The Lancet

Volume 363, Issue 9404, 17 January 2004, Pages 223-233

Seminar
Cholera

https://doi.org/10.1016/S0140-6736(03)15328-7 Get rights and content

Summary

Intestinal infection with Vibrio cholerae results in the loss of large volumes of watery stool, leading to severe and rapidly progressing dehydration and shock. Without adequate and appropriate rehydration therapy, severe cholera kills about half of affected individuals. Cholera toxin, a potent stimulator of adenylate cyclase, causes the intestine to secrete watery fluid rich in sodium, bicarbonate, and potassium, in volumes far exceeding the intestinal absorptive capacity. Cholera has spread from the Indian subcontinent where it is endemic to involve nearly the whole world seven times during the past 185 years. V cholerae serogroup O1, biotype El Tor , has moved from Asia to cause pandemic disease in Africa and South America during the past 35 years. A new serogroup, O139, appeared in south Asia in 1992, has become endemic there, and threatens to start the next pandemic. Research on case management of cholera led to the development of rehydration therapy for dehydrating diarrhoea in general, including the proper use of intravenous and oral rehydration solutions . Appropriate case management has reduced deaths from diarrhoeal disease by an estimated 3 million per year compared with 20 years ago. Vaccination was thought to have no role for cholera, but new oral vaccines are showing great promise.

Section snippets

Epidemiology

Cholera is often described as the classic water-borne disease because it is commonly associated with water. This description oversimplifies the transmission of V cholerae, because the bacterium can be transmitted by contaminated food also; contaminated water is frequently mixed with food, allowing either to act as a vehicle. For more developed countries, contaminated food (especially undercooked seafood) is the usual vehicle for transmission, and contaminated water is more common in less

Clinical features

After an incubation period of between about 18 h and 5days, symptoms are generally abrupt and include watery diarrhoea and vomiting. The most distinctive feature of cholera is the painless purging of voluminous stools resembling rice-water (figure 1). The stools are sometimes described as having a fishy odour. The vomitus is generally a clear, watery, alkaline fluid. In adults with severe cholera, the rate of diarrhoea may quickly reach 500–1000 mL/h, leading to severe dehydration. Signs of

Treatment

Without treatment the case-fatality rate for severe cholera is about 50%. However, treatment is very effective and simple and is based on the concept of replacing fluids as fast as they are being lost (panel). Replacement fluids should have a similar electrolyte composition to the fluids being lost. Initially, the fluids must be given sufficiently rapidly to make up for the volume that has already been lost to restore circulating blood volume. Additional maintenance fluids must then be given to

Antimicrobial resistance

Widespread antibiotic resistance in V cholerae was unheard of before 1977, but conjugative-plasmid-mediated multiply antibiotic-resistant (including to tetracycline) V cholerae O1 (MARV) emerged as a major problem first in Tanzania52 then in Bangladesh.53 During the past two decades, reports from several cholera-endemic countries of strains resistant to antibiotics including tetracycline, ampicillin, kanamycin, streptomycin, sulphonamides, trimethoprim, and gentamicin have appeared. Unlike

Clinical microbiology

V cholerae is a gram-negative, polar monotrichous, oxidase-positive, asporogenous curved rod that ferments glucose, sucrose, and mannitol and is positive in the lysine and ornithine decarboxylase tests. The organism is classified by biochemical tests and is further subdivided into serogroups based on the somatic O antigen. The O antigen shows enormous serological diversity, with over 200 serogroups.63 Only the O1 and O139 serogroups cause epidemic and pandemic disease. Strains identified by

Subtypes of V cholerae

The O1 serogroup is divided into two biotypes, classical and El Tor, that can be differentiated by use of assays of haemolysis, haemagglutination, phage, polymyxin B sensitivity, and the Voges-Proskauer reaction. The latest approach, however, is to use biotype-specific genes (eg, tcpA, rtxC) to differentiate between the two biotypes. Each of the O1 biotypes can be further subdivided into two major serotypes, Ogawa and Inaba. Ogawa strains produce the A and B antigens and a small amount of C,

Clinical pathophysiology

Ingested vibrios from contaminated water or food must pass through the acid stomach before they are able to colonise the upper small intestine. Colonisation is aided by way of fimbria, filamentous protein structures called toxin coregulated pilus (TCP) extending from the cell wall, that attach to receptors on the mucosa,82 and by the bacterium's motility, which helps to penetrate the mucus overlying the mucosa. V cholerae adhering to the M cells in rabbit intestine without causing any tissue

Virulence factors

At the molecular level, the pathogenesis of cholera is a multifactorial process and involves several genes encoding virulence factors that aid the pathogen in its colonisation, coordinated expression of virulence factors, and toxin action. In V cholerae, the major virulence genes required for pathogenesis are in clusters and can apparently propagate laterally and disperse among different strains. Genetic analyses have revealed the presence of two important genetic elements that distinguish a

Ecology of V cholerae

The general assumption, until quite recently, was that cholera was spread only by infected people to other susceptible individuals via faecal contamination of water and food and that global movement of populations accounted for the global movement of the disease. Recent studies of the aquatic environment, however, have shown that V cholerae, including strains of O1 and O139, are normal inhabitants of surface water, particularly brackish waters, and survive and multiply in association with

Prevention of cholera and vaccines

Contaminated food and water are the main vehicles of transmission of V cholerae and much can be done to keep transmission rates to a minimum. The measures include ensuring a safe water supply, (especially for municipal water systems), improving sanitation, making food safe for consumption by thorough cooking of high-risk foods (especially seafood), and health education through mass media. Some important messages for the media during outbreaks include the importance of purifying water and

Conclusion

At the beginning of the 21st century, cholera remains an epidemic or endemic disease in much of the world. Research has revealed much about the pathogenesis and the genetics of V cholerae, and has provided simple and effective methods for treatment. New epidemic strains are likely to develop, evolve, and spread. V cholerae cannot be eradicated; it is a part of the normal flora and ecology of the surface water of our planet. Thus, we have to learn to coexist with the vibrios. An understanding of

Search strategy

We carried out a PubMed search with the terms "cholera" and "Vibrio cholerae" from 1966 onwards and selected references that were pertinent to this review. These articles were supplemented by additional references from the WHO and historical articles in our personal collections.
Conflict of interest statement
None declared.

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