H-pylori cagA+ and milder duodenal histological changes
This week we suggest an article published in August 2017 on Frontiers in cellular and infection microbiology, Helicobacter pylori cagA+ is associated with milder duodenal histological changes in Chilean celiac patients. You can find the full article here.
SUMMARY:Celiac disease (CD) is an immune-mediated systemic disorder, triggered by ingested gluten and related prolamines in genetically susceptible individuals. CD has progressively increased in prevalence and is associated with significant morbidity, impacting quality of life and health care costs. Overall prevalence is nearly 1%; in Chile, the prevalence of anti-transglutaminase (tTG) antibodies detection, in individuals older than 15 years of age, is 0.8%.The intestinal microbiota is currently under intense evaluation as a potentially relevant pathogenic factor in CD. Helicobacter pylori (H. pylori), a Gram negative spiral bacterium capable of infecting human gastric mucosa, has also been isolated from the duodenum. There is evidence that H. pylori is associated with an increased regulatory T cell response in blood and gastric mucosa, with higher number of Foxp3+ T cells and higher expression of Foxp3 and TGF-b mRNA/protein and a protective role against atopy. Particularly, CagA, a pleomorphic virulence factor of H. pylori, involved in oncogenesis and epithelial barrier disfunction, has also been involved in T-reg pathway activation, and some studies have supposed a modulator role in CD.The authors reported the results of a multicenter, prospective study, performed in Santiago (Chile), in which, between January 2013 and July 2015, a total of 116 patients (1 to 50 years of age) were enrolled: 66 with CD and 50 non-CD. The diagnosis of CD was determined through the anti-tTG, upper gastrointestinal endoscopy and HLA typing. Patients were classified in three groups: active-CD, potential-CD and non-CD patients.A trend toward higher frequency of DQ2/DQ2 and DQ2/DQ8 haplotypes, the presence of abdominal distension and steatorrhea were observed in the active-CD group, compared to potential-CD individuals. Female gender was more frequent, and anti-tTG titers were higher in active-CD, compared to potential-CD patients.Overall H. pylori infection rates were similar between subjects with and without CD, and were independent of the severity of duodenal atrophy in the latter. However, in individuals infected by H. pylori, detection of cagA+ strains was significantly more common among individuals with potential-CD compared to active-CD and non-CD patients (p = 0.02). Among infected subjects, the presence of cagA+ strains was significantly associated with milder histological damage.Overall histological gastritis was more common in non-CD subjects infected with H. pylori, compared to non-infected patients (p = 0.003); however, there was only a trend toward increased gastritis in H. pylori positive individuals in the potential-CD (p = 0.069) and active-CD groups (p = 0.091). There was no association between histological gastritis and cagA+ strains. In patients with active-CD, infected with H. pylori cagA+, the number of Foxp3 positive cells was significantly higher, compared to all the other active-CD groups, as well as to potential-CD subjects infected by cagA+ H. pylori (p < 0.05).TGF-b1 protein concentration, in duodenal biopsies, showed a tendency to be higher in active-CD, compared to potential CD overall (p = 0.19). Individuals infected by cag+ H. pylori strains had lower TGF-b1 levels than non-infected individuals, that was statistically significant in the potential-CD group (p = 0.04).The authors concluded that the similar H. pylori infection rates, among individuals with and without CD, and the association between cagA+ strains and milder histological damage in celiac patients, infected by H. pylori, and in active-CD cases could suggest that infection by cagA+ H. pylori may be protective for CD progression, or conversely, that these strains are prone to colonize when intestinal damage is less severe.
AUTHORS: Lucero Y, Oyarzún A, O'Ryan M, Quera R, Espinosa N, Valenzuela R, Simian D, Alcalde E, Arce C, Farfán MJ, Vergara AF, Gajardo I, Mendez J, Carrasco J, Errázuriz G, Gonzalez M, Ossa JC, Maiza E, Perez-Bravo F, Castro M, Araya M.
MDR-TB and beyond: current evidence on bedaquiline
The article we suggest this week,"Multidrug-resistant tuberculosis and beyond: an updated analysis of the current evidence on bedaquiline", has been published recently on the European Respiratory Journal.
AUTHORS: Emanuele Pontali, Lia D’Ambrosio, Rosella Centis, Giovanni Sotgiu and Giovanni Battista Migliori
SUMMARY: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) continue to be challenging at both the patient and programme level. Unfortunately, MDR-TB treatment outcomes are still suboptimal (e.g 52% success rate in a 2013 cohort, which did not discriminate between MDR- (cases resistant to rifampicin and isonizazid),pre-XDR- (additional resistance to either a fluoroquinolone or a second-line injectable drug), XDR-(MDR-TB with additional resistance to both fluoroquinolones and injectables) and “beyond XDR-TB”patients, where success rates were <20%).
Clinicians managing patients with MDR- and XDR-TB are well aware of the duration, expenses and complications (due to the frequently observed adverse events) involved in treating these cases in the absence of new drugs. The main difficulty is, in fact, to identify at least four active drugs necessary to design an effective regimen .New opportunities can be offered by the new drugs delamanid and bedaquiline, as well as by other repurposed drugs such as linezolid, carbapenems and clofazimine. The European Respiratory Journal, has put together a special issue on the occasion of the World TB Day 2017, aimed at presenting new guidelines and systematically summarising the evidence on bedaquiline. For this drug further evidence has been published on its tolerability, and its safety profile seems better today than initially expected. Better results will be obtained if programmes could ensure adequate treatment and follow-up in specialised centres with comprehensive patient support, appropriate management of adverse events,free-of-charge treatment, and social support for vulnerable populations, availability of quality DST in laboratories, tailored treatment regimens and lung surgery when indicated. Prolonged treatment with bedaquiline could further improve treatment outcomes, although more evidence is needed.