Disease Treatment and Management

Disease Treatment and Management

Due to the development of resistance among serogroups O1 and O139, the number of available antimicrobrial drugs that are effective in combating the bacteria is limited. Having said this, tetracycline and its derivatives have been the most widely used antibiotics over the course of the past 40 years (Saha 2006). Tetracyclines have a 4-ring structure and are a subclass of polyketide antibiotics that inhibit bacterial protein synthesis by preventing the association of aminoacyl-tRNA with the bacterial ribosome. Tetracyclines traverse the outer membrane of gram-negative enteric bacteria through the OmpF and OmpC porin channels (Chopra 2001).

Fig. 6. Structure of the antibiotic tetracycline. Tetracycline functions by inhibiting bacterial protein synthesis by preventing the association of aminoacyl-tRNA with the bacterial ribosome.
Fig. 6. Structure of the antibiotic tetracycline. Tetracycline functions by inhibiting bacterial protein synthesis by preventing the association of aminoacyl-tRNA with the bacterial ribosome.

Erythromycin is also often used as an alternative to tetracycline. Unlike the tetracyclines, however, erythromycin has not been shown to be effective in a single dose, and currently recommended courses of treatment require 12 doses over a period of three days. As compared with erythromycin, azithromycin, a macrolide antibiotic derived from erythromycin, has better in vitro activity against V. cholerae, and exhibits a longer half-life, and has less gastrointestinal toxicity.

Management of cholera symptoms often also includes rehydration methods using Oral Rehydration Solution (ORS), which constitute equimolar concentrations of sodium and glucose to in order maximize sodium uptake in the small intestine, and account for preceding and ongoing fluid losses (Harris 2012).  Another management technique that has emerged recently is zinc therapy. Administration of zinc reduces cAMP concentration and therefore cholera toxin-induced ion secretion (Qadir 2013). A recent study by Reddy et al. also highlights the use of grape seed extract as an emerging form of cholera management. The investigators found that the application of the extracts up to an hour after toxin exposure still generated the toxin-resistant phenotype among cultured cells. The authors demonstrated that toxin inhibition could be induced along multiple steps during the intoxication process, with those being CTB binding to the plasma membrane, CTA1 unfolding in the ER, CTA1 translocation to the cytosol, and CTA1 ADP-ribosylation activity. However, the toxin trafficking to the ER, CTA1/CTA2 redox states, and CTA1 disassembly from the holotoxin were not affected (Reddy 2013).

According to the WHO, there is a small number of vaccines currently available that provide protection against cholera. There currently available oral killed vaccines that are licensed and commercially available include Dukoral, and Schancol and mORCVAX. Dukoral contains multiple biotypes of V. cholerae O1 supplemented with 1 mg/dose of recombinant cholera toxin B subunit. Shanchol and mORCVAX contain multiple biotypes of V. cholerae O1 as well as V. cholerae O139 without supplemental cholera toxin B subunit. The vaccines generally have 60-80% efficacy for approximately 2-3 years (Harris 2012) (WHO 2010).

 

Fig. 7. Dukoral is an oral vaccine that contains killed whole cells of Vibrio cholerae.
Fig. 7. Dukoral is an oral vaccine that contains killed whole cells of Vibrio cholerae.
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