Throughout history, severe cholera epidemics have periodically devastated people on every continent. The etiopathogenesis, treatment and prevention guidelines by WHO for cholera are elucidated in this article. 

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Cholera

Vibrio cholerae causes intestinal cholera infection. The condition is characterised by copious, secretory diarrhoea. Cholera is capable of becoming endemic, epidemic, and pandemic. Despite significant improvements in knowledge, the illness continues to pose a barrier to contemporary medicine. Even though it may be asymptomatic or moderate, severe cholera may cause dehydration and death within hours of beginning.

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Perspective from the past

In 1993, outbreaks of the cholera strain V cholerae serogroup O139 (Bengal) occurred in Bangladesh and India. This strain of the disease has become prevalent in at least eleven nations. The Indian subcontinent is susceptible to this illness owing to its extensive coasts, inadequate sanitation, hazardous drinking water, and overpopulation. Recent research has shown that climate also has a significant effect on the persistence and spread of cholera.

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Etiopathogenesis

An epidemic or pandemic outbreak of Cholera may occur at any time. The initiation and maintenance of epidemic and pandemic diseases caused by V cholerae are the consequence of human infection and inadequate sanitation, aided by human migration and the seasonal warming of coastal waters.

V cholerae is a comma-shaped, gram-negative, aerobic or facultatively anaerobic bacillus ranging in size from 1-3 µm by 0.5-0.8 µm. To reach the small intestine, however, the organism must overcome the GI tract's usual defensive systems. Due to its lack of acid resistance, the organism relies on its high inoculum size to tolerate stomach acidity. As a consequence of decreased stomach acidity, the use of antacids, histamine receptor blockers, and proton pump inhibitors increases the risk of cholera infection and predisposes individuals to a more severe illness.

Patients with chronic gastritis due to Helicobacter pylori infection and those who have had a gastrectomy are affected similarly. V cholerae O1 and V cholerae O139 produce an enterotoxin that stimulates the release of fluid and electrolytes into the lumen of the small intestine, hence causing clinical illness.

The consequence is diarrhoea with electrolyte values that are isotonic to plasma. The duodenum and upper jejunum are responsible for fluid loss; the ileum is less impacted. Due to its relative insensitivity to the toxin, the colon is typically in an absorption stage. Nevertheless, the huge amount of fluid generated in the upper intestine exceeds the absorption capacity of the lower intestine, resulting in severe diarrhoea. Unless lost fluids and electrolytes are restored sufficiently, the infected individual may suffer shock from severe dehydration and acidosis from bicarbonate loss.

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Clinical presentation

A 24- to 48-hour incubation period precedes the beginning of symptoms, which start with an abrupt onset of painless, watery diarrhoea that may rapidly become copious and is often followed by vomiting. The patient may have stomach pains as a consequence of the significant amount of intestinal secretions, most likely due to the distention of tiny bowel loops. Generally, fever is absent.

However, the majority of Vibrio cholerae infections are asymptomatic and mild to severe diarrhoea caused by a V cholerae infection may not be identifiable from other causes of gastroenteritis. An estimated 5 per cent of people infected with cholera may develop cholera gravis, characterised by severe diarrhoea, vomiting, and dehydration.

Diarrhoea

Cholera is characterised by copious, watery diarrhoea. Cholera should be suspected when a patient older than 5 years gets severe dehydration due to acute, severe, watery diarrhoea (typically without vomiting) or when a patient older than 2 years with acute watery diarrhoea is in an area where cholera has been identified as an epidemic.

Cholera stool volume is greater than that of other infectious diarrhoeas. Patients with severe illness may have a 24-hour stool volume of more than 250 mL/kg body weight. Cholera patients have frequent and often uncontrollable bowel motions due to the amount of their diarrhoea.

Early in the course of clinical disease, faeces may be present in the stool. The cholera stool is an opaque, white, odourless liquid that is sometimes characterised as having the look of "rice water." (ie, in colour and consistency, it resembles water that has been used to wash or cook rice).

Vomiting

Even while vomiting is a major symptom, it may not always be present. Early in the illness course, vomiting is induced by impaired gastric and intestinal motility; later in the disease course, vomiting is more likely to be caused by acidemia.

Dehydration

Diarrhoea and vomiting, if left untreated, may lead to isotonic dehydration, acute tubular necrosis, and renal failure. Patients with severe illness may have vascular collapse, shock, and death. Dehydration may develop astonishingly quickly, within hours after the commencement of symptoms. This is in contrast to diseases caused by any other enteropathogens.

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Clinical examination

The clinical manifestations of cholera mirror the degree of volume constriction. The quantity of fluid loss and the clinical manifestations of cholera are as follows:

1. 3-5% loss of normal body weight - Excessive thirst.
2. 5-8% loss of normal body weight - Postural hypotension, tachycardia, weakness, fatigue, dry mucous membranes or dry mouth.
3. >10% loss of normal body weight - Oliguria, glassy or sunken eyes, sunken fontanelles in infants; weak, thready, or absent pulse, wrinkled "washerwoman" skin, somnolence, coma.

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Assessment for dehydration

To assist in treatment, the World Health Organisation has divided dehydration in individuals with diarrhoea into three categories:

• Severe
• Some (previously termed moderate, in the WHO criteria)
• None (previously termed mild, in the WHO criteria)

Children who are not clinically dehydrated (i.e., have lost less than 5% of their body weight) may experience an increase in thirst. In children with mild dehydration, cardiac output and vascular resistance are normal, and interstitial and intracellular volume alterations are the major signs of disease. A reduction in skin turgor is indicated by prolonged skin tenting in response to a skin pinch (the most accurate indicator of isotonic dehydration) and a normal pulse.

Before releasing the skin from the squeeze, it is essential to pinch the skin longitudinally rather than horizontally for a few seconds. In individuals with marasmus (severe wasting), kwashiorkor (severe malnutrition with oedema), or obesity, the skin pinch may be less effective.

Other indications of severe dehydration in adults and children older than 5 years include tachycardia, absence or scarcely detectable peripheral pulses, and hypotension.

Tachypnea and hypercapnia are also part of the clinical picture and are caused by the metabolic acidosis that is typically present in dehydrated individuals with cholera.

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Other features 

In children, hypoglycemia is the leading cause of death after dehydration. Hypoglycemia is caused by decreased food intake during an acute illness, depleted glycogen reserves, and faulty gluconeogenesis as a consequence of inadequate gluconeogenic substrate stores in fat and muscle.

Hypokalemia is caused by potassium loss in the faeces, with an average potassium content of around 3.0 mmol/L. Hypokalemia is especially severe in children with a history of malnutrition and depleted potassium reserves, which may present as paralytic ileus.

Rehydration treatment with fluids containing bicarbonate may potentially induce hypocalcemia by lowering the fraction of ionised blood calcium. Frequently, Chvostek and Trousseau symptoms are present, and spontaneous tetanic contractions might occur.

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Diagnosis

The treatment of cholera patients does not need a definitive diagnosis. Priority is given to restoring lost fluids and electrolytes and administering an antibacterial medication when needed in the treatment of diarrhoea.

According to the official case definition of the World Health Organisation (WHO), cholera is suspected when the following symptoms are met:

1. A patient aged 5 or older suffers severe dehydration or dies from acute watery diarrhoea in a region where the illness is not known to be prevalent.
2. A patient aged 5 or older suffers acute watery diarrhoea, with or without vomiting, in an area where cholera is epidemic.

In endemic regions, biochemical confirmation and isolate characterisation are often unnecessary. In regions where Vibrio cholerae is an infrequent isolate, these actions may be valuable. If organism identification is necessary, direct microscopic examination of faeces (including dark-field inspection), Gram stain, culture, and serotype and biotype identification are advised. To detect V cholerae, polymerase chain reaction (PCR) techniques have been established. Both sensitivity and specificity are rather high.

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Treatment

Treatment considerations

The primary priority in treating cholera is rehydration. There are two steps to rehydration: rehydration and maintenance.

The objective of the rehydration phase is to restore normal hydration within four hours. Set the intravenous infusion rate for individuals who are extremely dehydrated between 50 and 100 mL/kg/hour. Since saline does not restore metabolic acidosis, lactated Ringer solution is favoured over isotonic sodium chloride solution.

The objective of the maintenance phase is to maintain normal hydration levels by compensating for continuous losses. The oral route is preferable, and 500-1000 mL/hr of oral rehydration solution (ORS) should be administered.

Rehydration

The WHO has issued guidelines for fluid supplementation in dehydrated individuals. The advice includes suggestions for fluid replenishment in cases of severe dehydration, some dehydration, and no dehydration.

Fluid replacement for dehydration

Severe dehydration

To replenish fluid loss, provide intravenous (IV) fluids soon. If lactated Ringer solution is unavailable, use an isotonic sodium chloride solution instead. If the patient can drink, start administering oral rehydration salt solution (ORS) while the drip is being set up; ORS may supply potassium, bicarbonate, and glucose that saline solution lacks.

For patients older than 1 year, give 100 mL/kg IV in 3 hours—30 mL/kg as rapidly as possible (within 30 min) then 70 mL/kg in the next 2 hours. For patients younger than 1 year, administer 100 mL/kg IV in 6 hours—30 mL/kg in the first hour then 70 mL/kg in the next 5 hours.

Frequent monitoring of the patient is necessary. Following the first administration of 30 mL/kg, the radial pulse and blood pressure should be normal. If the pulse is not yet strong, continue to quickly provide IV fluids. In addition to IV fluids, provide ORS solution (about 5 mL/kg/h) as soon as the patient can swallow.

Reevaluate the hydration condition 3 hours later (infants after 6 h). In the unlikely event that the patient continues to display indications of severe dehydration, repeat the previously administered IV treatment. If any dehydration symptoms are evident, proceed as described below. Maintain hydration if there are no indications of dehydration by replenishing continuous fluid losses.

Some dehydration

Administer ORS solution. WHO ORS contains the following:

• Sodium – 75 mmol/L
• Chloride – 65 mmol/L
• Potassium – 20 mmol/L
• Bicarbonate – 30 mmol/L
• Glucose – 111 mmol/L

A homemade counterpart consists of six tablespoons of sugar and one-half teaspoon of salt in one litre of water; a half cup of orange juice or banana purée may add potassium.

If the patient's weight is unknown, simply use their age. The estimated quantity of ORS needed (in mL) may also be determined by multiplying the patient's weight (in kilograms) by 75.

No signs of dehydration

Patients who first exhibit no indications of dehydration may be treated at home. Give these patients enough ORS packets for two days to take home. Show how to prepare and provide the answer. Instruct the patient or caregiver to return to the hospital if any of the following symptoms develop:

1. Increased number of watery stools.
2. Eating or drinking poorly.
3. Marked thirst.
4. Repeated vomiting.
5. Any signs indicating other problems (eg, fever, blood in stool).

Maintenance of hydration

Patients who exhibit severe or some dehydration should continue to be hydrated. Replace fluids lost continuously until the diarrhoea ceases.

When a patient who has been rehydrated with IV fluids or ORS solution is reviewed and no indications of dehydration are present, continue administering ORS solution to maintain normal hydration. The goal is to replace stool losses with an equal quantity of ORS solutions as they occur.

At least every four hours, reevaluate the patient for indications of dehydration to verify that sufficient ORS solution is being administered. Patients with persistent diarrhoea must be monitored more often. Before continuing with therapy to maintain hydration, the patient should be rehydrated if certain indicators of dehydration are seen.

Antibiotic treatment

In individuals with severe cholera, an efficient antibiotic may lessen the amount of diarrhoea and minimise the time that V cholerae O1 is expelled. Additionally, it often stops diarrhoea within 48 hours, hence reducing hospitalisation time. Antibiotic treatment should be directed wherever feasible by susceptibility reports.

Antibiotic therapy is suggested for kids older than 2 years who are severely dehydrated. After the patient has been rehydrated (typically within 4-6 hours) and vomiting has ceased, begin antibiotic medication. There is no benefit to taking pricey injectable antibiotics. No additional medications should be used to treat cholera. Typically, antimicrobial medicines are used for 3-5 days (see Table 6). However, it has been proven that a single dosage of tetracycline, doxycycline, furazolidone or ciprofloxacin may reduce the length and severity of diarrhoea. Because it has been shown that a single dosage of doxycycline is equally effective as numerous doses of tetracycline, this regimen has become the standard of care.

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WHO guidelines for cholera management

1. Evaluate dehydration
2. Maintain hydration
3. Replenish continuous fluid losses until diarrhoea subsides.
4. Administer an oral antibiotic to the severely dehydrated patient
5. Feed the individual

The following are more specific instructions for the management of cholera:

1. Evaluate the patient's degree of dehydration upon arrival. • Rehydrate the patient in two phases: rehydration (for 2 to 4 hours) and maintenance (until diarrhoea abates).
2. Record output and intake quantities on predesigned charts and examine these data frequently.
3. Use the intravenous route only during the rehydration phase for severely dehydrated patients for whom an infusion rate of 50-100 mL/kg/h is recommended, for moderately dehydrated patients who cannot tolerate the oral route, and during the maintenance phase for patients considered to be high stool purgers (i.e. >10 mL/kg/d).
4. Utilise oral rehydration solution at a rate of 800–1000 mL/h during the maintenance phase; match continued losses with ORS administration.
5. Discharge patients if their oral tolerance is at least 1000 mL/h, their urine volume is at least 40 mL/h, and their stool volume is at least 400 mL/h.

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Prevention

Preventing the spread: Cholera prevention begins with a clean water source and proper sanitation.

WHO advises that oral cholera vaccinations be included in cholera control programs in endemic regions, in addition to existing preventative and control techniques.

Oral cholera vaccines with international licensure and commercial availability include :

1. Bivalent killed whole-cell vaccine (eg, Shanchol, Shantha Biotechnics-Sanofi Pasteur, India; or Euvichol, EuBiologics, Republic of Korea) – Contains killed whole cells of several biotypes and serotypes of V. cholerae O1 and V. cholerae O139 without supplemental cholera toxin B subunit. Its efficacy has been evaluated in several trials in India and Bangladesh [86-90]. Vaccine efficacy in these trials ranged from 53 to per cent and persisted for five years following vaccination.
2. WC-rBS (eg, Dukoral, Crucell, Sweden): It contains killed whole cells of several biotypes and serotypes of V. cholerae O1 in addition to recombinant cholera toxin B subunit. The vaccine was associated with 78 per cent protection.

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This is the next article of our monsoon series. To read the earlier articles of the series, click here:Managing dengue fever: What you should know; Malaria in monsoon: Recent updates ;Leptospirosis: A commonly misdiagnosed disease

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.