CHOLERA

Overview of Cholera

• what causes cholera
  • Cholera is an acute diarrhoeal disease caused by V Cholerae
    • O1 
      • classical 
      • El Tor
    • O139.

• It is now commonly due to the El Tor biotype and O139.
• Currently the 7th pandemic powered by el tor strain of vibrio cholera is underway

• Cases range from symptomless to severe infections.
• The majority of infections are mild or asymptomatic.
• Typical cases are characterized by
  • the sudden onset of
    • profuse,
    • effortless,
    • watery diarrhoea
  • followed by
    • vomiting,
    • rapid dehydration,
    • muscular cramps and
    • suppression of urine.
  • Unless there is rapid replacement of fluid and electrolytes,
  • the case fatality may be as high as 30 to 40 per cent.

Problem statement

World

• The number of cholera cases reported to WHO continues to rise.
• • According to the European Centre for Disease Prevention and Control (ECDC), 
  • since their last update on 20 December 2022, 
  • 74,761 cholera cases, including 745 fatalities, 
  • have been reported worldwide. 
  • Countries and territories reporting new cases since the previous update are 
  • Afghanistan, 
  • Bangladesh, 
  • Burundi, 
  • Cameroon, 
  • the Democratic Republic of the Congo, 
  • the Dominican Republic, 
  • Haiti, 
  • Iraq, 
  • Kenya, 
  • Lebanon, 
  • Malawi, 
  • Mozambique, 
  • Nigeria, 
  • the Philippines, 
  • Somalia, 
  • Syria, 
  • and Tanzania.
• Many more cases were unaccounted for
  • due to
    • limitations in surveillance systems and
    • fear of trade and travel sanctions.
• The true burden of the disease
• is estimated to be
• 1.3-4.0 million cases and
• 21,000-143,000 deaths annually (1) .

  Outbreak causing serogroups

• 
  

• Two serogroups of V cholerae cause outbreaks.
  1. O1 (classical and El Tor)
     • V cholerae O1 causes the majority of outbreaks,
       • Recently, new El Tor variant strains have been detected in several parts of Asia and Africa.
  2. O139
     • while O139
       • first identified in Bangladesh in 1992
       • is confined to South-East Asia.
  3. Observations suggest that these strains cause more severe cholera with higher case fatality rates.
  4. Careful epidemiological monitoring of circulating strains is recommended (2).
• Non-O1 and non-O139 V cholerae can cause mild diarrhoea
  • but do not generate epidemics.

Factors leading to Increased transmission

• Recent studies indicate that global warming creates a favourable environment for the bacteria.
• Cholera transmission is closely linked to inadequate environmental management.
• Typical at-risk areas include
  • peri-urban slums,
  • where basic infrastructure is not available and
  • in areas, where as a consequence of a disaster,
    • disruption of water and sanitation system takes place, or
    • the displacement of population to inadequate and overcrowded camps.
• Risk of cholera transmission increases,
  • should the bacteria be present or introduced.
• Epidemics have never arisen from dead bodies (2).

Relevance of cholera in public health

• Cholera remains a global threat to public health and
  • a key indicator of lack of social development.
• The dynamics of cholera occurrences since 2005,
  • combined with the emergence of new strains that lead to a more severe clinical presentation;
  • increased antimicrobial resistance and climate change,
    • suggest that cholera may well return to the forefront of the global public health agenda (3)

INDIA

• Since the introduction of Cholera El Tor Biotype in 1964,
  • the geographic distribution of cholera in India has considerably changed.
• West Bengal has lost its reputation as the home of cholera.
• Many of the states which never had cholera or were free from it for a long time,
  • got infected and became an endemic foci of El Tor infection.
  • In several of the invaded areas, the disease is seen persisting as a smouldering infection.
• The classical severe epidemics with mortality are now uncommon.
• Explosive outbreak particularly following large fairs and festivals are also now rare.
• The bacteriology of cholera also presents a changed picture
  • For reasons that are not known,
    • there has been no large scale epidemic of classical cholera since 1964.
• In short,
  • the El Tor biotype of V Cholerae O1
  • has rapidly replaced the classical biotype
  • in all parts of the country.
• Most of the El Tor biotype isolated today
  • belong to the serotype Ogawa.

Epidemiological features

• Cholera is both an epidemic and endemic disease.
• The epidemic and endemicity of a disease will depend on the
  • characteristics of the agent,
    • Characteristics of the agent which influence its distribution include
      • its ability to survive in a given environment,
      • its virulence,
      • the average number of organisms required to cause infection, etc.
  • and those of the system (environment).
    • Characteristics of the system which affect the distribution of the agent include
      • the number of susceptibles,
      • and the opportunities it provides for transmission of the infection.
• Global experience has shown that
  • the introduction of cholera into any country cannot be prevented,
  • but cholera can create a problem only in areas where sanitation is defective.
• Epidemics of cholera
  • are characteristically abrupt and often create an acute public health problem.
  • They have a high potential to spread fast and cause deaths.
  • The epidemic reaches a peak and subsides gradually as the “force of infection” declines.
  • Often-times, by the time control measures are instituted the epidemic has already reached its peak and is waning.
  • Thus, cholera epidemic in a community is self-limiting.
    • This is attributed to
      • the acquisition of temporary immunity, as well as due to
      • the occurrence of a large number of subclinical cases.
• The force of infection” is composed of 2 components, namely
  • the force of infection through water and
  • the force of infection through contacts (5).
• It is well-known that
  • the elimination of contaminated water does not immediately bring an outbreak to an end,
  • but a so-called “tail” of the epidemic is produced.
  • This is due to the continuation of transmission through contacts (5).
• In areas where cholera is endemic, it does not show a stable endemicity like typhoid fever (5).
  • It undergoes seasonal fluctuations as well as epidemic outbreaks.
  • The seasonal variation differs
    • between countries and
    • even between regions of the same country.
• The seasonal incidence is also subject to change.
  • For example,
    • the disease used to be most common
      • in the summer in Kolkata and
      • in the early winter in Bangladesh;
    • now- in both places,
      • it is most frequent in the autumn (6).
  • In some parts of India, the peak incidence is in August
• The El Tor biotype,
  • wherever it has spread,
  • has become endemic with periodic outbreaks.
  • It appears to have greater “endemic tendency”
    • than its classical counterpart
    • in that it causes a higher infection—to—case ratio
      • (i.e., inapparent infections and mild cases).
• Cholera occurs at intervals even in endemic areas.
• A question that is frequently asked is about
  • the fate of V cholerae
  • in the inter-epidemic periods.
  • Three explanations are offered :
    • (a) the existence of long-term carriers (7);
    • (b) the existence of diminished but continuous transmission
      • involving asymptomatic cases (3), and
    • (c) the persistence of the organism
      • in a free-living, perhaps altered form
      • in the environment (9, 10).
        • The existence of a free-living cycle may explain
          • why cholera became endemic for varying periods in certain areas after introduction of the current pandemic strains (9, 10).
  • Atypical non-toxigenic V. cholerae O1 of the El Tor biotype have sometimes been found
    • in surface waters in endemic and non-endemic areas
    • without any related human infection or disease (11).
    • A question of considerable epidemiological significance is
      • whether transmission of somatic antigen can occur in the natural environment,
        • i.e., can non-O1 V cholerae become V. cholerae O1? (12).
      • Such “transformation” has been claimed by many workers (13).

Epidemiological determinants

Agent factors

(a) AGENT :

• The organism that causes cholera is labelled as
  • V cholerae O Group 1 or Vibrio cholerae
    • O1 and
    • O139.
• The term “epidemic strain” has also been used for these vibrios.
• Vibrios
  • that are biochemically similar to the epidemic strains
    • (V. cholerae O1 and O139)
  • but do not agglutinate in V. cholerae O1 and O139 antiserum
  • have been referred to in the past as
    • non-agglutinating ([[NAG]]) vibrios or as
    • non-cholera vibrios ([[NCV]]).
  • These are now included in the species V. cholerae and
    • are referred to as
      • non-O Group 1V/ O139 cholerae
      • (non-epidemic strains).
  • It is now recognized that the NCV/NAG vibrios include some species
    • that are pathogenic for humans
    • (e g., Vibrio parahaemolyticus)
    • which have caused outbreaks of cholera like diarrhoea.
• It is, therefore, necessary to identify V. cholerae O1 and O139 for specific diagnosis of cholera.
• Within the O-Group 1,
  • two biotypes –
    • classical and
    • El Tor,
      • It may be mentioned that the El Tor biotype was first isolated at the El Tor quarantine station in Egypt in 1905.
  • have been differentiated.
• Cholera is now caused mostly by the El Tor biotype and O139.
• Classical and El Tor vibrios are further divided each into 3 serological types namely
  1. Inaba,
  2. Ogawa
     • Most of the El Tor vibrios isolated in India belong to the Ogawa serotype.
  3. Hikojima.
• The El Tor biotype
  • which are known for their haemolytic property,
  • lost this property as the pandemic progressed.
• They may be distinguished from classical vibrios by the following tests :
  • (1) El Tor vibrios agglutinate chicken and sheep erythrocytes
  • (2) they are resistant to classical phage IV
  • (3) they are resistant to polymyxin B-50-unit disc, and
  • (4) the VP reaction and haemolytic test do not give consistent results.

(b) RESISTANCE :

• V. cholerae are killed within
  • 30 minutes by heating at 56 deg.C or
  • within a few seconds by boiling.
• They remain in ice
  • for 4-6 weeks
  • or longer.
• Drying and sunshine will kill them
  • in a few hours.
• They are easily destroyed by coal tar disinfectants
  • such as cresol.
• Bleaching powder is another good disinfectant
  • which kills vibrios instantly at 6 mg/litre.
• The El Tor biotype tends to be more resistant
  • than do classical vibrios.

(c) TOXIN PRODUCTION:

• The vibrios
  • multiply in the lumen of the small intestine and
  • produce an exotoxin
    • (enterotoxin).
• This toxin produces diarrhoea
  • through its effect on the adenylate cyclase-cyclic AMP system
  • of mucosal cells
  • of the small intestine.
• The exotoxin has no effect
• on any other tissue
• except the intestinal epithelial cells,

(d) RESERVOIR OF INFECTION:

• The human being is the only known reservoir of cholera infection.
• He may be a
  • case or
  • carrier,

(i) Cases :

• Cases range from inapparent infections to severe ones.
• Asymptomatic
  • About 75 per cent of people infected with V. cholerae do not develop any symptoms,
  • although the bacteria are present in their faeces
  • for 7-14 days after infection
  • and are shed back into the environment,
    • potentially infecting other people.
• Symptomatic
  • Among people who develop symptoms,
    • about 20 per cent develop acute watery diarrhoea with severe dehydration.
      • People with low immunity,
      • e.g., malnourished children and people living with HIV are at a greater risk of death if infected (1).
    • 80 % mild symptomatic
      • It is the mild and
      • asymptomatic cases that play a significant role in maintaining endemic reservoir,

(ii) Carriers ;

• The carriers are
  • usually temporary,
  • rarely chronic.
• They also make an important contribution to the reservoir of infection.
• Since carriers excrete fewer vibrios than clinical cases,
  • carriers are best detected by bacteriological examination of
  • the purged stool
    • induced by the administration of
    • 30-60 gram of magnesium sulphate in 100 ml of water
    • by mouth,

(e) INFECTIVE MATERIAL :

• The immediate sources of infection are
  • the stools and vomit
  • of cases and carriers.
• Large numbers of vibrios
  • (about 107-109 vibrios per ml of fluid)
  • are present in the watery stools of cholera patients;
• and an average patient excretes 10-20 litres of fluid.
• Carriers excrete fewer vibrios than cases,
  • 102-105 vibrios per gram of stools,

(f) INFECTIVE DOSE :

• Cholera is dose-related.
• Infection occurs when
  • the number of vibrios ingested
  • exceeds the dose that is infective for the individual.
• Experimental work suggests that in the normal person
• a very high dose-something like organisms = \huge 10^{11}
• is required to produce the clinical disease.

(g) PERIOD OF COMMUNICABILITY :

• A case of cholera is infectious for a period of 7-10 days.
• Convalescent carriers are infectious for 2-3 weeks.
• The chronic carrier state may last
  • from a month
  • up to 10 years or more.

Carriers in cholera 

• A cholera carrier may be defined as
  • an apparently healthy person
  • who is excreting V. cholerae O1 (classical or El Tor) in stools.
• Four types of cholera carriers have been described (16) :

(a) PRECLINICAL OR INCUBATORY CARRIERS :

• Since the incubation period of cholera is short (1-5 days),
  • incubatory carriage is of short duration.
• The incubatory carriers are potential patients,

(b) CONVALESCENT CARRIER :

• The patient who has recovered from an attack of cholera
  • may continue to excrete vibrios,
  • during his convalescence for 2-3 weeks.
• Convalescent state has been found to occur in patients
  • who have not received effective antibiotic treatment.
• The convalescent carriers can often become chronic or long-term carriers,

(c) CONTACT OR HEALTHY CARRIER :

• This is the result of subclinical infection
  • contracted through association with a source of infection,
    • be it
      • a case or
      • infected environment.
• The duration of contact carrier state is usually less than 10 days;
  • the gall bladder is not infected,
  • and the stool culture is frequently positive for V cholerae O1.
• Contact carriers probably play an important role in the spread of cholera,

(d) CHRONIC CARRIER :

• A chronic carrier state
  • occurs infrequently.
• The longest carrier state was found to be over 10 years (16).
• Studies indicate that gall bladder is infected in chronic carriers.
• Since carriers excrete fewer vibrios than cases,
  • selective media and
  • proper enrichment
  • are important for their diagnosis.
• In carriers, the antibody titre against V. cholerae O1 rises and
  • remains positive as long as the person harbours the organism.
• This method may be used to detect long-term carriers
  • along with bacteriological examination of stools.

Host factors

(a) AGE AND SEX :

• Cholera affects all ages and both sexes.
• In endemic areas, attack rate is highest in children,

(b) GASTRIC ACIDITY :

• An effective barrier.
• The vibrio is destroyed in an acidity of pH 5 or lower.
• Conditions that reduce gastric acidity may influence individual susceptibility (19).

(c) POPULATION MOBILITY :

• Movement of population (
  • e.g.,
    • pilgrimages,
    • marriages,
    • fairs and
    • festivals)
  • results in increased risk of exposure to infection.
• In this jet age, cases and carriers can easily transfer infection to other countries,

(d) ECONOMIC STATUS :

• The incidence of cholera
  • tends to be the highest
  • in the lower socio-economic groups,
• and this is attributable mainly to poor hygiene,

(e) IMMUNITY :

• An attack of cholera is followed by immunity to reinfection,
  • but the duration and degree of immunity are not known.
• In experimental animals specific IgA antibodies occur in the lumen of the intestine.
• Similar antibodies in serum develop after the infection
  • but only last a few months.
• Vibriocidal antibodies in serum (titer > 1:20) have been associated with protection against colonization and disease.
• The presence of antitoxin antibodies
  • has not been associated with protection (17).
• Vaccination
  • gives only temporary,
  • partial immunity
  • for 3-6 months.

Environmental factors

• Vibrio transmission is readily possible in a community with poor environmental sanitation.
• The environmental factors of importance include contaminated water and food.
• Flies may carry V cholerae but not vectors of proven importance.
• Numerous social factors have also been responsible for the endemicity of cholera in India.
• These comprise
  • certain human habits favouring water and soil pollution,
  • low standards of personal hygiene,
  • lack of education and
  • poor quality of life.

Mode of transmission

Transmission occurs from man to man Via

(a) FAECALLY CONTAMINATED WATER :

• Uncontrolled water sources
  • such as
    • wells,
    • lakes,
    • ponds,
    • streams and
    • rivers
  • pose a great threat,

(b) CONTAMINATED FOOD AND DRINKS :

• Ingestion of contaminated food and drinks have been associated with outbreaks of cholera.
• Bottle feeding could be a significant risk factor for infants.
• Fruits and vegetables
  • washed with contaminated water
  • can be a source of infection.
• After preparation,
  • cooked food may be contaminated through
  • contaminated hands and flies.
• There is growing opinion that El Tor cholera may in some instances be transmitted
  • through a complex interaction of contaminated food, water and environment
  • rather than through public drinking water supplies (18).

(c) DIRECT CONTACT :

• In developing countries, a considerable proportion of cases may result from secondary transmission, i.e.,
  • person to person transmission
  • through contaminated fingers
  • while carelessly handling excreta and vomit of patients
  • and contaminated linen and fomites.

Incubation period

• From a few hours upto 5 days, but commonly 1-2 days.

Pathogenesis

• The main symptom of cholera is diarrhoea.
• Historical perspective
  • Diarrhoea in cholera was attributed in the past to such factors as
  • increased permeability of the intestinal epithelial cells,
  • increased peristalsis,
  • mucosal damage,
  • an increase in mesenteric blood flow and
  • failure of the “sodium pump”,
    • i.e.. interference with the passage of sodium from the lumen to the plasma.
  • None of these theories stood the test of time (19).
• According to current concepts,
• the cholera vibrio get through the mucus which overlies the intestinal epithelium.
• It probably secretes mucinase,
  • which helps it move rapidly through the mucus.
• Then it gets attached or adhered to the intestinal epithelial cells,
• and this it probably does
• by an adherence factor
• on its surface.

• When the vibrio becomes adherent to the mucosa,
  • it produces its enterotoxin
  • which consists of 2 parts –
    • the light or L toxin and
      • The L toxin combines with substances in the epithelial cell membrane
        • called gangliosides and
      • this binds the vibrio to the cell wall.
      • Binding is irreversible.
    • the heavy or H toxin.
      • The mode of action of H toxin is not fully clear.
      • What we know is that there is a substance called “adenyl cyclase” in the intestinal epithelial cells, and
      • H toxin activates this substance.
      • The activated adenyl cyclase causes a rise in another substance, called 3. 5-adenosine monophosphate,
        • better known as cyclic or cAMP (A physiologist got Noble Prize for describing this substance).
      • cAMP provides energy which drives fluid and ions into the lumen of the intestine.
      • This fluid is isotonic and is secreted by all segments of small intestine.
      • The increase in fluid is the cause of diarrhoea, and not increased peristalsis.
• There is no evidence that V. cholerae invades any tissue,
  • nor the enterotoxin to have any direct effect on any organ other than the small intestine (19).

Clinical features

• The severity of cholera
  • is dependent on
    • the rapidity and
    • duration of fluid loss.

Mild vs Severe

• The classical form of severe cholera occurs in only 5-10 per cent of cases
• In the rest, the disease tends to be mild characterized bv diarrhoea with or without vomiting or marked dehydration
• As a rule, mild cases recover in 1-3 days.
• Epidemiological studies have shown that
  • more than 90 per cent of El Tor cholera cases are mild and
  • clinically indistinguishable from other acute diarrhoeas (20).
• However, a typical case of cholera shows 3 stages :

Stages of Cholera

(a) STAGE OF EVACUATION :

• The onset is abrupt
  • with
    • profuse,
    • painless,
    • watery diarrhoea
  • followed by vomiting.
• The patient may pass as many as 40 stools in a day.
• The stools may have a “rice water” appearance,

(b) STAGE OF COLLAPSE :

• The patient soon passes into a stage of collapse
  • because of dehydration.
• The classical signs are :
  • sunken eyes,
  • hollow cheeks,
  • scaphoid abdomen,
  • subnormal temperature,
  • washer man’s hands and feet,
  • absent pulse,
  • unrecordable blood pressure,
  • loss of skin elasticity,
  • shallow and quick respirations.
• The output of urine decreases and may ultimately cease.
• The patient becomes restless, and
  • complains of intense thirst and cramps in legs and abdomen.
• Death may occur at this stage,
  • due to dehydration and acidosis
  • resulting from diarrhoea,

(c) STAGE OF RECOVERY :

• If death does not occur, the patient begins to show signs of clinical improvement.
• The blood pressure begins to rise, the temperature returns to normal, and urine secretion is re-established.
• If anuria persists, the patient may die of renal failure.

Epidemiological difference between El tor and classical cholera

• Epidemiologically, cholera due to El Tor biotype differs from classical cholera in the following respects :
  • (a) a hiqher incidence of mild and asymptomatic infection
    • This implies that the characteristic picture of rice-water stools and other signs of classical cholera described above may not be seen often;
  • (b) fewer secondary cases in the affected families-
  • (c) occurrence of chronic carriers, and
  • (d) since El Tor vibrios are more resistant than classical cholera vibrios they survive longer in the extra-intestinal environment.

Laboratory diagnosis of cholera

• The diagnosis of cholera can never be made with certainty on clinical grounds.
• Laboratory methods of diagnosis are required to confirm the diagnosis :

(a) COLLECTION OF STOOLS :

• A fresh specimen of stool should be collected for laboratory examination.
• Sample should be collected before the person is treated with antibiotics.
• Collection may be made generally in one of the following ways :
  • (i) Rubber catheter :
    • Collection by the catheter is the best method
      • but is complicated under field conditions.
    • Soft rubber catheter (No.26-28)
      • sterilized by boiling should be used.
    • The catheter is introduced
      • (after lubrication with liquid paraffin)
      • for at least 4-5 cm into the rectum.
    • The specimen voided may be collected directly into a transport (holding) media,
      • e.g.,
        • Venkatraman-Ramakrishnan (VR) medium,
        • alkaline peptone water,
  • (ii) Rectal swab :
    • Swabs consisting of 15-20 cm long wooden sticks,
      • with one end wrapped with absorbent cotton,
      • sterilized by autoclaving have been found to be satisfactory.
    • Rectal swabs should be
      • dipped into the holding medium
      • before being introduced into the rectum,
  • (iii) If no transport medium is available,
    • a cotton-tipped rectal swab should be soaked in the liquid stool,
    • placed in a sterile plastic bag,
    • tightly sealed and sent to the testing laboratory (22).

(b) VOMITUS :

• This is practically never used
  • as the chances of isolating vibrios are much less
  • and there is no advantage.

(c) WATER :

• Samples containing
  • 1-3 litres of suspect water
    • should be collected in sterile bottles
    • (for the filter method),
  • or
    • 9 volumes of the sample water
    • added to 1 volume of
    • 10 per cent peptone water,
• and despatched to the laboratory
  • by the quickest method of transport,

(d) FOOD SAMPLES :

• Samples of food suspected to be contaminated with V. cholerae
  • (or other enteric bacteria)
• amounting to 1 to 3 g
• are collected in transport media
• and sent to the laboratory,

(e) TRANSPORTATION :

• (i) The stools should be transported in
  • sterilized McCartney bottles,
    • 30 ml capacity
    • containing
      • alkaline peptone water or
      • VR medium.
  • VR medium can be used if larger stool specimens can be collected.
  • The specimen should be transported in alkaline peptone water or Cary-Blair medium if it is collected by a rectal swab.
  • One Gram or one ml of faeces in 10 ml of the holding medium will suffice.
  • Rectal swabs should have their tops broken off
    • so that caps of the containers can be replaced
• (ii) If suitable plating media are available (e.g., bile salt agar) at the bed-side,
  • the stools should be streaked on to the media and
  • forwarded to laboratory with the transport media,

(f) DIRECT LAMINATION :

• If a microscope with dark field illumination is available,
  • it may be possible to diagnose about 80 per cent the cases
    • within a few minutes,
  • and more cases
    • after 5 to 6 hours of incubation
    • in alkaline peptone water.
• In the dark field,
  • the vibrios evoke the image of many shooting stars
  • in a dark sky.
• If motility ceases on mixing with polyvalent anti-cholera diagnostic serum,
  • the organisms are presumed to be cholera vibrios.
• A presumptive diagnosis of cholera can thus be established,

(g) CULTURE METHODS :

• On arrival at the laboratory,
  • the specimen in holding fluid is well shaken,
  • and about 0.5 to 1.0 ml of material is inoculated into Peptone Water Tellurite (PWT) medium
  • for enrichment.
• After 4 to 6 hours incubation
  • at 37 deg. C,
  • a loopful of the culture from the surface is sub cultured
  • on Bile Salt Agar medium (BSA. pH 8.6).
• After overnight incubation,
  • the plates are screened under oblique light illumination
  • for vibrio colonies.

(h) CHARACTERIZATION :

• V cholerae usually appears on bile salt agar (BSA)
  • as translucent, moist, raised, smooth and easily emulsifiable colonies
  • about 1 mm in diameter.
• The typical colonies are picked up and tested as follows :
  • (i) Gram’s stain and motility :
    • Gram negative and curved rods
    • with characteristic scintillating type of movement in hanging drop preparations
    • are very characteristic of V. cholerae
  • (ii) Serological test:
    • Slide agglutination test is done
      • by picking up suspected colonies and
      • making a homogeneous suspension in 0.85 per cent sterile saline and
      • adding one drop of polyvalent anti-cholera diagnostic serum.
    • If agglutination is positive,
      • the test is repeated with Inaba and Ogawa antisera,
      • to determine the subtype.

(i) BIOCHEMICAL TESTS :

• Serologically positive colonies should be subcultured
  • in one tube each of the sugar broths (mannose, sucrose, arabinose) and
    • a tube of peptone water pH 7.2
      • for the cholera red reaction.
• Production of acid in sucrose and mannose, but not arabinose
  • is characteristic of V cholerae.

(j) FURTHER CHARACTERIZATION :

• For further characterization of biotypes of V cholerae
  • organisms are identified by slide agglutination tests
  • using anti-O1 or group 139 antisera and
  • by biochemical reaction patterns.
• Suspicious colonies
  • that do not agglutinate with anticholera sera
  • are tested further by the
    • oxidase and
    • string tests (19).

CONTROL OF CHOLERA

• It is now considered that
  • the best way to control cholera
  • is to develop and implement a national programme
  • for the control of ALL diarrhoeal diseases
  • because of similarities in the
    • epidemiology,
    • pathophysiology,
    • treatment and
    • control
  • of cholera and other acute diarrhoeal diseases (23).
• The following account is based on the “Guidelines for Cholera Control” proposed by the WHO (11).

1.Verification of the diagnosis

• It is important to have confirmation of the outbreak as quickly as possible.
• All cases of diarrhoea should be investigated even on the slightest suspicion.
• For the specific diagnosis of cholera,
  • it is important to identify V. cholerae O1
  • in the stools of the patient.
• Once the presence of cholera has been proved,
  • it is not necessary to culture stools of all cases or contacts.
• Bacteriological diagnosis of cholera envisages
  • a well-organized system of laboratory services
  • in the community.

2.Notification

• Cholera is a notifiable disease locally and nationally.
• Since 2005 cholera notification is no longer mandatory internationally.
• Health workers at all levels
  • (particularly those who are closest to the community such as the community health workers and the multi-purpose workers)
  • should be trained to identify and
  • notify cases immediately
  • to the local health authority.
• Under the International Health Regulations,
  • cholera is notifiable to the WHO within 24 hours of its occurrence by the National Government;
  • the number of cases and deaths are also to be reported daily and weekly till the area is declared free of cholera.
• An area is declared free of cholera when twice the incubation period (i.e., 10 days) has elapsed since the death, recovery or isolation of the last case (24).

3.Early case-finding

• An aggressive search for cases
  • (mild, moderate, severe)
  • should be made in the community
  • to be able to initiate prompt treatment.
• Early detection of cases
  • also permits
  • the detection of infected household contacts and
  • helps the epidemiologist
  • in investigating the means of spread
  • for deciding on specific intervention.

4.Establishment of treatment centres

• In the control of cholera, no time should be lost in providing treatment for the patients.
• To achieve this objective, it is necessary to establish easily accessible treatment facilities in the community.
• The mildly dehydrated patients
  • (which account for over 90 per cent of cases)
  • should be treated at home with oral rehydration fluid.
• Severely dehydrated patients,
  • requiring intravenous fluids,
  • should be transferred to the nearest treatment centre or hospital:
  • if possible, they should receive oral rehydration
  • on the way to the hospital or treatment centre.
• If there is no hospital or treatment centre within a convenient distance,
  • a local school or public building should be taken over and
  • converted into a temporary treatment centre,
  • as close to the site of epidemic as possible.
• Transportation of cases over long distances is not desirable;
  • it has been linked with the spread of the disease.
• In areas
  • where
    • peripheral health services are poor and
    • cholera is endemic or threatening,
  • mobile teams should be established at the district level.
  • When needed,
    • these teams should be brought promptly into the epidemic area
    • to assist the local workers.

5.Rehydration therapy

• Cholera is now the most effectively treated disease.
• Mortality rates have been brought down to less than 1 per cent
  • by effective rehydration therapy.
• The rehydration may be oral or intravenous.
• The guidelines for ORT and intravenous rehydration are discussed in detail
• [[Oral Rehydration Therapy]]
• [[Intravenous rehydration]]
• [[Maintenance rehydration therapy]]

6.Adjuncts to therapy

• Antibiotics should be given as soon as vomiting has stopped,
  • which is usually after 3 to 4 hours of oral rehydration.
• Injectable antibiotics have no special advantages.
• The commonly used antibiotics for the treatment of cholera are
  • flouroquinolones,
  • tetracycline,
  • Azithromycin,
  • ampicilline and Trimethoprim TMP
  • Sulfamethoxazole (SMX).
• No other medication should be given to treat cholera,
  • like
    • antidiarrhoeals,
    • antiemetics,
    • antispasmodics,
    • cardiotonics and
    • corticosteroids.
• In regions where cholera is present,
  • it is important to identify those antibiotics
  • to which the vibrio cholerae O1 is resistant.
• If diarrhoea persists after 48 hours of treatment,
  • resistance to antibiotic should be suspected.

7.Epidemiological investigations

• General sanitation measures must be applied at the onset of an outbreak (see under sanitation measures).
• At the same time, epidemiological studies must be undertaken
  • to
    • define the extent of the outbreak and
    • identify the modes of transmission
  • so that more effective and specific control measures can be applied.
• The epidemiologist must maintain contact
  • with all health and civic units in his area
  • to ensure detection of new foci of disease.
• There are certain institutions which are able to assist in investigating outbreaks.
  • These include
    • the National Institute of Communicable Diseases, Delhi and
    • the All India Institute of Hygiene and Public Health, Kolkata,
  • where epidemiological teams are available for investigating epidemics.
• In addition, stools for phage typing may be sent to
  • the National Institute of Cholera and Enteric Diseases, 3, Dr Isaque Road, Kolkata-700016,
  • where the WHO International Centre for Vibrios is located.

8.Sanitation measures

(a) WATER CONTROL :

• As water is the most important vehicle of transmission of cholera,
  • all steps must be taken to provide properly treated or otherwise safe water to the community for all purposes (drinking, washing and cooking).
• Various approaches have been described for supplying safe water quickly and with limited resources (25).
• Facilities selected and installed should be appropriate and acceptable to the community.
• The ultimate aim should be provision of piped water supply on a permanent basis and elimination of alternative unsafe water sources.
• Because of financial limitations and other competitive priorities, this measure cannot be applied immediately on a large scale in developing countries, such as India.
• As an emergency measure, in urban areas, properly treated drinking water containing free residual chlorine should be made available to all families; this water should be stored in the household in narrow-mouthed, covered containers.
• In rural areas, water can be made safe by boiling or by chlorination.
• The emergency measures should be followed by the development of more permanent facilities.

(b) EXCRETA DISPOSAL :

• Provision of simple, cheap and effective excreta disposal system (sanitary latrines) is a basic need of all human settlements.
• When cholera appears in a community, the need for these facilities becomes vital.
• With the cooperation of the community, sanitary system should be selected and constructed (25), taking into consideration the customs and practices of the population, the existing terrain and geology, and the available resources.
• Simultaneously, health education messages should stress the proper use of such facilities, the dangers involved in depositing faeces on the ground, and in or near water, and the importance of handwashing with soap after defecation.

(c) FOOD SANITATION :

• Since food may be an important vehicle of infection, steps should be taken to improve food sanitation, particularly sale of foods under hygienic conditions.
• Health education must stress the importance of eating cooked hot food and of proper individual food handling techniques.
• Cooking utensils should be cleaned and dried after use.
• The housefly plays a relatively small role in transmitting cholera, but its prevalence is a general indicator of the level of sanitation

(d) DISINFECTION

• Disinfection should be both concurrent and terminal.
• The most effective effective disinfectant for general use is a coal tar disinfectant with a [[Rideal Walker (RD) coefficient]] of 10 or more
  • such as cresol.
• A disinfectant of RW coefficient of less than 5 should not be used.
• Bleaching powder, if used, should be of good quality.
• For – disinfection, attention should be paid to the following
  • patient’s stools and vomit;
  • clothes that may have been contaminated;
  • the latrine, if any
  • the patient s house and neighbourhood.

9.Chemoprophylaxis

• Studies have shown that approximately 10-12 per cent of close household contacts of a cholera case may be bacteriologically positive, and some of these develop clinical illness.
• In contrast, a very small proportion (0.6-1 per cent) in the community may be excreting vibrios.
• Mass chemoprophylaxis is not advised for the total community because in order to prevent one serious case of cholera, some 10,000 persons must be given the drug.
• Further, the drug’s effect is only short-lived for a few days.
• Whenever mass chemoprophylaxis was attempted, it failed to stop the spread of cholera.
• Because of these reasons,
  • chemoprophylaxis is advised only for
    • household contacts or
    • of a closed community
  • in which cholera has occurred.
• Tetracycline is the drug of choice for chemoprophylaxis.
• It has to be given over a 3-day period in
  • a twice-daily dose of 500 mg for adults,
  • 125 mg for children aged 4-13 years, and
  • 50 mg for children aged 0-3 years.
• Alternatively, the long acting tetracycline (doxycycline) may be used for chemoprophylaxis,
  • if the prevailing strains are not resistant.
• A single oral dose of doxycycline
  • (300 mg for adults and
  • 6 mg/kg for children under 15 years)
  • has proved to be effective.

10.Vaccination

ORAL VACCINE (27)

• The live attenuated single-dose vaccine (CVD103-HgR) is no longer produced.
• Three types of oral cholera vaccines are available :
  • (a) Dukoral (WC-rBS).
  • (b) Sanchol and mORCVAX
  • (c) Euvichol.

(a) Dukoral (WC-rBS)

• Dukoral is a monovalent vaccine
  • based on
    • formalin and
    • heat-killed
    • whole cells (WC) of V cholerae O1
      • (classical and El Tor, Inaba and Ogawa)
    • plus recombinant cholera toxin B subunit.
• The vaccine is provided in 3 ml single-dose vials
  • together with the bicarbonate buffer
  • (effervescent granules in sachets to protect the toxin B subunit from being destroyed by gastric acid).
• Vaccine and buffer are mixed
  • in 150 ml of water (chlorinated or not)
    • for persons aged >5 years and
  • in 75 ml of water
    • for children aged 2 to 5 years.
• The vaccine
  • has a shelf life of 3 years
    • at 2-8 C and
  • remains stable for 1 month
    • at 37°C.

Vaccine schedule and administration

• According to the manufacturer,
  • Primary immunisation consists of 2 oral doses
  • given

    • 7 days apart

    • (but < 6 weeks apart)
  • for adults and children aged >6 years.
• Children aged 2 – 5 years
  • should receive 3 doses

  • 7 days apart

  • ( but < 6 weeks apart).
• Intake of food and drink should be avoided for 1 hour before and after vaccination.
• If the interval between primary immunization doses is delayed
  • for > 6 weeks
  • primary immunization should be restarted.
• Protection may be expected
  • about 1 week
  • after the last scheduled dose.
• Provided there is continued risk of V. cholerae infection,
  • 1 booster dose is recommended by manufacturer,
  • after 2 years
  • for
    • adults and
    • children aged >6 years.
• If the interval
  • between
    • the primary series and
    • booster immunization
  • is>2 years,
  • primary immunization must be repeated.
• For children aged 2-5 years
  • 1 booster dose is recommended every 6 months,
  • and if the interval between primary immunization and the booster is >6 months,
    • primary immunization must be repeated.
• Dukoral is not licensed for children aged <2 years.

(b) Sanchol and mORCVAX

• The closely related bivalent oral cholera vaccines are based on serogroups O1 and O139.
• Unlike Dukoral.
  • these vaccines do not contain the bacterial toxin B subunit
  • therefore It does not require buffer.
• According to the manufacturer,
  • vaccine should be administered orally
  • in 2 liquid doses
  • 14 days apart
  • for individuals aged >=l year.
• A booster dose is recommended after 2 years (27).

(c) Euvichol

• It was prequalified in December 2015 and has same characteristics as Sanchol (2).

11. Health education

• The most effective prophylactic measure is perhaps health education.
• It should be directed mainly to
  • (a) the effectiveness and simplicity of oral rehydration therapy
  • (b) the benefits of early reporting for prompt treatment
  • (c) food hygiene practices
  • (d) hand washing after defecation and before eating, and
  • (e) the benefit of cooked, hot foods and safe water.
• Since cholera is mainly a disease of the poor and ignorant, these groups should be tackled first.

Diarrhoeal Diseases Control Programme

• The incidence of cholera cases and deaths has decreased in recent years.
• During the year 1980-81, strategy of the National Cholera Control Programme has undergone changes (28).
• It is now termed as Diarrhoeal Diseases Control Programme (29).
• Oral Rehydration Therapy Programme was started in 1986-87 in a phased manner.
• The main objective of the programme is to prevent diarrhoea-associated deaths in children due to dehydration.
• The training programme and health education material highlight
  • the rational management of diarrhoea in children,
  • including increased intake of home available fluids
  • and breast feeding.
• ORS is promoted as first line of treatment.
• ORS is being supplied as a part of the sub-centre kits (30).