The oral-formalin inactivated whole cell enterotoxigenic Escherichia coli (ETEC) vaccine needs to be further tested in developing countries in order to determine the dose at which it will be safe and immunogenic for infants who are the target population for the vaccine. To determine the immunogenicity of reduced doses, studies were first carried out in children, 2-12 years of age (n = 60). The full, half or a quarter doses of the vaccine were comparable in immunogenicity with similar frequency of responses seen to the different antigens (P = NS). Following this result, a pilot study carried out in infants, 6-17 months of age (n = 50), showed that the frequency of episodes of vomiting was lowest when a quarter of the full dose was used. The infants however showed comparable immune responses to the half and quarter dose of vaccine that was tested (P = NS). Based on these results in the infants, a randomized double blind placebo-controlled Phase II study was carried out in 158 children, 6-17 months of age, where a quarter dose of the ETEC vaccine was tested. Adverse events of mild vomiting were seen in only 4% of vaccinees and in 2.5% of placebo recipients. The IgA-antibody secreting cell (ASC) responses to CFA/I (GM: 28.1 ASC/10(7) PBMC) and BS (GM: 55.7 ASC/10(7) PBMC) were elevated compared to placebo recipients (CFA/I-2.0; BS-4.8 ASC/10(7) PBMC) (P = 0.01 to < 0.001). The plasma-IgA antibody titers in vaccinees were also significantly elevated to CFA/I (GM-93.00), CS1 (GM-62.0), CS2 (GM-55.0), CS4 (GM-66.0) and BS (1057.0) compared to preimmune levels or responses or levels in placebo recipients (P < or = 0.05-0.001). This study thus demonstrates that reduced doses of the ETEC vaccine is immunogenic in children and infants as well as safe in infants down to 6 months of age.

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To evaluate the probiotic, Bifidobacterium breve strain Yakult (BBG-01), for safety and enhancement of immunogenicity in an oral inactivated cholera vaccine, a randomized double-blind placebo-controlled study was performed. Bangladeshi children under 5-year-old received BBG-01 or placebo for 4 weeks with two doses of oral cholera vaccine. Serum/fecal antibodies and fecal bacterial flora in the study participants were monitored. All adverse events were mild and transient and had no significant difference between the two groups. Immunological responses were similar comparing the two groups. A negative correlation between Bifidobacterium and Enterobacteriaceae in the probiotic group suggests a possible involvement of BBG-01 in alteration of the enteric bacterial flora. In conclusion, BBG-01 is well tolerated by Bangladeshi children although the post vaccinal immunostimulatory effect of BBG-01 was not evident.

The 1966-67 cholera vaccine field trials in East Pakistan tested 1- and 2-dose schedules of a commercial cholera vaccine in 40 000 children aged 3 months to 14 years. Randomsample serological surveys, made prior to the inoculations and 3 months and 6 months after the inoculations, demonstrated that there was a rise in the vibriocidal titres of the vaccinated children during the first 3 months after inoculation and a subsequent fall by the end of the second 3 months. The antibody response to 2 doses of cholera vaccine was better than the response to a single dose in children under 5 years of age. In children aged 5-14 years, the antibody response was similar for both inoculation schedules. Since the majority of the older children had vibriocidal antibodies before inoculation, the data suggest that the single dose acted as a booster, and this effect was not enhanced by a second inoculation.Serological studies of the hospitalized cholera patients indicated that the majority had low vibriocidal titres on admission to hospital. By comparing the distribution of admission titres of the hospitalized patients with the distribution of titres found in the population survey, it was possible to demonstrate a progressive reduction in the cholera case rate for the population with high levels of vibriocidal antibody.The sample surveys from the control population revealed a rise in titre following the peak of the cholera season, and a fall 3 months later. The data suggest that the rate of infection with V. cholerae for the 10 000 children in the control group during the cholera season may have been as high as 27%, while the clinical case rate was only 0.26%.

La introducción de los tratamientos antirretrovirales de gran actividad (TARGA), generó una profunda transformación en la vida de las personas diagnosticadas con

VIH:

habitan un nuevo espacio vital, la enfermedad crónica caracterizada por un envejecimiento prematuro causado por la inflamación crónica del sistema inmune. Se plantea que la condición crónica del paciente VIH desborda el efecto puramente biológico o biomédico y se define por el establecimiento de lo que se denomina régimen de vitalidad. A partir de metodología cualitativa, se analiza la producción de un nuevo tipo de ciudadano crónico que, conducido por la norma biomédica y el dato biológico, se autogobierna en relación con representaciones del VIH.

In developing countries, the microbial contamination of household drinking water is implicated in the prevalence of various diseases. This systematic review is concerned with two health outcomes, general diarrhoea and cholera, and their relationship with water quality at point-of-use. Observational studies investigating this relationship are reviewed, as well as studies of home water treatment and storage interventions. For cholera, a clear relationship was found with contaminated water. Home water treatment and storage interventions were also found to reduce cholera. For general diarrhoea, no clear relationship was found with point-of-use water quality, although interventions did significantly reduce diarrhoeal incidence. Reasons for these apparently contradictory results concerning general diarrhoea are discussed and suggestions for further research offered. The policy implications of the findings are also discussed.

BACKGROUND:

Infection with enterotoxigenic Escherichia coli (ETEC) bacteria is a common cause of diarrhoea in adults and children in developing countries and is a major cause of 'travellers' diarrhoea' in people visiting or returning from endemic regions. A killed whole cell vaccine (Dukoral®), primarily designed and licensed to prevent cholera, has been recommended by some groups to prevent travellers' diarrhoea in people visiting endemic regions. This vaccine contains a recombinant B subunit of the cholera toxin that is antigenically similar to the heat labile toxin of ETEC. This review aims to evaluate the clinical efficacy of this vaccine and other vaccines designed specifically to protect people against diarrhoea caused by ETEC infection.

OBJECTIVES:

To evaluate the efficacy, safety, and immunogenicity of vaccines for preventing ETEC diarrhoea.

SEARCH METHODS:

We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and http://clinicaltrials.gov up to December 2012.

SELECTION CRITERIA:

Randomized controlled trials (RCTs) and quasi-RCTs comparing use of vaccines to prevent ETEC with use of no intervention, a control vaccine (either an inert vaccine or a vaccine normally given to prevent an unrelated infection), an alternative ETEC vaccine, or a different dose or schedule of the same ETEC vaccine in healthy adults and children living in endemic regions, intending to travel to endemic regions, or volunteering to receive an artificial challenge of ETEC bacteria.

DATA COLLECTION AND ANALYSIS:

Two authors independently assessed each trial for eligibility and risk of bias. Two independent reviewers extracted data from the included studies and analyzed the data using Review Manager (RevMan) software. We reported outcomes as risk ratios (RR) with 95% confidence intervals (CI). We assessed the quality of the evidence using the GRADE approach.

MAIN RESULTS:

Twenty-four RCTs, including 53,247 participants, met the inclusion criteria. Four studies assessed the protective efficacy of oral cholera vaccines when used to prevent diarrhoea due to ETEC and seven studies assessed the protective efficacy of ETEC-specific vaccines. Of these 11 studies, seven studies presented efficacy data from field trials and four studies presented efficacy data from artificial challenge studies. An additional 13 trials contributed safety and immunological data only.
Cholera vaccines
The currently available, oral cholera killed whole cell vaccine (Dukoral®) was evaluated for protection of people against 'travellers' diarrhoea' in a single RCT in people arriving in Mexico from the USA. We did not identify any statistically significant effects on ETEC diarrhoea or all-cause diarrhoea (one trial, 502 participants, low quality evidence).
Two earlier trials, one undertaken in an endemic population in Bangladesh and one undertaken in people travelling from Finland to Morocco, evaluated a precursor of this vaccine containing purified cholera toxin B subunit rather than the recombinant subunit in Dukoral®. Short term protective efficacy against ETEC diarrhoea was demonstrated, lasting for around three months (RR 0.43, 95% CI 0.26 to 0.71; two trials, 50,227 participants). This vaccine is no longer available.
ETEC vaccines
An ETEC-specific, killed whole cell vaccine, which also contains the recombinant cholera toxin B-subunit, was evaluated in people travelling from the USA to Mexico or Guatemala, and from Austria to Latin America, Africa, or Asia. We did not identify any statistically significant differences in ETEC-specific diarrhoea or all-cause diarrhoea (two trials, 799 participants), and the vaccine was associated with increased vomiting (RR 2.0, 95% CI 1.16 to 3.45; nine trials, 1528 participants). The other ETEC-specific vaccines in development have not yet demonstrated clinically important benefits.

AUTHORS' CONCLUSIONS:

There is currently insufficient evidence from RCTs to support the use of the oral cholera vaccine Dukoral® for protecting travellers against ETEC diarrhoea. Further research is needed to develop safe and effective vaccines to provide both short and long-term protection against ETEC diarrhoea.

ANTECEDENTES:

El cólera es una causa de diarrea líquida que puede producir deshidratación y muerte si no es tratada de forma adecuada. Suele presentarse en epidemias, y está asociada con la pobreza y con el saneamiento deficiente. Las vacunas pueden ayudar a prevenir las epidemias, además son efectivas, económicas y fáciles de administrar.

OBJETIVOS:

Evaluar la efectividad y la seguridad de las vacunas anticoléricas orales en la prevención de nuevos casos de cólera y de mortalidad por cólera.

ESTRATEGIA DE BÚSQUEDA:

En octubre 2010, se hicieron búsquedas en el Registro Especializado de Ensayos Controlados del Grupo Cochrane de Enfermedades Infecciosas (Cochrane Infectious Disease Group Specialized Register); Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials, CENTRAL); MEDLINE; EMBASE; LILACS; el metarregistro de los Ensayos Controlados (mRCT, por sus siglas en inglés, metaRegister of Controlled Trials), y la Plataforma Internacional de Registro de Ensayos Clínicos (ICTRP, por sus siglas en inglés, WHO International clinical Trials Registry Platform) de la OMS en busca de ensayos relevantes, publicados y en curso.

CRITERIOS DE SELECCIÓN:

Ensayos controlados con asignación aleatoria o cuasialeatoria de vacunas anticoléricas orales en niños y adultos sanos.

OBTENCIÓN Y ANÁLISIS DE LOS DATOS:

Dos autores, de manera independiente, evaluaron la elegibilidad y el riesgo de sesgo de cada uno de los ensayos. Los datos fueron extraídos por dos revisores independientes y analizados utilizando el programa informático Review Manager 5. Los resultados se informan como eficacia protectora de la vacuna (EPV) con los intervalos de confianza del 95% (IC).

RESULTADOS PRINCIPALES:

Siete ensayos amplios de eficacia, cuatro estudios pequeños de exposición artificial y 29 ensayos sobre la seguridad aportaron datos para esta revisión.
Se evaluaron cinco variantes de vacunas de células enteras inactivadas en ensayos de eficacia a gran escala (cuatro ensayos, 249 935 participantes). La eficacia global de la vacuna durante el primer año fue del 52% (IC del 95%: 35% a 65%), y durante el segundo año fue del 62% (IC del 95%: 51% a 62%). La eficacia protectora fue inferior en los niños menores de cinco años de edad; 38% (IC del 95%: 20% a 53%) comparados con los adultos y los niños de más edad; 66% (IC del 95%:57% a 73%).
Un ensayo de una vacuna de células enteras inactivadas en reclutas militares halló una eficacia protectora del 86% (IC del 95%: 37% a 97%) en una epidemia menor que ocurrió cuatro semanas después del calendario de dos dosis (un ensayo, 1 426 participantes). Los datos sobre la eficacia no están disponibles para los períodos mayores que dos años de las formulaciones de vacunas disponibles, pero según los datos de ensayos más antiguos es improbable que la eficacia dure más de tres años.
Los datos sobre la seguridad de las vacunas con células enteras inactivadas disponibles no revelaron un aumento clínicamente significativo en los eventos adversos comparado con el placebo.
Una sola vacuna de microbios vivos atenuados alcanzó la Fase III de la evaluación clínica y no resultó efectiva (un ensayo, 67 508 participantes). Se halló que dos nuevas vacunas candidatas de microbios vivos atenuados poseían efectividad clínica en estudios pequeños de exposición artificial, pero todavía están en etapa de desarrollo.

CONCLUSIONES DE LOS AUTORES:

Las vacunas con células enteras inactivadas actualmente disponibles pueden prevenir el 50% al 60% de los episodios de cólera durante los primeros dos años posteriores al calendario de vacunación primaria. La repercusión y la relación costoefectividad de incorporar las vacunas anticoléricas orales al calendario de vacunación sistemática de los países endémicos dependerá de la prevalencia del cólera, la frecuencia de las epidemias y el acceso a los servicios básicos que provean tratamientos para una rápida rehidratación.

OBJECTIVE:

To compare the safety and efficacy of a hyposmolar oral rehydration solution (H-ORS) (245 mmol/liter) with the World Health Organization oral rehydration solution (WHO ORS) in cholera and acute non-cholera diarrhea.

DESIGN:

Controlled clinical trial.

SETTING:

Diarrhea training and treatment unit.

METHODS:

Thirty-five culture proven cholera and 135 acute non-cholera diarrheal patients randomly received H-ORS or WHO-ORS. Intake and output were measured every 4 hours.

RESULTS:

Analysis of the total cases revealed rehydration phase (p=0.048, 95% CI 0.64-0.99) and overall (p=0.046, 95% CI 0.70-0.99) frequency of stools to be significantly less in the H-ORS group. In the severely malnourished, the rehydration phase (p=0.032, 95% CI 0.55-97), maintenance phase (p=0.035, 95% CI 0.51-0.97) and overall (p=0.011; 0.95% CI 0.55-0.93) stool frequency were significantly decreased in the H-ORS group. The amount of ORS consumed in the maintenance phase of the cholera cases was significantly (p=0.04, 95% CI 0.44-0.98) less in the H-ORS group. All other parameters, despite showing a decreasing trend, were statistically comparable in the cholera, non-cholera and total cases. The amount of intravenous fluid needed was significantly more in the noncholera and total cases on H-ORS. In the non-breastfed cases, under two years of age, the total duration of diarrhea was significantly decreased (p=0.03; 95% CI 11.07-11.45) but the need for intravenous fluids significantly increased (p=0.02; 95% CI 109.8-112.1) in the H-ORS group. The proportion of children vomiting, the weight gain, urine passed in 24 hours, serum sodium, caloric intake and failure rate were comparable.

CONCLUSIONS:

H-ORS is as safe and effective as the WHO-ORS and may have some additional benefits in malnourished children.

In Vietnam, shigellosis, typhoid fever, and cholera are important enteric diseases. To determine their magnitude and geographical distribution, and explore associated risk factors, we examined national surveillance data from 1991 to 2001 and potential ecological determinants. Average annual incidence rates were calculated and mapped for each province. Bivariate and multiple regression analyses were used to explore associations with selected environmental and human risk factors. Overall, shigellosis rates per 100,000 population (median, 41; mean, 70) were higher and more widespread than rates for typhoid fever (median, 7; mean, 23) and cholera (median, 0.3; mean, 2.7). Shigellosis was highest in the Central Highlands and was significantly associated with rainfall and urban poverty; typhoid fever prevailed in the Mekong River Delta and was most associated with vapor pressure and river/stream drinking water; and cholera predominated along the Central Coastal regions and correlated positively with rainfall and public well drinking water. The distinct geographical patterns of each disease appear to be driven by a combination of different ecological factors.