent of the homology was not particularly high, the genetic organization
of other filamentous phages appears to be preserved in fs-2. The phage was not integrated
into the chromosome of its host, but a 715 nucleotide fragment located in the large
intergenic region of fs-2 was highly homologous to a part of region RS2 (repetitive
sequence 2) of the V. cholerae CTXU sequence which is speculated to be required for
integration of the phage into the V. cholerae chromosome at a specific site.

Vibrio cholerae has two distinct life cycles — one in the environment and one in humans.

Cholera bacteria in the environment

Cholera bacteria occur naturally in coastal waters, where they attach to tiny crustaceans
called copepods. As many as 10,000 bacteria may adhere to a single crustacean. The
cholera bacteria travel with their hosts, spreading worldwide as the crustaceans follow
their food source — certain types of algae and plankton that grow explosively when
water temperatures rise. Algae growth is further fueled by the urea found in sewage and
in agricultural runoff.

Most cholera outbreaks occur in spring and fall when ocean surface temperatures and
algae blooms are at their height. More algae mean more copepods, and more copepods
mean more cholera bacteria.

Cholera bacteria in people

When humans ingest cholera bacteria, they may not become sick themselves, but they
still excrete the bacteria in their stool and can pass cholera disease to others through the
fecal-oral route. This mainly occurs when human feces contaminate food or water
supplies, both of which can serve as ideal breeding grounds for the cholera bacteria.
Because more than a million cholera bacteria — approximately the amount you'd find in
a glass of contaminated water — are needed to cause illness, cholera usually isn't
transmitted through casual person-to-person contact.

Disease Transmission:

Cholera is a highly contagious disease, and is transmitted primarily by ingestion of

faecally contaminated water by susceptible persons. Besides water, foods have also been
recognized as an important vehicle for transmission of cholera. Foods are likely to be
faecally contaminated during preparation, particularly by infected food handlers in an
unhygienic environment. The physicochemical characteristics of foods that support
survival and growth of V. cholerae O1 and O139 include high-moisture content, neutral
or an alkaline pH, low temperature, high-organic content, and absence of other competing
bacteria. Sea foods, including fish, shellfish, crabs, oysters and clams, have all been
incriminated in cholera outbreaks in many countries, including the United States and
Australia. Contaminated rice, millet gruel, and vegetables have also been implicated in
several outbreaks. Other foods, including fruits (except sour fruits), poultry, meat, and
dairy products, have the potential of transmitting cholera.

Vibrio cholerae is usually found in impure water supplies because of the unsanitary
disposal of excrement. Person-to-person transmission is rare. It is usually transmitted by
consuming contaminated food or water from:

• Municipal water supplies

• Ice made from municipal water
• Foods and beverages bought from street vendors
• Vegetables irrigated with fresh sewage
• Raw or inadequately cooked fish and seafood taken from sewage-polluted waters

Geographical distribution of Cholera

Cholera is most common in Africa, southern and Southeast Asia, and the Middle East,
although outbreaks have occurred in Japan, Australia, and Europe. Infection also occurs
after eating shellfish from recognized environmental reservoirs of cholera, including one
that's along the United States’ Gulf of Mexico coast. In India, it's common among
children ages 1 to 5, but in other endemic areas, it's equally distributed among all age
groups.

Symptoms of Cholera

The most common symptoms are: sudden onset of watery diarrhea, up to 1 liter (quart)
per hour diarrhea has a "rice water" appearance, where the stool looks like water with
flecks of rice in it diarrhea has a "fishy" odor dehydration rapid heart rate dry skin dry
mucus membranes or dry mouth excessive thirst "glassy" eyes or sunken eyes unusual
sleepiness or tiredness low urine output abdominal cramps nausea vomiting It is very
important to visit a doctor so cholera can be treated immediately.

Most people who become sick with cholera experience only mild or moderate diarrhea
that's often hard to distinguish from diarrhea caused by other problems.

Only about one in 10 infected people develops the typical signs and symptoms of cholera,
which include:

• Severe, watery diarrhea. The incubation time for cholera is brief — usually one
to five days after infection. Diarrhea comes on suddenly. Cholera diarrhea often is
voluminous, flecked with mucus and dead cells, and has a pale, milky appearance
that resembles water in which rice has been rinsed (rice-water stool). What makes
 cholera diarrhea so deadly is the loss of large amounts of fluids in a short time —
as much as a quart an hour.
• Nausea and vomiting. Occurring in both the early and later stages of cholera,
vomiting may persist for hours at a time.
• Muscle cramps. These result from the rapid loss of salts such as sodium, chloride
and potassium.
• Dehydration. This can develop within hours after the onset of cholera symptoms
— far more quickly than in other diarrheal diseases. Depending on how much
body fluids have been lost, dehydration can range from mild to severe. A loss of
10 percent or more of total body weight indicates severe dehydration. Signs and
symptoms of cholera dehydration include irritability, lethargy, sunken eyes, a dry
mouth, extreme thirst, dry, shriveled skin that's slow to bounce back when
pinched into a fold, little or no urine output, low blood pressure, and an irregular
heartbeat (arrhythmia). The patient gets severe cramps in the stomach, and feels
very thirsty and restless. The temperature rises, but the skin is generally cold and
clammy and the pulse is weak. In the next stage, the body becomes colder; the
skin dry, wrinkled, and purple; the voice weak and husky; and the urine, scanty
and dark.
• Shock. Hypovolemic shock is one of the most serious complications of cholera
dehydration. It occurs when low blood volume causes a drop in blood pressure
and a corresponding reduction in the amount of oxygen reaching your tissues. If
untreated, severe hypovolemic shock can cause death in a matter of minutes. The
blood pressure falls, the cramps are agonizing, and signs of collapse appear
rapidly.

Signs and symptoms of cholera in children

In general, children with cholera have the same signs and symptoms adults do, but they
may also experience:

• Extreme drowsiness or even coma

• Fever
• Convulsions

To reduce the risk of food-borne transmission of cholera, it is recommended that foods

should be prepared, served, and eaten in an hygienic environment, free from faecal
contamination. Proper cooking, storing, and re-heating of foods before eating, and hand-
washing with safe water before eating and after defecation are important safety measures
for preventing food-borne transmission of cholera.

Diagnosis of cholera:

In order to make a cholera diagnosis, the doctor will ask a number of questions about the
following topics:

• Recent history of foods or drinks that have been consumed

• Recent travel history
• Current medical conditions
• Current medicines.
• As part of making a cholera diagnosis, the doctor will also perform a physical
exam to look for signs of cholera and fluid loss. If the doctor suspects cholera, he or she
 will ask for a stool sample. A dark-field microscopic examination of fresh feces showing
rapidly moving bacilli (like shooting stars) allows for a quick, tentative diagnosis.
Immunofluorescence also allows rapid diagnosis.

A simple method for the laboratory diagnosis of cholera is presented:

(a) Peptone water is inoculated with fresh stool and incubated 8 hours,
(b) Alkaline nutrient agar plates are streaked and incubated overnight,
(c) Transparent colonies are tested for agglutination with anti-cholera O serum.
(d) Agglutinable vibrio are tested for hemolysis using 5 per cent sheep or goat
cells.

Precaution

• Routine surveillance activities to detect the early signs of the disease

• To provide safe and protected drinking water to the community
• Health education to the community regarding personnel and domestic hygiene as
well as environmental sanitation
• Monitoring the hygienic conditions and safe drinking availability in hotels,
Restaurants and food catering units.
• Appropriate control measures at huge public gathering places like Jarheads or any
social events
• Periodical chlorination of drinking water sources.

Pathogenicity and Clinical Significance of cholera

The bacterial species Vibrio cholerae includes harmless aquatic strains as well as strains
capable of causing epidemics and global pandemics of cholera. While investigating the
relationship between pathogenic and nonpathogenic strains, we identified a chromosomal
pathogenicity island (PAI) that is present in epidemic and pandemic strains but absent
from nonpathogenic strains. Initially, two ToxR-regulated genes (aldA and tagA) were
studied and were found to be associated with epidemic and pandemic strains but absent in
nontoxigenic strains. The region containing aldA and tagA comprises 13 kb of previously
unidentified DNA and is part of a PAI that contains a regulator of virulence genes (ToxT)
and a gene cluster encoding an essential colonization factor and the cholera toxin phage
receptor (toxin-coregulated pilus; TCP). The PAI is 39.5 kb in size, has low %G+C
(35%), contains putative integrase and transposase genes, is flanked by att sites, and
inserts near a 10Sa RNA gene (ssrA), suggesting it may be of bacteriophage origin. We
found this PAI in two clinical non-O1/non-O139 cholera toxin-positive strains,
suggesting that it can be transferred within V. cholerae. The sequence within this PAI
includes an ORF with homology to a gene associated with the type IV pilus gene cluster
of enteropathogenic Escherichia coli, a transposase from Vibrio anguillarum, and several
ORFs with no known homology. As the PAI contains the CTXΦ receptor, it may
represent the initial genetic factor required for the emergence of epidemic and pandemic
cholera.

Treatment:

Mortality rate has been brought down to less than 1 %, by effective rehydration therapy
which may be oral or intravenous. Oral rehydration of the mildly, dehydrated patients
(90%) can be treated at home with oral dehydration fluids, which contains glucose, salts
and water, are capable of correcting the electolytes and water deficit in the body. ORS
sachets are widely available in all the health institutions in the State including sub centers
at village level. Intravenous dehydration is required only for the initials dehydration of
severely dehydrated patients, who are in shock or unable to drink. The choice of IV fluids
are ringer's lactate.

Antibiotics like doxycycline or tetracycline or trimethoprim – sulfamethoxazole or

Furazoladine can be used soon after the vomit stops, in severe cases of cholera.
Vaccination for cholera is not recommended for its ineffectiveness in controlling Cholera.