Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Differential activation of mitogen-activated protein kinases in AGS gastric epithelial cells by cag+ and cag- Helicobacter pylori.

The aim of this study was to determine whether Helicobacter pylori activates mitogen-activated protein (MAP) kinases in gastric epithelial cells. Infection of AGS cells with an H. pylori cag+ strain rapidly (5 min) induced a dose-dependent activation of extracellular signal-regulated kinases (ERK), p38, and c-Jun N-terminal kinase (JNK) MAP kinases, as determined by Western blot analysis and in vitro kinase assay. Compared with cag+ strains, cag- clinical isolates were less potent in inducing MAP kinase, particularly JNK and p38, activation. Isogenic inactivation of the picB region of the cag pathogenicity island resulted in a similar loss of JNK and p38 MAP kinase activation. The specific MAP kinase inhibitors, PD98059 (25 microM; MAP kinase kinase (MEK-1) inhibitor) and SB203580 (10 microM; p38 inhibitor), reduced H. pylori-induced IL-8 production in AGS cells by 78 and 82%, respectively (p < 0.01 for each). Both inhibitors together completely blocked IL-8 production (p < 0.001). However, the MAP kinase inhibitors did not prevent H. pylori-induced IkappaBalpha degradation or NF-kappaB activation. Thus, H. pylori rapidly activates ERK, p38, and JNK MAP kinases in gastric epithelial cells; cag+ isolates are more potent than cag- strains in inducing MAP kinase phosphorylation and gene products of the cag pathogenicity island are required for maximal MAP kinase activation. p38 and MEK-1 activity are required for H. pylori-induced IL-8 production, but do not appear to be essential for H. pylori-induced NF-kappaB activation. Since MAP kinases regulate cell proliferation, differentiation, programmed death, stress, and inflammatory responses, activation of gastric epithelial cell MAP kinases by H. pylori cag+ strains may be instrumental in inducing gastroduodenal inflammation, ulceration, and neoplasia

Update on the immunologic basis of Helicobacter pylori gastritis

PURPOSE OF REVIEWHelicobacter pylori is a ubiquitous bacterial pathogen that has evolved to chronically infect the gastric mucosal surface, evade host immune clearance, and cause peptic ulcer disease or gastric neoplasia in a significant minority of infected individuals. Understanding the colonization, persistence, and virulence determinants of the bacterium as well as the innate and adaptive immune responses of the host are critically important if we are to develop novel treatment strategies for eradication of infection and prevention of H. pylori-induced gastroduodenal disease. RECENT FINDINGSSubstantial progress has been made in understanding the role of CagA in altering gastric epithelial cell signaling pathways. Intracellular CagA has been shown to activate the Ras/MEK/ERK mitogen activated protein kinase cascade and to associate with epithelial tight-junction scaffolding protein ZO-1. CagA was shown to regulate cellular responses and possibly contribute to gastritis by phosphorylation-dependent pathways. A phosphorylation-independent mechanism for CagA intracellular effects has also been proposed. The potential for CagA to disrupt the apical junctional barrier and for the outer membrane protein oipA to promote IL-8 secretion and gastric inflammation have also been explored. A number of different mechanisms by which H. pylori escapes and evades host immune attack to cause chronic indolent inflammation have been uncovered. Meanwhile, the examination and development of new adjuvants and vaccine delivery mechanisms to induce mucosal immune responses against key bacterial antigens has been a continuing focus of investigation in both animal and human studies. SUMMARYH. pylori induces gastritis through production of a variety of antigens, virulence factors, and soluble mediators. The bacterium also dysregulates, disarms, and evades host immune responses to maintain chronic colonization of the gastric mucosa. Understanding the mechanisms of its growth and survival in the human stomach are essential for the development of an effective vaccine and other novel eradication strategies