Nicolas Kalach

Cow's milk epicutaneous immunotherapy in children: A pilot trial of safety, acceptability, and impact on allergic reactivity

REFERENCES 1. Enright PL, McClelland RL, Newman AB, Gottlieb DJ, Lebowitz MD. Underdiagnosis and undertreatment of asthma in the elderly. Chest 1999;116:603-13. 2. Moorman JE, Rudd RA, Johnson CA, King M, Minor P, Bailey C, et al. National Surveillance for AsthmaUnited States, 1980-2004. MMWR Surveill Summ 2007;56:1-54. 3. Jatakanon A, Uasuf C, Maziak W, Lim S, Chung KF, Barnes PJ. Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med 1999;160: 1532-9. 4. Simpson JL, Scott RJ, Boyle MJ, Gibson PG. Differential proteolytic enzyme activity in eosinophilic and neutrophilic asthma. Am J Respir Crit Care Med 2005;172: 559-65. 5. Cundall M, Sun YC, Miranda C, Trudeau JB, Barnes S, Wenzel SE. Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucocortcoids. J Allergy Clin Immunol 2003;112:1064-71. 6. Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet 2006;368: 804-13. 7. Meyer KC, Rosenthal NS, Soergel P, Peterson K. Neutrophils and low-grade inflammation in the seemingly normal aging human lung. Mech Ageing Dev 1998;104: 169-81. 8. Mathur SK, Schwantes EA, Jarjour NN, Busse WW. Age-related changes in eosinophil function in human subjects. Chest 2008;133:412-9. 9. Banerji A, Clark S, Afilalo M, Blanda MP, Cydulka RK, Camargo CA. Prospective multicenter study of acute asthma in younger versus older adults presenting to the emergency department. J Am Geriatr Soc 2006;54:48-55.

Prospective multicentre study on antibiotic resistance of Helicobacter pylori strains obtained from children living in Europe

Aim: To prospectively assess the antibacterial resistance rate in Helicobacter pylori strains obtained from symptomatic children in Europe. Methods: During a 4-year period, 17 paediatric centres from 14 European countries reported prospectively on patients infected with H pylori, for whom antibiotic susceptibility was tested. Results: A total of 1233 patients were reported from Northern (3%), Western (70%), Eastern (9%) and Southern Europe (18%); 41% originated from outside Europe as indicated by mother’s birth-country; 13% were <6 years of age, 43% 6–11 years of age and 44% >11 years of age. Testing was carried out before the first treatment (group A, n = 1037), and after treatment failure (group B, n = 196). Overall resistance to clarithromycin was detected in 24% (mean, A: 20%, B: 42%). The primary clarithromycin resistance rate was higher in boys (odds ratio (OR) 1.58; 1.12 to 2.24, p = 0.01), in children <6 years compared with >12 years (OR 1.82, 1.10 to 3.03, p = 0.020) and in patients living in Southern Europe compared with those living in Northern Europe (OR 2.25; 1.52 to 3.30, p<0.001). Overall resistance rate to metronidazole was 25% (A: 23%, B: 35%) and higher in children born outside Europe (A: adjusted. OR 2.42, 95% CI: 1.61 to 3.66, p<0.001). Resistance to both antibiotics occurred in 6.9% (A: 5.3%, B: 15.3%). Resistance to amoxicillin was exceptional (0.6%). Children with peptic ulcer disease (80/1180, 6.8%) were older than patients without ulcer (p = 0.001). Conclusion: The primary resistance rate of H pylori strains obtained from unselected children in Europe is high. The use of antibiotics for other indications seems to be the major risk factor for development of primary resistance.

Conditions of bifidobacterial colonization in preterm infants : A prospective analysis

Background: Premature birth results in a delayed and abnormal qualitative pattern of gut colonization. This abnormal pattern is thought to affect intestinal development and contribute to a higher risk of gastrointestinal infectious diseases such as neonatal necrotizing enterocolitis (NEC). In particular, bifidobacteria are thought to play a major role. We therefore studied bifidobacterial colonization in preterm infants during the first month of life. Patients and Methods: Fecal samples were prospectively analyzed in 52 infants born at a gestational age ranging from 30 to 35 weeks fed with a preterm formula alone and, in 18, with their mothers milk. Fecal samples were collected twice per week during the hospital stay. Bifidobacterial colonization was analyzed with culture and a molecular method. Results: Bifidobacterial colonization occurred in 18 infants at a median age of 11 days, always greater than the corrected mean gestational age of 35.4 weeks (SD, 0.9) and greater than 34 weeks for 16 of 18. Colonization by bifidobacteria was affected by neither birthweight nor mode of delivery nor antibiotics given to the mother or infant. In contrast, birth gestational age had a significant impact on colonization by bifidobacteria (P < 0.05), which always occurred in children born at a birth gestational age greater than 32.9 weeks (P < 0.05). Conclusions: Birth gestational age seems to act as a major determinant of bifidobacterial colonization in the premature infant, suggesting the role of gut maturation, a finding that should probably be taken into account in manipulations of the gut flora aimed at reducing NEC.

Helicobacter pylori diagnostic tests in children: review of the literature from 1999 to 2009

The array of tests that can be used for diagnosis of Helicobacter pylori infection is large, and it can be confusing to define which test to use particularly in children where results may not be comparable to those obtained in adult patients. Using PubMed, we reviewed the English literature from January 1999 to May 2009 to identify articles that determined sensitivity and specificity of H. pylori invasive and non-invasive diagnostic tests in children. We excluded articles that presented a review of the literature, abstracts, case reports, or series where children’s results could not be separated from adult populations. Of the tissue based methods, rapid urease tests have better sensitivity than histology to detect presence of H. pylori; however, histology can detect the pathology associated with disease including gastritis, intestinal metaplasia, and other conditions that could be the cause of the child’s symptoms. Culture of gastric tissues or stool has 100% specificity but sensitivity is low. Of the serologic tests, immunoblot has the best sensitivity. The urea breath tests have >75% sensitivity for detection of H. pylori before and after treatment. Immunoassays in stool using monoclonal antibodies have >95% sensitivity for detection of H. pylori before and after treatment. PCR testing can be performed in tissue and stool samples and can detect genes associated to antibiotic resistance. In summary, the current commercial non-invasive tests have adequate sensitivity and specificity for detecting the presence of H. pylori; however, endoscopy with histopathology is the only method that can detect H. pylori and lesions associated with the infection.

Results from the pediatric European register for treatment of Helicobacter pylori (PERTH).

Background and Aim:  Data on the eradication treatment for childhood Helicobacter pylori are scanty. A register was established on the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) website to collect data on treatment performed by European pediatricians to ascertain what is practiced in the field.

Increased poliovirus-specific intestinal antibody response coincides with promotion of Bifidobacterium longum-infantis and Bifidobacterium breve in infants: a randomized, double-blind, placebo-controlled trial.

To determine whether the size of the intestinal bifidobacterial population can influence the immune response to poliovirus vaccination in infants, we set up a randomized, placebo-controlled trial. From birth to 4 mo, infants were given a fermented infant formula (FIF) or a standard formula (placebo). Bifidobacteria were quantified monthly in infant stools. Antipoliovirus IgA response to Pentacoq® was assessed before and 1 mo after the second vaccine injection. Thirty infants were randomized, and 20 completed the study (nine in the placebo group and 11 in the FIF group). Fecal bifidobacterial level was significantly higher with the FIF group at 4 mo of age (p = 0.0498). Furthermore, B. longum/B. infantis carriage was higher at 4 mo in the FIF group (p = 0.0399). Antipoliovirus IgA titers increased after Pentacoq® challenge (p < 0.001), and the rise was significantly higher in the FIF group (p < 0.02). Antibody titers correlated with bifidobacteria, especially with B. longum/B. infantis and B. breve levels (p < 0.002). Infants who harbored B. longum/B. infantis also exhibited higher levels of antipoliovirus IgAs (p < 0.002). In conclusion, the present results indicate that antipoliovirus response can be triggered with a fermented formula that is able to favor intestinal bifidobacteria. Whether this effect on the immune system is achieved through the bifidogenic effect of the formula (mainly through B. longum/B. infantis and B. breve stimulation) or directly linked to compounds (i.e. peptides) produced by milk fermentation remains to be investigated.

High level of antimicrobial resistance in French Helicobacter pylori isolates.

Background: Helicobacter pylori is a human pathogen responsible for serious diseases including peptic ulcer disease and gastric cancer. The recommended triple therapy included clarithromycin but increasing resistance has undermined its effectiveness. It is therefore important to be aware of the local prevalence of antimicrobial resistance to adjust treatment strategy.

The 13carbon urea breath test for the noninvasive detection of Helicobacter pylori in children: comparison with culture and determination of minimum analysis requirements.

BACKGROUND The purpose of the study was to determine the accuracy of the labelled 13carbon urea breath test for the diagnosis of Helicobacter pylori in children and to simplify the 13carbon urea breath test in identifying the most discriminating sampling time. METHODS H. pylori was searched for in 100 children aged 10.5+/-4.5 years by histology, bacteriological counts, and culture on antral biopsies together with serology and 13carbon urea breath test. Breath samples were obtained before ingestion (T0) of 75 mg urea-13C and every 10 minutes after until T60. 13CO2 excess ratio was measured by isotope ratio mass spectrometry, and values expressed as delta per mil over baseline enrichment (delta 13CO2). The arithmetic mean (Mdelta 13CO2) of T20 to T60 values was calculated and the test considered positive with Mdelta 3CO2 higher than Mdelta 13CO2 + 3 SD as determined in noninfected children. RESULTS Mdelta 13CO2 of noninfected children as assessed by culture was 1.4+/-0.6 per mil, determining a positive cut-off value of 3.44 per mil. Mdelta 13CO2 was correlated in 11 children with biopsy bacteriological counts. Both culture and 13carbon urea breath test were positive in 38 of 100 children, without any discordance. Plotting 13carbon urea breath test results at each sampling time versus Mdelta 13CO2 showed weaker correlations at T20, T30, T50, and T60, than at T40. The two-sample method at T0 and T30, T40, T50, had high sensitivity and specificity. Single-sample analysis obtained at T40 gave a comparable sensitivity and a slightly reduced specificity. CONCLUSION 13carbon urea breath test is sensitive and specific in children. Two samples collected at T0 and T40 provide the most discriminating procedure.

Genetic and transmission analysis of Helicobacter pylori strains within a family.

Point mutations, intragenic recombination, and introduction of foreign alleles enhanced strain diversity within the family.

High levels of resistance to metronidazole and clarithromycin in Helicobacter pylori strains in children.

ABSTRACT The aim of the study was to evaluate the prevalence of resistance to amoxicillin, metronidazole, and clarithromycin before treatment ofHelicobacter pylori infection in children and to assess the evolution of resistance with time. The study was carried out between 1994 and 1999 with 150 H. pylori-positive children through gastric culture (antimicrobial susceptibility) and histology. All cultured H. pylori strains were sensitive to amoxicillin, 64 (43%) were resistant to metronidazole, 32 (21%) were resistant to clarithromycin, and 14 (9%) were resistant to both metronidazole and clarithromycin. The overall prevalence of resistance to metronidazole and clarithromycin did not change significantly with time. The study highlights the generalized high-level and stable metronidazole and clarithromycin resistance of H. pylori strains from children.