Cholera

CHOLERA

Synonymous – Father of public health

Definition – It is an acute bacterial diarrhoeal disease caused by vibrio cholera, the cases may be asymptomatic to severe. Symptomatic cases are charecterised by sudden onset of acute diarrhea followed by vomiting to severe dehydration or muscular cramps and death. Diarrhoea first, then after rice water vomiting occur.

V. Cholerae

Key facts –

ü  Cholera is an acute diarrhoeal disease that can kill within hours if left untreated.

ü  Researchers have estimated that each year there are 1.3 million 4.0 million cases of cholera, and 21,000 – 143,000 deaths worldwide due to cholera.

ü  Up to 80% of cases can be successfully treated with oral rehydration solution (ORS).

ü  Severe cases will need rapid treatment with intravenous fluids and antibiotics.

ü  Safe oral cholera vaccines should be used in conjunction with improvements in water and sanitation to control cholera outbreaks and for prevention in areas known to be high risk for cholera.

ü  A global strategy on cholera control with a target to reduce cholera deaths by 90% was launched in 2017.

History – During the 19^th century, cholera spread across the world from its original reservoir in the Ganges delta in India. Six subsequent pandemics killed millions of people across all continents. The current (7^th) pandemic started in south Asia in 1961, and reached Africa in 1971 and the Americas in 1991. Cholera is now endemic in many countries.

Epidemiology - Cholera can be endemic or epidemic. A cholera endemic area is an area where confirmed cholera cases were detected during the last 3 years with evidence of local transmission (meaning the cases are not imported from elsewhere). A cholera outbreak / epidemic can occur in both endemic countries and in countries where cholera does not regularly occur. An outbreak is defined by the occurrence of at least 1 confirmed case of cholera with evidence of local transmission in an area where there is not usually cholera.

The number of cholera cases reported to WHO has continued to be high over the last few years. During 2017, 1227391 cases were notified from 34 countries, including 5654 deaths.

Agent factors –

(a). AGENT - V. cholera O Group 1 or Vibrio cholerae 01. The term “epidemic strain” has also been used for these vibrios. Vibrios that are biochemically similar to the epidemic strains (V. cholerae 01) but do not agglutinate in V. cholerae 01 antiserum have been referred to in the past non-agglutinating vibrios or non-cholera vibrios but now these included in the species V. cholerae and referred to as non-O Group 1 V. cholerae (non-epidemic strains). Some species that are pathogenic for humans (e.g. Vibrio parahaemolyticus) which have caused outbreak of cholera like diarrhoea.

Within the O Group 1, two biotypes – classical and EI Tor, have been differentiated. EI Tor biotype was first isolated at the EI Tor quarantine station in the Egypt in 1905. Cholera is now caused mostly by the EI Tor biotype.

Classical and EI Tor vibrios are further divided each into 3 serological types namely Inaba, Ogawa and Hikojima. Most of the EI Tor vibrios isolated in India belong to the Ogawa serotype.

(b). RESISTANCE – Vibrio cholera are killed within 30 minutes by heating at 56°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 EI Tor biotype tends to be more resistance than do classical vibrios.

(c). TOXIN PRODUCTION – The vibrios multiply in the lumen of the small intestine and produce an exotoxin (enterotoxin) that caused diarrhoea which due its effect on the adenylate cyclase-syclic AMP system of the mucosal cells of small intestine.

(d). RESERVOIR OF INFECTION – The human being is only known reservoir of cholera. It may be a case (subclinical, mild and severe) or carrier (Preclinical or incubatory, convalescent, healthy and chronic carrier. First 3 carriers are temporary and other one is permanent).

(e). INFECTIVE MATERIAL – Stools and vomit of cases and carriers. Large numbers of vibrios (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/gram of stools.

(f). INFECTIVE DOSE – Cholera is dose related. The dose is 10¹¹ organism are required to produce the clinical disease.

(g). PERIOD OF COMMUNICABILITY – Case of cholera (7-10 days), Convalescent carriers (2-3 weeks) and the chronic carrier state may last from a month up to 10 years or more.

Host factors –

(a). AGE AND SEX – Cholera affected 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.

(c). POPULATION MOBILITY – Movement of population (e.g. pilgrimages, marriages, fairs and festivals) may increase risk of exposure of infection.

(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 - Natural infection confers quite effective immunity. Vaccination gives only temporary, partial immunity for 3-6 months.

Environmental factors – Poor environmental sanitation, personal hygiene, contaminated water, soil, lack of education and poor quality of life.

Mode of transmission – Faecally contaminated water, contaminated food & drinks and direct contact.

Incubation period – From a few hours up to 5 days, but commonly 1-2 days.

Pathogenesis – Vibrio cholera get through the mucus which overlies the intestinal epithelium. It probably secretes the mucinase, which helps it move rapidly thorough the mucus. Then it attached to the intestinal epithelium with the help of adherence factors which is present on its surface. At the time of adherent, it produces exotoxin or enterotoxin which is consists of 2 parts – the light or L toxin and the heavy or H toxin.

Pathogenesis of V. cholerae

The L toxin combines with substances in the epithelial cell membrane called gangliosides and this binds the vibrio to the cell wall, this binding is irreversible.

The mode of action is H toxin is fully not clear. What we know is that there is it activates the “adenyl cyclase” which is present in the intestinal epithelial cells. The activated adenyl cyclase causes a rise in another substance, called 3,5-adenosine monophosphate (cAMP). 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.

Vibrio cholera can attach only intestinal epithelium due to presence of mucinase.

Clinical features – A typical case of cholera shows 3 stages –

(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 stool may have a “rice water” appearance.

(b). STAGE OF COLLAPSE – The patient soon passes due to dehydration and acidosis. The classical signs are – sunken eyes, hollow cheeks, scaphoid abdomen, sub-normal temperature, washerman’s hands and feet, absent pulse, unrecordable blood pressure, loss of skin elasticity, shallow and quick respirations. The output of urine is decrease or cease. The patient become restless, intense thirsty, and complaints cramps in legs and abdomen. Death may occur at this stage.

(c). STAGE OF RECOVERY – If death does not occur, the patient begins to show signs of clinical improvement. The blood pressure to begins to rise, the temperature to return to normal, and urine secretion is re-established. If anuria persists, the patient may die or renal failure. The classical form of severe cholera occurs in only 5-10% cases. In the rest, the disease tends to be mild characterised by diarrhoea with or without vomiting or marked dehydration. As a rule, mild cases recover in 1-3 days.

Laboratory diagnosis of cholera –

REQUIREMENT –

(a). Collection of stools – Sample should be collected before the treatment. Collection may be made generally one of the following ways -

·        Rubber catheter – sterilized, lubricated (paraffin) rubber catheter should be introduced for at least 4-5 cm into the rectum.

·        Rectal swab – It consists 15-20 cm long sterilized (autoclaving) wooden stick with one end cotton based are use.

·        If transport medium unavailable – Cotton tipped soaked in liquid stool and packed in (sterile) plastic bag then sent to laboratory.

(b). Water – 1-3 litre suspected water should be collected in sterile bottle or 90% suspected water with addition of 10% peptone water sent to the laboratory.

(c). Food sample – Suspected food may be contaminated with v. cholera or other enteric bacteria, 1-3 gm food collect and sent to laboratory.

(d). Transportation – Sample transported through McCartney bottle (30 ml capacity), VR (Venkatraman-Ramakrishnan) medium which contain alkaline peptone water.

(e). Direct examination – 80% cases are diagnosed in few minutes If the microscope with dark field illumination is available, remain cases are diagnose after incubation (5-6 hours) in alkaline peptone water.

In the dark field, the vibrios evoke the image of many shooting stars in a dark sky.

(f). Culture method – 0.5-1.0 ml of well shaken sample material is inoculated in Peptone Water Tellurite (PWT). After 4-6 hours (incubation) at 37°C, a loop of the culture from the surface is subcultured on bile salt Agar medium (BSA, pH 8.6). After overnight incubation, the plates are screened under oblique light illumination for vibrio colonies.

(g). Characterisation – V. cholera usually appear on bile salt agar as translucent, moist, raised, smooth and easily emulsifiable colonies about 1 mm in diameter. For categorization of subtypes, Gram stain and motility and Serological test also done.

(h). Biochemical test – Serologically positive colonies should be subcultured in this test.

Control of cholera – Among the people developing symptoms, 80% of episodes are of mild or moderate severity. The remaining 10-20% of cases develops severe watery diarrhoea with signs of dehydration. Once an outbreak is detected, the usual intervention strategy aims to reduce mortality ideally below 1% by ensuring access to treatment and controlling the spread of disease.

The main tools of cholera control are –

1. VERIFICATION OF THE DIAGNOSIS – Confirmation of outbreak as soon as possible.

2. NOTIFICATION – Cholera is a notifiable disease locally, nationally and internationally. Under the international health regulations, cholera is notifiable to 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 decided free of cholera.

 3. EARLY CASE FINDING – An aggressive search for cases should be made in the community to be able to initiate prompt treatment.

4. ESTABLISHMENT OF TREATMENT CENTRE – 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 acceptable treatment facilities in the community.

5. REHYDRATION THERAPY – Basically it has two types oral and intravenous rehydration –

(a). Oral rehydration – The introduction of oral rehydration, by WHO in 1971, has greatly simplified the treatment of cholera and other acute diarrhoeal diseases. The aim of oral fluid therapy is to prevent dehydration and reduce mortality.

           Oral fluid therapy is based on the observation that glucose given orally enhances the intestinal absorption of salt and water, and is capable of correcting the electrolyte and water deficit.

Composition of ORS – bicarbonate and ORS –citrate
Ingredient	ORS – bicarbonate	ORS – citrate
Sodium chloride (Nacl)	3.5 gm	3.5 gm
Sodium bicarbonate (NaHCO3)	2.5 gm	--
Trisodium citrate dehydrate (Na3C6H5O7)	--	2.9 gm
Potassium chloride (Kcl)	1.5 gm	1.5 gm
Glucose (C6H12O6)	20.0 gm	20.0 gm
Potable water	1 litre	1 litre

The inclusion of trisodium citrate in place of sodium bicarbonate has made the product more stable and increasing intestinal absorption of sodium and water. The WHO and UNICEF also recommend ORS –citrate to use.

Packets of “oral rehydration mixture” are now freely available at all primary centres, sub-centres and hospitals. The contents of packet dissolved in one litre water and used within 24 hours. It should not be boiled or sterilized.

If the WHO mixture of salt is not available, a simple mixture consisting of table salt (5gm) and sugar (20gm) and dissolved in one litre drinking water.

Assessment of dehydration
	DEHYDRATION
	Mild	Severe
Patient’s appearance	Thirsty, alert, restless	Drowsy; limp, cold Sweaty; may be comatose
Radial pulse	Normal rate and volume	Rapid, feeble, sometime impalpable.
Blood pressure	Normal	Less than 80 mmHg; may be unrecordable.
Skin elasticity	Pinch retracts immediately	Pinch retracts very slow (more than 2 seconds)
Tongue	Moist	Very dry
Ant. Fontanelle	Normal	Very sunken
Urine flow	Normal	Little or none
% body weight loss	4-5%	10% or more
Estimated fluid deficit	40-50 ml/kg	100-110 ml/kg

Guidelines for oral rehydration therapy (for all ages during the first 4 hours)
Age (*)	Under 4 months	4-11 months	1-2 years	2-4 years	5-14 years	15 years or above
Weight (kg)	Under 5	5-7.9	8-10.9	11-15.9	16-29.9	30+
ORS solution (ml)	200-400	400-600	600-800	800-1200	1200-2200	2200-4000
The patient’s age should only be used if weight is unknown. The approximate amount of ORS in ml. May also be calculated by multiplying the patient weight (kg) by 75. As per requirement ORS solution given more than measure but not less.

(b). Intravenous rehydration – Intravenous infusion is usually required only for the initial rehydration of severely dehydrated patients who are in shock or unable to drink. Such patients are best transferred to the nearest hospital or treatment centre.

The solution recommended by WHO for intravenous infusion are –

a.       Ringer’s lactate solution (Hartmann’s solution for injection).

b.      Diarrhoea treatment solution (DTS) – It contain in 1 litre, sodium chloride 4g, sodium acetate 6.5g, potassium chloride 1g and glucose 10g.

c.       Normal saline – If other one is unavailable. It is the poorest fluid because it will not correct the acidosis and not replace the potassium losses.

The recommended dose of I.V. fluid to be given is 100 ml/kg, divided as follows –

Treatment plan for rehydration therapy
Age	First give 30 ml/kg in	Then give 70/kg in
Infants (<12months)	1 hour	5 hours
Older	30 minutes	2 ½ hours

The initial rehydration should be fast until an easily palpable pulse is present. Reassess the patient every 1-2 hours. If the dehydration is not improving give the IV drip more rapidly. When the patient capable to drink orally then given ORS about 5 ml/kg/hour. Sometimes if too much rehydration fluid is given, the eye lids become puffy; if this occurs, IV fluid should be stopped.

(c). Maintenance therapy –

Maintenance therapy
Amount of diarrhoea	Amount of oral fluid
Mild diarrhoea (less than 5 ml/kg/hour)	100 ml/kg body weight/day until diarrhoea stops
Severe diarrhoea (more than 5 ml/kg/hour)	10-15 ml/kg body weight/hour

6. ADJUNCTS TO THERAPY – Antibiotics should be given as soon as vomiting has stopped, which is usually after 3-4 hours of oral rehydration.

Antibiotics used in the treatment of cholera
Antibiotics(a)	Children	Adults
Doxycycline once	---	300mg (b)
Tetracycline (4 times a day for 3 days)	12.5 mg/kg	500 mg
Trimethroprim (TMP), sulfamethoxazole (SMX) – twice a day for 3 days	TMP 5 mg/kg and SMX 25 mg/kg (c)	TMP 160 mg, SMX 800 mg
Furazolidone (4 times a day for 3 days)	1.25 mg/kg	100 mg (d)
a.       Erythromycin and chloramphenicol may also be used when none of the other recommended antibiotics are available, or when Vibrio Cholerae 01 is resistant to the latter. b.      Doxycycline is the antibiotic of choice for adults (excepting pregnant women), since a single dose suffices. c.       TMP-SMX is antibiotic of choice for children. Tetracycline is equally effective, but is not available everywhere in paediatric form. d.      Furazolidone is the antibiotic of choice for pregnant women.

7. SANITATION MEASURES – Water control, excreta disposal, food sanitation and disinfection, these are the measures of sanitation which helps in prevention of cholera.

8. CHEMOPROPHYLAXIS – 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 (4-13 years) and 50 mg for children (0-3 years).

9. VACCINATION –

·        Types of vaccine -

a.       Killed oral 01 with whole-cell with B-subunit

b.      Killed oral 01 and 0139

·        Number of doses –

a.       Two doses (minimum 1 week and maximum 6 weeks apart). Three doses for children aged 2-5 years (minimum 1 week and maximum 6 weeks apart). Intake of food and drinks should be avoided for 1 hour before and after vaccination.

b.      Two doses 14 days apart for individuals aged 2 years or more than 2 years. One booster dose is recommended after 2 years.

·        Contraindications – Hypersensitivity to previous dose.

·        Adverse reactions – Mild gastrointestinal disturbances.

·        Consider for – Travellers at high risk (e.g. emergency / relief workers)

·        Special precautions – None.

10. HEALTH EDUCATION – About –

a.       Effectiveness and simplicity of oral rehydration therapy.

b.      Benefits of early reporting for prompt treatment.

c.       Food hygiene practices.

d.      Hand washing after defecation and before eating.

e.       The benefit of cooked, hot food and safe water.

Diarrhoeal Diseases Control Programme – The diarrhoeal disease control programme was started in 1978, With the objective of reducing the mortality and morbidity due to diarrhoeal diseases. From 1992-1993, the programme has become a part of child survival & safe motherhood programme. And present, it is a part of NRHM.

Components – Short term ( Appropriate clinical management), Long term ( Better MCH care practices, preventive strategies and preventive diarrhoeal epidemic).

References –

·        Park’s Textbook of PREVENTIVE AND SOCIAL MEDICINE (18^th edition).

·        Kitab at-taadiya.

·        www.who.int (World Health Organization).

·        www.slideshare.net.

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