Shufang Yang

Infection with Helicobacter pylori is associated with protection against tuberculosis.

Background Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. Methodology/Principal Findings We first examined M. tuberculosis-specific IFN-γ and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-γ responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36–0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63–2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12–0.80], p = 0.04). Conclusions/Significance H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and disease control.

Gastroenteritis and Transmission of Helicobacter pylori Infection in Households

In northern California homes, exposure to gastroenteritis in an H. pylori–infected contact markedly increased H. pylori infection.

Reproducibility of QuantiFERON-TB Gold In-Tube Assay

ABSTRACT Studies are needed to characterize the reproducibility of QuantiFERON-TB Gold (QFT-G) for targeted U.S. screening populations. Members of northern California households were tested with the QFT-G in-tube assay (QFT-G-IT) at two home visits 3 months apart. Reproducibility and agreement with the tuberculin skin test (TST) were assessed. Monte Carlo simulation was used to evaluate the role of test-related error. Of 63 individuals (49 adults and 14 children) completing QFT-G-IT at both time points, 79% were foreign-born (98% from Latin America) and 68% reported Mycobacterium bovis BCG vaccination. At the baseline visit, 23 (37%) were TST positive and 15 (24%) were QFT-G-IT positive (κ = 0.48 [± 0.11]). At 3 months, 3/48 (6.3%; 95% confidence interval [95CI], 2 to 17) of those initially QFT-G-IT negative converted, and 5/15 (33%; 95CI, 15 to 58) of those initially QFT-G-IT positive reverted. Among the 8 individuals with inconsistent QFT-G-IT results, the maximum gamma interferon response at either visit was 0.68 IU/ml versus means of 4.99 (± 3.74) and 6.95 (± 5.6) for 10 persistent positives at the first and second visits, respectively. Expected false-reversion and -conversion rates were 32% (90CI, 25 to 39%) and 6.95% (90CI, 4.6 to 9.8%) when the sensitivity and specificity were assumed to average 70% and 98%, respectively. Transient responses to QFT-G-IT are common, and low positive results need to be interpreted with caution. Further studies are needed to characterize the predictive value of the test for U.S. foreign-born and other targeted screening populations.

Seroprevalence of CagA-Positive Strains among Helicobacter pylori—Infected, Healthy Young Adults

Helicobacter pylori is categorized into two phenotypes on the basis of the presence or absence of the CagA protein. CagA protein-positive H. pylori are more closely associated with peptic ulcer disease and cancer. Whether CagA-positive strains are similarly represented among racial or ethnic groups in northern California was investigated. Sera from 152 H. pylori-infected healthy young adults were tested by ELISA for IgG against CagA. CagA antibodies were detected in 79.4% of blacks, 63.8% of Hispanics, and 50% of whites. After adjusting for demographic factors, blacks had significantly more infections with CagA-positive H. pylori than did whites (odds ratio [OR] = 5.0; 95% confidence interval [CI] = 1.6-15.3) or Hispanics (OR = 5.5, 95% CI = 1.9-16.0). Also, there was a higher prevalence of CagA in persons born in developing countries than in persons born in industrialized nations (OR = 3.5, 95% CI = 1.3-9.4). This suggests either a genetic predisposition of racial or ethnic groups to infection with particular H. pylori phenotypes or transmission of H. pylori within relatively segregated population groups.

Helicobacter pylori and Risk of Gastroenteritis

BACKGROUND Helicobacter pylori infection is thought to modify susceptibility to gastroenteritis. METHODS Members of northern California households with an index case of gastroenteritis were interviewed regarding recent episodes and tested for H. pylori. Conditional logistic regression was used to evaluate the risk of secondary gastroenteritis within households matched for members with secondary gastroenteritis (cases) and those without symptoms (control subjects). Case and control subjects were also tested for hepatitis A virus (HAV). RESULTS Of 801 households, 205 (26%) had at least 1 member with secondary gastroenteritis, of which 116 (56%) also included at least 1 member without symptoms (158 case and 285 control subjects). Compared with uninfected members and adjusting for age, those with antibodies to only 1 infection were at a decreased risk of secondary gastroenteritis (odds ratio [OR] for H. pylori infection, 0.25 [95% confidence interval [CI], 0.08-0.82]; OR for HAV, 0.45 [95% CI, 0.23-0.87]). Having antibodies to both H. pylori and HAV did not add to this negative effect (adjusted OR, 0.39 [95% CI, 0.18-0.84]). CONCLUSIONS H. pylori did not increase the risk of gastroenteritis in these households. A strong negative association between H. pylori infection and gastroenteritis is likely explained by prior exposure and immunity to other enteric pathogens.

Changes of Gene Expression in Gastric Preneoplasia following Helicobacter pylori Eradication Therapy

Helicobacter pylori causes gastric preneoplasia and neoplasia. Eradicating H. pylori can result in partial regression of preneoplastic lesions; however, the molecular underpinning of this change is unknown. To identify molecular changes in the gastric mucosa following H. pylori eradication, we used cDNA microarrays (with each array containing ∼30,300 genes) to analyze 54 gastric biopsies from a randomized, placebo-controlled trial of H. pylori therapy. The 54 biopsies were obtained from 27 subjects (13 from the treatment and 14 from the placebo group) with chronic gastritis, atrophy, and/or intestinal metaplasia. Each subject contributed one biopsy before and another biopsy 1 year after the intervention. Significant analysis of microarrays (SAM) was used to compare the gene expression profiles of pre-intervention and post-intervention biopsies. In the treatment group, SAM identified 30 genes whose expression changed significantly from baseline to 1 year after treatment (0 up-regulated and 30 down-regulated). In the placebo group, the expression of 55 genes differed significantly over the 1-year period (32 up-regulated and 23 down-regulated). Five genes involved in cell-cell adhesion and lining (TACSTD1 and MUC13), cell cycle differentiation (S100A10), and lipid metabolism and transport (FABP1 and MTP) were down-regulated over time in the treatment group but up-regulated in the placebo group. Immunohistochemistry for one of these differentially expressed genes (FABP1) confirmed the changes in gene expression observed by microarray. In conclusion, H. pylori eradication may stop or reverse ongoing molecular processes in the stomach. Further studies are needed to evaluate the use of these genes as markers for gastric cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(2):272–80)

The immune response to tuberculosis infection in the setting of Helicobacter pylori and helminth infections.

We screened 176 healthy, adult (aged 18-55 years) US refugees from tuberculosis (TB)-endemic countries to evaluate whether cytokine responses to latent TB infection (LTBI) are modified in the setting of concurrent H. pylori and helminth infection. As measured by the Quantiferon-TB GOLD interferon-γ release assay, a total 38 (22%) subjects had LTBI, of which 28 (74%) also were H. pylori seropositive and/or helminth infected. Relative to ten subjects with LTBI only, 16 subjects with concurrent H. pylori infection had significantly elevated levels of IFN-γ, and nine subjects with both H. pylori and helminth infection had significantly elevated levels of IFN-γ, IL-2, IL-13, and IL-5. H. pylori is associated with enhanced IFN-γ responses to TB, even in the setting of concurrent helminth infection. Efficacy of TB vaccines may vary with the co-existence of these three infections in the developing world.

Stanford's Outcomes Research in Kids (STORK): a prospective study of healthy pregnant women and their babies in Northern California

Purpose Stanfords Outcomes Research in Kids (STORK) is an ongoing prospective cohort of healthy pregnant women and their babies established to determine the effect of infectious diseases on weight, linear growth and immune system development during childhood. Additionally, a nested randomised intervention of household and personal cleaning products tests the effects of the microbicides triclosan and triclocarban on these outcomes and incidence of infection. Participants Healthy pregnant women were identified and enrolled primarily at public clinics; their babies, enrolled shortly after birth, are followed to age 36 months. Automated weekly surveys assess daily health status, infectious disease symptoms, healthcare provider visits and antibiotic use, in the mother during pregnancy and the baby once born. At 4-monthly household visits, information and samples are collected from the mother (urine, stool, saliva, skin swab), the baby (blood by heel/toe stick, urine, stool, saliva, skin swab) and the household (environmental swabs). Annual blood samples are obtained by venipuncture (mother and baby). Medical charts are abstracted for allergy and infectious illness in the mother during pregnancy and the baby. Findings to date From 7/2011 to 2/2015, 158 mothers were enrolled at approximately 20 weeks gestation; 127 babies were enrolled. Two-thirds of mothers are Hispanic, one-third are non-US born and one-third speak primarily Spanish; mean years of education is 13 (SD 6.2) years. Households have on average 4.5 residents. Most households (97%) were randomised to participate in the intervention. Completion of weekly surveys (86%) and follow-up (75% after 14 months) is excellent in this young, mobile population; collection of samples is ongoing with thousands of specimens stored. Future plans Enrolled babies will be followed until age 36 months (last anticipated visit: 07/2018) with medical chart review completed soon thereafter. All epidemiological information and samples will be available for collaborative hypothesis testing. Trial registration number NCT01442701; Pre-results.