Abstract
Cholera, caused by an infection resulting from the bacterium Vibrio cholerae entering into the host’s body, is a severe disease characterised by acute secretory diarrhea. This illness affects up to an estimated four million individuals across the globe annually. The condition is marked by disturbances in the electrolytic balance, and significant fluid loss; this can lead to hypovolemic shock and even death in severe cases. This article aims to provide an overview of the etiology and method of transmission utilised by the bacterium, and to describe the epidemiology and pathophysiology of the disease. Additionally, it will list the treatment measures administered to recover from the disease.
Introduction
Cholera is a severe diarrheal disease resulting from the ingestion of food or water that is contaminated with the bacterium Vibrio cholerae shown in Figure 1.1[1][2] - a motile, rod-shaped, served, Gram-negative prokaryotic organism that thrives in aquatic environments[3]. This disease continues to pose a significant global health risk and is a representative marker of social inequity and lack of development. Figures gathered by organisations like the World Health Organisation (WHO) suggest that there are between 1.3 and 4.0 million cholera cases per year of which 21,000 to 143,000 are fatalities internationally[2].
Cholera can lead to acute watery diarrhea and severe dehydration. The symptoms typically manifest within 12 hours to 5 days following the consumption of the aforementioned contaminated substances. Both children and adults are susceptible to the disease which can be fatal within hours if the patient does not receive prompt treatment. Individuals residing in areas with unsafe drinking water, insufficient sanitation and poor hygiene practices are especially vulnerable to cholera, making it a critical public health crisis particularly in regions with substandard sanitary conditions and countries impacted by natural disasters, where access to safe drinking water is restricted[1][2].
While many individuals infected with Vibrio cholerae remain asymptomatic, the bacterium can still be found in their feces 1 to 10 days post-infection. This allows for potential transmission to others which is accelerated in areas with inadequate sanitization. However, cholera is often predictable and preventable. It can be effectively eradicated in communities, provided that they are supplied with reliable access to clean water, proper facilities, and the implementation of good hygiene practices for the entire population living in that region[2].
Etiology and Method of Transmission
Vibrio cholerae is commonly found in developing countries. Two serotypes, O1 and O139, have been recognised and deemed responsible for cholera outbreaks. The O1 serotype is linked to all recent epidemics, while the O139 serotype is associated with sporadic cases in Asia in particular. There is no significant etiological distinction between the two serotypes. Vibrio cholerae is typically present in food, especially shellfish, in water that is inadequately sanitized, or the feces of a previously infected individual. Consequently, the transmission of this bacterium occurs by either the consumption of contaminated water and food, ingesting uncooked/raw shellfish or the fecal-oral route. This makes it endemic in regions where the hygiene is insufficient[1][4].
The substantial amount of bacteria needs to be ingested for the infection to occur. Several factors can heighten susceptibility to cholera, including[4]:
The use of proton pump inhibitors (PPIs): PPIs may elevate the risk of cholera by modifying the gut microbiome and diminishing gastric acid production, thereby facilitating the invasion of pathogens into the gastrointestinal system[5].
Individuals with type O blood: The expression of blood group O by gastrointestinal epithelial cells facilitate a quicker response to CT, the primary effector molecule of Vibrio cholerae that is responsible for cholera related diarrhea[6].
Previous vagotomy: Vagotomy is a surgical intervention that involves the removal of a portion of the vagus nerve. This may lead to diarrhea as a potential complication. Diarrhea is a characteristic symptom associated with cholera and can occur following vagotomy due to a phenomenon known as gastric dumping- a condition that triggers an influx of water into the gastrointestinal lumen, ultimately leading to diarrhea[7].
Epidemiology
When cholera emerged in the form of an epidemic within a population that has not previously been exposed to the bacterium, it can affect individuals encompassing all age demographics. Oppositely, in areas where cholera is endemic, a significant portion of the adult population will have developed some sort of natural immunity due to prior infections. In such environments, the disease predominantly impacts young children who are encountering Vibrio cholerae for the first time. It may also affect the elderly who experienced reduced gastric acid production and have a diminished immunity. Vulnerable populations are particularly at risk because they often lack access to clean water fit for consumption, they struggle to maintain adequate hygiene practices at home and may rely on unregulated sources like street vendors for food and beverages [8].
Globally, there are approximately four million cholera cases reported each year, resulting in over 140,000 fatalities linked to the disease. Nearly 1.8 million individuals worldwide source their drinking water from locations contaminated with human feces, which can serve as a reservoir for cholera bacteria[1][2]. Outbreaks are particularly prevalent in developing countries where sanitation and water purification standards are often inadequate. Currently, cholera is endemic in around 50 countries, primarily in Asia and Africa. The incidence of the disease is associated with seasonal patterns, influenced by the timing of the local rainy season. However, epidemics can extend beyond these regions, affecting areas such as South and Central America. The introduction of cholera to a new area, particularly following a breakdown in hygiene and health services, has been known to trigger widespread epidemics[9].
Pathophysiology
Pathophysiology examines the mechanisms by which diseases caused by bacteria, viruses and fungi etc or injuries disrupt the usual functioning of the body’s systems, a disarrangement that leads to biochemical and functional alterations[11].
Vibrio cholerae, as stated before, is a gram-negative, comma-shaped bacillus that thrives in both aerobic and anaerobic conditions. Its antigenic composition includes a somatic O antigen and flagellar H antigen, the latter of which is used to differentiate pathogenic strains of the bacteria from nonpathogenic ones. In order to reach the small intestine, Vibrio cholerae must endure the stomach’s acidic environment as it is not inherently resistant to acid. Due to this very reason, a substantial inoculum is necessary for it to withstand gastric acid[10][12]. Upon successfully passing through the stomach, Vibrio cholerae colonizes the small intestine. It attaches to the epithelial cells and proliferates while producing the cholera toxin. This toxin is subsequently internalised by the epithelial cells of the intestine.
The cholera toxin contains the toxic A subunit and five B subunits, which are responsible for receptor binding. Once bound to GM1 receptors, cholera toxin is endocytosed and trafficked to the endoplasmic reticulum where the A and B subunits dissociate. That activates a chemical called adenylate cyclase - this results in an increase in cyclic adenosine monophosphate (cAMP) levels. Elevated (cAMP) levels activate a protein known as kinase A; this inhibits the absorption of sodium and chloride ions from the microvilli while simultaneously promoting the secretion of chloride and water from the crypt cells.The resulting osmotic gradient leads to an overall movement of water into the intestinal lumen, resulting in the secretory diarrhoea characteristic of cholera. The toxin also changes electrolyte channels within the epithelial cells. This causes a loss of endoluminal fluid that is rich in chloride, bicarbonate, sodium and potassium. Once excreted into the environment, Vibrio cholerae remains infectious for a while, which may play a significant role in the rapid spread of cholera outbreaks[10]. Figure 1.2 shows the mechanism of the virus.
A host’s susceptibility to infection is influenced by prior exposure to bacterium as being infected previously can confer immunity. However, this immunity is varied based on the biotype and serotype of the strain encountered before. As a labile acid organism, a considerable inoculum is necessary to induce infection in a healthy adult. This requirement explains why reduced gastric acidity can lower the threshold for infection by the bacteria[1].
Treatment for Cholera
The alterations caused by the bacterium present clinically as a passage of large volumes of stools that resemble rice water, hence the term ‘rice water stools’ is used to describe the condition observed in severe cases of cholera. This results in significant dehydration. The primary approach to managing cholera-related diarrhea involves the administration of oral rehydration solutions (ORS) to replenish the fluids and electrolytes lost in the form of stool. WHO advocates for the use of rice-based ORS specifically for cholera-diarrhea management[14].
Initial attempts to employ oral rehydration as a treatment option administered to the patient was only partly effective due to the lack of understanding regarding the physiological needs for sodium-glucose co-transport. The development of ORS in the late 1960s marked a significant advancement in cholera management as it used equal molar concentrations of sodium and glucose to enhance sodium absorption in the small intestine while systematically addressing the fluid losses[13].
Despite various efforts to enhance ORS formulations, further research is required to assess some of the proposed modifications. This includes the incorporation of amylase-resistant starch, the addition of zinc and the utilisation of amino acids like glycine, alanine and glutamine to ORS to make it more effective and efficient[14].
Alternatively, antibiotics serve as a supplementary treatment for individuals with moderate to severe dehydration due to cholera. Antibiotics are a class of medicinal drugs that directly attack the causative bacteria, in this case Vibrio cholerae. Similar to other infectious diseases, the use of antibiotics in cholera can lead to an increase in antimicrobial resistance. Nevertheless, effective antibiotics can significantly decrease the duration of diarrhea and lessen stool output by as much as 50%. These medications also shorten the time period during which viable organisms are present in the stool egested out. They are able to reduce it from several days to a maximum of 2 days. It is recommended by professionals that antibiotics be administered after the initial fluid deficit has been addressed with measures such as ORS and the vomiting has subsided. It should ideally be within four hours of starting treatment[15].
Conclusion
Cholera poses a considerable public health challenge and it necessitates the cooperation of a multidisciplinary healthcare team. Enhancing health outcomes for individuals affected by Vibrio cholerae in developing nations where resources tend to be scarce is a pressing concern in the domain of public health. It is essential to implement collaborative efforts at both a local and global, national and international level to assess, diagnose, and treat cholera patients and prevent its spread. Additionally, while clean water, sanitation and hygiene systems are instrumental in reducing its transmission, vaccination is a viable, cost effective and ultimately safer option for controlling outbreaks in high-risk areas.
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