Faculty Bibliography

BACKGROUND: In developing countries, more than 50% of children have serological evidence of Helicobacter pylori infection. However, serological tests for H. pylori did not differentiate between active and past infection. The objectives of this study were to estimate the frequency of active and past H. pylori infection utilizing functional urea breath test (UBT) and serological tests and evaluate factors associated with the infection. METHODS: A total of 675 school children, 6-13 years of age, participated. UBT was performed to detect active H. pylori infection. Blood samples were obtained to determine iron status and Immunoglobulin G (IgG) responses to the H. pylori whole-cell and to Cag A antigens by antigen-specific enzyme-linked immunosorbent assays. Weight, height, and sociodemographic characteristics were recorded. RESULTS: A total of 37.9% (95% Confidence Intervals (CI): 34.2-41.6) of school children had active or past H. pylori infection; of them, 73.8% (CI95% 68.4-79.2) were carrying CagA-positive strain, 26.5% (CI95% 23.2-29.8) had active infection, and 11.4% (95%CI: 9.0-13.8) had evidence of past H. pylori infection. School children with iron deficiency and low height for age had higher risk of H. pylori infection: [OR to active or past infection was 2.30 (CI 95% 1.01-5.23) and to active infection it was 2.64 (CI 95% 1.09-6.44)] compared to school children with normal iron status and height for age or with normal iron status but low height for age or with iron deficiency and normal height for age. CONCLUSIONS: The estimated prevalence of infection depends of the test utilized. Frequency of H. pylori infection and carrying CagA-positive strains was high in this population. Malnutrition was associated with active H. pylori infection.

Campylobacter fetus are important animal and human pathogens and the two major subspecies differ strikingly in pathogenicity. C. fetus subsp. venerealis is highly niche-adapted, mainly infecting the genital tract of cattle. C. fetus subsp. fetus has a wider host-range, colonizing the genital- and intestinal-tract of animals and humans. We report the complete genomic sequence of C. fetus subsp. venerealis 84-112 and comparisons to the genome of C. fetus subsp. fetus 82-40. Functional analysis of genes predicted to be involved in C. fetus virulence was performed. The two subspecies are highly syntenic with 92% sequence identity but C. fetus subsp. venerealis has a larger genome and an extra-chromosomal element. Aside from apparent gene transfer agents and hypothetical proteins, the unique genes in both subspecies comprise two known functional groups: lipopolysaccharide production, and type IV secretion machineries. Analyses of lipopolysaccharide-biosynthesis genes in C. fetus isolates showed linkage to particular pathotypes, and mutational inactivation demonstrated their roles in regulating virulence and host range. The comparative analysis presented here broadens knowledge of the genomic basis of C. fetus pathogenesis and host specificity. It further highlights the importance of surface-exposed structures to C. fetus pathogenicity and demonstrates how evolutionary forces optimize the fitness and host-adaptation of these pathogens.

BACKGROUND: Psoriasis is a common chronic inflammatory disease of the skin. We sought to characterize and compare the cutaneous microbiota of psoriatic lesions (lesion group), unaffected contralateral skin from psoriatic patients (unaffected group), and similar skin loci in matched healthy controls (control group) in order to discern patterns that govern skin colonization and their relationship to clinical diagnosis. RESULTS: Using high-throughput 16S rRNA gene sequencing, we assayed the cutaneous bacterial communities of 51 matched triplets and characterized these samples using community data analysis techniques. Intragroup Unifrac beta diversity revealed increasing diversity from control to unaffected to lesion specimens. Likewise, principal coordinates analysis (PCoA) revealed separation of the lesion samples from unaffected and control along the first axis, suggesting that psoriasis is a major contributor to the observed diversity. The taxonomic richness and evenness decreased in both lesion and unaffected communities compared to control. These differences are explained by the combined increased abundance of the four major skin-associated genera (Corynebacterium, Propionibacterium, Staphylococcus, and Streptococcus), which present a potentially useful predictor for clinical skin type. Psoriasis samples also showed significant univariate decreases in relative abundances and strong classification performance of Cupriavidus, Flavisolibacter, Methylobacterium, and Schlegelella genera versus controls. The cutaneous microbiota separated into two distinct clusters, which we call cutaneotypes: (1) Proteobacteria-associated microbiota, and (2) Firmicutes-associated and Actinobacteria-associated microbiota. Cutaneotype 2 is enriched in lesion specimens compared to control (odds ratio 3.52 (95% CI 1.44 to 8.98), P <0.01). CONCLUSIONS: Our results indicate that psoriasis induces physiological changes both at the lesion site and at the systemic level, which select for specific differential microbiota among the assayed clinical skin types. These differences in microbial community structure in psoriasis patients are potentially of pathophysiologic and diagnostic significance.

The persistence of Helicobacter pylori infection plays a fundamental role in the development of H. pylori-associated complications. Since the majority of infected persons acquire the bacteria during early childhood, an examination of the immunobiology of H. pylori infection in children compared with that of adults may help identify host factors that contribute to persistent infection. Therefore, we begin our review of the role of persistence in H. pylori disease with an assessment of the clinical features of H. pylori infection in children. We next review the bacterial factors that promote colonization and evasion of host defense mechanisms. We then focus our attention on the early host immunological factors that promote persistence of the infection and its complications in humans and mouse models. We also highlight topics in which further research is needed. An examination of how immunological factors cause divergent manifestations of H. pylori infection in children compared with adults may provide new insight for therapeutic modification or prevention of persistent H. pylori infection and its complications.

A total of 135 stomach samples from patients with gastrointestinal diseases and normal controls were examined for Helicobacter pylori infection and Candida colonization. Candida krusei was found in specimens from 20% bleeding, 52% ulcer, and 100% gastritis patients, whereas H. pylori infection rates were 82%, 35% and 30%, respectively, for the same groups of patients. C. krusei was not detected in stomach samples from normal controls.

BACKGROUND AND AIM: At the same time that Helicobacter pylori prevalence is declining in Western countries, immigrants from developing countries with high H. pylori prevalence have settled in Western urban areas. Actual epidemiological data on H. pylori in a migrant community may help in realizing a more selective approach to assess H. pylori-related diseases. We aimed to define H. pylori prevalence as well as risk groups for H. pylori in a cohort of young women living in a multi-ethnic European city. METHODS: We measured Immunoglobulin G (IgG) anti-H. pylori and CagA-antibodies in serum of pregnant women included in a population-based prospective cohort study, the Generation R study. Information on demographics and socioeconomic status was collected by questionnaires. Chi-square and logistic regression were used. RESULTS: In total, 3146 (46%) of the 6837 tested women (mean age 29.7 +/- 5.3) were H. pylori-positive and 1110 (35%) of them were CagA-positive. The H. pylori prevalence in Dutch women was 24%, which was significantly lower than in non-Dutch women (64%; P < 0.001). In particular, H. pylori positivity was found in 92% of Moroccan (odds ratio 19.2; 95% confidence interval 11.8-32.0), 80% of Cape Verdean (7.6; 5.0-11.5), 81% of Turkish (9.0; 6.7-12.1), 60% of Dutch Antillean (3.3; 2.3-4.7), and 58% of Surinamese women (3.0; 2.3-3.8). Among H. pylori-positive Dutch subjects, 19% were CagA-positive compared with 40% of the non-Dutch subjects (P < 0.001). CONCLUSIONS: Despite a general trend of declining prevalence in Western countries, H. pylori remains highly prevalent in migrant communities, which may constitute target groups for screening and eradication to prevent H. pylori-related diseases.

INTRODUCTION: Preeclampsia (PE) is characterized by endothelial dysfunction and related hypertension and coagulative disorders. It is a leading cause of perinatal and maternal morbidity and mortality. Although the exact pathogenesis is still unknown, certain infectious agents seem to play a role. Helicobacter pylori (H. pylori) has been reported to induce platelet aggregation, and we therefore hypothesized that this bacterium could be associated with PE. AIMS&METHODS: The objective of this study was to assess the association between H. pylori colonization and PE. We measured IgG anti-H. pylori and CagA-antibodies in serum of pregnant women of the Generation R study, a population-based prospective cohort study in Rotterdam, the Netherlands. Delivery and medical records were retrieved for identification of subjects with PE, which were defined according to standard criteria. Information on demographics, education, and maternal risk factors was collected by questionnaires. Only women with a live born singleton pregnancy were included. Subjects with chronic hypertension, systemic lupus erythematosus, lupus anticoagulants or chronic heart disease were excluded from analyses. Odds ratios (OR) of PE for H. pylori colonization were calculated using logistic regression analyses after adjustment for potential confounders including maternal age, ethnicity, parity, smoking, body mass index and education level. RESULTS: Serum of 6348 pregnant women was analyzed (mean age 29.7 +/- SD 5.3). In total, 2923 women were H. pylori positive (46%) and 1028 of them were CagA-positive (35%). For 132 women pregnancy was complicated with PE (2.1%). H. pylori colonization rate in women with PE was 56% compared to 44% in subjects without PE (p=0.02). CagA-positivity rate was 20% in women with and 16% in women without PE (p=0.30). Adjusted for potential confounding effects, women colonized with H. pylori were more likely to develop PE (final OR 1.53; 95% confidence interval 1.04-2.26). CagA-positivity was not associated with PE. CONCLUSION: Our data demonstrate that H. pylori colonization in pregnant women is associated with PE. H. pylori may be involved in different inflammatory mechanisms, which might potentially affect the pathogenesis of PE. Understanding and further validation of this association may contribute to effective intervention (e.g. H. pylori eradication treatment) for reducing morbidity and mortality from this disease

INTRODUCTION: Helicobacter pylori (H. pylori) is usually acquired during childhood. Although colonization rates have been declining inWestern countries, less is known about H. pylori prevalence and risk factors among children living in a multi-ethnic Western city. AIMS&METHODS: We therefore aimed to identify H. pylori and CagA status and H. pylori-related risk factors in young children living in Rotterdam, a large European city. IgG anti-H. pylori and CagA-antibodies were measured in serum of children participating in the Generation R study, a population-based prospective cohort study. Information on demographics and maternal characteristics was collected by questionnaires. Chi-square tests and logistic regression were used. Odds ratios (OR) for H. pylori colonization were adjusted for children's age, gender, ethnicity, day care attendance and maternal parity and education level. RESULTS: Serum of 4467 children was analysed (mean age 6.2 years +/- 0.48 SD), of which 2164 were female (48%). Overall, 438 children were H. pylori positive (10%), and 142 of them were CagA-positive (32%). The highest colonization rate was found in children of Moroccan ethnicity (27%), followed by children originating from Cape Verde (23%), Dutch Antilles (15%), Turkey (13%), other non-western countries (12%), Surinam (10%), other western countries (10%), and the Netherlands (6%) respectively (p<0.001). The colonization rate if all non-Dutch children were pooled together was 15% compared with 6% of the Dutch children (p<0.001). Multivariate regression analyses revealed the following associations with childhood H. pylori colonization: non-Dutch ethnicity (OR 2.30; 95% confidence interval 1.82-2.90), male gender (0.69; 0.56-0.84), and day care attendance (0.60; 0.41-0.88). H. pylori-positive Dutch children were CagA-positive in 15% of the cases compared with 39% of the non-Dutch subjects (p<0.001). CONCLUSION: We identified large differences in colonization rates among children living in a multi-ethnic population. Highest H. pylori and CagA prevalence was found in children from non-Western countries, implying that in coming decades H. pylori and related diseases will be prevalent in this multi-ethnic population