Cholera
Student notes on the causative agent, history, pathogenesis, clinical features, epidemiology, diagnosis, immunity, treatment and prevention.
Cholera is an acute diarrhoeal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. Cholera remains a global threat to public health and an indicator of inequity and lack of social development. The World Health Organization (WHO) estimates that annually there are 1.4 to 4.0 million cases and 21,000 to 143,000 deaths worldwide from cholera (Ali et al., 2015; Clemens et al., 2017).
During the 19th 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 (seventh) pandemic started in South Asia in 1961, reached Africa in 1971 and the Americas in 1991. Cholera is now endemic in Latin and Central America and sub-Saharan Africa (Kanungo et al., 2022).
Between 1849 and 1854, the London physician John Snow put forth the idea that cholera was an infectious disease transmitted between individuals, with feces containing the infectious agent. He proposed that this agent could contaminate drinking water sources, leading to the spread of cholera. Independently, in 1854, Filippo Pacini in Italy made the initial microscopic observation of comma-shaped bacteria in cholera samples. Later, in 1884, Robert Koch succeeded in isolating Vibrio cholerae in pure culture during his research that began in Egypt and continued in Calcutta (now Kolkata), India (Finkelstein, 1996).
Cholera is caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. V. cholerae is a gram-negative, comma-shaped bacterium that causes acute, large-volume, watery diarrhea that can result in rapid dehydration and hypovolemia. Vibrio cholerae is categorized into over 200 serogroups based on the O antigen present in its lipopolysaccharide. Among these, only the O1 and O139 serogroups are responsible for causing epidemic cholera (Finkelstein, 1996; Mohammadi Barzelighi, Bakhshi, & Boustanshenas, 2016).
V. cholerae O1 has caused all recent outbreaks. Furthermore, O1 strains are divided into three serotypes—Ogawa, Inaba, and Hikojima—classified according to the methylation status of the terminal perosamine of the LPS. Serogroup O1 is also classified into Classical and El Tor biotypes, based on phenotypic and genetic markers (Mohammadi Barzelighi et al., 2016; Clemens et al., 2017). V. cholerae O139, first identified in Bangladesh in 1992, caused outbreaks in the past but has recently only been identified in sporadic cases and has never been detected outside Asia. There is no difference in illness severity caused by the two serogroups (Morris, 2003).
Cholera transmission occurs via the fecal-oral route, with V. cholerae surviving stomach acidity to colonize the small intestine. The bacterium produces cholera enterotoxin (CT), which binds to intestinal epithelial cells and activates adenylate cyclase, elevating cyclic adenosine monophosphate (cAMP) levels. This biochemical cascade causes massive secretion of electrolytes and water into the intestinal lumen, resulting in profuse watery diarrhea (Ali et al., 2015; Clemens et al., 2017). Additionally, the toxin-coregulated pilus (TCP) facilitates bacterial adherence and colonization, an essential step for infection establishment (Clemens et al., 2017).
V. cholerae can persist in environmental reservoirs, including brackish water and estuaries, often associated with plankton and shellfish. Environmental factors such as temperature and rainfall influence the bacterium’s survival and transmission dynamics, contributing to seasonal cholera outbreaks (Morris, 2003).
Cholera is a highly virulent disease that causes severe acute watery diarrhea, often described as “rice water stools.” Symptoms typically appear 12 hours to 5 days after ingesting contaminated food or water (Azman, Rudolph, Cummings, & Lessler, 2013). Cholera affects individuals of all ages and can be fatal within hours if untreated. Most infected persons are asymptomatic, though they shed bacteria in feces for 1 to 10 days, contributing to transmission. Among symptomatic individuals, the majority experience mild to moderate illness, while a minority develop severe dehydration that can lead to hypovolemic shock and death without prompt treatment (Kanungo et al., 2022).
Cholera continues to pose a major public health threat, particularly in low- and middle-income countries. Recent data indicate that nearly three-quarters of cholera outbreaks occur in Africa, with the remainder primarily affecting Asia. Poverty, inadequate water, sanitation, and hygiene (WASH) infrastructure, seasonal rainfall, population density, and population movement are key factors facilitating cholera transmission (Ali et al., 2015; WHO, 2024). In 2024, the World Health Organization reported over 733,000 cases of cholera and acute watery diarrhea across 33 countries, with more than 5,000 deaths (WHO, 2024). Conflict and displacement further exacerbate outbreak risks by disrupting water and sanitation systems, as recently observed in Sudan. Additionally, climate extremes such as floods and droughts have increased cholera transmission by compromising water quality (Azman et al., 2013; Morris, 2003).
Timely and accurate diagnosis is critical for effective cholera control. While clinical diagnosis based on symptoms is often used in resource-limited settings, laboratory confirmation through stool culture or rapid diagnostic tests (RDTs) remains the standard. Recent reviews indicate that although rapid dipstick tests provide practical benefits in outbreak settings, their sensitivity and specificity can vary depending on sample preparation and field conditions (Morris, 2003; Ali et al., 2015). Despite these limitations, RDTs enable prompt public health responses, such as targeted vaccination campaigns and water sanitation interventions (Mayo Clinic, 2023).
Natural infection with Vibrio cholerae typically induces strong immunity, particularly after symptomatic disease. Observational and challenge studies suggest that protection can last for at least three years, although antibody levels often decline within one year post-infection (Finkelstein, 1996; Clemens et al., 2017). The immune response involves both mucosal and systemic components, including memory B cells and secretory IgA, which contribute to long-lasting protection. Older individuals tend to mount more robust immune responses, correlating with lower risk of reinfection (Mohammadi Barzelighi et al., 2016). Oral cholera vaccines (OCVs) mimic natural infection by inducing mucosal and systemic immunity, including antigen-specific IgA and memory B cells. Booster doses enhance immunity and prolong protection (Kanungo et al., 2022).
Oral rehydration solutions (ORS) remain the cornerstone of cholera treatment, with aggressive volume replacement tailored to the severity of dehydration. Initial volume deficits should be replaced within the first 4 to 6 hours, with a total of approximately 350 mL/kg administered within the first 24 hours. Close monitoring of ongoing fluid losses is essential to reduce mortality. Antibiotics such as tetracyclines and macrolides can shorten the duration and severity of symptoms and are used as adjunct therapy (Finkelstein, 1996).
Adequate water, sanitation, and hygiene infrastructure constitute the primary preventive measures against cholera. Oral cholera vaccines (OCVs) offer safe, effective, and affordable outbreak control in high-risk endemic areas. Currently, three WHO-prequalified OCVs—Dukoral®, Euvichol-Plus®, and Euvichol-S®—are available, with two doses required for complete adult protection. Single doses of Euvichol-Plus® or Euvichol-S® provide effective short-term immunity. Euvichol-S®, a simplified variant of Euvichol-Plus®, received WHO prequalification in 2024. The Shancol vaccine is no longer produced (WHO, 2024).
- Ali, M., Nelson, A. R., Lopez, A. L., & Sack, D. (2015). Updated global burden of cholera in endemic countries. PLoS Neglected Tropical Diseases, 9(6), e0003832. https://doi.org/10.1371/journal.pntd.0003832
- Azman, A. S., Rudolph, K. E., Cummings, D. A., & Lessler, J. (2013). The incubation period of cholera: a systematic review. Journal of Infection, 66(5), 432-438. https://doi.org/10.1016/j.jinf.2012.11.013
- Clemens, J. D., Nair, G. B., Ahmed, T., Qadri, F., & Holmgren, J. (2017). Cholera. The Lancet, 390(10101), 1539-1549. https://doi.org/10.1016/S0140-6736(17)30559-7
- Finkelstein, R. A. (1996). Cholera, Vibrio cholerae O1 and O139, and other pathogenic vibrios. In S. Baron (Ed.), Medical Microbiology (4th ed., Chapter 24). University of Texas Medical Branch. https://www.ncbi.nlm.nih.gov/books/NBK8407/
- Kanungo, S., Azman, A. S., Ramamurthy, T., Deen, J., & Dutta, S. (2022). Cholera. The Lancet, 399(10333), 1429-1440. https://doi.org/10.1016/S0140-6736(12)60436-X
- Mohammadi Barzelighi, H., Bakhshi, B., & Boustanshenas, M. (2016). Genetic determinants differences between Vibrio cholerae biotypes. Infectious Epidemiology & Medicine, 2(2), 26–30. https://doi.org/10.18869/modares.iem.2.2.26
- Morris, J. G. Jr. (2003). Cholera and other types of vibriosis: a story of human pandemics and oysters on the half shell. Clinical Infectious Diseases, 37(2), 272-280. https://doi.org/10.1086/375600
- World Health Organization. (2024). Cholera. https://www.who.int/news-room/fact-sheets/detail/cholera
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