Browsing by Author "Lopes, Ana Isabel"
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- Helicobacter pylori - Associated Dyspepsia in PaediatricsPublication . Roxo-Rosa, Mónica; Oleastro, Mónica; Lopes, Ana IsabelHelicobacter pylori ubiquitously infects the human gastric mucosa since time immemorial,predictably before the man’s diaspora out of East Africa around 58,000 years ago [1].Colonization may have been somehow beneficial for human carriers, allowing the coevolutionof this gram-negative bacterium and its host over the centuries. Yet, at leastnowadays [2], this may not be a peaceful association, with infection almost invariablycausing an acute host immune response. However, in a fully adapted manner, H. pyloriavoids recognition and, thus, clearance, by the host immune system, with both infectionand the consequent gastritis persisting throughout the patients’ life. The clinical outcomeof this persistence is dependent on a sophisticated crosstalk between the host and thepathogen. If often asymptomatic, the H. pylori-associated non-ulcer dyspepsia is clearly thestrongest aetiological factor for severe gastric diseases that will develop late in adult life ina minority of infected patients, i.e., peptic ulcer disease, both gastric and duodenal ulcers,and gastric cancer, namely, adenocarcinoma and mucosa associated lymphoid tissue(MALT) lymphoma (reviewed in [3]). Peptic ulcer disease rarely occurs soon after H. pyloriinfection [4-8] that generally starts in childhood; this presumably reflects marked differencesin the virulence [9-16] and/or in the susceptibility of young patients [17-19].This chapter, focussing on the paediatric population, seeks to explore: the prevalence of H.pylori infection; the molecular mechanism used by H. pylori during colonization and infection;the role of this bacterium in the development of peptic ulcer-related organic dyspepsia; andthe genetic/proteome profile of the H. pylori-strains associated with peptic ulcer disease.
- Helicobacter pylori Infection in Pediatric Patients Living in Europe: Results of the EuroPedHP Registry 2013 to 2016Publication . Kori, Michal; Le Thi, Thu Giang; Werkstetter, Katharina; Sustmann, Andrea; Bontems, Patrick; Lopes, Ana Isabel; Oleastro, Monica; Iwanczak, Barbara; Kalach, Nicolas; Misak, Zrinjka; Cabral, José; Homan, Matjaž; Cilleruelo Pascual, Maria Luz; Pehlivanoglu, Ender; Casswall, Thomas; Urruzuno, Pedro; Martinez Gomez, Maria José; Papadopoulou, Alexandra; Roma, Eleftheria; Dolinsek, Jernej; Rogalidou, Maria; Urbonas, Vaidotas; Chong, Sonny; Kindermann, Angelika; Miele, Erasmo; Rea, Francesca; Cseh, Áron; Koletzko, Sibylle; Helicobacter pylori Working Group of ESPGHANObjectives: The aim of the study was to assess clinical presentation, endoscopic findings, antibiotic susceptibility and treatment success of Helicobacter pylori (H. pylori) infected pediatric patients. Methods: Between 2013 and 2016, 23 pediatric hospitals from 17 countries prospectively submitted data on consecutive H. pylori-infected (culture positive) patients to the EuroPedHP-Registry. Results: Of 1333 patients recruited (55.1% girls, median age 12.6 years), 1168 (87.6%) were therapy naïve (group A) and 165 (12.4%) had failed treatment (group B). Patients resided in North/Western (29.6%), Southern (34.1%) and Eastern Europe (23.0%), or Israel/Turkey (13.4%). Main indications for endoscopy were abdominal pain or dyspepsia (81.2%, 1078/1328). Antral nodularity was reported in 77.8% (1031/1326) of patients, gastric or duodenal ulcers and erosions in 5.1% and 12.8%, respectively. Primary resistance to clarithromycin (CLA) and metronidazole (MET) occurred in 25% and 21%, respectively, and increased after failed therapy. Bacterial strains were fully susceptible in 60.5% of group A, but in only 27.4% of group B. Primary CLA resistance was higher in Southern and Eastern Europe (adjusted odds ratio [ORadj] = 3.44, 95% confidence interval [CI] 2.22–5.32, P < 0.001 and 2.62, 95% CI: 1.63–4.22, P < 0.001, respectively) compared with Northern/Western Europe. Children born outside Europe showed higher primary MET resistance (ORadj = 3.81, 95% CI: 2.25–6.45, P < 0.001). Treatment success in group A reached only 79.8% (568/712) with 7 to 14 days triple therapy tailored to antibiotic susceptibility. Conclusions: Peptic ulcers are rare in dyspeptic H. pylori-infected children. Primary resistance to CLA and MET is markedly dependent on geographical regions of birth and residence. The ongoing survey will show whether implementation of the updated ESPGHAN/NASPGHAN guidelines will improve the eradication success.
- Infeção por H. pylori em endoscopia digestiva: evolução da prevalência e perfil clínicoPublication . Almeida, Mónica; Rodrigues, Teresa; Palha, Ana; Oleastro, Mónica; Lopes, Ana IsabelIntrodução: A diminuição da prevalência da infecção por H. pylori (Hp) tem sido reportada mundialmente, paralelamente à melhoria das condições socio‑económicas. Tanto quanto é do nosso conhecimento, não existem em Portugal estudos de prevalência em crianças sintomáticas submetidas a endoscopia digestiva. Objectivos: Constituíram objectivos deste estudo: avaliar a prevalência da infecção por Hp num período de 10 anos (3 anos representativos) numa amostra da população pediátrica Portuguesa sintomática submetida a endoscopia digestiva; descrever aspectos clínicos associados à infecção na mesma amostra. Métodos: Estudo descritivo e analítico retrospectivo. Efectuada revisão de 359 endoscopias diagnósticas realizadas em 2002, 2006 e 2011 num centro terciário de Gastroenterologia Pediátrica (Lisboa), idade ≤18 anos, com realização de biopsia gástrica, para avaliação da prevalência global de infecção e associação do status Hp com variáveis clínicas, indicações para realização de endoscopia, achados endoscópicos e histológicos. Considerou‑se status Hp(+) se histologia e/ou cultura positivas; status Hp(‑) se histologia e cultura simultaneamente negativas. Estatística: teste Qui‑quadrado, teste Exacto de Fisher; α=0,05. Resultados: A indicação mais frequente para endoscopia foi dor abdominal/ epigastralgias (53.8%); 175 (48,7%) crianças/jovens evidenciaram status Hp(+): 11,4% ≤5anos, 48% 5≤11anos, 40.6% 11≤18 anos. A prevalência média da infecção foi de 57.1% em 2002, 55.5% em 2006 e 41,3% em 2011, sendo a diminuição significativa no último período (p=0,02). Diminuição verificada nos três subgrupos etários, significativa apenas no subgrupo 5≤11 anos (p=0,042). Achados endoscópicos associados ao status Hp(+) VS Hp(‑): esófago normal (p=0,032), nodularidade antral/corpo (p<0,001) e úlcera duodenal (p=0,013); achados histológicos associados ao status Hp(+) VS Hp(‑): inflamação moderada (p<0,001), actividade ligeira e moderada (p<0,001) e presença de folículos/ agregados linfóides (p<0,005). Conclusões: Contrariamente a estudos efectuados em idêntico contexto noutras populações, constatou‑se uma prevalência ainda elevada da infecção por Hp, sugerindo embora uma tendência recente para a sua diminuição, principalmente em crianças em idade escolar. Alguns achados endoscópicos e histológicos associaram‑se de forma significativa à presença de infecção por Hp. Estes resultados enfatizam a relevância da infecção por Hp na população pediátrica Portuguesa sintomática e a necessidade de adopção de estratégias de abordagem com adequada relação custo‑efectividade
- Prevalence and incidence of Helicobacter pylori Infection in a healthy pediatric population in the Lisbon areaPublication . Oleastro, Mónica; Pelerito, Ana; Nogueira, Paulo; Benoliel, João; Santos, Andrea; Cabral, José; Lopes, Ana Isabel; Ramalho, Paulo; Monteiro, LurdesBACKGROUND: Helicobacter pylori is mainly acquired in childhood. Although adult studies reported a high prevalence of H. pylori infection in Portugal, the actual rate in children remains unknown. This study aimed to determine the prevalence and the incidence of H. pylori infection in an asymptomatic pediatric population of the Lisbon area and to correlate prevalence with sociodemographic determinants. MATERIALS AND METHODS: Helicobacter pylori infection was determined by stool antigen test in 844 asymptomatic children (age 0-15 years; 49.4% boys). For the incidence study, H. pylori-negative children in the prevalence study were followed-up every 6 months over a 3-year period. RESULTS: The global prevalence of H. pylori infection was 31.6%, increasing with age (19.9, 37.0 and 51.5%, in age groups 0-5, 6-10, and 11-15, respectively), but was similar among genders (34.5% in boys and 28.4% in girls). Older age and attendance of nursery/kindergarten during preschool constituted independent risk factors. The overall estimated incidence was 11.6 per 100 child-years (CY). Although 47.5% of children acquired H. pylori infection before 5 years of age, the mean age of acquisition was 6.3. The incidence of infection was similar among the three age groups (11.5, 13.0, and 10.5 per 100 CY, in age groups 0-5, 6-10, and 11-15, respectively). CONCLUSIONS: The prevalence of H. pylori infection in the Portuguese pediatric population is still high. Although this study confirmed that the highest acquisition rate occurs at young age, it showed that in high-prevalence populations, older children can also acquire H. pylori infection at a rate similar to that of young children.
- Primary antibiotic resistance of Helicobacter pylori strains isolated from Portuguese children: a prospective multicentre study over a 10 year periodPublication . Oleastro, Mónica; Cabral, José; Ramalho, Paulo; Lemos, Piedade Sande; Benoliel, João; Paixão, Eleonora; Santos, Andrea; Lopes, Ana IsabelOBJECTIVES: The aim of this study was to prospectively assess the pattern of evolution of primary resistance to antibiotics in Helicobacter pylori strains isolated from Portuguese children over a 10 year period (2000-09). METHODS: A total of 1115 H. pylori strains were tested for antibiotic susceptibility to clarithromycin, metronidazole, amoxicillin, ciprofloxacin and tetracycline. RESULTS: H. pylori strains were isolated from children and adolescents [ages 4 months-18 years (mean age 10.17 ± 4.03 years)], comprising 562 (50.4%) boys and 553 (49.6%) girls. Overall, the primary resistance rate was 34.7% to clarithromycin, 13.9% to metronidazole and 4.6% to ciprofloxacin, while 6.9% were resistant to two of these antibiotics simultaneously. Resistance to amoxicillin and to tetracycline was not detected. In general, the resistance rate was not associated with gender or the children's age. European ethnicity, when compared with an African background, was associated with clarithromycin resistance [P = 0.002; odds ratio (OR) = 0.30; 95% confidence interval (CI) 0.14-0.66], while the inverse situation was observed for metronidazole (P < 0.001; OR = 3.50; 95% CI 1.90-6.45). No significant temporal trend was noticed for resistance to clarithromycin and metronidazole, whereas ciprofloxacin and double-resistance rates have significantly increased over time (P = 0.004 and P = 0.05, respectively). CONCLUSIONS: The primary resistance rate of H. pylori strains isolated from Portuguese children to the commonly used anti-H. pylori antibiotics used is high. Additionally, the increasing trend of ciprofloxacin-resistant and double-resistant strains may compromise H. pylori eradication in a high-prevalence population.
- The ulcerogenic profile of Helicobacter pylori paediatric strains associated with peptic ulcer disease.Publication . Vitoriano, Inês; Saraiva-Pava, Kathy; Rocha-Gonçalves, António; Alves-Matos, Pedro; Vale, Filipa; Santos, Andrea; Lopes, Ana Isabel; Oleastro, Mónica; Roxo-Rosa, MónicaHelicobacter pylori infection is the major cause of paediatric peptic ulcer disease (PUD). In children with no other aetiology for the disease, this rare event occurs shortly after infection, presuming a still poorly understood higher susceptibility of the patient and highlighting the virulence of the implicated strain. Recently, we showed that the enhanced virulence of a group of paediatric ulcerogenic-strains result from a synergy between their ability to better adapt to the hostility of their niche and the expression of cagA, vacAs1, oipA ‘‘on’’ status, homB and jhp5621. Accordingly, these ulcerogenic strains share a particular proteome profile, providing them with better antioxidant defences, a metabolism favouring the biosynthesis of aromatic amino acids and higher motility1. Corroborating these findings, our preliminary data on electronic microscopic analyses demonstrated the presence of more abundant flagella in PUD-associated paediatric strains, in contrast to the control strain, a paediatric strain associated with non-ulcer dyspepsia (NUD). Compared with paediatric NUD-associated isolates, ulcerogenic H. pylori strains present a greater ability to induce a marked decrease in the gastric cells’ viability and to cause them severe cytoskeleton damage and mucins’ production/secretion impairment1. To uncover the underlying molecular mechanisms, we are now characterizing the modifications induced by these strains in the proteome of human gastric cells, during in vitro infection, by two-dimensional gel electrophoresis followed by mass-spectrometry.
- Time trend prevalence of helicobacter pylori infection and endoscopic findings in symptomatic children in Portugal: A retrospective study based on three time points in 2009, 2014, and 2019Publication . Antunes, Raquel; Oleastro, Monica; Nogueira, João Paulo; Lopes, Ana IsabelBackground: Helicobacter pylori infection acquisition occurs mainly in childhood and may be a critical factor in developing long-term complications. In contrast to other developed countries, previous studies have reported a relatively high H. pylori infection prevalence in Portugal, both in children and adults. However, there are no recent data concerning pediatric population. Materials and Methods: We performed a retrospective observational study concerning an 11 years period (2009, 2014, 2019), that included patients under 18 years old who underwent upper endoscopy at a pediatric tertiary center. Demographic, clinical-pathological, and microbiological data were collected. Results: Four hundred and sixty one children were included. The average age was 11.7 ± 4.4 years. In total, H. pylori infection was confirmed in 37.3% of cases (histology and/or culture) and a decreasing infection trend was observed (p = .027). The most common indication for endoscopy was abdominal pain, which was a good predictor of infection. Antral nodularity was present in 72.2% of the infected children (p < .001). In the oldest age groups, moderate/severe chronic inflammation, H. pylori density and lymphoid aggregates/follicles were positive predictors for the presence of antral nodularity. For all ages, the presence of antral nodularity, neutrophilic activity in the antrum and corpus and lymphoid follicles/aggregates in the antrum were positive predictors for the presence of H. pylori infection. Among the 139 strains tested for antibiotic susceptibility, 48.9% were susceptible to all tested antibiotics. Resistance to clarithromycin, metronidazole, and both was detected in 23.0%, 12.9%, and 6.5% of the strains, respectively; furthermore, resistance to ciprofloxacin and to amoxicillin was observed in 5.0% and 1.4% of the strains, respectively. Conclusions: The present study reports (for the first time in Portugal) a significant decreasing trend in the prevalence of pediatric H. pylori infection, although it remains relatively high compared to the recently reported prevalence in other South European countries. We confirmed a previously recognized positive association ofsome endoscopic and histological features with H. pylori infection, as well as a high prevalence rate of resistance to clarithromycin and to metronidazole. The clinical relevance of these findings requires confirmation with further studies at a national level, taking into account the high incidence rate of gastric cancer in Portugal and the potential need for country-specific intervention strategies.
- Ulcerogenic Helicobacter pylori Strains Isolated from Children: A Contribution to Get Insight into the Virulence of the BacteriaPublication . Vitoriano, Inês; Saraiva-Pava, Kathy; Rocha-Gonçalves, Alexandra; Santos, Andrea; Lopes, Ana Isabel; Oleastro, Mónica; Roxo-Rosa, MónicaInfection with Helicobacter pylori is the major cause for the development of peptic ulcer disease (PUD). In children, with no other etiology for the disease, this rare event occurs shortly after infection. In these young patients, habits of smoking, diet, consumption of alcohol and non-steroid anti-inflammatory drugs and stress, in addition to the genetic susceptibility of the patient, represent a minor influence. Accordingly, the virulence of the implicated H. pylori strain should play a crucial role in the development of PUD. Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD) showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins. To uncover virulence features, we compared the proteome of these two groups of H. pylori strains. Two-dimensional gel electrophoresis followed by mass-spectrometry allowed us to detect 27 differentially expressed proteins between them. In addition to the presence of genes encoding well established virulence factors, namely cagA, vacAs1, oipA "on" status, homB and jhp562 genes, the pediatric ulcerogenic strains shared a proteome profile characterized by changes in the abundance of: motility-associated proteins, accounting for higher motility; antioxidant proteins, which may confer increased resistance to inflammation; and enzymes involved in key steps in the metabolism of glucose, amino acids and urea, which may be advantageous to face fluctuations of nutrients. In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence factors.
- Ulcerogenic profile of helicobacter pylori pediatric strains: a contribution to get insight into the virulence of the BacteriaPublication . Vitoriano, Inês; Saraiva-Pava, Kathy; Rocha-Gonçalves, Alexandra; Santos, Andrea; Lopes, Ana Isabel; Oleastro, Mónica; Roxo-Rosa, Mónica