Introduction

Definition and background of cholera 

Cholera is an acute diarrhoeal disease caused by the bacterium Vibrio cholerae, particularly strains belonging to the serogroups O1 and O139.¹ It has historically ravaged regions with poor infrastructure, sanitation, and limited access to clean water, and is especially prevalent in developing countries. Cholera thrives in environments during natural disasters or refugee crises.¹ Vibrio cholerae can exist in two main environments: brackish-water ponds and the human gut.¹ It spreads from environmental reservoirs to humans primarily through contaminated food or water.

The infectious dose (amount of bacteria needed to cause disease) of V. cholerae is high, as most bacteria die after their initial exposure to our stomach acid. However, once in the intestine, V. cholerae colonises the gut and secretes cholera toxin (CT), which disrupts ion transport in the gut, leading to severe diarrhoea and vomiting. 

Understanding the epidemiology, genetics, and ecology of toxin-producing V. cholerae is crucial for controlling and preventing cholera outbreaks. The bacterium's ability to persist in water sources and its complex interactions with environmental factors contribute to the emergence of new epidemic strains. Despite advancements in treatment and vaccination efforts, cholera remains a significant public health concern, causing millions of cases and tens of thousands of deaths annually. 

Importance of understanding cholera symptoms

Understanding cholera is crucial for several reasons:

• Epidemiological insights: cholera outbreaks exhibit a high degree of clustering by location and season, affecting many developing countries. Recognizing these patterns helps public health officials anticipate and respond to outbreaks effectively. Additionally, understanding which groups are most vulnerable to infection (namely children aged 1 to 5 years in endemic areas) informs targeted intervention strategies.
• Antibiotic resistance monitoring: cholera strains frequently develop antibiotic resistance, posing challenges for treatment. Monitoring these resistance patterns is essential for selecting appropriate antibiotic therapies and preventing the spread of resistant strains.
• Historical context: studying the history of cholera pandemics provides valuable insights into the evolution and spread of the disease. Lessons learned from past pandemics, such as the seventh pandemic that began in 1961 and the emergence of V. cholerae O139 in the early 1990s, inform current prevention and control efforts.²
• Transmission dynamics: understanding how cholera spreads through the faecal-oral route, both directly between individuals and indirectly through contaminated water and food sources, is essential for implementing preventive measures. Factors such as mass gatherings, inadequate sanitation, and population movements can exacerbate transmission, highlighting the importance of sanitation and hygiene interventions.
• Genetic and ecological considerations: genetic analysis of cholera strains provides insights into the diversity of epidemic strains and their adaptation to different environments. Furthermore, studying the survival of V. cholerae on various surfaces and its potential transmission by flies and fomites informs strategies for controlling environmental reservoirs and interrupting transmission routes.
• Public health interventions: improved sanitation, hygiene practices, access to safe water, and vaccination campaigns are crucial for cholera prevention and control. Understanding the effectiveness of these interventions and their impact on reducing the cholera burden is essential for guiding public health policies and resource allocation.

What is the clinical presentation of cholera?

Symptoms at a glance 

Cholera, caused by V. cholerae bacteria, presents a spectrum of symptoms ranging from mild to severe, with the most severe cases termed cholera gravis. Here's a description of the symptoms:^3,4

• Incubation period: The time between exposure to the bacteria and the onset of symptoms can vary, ranging from several hours to 5 days.
• Onset of illness: symptoms may begin suddenly or occur before signs such as weight loss, abdominal discomfort, and simple diarrhoea.
• Diarrhoea: the hallmark symptom is profuse, watery diarrhoea. Initially, the stool may contain faecal matter, but it soon becomes pale grey with a characteristic rice-watery appearance due to mucus. The feeling of passing stools is absent, and there's often a feeling of relief as large amounts of fluid are effortlessly passed.
• Vomiting: vomiting often accompanies diarrhoea, and usually appears a few hours after the onset of diarrhoea.
• Cholera gravis: in severe cases, the rate of diarrhoea and/or vomiting can be extremely high, leading to dehydration. This dehydration can lead to a higher heart rate, low blood pressure, and collapse of blood vessels. Furthermore, skin elasticity becomes poor, eyes appear sunken, and hands and feet may become wrinkled. Severe dehydration can cause patients to become extremely thirsty and lethargic or restless, and it may also impair their phonation - meaning they can only speak in a whisper. Major mental status alterations are uncommon in adults.
• Muscle Cramps: painful muscle cramps may occur, likely due to low potassium levels.
• Temperature: body temperature is usually normal or subnormal, although low-grade fever can occur in up to 20% of individuals.³
• Dehydration: dehydration is reflected in higher plasma protein concentration, number of red blood cells, serum creatinine, urea nitrogen, and plasma specific gravity. Loss of bicarbonate in the stool and build of lactate in the blood associated with dehydration can result in too much acid in the blood. Despite profound potassium loss, uncorrected acid levels in fluid levels may result in a normal or high serum potassium level. Decreased blood flow and oxygenation of kidney tissue due to prolonged circulatory collapse may be seen in patients with delayed or inadequate treatment.
• Children: low blood glucose levels with coma and convulsions may occur in children.

Manifestation of symptoms in different stages 

Cholera manifests in distinct stages, each marked by specific symptoms:^5,6,7

1. Incubation period: bacteria often multiply in the small intestine during the first few hours and five days. There are often little or no symptoms at all. 
2. Acute stage: this stage can begin suddenly and progress rapidly within a few hours to a couple of days after the ingestion of any contaminated food or water. The symptoms include severe watery diarrhoea, which can lead to dehydration and electrolyte imbalance. This diarrhoea can be painless whilst plentiful and frequent, leading to significant fluid loss. Other symptoms may also include vomiting, making dehydration worse. Signs of severe dehydration are rapid heart rate, low blood pressure and sunken eyes. Decreased blood volume and electrolyte imbalances may cause muscle cramps, cold skin and weakened pulse. 
3. Recovery stage: the recovery stage typically begins within a few days with prompt and adequate treatment. Symptoms gradually improve with a decrease in frequency and severity of diarrhoea and vomiting. Additional complications, like shock and organ failure, can be prevented by rehydration therapy because it replaces lost fluids and electrolytes, allowing the body to regain balance. 
4. Post-recovery stage: as individuals get over the acute illness of cholera, they may continue to have bacteria released in their stools for up to two weeks. Whilst the body recovers, some individuals may experience a period of weakness or fatigue. Depending on the severity of the infection and the individual’s overall health, the time to regain full strength and energy may be long.

Cholera can be life-threatening if it is not diagnosed and treated quickly. As such, it is vital that the symptoms of cholera are recognised early so that appropriate medical interventions - including rehydration therapy and antibiotics - can be given.

How are cholera symptoms managed effectively?

Rehydration therapy 

Rehydration therapy is the primary treatment for cholera. It aims to replace the lost fluids and electrolytes caused by V. cholerae infection. Oral rehydration therapy (ORT) has been a major breakthrough since its introduction in 1964, significantly reducing the mortality rate associated with cholera.⁸

Glucose-based formulations are particularly effective as they help stimulate the absorption of electrolytes, such as sodium (salt), into the small intestine. However, rice-based formulations can also be successfully used. Starch-based ORT formulations have shown particular promise due to their resistance to metabolic degradation in the gut. Therefore, starch can remain longer than glucose and stimulate the synthesis of fatty acids, which also support electrolyte absorption.

For severely dehydrated patients, intravenous (IV) fluid therapy may be necessary, using solutions such as Ringer’s lactate or the “Dhaka solution” which contains glucose, potassium, and bicarbonate to prevent electrolyte imbalances.⁶ These patients must be carefully monitored and may need a high-energy diet post-rehydration to prevent complications. 

Antibiotic therapy 

Several antibiotics are effective against V cholerae, including tetracycline, azithromycin, and doxycycline.⁶ Azithromycin is recommended for most patients - including pregnant women and children - due to its safety profile. However, the choice of antibiotic may vary depending on several factors, such as local antibiotic susceptibility patterns and individual patient characteristics.

Antibiotic resistance in V. cholerae has become a global concern, as it significantly complicates treatment strategies. Resistance has been observed against various antibiotics commonly used for cholera treatment, including tetracycline, ciprofloxacin, and trimethoprim-sulfamethoxazole.⁶ This resistance can emerge due to chromosomal mutations and the transfer of mobile genetic elements (MGEs) conferring drug resistance between different bacterial species.

Role of supportive care in symptom management 

Supportive care plays a crucial role in cholera management, focusing on alleviating the severity of symptoms, enhancing immune response, and preventing complications. This may involve:

• Probiotics: probiotic bacteria can play a significant role in preventing the colonisation and multiplication of V. cholerae in the gut.⁶ 
• Prevention of disease using antibiotics: Antibiotics can be used to prevent cholera from spreading, particularly among close contacts with cholera patients.
• Micronutrient supplementation: micronutrients, such as zinc and vitamin A, play a crucial role in reducing the severity and duration of cholera symptoms, particularly in children.⁶ Further, maintaining a high-calorie diet can help prevent several complications of cholera such as potassium deficiency, low glucose levels, and malnutrition - even if diarrhoea is still present.

Summary

Understanding how cholera causes disease and spreads is essential for effectively managing outbreaks, reducing the morbidity and mortality of infections, and eliminating the disease as a global public health threat. The symptoms of cholera (namely diarrhoea and vomiting) can appear and worsen rapidly, leading to severe dehydration and electrolyte imbalances if not promptly treated. Early recognition and intervention are crucial to prevent complications and reduce mortality.