Cholera (social preventive pharmacy)

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d. Control and/or prevention of diarrhoeal

This requires strengthening of epidemiological
Cholera is an acute diarrhoeal disease caused by
surveillance systems.
V. Cho/erae 01 (classical or El Tor) and 0139. It is now

e. The Integrated Global Action Plan for the commonly due to the El Tor biotype and 0 1 3 9 . Cases range

from symptomless to severe infections. The majority of
Prevention and Control of Pneumonia and
infections are mild or asymptomatic. Typical cases are
characterized by the sudden onset of profuse, effortless,
Please refer to page 1 7 4 for details.
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
The concept of primary health care involves the delivery
may be as high as 30 to 40 per cent.
of a package of curative and preventive services at the

community level. An intersectoral approach centred upon
Problem statement
primary health care involving activities in the fields of water
The number of cholera cases reported to WHO continues
supply and excreta disposal, communicable disease control,
to rise. For 2013 alone, a total of 129,060 cases were
mother and child health, nutrition and health education is
notified from 47 countries, including 2, 102 deaths. Many
regarded as essential for the ultimate control of diarrhoeal
more cases were unaccounted for due to limitations in
surveillance systems and fear of trade and travel sanctions.

Diarrhoeal Diseases Control Programme in India The true burden of the disease is estimated to be 1.4-4.3

million cases and 28,000-142,000 deaths annually ( 1 , 2).
The Diarrhoeal Disease Control Programme was started

in 1978 with the objective of reducing the mortality and Two serogroups of V. cholerae – 0 1 and 0 1 3 9 – cause

morbidity due to diarrhoeal diseases. Since 1985-86, with outbreaks. V. cho/erae 0 1 causes the majority of outbreaks,

the inception of the National Oral Rehydration Therapy while 0139 – first identified in Bangladesh in 1992 – is

· Programme, the focus of activities has been on confined to South-East Asia. Non-01 and non-0139

strengthening case management of diarrhoea for children V. cholerae can cause mild diarrhoea but do not generate

under the age of 5 years and improving maternal knowledge epidemics. Recently, new El Tor variant strains have been

related to use of home available fluids, use of ORS and detected in several parts of Asia and Africa. Observations

continued feeding. For details, refer to chapter 7 and 9. suggest that these strains cause more severe cholera with

higher case fatality rates. Careful epidemiological
monitoring of circulating strains is recommended ( 1 ) .
1. WHO (2005), The Treatment of Diarrhoea, A manual for physicians
Recent studies indicate that global warming creates a
and other senior health workers, Department of Child and Adolescent

Health and Development, WHO. favourable environment for the bacteria.

2. UNICEF ( 2 0 1 3 ) , Committing to child s u r v i v a l : A Promise Renewed,
Cholera transmission is closely linked to inadequate
Progress Report 2 0 1 3 .
environmental management. Typical at-risk areas include
3. WHO (2008), Health Situation in the South-East Asia Region, 2 0 0 1 –
peri-urban slums, where basic infrastructure is not available
and in areas, where as a consequence of a disaster,
4. Govt. of India (2014), National Health Profile 2013 (Jan-Dec.),

DGHS, Central Bureau of Health Intelligence, Ministry of Health and disruption of water and sanitation system takes place, or the

Family Welfare, New Delhi. displacement of population to inadequate and overcrowded
5. WHO, UNICEF (2009), Diarrhoea : Why children are still dying and camps. Risk of cholera transmission increases, should the
what can be done.
bacteria be present or introduced. Epidemics have never
6. Stephen J . McPHEE, MAXINEA ( 2 0 1 0 ) , Current Medical Diagnosis
arisen from dead bodies ( 1 ) .
and Treatment, 49th E d . , A Lange publication.

7. Fricker, J., Children in the Tropics 1993 – No.204. Cholera remains a global threat to public health and a

8. UNICEF ( 2 0 1 2 ) , Pneumonia and Diarrhoea, tackling the deadliest key indicator of lack of social development.
disease for the world’s poorest children.
The dynamics of cholera occurrences since 2005,
9. WHO (2007), Weekly Epidemiological Record, No. 37, 10th Oct,
combined with the emergence of new strains that lead to a
more severe clinical presentation; increased antimicrobial
10. WHO (2006), Weekly Epidemiological Record, No. 11, 1 7 March,

2006. resistance and climate change, suggest that cholera may well

11. Christie, A.B. (1980) Infectious Diseases : Epidemiology and Clinical return to the forefront of the global public health agenda (3).
Practice (3rd Ed), Churchill Livingstone.

12. WHO (2006), Weekly Epidemiological Record No. 6, 10th Feb., 2006. INDIA
13. WHO ( 1 9 8 0 ) Bull WHO, 58 (6) 819-830.
Since the introduction of Cholera El Tor biotype in 1964,
14. WHO ( 1 9 9 2 ) Readings on diarrhoea, Student Manual.
the geographic distribution of cholera in India has
15. Pizzarro, D. ( 1 9 8 5 ) . Dialogue on Diarrhoea, Issue No.22 Sept.1985,
considerably changed. West Bengal has lost its reputation as
AHRTAG, 85 Marylebone High Street, London.
the “home” of cholera. Many of the States which never had
16. WHO ( 1 9 8 1 ) . Surveillance and control of acute diarrhoeal diseases.

EURO Reports. Ser.No.44 Copenhagen, WHO. cholera or were free from it for a long time, got infected and

17. R . G . Feachem (1984) Bull WHO 62 (3) 467-476. became endemic foci of El Tor infection. In several of the

18. De, S. et al ( 1 9 7 5 ) , J. Com. Dis., 7 : 124 – 128. recently invaded areas, the disease is seen persisting as a

19. WHO, UNICEF (2004), Clinical Management of Acute Diarrhoea, smouldering infection. The classical severe epidemics with
WHO I UNICEF Joint Statement.
high mortality are now uncommon. Explosive outbreaks,
20. Govt. of India ( 1 9 9 8 ) , Health Information of India 1995 and 1996,
particularly following large fairs and festivals are also now
Ministry of Health and Family Welfare, New Delhi.
21. WHO ( 1 9 8 0 ) , A Manual for the treatment of Acute Diarrhoea, WHO I

COD I SER I 80.2. The bacteriology of cholera also presents a changed


picture. For reasons that are not known, there has been no form in the environment (9, 10). The existence of a free­

large scale epidemic of classical cholera since 1964. In short, living cycle may explain why cholera became endemic for

the El Tor biotype of V. Cholerae 01 has rapidly replaced varying periods in certain areas after introduction of the

the classical biotype in all parts of the country. Most of the El current pandemic strains (9, 10). Atypical non-toxigenic

Tor biotype isolated today belong to the serotype Ogawa. V. cholerae 01 of the El Tor biotype have sometimes been

found in surface waters in e n d e m i c and non-endemic areas
During 2 0 1 3 , about 1 , 1 2 7 cholera cases were reported in
without any related human infection or disease (11). A
India with 5 deaths. The majority cases were reported from
question of considerable epidemiological significance is
Gujarat (327) followed by Maharashtra (247). Karnataka
whether “transmission” of somatic antigen can occur in the
reported 105 cases, Tamil Nadu 93, and West Bengal 120
natural environment, i.e., can non-01 V. cholerae become
cases (4).
V. cholerae 01? (12). Such “transformation” has been

claimed by many workers ( 1 3 ) .
E p i d e m i o l o g i c a l features

Cholera is both an epidemic and endemic disease. The E p i d e m i o l o g i c a l determinants
epidemicity and endemicity of a disease will depend on the

characteristics of the agent, and those of the system Agent factors

(environment). Characteristics of the agent which influence
(a) AGENT : The organism that causes cholera is labelled
its distribution include its ability to survive in a given
as V. cholerae O Group 1 or Vibrio cho/erae 01 and 0 1 3 9 .
environment, its virulence, the average number of
The term “epidemic strain” has also been used for these
organisms required to cause infection, etc. Characteristics of
vibrios. Vibrios that are biochemically similar to the
the system which affect the distribution of the agent include
epidemic strains (V. cholerae 01 and 0139) but do not
the number of susceptibles, and the opportunities it provides
agglutinate in V. cholerae 01 and 0139 antiserum have
for transmission of the infection. Global experience has
been referred to in the past as non-agglutinating (NAG)
shown that the introduction of cholera into any country
vibrios or as non-cholera vibrios (NCV). These are now
cannot be prevented, but cholera can create a problem only
included in the species V. cholerae and are referred to as
in areas where sanitation is defective.
non-0 Group 1 V/ 0 1 3 9 cho/erae (non-epidemic strains). It
Epidemics of cholera are characteristically abrupt and is now recognized that the NCV/NAG vibrios include some
often create an acute public health problem. They have a species that are pathogenic for humans (e.g., Vibrio
high potential to spread fast and cause deaths. The epidemic parahaemolyticus) which have caused outbreaks of cholera­
reaches a peak and subsides gradually as the “force of like diarrhoea. It is, therefore, necessary to identify
infection” declines. Often-times, by the time control V. cholerae 01 and 0139 for specific diagnosis of cholera.
measures are instituted the epidemic has already reached its Within the 0-Group 1 , two biotypes – classical and El Tor,
peak and is waning. Thus, cholera epidemic in a community have been differentiated. It may be mentioned that the El
is self-limiting. This is attributed to the acquisition of
Tor biotype was first isolated at the El Tor quarantine station
temporary immunity, as well as due to the occurrence of a
in Egypt in 1905. Cholera is now caused mostly by the El
large number of subclinical cases.
Tor biotype and 0139. Classical and El Tor vibrios are

The “force of infection” is composed of 2 components, further divided each into 3 serological types namely Inaba,

namely the force of infection through water and the force of Ogawa and Hikojima. Most of the El Tor vibrios isolated in

infection through contacts (5). It is well-known that the India belong to the Ogawa serotype. The El Tor biotype

elimination of contaminated water does not immediately which are known for their haemolytic property, lost this

bring an outbreak to an end, but a so-called “tail” of the property as the pandemic progressed. They may be

epidemic is produced. This is due to the continuation of distinguished from classical vibrios by the following tests :

transmission through contacts ( 5 ) .
( 1 ) El Tor vibrios agglutinate chicken and sheep
In areas where cholera is endemic, it does not show a
stable endemicity like typhoid fever (5). It undergoes
( 2 ) they are resistant to classical phage IV
seasonal fluctuations as well as epidemic outbreaks. The
(3) they are resistant to polymyxin B-50-unit disc, and
seasonal variation differs between countries and even

between regions of the same country. The seasonal (4) the VP reaction and haemolytic test do not give

incidence is also subject to change. For example, the disease consistent results.

used to be most common in the summer in Kolkata and in
(b) RESISTANCE : V. cho/erae are killed within 30
the early winter in Bangladesh; now in both places, it is most
minutes by heating at 56 d e g . C or within a few seconds by
frequent in the autumn (6). In some parts of India, the peak
boiling. They remain in ice for 4-6 weeks or longer. Drying
incidence is in August.
and sunshine will kill them in a few hours. They are easily

The El Tor biotype, wherever it has spread, has become destroyed by coal tar disinfectants such as cresol. Bleaching

endemic with periodic outbreaks. It appears to have greater powder is another good disinfectant which kills vibrios

“endemic tendency” than its classical counterpart in that it instantly at 6 mg/litre. The El Tor biotype tends to be more
causes a higher infection-to-case ratio (i.e., inapparent resistant than do classical vibrios. (c) TOXIN PRODUCTION
infections and mild cases). : The vibrios multiply in the lumen of the small intestine and

Cholera occurs at intervals even in endemic areas. produce an exotoxin (enterotoxin). This toxin produces

A question that is frequently asked is about the fate of diarrhoea through its effect on the adenylate cyclase-cyclic

V. cholerae in the inter-epidemic periods. Three AMP system of mucosa! cells of the small intestine. The

explanations are offered : (a) the existence of long-term exotoxin has no effect on any other tissue except the

carriers ( 7 ) ; ( b ) the existence of diminished but continuous intestinal epithelial cells. (d) RESERVOIR OF INFECTION:

transmission involving asymptomatic cases (8), and (c) the The human being is the only known reservoir of cholera

persistence of the organism in a free-living, perhaps altered infection. He may be a case or tarrier. (i) Cases : Cases


range from inapparent infections to severe ones. About 75 H o s t factors

per cent of people infected with V cholerae do not develop
(a) AGE AND SEX : Cholera affects all ages and both
any symptoms, although the bacteria are present in their
sexes. In endemic areas, attack rate is highest in children.
faeces for 7-14 days after infection and are shed back into
{b) GASTRIC ACIDITY : An effective barrier. The vibrio is
the environment, potentially infecting other people. Among
destroyed in an acidity of pH 5 or lower. Conditions that
people who develop symptoms, about 20 per cent develop
reduce gastric acidity may influence individual
acute watery diarrhoea with severe dehydration. People with
susceptibility ( 1 9 ) . (c) POPULATION MOBILITY: Movement
low immunity, e . g . , malnourished children and people living
of population (e.g., pilgrimages, marriages, fairs and
with HIV are at a greater risk of death if infected ( 1 ) . It is the
festivals) results in increased risk of exposure to infection. In
mild and asymptomatic cases that play a significant role in
this jet age, cases and carriers can easily transfer infection to
maintaining endemic reservoir. (ii) Carriers : The carriers
other countries. ( d ) ECONOMIC STATUS: The incidence of
are usually temporary, rarely chronic. They also make an
cholera tends to be the highest in the lower socio-economic
important contribution to the reservoir of infection. Since
groups, and this is attributable mainly to poor hygiene.
carriers excrete fewer vibrios than clinical cases, carriers are
{e) I M M U N I T Y : An attack of cholera is followed by immunity
best detected by bacteriological examination of the purged
to reinfection, but the duration and degree of immunity are
stool induced by the administration of 30-60 gram of
not known. In experimental animals specific lgA antibodies
magnesium sulphate in 100 ml of water by mouth.
occur in the lumen of the intestine. Similar antibodies in
(e) INFECTIVE MATERIAL : The immediate sources of
serum develop after the infection but only last a few m o n t h s .
infection are the stools and vomit of cases and carriers. Vibriocidal antibodies in serum (titer :2: 1:20) have been
7 9
Large numbers of vibrios (about 1 0 – 1 0 vibrios per ml of associated with protection against colonization and disease.
fluid) are present in the watery stools of cholera patients; The presence of antitoxin antibodies has not been associated
and an average patient excretes 10-20 litres of fluid. with protection (17). Vaccination gives only temporary,
2 5
Carriers excrete fewer vibrios than cases, 10 -10 vibrios per partial immunity for 3-6 months.
gram of stools. (f) INFECTIVE DOSE : Cholera is dose­

related. Infection occurs when the number of vibrios E n v i r o n m e n t a l factors

ingested exceeds the dose that is infective for the individual. Vibrio transmission is readily possible in a community
Experimental work suggests that in the normal person a very with poor environmental sanitation. The environmental
high dose-something like 10 organisms – is required to factors of importance include contaminated water and food.
produce the clinical disease (14). (g) PERIOD OF Flies may carry V cholerae but not vectors of proven
COMMUNICABILITY : A case of cholera is infectious for a importance. Numerous social factors have also been
period of 7 – 1 0 days. Convalescent carriers are infectious for responsible for the endemicity of cholera in India. These
2-3 weeks. The chronic carrier state may last from a month comprise certain human habits favouring water and soil
up to 10 years or more. pollution, low standards of personal hygiene, lack of

education and poor quality of life.
Carriers in cholera ( 1 5 )

Mode of transmission
A cholera carrier may be defined as an apparently

healthy person who is excreting V cholerae 01 (classical or El Transmission occurs from man to man via (a) FAECALLY

Tor) in stools. Four types of cholera carriers have been CONTAMINATED WATER : Uncontrolled water sources such

described (16) : (a) PRECLINICAL OR INCUBATORY as wells, lakes, ponds, streams and rivers pose a great threat.

CARRIERS : Since the incubation period of cholera is {b) CONTAMINATED FOOD AND DRINKS : Ingestion of

short (1-5 days), incubatory carriage is of short duration. contaminated food and drinks have been associated with

The incubatory carriers are potential patients. outbreaks of cholera. Bottle-feeding could be a significant

(b) CONVALESCENT CARRIER : The patient who has risk factor for infants. Fruits and vegetables washed with

recovered from an attack of cholera may continue to excrete contaminated water can be a source of infection. After

vibrios, during his convalescence for 2-3 weeks. preparation, cooked food may be contaminated through

Convalescent state has been found to occur in patients who contaminated hands and flies. There is growing opinion that

have not received effective antibiotic treatment. The El Tor cholera may in some instances be transmitted through

convalescent carriers can often become chronic or long-term a complex interaction of contaminated food, water and

carriers. (c) CONTACT OR HEALTHY CARRIER : This is the environment rather than through public drinking water

result of subclinical infection contracted through association supplies (18). (c) DIRECT CONTACT : In developing

with a source of infection, be it a case or infected countries, a considerable proportion of cases may result from

environment. The duration of contact carrier state is usually secondary transmission, i . e . , person to person transmission

less than 1 0 days; the gall bladder is not infected, and the through contaminated fingers while carelessly handling

stool culture is frequently positive for V cholerae 0 1 . Contact excreta and vomit of patients and contaminated linen and

carriers probably play an important role in the spread of fomites.

cholera. (d) CHRONIC CARRIER : A chronic carrier state
Incubation period
occurs infrequently. The longest carrier state was found to be

over 10 years (16). Studies indicate that gall bladder is From a few hours up to 5 days, but commonly 1-2 days.

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 The main symptom of cholera is diarrhoea. Diarrhoea in

titre against V cholerae 0 1 rises and remains positive as long cholera was attributed in the past to such factors as increased

as the person harbours the organism. This method may be permeability of the intestinal epithelial cells, increased

used to detect long-term carriers along with bacteriological peristalsis, mucosa! damage, an increase in mesenteric blood

examination of stools. flow and failure of the “sodium p u m p ” , i . e . , interference with


the passage of sodium from the lumen to the plasma. None Laboratory d i a g n o s i s of cholera (21)
of these theories stood the test of time ( 1 9 ) .
The diagnosis of cholera can never be made with certainty

According to current concepts, the cholera vibrio get on clinical grounds. Laboratory methods of diagnosis are
through the mucus which overlies the intestinal epithelium. It required to confirm the diagnosis : (a) COLLECTION OF
probably secretes mucinase, which helps it move rapidly STOOLS : A fresh specimen of stool should be collected for
through the mucus. Then it gets attached or adhered to the laboratory examination. Sample should be collected before
intestinal epithelial cells, and this it probably does by an the person is treated with antibiotics. Collection may be made

adherence factor on its surface. When the vibrio becomes generally in one of the following ways : (i) Rubber catheter :

adherent to the mucosa, it produces its enterotoxin which Collection by the catheter is the best method but is
consists of 2 parts – the light or L toxin and the heavy or complicated under field conditions. Soft rubber catheter
H toxin. The L toxin combines with substances in the epithelial (No.26-28) sterilized by boiling should be used. The catheter
cell membrane called gangliosides and this binds the vibrio to is introduced (after lubrication with liquid paraffin) for at least
the cell wall. Binding is irreversible. The mode of action of 4-5 cm into the rectum. The specimen voided may be

H toxin is not fully clear. What we know is that there is a collected directly into a transport (holding) media, e.g.,

substance called “adenyl cyclase” in the intestinal epithelial Venkatraman-Ramakrishnan (VR) medium, alkaline peptone
cells, and H toxin activates this substance. The activated water. (ii) Rectal swab : Swabs consisting of 15-20 cm long

adenyl cyclase causes a rise in another substance, called 3, wooden sticks, with one end wrapped with absorbent cotton,

5-adenosine monophosphate, better known as cyclic or sterilized by autoclaving have been found to be satisfactory.
cAMP (A physiologist got Noble Prize for describing this Rectal swabs should be dipped into the holding medium
substance). cAMP provides energy which drives fluid and ions before being introduced into the rectum. ( i i i } If no transport

into the lumen of the intestine. This fluid is isotonic and is medium is available, a cotton-tipped rectal swab should be

secreted by all segments of small intestine. The increase in soaked in the liquid stool, placed in a sterile plastic bag,

fluid is the cause of diarrhoea, and not increased peristalsis. tightly sealed and sent to the testing laboratory (22).

There is no evidence that V. cholerae invades any tissue, nor ( b ) VOMITUS : This is practically never used as the chances

the enterotoxin to have any direct effect on any organ other of isolating vibrios are much less and there is no advantage.

than the small intestine ( 1 9 ) . (c) WATER : Samples containing 1-3 litres of suspect water

should be collected in sterile bottles (for the filter method), or
Clinical features 9 volumes of the sample water added to 1 volume of 10 per

The severity of cholera is dependent on the rapidity and cent peptone water, and despatched to the laboratory by the

duration of fluid loss. Epidemiological studies have shown quickest method of transport. (d) FOOD S A M P L E S : Samples

that more than 90 per cent of El Tor cholera cases are mild of food suspected to be contaminated with V. cho/erae (or

and clinically indistinguishable from other acute diarrhoeas other enteric bacteria} amounting to 1 to 3 g are collected in

(20). However, a typical case of cholera shows 3 stages : transport media and sent to the laboratory.

( e ) TRANSPORTATION: ( i } The stools should be transported
(a) STAGE OF EVACUATION : The onset is abrupt with
in sterilized McCartney bottles, 30 ml capacity containing
profuse, painless, watery diarrhoea followed by vomiting.
alkaline peptone water or VR m e d i u m . VR medium can be
The patient may pass as many as 40 stools in a day. The
used if larger stool specimens can be collected. The specimen
stools may have a “rice water” appearance. ( b ) STAGE OF
should be transported in alkaline peptone water or Cary­
COLLAPSE : The patient soon passes into a stage of collapse
Blair medium if it is collected by a rectal swab. One gram or
because of dehydration. The classical signs are : sunken eyes,
one ml of faeces in 10 ml of the holding medium will suffice.
hollow cheeks, scaphoid abdomen, sub-normal temperature,
Rectal swabs should have their tops broken off so that caps of
washerman’s hands and feet, absent pulse, unrecordable
the containers can be replaced ( i i } If suitable plating media
blood pressure, loss of skin elasticity, shallow and quick
are available ( e . g . , bile salt agar) at the bed-side, the stools
respirations. The output of urine decreases and may
should be streaked on to the media and forwarded to the
ultimately cease. The patient becomes restless, and
laboratory with the transport media. (f) DIRECT
complains of intense thirst and cramps in legs and abdomen.
EXAMINATION : If a microscope with dark field illumination
Death may occur at this stage, due to dehydration and
is available, it may be possible to diagnose about 80 per cent
acidosis resulting from diarrhoea. (c) STAGE OF
of the cases within a few minutes, and more cases after 5-6
RECOVERY : If death does not occur, the patient begins to
hours of incubation in alkaline peptone water. In the dark
show signs of clinical improvement. The blood pressure
field, the vibrios evoke the image of many shooting stars in a
begins to rise, the temperature returns to normal, and urine
dark sky. If motility ceases on mixing with polyvalent anti­
secretion is re-established. If anuria persists, the patient may
cholera diagnostic serum, the organisms are presumed to be
die of renal failure. The classical form of severe cholera
cholera vibrios. A presumptive diagnosis of cholera can thus
occurs in only 5 – 1 0 per cent of cases. In the rest, the disease
be established. (g) CULTURE METHODS : On arrival at the
tends to be mild characterized by diarrhoea with or without
laboratory, the specimen in holding fluid is well shaken, and
vomiting or marked dehydration. As a rule, mild cases
about 0 . 5 to 1 . 0 ml of material is inoculated into Peptone
recover in 1-3 days.
Water Tellurite (PWT) medium for e n r i c h m e n t . After 4 to 6

Epidemiologically, cholera due to El Tor biotype differs hours incubation at 37 deg. C, a loopful of the culture from

from classical cholera in the following respects : (a} a higher the surface is subcultured on Bile Salt Agar medium (BSA, pH

incidence of mild and asymptomatic infection. This implies 8.6). After overnight incubation, the plates are screened

that the characteristic picture of rice-water stools and other under oblique light illumination for vibrio colonies.

signs of classical cholera described above may not be seen (h) CHARACTERIZATION : V. cho/erae usually appears on

often; (b) fewer secondary cases in the affected families; bile salt agar (BSA) as translucent, moist, raised, smooth and

(c) occurrence of chronic carriers, and (d) since El Tor easily emulsifiable colonies about 1 mm in diameter. The

vibrios are more resistant than classical cholera vibrios, they typical colonies are picked up and tested as follows :

survive longer in the extra-intestinal e n v i r o n m e n t . (i) Gram’s stain and m o t i l i t y : Gram negative and curved rods


with characteristic scintillating type of movement in hanging 4. E s t a b l i s h m e n t of treatment centres

drop preparations are very characteristic of V cholerae
In the control of cholera, no time should be lost in
(ii) Serological test: Slide agglutination test is done by picking
providing treatment for the patients. To achieve this
up suspected colonies and making a homogeneous
objective, it is necessary to establish easily accessible
suspension in 0.85 per cent sterile saline and adding one drop
treatment facilities in the community.
of polyvalent anti-cholera diagnostic serum. If agglutination
The mildly dehydrated patients (which account for over
is positive, the test is repeated with Inaba and Ogawa
90 per cent of cases) should be treated at home with oral
antisera, to determine the subtype. (i) BIOCHEMICAL
rehydration fluid. Severely dehydrated patients, requiring
TESTS : Serologically positive colonies should be subcultured
intravenous fluids, should be transferred to the nearest
in one tube each of the sugar broths (mannose, sucrose,
treatment centre or hospital; if possible, they should receive
arabinose) and a tube of peptone water pH 7.2 for the
oral rehydration on the way to the hospital or treatment
cholera red reaction. Production of acid in sucrose and
centre. If there is no hospital or treatment centre within a
mannose, but not arabinose is characteristic of V cho/erae.
convenient distance, a local school or public building should
be taken over and converted into a temporary treatment
characterization of biotypes of V cholerae organisms are
centre, as close to the site of epidemic as possible.
identified by slide agglutination tests using anti – 01 or group
Transportation of cases over long distances is not desirable;
139 antisera and by biochemical reaction patterns.
it has been linked with the spread of the disease.
Suspicious colonies that do not agglutinate with
In areas where peripheral health services are poor and
anticholera sera are tested further by the oxidase and string

tests ( 1 9 ) . ·
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.

It is now considered that the best way to control cholera

is to develop and implement a national programme for the 5 . Rehydration therapy

control of ALL diarrhoeal diseases because of similarities in Cholera is now the most effectively treated disease.
the epidemiology, pathophysiology, treatment and control of
Mortality rates have been brought down to less than 1 per
cholera and other acute diarrhoeal diseases (23). The cent by effective rehydration therapy. The rehydration
following account is based on the “Guidelines for Cholera may be oral or intravenous. The guidelines for ORT
Control” proposed by the WHO ( 1 1 ) . and intravenous rehydration are discussed in detail on

page 224, 2 2 5 .
1 . Verification of the d i a g n o s i s

It is important to have confirmation of the outbreak as 6 . Adjuncts to therapy

quickly as possible. All cases of diarrhoea should be Antibiotics should be given as soon as vomiting has
investigated even on the slightest suspicion. For the specific stopped, which is usually after 3 to 4 hours of oral
diagnosis of cholera, it is important to identify V cho/erae 0 1 rehydration. Injectable antibiotics have no special
in the stools of the patient. Once the presence of cholera has advantages. The commonly used antibiotics for the
been proved, it is not necessary to culture stools of all cases or treatment of cholera are flouroquinolones, tetracycline,
contacts. Bacteriological diagnosis of cholera envisages a Azithromycin, ampicilline and Trimethoprim TMP­
well-organized system of laboratory services in the Sulfamethoxazole (SMX). No other medication should be
community. given to treat cholera, like antidiarrhoeals, antiemetics,

antispasmodics, cardiotonics and corticosteroids. In regions
2 . Notification where cholera is present, it is important to identify those

Cholera is a notifiable disease locally and nationally. Since antibiotics to which the vibrio cholerae 01 is resistant. If

2005 cholera notification is no · longer mandatory diarrhoea persists after 48 hours of treatment, resistance to

internationally. Health workers at all levels (particularly those antibiotic should be suspected.

who are closest to the community such as the community
7 . E p i d e m i o l o g i c a l investigations
health workers and the multi-purpose workers) should be

trained to identify and notify cases immediately to the local General sanitation measures must be applied at the onset

health authority. Under the International Health Regulations, of an outbreak (see under sanitation measures). At the same

cholera is notifiable to the WHO within 24 hours of its time, epidemiological studies must be undertaken to define

occurrence by the National Government; the number of cases the extent of the outbreak and identify the modes of

and deaths are also to be reported daily and weekly till the transmission so that more effective and specific control

area is declared free of cholera. An area is declared free of measures can be applied. The epidemiologist must maintain

cholera when twice the incubation period (i.e., 10 days) contact with all health and civic units in his area to ensure

has elapsed since the death, recovery or isolation of the last detection of new foci of disease.

case (24).
There are certain institutions which are able to assist in

investigating outbreaks. These include the National Institute
3 . Early case-finding
of Communicable Diseases, Delhi and the All India Institute

An aggressive search for cases (mild, moderate, severe) of Hygiene and Public Health, Kolkata, where

should be made in the community to be able to initiate epidemiological teams are available for investigating

prompt treatment. Early detection of cases also permits the epidemics. In addition, stools for phage typing may be sent

detection of infected household contacts and helps the to the National Institute of Cholera and Enteric Diseases, 3 ,

epidemiologist in investigating the means of spread for Dr lsaque Road, Kolkata-700016, where the WHO

deciding on specific intervention. International Centre for Vibrios is located.


8 . Sanitation measures mass chemoprophylaxis was attempted, it failed to stop the

spread of cholera. Because of these reasons,
(a) WATER CONTROL : As water is the most important
chemoprophylaxis is advised only for household contacts or
vehicle of transmission of cholera, all steps must be taken to
of a closed community in which cholera has occurred.
provide properly treated or otherwise safe water to the

community for all purposes (drinking, w a s h i n g and c o o k i n g ) . Tetracycline is the drug of choice for chemoprophylaxis. It

has to be given over a 3-day period in a twice-daily dose of
Various approaches have been described for supplying

500 mg for adults, 125 mg for c h i l d r e n aged 4 – 1 3 years, and
safe water quickly and with limited resources (25). Facilities

50 mg for children aged 0-3 years. Alternatively, the long­
selected and installed should be appropriate and acceptable

acting tetracycline (doxycycline) may be used for
to the community. The ultimate aim should be provision of

chemoprophylaxis, if the prevailing strains are not resistant.
piped water supply on a p e r m a n e n t basis and elimination of

A single oral dose of doxycycline (300 mg for adults and
alternative unsafe water sources. Because of financial

6 mg/kg for children under 15 years) has proved to be
limitations and other competitive priorities, this measure

cannot be applied immediately on a large scale in

developing countries, such as India. As an emergency
1 0 . Vaccination
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, Two types of oral cholera vaccines are available :

water can be made safe by boiling or by chlorination. The (a) Dukoral (WC-rBS) and (b) Sancho! and mORCVAX. The

emergency measures should be followed by the live attenuated single-dose vaccine (CVD103-HgR) is no

development of more p e r m a n e n t facilities. longer produced.


(b) EXCRETA DISPOSAL : Provision of simple, cheap

(a) Dukoral (WC-rBS)
and effective excreta disposal system (sanitary latrines) is a

basic need of all human settlements. When cholera appears Dukoral is a monovalent vaccine based on formalin and

in a community, the need for these facilities becomes vital. heat-killed whole cells (WC) of V. cholerae 01 (classical and

With the cooperation of the community, sanitary system El Tor, Inaba and Ogawa) plus recombinant cholera toxin B

should be selected and constructed (25), taking into subunit. The vaccine is provided in 3 ml single-dose vials

consideration the customs and practices of the population,
together with the bicarbonate buffer (effervescent granules

the existing terrain and geology, and the available resources.
in sachets to protect the toxin B subunit from being

Simultaneously, health education messages should stress the
destroyed by gastric acid}. Vaccine and buffer are mixed in

proper use of such facilities, the dangers involved in
150 ml of water (chlorinated or not) for persons aged >5

depositing faeces on the ground, and in or near water, and
years and in 75 ml of water for children aged 2-5 years. The

the importance of h a n d w a s h i n g with soap after defecation.
vaccine has a shelf life of 3 years at 2-8°C and remains

(c) FOOD SANITATION : Since food may be an stable for 1 month at 3 7 ° C .

important vehicle of infection, steps should be taken to
Vaccine schedule and administration
improve food sanitation, particularly sale of foods under

According to the manufacturer, primary immunization
hygienic conditions. Health education must stress the

consists of 2 oral doses given “2:.7 days apart (but <6 weeks
importance of eating cooked hot food and of proper

apart) for adults and children aged ;;:,:6 years. Children aged
individual food handling techniques. Cooking utensils

2-5 years should receive 3 doses ;;:,:7 days apart (but <6
should be cleaned and dried after u s e .

weeks apart). Intake of food a n d drink should be avoided for
The housefly plays a relatively small role in transmitting.
1 hour before and after vaccination. If the interval between
cholera, but its prevalence is a general indicator of the level
the primary immunization doses is delayed for > 6 weeks,
of s a n i t a t i o n .
primary immunization should be restarted. Protection may

(d) DISINFECTION : Disinfection should be both
be expected about 1 week after the last s c h e d u l e d dose.

concurrent and terminal. The most effective disinfectant for
Provided there is continued risk of V. cholerae infection,
general use is a coal tar disinfectant with a Rideal-Walker
1 booster dose is recommended by manufacturer, after
(RW) coefficient of 10 or more such as cresol. A disinfectant
2 years for adults and children aged ;;:,:6 years. If the interval
with a RW coefficient of less than 5 should not be used (26).
between the primary series and booster immunization is
Bleaching powder, if used, should be of good quality. For
> 2 years, primary immunization must be repeated. For
disinfection, attention should be paid to the following :
children aged 2-5 years 1 booster dose is recommended
patient’s stools and vomit; clothes and other personal items
every 6 months, and if the interval between primary
that may have been contaminated; the latrine, if any; the
immunization and the booster is > 6 months, primary
patient’s house and neighbourhood.

immunization must be repeated.


9 . Chemoprophylaxis Dukoral is not l i c e n s e d for children aged <2 years.


Studies have shown that approximately 10-12 per cent

(b) Sancho! and mORCVAX
of close household contacts of a cholera case may be

bacteriologically p o s i t i v e , and some of these develop clinical The closely related bivalent oral cholera vaccines are

illness. In contrast, a very small proportion (0.6-1 per cent) based on serogroups 01 and 0139. Unlike Dukoral, these

in the c o m m u n i ty may be excreting vibrios. Mass vaccines do not contain the bacterial toxin B subunit

chemoprophylaxis is not advised for the total community therefore it does not require buffer. According to the

because in order to prevent one serious case of cholera, manufacturer, vaccine should be administered orally in 2

some 10,000 persons must be given the drug. Further, the liquid doses 14 days apart for individuals aged ;;:,:1 year. A

drug’s effect is only short-lived for a few days. Whenever booster dose is recommended after 2 years (27).


1 1 . Health education
The most effective prophylactic measure is perhaps

health education. It should be directed mainly to (a) the
Typhoid fever is the result of systemic infection mainly by
effectiveness and simplicity of oral rehydration therapy
S. typhi found only in man. The disease is clinically
(b) the benefits of early reporting for prompt treatment
characterized by a typical continuous fever for 3 to 4 weeks
(c) food hygiene practices (d) hand washing after defecation
relative bradycardia with involvement of lymphoid tissues
and before eating, and (e) the benefit of cooked, hot foods
and considerable constitutional symptoms. The term
and safe water. Since cholera is mainly a disease of the poor
“enteric fever” includes both typhoid and paratyphoid
and ignorant, these groups should be tackled first.
fevers. The disease may occur sporadically, epidemically or

D i a r r h o e a l D i s e a s e s Control Programme

The incidence of cholera cases and deaths has decreased
Problem statement
in recent years. During the year 1980-81, strategy of the

National Cholera Control Programme has undergone WORLD
changes (28). It is now termed as Diarrhoeal Diseases Control
Typhoid fever occurs in all parts of the world where water
Programme (29). Oral Rehydration Therapy Programme was
supplies and sanitation are sub-standard. The disease is now
started in 1986-87 in a phased manner. The main objective
uncommon in the developed countries where most of the
of the programme is to prevent diarrhoea-associated deaths
cases that occur are either acquired abroad or imported by
in children due to dehydration. The training programme and
immigrants (1). Improved living conditions and the
health education material highlight the rational management
introduction of antibiotics in the late 1940s resulted in
of diarrhoea in children, including increased intake of home
drastic reduction of typhoid fever morbidity and mortality in
available fluids and breast feeding. ORS is promoted as first
industrialized countries. In developing areas of Asia, Africa,
line of treatment. ORS is being supplied as a part of the sub­
Latin America, however, the disease continues to be a public
centre kits (30).
health problem, albeit with incidence rate that vary

considerably between and within countries. In 2004,
WHO estimated the global typhoid fever disease burden
1. WHO ( 2 0 1 4 ) , Fact Sheet No. 107, Feb. 2014.
at 21 million cases annually, resulting in an estimated
2. WHO ( 2 0 1 4 ) , Weekly Epidemiological Record, No. 3 1 , lstAug. 2 0 1 4 .
2 1 6 , 0 0 0 – 6 0 0 , 0 0 0 deaths per year, predominantly in children
3. WHO ( 2 0 1 0 ) , Weekly Epidemiological Record, No. 3 1 , 30th July 2 0 1 0 .
of school age or younger. Majority of this burden occurs in
4. Govt. of India (2014), National Health Profile 2013, Central Bureau of

Health Intelligence, DGHS, Ministry of Health and Family Welfare, Asia (2).

New D e l h i .
Since 1950, the organism’s resistance to antibiotics has
5. Cvjetanovic, B. et al ( 1 9 7 8 ) . Bull WHO, 56 Supplement N o . 1 , p. 76.
also been a growing problem; by 1989 resistance was
6. WHO ( 1 9 8 0 ) Programme for Control of Diarrhoeal Diseases, Scientific
reported in a number of countries, particularly in Asia and
Working Group Reports 1 9 7 8 – 1 9 8 0 , C D D / 8 0 . 1 , WHO, Geneva.
Middle East. Resistant strains have caused outbreaks of the
7. Azurin, J . C . e t a ! ( 1 9 6 7 ) . Bull WHO, 3 7 : 745-749.

8. S i n h a , R. e t a l ( 1 9 6 7 ) . Bull WHO, 3 7 : 89-100. disease in India and Pakistan in recent years. In South-East

9. Nalin, D . R . ( 1 9 7 6 ) . Lancet, 2 : 958. Asia, 50 per cent or more of the strains of the bacteria

10. Levine, M . M . ( 1 9 8 0 ) . N. Eng.J.Med., 302 (6) 345. may already be resistant to several antibiotics (3).

11. WHO ( 1 9 8 0 ) . Guidelines for Cholera Control, WHO/CDD/SER/80.4, Typhoid fever caused by multidrug-resistant (MOR) strains of
S. typhi – that is resistant to all 3 of the first line of
12. Blake, Paul A ( 1 9 8 0 ) . in A n n u a l Review of Microbiology, 3 4 : 3 5 1 .
antibiotics (chloramphenicol, ampicillin and cotrimoxazole)
13. Seal, S . C . ( 1 9 7 7 ) . Ind. J. Pub. Health, 2 1 (2) 48.
– is associated with more severe illness and higher rates of
14. Mackay, D . M . ( 1 9 7 9 ) . Trans. Roy.Soc. Trop.Med & Hyg., 73 ( 1 ) 1 .
complications and death, especially in children aged
15. Seal, S . C . ( 1 9 7 7 ) . Ind. J. Pub. Health, 2 1 (2) 48.
less than 2 years. Also, compared with typhoid fever
16. Shrivastava, D . L . ( 1 9 6 8 ) . J . I n d i a n M.A., 5 0 : 5 8 1 .
caused by sensitive strains, a ten-fold higher rate of
17. Jawetz. Melnick & Adelberg’s Medical Microbiology, 25th Ed. 2010,

A Lange Publications. post-treatment symptomatic bacterial carriers has been

18. Gunn, R.A. e t a l ( 1 9 8 1 ) . Bull WHO, 59 ( 1 ) 65. reported with MOR S . typhi infection (2). Without effective

19. Christie, A . B . ( 1 9 8 0 ) . Infectious Diseases: Epidemiology and Clinical treatment, typhoid fever kills almost 10 per cent of those
Practice, 3rd e d . , Churchill Livingstone. · infected (3).
20. WHO (2004), Weekly Epidemiological Record, N o . 3 1 , July 30, 2004.
The socio-economic impact of the disease is huge,
21. WHO ( 1 9 7 4 ) . Guidelines for the Laboratory Diagnosis of Cholera.
because typhoid survivors may take several months to
22. WHO ( 2 0 0 1 ) , Weekly Epidemiological Record, No. 3 1 , 3 Aug. 2 0 0 1 .
recover and resume work.
23. WHO ( 1 9 7 8 ) . Development of a Programme for Diarrhoeal Diseases

Control, Report of an Advisory Group, WHO/DDC/78.1.

24. Del_on, P.J. (1975). International Health Regulations, A Practical INDIA

G u i d e , WHO, Geneva.
Typhoid fever is endemic in India. Reported data for the
25. Rajagopalan, S. and Shiffman, M.A. ( 1 9 7 4 ) . Guide to Simple Sanitary
year 2013 shows 1.53 million cases and 361 deaths.
Measures for the Control of Enteric Diseases, Geneva, WHO.

26. ICMR ( 1 9 5 9 ) . Report of the Central Expert Committee on Smallpox Maximum cases were reported from Bihar (261,791 cases

and Cholera, New D e l h i . . with 2 deaths) followed by Andhra Pradesh ( 2 3 3 , 2 1 2 cases

27. WHO (2010), Weekly Epidemiological Record, No. 1 3 , 26th March with 5 deaths). The other states having large number of
cases are, Uttar Pradesh (223, 066 cases and 161 deaths),
28. Govt. of India, Ministry of Health and Family Welfare ( 1 9 8 1 ) . Report
Madhya Pradesh (114,578 cases and 28 deaths),
1 9 8 0 –8 1 , Department of Health and Family Welfare, New Delhi.
West Bengal (108,695 cases and 39 deaths), Maharashtra
29. Govt. of India, Ministry of Health & Family Welfare ( 1 9 8 2 ) . Annual
(82,852 cases and 1 death), Odisha (53,743 cases and 35
Report 1981-1982.

30. Govt. of India, A n n u a l Report 1993-94, DGHS, New D e l h i . deaths) ( 5 ) .