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Subramaniam P.,Rutgers University | Lee K.-B.,Rutgers University | Garfunkel E.,Rutgers University | Mainelis G.,Rutgers University | And 8 more authors.
PLoS ONE | Year: 2014

Acting as fuel combustion catalysts to increase fuel economy, cerium dioxide (ceria, CeO2) nanoparticles have been used in Europe as diesel fuel additives (Envirox™). We attempted to examine the effects of particles emitted from a diesel engine burning either diesel (diesel exhaust particles, DEP) or diesel doped with various concentrations of CeO2 (DEP-Env) on innate immune responses in THP-1 and primary human peripheral blood mononuclear cells (PBMC). Batches of DEP and DEP-Env were obtained on three separate occasions using identical collection and extraction protocols with the aim of determining the reproducibility of particles generated at different times. However, we observed significant differences in size and surface charge (zeta potential) of the DEP and DEP-Env across the three batches. We also observed that exposure of THP-1 cells and PBMC to identical concentrations of DEP and DEP-Env from the three batches resulted in statistically significant differences in bioreactivity as determined by IL-1β, TNF-α, IL-6, IFN-γ, and IL-12p40 mRNA (by qRT-PCR) and protein expression (by ELISPOT assays). Importantly, bioreactivity was noted in very tight ranges of DEP size (60 to 120 nm) and zeta potential (-37 to -41 mV). Thus, these physical properties of DEP and DEP-Env were found to be the primary determinants of the bioreactivity measured in this study. Our findings also point to the potential risk of over- or under- estimation of expected bioreactivity effects (and by inference of public health risks) from bulk DEP use without taking into account potential batch-to-batch variations in physical (and possibly chemical) properties. © 2014 Sarkar et al.


Tissera H.,Epidemiology Unit | Amarasinghe A.,Epidemiology Unit | Amarasinghe A.,Korean International Vaccine Institute | De Silva A.D.,Genetech Research Institute | And 6 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2014

Dengue is the most significant arthropod-borne viral infection of humans. Persons infected with dengue viruses (DENV) have subclinical or clinically apparent infections ranging from undifferentiated fever to dengue hemorrhagic fever/shock syndrome. Although recent studies estimated that the Indian subcontinent has the greatest burden of DENV infection and disease worldwide, we do not have reliable, population-based estimates of the incidence of infection and disease in this region. The goal of this study was to follow-up a cohort of 800 children living in a heavily urbanized area of Colombo, Sri Lanka to obtain accurate estimates of the incidence of DENV infection and disease. Annual blood samples were obtained from all children to estimate dengue seroprevalence at enrollment and to identify children exposed to new DENV infections during the study year. Blood was also obtained from any child in whom fever developed over the course of the study year to identify clinically apparent DENV infections. At enrollment, dengue seroprevalence was 53.07%, which indicated high transmission in this population. Over the study year, the incidence of DENV infection and disease were 8.39 (95% confidence interval = 6.56-10.53) and 3.38 (95% confidence interval = 2.24-4.88), respectively, per 100 children per year. The ratio of clinically inapparent to apparent infections was 1.48. These results will be useful for obtaining more accurate estimates of the burden of dengue in the region and for making decisions about testing and introduction of vaccines. Copyright © 2014 by The American Society of Tropical Medicine and Hygiene.


Osornio-Vargas A.,University of Alberta | Quintana-Belmares R.,Laboratory of Environmental Toxicology | Meng Q.,Center for Global Public Health | Kirn T.J.,New Brunswick Laboratory | And 4 more authors.
Infection and Immunity | Year: 2015

Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 μm(PM2.5) and 10 μm(PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human β-defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB. © 2015, American Society for Microbiology.


PubMed | Center for Global Public Health, Laboratory of Environmental Toxicology, University of Alberta, Desert Research Institute and 2 more.
Type: Journal Article | Journal: Infection and immunity | Year: 2015

Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 m (PM2.5) and 10 m (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human -defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB.


Emmanuel F.,University of Manitoba | Salim M.,National Institute of Health | Akhtar N.,National Institute of Health | Arshad S.,Center for Global Public Health | Reza T.E.,National Institute of Health
Sexually Transmitted Infections | Year: 2013

Objectives In an effort to fully analyse and understand the HIV situation and its epidemiology in Pakistan, a bilateral collaboration between the National AIDS Control Program and the Canadian International Development Agency resulted in the establishment of an effective second-generation surveillance (SGS) system for HIV/AIDS between 2004 and 2012 in accordance with the published guidelines. This paper presents findings from the 4th round of SGS. Methods A mapping exercise was initially conducted for size estimations of the key vulnerable populations: people who inject drugs (PWIDs), male sex workers (MSWs), hijra sex workers (HSWs), and female sex workers (FSWs), followed by an Integrated Behavioral and Biological Surveillance in 20 selected cities across Pakistan. Results The estimated sizes of the four key populations mapped in the 20 cities were 89 178 FSWs, 46 351 PWIDs, 23 317 HSWs and 19 119 MSWs. The HIV sero-prevalence among PWIDs was the highest among all key populations surveyed at 37.8% (CI 37.3 to 38.3) nationally, followed by a prevalence of 7.2% (CI 6.8 to 7.5) among HSWs, 3.1% (CI 2.8 to 3.4) among MSWs and 0.8% (CI 0.4 to 1.0) for FSWs. Various key risk behaviours, that is, sharing of syringes by PWIDs and inconsistent use of condoms by sex workers, were documented. Conclusions Pakistan's HIV epidemic that once was characterised primarily by transmission among PWIDs is now increasingly characterised by significant sexual transmission, and all types of sex workers (male, hijra and female) exhibit epidemiological proportions of infection. There is a need to develop concrete strategic plans for each vulnerable subpopulation, initially focusing prevention resources on those with a higher risk or vulnerability.


Rivas-Santiago B.,Mexican Institute of Social Security IMSS | Castaneda-Delgado J.E.,Mexican Institute of Social Security IMSS | Castaneda-Delgado J.E.,Autonomous University of San Luis Potosi | Rivas Santiago C.E.,National Institute of Medical science and Nutrition Salvador Zubiran | And 10 more authors.
PLoS ONE | Year: 2013

Tuberculosis is an ongoing threat to global health, especially with the emergence of multi drug-resistant (MDR) and extremely drug-resistant strains that are motivating the search for new treatment strategies. One potential strategy is immunotherapy using Innate Defence Regulator (IDR) peptides that selectively modulate innate immunity, enhancing chemokine induction and cell recruitment while suppressing potentially harmful inflammatory responses. IDR peptides possess only modest antimicrobial activity but have profound immunomodulatory functions that appear to be influential in resolving animal model infections. The IDR peptides HH2, 1018 and 1002 were tested for their activity against two M. tuberculosis strains, one drug-sensitive and the other MDR in both in vitro and in vivo models. All peptides showed no cytotoxic activity and only modest direct antimicrobial activity versus M. tuberculosis (MIC of 15-30 μg/ml). Nevertheless peptides HH2 and 1018 reduced bacillary loads in animal models with both the virulent drug susceptible H37Rv strain and an MDR isolate and, especially 1018 led to a considerable reduction in lung inflammation as revealed by decreased pneumonia. These results indicate that IDR peptides have potential as a novel immunotherapy against TB. © 2013 Rivas-Santiago et al.


Schwander S.,Center for Global Public Health | Okello C.D.,Makerere University | Freers J.,Makerere University | Chow J.C.,Desert Research Institute | And 3 more authors.
Journal of Environmental and Public Health | Year: 2014

Air quality in Kampala, the capital of Uganda, has deteriorated significantly in the past two decades. We made spot measurements in Mpererwe district for airborne particulate matter PM2.5 (fine particles) and coarse particles. PM was collected on Teflon-membrane filters and analyzed for mass, 51 elements, 3 anions, and 5 cations. Both fine and coarse particle concentrations were above 100 μg/m3 in all the samples collected. Markers for crustal/soil (e.g., Si and Al) were the most abundant in the PM 2.5 fraction, followed by primary combustion products from biomass burning and incinerator emissions (e.g., K and Cl). Over 90% of the measured PM2.5 mass can be explained by crustal species (41% and 59%) and carbonaceous aerosol (33%-55%). Crustal elements dominated the coarse particles collected from Kampala. The results of this pilot study are indicative of unhealthy air and suggest that exposure to ambient air in Kampala may increase the burden of environmentally induced cardiovascular, metabolic, and respiratory diseases including infections. Greater awareness and more extensive research are required to confirm our findings, to identify personal exposure and pollution sources, and to develop air quality management plans and policies to protect public health. © 2014 Stephan Schwander et al.


Nakamura T.,Pain and Fatigue Study Center | Schwander S.,UMDNJ New Jersey Medical School | Schwander S.,Center for Global Public Health | Donnelly R.,UMDNJ New Jersey Medical School | And 9 more authors.
Clinical and Vaccine Immunology | Year: 2013

A major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is immune dysregulation, thought to be reflected in upregulated proinflammatory cytokines leading to the symptoms that are characteristic of this illness. Because the symptoms worsen with physical exertion or sleep loss, we hypothesized that we could use these stressors to magnify the underlying potential pathogenic abnormalities in the cytokine systems of people with CFS. We conducted repeat blood sampling for cytokine levels from healthy subjects and CFS patients during both postexercise and total sleep deprivation nights and assayed for protein levels in the blood samples, mRNA activity in peripheral blood lymphocytes (PBLs), and function in resting and stimulated PBLs. We found that these environmental manipulations did not produce clinically significant upregulation of proinflammatory cytokines. These data do not support an important role of immune dysregulation in the genesis of stress-induced worsening of CFS. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Dheda K.,UCT | Dheda K.,University of Cape Town | Dheda K.,University College London | Dheda K.,Groote Schuur Hospital | And 4 more authors.
Respirology | Year: 2010

Tuberculosis (TB) is an international public health priority and kills almost two million people annually. TB is out of control in Africa due to increasing poverty and HIV coinfection, and drug-resistant TB threatens to destabilize TB control efforts in several regions of the world. Existing diagnostic tools and therapeutic interventions for TB are suboptimal. Thus, new vaccines, immunotherapeutic interventions and diagnostic tools are urgently required to facilitate TB control efforts. An improved understanding of the immunopathogenesis of TB can facilitate the identification of correlates of immune protection, the design of effective vaccines, the rational selection of immunotherapeutic agents, the evaluation of new drug candidates, and drive the development of new immunodiagnostic tools. Here we review the immunology of TB with a focus on aspects that are clinically and therapeutically relevant. An immunologically orientated approach to tackling TB can only succeed with concurrent efforts to alleviate poverty and reduce the global burden of HIV. © 2010 Asian Pacific Society of Respirology.


Schwander S.,University of Medicine | Schwander S.,Center for Global Public Health | Dheda K.,University of Cape Town | Dheda K.,University College London
American Journal of Respiratory and Critical Care Medicine | Year: 2011

The study of human pulmonary immunity against Mycobacterium tuberculosis (M.tb) provides a unique window into the biological interactions between the human host and M.tb within the bronchoalveolar microenvironment, the site of natural infection. Studies of bronchoalveolar cells (BACs) and lung tissue evaluate innate, adaptive, and regulatory immune mechanisms that collectively contribute to immunological protection or its failure. In aerogenically M.tb-exposed healthy persons lung immune responses reflect early host pathogen interactions that may contribute to sterilization, the development of latent M.tb infection, or progression to active disease. Studies in these persons may allow the identification of biomarkers of protective immunity before the initiation of inflammatory and disease-associated immunopathological changes. In healthy close contacts of patients with tuberculosis (TB) and during active pulmonary TB, immune responses are compartmentalized to the lungs and characterized by an exuberant helper T-cell type 1 response, which as suggested by recent evidence is counteracted by local suppressive immune mechanisms. Here we discuss how exploring human lung immunity may provide insights into disease progression and mechanisms of failure of immunological protection at the site of the initial host-pathogen interaction. These findings may also aid in the identification of new biomarkers of protective immunity that are urgently needed for the development of new and the improvement of current TB vaccines, adjuvant immunotherapies, and diagnostic technologies. To facilitate further work in this area, methodological and procedural approaches for bronchoalveolar lavage studies and their limitations are also discussed.

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