A comprehensive review of therapeutic approaches available for the treatment of cholera.

OBJECTIVES: The oral rehydration solution is the most efficient method to treat cholera; however, it does not interfere in the action mechanism of the main virulence factor produced by Vibrio cholerae, the cholera toxin (CT), and this disease still stands out as a problem for human health worldwide. This review aimed to describe therapeutic alternatives available in the literature, especially those related to the search for molecules acting upon the physiopathology of cholera. KEY FINDINGS: New molecules have offered a protection effect against diarrhoea induced by CT or even by infection from V. cholerae. The receptor regulator cystic fibrosis channel transmembrane (CFTR), monosialoganglioside (GM1), enkephalinase, AMP-activated protein kinase (AMPK), inhibitors of expression of virulence factors and activators of ADP-ribosylarginine hydrolase are the main therapeutic targets studied. Many of these molecules or extracts still present unclear action mechanisms. CONCLUSIONS: Knowing therapeutic alternatives and their molecular mechanisms for the treatment of cholera could guide us to develop a new drug that could be used in combination with the rehydration solution.

Vibrio cholera and V. parahaemolyticus coinfection in an oncology patient with gastroenteritis.

Vibrio-related gastroenteritis in the United States is mostly associated with the consumption of raw or improperly cooked seafood. We describe a case of a stage IV lung adenocarcinoma patient who became ill after eating crab while visiting Upstate New York. Molecular testing and culture confirmed a coinfection with V. parahaemolyticus and a nontoxigenic strain V. cholera.

Caracterización clínica-epidemiológica según la edad de pacientes diagnosticados con cólera / Clinic-epidemiological description according to the age of patients diagnosed with cholera

Introducción: Se estima que 1,4 billones de personas están en riesgo de infectarse por cólera y la mitad de los fallecidos son menores de 5 años. Objetivo: Caracterizar clínica y epidemiológicamente a los pacientes afectados por vibrión colérico según la edad de los enfermos y el tiempo que medió entre la aparición de los síntomas de la enfermedad y la asistencia al Sistema Nacional de Salud. Métodos: Estudio clínico, epidemiológico, descriptivo y prospectivo desde 2013-2017 a los pacientes que se les confirmó por coprocultivo el V. cholerae como causa de enfermedad diarreica aguda en el hospital pediátrico de Centro Habana. Se analizaron variables cualitativas y cuantitativas. Resultados: Se registraron 115 niños mayores de 5 años y 44 menores de 5 años afectados por el cólera. El 54,7 por ciento del total de pacientes estudiados estuvo en la zona afectada, el 94,3 por ciento presentó deposiciones líquidas, el 18,2 por ciento con aspecto de agua de arroz, el 7,5 por ciento con olor a pescado, el 47,2 por ciento presentó vómitos, el 6,9 por ciento fiebre y el 12,8 por ciento dolor abdominal. El valor de la mediana del tiempo que medio entre la aparición de los síntomas y la asistencia al médico fue de 24 horas. Conclusiones: Los pacientes más afectados son los mayores de 5 años y los que más tardíamente acudieron al Sistema Nacional de Salud. En todos predomina la procedencia de la zona afectada, las deposiciones líquidas y los vómitos(AU)

Introduction: It is estimated that 1.4 billion people are at risk of being infected by cholera and half of them are children under 5 years old. Objective: To describe clinically and epidemiologically the patients affected by Vibrio cholerae according to their age and the time passed from the onset of symptoms of disease to their attendance to the National Health System. Methods: Clinical, epidemiological, descriptive and prospective study from 2013 to 2017 in patients with confirmed V. cholerae by stool culture as a cause of acute diarrheal disease in the Pediatric Hospital of Centro Habana municipality.Qualitative and quantitative variables were analyzed. Results: There was a record of 115 children over 5 years and 44 children under 5 years affected by cholera. The 54.7percent of the total number of patients studied was in the affected area, 94.3 percent presented liquid stool, 18.2 percent of those looked like rice water, 7.5 percent with fishy smell; 47.2 percent of the patients presented vomiting, and 6.9 percent fever and 12.8 percent abdominal pain. The value of the mean time between the onset of symptoms and the assistance to the physician was of 24 hours. Conclusions: Most affected patients and that attended late to the National Health System were the ones over 5 years. In all predominated coming from the affected area, liquid stools and vomiting(AU)

Selection of affinity peptides for interference-free detection of cholera toxin.

Cholera toxin is a major virulent agent of Vibrio cholerae, and it can rapidly lead to severe dehydration, shock, causing death within hours without appropriate clinical treatments. In this study, we present a method wherein unique and short peptides that bind to cholera toxin subunit B (CTX-B) were selected through M13 phage display. Biopanning over recombinant CTX-B led to rapid screening of a unique peptide with an amino acid sequence of VQCRLGPPWCAK, and the phage-displayed peptides analyzed using ELISA, were found to show specific affinities towards CTX-B. To address the use of affinity peptides in development of the biosensor, sequences of newly selected peptides were modified and chemically synthesized to create a series of affinity peptides. Performance of the biosensor was studied using plasmonic-based optical techniques: localized surface plasmon resonance (LSPR) and surface-enhanced Raman scattering (SERS). The limit of detection (LOD) obtained by LSPR with 3σ-rule was 1.89ng/mL, while SERS had a LOD of 3.51pg/mL. In both cases, the sensitivity was much higher than the previously reported values, and our sensor system was specific towards actual CTX-B secreted from V. cholera, but not for CTX-AB5.

Control de foco de un brote de Cólera. Matanzas 2014 / Control of Focus in front of a Bud of Cholera. Matanzas 2014

Se presenta un estudio de control de foco de un brote de cólera, mediante la técnica observacional del tipo serie de casos, en el mes de julio de 2014 en el Municipio Matanzas, donde se describe, según el método epidemiológico, la relación de los casos detectados con el caso índice; se analiza el problema detectado teniendo en cuenta el enfoque de riesgo del cólera. Se realiza una evolución clínico-epidemiológica de los casos detectados y se analizan las medidas de control de foco aplicadas. Se revisan tanto las historias clínicas individuales en el consultorio del médico de la familia, como las encuestas epidemiológicas y el expediente de control de foco en el departamento de Epidemiología (AU).

A study of control of focus of a bud of cholera is presented, by means of the observational technique of the type series of cases, in the month of July of 2014 in the Municipality Matanzas, where it is described, according to the epidemic method, the relationship of the cases detected with the index case; the detected problem is analyzed keeping in mind the focus of risk of the cholera. He/she is carried out a clinical-epidemic evolution of the detected cases and of the applied measures of focus control. They are revised the clinical histories so much in the clinic of the doctor of the family, as the epidemic surveys and the file of focus control in the department of epidemiology (AU).

Prevalence of Vibrio cholerae O1 serogroup in Assam, India: A hospital-based study.

BACKGROUND & OBJECTIVES: Although cholera remains to be an important public health problem, studies on reliable population-based estimates of laboratory confirmed cholera in endemic areas are limited worldwide. The aim of this hospital-based study was to evaluate the prevalence of Vibrio cholerae serogroup in Assam, India, during 2003-2013. METHODS: Stool samples/rectal swabs were collected from acute watery diarrhoea (AWD) cases during 2003-2013 and processed by standard microbiological procedures. Antibiotic sensitivity test was done following the Clinical and Laboratory Standards Institute guidelines. Year-wise epidemiological trend of cholera was analyzed. RESULTS: Cholera contributed to 3.93 per cent of AWD cases. In Assam, cholera was found to be more prevalent in the rural areas (6.7%) followed by the tea gardens (5.06%), urban slum (1.9%) and urban areas (1.4%). Highest proportion of cholera (13.7%) was observed in 0-10 yr age group. Of them, 11.5 per cent belonged to 0-5 yr age group. V. cholerae O1 El Tor serotype Ogawa was the predominant isolate. Multiple drug-resistant isolates of V. cholerae O1 Ogawa were reported in the study. INTERPRETATION & CONCLUSIONS: Emergence of resistance amongst V. cholerae towards many antibiotics is a matter of concern. Hence, continuous surveillance for diarrhoeal disorders is necessary to control the future outbreaks of cholera in this region.

Electrochemical genosensor assay using lyophilized gold nanoparticles/latex microsphere label for detection of Vibrio cholerae.

Vibrio cholerae is a Gram-negative bacterium that causes cholera, a diarrheal disease. Cholera is widespread in poor, under-developed or disaster-hit countries that have poor water sanitation. Hence, a rapid detection method for V. cholerae in the field under these resource-limited settings is required. In this paper, we describe the development of an electrochemical genosensor assay using lyophilized gold nanoparticles/latex microsphere (AuNPs-PSA) reporter label. The reporter label mixture was prepared by lyophilization of AuNPs-PSA-avidin conjugate with different types of stabilizers. The best stabilizer was 5% sorbitol, which was able to preserve the dried conjugate for up to 30 days. Three methods of DNA hybridization were compared and the one-step sandwich hybridization method was chosen as it was fastest and highly specific. The performance of the assay using the lyophilized reagents was comparable to the wet form for detection of 1aM to 1fM of linear target DNA. The assay was highly specific for V. cholerae, with a detection limit of 1fM of PCR products. The ability of the sensor is to detect LAMP products as low as 50ngµl(-1). The novel lyophilized AuNPs-PSA-avidin reporter label with electrochemical genosensor detection could facilitate the rapid on-site detection of V. cholerae.

Development of an immunochromatographic lateral flow device for rapid diagnosis of Vibrio cholerae O1 serotype Ogawa.

OBJECTIVES: Cholera is an acute malignant infectious disease caused by the bacteria Vibrio cholerae leading to severe dehydrating diarrhea and vomiting, even high rates of mortality in some cases. However, the prevention of the epidemic disease is achievable if proper sanitation practices are followed, provided the accurate and prompt diagnosis of each prevalent serotype in cholera epidemic. The current gold standard of bacterial culture is inadequate for rapid diagnosis. Our aim is to develop an immunochromatographic test format for O1 serotype Ogawa diagnosis and provide the need for better epidemic prevention and early response. DESIGN AND METHODS: The monoclonal antibodies were raised in conventional method and subsequently screened for a match pair. A variety of related and unrelated bacteria strains recruited were employed to test their sensitivity, specificity etc. by indirect ELISA. The human fecal samples were used to test the final lateral-flow device product to satisfy the measurement requirement. RESULTS: A new monoclonal antibody (McAb) pair, named IXiao3G6 and IXiao1D9, was generated, which is specifically against V. cholerae O1 serotype Ogawa. Additionally, we developed an immunochromatographic lateral flow device (LFD) using this McAb pair for the highly specific and rapid (5 min) detection of Ogawa. CONCLUSIONS: Our product has advantages of simplicity and precision, and can benefit the scene and elementary medical institutions.

Quantitative detection of Vibrio cholera toxin by real-time and dynamic cytotoxicity monitoring.

We report here the quantitative detection of Vibrio cholerae toxin (CT) in isolates and stool specimens by dynamic monitoring of the full course of CT-mediated cytotoxicity in a real-time cell analysis (RTCA) system. Four cell lines, including Y-1 mouse adrenal tumor cells, Chinese hamster ovary (CHO) cells, small intestine epithelial (FHs74Int) cells, and mouse adrenal gland (PC12-Adh) cells, were evaluated for their suitability for CT-induced cytotoxicity testing. Among them, the Y-1 line was demonstrated to be the most sensitive for CT-mediated cytotoxicity, with limits of detection of 7.0 pg/ml for purified CT and 0.11 ng/ml for spiked CT in pooled negative stool specimens. No CT-mediated cytotoxicity was observed for nontoxigenic V. cholerae, non-V. cholerae species, or non-V. cholerae enterotoxins. The CT-RTCA assay was further validated with 100 stool specimens consecutively collected from patients with diarrhea and 200 V. cholerae isolates recovered from patients and the environment, in comparison to a reference using three detection methods. The CT-RTCA assay had sensitivities and specificities of 97.5% and 100.0%, respectively, for V. cholerae isolates and 90.0% and 97.2% for stool specimens. For stool specimens spiked with CT concentrations ranging from 3.5 pg/ml to 1.8 ng/ml, the inoculation-to-detection time was 1.12 ± 0.38 h, and the values were inversely correlated with CT concentrations (ρ = -1; P = 0.01). The results indicate that the CT-RTCA assay with the Y-1 cell line provides a rapid and sensitive tool for the quantitative detection of CT activities in clinical specimens.

Fatal diarrheal disease caused by Vibrio cholerae O67 in a patient with myelodysplastic syndrome.

A 71-year-old man with myelodysplastic syndrome (MDS) receiving treatment with azacitidine developed extensive watery diarrhea for three consecutive days. As a result of high-grade dehydration, the patient was urgently admitted to the hospital and fluid replacement therapy was initiated. However, the patient's diarrhea did not improve. Vibrio cholerae non-O1/non-O139 was detected in a fecal culture. On the fourth day, the patient died due to circulatory collapse. An autopsy revealed extensive necrosis of the intestinal mucosa. Vibrio cholerae non-O1/non-O139-induced diarrheal disease often develops in patients with hepatic cirrhosis and has a serious clinical course. We herein report a fatal outcome of Vibrio cholerae O67 infection in an immunocompromised MDS patient.

Cólera en Haití: lecciones aprendidas por la Brigada Médica Cubana / Cholera in Haiti: lessons learned by the Cuban Medical Brigade

El libro relata la experiencia de la Brigada Médica Cubana en Haití, es el resultado del trabajo práctico en el terreno desde una posición científica avalada por toda la experiencia internacional y en Cuba para la prevención y control del cólera, el uso en los servicios de salud y la investigación. Constituye una herramienta de gran utilidad para los profesionales de la salud sobre la actualización del Plan de Prevención y Control del Cólera.

Spontaneous bacterial empyema due to non-O1, non-O139 Vibrio cholerae in a cirrhotic patient with hepatocellular carcinoma.

Vibrio cholerae is known as a common etiology of epidemic diarrheal disease and rarely causes extra-intestinal infections. In this report, we described a cirrhotic patient with hepatocellular carcinoma who developed spontaneous bacterial empyema due to non-O1, non-O139 V. cholerae. The patient was successfully treated with antimicrobial agents and percutaneous drainage.

Role of faecal gas analysis for the diagnosis of IBD.

The diagnosis of IBD (inflammatory bowel disease) is based on the clinical evaluation of symptoms and signs leading to a series of investigations. The investigations used are often unpleasant for patients; they are invasive, costly and potentially dangerous. Patients often report that the odour of flatus, or the gas emitted from faeces, is abnormal during a flare of their IBD. Our group has characterized the VOCs (volatile organic compounds) in the headspace gas emitted from faecal samples from healthy subjects, from patients with infectious diarrhoea and from those with Crohn's disease or ulcerative colitis, both in relapse and remission. Painstaking analysis of gas chromatography-MS data (VOC profiling) has revealed patterns of compounds that are strongly associated with specific infectious diseases and with IBD. These compounds represent a change in the microflora and/or the metabolism of bacteria and/or the epithelium in disease states. These profiles offer a potential for rapid non-invasive assessment of a range of infectious and non-infectious gastrointestinal diseases. The study of VOCs may lead to a better understanding of the pathogenesis of IBD.

[Cholera--once and nowadays].

HISTORY: Cholera is an acute intestinal infection which raged in India in the nineteenth century and it broke out in six great pandemics out in Europe. ETIOLOGY: Cholera is caused by bacteria Vibrio cholerae, which produce an enterotoxin causing massive diarrhoea. There are two biotypes--classic and El Tor. EPIDEMIOLOGY: The source of Vibrio cholerae is a man. Cholera is a typical faecally-oral infection. PATHOGENESIS: Ingested by contaminated water and food, Vibrio cholerae comes to the intestinal wall. The tightness is intermediated with toxin-coregulated pilus. There it produces enterotoxin and activates adenilate cyclase which accumulate intracellular cyclic adenosine monophosphate. The result is isotonic watery diarrhoea. CLINICAL FEATURES: Cholera can occur as asymptomatic infection, then enteritis and deathly classic cholera. Patients suffer from explosive, unremitting, watery diarrhoea (known as "rice water"). DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS: The diagnosis is based on clinical features, epidemiological data and laboratory diagnostic methods. The most important is to isolate Vibrion cholerae from the stool. THERAPY: The most important treatment for cholera is fluid containing minerals. The best antibiotics available are tetracycline. PREVENTION: The best preventive measures are water supply, sanitation, food safety and community awareness. The importance of vaccines comes second. CHOLERA NOWADAYS: Cholera has been known since ancient times, but it is present even nowadays. It has been developed as a biological weapon. CONCLUSION: Cholera is a dreadful intestinal disease with severe clinical features. One thing is known for certain: hygienic and sanitary measures are the main prevention.

[Dynamics of the isolation and biological properties of Vibrio cholerae cultures, serogroups 01 and 0139, isolated from water reservoirs and sewage water on the territory of the city of Rostov-on-Don]. / Dinamika vydeleniia i biologicheskie svoistva kul'tur kholernykh vibrionov 01 i 0139 serogrupp, vydelennykh iz poverkhnostnykh vodoemov i stochnykh vod na territorii g. Rostov-na-Donu.

The dynamics of the isolation of V. cholerae cultures from various water objects on the territory of Rostov-on-Don during the period of 1994-2001 was analyzed and biological properties of 14 such cultures were studied. In the absence of epidemic complications during the above-mentioned period, a growth in the amount of V. cholerae isolates, serogroups 01 and 0139, including toxigenic V. cholerae 01, was registered. The microbiological and epidemiological aspects of the monitoring of surface reservoirs and sewage were considered and the expediency of the profound and systematic study of its results for epidemiological surveillance on cholera was emphasized.

Validação do critério diagnóstico clínico-epidemiológico para confirmação da cólera / Validation of clinical and epidemiological diagnosis criterion for confirming cholera

OBJETIVO: Validar o critério diagnóstico clínico-epidemiológico para confirmaçäo de casos suspeitos da cólera. MÉTODOS: Foram estudados pacientes em um hospital público em Maceió, sendo 2.687 do ano de 1992 e 716 de 1997. Nos pacientes admitidos com diarréia, que realizaram pesquisa do Vibrio cholerae O1 (Koch, 1884) pelo cultivo em TCBS-agar, foi aplicado o critério clínico-epidemiológico comparando-o com o padräo-ouro. A análise foi feita por faixa etária - menor que cinco anos e igual ou maior a cinco anos - em 1992 e 1997. RESULTADOS: Foram estudados 833 pacientes, 517 em 1992 e 316 em 1997; 72 com idade menor que cinco anos e 761 com idade igual ou maior a cinco anos. Nos pacientes menores que cinco anos, em 1992, a sensibilidade foi de 40por cento, enquanto a especificidade foi de 84,6por cento. Para a mesma faixa etária, em 1997, a sensibilidade foi de 28,6por cento. Já a especificidade foi de 62,5por cento. Nos pacientes com idade igual ou superior a cinco anos, em 1992, a sensibilidade e a especificidade foram de 99por cento e 1,2por cento; respectivamente. Para a mesma faixa etária, em 1997, a sensibilidade foi de 86,9por cento, enquanto a especificidade foi de 8,7por cento. CONCLUSAO: A elevada sensibilidade do critério diagnóstico clínico-epidemiológico da cólera nos pacientes com idade igual ou maior que cinco anos, nos dois anos estudados, recomenda sua aplicaçäo nos períodos de epidemia. Quando a incidência baixa, todos os casos devem ter confirmaçäo laboratorial