Cholera is the pandemic that just won’t go away. Worse yet, it preys on us when we are at our most vulnerable, after a natural or man-made disaster. We know how to prevent it but in times of natural disaster or in areas where infrastructure is inadequate, those conditions can be hard to maintain. A review of cholera’s chain of infection illustrates the challenges of containing cholera.
Scientific name: Vibrio cholerae
Common names: cholera, Asiatic cholera
The causative agent of cholera is Vibrio cholerae, a facultative, gram-negative bacterium. There are 155 known serogroups, differentiated by their O antigen. Only two serogroups, O1 and O139, are responsible for all epidemic and endemic cholera. The O1 serogroup can be further differentiated into three serotypes, Ogawa, Inaba, and (rarely) Hikojima, that can themselves be divided into two biotypes (genotypes), classical and El Tor (Faruque, Albert, & Mekalanos, 1998). V. cholerae O139, which is responsible for the on-going epidemic in Bangladesh and India, evolved from the El Tor biotype of serogroup O1 (Heymann, 2004). This chain of infection is restricted to serogroups O1 and O139, which have epidemic potential.
There are two major virulence factors of pathogenic V. cholerae. The primary virulence factor is cholera toxin responsible for the rice water diarrhea. The toxin gene is carried by a lysogenic bacteriophage (bacterial virus) ensuring that this mobile toxin gene will continue to create new pathogenic strains (Nelson et al, 2009). Haiti’s current outbreak by an altered El Tor strain with a classical B toxin gene is an example of the bacteriophage’s effect on V. cholerae‘s diversity. Biofilms are important in both the intestinal and aquatic environments. V. cholerae’s other major virulence factor, toxin co-regulated pilus, binds together islands of bacteria (Nelson et al, 2009). Another bacteriophage carries an island of antibiotic resistance genes (Nelson et al, 2009). However, antibiotics are usually not critical to cholera treatment because its not an invasive pathogen.
There are two reservoirs for V. cholerae O1 and O139: humans and the aquatic environment. Humans are considered the primary reservoir and can be asymptomic carriers (Heymann, 2004). These bacteria are considered hyperinfective immediately upon release from the human body as defined by a significantly lower infectious dose required to cause an infection (Nelson et al, 2009). It has been shown that V. cholerae changes its gene transcription pattern shortly before release from the intestine as part of its ‘escape response’ to prepare it for survival in the aquatic environment (Nelson et al, 2009).
V. cholerae exists in both fresh water, such as the Ganges River delta, and marine environments. In the Ganges River delta, where V. cholerae has been endemic for centuries (at least), it exists in wide variety of serotypes, toxigenic and non-toxigenic, though only toxigenic O1 El Tor and O139 serotypes are found in symptomatic patients (Nelson et al, 2009). An aquatic reservoir exists in Bangladesh where V. cholerae O139 has been shown to be a strain adapted to flourish in an environment changed by global warming (Koelle, Pascule, & Yunus, 2005). A poorly defined reservoir exists in the Gulf of Mexico associated with shellfish. Two cases of V. cholerae O1 were identified in a couple who ate poorly cooked shellfish after Hurricanes Katrina and Rita in Louisiana in 2005 (Straif-Bourgeois et al., 2006)
Portal of Exit
The portal of exit from the human reservoir is from the anus in fecal waste. Faruque et al. (2006) has shown that humans shed fragments of V. cholera biofilm into the environment. Symptomatic patients begin shedding hyperinfectious bacteria from before diarrhea begins and continue to shed for one to two weeks (Nelson et al, 2009). Asymptomatic cases are believed to shed bacteria for only a day (Nelson et al, 2009). The portal of exit from the aquatic reservoir is in water used for drinking or food preparation, or in contaminated shellfish (Heymann, 2004).
Mode of Transmission
Whether the reservoir is human or aquatic, the primary mode of transmission is ingestion of water or food prepared with water containing V. cholerae. During an outbreak, there can be hand-to-mouth communication of V. cholerae (Heymann, 2004). Rare epidemics and sporadic cases of V. cholerae O1 have been contracted from eating poorly cooked shellfish in waters that have not been contaminated with sewage (Heymann, 2004). It is also a category B bioterrorism agent for water contamination (Boatwright & Greenfield, 2005).
Portal of Entry
The portal of entry is through the mouth in contaminated water or food.
Previous infection produces variable immunity depending on the initial infection biotype (Heymann, 2004). Herd immunity appears to be a protective factor in endemic areas but its nature is not well understood. In endemic areas hospitalizations are highest among young children, peaking around age 2 years (Nelson et al, 2009). In epidemics where there is no herd immunity cholera infects all age groups (Nelson et al, 2009).
V. cholerae responds differently to the human ABO blood groups. Paradoxically, blood group O has a lower risk of infection but those who are infected have more serious symptoms and worse outcomes (Nelson et al, 2009). The mechanism(s) at play here are not well understood. Blood group O’s “low prevalence in the Ganges River delta suggests that there is selection against this phenotype in a cholera-endemic area” (Nelson et al 2009: 694).
Vulnerable populations include anyone put at risk by dehydration. This would include all infants, young children, pregnant women, the elderly, and people with other health conditions where hydration levels must be closely monitored. Fluid losses can be has high as 1 liter per hour causing rapid, severe dehydration and metabolic acidosis (Nelson et al, 2009).
Vaccine trials are underway. There is no approved cholera vaccine for the United States.
Boatwright, D. T. & Greenfield, R. A. (2005). Bioterrorism and threats to water safety: cholera and cryptosporidiosis. In Biodefense: Principles and Pathogens (pp. 587-618). Bronze, M. S. & Greenfield, R.A. (Eds). Norfolk, England: Horizon Bioscience.
Faruque SM, Albert MJ, & Mekalanos JJ (1998). Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae. Microbiology and molecular biology reviews : MMBR, 62 (4), 1301-14 PMID: 9841673
Faruque SM, Biswas K, Udden SM, Ahmad QS, Sack DA, Nair GB, & Mekalanos JJ (2006). Transmissibility of cholera: in vivo-formed biofilms and their relationship to infectivity and persistence in the environment. Proceedings of the National Academy of Sciences of the United States of America, 103 (16), 6350-5 PMID: 16601099
Heymann, D. L. (Ed.). (2004). Cholera and other Vibroses: I. Vibrio cholerae serogroups O1 and O139. In Control of Communicable Disease Manual. (p. 103-111). 18th ed. Washington, DC: American Public Health Association.
Koelle, K., Pascual, M., & Yunus, M. (2005). Pathogen adaptation to seasonal forcing and climate change Proceedings of the Royal Society B: Biological Sciences, 272 (1566), 971-977 DOI: 10.1098/rspb.2004.3043
Nelson EJ, Harris JB, Morris JG Jr, Calderwood SB, & Camilli A (2009). Cholera transmission: the host, pathogen and bacteriophage dynamic. Nature reviews. Microbiology, 7 (10), 693-702 PMID: 19756008
Straif-Bourgeois, S., Sokol, T, Thomas, A, Ratard, R, Greene, KD, Mintz, E, et al. (2006). Two cases of toxigenic Vibrio cholerae 01 infection after hurricanes Katrina and Rita – Louisiana, October 2005, Morbidity & Mortality Weekly Report, 55, 31-32.
For more information see:
Todar, Kenneth. (2011) Vibrio cholerae and Asiatic Cholera, Todar’s Online Textbook of Bacteriology, retrieved February 2011.