Helicobacter bizzozeronii infection in a girl with severe gastric disorders in México: case report.

BACKGROUND: Gastric non-Helicobacter pylori helicobacters (NHPH) naturally colonize the stomach of animals. In humans, infection with these bacteria is associated with chronic active gastritis, peptic ulceration and MALT-lymphoma. H. bizzozeronii belongs to these NHPH and its prevalence in children is unknown. CASE PRESENTATION: This case report describes for the first time a NHPH infection in a 20-month-old girl with severe gastric disorders in Mexico. The patient suffered from melena, epigastric pain, and bloating. Gastroscopy showed presence of a Hiatus Hill grade I, a hemorrhagic gastropathy in the fundus and gastric body, and a Forrest class III ulcer in the fundus. Histopathologic examination revealed a chronic active gastritis with presence of long, spiral-shaped bacilli in the glandular lumen. Biopsies from antrum, body and incisure were negative for presence of H. pylori by culture and PCR, while all biopsies were positive for presence of H. bizzozeronii by PCR. Most likely, infection occurred through intense contact with the family dog. The patient received a triple therapy consisting of a proton pump inhibitor, clarithromycin, and amoxicillin for 14 days, completed with sucralfate for 6 weeks, resulting in the disappearance of her complaints. CONCLUSION: The eradication could not be confirmed, although it was suggested by clear improvement of symptoms. This case report further emphasizes the zoonotic importance of NHPH. It can be advised to routinely check for presence of both H. pylori and NHPH in human patients with gastric complains.

On-person adaptive evolution of Staphylococcus aureus during treatment for atopic dermatitis.

The opportunistic pathogen Staphylococcus aureus frequently colonizes the inflamed skin of people with atopic dermatitis (AD) and worsens disease severity by promoting skin damage. Here, we show, by longitudinally tracking 23 children treated for AD, that S. aureus adapts via de novo mutations during colonization. Each patient's S. aureus population is dominated by a single lineage, with infrequent invasion by distant lineages. Mutations emerge within each lineage at rates similar to those of S. aureus in other contexts. Some variants spread across the body within months, with signatures of adaptive evolution. Most strikingly, mutations in capsule synthesis gene capD underwent parallel evolution in one patient and across-body sweeps in two patients. We confirm that capD negativity is more common in AD than in other contexts, via reanalysis of S. aureus genomes from 276 people. Together, these findings highlight the importance of the mutation level when dissecting the role of microbes in complex disease.

Frequency of malnutrition in children and adolescents with child maltreatment.

Introduction: Introduction: child maltreatment (CM) can have a negative impact on physical and mental health in childhood and throughout life. Objective: to determine the frequency of malnutrition in cases of CM from the Clínica de Atención Integral al Niño Maltratado (CAINM) of the Instituto Nacional de Pediatría (INP), Mexico. Material and methods: this was a cross-sectional, retrospective, descriptive study of children with CM. Height/age, weight/height, and body mass index/age were used to determine malnutrition status (undernutrition and overweight or obesity). The frequency of malnutrition by age group and sex were compared using X2 tests. The prevalence of malnutrition at CAINM was compared to that expected in Mexico (ENSANUT-2012), serving as a reference for children without CM, using one-sample Poisson tests. Results: of the 117 cases, 41 % presented wasting or overweight/obesity, and 25 % were growth-stunted. Neither wasting nor stunting displayed any difference between age groups (p > 0.05). Overweight/obesity was observed more frequently in adolescents than in schoolchildren (p < 0.05). Being overweight or obese was most frequently associated with sexual abuse, and wasting and stunting were most often associated with neglect. Compared to the population without CM, the group under 5 years of age had a higher prevalence of wasting (p < 0.01), and those aged 5 to 11 years had a higher prevalence of both wasting and stunting (p < 0.001). Conclusions: CM cases were characterized by acute undernutrition and stunting as well as by adolescents who were overweight or obese. Malnutrition in the pediatric population should be analyzed from a wider perspective, including possible CM.

Introducción: Introducción: el maltrato infantil (MI) puede afectar la salud física y mental en la niñez y a largo plazo. Objetivo: determinar las frecuencias de mala nutrición en casos de MI de la Clínica de Atención Integral al Niño Maltratado (CAINM), perteneciente al Instituto Nacional de Pediatría de México. Métodos: estudio transversal, retrospectivo y descriptivo. Se utilizaron los cocientes de peso/talla, talla/edad e IMC/edad. Las frecuencias de mala nutrición (desnutrición y sobrepeso/obesidad) se compararon entre los grupos de edad y sexo a través de la prueba del X2. Utilizando pruebas de Poisson para una sola muestra se compararon las prevalencias de la mala nutrición con las esperadas en México (ENSANUT-2012). Resultados: de los 117 casos de MI, el 41 % presentaban emaciación o sobrepeso/obesidad, y el 25 % talla baja. Ni por emaciación ni por talla baja hubo diferencias entre los grupos de edad (p > 0,05). La frecuencia del sobrepeso/obesidad fue mayor en los adolescentes que en los escolares (p < 0,05). En el grupo de abuso sexual destacó el sobrepeso/obesidad; en el de negligencia, la emaciación y la talla baja. En comparación con las prevalencias de los niños sin MI, los niños < 5 años tuvieron prevalencias más altas de emaciación (p < 0,01); los de 5 a 11 años, de emaciación y talla baja (para ambas, p < 0,001). Conclusiones: los niños con MI se caracterizaron por desnutrición y talla baja, así como también por sobrepeso/obesidad en los adolescentes. La mala nutrición en las poblaciones pediátricas debe analizarse desde una perspectiva amplia, incluido el posible maltrato infantil.

The Skin Microbiome of Patients With Atopic Dermatitis Normalizes Gradually During Treatment.

Background: Atopic dermatitis (AD) is characterized by an altered skin microbiome dominantly colonized by S. aureus. Standard treatment includes emollients, anti-inflammatory medications and antiseptics. Objectives: To characterize changes in the skin microbiome during treatment for AD. Methods: The skin microbiomes of children with moderate-to-severe AD and healthy children were investigated in a longitudinal prospective study. Patients with AD were randomized to receive either standard treatment with emollients and topical corticosteroids or standard treatment with the addition of dilute bleach baths (DBB) and sampled at four visits over a three-month period. At each visit, severity of AD was measured, swabs were taken from four body sites and the composition of the microbiome at those sites was assessed using 16S rRNA amplification. Results: We included 14 healthy controls and 28 patients. We found high relative abundances of S. aureus in patients, which correlated with AD severity and reduced apparent alpha diversity. As disease severity improved with treatment, the abundance of S. aureus decreased, gradually becoming more similar to the microbiomes of healthy controls. After treatment, patients who received DBB had a significantly lower abundance of S. aureus than those who received only standard treatment. Conclusions: There are clear differences in the skin microbiome of healthy controls and AD patients that diminish with treatment. After three months, the addition of DBB to standard treatment had significantly decreased the S. aureus burden, supporting its use as a therapeutic option. Further study in double-blinded trials is needed.

Distinct innate immune responses between sublethal and lethal models of disseminated candidiasis in newborn BALB/c mice.

Invasive candidiasis is associated with a high incidence and mortality rates in infants, especially in preterm newborns. The immunopathogenesis of the mycosis during the neonatal period is poorly understood. Although several in vivo models exist to study invasive candidiasis, the majority of studies employ distinct routes of infection and use 2 to 6 day-old mice that could be less comparable in studying candidiasis in preterm infants. In this study, by using 0-days-old mice we developed a new neonatal murine model of intravenous Candida albicans infection. Using different inoculums of Candida albicans we evaluated survival, dissemination of the fungus, frequency of CD45+ cells, and cytokine production in the liver, brain, and kidneys of newborn and adult BALB/c mice. Unexpectedly, the newborn mice infected with a low inoculum (1×105 cfu per mouse) of Candida albicans survive to the infection. Compared to adult mice, the liver and brain of newborn animals had the greatest fungal burden, fungal invasion and leukocyte infiltrate. A moderate production of TNFα, IL-1ß, IL-6 and IFNγ was detected in tissues of newborn mice infected with a non-lethal inoculum of Candida albicans. In contrast, overproduction of TNFα, IL-1ß, IL-6 and IL-10 was determined when injecting with a lethal inoculum. In agreement, flow cytometry of brain and liver showed an inoculum-dependent CD45+ leukocyte infiltration in newborn mice infected with Candida albicans. Overall, our data shows that Candida albicans infection in newborn mice affects mainly the brain and liver and a 2-fold increase of the inoculum rapidly becomes lethal probably due to massive fungal invasion and exacerbated CD45+ leukocyte infiltrate and cytokine production. This study is the first analysis of innate immune responses in different tissues during early neonatal disseminated candidiasis.

Infections With Enterohepatic Non-H. pylori Helicobacter Species in X-Linked Agammaglobulinemia: Clinical Cases and Review of the Literature.

The genus Helicobacter is classified into two main groups according to its habitat: gastric and enterohepatic. Patients with X-linked agammaglobulinemia (XLA) appear to be associated with invasive infection with enterohepatic non-Helicobacter pylori species (NHPH), mainly H. cinaedi and H. bilis. Such infections are difficult to control and have a high potential for recurrence. The spectrum of illnesses caused by these species includes recurrent fever, bacteremia, arthritis, osteomyelitis, cellulitis, abdominal abscesses, and pyoderma gangrenosum-like ulcer. The presence of these Helicobacters is particularly difficult to diagnose and eradicate, as they are very fastidious bacteria and present resistance to several types of antibiotics. We report two clinical cases of XLA patients infected with H. bilis. These infections were chronic in these patients and could not be eradicated in one of them. We also review the cases of enterohepatic non-Helicobacter pylori species (NHPH) in patients with this inborn error of immunity.

Detection of Epstein-Barr Virus DNA in Gastric Biopsies of Pediatric Patients with Dyspepsia.

In this study, we assessed the presence of Epstein-Barr virus (EBV) in gastric samples derived from pediatric patients with dyspeptic symptoms, aiming to understand whether EBV participates in the development of early gastric lesions influencing chronic inflammation, in conjunction with the Helicobacter pylori (Hp) bacterium. We analyzed EBV load in 236 gastric biopsies derived from 186 pediatric patients with chronic dyspepsia and compared it with EBV serology, Hp load and serology, and with immune cell infiltration. We found that 7.5% of patients were positive for EBV load, ranging from 240 to 29,685 genomic copies/µg of DNA. Hp genomic sequences were found in 24.7% of patients. EBV positive samples did not correlate with Hp status and were characterized by absent to moderate immune cell infiltration. To our knowledge, this is the first study addressing EBV load in the stomach in a large cohort of pediatric patients with dyspeptic symptoms, providing evidence of EBV localization in the gastric mucosa in early inflammatory lesions. The lack of correlation between EBV and both Hp infection and inflammation is perhaps explained by independent pathogenic mechanisms or because of the randomness of the gastritis sampling. This is also supported by a moderate association between EBV load and serology.

Helicobacter pylori infection and serum leptin, obestatin, and ghrelin levels in Mexican schoolchildren.

BackgroundThere is little information about the possible role of Helicobacter pylori infection on appetite-regulating peptides in children. This study evaluated the association between H. pylori infection and serum levels of ghrelin, leptin, and obestatin in schoolchildren.MethodsOne hundred seventy-eight schoolchildren, students at boarding schools in Mexico City, participated. H. pylori infection status was determined every 6 months for 1 year by a breath test using 13C-urea; schoolchildren with consistently positive or negative results were selected to participate. Age, sex, and body mass index (BMI) were recorded. Serum concentrations of total ghrelin, leptin, and obestatin via specific enzyme-linked immunosorbent assays were determined.ResultsSchoolchildren with H. pylori infection had lower concentration of leptin, -0.54 pg/ml (95% CI: -0.98 to -0.09), compared to the schoolchildren without infection, after adjustment by age, gender, and BMI. And the children with the infection had a median of obestatin lower in 0.99 ng/ml (95% CI: -1.93 to -0.06) compared with the uninfected children after adjustment by BMI.ConclusionAssociation was found between H. pylori infection and decreased serum concentrations of leptin and obestatin. These results suggest that in schoolchildren, H. pylori infection affects the levels of hormones implicated in regulating appetite and energy homeostasis.

Plasticity Region Genes jhp0940, jhp0945, jhp0947, and jhp0949 of Helicobacter pylori in Isolates from Mexican Children.

BACKGROUND: The genes jhp0940, jhp0945, jhp0947, and jhp0949 belong to the plasticity region of the Helicobacter pylori genome. Due to their prevalence in isolates from patients with gastritis, duodenal ulcer, and gastric cancer, they have been proposed as markers of gastroduodenal diseases. These genes are associated with pro-inflammatory cytokine induction through the NF-κB activation pathway. Nevertheless, the status of these genes is unknown in H. pylori isolates from children. The aim of the present work was to determine the frequency of the jhp0940-jhp0945-jhp0947-jhp0949 genes in H. pylori isolates from children. MATERIALS AND METHODS: We identified the jhp0940, jhp0945, jhp0947, and jhp0949 genes and the relationship of each with the virulence factors cagA, cagPAI, and dupA by PCR in 49 isolates of H. pylori from children. The results were corroborated using dot blots. In addition, we compared the prevalence of these genes with the prevalence in adults. RESULTS: The prevalence of jhp0940 (53.1%), jhp0945 (44.9%), jhp0947 (77.6%), and jhp0949 (83.7%) was determined in the isolates from children, as was the prevalence of the virulence genes cagA (63.3%), cagPAI (71.4%), and dupA (37.5%). No association was found between the four genes of the plasticity region and the virulence genes. The presence of the intact locus integrated by jhp0940-jhp0945-jhp0947-jhp0949 was very common among the isolates from children. CONCLUSION: The genes jhp0940, jhp0947, and jhp0949 were present in more than 50% of the H. pylori isolates, and the joint presence of jhp0940-jhp0945-jhp0947-jhp0949 was very frequent. The frequency of these genes in isolates from children could contribute to the virulence of H. pylori and the evolution of the infection.

Differences in genome content among Helicobacter pylori isolates from patients with gastritis, duodenal ulcer, or gastric cancer reveal novel disease-associated genes.

Helicobacter pylori establishes a chronic infection in the human stomach, causing gastritis, peptic ulcer, or gastric cancer, and more severe diseases are associated with virulence genes such as the cag pathogenicity island (PAI). The aim of this work was to study gene content differences among H. pylori strains isolated from patients with different gastroduodenal diseases in a Mexican-Mestizo patient population. H. pylori isolates from 10 patients with nonatrophic gastritis, 10 patients with duodenal ulcer, and 9 patients with gastric cancer were studied. Multiple isolates from the same patient were analyzed by randomly amplified polymorphic DNA analysis, and strains with unique patterns were tested using whole-genome microarray-based comparative genomic hybridization (aCGH). We studied 42 isolates and found 1,319 genes present in all isolates, while 341 (20.5%) were variable genes. Among the variable genes, 127 (37%) were distributed within plasticity zones (PZs). The overall number of variable genes present in a given isolate was significantly lower for gastric cancer isolates. Thirty genes were significantly associated with nonatrophic gastritis, duodenal ulcer, or gastric cancer, 14 (46.6%) of which were within PZs and the cag PAI. Two genes (HP0674 and JHP0940) were absent in all gastric cancer isolates. Many of the disease-associated genes outside the PZs formed clusters, and some of these genes are regulated in response to acid or other environmental conditions. Validation of candidate genes identified by aCGH in a second patient cohort allowed the identification of novel H. pylori genes associated with gastric cancer or duodenal ulcer. These disease-associated genes may serve as biomarkers of the risk for severe gastroduodenal diseases.