Economic development has been accompanied by dramatic changes in the prevalence of some chronic infections. H. pylori, for example, is nearing extinction in industrialized countries. In developing countries, however, chronic infections remain common and act on the host simultaneously, resulting in competing signals to the immune system. In our prior submission, we identified protective effects of H. pylori on gastroenteritis incidence. This finding exemplifies the complex interactions that can occur among infectious agents in a single host to affect disease outcome. The objective of our current proposal is to better characterize how infections interact within humans. Specifically, we wish to see how host response to gastric infection with H. pylori varies in the setting of strong chronic inducers of Thl response (M. tuberculosis) or Th2 response (intestinal helminths).
Specific aims are 1) to characterize the joint distribution of the three target pathogens in a defined population;2) to characterize gastric and systemic immunologic profiles of mixed infections, and 3) to assess changes in these immunologic profiles after treatment of infection. In the setting of mixed infection, we speculate helminths cause down-regulation of cell-mediated immune responses to H. pylori whereas latent Mycobacterium tuberculosis (LTBI) upregulates the response. We further hypothesize that eradication of either helminths or LTBI reverses these effects. To be conducted in recent immigrants in Santa Clara county, the proposed research will have three parts. In Part 1, community surveys will be carried out and the distributions of infection in 1750 subjects will be evaluated. In Part 2, a subset of 200 subjects from phase one will undergo more extensive immunologic profiling to evaluate the effects of individualand co-infection on systemic cytokine arid immunoglobulin levels. In Part three, subjects who participated in Part II will undergo treatment of either helminths, latent tuberculosis infection or no treatment and changes in systemic immunologic outcomes will be assessed;in a subset of 75, immune responses to H. pylori in the stomach will also be assessed with endoscopy and biopsy. How humans respond to the spectrum of chronic infections that they harbor is a question of critical importance to vaccine development and to our understanding of the variability in manifestations of human disease. In addition to shedding light on why outcomes of H. pylori differ from person-to-person and from population-to-population, we hope this study will also expand the toolkit of immunoepidemiology for further studies in human populations.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IRAP-Q (01))
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Mills, Melody
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Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
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Perry, S; Chang, A H; Sanchez, L et al. (2013) The immune response to tuberculosis infection in the setting of Helicobacter pylori and helminth infections. Epidemiol Infect 141:1232-43
Chang, Alicia H; Perry, Sharon; Du, Jenny N T et al. (2013) Decreasing intestinal parasites in recent Northern California refugees. Am J Trop Med Hyg 88:191-7
Yu, Guixia; Greninger, Alexander L; Isa, Pavel et al. (2012) Discovery of a novel polyomavirus in acute diarrheal samples from children. PLoS One 7:e49449
Perry, S; Hussain, R; Parsonnet, J (2011) The impact of mucosal infections on acquisition and progression of tuberculosis. Mucosal Immunol 4:246-51
Chiu, C Y; Greninger, A L; Chen, E C et al. (2010) Cultivation and serological characterization of a human Theiler's-like cardiovirus associated with diarrheal disease. J Virol 84:4407-14
Perry, Sharon; de Jong, Bouke C; Solnick, Jay V et al. (2010) Infection with Helicobacter pylori is associated with protection against tuberculosis. PLoS One 5:e8804
Greninger, Alexander L; Runckel, Charles; Chiu, Charles Y et al. (2009) The complete genome of klassevirus - a novel picornavirus in pediatric stool. Virol J 6:82
Perry, Sharon; de la Luz Sanchez, Maria; Yang, Shufang et al. (2006) Gastroenteritis and transmission of Helicobacter pylori infection in households. Emerg Infect Dis 12:1701-8
Garg, P K; Perry, S; Sanchez, L et al. (2006) Concordance of Helicobacter pylori infection among children in extended-family homes. Epidemiol Infect 134:450-9
Tsai, Chiaojung J; Perry, Sharon; Sanchez, Luz et al. (2005) Helicobacter pylori infection in different generations of Hispanics in the San Francisco Bay Area. Am J Epidemiol 162:351-7

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