Research progress of Helicobacter pylori vaccine / 细胞与分子免疫学杂志

Helicobacter pylori (Hp) is one of most common pathogens causing gastrointestinal disorder including gastric ulcer, duodenal ulcer and gastric cancer, etc. It has been verified as class I carcinogen by WHO. Nowadays, combination antibiotics and proton pump inhibitor are mainly used to erase Hp in clinical application. However, with the increased resistance of Hp, the vaccine against Hp might become the best strategy to eradicate Hp. Elements including urease, virulence factor, outer membrane protein, flagella, play an important role in Hp infection, colonization and reproduction. They have become potential candidate antigens in the development of Hp vaccine, as reported in previous studies. Presently, these antigens-centric vaccines have been tested in animal models. Therefore, this article reviews the studies on Hp vaccine with urease, virulence genes, outer membrane protein and flagella as their candidate antigens, in an attempt to provide insights for research in this regard.

Adaptación a la realidad de Latinoamérica de la Guía Clínica NASPGHAN/ESPGHAN 2016 sobre Diagnóstico, Prevención y Tratamiento de Infección por Helicobacter pylori en Pediatría / Adaptation to the reality of Latin America of the NASPGHAN/ESPGHAN 2016 Guidelines on the Diagnosis, Prevention and Treatment of Helicobacter pylori Infection in Pediatrics

Resumen: Introducción: Las últimas guías clínicas conjuntas de NASPGHAN y ESPGHAN en relación a la infección por H. pylori publicadas el año 2016, contienen 20 afirmaciones que han sido cuestionadas en la práctica respecto a su aplicabilidad en Latinoamérica (LA); en particular en relación a la preven ción del cáncer gástrico. Métodos: Se realizó un análisis crítico de la literatura, con especial énfasis en datos de LA y se estableció el nivel de evidencia y nivel de recomendación de las afirmaciones mas controversiales de las Guías Conjuntas. Se realizaron 2 rondas de votación de acuerdo a la técnica Delfi de consenso y se utilizó escala de Likert (de 0 a 4) para establecer el "grado de acuerdo" entre un grupo de expertos de SLAGHNP. Resultados: Existen pocos estudios en relación a diagnóstico, efectividad de tratamiento y susceptibilidad a antibióticos de H. pylori en pacientes pediátricos de LA. En base a estos estudios, extrapolaciones de estudios de adultos y la experiencia clínica del panel de expertos participantes, se realizan las siguientes recomendaciones. Recomendamos la toma de biopsias para test rápido de ureasa e histología (y muestras para cultivo o técnicas moleculares, cuando estén disponibles) durante la endoscopia digestiva alta sólo si en caso de confirmar la infección por H. pylori, se indicará tratamiento de erradicación. Recomendamos que centros regionales seleccio nados realicen estudios de sensibilidad/resistencia antimicrobiana para H. pylori y así actúen como centros de referencia para toda LA. En caso de falla de erradicación de H. pylori con tratamiento de primera línea, recomendamos tratamiento empírico con terapia cuádruple con inhibidor de bomba de protones, amoxicilina, metronidazol y bismuto por 14 días. En caso de falla de erradicación con el esquema de segunda línea, se recomienda indicar un tratamiento individualizado considerando la edad del paciente, el esquema indicado previamente y la sensibilidad antibiótica de la cepa, lo que implica realizar una nueva endoscopía con extracción de muestra para cultivo y antibiograma o es tudio molecular de resistencia. En niños sintomáticos referidos a endoscopía que tengan antecedente de familiar de primer o segundo grado con cáncer gástrico, se recomienda considerar la búsqueda de H. pylori mediante técnica directa durante la endoscopia (y erradicarlo cuando es detectado). Con clusiones: La evidencia apoya mayoritariamente los conceptos generales de las Guías NASPGHAN/ ESPGHAN 2016, pero es necesario adaptarlas a la realidad de LA, con énfasis en el desarrollo de centros regionales para el estudio de sensibilidad a antibióticos y mejorar la correcta selección del tratamiento de erradicación. En niños sintomáticos con antecedente familiar de primer o segundo grado de cáncer gástrico, se debe considerar la búsqueda y erradicación de H. pylori.

Abstract: Introduction: The latest joint H. pylori NASPGHAN and ESPGHAN clinical guidelines published in 2016, contain 20 statements that have been questioned in practice regarding their applicability in Latin America (LA); in particular in relation to gastric cancer prevention. Methods: We conduc ted a critical analysis of the literature, with special emphasis on LA data and established the level of evidence and level of recommendation of the most controversial claims in the Joint Guidelines. Two rounds of voting were conducted according to the Delphi consensus technique and a Likert scale (from 0 to 4) was used to establish the "degree of agreement" among a panel of SLAGHNP ex perts. Results: There are few studies regarding diagnosis, treatment effectiveness and susceptibility to antibiotics of H. pylori in pediatric patients of LA. Based on these studies, extrapolations from adult studies, and the clinical experience of the participating expert panel, the following recom mendations are made. We recommend taking biopsies for rapid urease and histology testing (and samples for culture or molecular techniques, when available) during upper endoscopy only if in case of confirmed H. pylori infection, eradication treatment will be indicated. We recommend that selected regional centers conduct antimicrobial sensitivity/resistance studies for H. pylori and thus act as reference centers for all LA. In case of failure to eradicate H. pylori with first-line treatment, we recommend empirical treatment with quadruple therapy with proton pump inhibitor, amoxi cillin, metronidazole, and bismuth for 14 days. In case of eradication failure with the second line scheme, it is recommended to indicate an individualized treatment considering the age of the pa tient, the previously indicated scheme and the antibiotic sensitivity of the strain, which implies performing a new endoscopy with sample extraction for culture and antibiogram or molecular resistance study. In symptomatic children referred to endoscopy who have a history of first or se cond degree family members with gastric cancer, it is recommended to consider the search for H. pylori by direct technique during endoscopy (and eradicate it when detected). Conclusions: The evidence supports most of the general concepts of the NASPGHAN/ESPGHAN 2016 Guidelines, but it is necessary to adapt them to the reality of LA, with emphasis on the development of regional centers for the study of antibiotic sensitivity and to improve the correct selection of the eradication treatment. In symptomatic children with a family history of first or second degree gastric cancer, the search for and eradication of H. pylori should be considered.

Infección por Helicobacter pylori: mecanismos de contagio y prevención / Helicopabter pylori: infection and prevention mechanisms

H. pylori infection is a fascinating history, which combines the roles as one of the most prevalent commensal and a a pathogen responsible for severe diseases, some of them unimaginable until the end of last century, such as gastric cancer. In this review we present the available evidence that might help to identify the main mode of transmission of H. pylori and we discuss which could be the potential approaches to prevent the transmission of this bacterium in countries with high and low prevalence.

La infección por Helicobacter pylori es una historia fascinante, en donde se combinan el papel de un comensal con el de un patógeno humano que produce enfermedades graves, algunas inimaginables hasta hace menos de 30 años, como es el caso de cáncer gástrico. En esta revisión discutimos las evidencias disponibles en función de la prevalencia e incidencia de H. pylori tanto en países económicamente desarrollados como en proceso de desarrollo y tratamos de establecer cuál es el principal modo de transmisión de este organismo. Finalmente, se discuten cuáles pueden ser las mejores medidas de prevención, tanto en países con baja prevalencia como en aquellos con una alta prevalencia.

Characterization of Lactobacillus fermentum UCO-979C, a probiotic strain with a potent anti-Helicobacter pylori activity

Background: Helicobacter pylori is considered as the main risk factor in the development of gastric cancer. In the present study, we performed a detailed characterization of the probiotic properties and the anti-H. pylori activity of a previously isolated lactobacillus strain ­ Lactobacillus fermentum UCO-979C ­ obtained from human gut. Results: The strain tolerated pH 3.0; grew in the presence of 2% bile salts; produced lactic acid and hydrogen peroxide; aggregated in saline solution; showed high hydrophobicity; showed high adherence to glass; Caco-2 and gastric adenocarcinoma human cells (AGS) cells; showed an efficient colonization in Mongolian Gerbils; and potently inhibited the growth and urease activity of H. pylori strains. L. fermentum UCO-979C significantly inhibited H. pylori-induced IL-8 production in AGS cells and reduced the viability of H. pylori. With regard to innocuousness, the strain UCO-979C was susceptible to several antibiotics and did not produce histamine or beta-haemolysis in blood agar containing red blood cells from various origins. Conclusion: The results demonstrated that L. fermentum UCO-979C is a very good candidate as a probiotic for the protection of humans against H. pylori infections.

La infección materna por Helicobacter pylori no aumenta el riesgo de contraer la bacteria en el primer trimestre de vida de sus lactantes / Maternal infection due to Helicobacter pylori does not increase the risk of the infection in the first trimester of the life of their infants

Introducción: La infección por H. pylori se adquiere tempranamente en la infancia. Sin embargo, existe escasa información acerca del rol de la lactancia materna y la adquisición de la bacteria en la etapa neonatal/lactante. Objetivo: Evaluar algunos factores que afectan la adquisición de H. pylori en recién nacidos y lactantes hijos de madres infectadas. Pacientes y método: Reclutamiento consecutivo de binomios madre-hijo en maternidad, inmediatamente posparto. Luego de la firma de consentimiento informado, se obtuvo una muestra de deposición de la madre, previo al alta. Posteriormente se obtuvieron 3 muestras de deposición de los recién nacidos/lactantes a los 15, 60 y 90 días de vida, para la detección de antígeno en deposición de H. pylori (HpSAg monoclonal, sensibilidad 94% y especificidad 97%). Además se registraron variables socio-epidemiológicas y biomédicas. Resultados: Se reclutaron 32 binomios madre-hijo, 64 sujetos. Promedio de edad materna de 30,1 ± 5,1 años, 53% parto eutócico, 85% con lactancia materna exclusiva al final del seguimiento. Se encontró 13 madres (40%) infectadas por H. pylori. No hubo infección por H. pylori en los recién nacidos y lactantes a los 3 meses de seguimiento. No hubo diferencia significativa en el nivel socioeconómico entre madres infectadas versus no infectadas (ambos grupos en nivel socioeconómico muy alto: 28% y 32% respectivamente, p = 0,15), ni en el número de habitantes por domicilio entre madres infectadas y no infectadas (3,8 ± 0,8 vs 4,2 ± 1,8 personas, p = 0,18). Conclusión: A pesar de tener un alto porcentaje de madres infectadas por H. pylori, no hubo recién nacidos/lactantes infectados al tercer mes de vida. El rol protector de la lactancia maternal no se puede descartar.

Introduction: H. pylori infection is acquired early in childhood. However, there is little information available regarding the role of breastfeeding and neonatal acquisition of the infection. Objective: To evaluate factors affecting the acquisition of H. pylori in newborns and infants from infected mothers. Patients and method: Consecutive mothers and their newborns were recruited into the study from the maternity unit, immediately after delivery. After signing informed consent, one stool sample from the mother was obtained before hospital discharge. Three stool samples of the newborns were then collected at home at 15, 60, and 90 days of life, for the detection of H. pylori antigen (Monoclonal HpSAg, sensitivity 94% and specificity 97%). The socio-epidemiological and biomedical variables were also analysed using a questionnaire. Results: A total of 32 mother-child pairs (64 subjects) were enrolled. The mean maternal age was 30.1 ± 5.1 years, with 53% vaginal delivery, and 85% exclusively breastfed. There were 13 (40%) infected mothers. No H. pylori infection was detected in newborns and infants up to 3 months of follow-up. No significant differences were found in socioeconomic level between infected versus non-infected mothers (both groups mostly in the very high socioeconomic category: 28% and 32%, respectively, P = .15) and in the number of family members between infected versus non-infected mothers (3.8 ± 0.8 vs 4.2 ± 1.8 persons, P = .18). Conclusion: Despite having a significant percentage of H. pylori-infected mothers, no newborn was infected at the third month of life. The protective role of breastfeeding cannot be ruled out.

Recurrence rate of helicobacter pylori in patients with peptic ulcer five years or more after successful eradication / Taxa de reinfecção por Helicobacter pylori em pacientes com úlcera péptica cinco anos após erradicação

ABSTRACT Background Infection with Helicobacter pylori is highly prevalent worldwide, especially in developing countries. Its presence in the gastroduodenal mucosa is related with development of peptic ulcer and other illnesses. The eradication of H. pylori improves mucosal histology in patients with peptic ulcers. Objective This study was aimed to verify if H. pylori recurrence occurs five years or more after confirmed eradication in patients with peptic ulcer. Moreover, we sought to determine the recurrence rate. Methods Retrospective and longitudinal, this study was based on a sample of 201 patients from western Paraná, Brazil. The patients were diagnosed with peptic ulcer disease, in the period of 1990-2000, and followed for five years or more after successful H. pylori eradication. Patients with early recurrence - prior to five years after eradication - were excluded from the sample. Results During an average follow-up of 8 years, 180 patients (89.55%) remained negative, and 21 (10.45%) became positive for H. pylori infection. New ulcers appeared in two-thirds of the patients with H. pylori recurrence. Conclusion The recurrence of H. pylori in patients with peptic ulcer can occur in the long-term - even if the infection had been successfully eradicated and the patients had remained free of recurrence in the first years of follow-up.

RESUMO Contexto A infecção por Helicobacter pylori é altamente prevalente no mundo, especialmente nos países em desenvolvimento, e sua presença na mucosa gastroduodenal está associada com o desenvolvimento de úlcera péptica e outras patologias. A erradicação do H. pylori melhora a histologia da mucosa em pacientes com úlcera péptica. Objetivo Determinar se a recorrência da infecção por H. pylori ocorre cinco anos ou mais após a erradicação confirmada em pacientes com úlcera péptica. Além disso, buscou-se determinar a taxa de recorrência. Método Retrospectivo e longitudinal, o estudo foi baseado em uma amostra de 201 pacientes oriundos da região Oeste do Paraná, Brasil. Os pacientes foram diagnosticados com úlcera gástrica e/ou duodenal, no período de 1990-2000, e foram seguidos por pelo menos cinco anos após a erradicação com sucesso do H. pylori. Pacientes com recorrência precoce - nos primeiros cinco anos após a erradicação - foram excluídos da amostra. Resultados - Após um tempo médio de seguimento de oito anos, 180 pacientes (89,55%) permaneceram negativos e 21 (10,45%) tornaram-se positivos para a presença de H. pylori. Novas úlceras apareceram em dois terços dos pacientes com recorrência da bactéria. Conclusão A recorrência da infecção por H. pylori ocorre em longo prazo - mesmo se a infecção tiver sido erradicada com sucesso e os pacientes permanecido livres de recorrência nos primeiros cinco anos de seguimento.

Análisis cualitativo del deterioro de la calidad del agua y la infección por Helicobacter pylori en una comunidad de alto riesgo de cáncer de estómago (Cauca, Colombia) / Qualitative analysis of water quality deterioration and infection by Helicobacter pylori in a community with high risk of stomach cancer (Cauca, Colombia)

Este estudio aborda aspectos de la salud ambiental de la población rural de Timbío (Cauca, Colombia) con relación al deterioro de la calidad del agua. La información se obtuvo mediante métodos de investigación participativa, relacionadas al manejo y uso del agua, fuentes de contaminación y percepción de la calidad del agua y su relación con la infección por Helicobacter pylori. Los resultados forman parte del análisis cualitativo de una primera fase de caracterización de la problemática hídrica y sanitaria y su relación con enfermedades infecciosas emergentes y soluciones comunes, llevada a cabo entre noviembre de 2013 y agosto de 2014. Los resultados de esta investigación se discuten desde un enfoque ecosistémico de la salud humana, que reconoce la complejidad de los conflictos ambientales relacionados con el recurso hídrico y su impacto en la salud de las poblaciones. A través de la metodología empleada, este estudio permitió conocer y visualizar los problemas prioritarios y las causas frecuentes de la contaminación del recurso hídrico, para postular algunas soluciones a través de una agenda compartida con los actores sociales.

This study looks at aspects of the environmental health of the rural population in Timbío (Cauca, Columbia) in relation to the deterioration of water quality. The information was obtained through participatory research methods exploring the management and use of water, the sources of pollution and the perception of water quality and its relation to Helicobacter pylori infection. The results are part of the qualitative analysis of a first research phase characterizing water and sanitation problems and their relation to emerging infectious diseases as well as possible solutions, which was carried out between November 2013 and August 2014. The results of this research are discussed from an ecosystemic approach to human health, recognizing the complexity of environmental conflicts related to water resources and their impacts on the health of populations. Through the methodology used, it is possible to detect and visualize the most urgent problems as well as frequent causes of contamination of water resources so as to propose solutions within a joint agenda of multiple social actors.

Quadruple therapy versus standard triple therapy for eradication of Helicobacter pylori in Kuwait

Background and study aims: Chronic infection caused by Helicobacter pylori [H. pylori] is associated with chronic gastritis, peptic ulcer disease, and gastric cancer. Eradication of H. pylori reduces morbidity of chronic gastritis and incidence of gastric cancer in high-risk population. We aimed at testing the efficacy of clarithromycin-based triple therapy and bismuth-based quadruple therapy for eradicating H. pylori in patients with chronic gastritis in Kuwait

Patients and methods: A total of 218 dyspeptic patients from different countries who were proved to have chronic gastritis by endoscopy and gastric biopsy were enroled. All of them were naïve to H. pylori eradication therapy. They were randomised into two groups: group A, received triple therapy [omeprazole, amoxicillin, and clarithromycin] for 10 days, and group B, received quadruple therapy [omeprazole, bismuth subcitrate potassium, tetracycline, and metronidazole] for 10 days. All patients were tested for eradication of H. pylori by carbon-13 urea breath test 4 weeks after treatment

Results: Total response rate of eradication therapy in both groups was 77.5% [n = 169]. However, group B [n = 100] had a higher eradication rate [88%] than group A [n = 118] [68.6%]. H. pylori eradication rate was significantly higher in males [84.2%] than females [70.2%] in both groups [p < 0.01]. There were no differences in eradication rates with regard to median age or nationality

Conclusion: Bismuth-based quadruple therapy is more effective as a first-line therapy than clarithromycin-based triple therapy for eradicating H. pylori in patients with H. pylori-related chronic gastritis in Kuwait

Epidemiology of Helicobacter pylori infection among Iranian children

Background and study aims: Infection with Helicobacter pylori [HP] either in children or in adults is a risk factor for gastric cancer. The Golestan province located in northeast Iran has been known to be a high-risk area for oesophageal and gastric cancers. This study was conducted to assess the epidemiology of this infection in the children of Golestan

Patients and methods: This study was carried out in 2009 on healthy children [1-15 years] of the Golestan province. Serum immunoglobulin G [Ig G] antibody against HP was tested in these children and positive samples were tested for anti-cytotoxin-associated antigen A [anti-CagA] antibody. To assess the relationship between HP infection and the risk of gastric cancer, the Golestan province was divided into high- and low-risk areas based on the incidence rate of gastric cancer. The chi-squared test was used to assess the relationship between variables

Results: Totally, 194 subjects were recruited. The prevalence of HP infection in our area was 50.5%. The prevalence of HP infection was significantly higher in the high-risk than in the low-risk area for stomach cancer [p = 0.004]. The seropositivities of HP [p = 0.03] and CagA [p = 0.04] were significantly lower in children <5 years than in others

Conclusion: Our results showed a high prevalence of HP infection in children of the Golestan province of Iran. We also found a significant positive relationship between childhood HP infection and the risk of gastric cancer. Hence, childhood HP infection may be considered a possible determinant of gastric cancer in this high-risk area. Implementation of preventive programmes may help to reduce the burden of childhood HP infection and, consequently, gastric cancer in this area

[ effects of docosahexaenoic acid [DHA] on helicobacter pylori eradication, some serum inflammatory factors and total antioxidant capacity]

As regard to high prevalence of Helicobacter pylori infection and complications of it's persistence, as well as anti-bacterial activity against of Helicobacter pylori and anti-inflammatory properties of omega-3 fatty acids, this study was conducted to evaluate the effects of supplementation with Docosahexaenoic Acid [DHA] on the eradication of Helicobacter pylori infection, some serum inflammatory markers and total antioxidant capacity. In a double-blind, placebo-controlled clinical trial, 66 H. pylori positive patients [33 in the intervention group and 33 in the control group], along with tetradrugs H. pylori eradication regimen, randomly received daily two grams morDHA supplement or Medium Chain Triglyceride [MCT] oil as placebo for 12 weeks. Dietary intake data was collected by 24 hour food recall and analyzed by Nutritionist IV software. Sampling from fasting blood and measuring weight, height, body mass index [BMI] and level of physical activity were done at the first and the end of the study. As well as, eradication test of the infection was performed for all patients at the end of the intervention. Eradication rate of the infection, the level of interleukin-6 [IL-6], high sensitivity C-reactive protein [hs-CRP] and total antioxidant capacity [TAC] didn't have significant difference between two groups at the end of the study [P>0.05], while the level of interleukin-8 [IL-8] was different between two groups [P=0.008]. Difference of the concentration between the beginning and the end of the study was not significant in any factors between two groups [P>0.05]. Intake of morDHA supplement didn't have significant effect on the eradication of H. pylori, serum levels of IL-6, hs-CRP and TAC, while it was effective on the level of IL-8.

Helicobacter pylori infection in India from a western perspective.

Helicobacter pylori is a common bacterial infectious disease whose manifestations predominately affect the gastrointestinal tract. India is the prototypical developing country as far as H. pylori infection is concerned and more than 20 million Indians are estimated to suffer from peptic ulcer disease. Considering the high level of medical research and of the pharmaceutical industry, one would expect that India would be the source of much needed information regarding new therapies and approaches that remain effective in the presence of antimicrobial resistance, new methods to reliably prevent reinfection, and the development of therapeutic and preventive vaccines. Here we discuss H. pylori as a problem in India with an emphasis on H. pylori infection as a serious transmissible infectious disease. We discuss the pros and cons of eradication of H. pylori from the entire population and come down on the side of eradication. The available data from India regarding antimicrobial use and resistance as well as the effectiveness of various treatments are discussed. Rigorous ongoing studies to provide current regional antibiotic resistance patterns coupled with data concerning the success rate with different treatment regimens are needed to guide therapy. A systematic approach to identify reliably effective (e.g., 90% or greater treatment success) cost-effective regimens is suggested as well as details of regimens likely to be effective in India. H. pylori is just one of the health care problems faced in India, but one where all the resources are on hand to understand and solve it.

Receptores tipo Toll, patogénesis y respuesta inmune a Helicobacter pylori / Toll-like receptors, pathogenesis and immune response to Helicobacter pylori

Helicobacter pylori coloniza el epitelio gástrico y la mayoría de las personas infectadas es asintomática, de 10 al 20 por ciento desarrolla gastritis atrófica, úlcera péptica, y menos de 3 por ciento genera cáncer gástrico. Estas patologías están determinadas por la relación entre los factores de virulencia de la bacteria y los factores del hospedero como predisposición genética y respuesta inmune. La inmunidad innata, representada principalmente por los receptores tipo Toll y tipo Nod, reconocen a sus ligandos específicos y activan factores de transcripción como NF-kB, AP-1, CREB-1, induciendo la producción de citocinas inflamatorias como IL-8, IL-12, IL-6, IL-1β, IL-18 y TNF-α, e IL-10. La inflamación crónica favorece los cambios de morfología gástrica, evita la apoptosis y favorece la angiogénesis, ocasionando lesiones neoplásicas y cáncer. El objetivo de esta revisión es analizar los mecanismos propuestos a la fecha de la respuesta inmune innata y adaptativa, involucrados en la infección por H. pylori, y se puntualiza en los mecanismos de eliminación o persistencia de la infección.

Helicobacter pylori colonize the gastric epithelial, most infected people are asymptomatic, 10 to 20 percent develop atrophic gastritis, peptic ulcer and less than 3 percent gastric cancer. These diseases are determined by the relationship between virulence factors of bacteria, host factors such as, genetic predisposition, and immune response. The innate immune response mainly represented by Toll-like receptors and Nod-like receptors that recognize their specific ligands, activate transcription factors as NF-kB, AP-1, CREB-1, inducing production of inflammatory cytokines such as IL -8, IL-12, IL-6, IL-1β, IL-18, TNF-α and IL-10. Chronic inflammation promotes gastric morphological changes, prevents apoptosis and allows angiogenesis generating neoplasic lesions and cancer. The aim of this review is to analyze the mechanisms proposed to date of the innate and adaptative immune response involved in H. pylori infection; remarking the mechanisms related in the elimination or persistence.

Helicobacter pylori infection in India from a western perspective.

Helicobacter pylori is a common bacterial infectious disease whose manifestations predominately affect the gastrointestinal tract. India is the prototypical developing country as far as H. pylori infection is concerned and more than 20 million Indians are estimated to suffer from peptic ulcer disease. Considering the high level of Medicine and of the pharmaceutical industry, one would expect that India would be the source of much needed information regarding new therapies and approaches that remain effective in the presence of antimicrobial resistance, new methods to reliably prevent reinfection, and the development of therapeutic and preventive vaccines. Here, we discuss H. pylori as an Indian problem with an emphasis on H. pylori infection as a serious transmissible infectious disease. We discuss the pros and cons of eradication of H. pylori from the entire population and come down on the side of eradication. The available data from India regarding antimicrobial use and resistance as well as the effectiveness of various treatments is discussed. Rigorous ongoing studies to provide current regional antibiotic resistance patterns coupled with data concerning the success rate with different treatment regimens are needed to guide therapy. A systematic approach to identify reliably effective (e.g., 90% or greater treatment success) cost-effective regimens is suggested as well as details of regimens likely to be effective in India. H. pylori is just one of the health care problems faced in India, but one where all the resources are on hand to understand and solve it.

Prevalencia de Helicobacter pylori y de genes asociados a virulencia en biopsias gástricas / Prevalence of Helicobacter pylori virulence genes in gastric biopsies in Chilean patients over a 10-year period

Introducción: La detección de genes asociados a virulencia en Helicobacter pylori constituye un buen marcadorgenético para predecir riesgo de enfermedades asociadas a la persistencia del patógeno. Objetivos: Determinar la prevalencia de cagA, vacA, babA2, iceA y dupA en pacientes chilenos, durante 10 años de seguimiento. Métodos: Se analizaron las biopsias gástricas de 1 577 pacientes (183 niños) obtenidas entre enero de 2003 y diciembre de 2007, mediante PCR convencional y cultivo bacteriano. En 374 individuos positivos se investigó la prevalencia de cagA, vacA (s1a, s1b, s2, m1, m2, i1 e i2), babA2, iceA (1 y 2) y dupA. Resultados: La prevalenciade H. pylori en adultos fue 48.7% y un 23.7% de los pacientes presentó más de un cepa bacteriana. La prevalenciapor genes fue: cagA 29.4%, vacAm1 52.7%, vacAm2 61.8%, vacAs1a 46.5%, vacAs1b 28.3%, vacAs2 41.7%, vacAi1 30.9%, vacAi2 12.0%, babA23.5%, iceA1 30.5%, iceA2 61.2% y dupA 28.9%. Se observó un 90% de concordancia en la prevalencia delos genes hpy, cagA, babA2, iceA e iceA2, y un 67.6% para vacAs1a, cuando se comparó biopsia y cultivo como fuente de ADN. Conclusiones: La mayoría de los genes de virulencia han mantenido su prevalencia en el tiempo,excepto vacAm1 y babA2 que la han aumentado. Sin embargo, la prevalencia de babA2 continúa siendo muy baja.

Background: Genes associated with virulence in Helicobacter pylori are good markers for prediction of risk of developing diseases due to persistent infection. Aim: To establish the prevalence of cagA, vacA, babA2,iceA and dupA among Chilean patients over a 10-year period. Methods: 1 577 gastric biopsies (183 children), collected from January 2003 to December 2007, were analyzed by conventional PCR and bacteriological culture. The prevalence of the genes cagA, vacA (s1a, s1b, s2, m1, m2, i1 and i2), babA2, iceA (1 and 2) and dupA were investigated in 374 positive individuals. Results: Prevalence of H. pylori in adults was 48.7%, with 23.7% of them presenting more than one infecting strain. Prevalence of genes was as follows: cagA 29.4%, vacAm152.7%, vacAm2 61.8%, vacAs1a 46.5%, vacAs1b 28.3%, vacAs2 41.7%, vacAi1 30.9%, vacAi2 12.0%, babA2 3.5%, iceA1 30.5%, iceA2 61.2% and dupA 28.9%. Ninety percent of agreement was observed in the prevalence of genes hpy, cagA, babA2, iceA and iceA2, by using DNA from both sources, but was only 67.6% for vacAs1a gene. Conclusion: The results suggest that all the genes conserved their prevalence in this period with the exception of vacAm1 and babA2, in which there was increased prevalence. Nonetheless, the prevalence of the gene babA2 continues to be very low.

Helicobacter pylori vaccine: mucosal adjuvant & delivery systems.

Vaccination, especially mucosal vaccination, is considered to be effective in the management of Helicobacter pylori infections. However, most antigens alone cannot induce immune responses when administered mucosally and need to be co-administered with adjuvants or delivery systems. The current research on the mucosal adjuvant and delivery systems of vaccine against H. pylori, including advantages and disadvantages, mechanisms and applications is discussed in this review. Mutants of cholera toxin (CT) and the heat labile enterotoxin of Escherichia coli (LT), CpG oligodeoxynucleotides, biocompatible and biodegradable polymers, and live attenuated bacterial vectors may be promising adjuvant and delivery systems for H. pylori vaccine.

Helicobacter pylori infection in developing countries: the burden for how long?

Approximately 50% [over 3 billion] of the world populations are known to be infected with Helicobacter pylori, mainly in the developing countries. Among those, hundreds of millions of people develop peptic ulceration during their lifetime and still tens of millions might progress to gastric cancer. Possible modes of H. pylori transmission generally described are through direct contact between family members and also through contaminated water and food. Because the high prevalence of infection occurs mainly in developing countries and because the test-and-treat strategy puts a huge economic burden on many of these countries, it is time to take an immediate action toward this bacterial infection and adopt a strategy to prevent it. To address this issue, an updated prevalence of infection, modes of transmission, economics of infection and preventative measures to block the infection process have been discussed

Probióticos: perspectivas médicas / Probiotics: medical perspectives

Este artigo revisa o tema probióticos com o objetivo de avaliar seus possíveis potenciais como agentes bioterapêuticos na prevenção e/ou tratamento de algumas doenças relacionadas com a via intestinal. Os probióticos representam uma área de pesquisa em extensão. Muitas publicações enfatizam o potencial significado dessa emergente área, entretanto muito ainda necessita ser comprovado e realizado no sentido de definir o real significado do termo probiótico; se for efetivo, quais as cepas que preenchem os critérios de um real microorganismo probiótico e em quais circunstâncias clínicas são indicadas

This article reviews the theme probiotics with the objective to evaluate their potentials as possible biotherapeutic agents for the prevention and/or treatment of some illnesses related tothe intestinal tract. Probiotics represents an expanding research area. Many publications emphasizes the potential significance of this emerging field, meanwhile, much still remains to be proved and to be done in order to standardize the real meaning of the term probiotic and, if they are real, which strains actually fulfill the criteria of true probiotics microorganisms and in which clinical circumstances they are really useful

Vacunas en desarrollo: Helicobacter pylori / Vaccines under development: Helicobacter pylori

La infección con Helicobacter pylori es la causa de patologías gastrointestinales como úlcera péptica y cáncer gástrico. Una vacuna contra H. pylori es relevante debido a la alta prevalencia de la infección y a la morbi-mortalidad asociada a ésta en nuestro país. El uso masivo de terapias antimicrobianas actuales no es una estrategia factible, especialmente en países en desarrollo, en parte debido al alto costo, los múltiples efectos adversos, el riesgo de reinfección y la emergencia de resistencia a los antimicrobianos. Numerosos modelos animales han sido utilizados durante años para determinar el curso de la infección por H. pylori y explorar la factibilidad de una vacuna, ya sea para erradicar o prevenir la infección. Dichos modelos, con la posible excepción de los monos, no son suficientes para responder preguntas fundamentales debido a resultados contradictorios. Un modelo humano de infección por H. pylori debe ser desarrollado con el principal propósito de seleccionar vacunas óptimas. El objetivo final es el desarrollo de estudios de campos de vacunas candidatas, pero el estado actual del conocimiento no proporciona una metódica adecuada para seleccionar tales vacunas candidatas promisorias. Dichos estudios pueden ser diseñados para proporcionar información relevante sobre la inmunidad y patogénesis de la infección por H. pylori.

El consumo regular de lactobacillus johnsonII LA1 interfiere con la colonización gástrica por Hepilobacter Pylori / Regular intake of lactobacillus JohnsonII LA1 interferes with Helicobacter Pylori colonization

La ingestión de probióticos ha sido recientemente propuesta como una posible "herramienta" en el manejo de los individuos colonizados por Helicobacter pylori (Hp). El objetivo de este estudio es evaluar si el consumo regular de un producto comercial con Lactobacillus johnsonii La1 (La1) puede interferir con la colonización gástrica por Hp, y si dicho efecto puede ser mayor a mayor frecuencia de ingestión del producto a lo largo del día. Un primer estudio clínico randomizado de doble ciego se realizó en niños de 6 a 17 años, de una escuela de nivel socioeconómico bajo de Santiago. Los niños determinados como Hp-positivos mediante el test de aire espirado con 13C-urea (13C-UBT) fueron distribuidos en 3 grupos para recibir durante 4 semanas 160 ml diarios de uno de tres productos: 1) uno con La1 vivo, 2) el mismo termizado con La1 muerto o 3) el mismo sin La1 (control). Un segundo 13C-UBT se les realizó al final del período. En el siguiente estudio se reclutaron 11 voluntarios Hp-positivos asintomáticos, que tomaron el producto con La1 vivo cada día y por 2 semanas a razón de 80 ml cada 2 horas de la 8:00h hasta las 22:00h (640 ml en total). Se les realizó un 13C-UBT antes y a 1 y 2 semanas de tomar el producto. Las muestras de aire de ambos estudios se analizaron por espectrometría de masa de relación isotópica y los resultados se expresaron como exceso por mil de 13C por sobre los niveles basales: DOB (por ciento). En el primer estudio se observó una disminución significativa (p<0.05) de 11.9 por ciento de los valores basales de DOB en los niños después de 4 semanas de consumo del producto con La1 vivo y que no hubo diferencia en los otros 2 grupos. En el estudio con voluntarios sanos, los valores de DOB fueron disminuyendo significativamente a lo largo del estudio, (Anova F=4.2, p<0.04), llegando a un disminución del 41 por ciento de los niveles basales de DOB. En ambos estudios se observó una correlación entre los valores basales de DOB y la amplitud de la disminución inducida por la ingestión del probiótico. Estos resultados indican que la ingestión regular del probiótico L. johnsonii La1 interfiere con Hp en los individuos colonizados por este patógeno:dicho efecto es mayor cuando el consumo de La1 es más frecuente a lo largo del día, y es proporcional a los niveles basales de colonización por Hp presentes en el sujeto.