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Dr. Chaisson proposed to provide support for patient oriented research on tuberculosis control in developing countries, mentoring of junior faculty and fellows in clinical research, and leadership of the Johns Hopkins Center for TB Research, which was founded at the time of the original award. All three aims have been executed with outstanding results. Dr. Chaisson''''''''''''''''s proposed community-randomized trial of alternative TB control strategies has been undertaken with support from a ICIDR program project grant and results will be available within a year. He has mentored a half-dozen junior faculty members and number of fellows, with notable success in terms of publications, funding and promotion. Finally, he has led the growth of the Center for TB Research from a $3 million enterprise to a world renowned center of excellence with more than $60 million in research funding. The renewal of the project proposed to continue the leadership and management of the Center for TB Research, provide ongoing mentoring to five junior faculty and to fellows and graduate students, and to conduct innovative research on TB control strategies in developing countries by conducting a cluster-randomized, phase implementation study of INH preventive therapy for HIV-infected patients in Rio de Janeiro, Brazil. Support for these activities will enable Dr. Chaisson to further strengthen and expand the scope of the Center for TB Research, assist young investigators with academic advancement and success, and contribute to global tuberculosis control by developing new paradigms for reducing the burden of HIV-related TB.
Researchers
Richard Chaisson
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Innovative public health interventions are necessary to combat the syngergistic devastation emerging from the dual TB and HIV epidemics in many regions of the world. This proposal will build upon a strong, long-standing working relationship between the Johns Hopkins Center for TB Research and the Rio de Janeiro Health Department to train a highly qualified epidemiologist to become an independent public health researcher in international TB and HIV research and to become proficient at designing and conducting clustered randomized trials (CRTs). Through close mentorship with two exceedingly qualified investigators, specific coursework, and leadership of a large scale clustered randomized trial, this training will be structured and substantial. The faculty at the Center for TB Research is highly distinguished and the epidemiologic instruction available at the Bloomberg School of Public Health is world renowned. The proposed study will determine if the routine detection and treatment of latent TB in HIV-infected patients in HIV clinics in Rio de Janeiro, Brazil, will reduce TB incidence in those clinics; and, determine the independent and combined effectiveness of isoniazid prophylactic therapy (IPT) and antiretroviral (ARV) therapy to reduce TB incidence in HIV-infected patients. The intervention will consist of implementing a comprehensive policy of screening for and treating latent TB in all HIV-infected patients. Approximately 20,000 patients in 29 HIV clinics will be followed for 5 years and the CRT will take a phased-implementation approach to ensure that all participating clinics will eventually have full coverage. TB incidence will be compared between clinics receiving the intervention and those not yet receiving the intervention. The impact of combined ARV and IPT programs is not known, but together these strategies could potentially reduce TB risk to extremely low levels. Mastering the techniques associated with clustered randomized trials will provide the candidate with important tools for exploring new approaches to reducing TB incidence and transmission. This K01 award will provide the epidemiological training and experience necessary to become a successful, independent public health investigator.
Researchers
Jonathan Golub
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The THRio study is designed to determine whether the routine detection and treatment of TB infection found in HIV infected patients in HIV clinics in Rio de Janeiro, Brazil, reduces TB incidence in the clinic population receiving HIV care. Involving an estimated 15,000 clinic patients, the intervention consists of implementing a comprehensive policy of screening for and treating latent TB infection in all HIV-infected patients. The trial takes a phased-implementation approach to ensure that all participating clinics eventually have full coverage. Phased implementation is a realistic and pragmatic method to effectively train all clinic personnel in the skills required to appropriately test and treat these patients. Brazil was the ideal location for this study because the government has made antiretroviral (ARV) therapy freely available for years. Although it is already known that treatment with ARV therapy reduces the risk of developing tuberculosis at the individual level, this study will inform us about additional protection afforded by TB preventive therapy in a population with free access to ARV therapy. The expected reduction in TB incidence is 60%, translating to 1,670 prevented cases of TB per 100,000 population per year.
Researchers
David Bishai
Richard Chaisson
Jonathan Golub
Jeanne Keruly
Richard Moore
Lawrence H. Moulton
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CDC funded multicenter study. Prospective, randomized Phase II clinical study of moxifloxacin-based regimen for intensive phase of active TB treatment. Collaborating institution: Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Researchers
Richard Chaisson
Susan Dorman
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Multicenter, prospective study of a novel liquid culture medium for detection of M. tuberculosis and M. tuberculosis drug resistance in clinical specimens. Collaborating institutions: Federal University of Rio de Janeiro (Rio de Janeiro, Brazil); National Thorax Institute (Tegucigalpa, Honduras).
Researchers
Susan Dorman
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The purpose of this study is to test the hypothesis that treatment of chronic hepatits B in HIV infected persons is more efficacious with Truvada compared to either lamivudine or emtricitabine alone. We are also investigating the development of drug-resistant virus.
Researchers
Chloe Thio
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HPTN 052 is a Phase III, two-arm, multi-site, randomized trial to determine the effectiveness of two treatment strategies in preventing the sexual transmission of HIV in HIV-serodiscordant couples.
Based on data collected in Africa and Thailand, there is a correlation between HIV viral load (blood levels) and HIV transmission. Specifically, the higher the viral load in the blood, the more likely the chance for transmission. Antiretroviral therapy (ART) reduces the viral load in the blood, as well as in genital secretions (for both men and women), and the drugs can be detected in semen and vaginal and cervical secretions. All of this information strongly suggests that ART may make HIV-infected people less contagious. HPTN 052 compares the HIV-infection rates of two groups of HIV-serodiscordant couples. The index case of the first group starts taking ART as soon as the couple is enrolled in the study, while the index case of the second group starts taking ART when his or her CD4+ cell count drops to 200 cells/mm3 or when he or she develops an AIDS-defining illness. Both groups will receive HIV primary care and couples counseling sessions to teach them how to reduce their risk of transmission.
Researchers
Robert Bollinger Jr.
David Celentano
Joel Gallant
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We host a 3 day conference on HIV infection every other year for Brazilian physicians, the attendance is usually 800-1000. I was originally the scientific coordinator and am now the conference president.
Researchers
Joel Gallant
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Demonstration-phase research. Clinical study to determine cost-effectiveness of MGIT for detection of TB in HIV-positive adults in Brazil, and to determine impact of MGIT(on morbidity, mortality, and TB incidence) if routinely implemented for TB diagnosis in HIV-positive adults in Brazil.
Researchers
Susan Dorman
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The goal of this core (Core B) is to provide purified peripheral blood mononuclear cell and relevant clinical data from a well-characterized, comprehensive cohort of dengue and hemorrhagic fever patients. These samples are critical for the development and validation of the dengue molecular diagnostics (Project 3), epitope mapping of immune responses (Projects 1,2), dengue immunopathology (Project 2), and the ex vivo evaluation of the immunogenicity of candidate vaccines (Projects 2, 4). The study cohort will be composed of dengue and hemorrhagic fever volunteer patients from the city of Recife, in the northeast region of Brazil, which has one of the highest incidences per capita of dengue in the world. The volunteers in the cohort will be enrolled by one of three distinct recruiting approaches: 1) acute cases with clinical diagnoses of dengue fever from among subjects admitted to five major emergency services; 2) healthy individuals living in the same house as an acute case volunteer and; 3) randomly selected patients from 10% of all dengue cases officially reported to the local health authorities. These patients will be classified as asymptomatic or having classic dengue, classic dengue with low platelet count, or dengue hemorrhagic fever with its sub-classifications. The clinical characterization will include, but not be limited to, clinical history and examination, complete hemogram, platelet count, liver enzymes, HLA typing of selected patients, investigation of concomitant diseases, dengue serology (IgM and IgG) and conventional dengue PCR diagnosis. Acute case volunteers will be examined on the first and fourth days of illness, with additional evaluations every 24 (hemorrhagic fever) or 48 (classic dengue) hr, depending on the clinical state of the patients. Additional sample characterization will be performed as needed for specific project applications. The data will be entered in digital form, in real time, through a wireless interface and validated within 24 hr. The study data will be integrated into a secure, Internet-based digital databank that will include complete clinical data, research results and the respective inventories of frozen samples of peripheral blood mononuclear cells (PBMCs), plasma and serum.
Researchers
Ernesto Marques
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Map epitopes of category A to C agents for vaccine development and diagnostic tests.
1. PI Brusic - Large-scale discovery of T-Cell epitopes will be applied to selected NIAID category A-C bioterrorism agents. Current computational methods of Hidden Markov models and artificial neural networks will be used to identify class I (HLA-A2 and -A3 supertype) and class II (HLA-DR) T-Cell epitopes. Additionally, these techni\ologies will be extended to other major supertypes of class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DQ) molecules. Emphasis will also be given to identification of promiscuous pan-HLA antigen peptide sequences containing multiple epitope "hotspots" suitable for vaccine development. Computational modeling will be conducted with category A agents (bacilus anthracis, Junin, Machupo and Guanarito arenoviruses, and Hantavirus); category B viruses (hepatitis A, West Nile and Japanese encephalitis); category C agents (yellow fever and rabies), and SARS coronavirus.
2. PI- Maciel and Marques - The organization of our current Brazilian dengue virus patient cohort will be expanded to other category A-C pathogens. This will include individuals previously infected with Junin, Machupo and Guanarito arenoviruses, hantavirus, hepatitis A, yellow fever and rabies viruses. The objective of these cohorts, one of the highest priorities of the Brazilian health ministry, is to provide a unique resource to the entire scientific community.
3. PI Marques - The discovered epitopes will be analyzed by ex vivo ELISPOT assays of memory T cell responses, where peripheral blood mononuclear cells PBMCs collected from the disease-specific patient populations are available, in order to define peptides that correspond to natural T cell epitopes and correlate with disease. The immune responses of human disease specific T cells will also be analyzed with sets of synthetic overlapping peptide libraries covering selected antigens. The data from human disease-specific cell assay will be used to refine the computational models for epitope selection.
4. PI August - Promiscuous peptide epitopes containing multiple epitope "hot-spots" will be selected by combination of computational modeling and testing of antigen-specific T cell activation. The "hot-spots" will be used for the development and analyzes of epitope-based genetic vaccines. These multi-epitope vaccines based on our unique MHC II targeting LAMP/antigen chimera technology will be synthesized and tested in vivo with HLA transgenic mice for epitope processing and presentation. Epitope-specific activation of the human T cells will be validated by ELISPOT assays of cells stimulated by peptides corresponding to each of the individual epitopes of the "hot-spots".
Researchers
Thomas August
Ernesto Marques
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Dr. Eshleman currently serves as Head of the Virology Core of this international HIV Prevention Network. A proposal to continue funding of this network is under consideration at the NIH. If continued funding for the HPTN is approved, Dr. Eshleman would serve as PI of the HPTN Network Laboratory, as well as Director of the HPTN Virology Core. Dr. Eshleman currently serves as Virologist/HPTN Central Lab. Rep. for HIVNET 012 and 023, and for HPTN 046, 050, 052, 057, 059. Her participation in those trials will continue, even if some of the trials are administratively transferred to other networks (e.g. IMPAACT or MTN).
Researchers
Susan Eshleman
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The neurological complications of Human African trypanosomiasis, or sleeping sickness, caused by Trypanosoma brucei gambiense and T. b. rhodesiense are attributed to the penetration of the central nervous system by trypanosomes. Yet, how the single-cell trypanosome protozoan parasites spread from the blood to brain over the blood-brain barrier (BBB) remains an unresolved issue. This barrier is comprised of brain microvascular endothelial cells (BMEC) especially designed to keep pathogens out. Safe drugs for treating sleeping sickness are lacking and alternative treatments are urgently required. Using our human BMEC BBB model, we previously found that a parasite protease, brucipain, induced calcium activation signals that allowed this barrier to open-up to parasite crossing. Because human BMEC express Protease-Activated Receptors (PARs) that trigger calcium signals in BMEC, we hypothesized a functional link between parasite brucipain and BMEC PARs. Utilizing RNA interference to block the production of one type of PAR called PAR-2, we hindered the ability of trypanosomes to both open-up and cross human BMEC. Using gene-profiling methods to interrogate candidate BMEC pathways specifically triggered by brucipain, several pathways that potentially link brain inflammatory processes were identified, a finding congruent with the known role of PAR-2 as a mediator of inflammation. Overall, our data support a role for brucipain and BMEC PAR in trypanosome BBB transmigration, and as potential triggers for brain inflammation associated with the disease. We have also recently also demonstrated that transmigration of the Lyme disease spirochete B. burgdorferi across the BBB also depends on the bacterium’s ability to influence Ca2+ responses in human BMEC. Careful examination of these processes could identify other pathways amenable to further investigation, even pharmacological prevention of disseminated disease in humans using advanced agonists or antagonists currently in clinical trials for other purposes.
Researchers
Dennis J Grab
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This project is an international collaboration with investigators at the International Agency for Research on Cancer (IARC) and the National Cancer Institute (NCI) to explore the hypothesis that dietary polycyclic aromatic hydrocarbons (PAH) may play a role in causing elevated rates of esophageal cancer (squamous cell carcinoma) in certain regions. Pilot studies using urinary 1-hydroxypyrene as a biomarker of PAH exposure have been conducted in Linxian, China; Golestan, Iran; and Rio Grande do Sul, southern Brazil.
Researchers
Paul Strickland
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The objective of this study is to assess exposure of bar and nightclub employees to secondhand tobacco smoke (SHS) in 23 countries throughout the world. For this project, which is just starting, we will sample 10 bars and up to 5 employees per bar in each country. SHS will be assessed using airborne nicotine and hair nicotine samples.
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Researchers
Erika Avila-Tang
Patrick Breysse
Ana Navas-Acien
Heather Wipfli
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Secondhand smoke (SHS) is an involuntary exposure that poses serious health risk to passive smokers. In Latin America, there is insufficient information regarding range of exposure and locations where passive smoking is taking place. The objective of this project is to develop a surveillance method for assessing SHS in public places in Latin American countries in order to support smoke-free policies and programs to reduce passive smoking in the region.
2001-2004
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Researchers
Ana Navas-Acien
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The study uses a common protocol in China, Mexico, Brazil, and Poland exploring relationship between smoking habits, cigarette content, and nicotine dose. Recent analyses have addressed differences between less and more addicted smokers, differences in cotinine in “light” and regular cigarette smokers, and gender smoking patterns and addiction.
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Researchers
Jonathan Samet
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The Institute for Global Tobacco Control has been actively involved in developing curriculum and providing training in tobacco control in the United States and across the world. Since 2003 the Institute has established Centers of Excellence for Education and Training in Tobacco Control in three countries: Brazil, China, and Mexico. The Centers are an expansion of our Fogarty International Center collaboration project with partner institutions in each country and allow for additional workshops and training sessions on tobacco control topics. They are a critical stepping stone for advancing tobacco control knowledge in Brazil, China, and Mexico.
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Researchers
Jonathan Samet
Frances Stillman
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Co-Chair of WHO Multicountry Study of Violence Against Women & Health: Bengaladesh, Brazil, Peru, Namibia, Tanzania, Ethiopia, Thailand, Serbia, Japan, New Zealand
Researchers
Jacquelyn C. Campbell
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no abstract provided
Researchers
David R. Holtgrave
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Initiative to establish international regional centers for the collection and harmonization of data and the establishment of an international research consortium to address unique and evolving research questions in HIV/AIDS currently unanswerable by single cohorts. More than 200,000 HIV-infected persons from 38 different countries are included. Questions regarding utilization and effectiveness of ARV therapy, toxicities, opportunistic disease and other co-morbidities (e.g., TB, hepatitis) and other topics will be addressed.
For more information visit, http://www.iedea-hiv.org/about/
Researchers
Richard Moore
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Supports TB community intervention trials in Brazil, South Africa, and Zambia
Researchers
Lawrence H. Moulton
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we are examining exposures to mercury among gold miners and fish consumers in Amazonian Brazil; outcomes include health status with an emphasis on interactions with malaria and other infectious diseases and assessment of molecular biomarkers for autoimmunity
Researchers
Ellen Silbergeld
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The THRio study is designed to determine whether the routine detection and treatment of TB infection found in HIV infected patients in HIV clinics in Rio de Janeiro, Brazil, reduces TB incidence in the clinic population receiving HIV care. Involving an estimated 15,000 clinic patients, the intervention consists of implementing a comprehensive policy of screening for and treating latent TB infection in all HIV-infected patients. The trial takes a phased-implementation approach to ensure that all participating clinics eventually have full coverage. Phased implementation is a realistic and pragmatic method to effectively train all clinic personnel in the skills required to appropriately test and treat these patients. Brazil was the ideal location for this study because the government has made antiretroviral (ARV) therapy freely available for years. Although it is already known that treatment with ARV therapy reduces the risk of developing tuberculosis at the individual level, this study will inform us about additional protection afforded by TB preventive therapy in a population with free access to ARV therapy. The expected reduction in TB incidence is 60%, translating to 1,670 prevented cases of TB per 100,000 population per year.
Researchers
Jonathan Golub
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In 2007, Johnson and Johnson engaged Johns Hopkins Medicine International experts to provide Leadership Academy sessions to selected Lain American CEOs and Johnson and Johnson internal staff.
In the course of 3 separate trips, JHI provided customized Leadership Academy session in each of the following countries: Columbia, Venezuela, Ecuador, Medico, Argentina, Paraguay, Brazil, and Chile.
Each session was customized with country-specific information and focused on:
- The key environmental forces in healthcare quality and patient safety and how they will impact hospitals and physician practice. This will reflect international trends, as well as customized information on local market influences and characteristics.
- The "Hopkins story" and Hopkins'' lessons learned on improving patient safety and clinical quality.
- Linking patient safety and clinical quality to organizational strategy.
- Specific leadership competencies and actions needed to raise organizational performance.
Researchers
Mark Shaver
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Setting up a study to assess the prevalence of depression among women during their 2nd/3rd trimester of pregnancy and 2-3 months postpartum. The sample will include both HIV infected and non-HIV infected women in order to assess the added burden HIV confers on the risk for depression during this highly vulnerable period.
Researchers
Judith K. Bass
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Highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in HIV-infected persons worldwide. However, early treatment failure (i.e. WHO stage 3 or 4 illnesses or death during the first 12 months of HAART) is >3-fold higher in resource limited settings (RLS) than in resource-rich settings. Early treatment failure is associated with low CD4 count, low body mass index, and anemia, but these markers are nonspecific and could reflect advanced HIV, co-infections, and/or malnutrition. The relative contribution of malnutrition to early treatment failure in RLS is unknown. Up to 40% of adults in RLS are malnourished due to protein-energy, iron or iron-deficiency anemia, or other micronutrient deficiencies, which are associated with immune dysfunction and increased morbidity and mortality. However, the significance of this malnutrition in HIV-infected persons initiating HAART in RLS is unclear. In addition to immune dysfunction, this malnutrition has been associated with impaired gut integrity, increased microbial translocation and immune activation. Recently, chronic HIV infection
has also been associated with a “leaky gut” and systemic immune activation. High levels of immune activation result in impaired immune restoration with HAART and HIV disease progression. Therefore, we hypothesize that baseline malnutrition is predictive of early treatment failure among HIV-infected adults in RLS and that early treatment failure is related to the synergistic deleterious effects of HIV and malnutrition on gut mucosal integrity leading to increased systemic immune activation. To address our hypotheses, we will utilize data and cryopreserved samples collected as part of an ongoing trial conducted by the Adults AIDS Clinical Trial Group (ACTG 5175). This NIH-funded study is evaluating the efficacy of HAART among 1571 HIV-infected adults in 8
RLS countries (Africa-3, Asia-2, Americas-3) and the United States. We propose three specific aims:1) To characterize baseline micronutrient status and assess its relationship to baseline disease stage, demographics and simple-to-measure nutritional indices among treatment-naïve HIV-infected adults initiating HAART; 2) To assess whether specific measures of baseline malnutrition are independent predictors of early treatment failure. 3) To determine whether malnutrition and treatment failure are associated with microbial translocation, immune activation, and reduced immune restoration. Our study has a high likelihood of success because our international
team includes leaders in HIV, immunology, statistics and nutrition research. Data and specimens for our study come from a NIH-funded trial that is ongoing but has completed enrolment. This will reduce the time needed to complete the planned studies and optimize cost-efficiency. Importantly, data generated from our study will fill a
critical knowledge gap in the understanding the role of malnutrition on early HAART outcomes in RLS. Such data are needed to 1) provide necessary evidence to guide the design of new trials that will optimize the benefits of HAART in RLS, where HIV, early treatment failure, food insecurity, and malnutrition are all common, and 2) further our insights on the relationship between malnutrition, immunity and infectious disease pathogenesis.
Researchers
Adriana Andrade
Robert Bollinger Jr.
Parul Christian
Amita Gupta
David Thomas
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A family based study of genetic susceptibility to visceral, cutaneous and mucosal leishmaniasis in Brazil. Leishmaniasis is a parasitic infection spread by a sandfly.
Researchers
Priya Duggal
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Data on the prevalence and risk factors associated with depression during pregnancy present a mixed picture. A recent national survey of psychiatric disorders during pregnancy and postpartum found that pregnant women were less likely than non-pregnant women to be suffering from a mood disorder (Vesga-Lopez et al., 2008). However, the same study showed that women experiencing pregnancy complications were at increased risk for psychiatric disorders compared to other pregnant women.
Mothers with HIV are at high risk for a range of mental health symptoms and disorders (McClure et al., 1996; McEnany et al., 1996; Semple et al., 1996). What is not yet known is whether HIV infection, particularly when good treatment is available and rates of mother-to child transmission are minimized, is one of the health problems that puts a woman into that ‘high risk’ category in relation to being at increased risk for experiencing depression during pregnancy.
The NIH provided funding for an investigation of the prevalence and risk factors for perinatal depression among HIV infected and uninfected women in Brazil (1R21TW008224 - 01A1). The first aim of this grant is to compare the prevalence of depression among pregnant HIV infected women with healthy pregnant non-HIV infected women to identify the added burden HIV infection brings to the risk for depression during pregnancy. The purpose of this global health submission is to add an additional sample of non-HIV infected women experiencing high risk pregnancies to compare the rates of depression among these women with those who are HIV infected. Including a sample of non-HIV infected high risk pregnant women will greatly strengthen the results of the overall investigation and improve chances for obtaining a subsequent R01 project to target an intervention study for prenatal depression.
Researchers
Judith K. Bass
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Bartonella are fastidious, hemotropic bacteria, which cause long-lasting bacteremia in mammals and are transmitted by animal bites, scratches, or a variety of vectors including sand flies, body lice, fleas and ticks. Throughout the world, Bartonella species are considered emerging pathogens. In humans, Bartonella spp. are the causative agents of cat-scratch disease (CSD), bacillary angiomatosis, bacillary peliosis, and endocarditis. There is also evolving evidence that supports a potential role for Bartonella spp. in patients with neurological and neuro-cognitive dysfunction and chronic illness associated with joint pain and fatigue. In Brazil, only one study has evaluated healthy subjects for exposure to these pathogens; however the study was delimited to a rural population. Our objective for this proposal is to detect the occurrence of active Bartonella spp. infection and/or exposure in a large blood donor population at a major public hospital in Campinas, Sao Paulo State. We would also like to collect samples from donor pets to establish preliminary data to suggest a zoonotic role for animals as reservoirs in pathogen amplification and transmission via competent vectors. Due the chronic and complex nature of disease caused by these bacterial infections, detection of infection in donors will justify implementation of screening procedures for these bacteria and education of blood donors, especially if there is a history of significant animal or vector exposure. We will utilize serology, PCR, sequencing, electron microscopy, and culture methods to adequately identify these pathogens from blood and determine the prevalence of exposure in this Brazilian population.
Researchers
Diana Scorpio
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Given the high global co-morbidity of HIV and major depressive disorder (MDD), understanding the negative synergistic effects of these two disabling conditions is increasingly important as comprehensive HIV care moves beyond biomedical concerns to include concurrent treatment of mental disorders. Our long-term research program uses perinatal depression (PD) in HIV-infected mothers in southern Brazil as an initial paradigm for intervention studies of the interaction of HIV and MDD. Brazil offers several major advantages for conducting prospective, focused, straight-forward studies of this complex global problem: > 98% of pregnant women receive free effective HIV-treatment; mother-to-child HIV transmission rates are <1%; integration of our research program with a large, well-established and successful NICHD-funded program (International Site Development Initiative - NISDI) that seeks to strengthen biomedical research infrastructure for studying HIV-infected women and their newborn children in Latin America; and a highly centralized HIV treatment program for pregnant women, providing access to large numbers of HIV-infected women presenting for care early in their pregnancies. This present bi-national, multidisciplinary project will enable collection of requisite pilot data on prevalence of PD, identification of risk factors and leverage points for subsequent intervention programs, development of effective strategies for integration of studies of PD into NISDI, and adaptation and validation of screening instruments among the local population. Using the NISDI infrastructure at the Faculty of Medicine, University of Caxias in southern Brazil interconnected studies will be conducted in Porto Alegre (population ~10 million) during the 24-month study period. Study 1: a qualitative study to delineate local concepts of depression, coping strategies, social support, and stigma; and Studies 2 and 3: PD screenings among 450 HIV-infected and 450 control HIV-uninfected women at two time points (during the second trimester of pregnancy and three-four months post-partum) at two large Brazilian Federation hospitals to establish PD prevalence rates and increase understanding of the impact of associated psychosocial factors (frequency of stressful life events, support systems, coping and stigma). This study seeks to use the high proclivity for seeking prenatal care and newborn health visits that frequently characterizes an often marginalized HIV-infected population of women who may otherwise not be available for study. PUBLIC HEALTH RELEVANCE: Currently there is little known about the nature of depression among HIV-infected women of child-bearing age; particularly in the context of effective HIV treatment programs, which are allowing infected women to live longer and significantly reducing mother-to-child transmission of the virus. This research will begin to address this issue by studying the nature, importance and causes of perinatal depression related to HIV infection and will be used to develop feasible and sustainable options for treating perinatal depression whose efficacy will be tested.
Researchers
Judith K. Bass
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Background: Brazil is the second world producer and top world exporter of unmanufactured tobacco leaf. As a ratifying country of the World Health Organization’s Framework Convention on Tobacco Control (FCTC), the government has made a commitment to enact legislation and programs that will support economically viable alternatives to and protect their citizens and the
environment from the detriments of tobacco farming. Children working on tobacco farms may be exposed to nicotine through dermal absorption from leaf contact and at increased risk for Green Tobacco Sickness (GTS). The National Program to Support Product Diversification in Tobacco Growing Areas spearheads the current effort by Brazil to transition families away from tobacco farming.
Objective: To characterize exposure to nicotine and prevalence of GTS among children and families of tobacco growing households participating in the Diversification Program in Rio Pardo Valley, Brazil, and to understand the families’ experience with the Program.
Design, Setting, and Participants: A cohort study of children and adults in 50 tobacco-farming households in Rio Pardo Valley, Brazil. Nicotine exposure will be assessed a two time points, during the harvest of the green leaf and during dry leaf classification. Families will be from nonsmoking households and in the initial or advanced stage of transition in the Program.
Significance: Results from this proposed study will be used to support advocacy efforts to
increase funding of the Brazilian Diversification Program. Additionally, the results will
contribute to the evidence base of the impacts of the use of child labor in tobacco farming.
Researchers
Erika Avila-Tang
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The Cochrane Eyes and Vision Group aims to prepare, maintain and promote access to systematic reviews of interventions used to prevent or treat eye diseases and/or visual impairment. The work of the CEVG is carried out by over 300 members in more than 30 countries. The CEVG editorial team is located in London, UK and the CEVG US Project (CEVG@US) is a US-based satellite at the Johns Hopkins Bloomberg School of Public Health.
The CEVG@US is funded by the National Eye Institute. The overall objective of CEVG@US is to develop a critical mass of US-based vision researchers and practitioners who are trained in preparing and using systematic reviews.
The CEVG@US aims to accomplish four main goals: 1) Expand awareness of evidence-based health care in general and in eyes and vision specifically, 2) Develop a critical mass of vision researchers who are able to perform and interpret systematic reviews, and train others to do the same; 3) Develop a critical mass of clinicians who use the results of systematic reviews as an evidence base to guide their practice, and to train others to do the same; 4) Generate an increased number of systematic reviews in priority vision research areas, published in The Cochrane Library and in the traditional vision research literature.
Researchers
Kay Dickersin
Ann-Margret Ervin
Barbara Hawkins
Roberta W. Scherer
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Tuberculosis (TB) is the second-leading cause of death by infection. Novel strategies are critically needed to shorten treatment duration and treat multidrug resistant (MDR) and extensively drug-resistant (XDR) TB. The applicant is pursuing joint training in Clinical Pharmacology and Infectious Diseases and will combine her expertise in these areas to lead the rational development of new treatments for TB. The K23 award would provide the ideal vehicle for her to complete her education and training so she may launch an independent career in academic clinical research focused on TB therapeutics. The overall goal of this proposal is to evaluate pharmacokinetic and pharmacodynamic (PK/PD) parameters of two promising new TB treatments. First, moxifloxacin- and rifapentine- (RPT) containing regimens are strikingly effective in mice. Defining the PK/PD parameters that predict treatment response in humans will be essential for developing rational dosing regimens. Rifamycin hypersensitivity, however, may occur with high-dose, intermittent RPT and impact its safety. Second, TMC207 is a new agent being developed for TB treatment that is active against MDR TB. It is metabolized by the cytochrome P450 isoenzyme 3A4 (CYP3A4), so drug interactions with agents used to treat human immunodeficiency virus (HIV) are likely. We propose: AIM 1: To identify, for RPT and moxifloxacin, the PK/PD parameters that correlate most strongly with treatment response. We will perform a PK study nested in a Phase II randomized trial comparing a moxifloxacin- and RPT-based regimen to standard therapy during intensive phase TB treatment in Brazil. AIM 2: To investigate the incidence and immunopathogenesis of rifamycin hypersensitivity syndrome in patients receiving high-dose, intermittent RPT in the context of the Phase II trial. AIM 3: To determine the impact of antiviral drugs (ARVs), beginning with efavirenz (EFV), on the steady state pharmacokinetics of TMC207 in healthy volunteers. These studies will be performed at Johns Hopkins University with AIDS Clinical Trials Group (ACTG) support. Through these studies, we will better understand the pharmacology of moxifloxacin- and RPT-based regimens, allowing for optimization of this potent new regimen which may shorten TB treatment. This work will also provide crucial information that will impact the treatment of TB/HIV coinfected patients worldwide.
Researchers
Kelly Dooley
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The TBTC is a collaboration of researchers from the CDC, domestic and international public health departments, academic medical centers, and selected Veterans Administration medical centers whose mission is to conduct programmatically relevant research concerning the diagnosis, clinical management, and prevention of tuberculosis (TB) infection and disease. The purposes of the TBTC are to conduct research that expands clinical and epidemiologic knowledge of TB and facilitates the diagnosis, clinical management, and prevention of tuberculosis infection and disease; to integrate research into the care of persons with TB infection and disease; to develop research questions that are relevant to program settings in general; to promote research within local TB control programs through collaboration on clinical research of relevance to public health settings; and to provide a forum for international collaborative research of importance to both domestic and international TB control.
Researchers
Richard Chaisson
Susan Dorman
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This project will develop a highly sensitive toolkit for prediction of dengue epidemics such that appropriate control measures can be put into place to reduce the impact of the disease on human populations.
Researchers
Gregory Glass
Douglas Norris
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