Intravenous replacement of the diarrhoeal fluid and electrolyte losses to restore a physiological state of hydration is well established as the basis for successful management of cholera patients. The use of oral tetracycline as an adjunct in reducing the volume and duration of diarrhoea, as well as eradicating the vibrio from the gastrointestinal tract, has been proven beneficial. An optimal dose schedule has not been established previously, and clinical or bacteriological relapses have been generally reported. Chloramphenicol and sulfaguanidine have also been mentioned as adjuncts. The present report shows that 3 g or 4 g of tetracycline in one of 3 dose schedules were predictably efficacious. Chloramphenicol, while of benefit, was not as effective and sulfaguanidine was of little benefit compared with the tetracycline regimens.

Objetivos. Caracterizar el brote de cólera ocurrido en Ecuador en 1998 durante el fenómeno de "El Niño", presentar los datos sobre la resistencia de las cepas circulantes de Vibrio cholerae a los antimicrobianos y describir las medidas preventivas tomadas por las autoridades sanitarias para reducir el impacto de la enfermedad. Métodos. Los datos epidemiológicos provienen de los registros de la Dirección Nacional de Epidemiología del Ministerio de Salud Pública de Ecuador y del Instituto Nacional de Higiene y Medicina Tropical, y el informe final del Programa de Formación para la Lucha contra el Cólera y las Enfermedades Diarreicas (PROCED ALA 93/25). Se procedió a aislar, identificar y serotipificar V. cholerae en las muestras de heces de 10 por ciento de los pacientes con posible cólera identificados entre el 1 de enero y el 31 de diciembre de 1998. Los casos sospechados se definieron por la aparición súbita de diarrea acuosa, con o sin deshidratación, en zonas epidémicas. Las cepas aisladas se sometieron a un antibiograma estándar por el método de difusión, en el que se probaron los siguientes antibióticos: amoxicilina, tetraciclina, sulfametoxazol con trimetoprim, compuesto vibriostático O/129, ácido nalidíxico, eritromicina, norfloxacino, ciprofloxacino, gentamicina, cloranfenicol y colistina. Resultados. En 1998 se notificaron 3 755 casos en 17 de las 21 provincias del país, lo que corresponde a una tasa de incidencia de 53,96 por 100 000 habitantes. Treinta y siete pacientes fallecieron, lo cual supone una tasa de letalidad del 0,97 por ciento. Se aislaron 301 cepas de V. cholerae en las 637 muestras con sospechosa de cólera que se procesaron; todas correspondieron a V. cholerae O:1, El Tor, subtipo Ogawa. La totalidad de las cepas fueron sensibles a la tetraciclina y a las quinolonas, y 5,6 por ciento resistentes a la eritromicina. La única cepa resistente a la amoxicilina fue multirresistente. Las autoridades nacionales pusieron en práctica una serie de medidas preventivas en la comunidad y se fortaleció el sistema de vigilancia para reducir el impacto de la enfermedad. Conclusiones. Las medidas preventivas contribuyeron a reducir el impacto de la nueva epidemia de cólera en el Ecuador, tanto en términos de letalidad como de incidencia

BACKGROUND:

Diarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development. Despite advances in the understanding of diarrheal disorders and management strategies, globally nearly 750,000 children die annually as a consequence of diarrhea.

METHODS:

We conducted a systematic review of the efficacy and effectiveness studies. We used a standardized abstraction and grading format and performed meta-analyses for all outcomes. The estimated effect of cholera, shigella, Enterotoxigenic Escherichia coli (ETEC) and rotavirus vaccines was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules.

RESULTS:

A total of 24 papers were selected and analyzed for all the four vaccines. Based on the evidence, we propose a 74% mortality reduction in rotavirus specific mortality, 52% reduction in cholera incidence due to their respective vaccines. We did not find sufficient evidence and a suitable outcome to project mortality reductions for cholera, ETEC and shigella in children under 5 years.

CONCLUSION:

Vaccines for rotavirus and cholera have the potential to reduce diarrhea morbidity and mortality burden. But there is no substantial evidence of efficacy for ETEC and shigella vaccines, although several promising vaccine concepts are moving from the development and testing pipeline towards efficacy and Phase 3 trials.

To determine the efficacy of single-dose doxycycline in the treatment of cholera, we carried out a randomized prospective trial in 65 patients. Treatment consisted of either a single dose of 200 mg of doxycycline (or 4 mg/kg in patients less than 15 years old) or multiple doses of doxycycline, 500 mg over 4 days (or 10 mg/kg in patients less than 15 years old). There were no differences between the groups in the volumes of intravenous fluid required, volumes of diarrheal stool, or durations of diarrhea. The mean duration of positive stool cultures for Vibrio cholerae was similar for the two groups, although in both groups several patients continued to excrete Vibrios in the stool for more than 3 days. Blood levels of antibiotic demonstrated that the doxycycline was absorbed in spite of the rapid transit time associated with severe diarrhea. These results suggest that although tetracycline remains the drug of choice for cholera, doxycycline is a reasonable alternative, and that a single dose of 200 mg (4 mg/kg in children) is effective clinically.

El Perú ha sido uno de los países más afectados por la séptima pandemia del cólera; así en 1991, se notificaron el 60% de todos los casos que se presentaron en el mundo. El departamento de Cajamarca fue uno de los que presentó las más altas de morbilidad y letalidad. Lo que presentamos a continuación, es una revisión realizada en los primeros semestres de los años de 1991-1992. Los casos existentes en el primer semestre de 1992 fueron constantes, teniendo brotes esporádicos como en los distritos de Jesús con 20 casos (fines de enero), Cajamarca con 72 casos (mediados de marzo) y la Encañada con 182 casos (fines de marzo). En cuanto a las tasas de la provincia de Cajamarca para el primer semestre de 1992 se mostraron como sigue: la morbilidad fue de 55.1 por 10,000; la mortalidad 1.7 por 10,000 y una letalidad de 3.1. El distrito más afectado fue el de Chetilla con una morbilidad de 218.2 por 10,000 y una mortalidad de 11.5 por 10,000. En cuanto a la letalidad, el distrito más afectado fue el de Baños del Inca con una tasa de 3.03%. Del presente trabajo se concluye lo siguiente: 1. El cólera debe ser considerado endémico en la provincia de Cajamarca. 2. El distrito de Chetilla tuvo el mayor riesgo de enfermar y morir durante el primer semestre de este año. 3. Los factores de establecimiento y diseminación de la enfermedad son el saneamiento ambiental deficiente, escaso o inexistente personal de salud en los distritos alejados, costumbres arraigadas, desconocimiento de la enfermedad en lugares alejados y la poca accesibilidad a los servicios de salud. 4. La coordinación y la participación comunitaria fue uno de los factores más importantes para el rápido y eficiente control de los brotes.

To explore the efficacy of single dose ciprofloxacin therapy in cholera, a randomized, open, controlled clinical trial was carried out. Seventy-four adult patients with positive Vibrio cholerae 01 isolates were assigned to receive either ciprofloxacin in a single dose of 1 g (CIP1), or ciprofloxacin 500 mg b.i.d., for 1 day (CIP2), or doxycycline 100 mg b.i.d., for 3 days (D), or, for control, no antibiotics. Mean liquid stool output volume did not show any statistically significant difference among CIP1, CIP2 and doxycycline groups. The mean duration of diarrhoea in CIP1 group, on the other hand, was significantly lower than that from the D group (p=0.004), and the control group (p<0.001). Bacteriologic clearance at the fourth day of treatment were 95.2% for CIP1, 89.5% for CIP2, 90.5% for D group and 15.4% for the control group. We conclude that a single 1 g ciprofloxacin dose is equivalent to doxycycline in its bacteriologic success but has advantages in shortening the duration of diarrhoea and simplicity of use as a single dose.

In a controlled trial of the effects of oral antibiotics in treating cholera in children in Dacca, East Pakistan, tetracycline was the most effective of 4 antibiotics tested in reducing stool volume, intravenous fluid requirement, and the duration of diarrhoea and positive stool culture. Increasing the duration of tetracycline therapy from 2 to 4 days, or increasing the total dose administered, resulted in shorter duration of positive culture, but did not affect stool volume or duration of diarrhoea. Only 1% of the children receiving tetracycline had diarrhoea for more than 4 days. Tetracycline was significantly more effective than intravenous fluid therapy alone, regardless of severity of disease.Chloramphenicol, while also effective, was inferior to tetracycline. Streptomycin and paromomycin exerted little or no effect on the course of illness or duration of positive culture. Therapeutic failures with these drugs were not due to the development of bacterial resistance.From these findings, tetracycline appears to be the drug of choice against Vibrio cholerae infection in children. Oral therapy for 48 hours is effective clinically, but is associated with 20% bacteriological relapses when the drug is discontinued; it is not known whether extending the therapy for a week or more would eliminate such relapses.

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A randomised clinical trial was carried out to explore the efficacy of single dose tetracycline therapy in cholera. One hundred and eighteen adult patients were assigned to receive either tetracycline in a single 1 g, or a single 2 g dose, or tetracycline 500 mg every six hours four times, or no antibiotics as controls. The means of total liquid stool volumes after treatment were lower in the single 1 g dose group (168.0 +/- 20.9 ml/kg), in single 2 g dose group (229.5 +/- 45.6 ml/kg), and multiple dose group (214 +/- 28.5 ml/kg), than in the control group (499.1 +/- 56.5 ml/kg) (p less than 0.05). Similarly, the means of durations of diarrhoea and intravenous fluid requirements were significantly lower in the single dose and multiple dose tetracycline groups, than in the controls (p less than 0.05). The mean durations of excretion of Vibrio cholerae were significantly shortened from 3.9 +/- 0.2 days in the control group to 1.9 +/- 0.2 days in single 1 g dose, to 2.2 +/- 0.4 days in single 2 g dose and 1.3 +/- 0.1 days in multiple dose groups, respectively (p less than 0.05). Three patients in the single 1 g dose group and two patients in single 2 g dose group had clinical relapses with excretion of V cholerae during the relapses, but this was not significantly more frequent than that in the multiple dose group (p greater than 0.05). These findings suggest that although multiple dose tetracycline therapy remains the best choice, a single dose of either 1 g or 2 g tetracycline appears to be a reasonable alternative for the treatment of cholera as an adjunct to rehydration therapy.

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