Introduction
Cholera is an acute diarrheal infectious disease caused by Vibrio cholera bacteria. The disease characteristics are acute rice water, severe diarrhea and vomiting, which may lead to dehydration, shock, and eventually death within hours if not treated. In underdeveloped countries, the disease is seasonal mainly in summer because of poor sanitation and ineffective infra structure for safe water supply. Epidemics (cholera outbreaks) occur at times of natural disasters that create complex emergencies (Deen et al, p. e173).
Organism
V. cholera is a gram negative curved motile bacillus that live normally in aquatic environment associated with plankton (Hsiao et al, p. 14542). Of the more 200 strains (serogroups) of V. cholera, only V. cholera O1 and O139 are responsible for epidemics. O refers to an organism antigen, O1 and O139 are lipopolysaccharides with a specific oligosaccharide; besides the capsule of the O139 serotype, they are responsible for adhesion to epithelial cells of the small intestine and consequently colonization (Schild et al, p. 131).
V. cholera O1 serotype is further classified into a classical and E1Tor according to polymyxine B sensitivity or resistance. Of the eight cholera pandemics since the 19th Century, V. cholera O1 of the classical type is blamed for six pandemics, O1 E1Tor and O139 each is responsible for one. The O139 serotype emerged in 1992 and is thought to be genetically related to E1Tor serotype but with new lipopolysaccharides and capsule biosynthesis genes. V. cholera is transmitted by fecal-oral route through contaminated water, and can live for sometime in fresh and salt water (Schild et al, pp. 131-136).
In their infection reservoir (water), V. cholera faces limited nutrient sources, osmolarity, and temperature challenges. In their host (humans), the challenges are different and include surface immunoglobulins secreted by epithelial cells and the mucin glycocalyx. V. cholera faces these challenges by toxT transcription regulator responsible for activating a set of virulence genes mediating colonization in the host environment (Hsiao et al, pp. 14542-14547).
Cholera pathogenesis
Cholera is a toxin-mediated disease. The cholera toxin is a protein that has five B subunits and one A subunit that are responsible for the symptoms of V. cholera infection. First the B pentamer (5 subunits) binds to the pentasaccharide moiety (bond) of ganglioside GM1 present on the cell membrane of the intestinal epithelial cells and modulates cell signal transduction. Together, the B pentamer and GM1 form a complex known as lipid raft, which helps to fix the toxin to the membrane for endocytosis of the A subunit. As the A subunit is endocytosed (engulfed) by the intestinal cell (a process that takes about 15 minutes), a disulphide bond breaks resulting in two compounds A1 and A2 subunits. The A1 subunit has enzyme activity increasing the intracellular cyclic AMP; thus, blocking sodium chloride absorption by intestinal microvilli with consequent water excretion from intestinal cell to preserve osmotic balance. This process is responsible for the severe diarrhea characteristic of cholera disease (Patocka and Streda, p. 9).
Epidemiology of cholera
In 2006, the WHO report on cholera in 2005 based on data collected from 52 countries pointed to 30% increase in the total number of cases reaching 131943 cases with a little over 1.7% mortality rate. In West Africa regions, serious outbreaks reported in 14 countries affecting 58% of the global cases in 2005 (WHO report (b), p. 297). Codeco and Coelho (p. e42) noticed that cholera outbreaks have two characteristic features; first, nearly simultaneous appearance in different areas, which suggest an environmental trigger. Second is the fulminating nature of the outbreak, which is not still fully explained.
Vaccination against cholera
Water and food sanitation and improving personal hygienic habits are essential to cholera prevention. However, this may not be easily achievable in many parts of the world; therefore, vaccination of high risk population is an important prevention measure especially during epidemics or in endemic areas (WHO report (a), p. 118). The protective immunity given by cholera vaccination is antibody mediated produced in intestinal mucosa. The antibodies inhibit bacterial colonization and block the toxin action, IgA antibodies are the most important in terms of protection, although IgM, IgG are also produced. Cholera antibodies develop naturally in patients recovering from the disease; however, their level returns to baseline in about six months post infection (WHO report (a), pp. 120-121).
There are two types of cholera vaccination; parenteral and oral. The parenteral vaccine is inactivated (phenol killed whole organism) V. cholera O1, and although available for over 40 years; yet, it has weak protection of short duration. It does not prevent transmission of the organism; in addition, it is not effective against V. cholera O139, which produce more serious outbreaks with higher mortality rates. It is administered intradermally or subcutaneously in two doses, separated by two weeks interval (WHO report (a), pp. 118, 122).
Oral vaccination against V. cholera carries the hope for a single dose long-lasting immunity. However, Provenzano et al (2006, p. 918) suggested that a universal one dose oral cholera vaccine is far from reality because of intrinsic difference in host immune response to different V. Cholera serotypes. In addition, host age, socioeconomic, and nutritional status all play a role in determining the response. According to the WHO report (a) (p. 118) oral vaccination is suitable for travelers to endemic areas.
Diagnosis of cholera
Diagnosis of cholera is often on clinical backgrounds depending on characteristic diarrhea, which is of acute onset, watery (rice water), and stools is of large volume about 1 liter per hour. Accompanying diarrhea is rapidly progressive dehydration, which may threaten life, with its secondary symptoms like sunken eyes, lethargy, dry mouth, and severe thirst. Nausea and vomiting may occur either early or late in the course of disease with muscle cramps because of electrolytes (especially sodium chloride). Shock will follow severe uncontrolled fluid loss. Laboratory diagnosis depends on identifying the organism in a stool sample examination (Mayo Clinic staff, 2009).
However, direct sample examination may not show the organism (mechanical wash out secondary to severe diarrhea). Therefore, stool culture is needed on enriched media like alkaline water peptone, or agar media enriched with thiosulphate, citrate, bile salts and sucrose (Bopp et al, p. 37).
Treatment of cholera
Rehydration is the main stay in treating a cholera case to avoid shock and possible death. It runs in two phases, phase 1is primary hydration, which can be by oral hydrating mixtures or more commonly parenteral as patient are usually too ill to compensate for fluid loss by mouth. Lactated ringer and or saline solution are given over four hours at a rate of 500 ml/kg/hour. When hydration is restored, therapy shifts to phase 2 that is maintaining hydration, where fluids are given in a dose of 500 to 1000 ml/hour guided by the stools volume (Page, p. 28).
Antibiotic therapy aims at decreasing the volume of diarrhea, reducing its duration, and decreasing the duration of excretion of V. cholera in the stools. Traditionally tetracyclines, erythromycin, and nalidixic acid were used. The evolution of resistant strain led to using ciprofloxacin as a first line of treatment; however, its minimal inhibitory concentration is beyond therapeutic doses especially in pediatric cases. The trend now is to use combinations of antibiotics like ampicillin and furazolidone, or adding neomycin or neomycin and streptomycin to the original combination (Das et al, p. 480).
Conclusion
Cholera is an acute diarrheal disease caused by the toxins of V. cholera O1 and O139. Dehydration and hypovolemic shock develop rapidly within hours and can be fatal. Prevention is by improving hygienic conditions; however during epidemics and for travelers, vaccination is useful. Diagnosis is based on the clinical features and isolating the organism in enriched culture media. Treatment consists of patient rehydration (primary and maintenance) and a combination antibiotic therapy.
Works Cited
Bopp, C, A, Ries, A, A, and Wells, J, G. Laboratory Methods for the Diagnosis of Epidemic Dysentery and Cholera. Atlanta, Georgia: Centers for Disease Control and prevention, 1999.
Coedco, C, T, and Coelho, F, C. “Trends in Cholera epidemiology.” PLoS Med 3(1) (2006): e42=e43. 2009.
Da, S, Saha, R, and Kaur, I, R. “Trend of antibiotic resistance of Vibrio cholerae strains from East Delhi.” Indian J Med Res vol 127 2008. p. 478-482.
Deen, JL, von Seidlein, L, Sur, D, Agtini, M etal. “The High Burden of Cholera in Children: Comparison of Incidence from Endemic Area in Asia and Africa.” PLoS Negl Trop Dis 2(2) (2008): e173. 2009. Web.
Hsiao, A, Liu, Z, Joelsson, A, and Zhu, J. “Vibrio cholerae virulence regulator-coordinated evasion of host immunity.” PNAS vol 103(39) 2006. p. 14542-14547.
Mayo Clinic Staff. “Cholera: Symptoms.” Mayo Clinic. 2009. Web.
Page, K., E.. “Cholera: Mechanism of Infection, History and Treatment.” South Carolina Journal of Molecular Medicine vol 5 2004. p. 26-29.
Patocka, J, and Streda, L. “Protein Biotoxins of Military Significance.” Acta Medica vol 49(1) 2006. p. 3-11.
Provenzano, D, Kovac, P, and Wade, W, F. “The ABSc (Antibody, B Cells, and Carbohydrate Epitopes) of Cholera Immunity: Considerations for an Improved Vaccine.” Microbiol. Immunol. vol 50(1) 2006. p. 899-927.
Schild, S, Bishop, A., L, Camilli, A. “Ins and Outs of Vibrio cholerae: Vibrio cholerae transition between the human gut and the aquatic environment are aided by specific shifts in gene expression.” Microbe vol 3(3) 2008. p. 131-136.
World Health Organization (WHO) (a). Cholera Vaccine: WHO position paper. 2001. Web.
World Health Organization (WHO) (b). Weekly epidemiological record: Cholera 2005. By The Global Task Force on Cholera. 2006.