Conjugated Linoleic Acid Reduces Cholera Toxin Production In Vitro and In Vivo by Inhibiting Vibrio cholerae ToxT Activity.

The severe diarrheal disease cholera is endemic in over 50 countries. Current therapies for cholera patients involve oral and/or intravenous rehydration, often combined with the use of antibiotics to shorten the duration and intensity of the disease. However, as antibiotic resistance increases, treatment options will become limited. Linoleic acid has been shown to be a potent negative effector of V. cholerae virulence that acts on the major virulence transcription regulator protein, ToxT, to inhibit virulence gene expression. ToxT activates transcription of the two major virulence factors required for disease, cholera toxin (CT) and toxin-coregulated pilus (TCP). A conjugated form of linoleic acid (CLA) is currently sold over the counter as a dietary supplement and is generally recognized as safe by the U.S. Food and Drug Administration. This study examined whether CLA could be used as a new therapy to reduce CT production, which, in turn, would decrease disease duration and intensity in cholera patients. CLA could be used in place of traditional antibiotics and would be very unlikely to generate resistance, as it affects only virulence factor production and not bacterial growth or survival.

Risk factors for severe cholera among children under five in rural and urban Bangladesh, 2000-2008: a hospital-based surveillance study.

BACKGROUND: Children under five bear the largest cholera burden. We therefore sought to identify modifiable risk factors among Bangladeshi children. METHODOLOGY/PRINCIPAL FINDINGS: We used multivariate Poisson regression to assess risk factors for severe cholera among diarrheal patients presenting at hospitals in Matlab (rural) and Dhaka (urban), Bangladesh. Risk increased with age. Compared to those under one, rural and urban four-year-olds had adjusted risk ratios (aRR) of 4.17 (95% confidence interval (CI) 2.43-7.15) and 6.32 (95% CI: 4.63-8.63), respectively. Breastfeeding halved the risk in both rural (aRR = 0.49, 95% CI: 0.35-0.67) and urban (aRR = 0.51, 95% CI: 0.41-0.62) settings. Rural children's risk decreased with maternal education (P-trend: <0.001) and increased among those with a family member with diarrhea in the past week (aRR = 1.61, 95% CI: 1.22-2.14) and those with prior vitamin A supplementation (aRR = 1.65, 95% CI: 1.12-2.43). Urban children whose mothers daily (aRR = 0.41, 95% CI: 0.21-0.79) or occasionally (aRR = 0.55, 95% CI: 0.36-0.84) read a newspaper experienced reduced risk. Urban children from households with incomes between 34-84 USD/month had a 30% increased risk compared to those from households with incomes >84 USD/month. CONCLUSION/SIGNIFICANCE: Increasing age, lower socioeconomic status, and lack of breastfeeding are key correlates of increased risk for cholera hospitalization among those under five in rural and urban Bangladesh. In addition, having a family member with diarrhea in the past week was associated with increased risk among rural children. Continued attention should be directed to the promotion of breastfeeding. Further research is needed to elucidate the relationship between maternal education and cholera risk. Renewed research regarding the use of chemoprophylaxis among family members of cholera cases may be warranted in rural endemic settings.

Salovum egg yolk containing antisecretory factor as an adjunct therapy in severe cholera in adult males: a pilot study.

Cholera involves stimulation of intestinal secretory process in response to cholera toxin leading to profuse watery diarrhoea that might cause death due to dehydration unless timely rehydration therapy is initiated. Efforts to identify and test potential antisecretory agents are ongoing. Antisecretory factor (AF) is a naturally-occurring protein produced in the human secretory organs, including the intestine, with antisectory properties demonstrated in animal and human models of secretory diarrhoea. Salovum egg yolk powder contains antisecretory proteins in a much higher (500 times) concentration than that of normal hen eggs. This is achieved by feeding hens with specially-processed cereals, capable of inducing antisecretory proteins in the yolk. The aim of the study was to examine the effect of Salovum egg yolk powder containing AF in the treatment of adult cholera patients. In an open, randomized controlled trial (pilot study), 40 adult male patients with severe cholera were studied: 20 received standard treatment (oral rehydration solution, antibiotic, and usual hospital diet) plus Salovum egg yolk powder (study group) and 20 received standard treatment alone (control group). All the patients received tablet doxycycline (300 mg) once immediately after randomization. Written informed consent was obtained from each subject before enrollment. The main outcome measures were stool weight and duration of diarrhoea. The demographic and baseline clinical characteristics of the study patients were comparable between the groups. No significant differences were found in the mean stool weight, g/kg of body-weight during the first 24 hours [study vs control group, mean +/- standard deviation (SD), 218 +/- 119 vs 195 +/- 136], second 24 hours (mean +/- SD, 23 +/- 39 vs 22 +/- 34), and cumulative up to 72 hours (mean +/- SD, 245 +/- 152 vs 218 +/- 169). The duration (hours) of diarrhoea after admission in the hospital was also similar in both the groups (mean +/- SD, 33 +/- 14 vs 32 +/- 10). No adverse effect was observed. Salovum egg powder containing AF as an adjunct therapy in the treatment of severe cholera could not demonstrate any beneficial effect. Further studies with higher doses of Salovum egg yolk powder might be considered in future to establish its antisecretory effect.

Intra- and extracellular water dynamics on rehydration in cholera and noncholera patients.

To estimate the intra- and extracellular body water compartments during rehydration of patients with cholera and noncholera diarrhea by bioimpedance analyzer, we studied 30 patients with acute watery diarrhea. Total body water (TBW), intracellular water (ICW), and extracellular water (ECW) of severely dehydrated adult patients were measured with a dual frequency bioimpedance analyzer at different phases of rehydration. Fluid compartments between cholera and noncholera patients were compared. Cholera patients gained more TBW than noncholera patients during recovery. Unlike patients with noncholera diarrhea, the gain in cholera patients was mainly contributed by the ICW (1.5 +/- 1.6 vs 3.0 +/- 1.2 liters, respectively, P < 0.01). It was also observed that the recovery of the ICW compartment in cholera patients occurred rapidly within the first 2 hr after infusion. Differential dynamics of body water compartments in cholera compared to noncholera patients as observed in this study may contribute further to understanding the mechanism of dehydration in diarrheal disease, which might help in improving case management.

Epidemiological, clinical and therapeutic evaluation of the Italian cholera epidemic in 1994.

In the period between 18 October and 4 December 1994, 12 indigenous cases of cholera were registered in the southern Italian region of Puglia, 10 of them were diagnosed in our Departments of Infectious Diseases. All patients were infected by consumption of raw fish or mussels. The patients had an elevated mean age and most were affected with systemic pathologies. The clinical course was mild and rarely complicated, although frequently the characteristic riziform diarrhoea was absent. In all patients V. cholerae serotype Ogawa biotype El Tor, was isolated; one patient was co-infected by Salmonella typhi. All strains showed resistance to cotrimoxazole and tetracycline. Nine of ten patients were treated with oral ciprofloxacin at 1 g/day for 10 days resulting in disappearance of the symptoms within a median of 36 hours and negative fecal cultures within a median of 24 hours. Our data suggest that Italy is at high risk of infection imported from nearby nations. The resistance to commonly used antibiotics for treatment of cholera and the good response to ciprofloxacin suggest including fluoroquinolones among the drugs of first choice geographical areas involved in the circulation of resistant strains of V. cholerae O1.

Mechanism and treatment of diarrhoea due to Vibrio cholerae and Escherichia coli: roles of drugs and prostaglandins.

The primary objectives of these studies were to determine the clinical efficacy and safety of the potential antisecretory and antimicrobial drugs in the treatment of diarrhoea due to Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC). The drugs evaluated were chlorpromazine (CPZ), nicotinic acid, berberine, indomethacin, chloroquine, tetracycline, furazolidone, and bioflorin. Additionally, the role of prostaglandins (PGs) in the pathogenesis of cholera diarrhoea has been studied. The drug studies were carried out as placebo-controlled, randomized clinical trials in patients with active diarrhoea due to vibrio cholerae and ETEC. All patients received intravenous (i.v.) or oral rehydration solutions (ORS), but no other medications except the study drugs. Results indicate that CPZ (1 mg/kg or 4 mg/kg), berberine (200 mg), and nicotinic acid (2 g) all reduced stool volumes from 30% to more than 50% in diarrhoeal patients without significant side effects. It appeared that berberine was more effective in ETEC diarrhoea than in cholera. However, chloroquine, indomethacin, clonidine, and bioflorin had no clinically useful effects. Among the antimicrobial agents, a single dose of tetracycline was found to be effective in cholera, because the drug significantly (p < 0.05) reduced the total stool volume from 20.9 +/- 15.9 to 10.5 +/- 8.6 (liters in 6-days, mean +/- SD) compared to furazolidone. Drugs other than antimicrobial and antisecretory agents were also evaluated in the treatment of cholera. It has been shown that treatment with bioflorin, which is a bacterial preparation of lyophilized Streptococcus faecium, did not significantly (p > 0.05) reduce fluid-loss in cholera. Additional studies in animals indicated that treatment with short chain glucose polymers, alone or in combination with a chloride blocking agent, anthracene-9-carboxylic acid (A9C), significantly reduced intestinal secretion in a rat model of secretory diarrhoea. For the first time it was demonstrated that jejunal prostaglandin (PG) E2 concentrations were significantly increased during acute cholera and correlated with the volumes of stool and duration of diarrhoea. Furthermore, it was shown that treatment with indomethacin, a potent inhibitor of PG synthesis, significantly reduced jejunal PGE2 output in adults with acute cholera, in addition to net secretion of water and electrolytes. In summarizing the results, it is concluded that: (1) CPZ, berberine, and nicotinic acid are potential antidiarrhoeal agents, (2) PGs are involved in the pathogenesis of cholera, (3) tetracycline and furazolidone are effective antimicrobial agents in cholera, (4) and glucose short-chain polymers (used with the chloride blocking agent, anthracene-9-carboxylic acid) are better sources of carbohydrates in oral rehydration solutions.

Colera y medicina homeopatica: la experiencia del Peru / Cholera and homeopathic medicine: the Peru experience

La organizacion HOMEOPATHES SANS FRONTIERES inicio en marzo de 1991 un programa de ayuda a los afectados por la epidemia de colera de Peru, que ha durado, en diversos periodos, hasta la primavera de 1992. El tratamiento homeopatico se realizo en combinacion con la rehidratacion. En el transcurso de la mision se realizo un protocolo de estudio con el objetivo de evaluar la importancia del uso de los medicamentos homeopaticos en asociacion con la rehidratacion en el tratamiento del colera, cuyos resultados estan actualmente en curso de analisis en la Universidad de Montpellier

The protective activity of tea catechins against experimental infection by Vibrio cholerae O1.

Tea catechins inhibited the fluid accumulation induced by cholera toxin in sealed adult mice. The catechins also reduced fluid accumulation by Vibrio cholerae O1 in ligated intestinal loops of rabbits. These findings suggest that tea catechins may possess protective activity against V. cholerae O1.