Approach
If treated properly, no patient with cholera should die. Making a formal diagnosis of cholera is not essential for treatment to begin. Many patients will present in the context of a larger outbreak. Urgent rehydration is fundamentally the most important feature of treatment and should be instituted as soon as possible.[2] Intravenous rehydration is usually started for severely volume-depleted patients, but oral replacement solution (ORS) is the mainstay of therapy for mild-to-moderate disease and should be added to intravenous therapy as soon as is clinically possible.
Antibiotics reduce both the severity and length of disease and should be used where possible. Rising resistance rates of Vibrio cholerae mean that careful choice based on local epidemiology is crucial. There is some evidence for adjuvant vitamin and micronutrient supplements in specific cases. Antisecretory agents have not been shown to be as useful as investigators initially thought.
Good medical and nursing care is important, but most treatments outlined can be given by allied health professionals, volunteers, and, in the context of epidemics, family members.
Notification and local infection, prevention, and control (IPC) measures
Regardless of the setting (endemic/non-endemic), healthcare professionals must follow appropriate notification mechanisms to report suspected or confirmed cholera cases to local health authorities. Equally important is to ensure all necessary IPC measures are in place to minimise the risk of onward transmission in healthcare and community settings.
The World Health Organization (WHO) offers a cholera case report form designed for data collection directly from patient findings and review of hospital or clinical notes of patients with suspected, probable, or confirmed cholera disease.[92]
Volume depletion severity
Degree of volume depletion is generally divided into those with severe (>10%) and mild-to-moderate (<10%) volume depletion.[3] Treatment can be provided accordingly.
Mild (<5% volume depletion): alert but tachycardic, dry mucous membranes, small postural blood pressure (BP) drop (<20 mmHg), able to drink fluids; in young children, anterior fontanelle palpable but not sunken.
Moderate (5% to 10% volume depletion): irritability, sunken eyes, dry mouth, significant (>20 mmHg) postural drop in BP, mildly decreased skin turgor, thirst.
Severe (>10% volume depletion): lethargy or coma, circulatory collapse (e.g., thready pulse, systolic BP <80 mmHg), sunken eyes, absent tears, dry mucous membranes, poor (>2 seconds) capillary return, decreased skin turgor, biochemical evidence of prerenal failure (e.g., elevated urea disproportionately higher than creatinine in a ratio of >20:1).
Rehydration and feeding
Appropriate rehydration is the most effective clinical intervention, reducing mortality from 40% to about 1%.[3] Starting intravenous rehydration is initially based on the degree of volume depletion and the availability of useful quantities in the developing world.
Patients should be given a normal diet as soon as they are able to eat, including reinstituting breastfeeding as soon as possible after the initial catch-up rehydration phase has been completed.
Severe volume depletion
Precisely calculating volume depletion is difficult. The equations provided may be used in balance with clinical judgement.
Catch-up fluid is given over the first 2 to 4 hours, followed by replacement fluid for ongoing losses. Calculating required fluid may be done using the simple equation: % dehydration x body weight (kg) = number of litres fluid required.
For example, a 60-kg patient who presents with severe (10%) volume depletion will need 6 litres of intravenous fluid over 2 to 4 hours or 1.5 to 3 litres per hour.
The WHO recommends 30 mL/kg over 30 minutes followed by 70 mL/kg over 2 to 3 hours.
WHO/UNICEF: clinical management of acute diarrhoea Opens in new window
Accounting for insensible losses is also important. For example, a 60-kg patient needs 480 to 960 mL every 24 hours or 20 to 40 mL per hour to make up for insensible losses. For a 6-kg child, using an assumption of 0.3 to 0.5 mL/kg/hour, the maintenance is 2 mL per hour to make up for insensible losses.
If intravenous fluid is not available, fluid can be given via a nasogastric tube in obtunded patients, providing that it is possible to check the position of the tube post-placement (e.g., chest x-ray or litmus paper testing confirming acidic aspirated stomach contents).
Because the secretory diarrhoea in cholera is high in sodium, potassium, and bicarbonate, Ringer's lactate or Hartmann solutions (rather than normal saline or 5% dextrose) should be used. With the loss of bicarbonate and potassium in the stool, cholera patients have a profound metabolic acidosis and total body potassium depletion. With correction of the acidosis, the potassium concentration decreases further. Thus, potassium should be replaced through inclusion of potassium in intravenous or oral fluids regardless of initial potassium level.
Mild-moderate volume depletion
If patients are able to take significant amounts of oral fluid when offered, oral rehydration is usually preferred. This has the added benefit of avoiding the complications of intravenous fluids, such as infection at the cannula site, pain, and needlestick injuries.
Duration of therapy: aggressive catch-up rehydration for 2 to 4 hours is followed by maintenance fluids until diarrhoea abatement, which is usually 2 to 5 days later. Accurate fluid balance is needed, hence the use of the cholera cot, which enables the patient to purge while lying flat and the medical staff to measure the enteric loss. The aim is to replace hourly losses with an equal volume of oral or intravenous fluids. Accounting for insensible losses is also important. For example, a 60-kg patient needs 480 to 960 mL every 24 hours or 20 to 40 mL per hour to make up for insensible losses. For a 6-kg child, using an assumption of 0.3 to 0.5 mL/kg/hour, the maintenance is 2 mL per hour to make up for insensible losses.
Several types of ORS are available: in the epidemic setting, the standard WHO ORS come pre-packed and contain (all in mmol/L) Na+ 75, K+ 20, Cl- 65, citrate 10, and glucose 75, with an osmolality of 245 mOsm/L. A Cochrane review comparing different osmolality ORS for people with diarrhoea due to cholera suggested that asymptomatic hyponatraemia might occur more frequently with lower osmolality ORS (≤270 mOsm/L) compared with ORS with an osmolality ≥310 mOsm/L.[93] [
]
However, if possible, rice-based ORS with a similar concentration of electrolytes should be used for cholera, because this reduces the volume of purging. The use of polymer‐based ORS (e.g., rice- or wheat-based products) may be associated with reduced stool volume and duration of diarrhoea compared with glucose-based ORS.[94] Care should be taken in the epidemic setting to ensure that the water used for ORS has been boiled or appropriately treated.
Antibiotic therapy
Antibiotics can reduce diarrhoea volume and duration and shorten the period of V cholerae shedding.[95]
Current guidelines recommend single-dose oral antibiotic treatment for patients who:[44][95][96][97][98]
Are severely ill
Have severe, or some level of, dehydration with high stool purging (one or more motion per hour during the first 4 hours of rehydration treatment)
Are pregnant
Have comorbidities (e.g., HIV) that pose elevated risk in cholera illness.
Antibiotic therapy should be given as soon as the patient can tolerate oral medicine.
Single-dose doxycycline is recommended as first-line treatment for adults (including pregnant women) and children. Historically, tetracyclines were contraindicated for pregnant women due to concerns about potential teratogenic effects, and for children younger than age 8 years (age <12 years in some countries such as the UK) due to risk of dental discoloration. However, a recent systematic review did not demonstrate such correlations with the use of doxycycline.[99]
While doxycycline is the preferred first-line treatment, the choice of antibiotic should be informed by local antibiotic susceptibility patterns.[2] If resistance to doxycycline is documented, a single dose of azithromycin or ciprofloxacin is recommended as an alternative option.[97][98] In the UK, tetracyclines are not recommended for use in children aged 12 years or under.
Systemic fluoroquinolone antibiotics, such as ciprofloxacin, may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[100]
Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability).
Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.
A Cochrane review of controlled clinical trials (randomised and quasi-randomised) in adults and children with cholera found that, compared with placebo or no treatment, antimicrobial therapy:[95]
[ ]
Shortened the mean duration of diarrhoea by about 1.5 days (mean difference -36.77 hours, 95% CI -43.51 to -30.03, 19 trials, 1013 participants)
Reduced the total stool volume by half (ratio of means 0.5, 95 % CI 0.45 to 0.56, 18 trials, 1042 participants)
Reduced the amount of rehydration fluids required by 40% (ratio of means 0.60, 95% CI 0.53 to 0.68, 11 trials, 1201 participants).
Furthermore, the review found that antimicrobial therapy reduced faecal V choleraeshedding by almost 3 days compared with placebo or no treatment (mean duration -2.74 days, 95% CI -3.07 to -2.40, 12 trials, 740 participants).[95]
Whenever possible, the choice of antibiotic should be guided by a knowledge of susceptibility patterns of recently isolated local V choleraestrains. In low-income countries, antibiotic choice is likely to be limited by what is available in sufficient quantities to cope with high demand, and susceptibility testing is likely to take longer than the mean duration of illness, forcing empirical therapy. A wide range of antibiotics have shown activity against V cholerae, including tetracyclines (e.g., doxycycline, tetracycline), fluoroquinolones (e.g., ciprofloxacin), sulfa drugs (e.g., trimethoprim/sulfamethoxazole), and macrolides (e.g., erythromycin, azithromycin).
In the Cochrane review of antimicrobial therapy for cholera, direct comparisons found tetracycline and doxycycline (three trials of very low quality, 230 participants) and tetracycline and ciprofloxacin (three trials of moderate quality, 259 participants) to be similarly efficacious with respect to reduction in the duration of diarrhoea and reduction in stool volume.[95] However, indirect comparisons (that included more trials) suggested that tetracycline may reduce diarrhoea duration and stool volume compared with doxycycline, and trimethoprim/sulfamethoxazole.[95]
Some evidence suggests that tetracycline and erythromycin given over a 3-day period may decrease shedding of V cholerae in the stool, but there is good evidence for using a single dose of some drugs such as doxycycline, ciprofloxacin, and azithromycin.[74][88][101][102]
Adjunctive therapies
Vitamins and micronutrients
There is little good evidence for vitamin and micronutrient supplements in the treatment of cholera, with the exception of zinc in children. A trial that looked at the effect of oral zinc supplementation in children with cholera showed that zinc supplementation significantly reduced the duration and severity of diarrhoea.[103] The mechanism is likely to be due to an effect on enterocyte ion transportation, with zinc opposing the cholera-toxin-induced electrolyte secretion.[104]
The WHO recommends vitamin A supplementation for children aged over 6 months in resource-poor settings where malnutrition is likely to be a problem. Children with diarrhoea in these settings are particularly at risk of vitamin A deficiency and should receive high-dose supplementation.[105][106][107] One Cochrane review has shown that in children aged 6 months to 5 years living in rural or urban/periurban settings, vitamin A supplementation is associated with a clinically meaningful reduced risk of all-cause mortality; specifically, with a 12% reduction in overall mortality and death due to diarrhoea.[108]
Antisecretory agents
There is no evidence that agents such as loperamide or antisecretory agents (e.g., somatostatin analogues or nicotinic acid) have any benefit in the treatment of cholera.
Nursing care
Patients with moderate and severe volume depletion and those with high rates of purging (e.g., >1 L/hour) should be nursed on a cholera cot. These simple beds, made with a hole in the middle and of material that can be disinfected between patients, allow close monitoring of fluid losses by recording hourly fluid losses and, thus, the following hour's target fluid replacement. Cholera cots can be made locally.
Isolation of cases is usually difficult in outbreaks but essential in developed-world settings when returning travellers are being managed. The organism is not difficult to kill with standard cleaning agents available in medical facilities.
Patients may excrete bacteria for up to 14 days in the recovery phase. They should be warned to use simple hygiene measures such as handwashing after bowel movements.
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