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Jerrold J. Ellner

Bio: Jerrold J. Ellner is an academic researcher from Rutgers University. The author has contributed to research in topics: Tuberculosis & Mycobacterium tuberculosis. The author has an hindex of 76, co-authored 347 publications receiving 17893 citations. Previous affiliations of Jerrold J. Ellner include Boston Medical Center & Makerere University.


Papers
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Journal ArticleDOI
TL;DR: Although active tuberculosis may be an independent marker of advanced immunosuppression in HIV-infected patients, it may also act as a cofactor to accelerate the clinical course of HIV infection.
Abstract: To determine the effect of active tuberculosis on survival and the incidence of opportunistic infections in HIV-infected patients, we performed a retrospective cohort study at four U.S. medical centers to compare the survival and incidence rate of opportunistic infections in 106 HIV-infected patients with active tuberculosis (cases) with that of 106 HIV-infected patients without tuberculosis (control subjects) but with a similar level of immunosuppression (measured by the absolute CD4+ lymphocyte count) as the cases. Cases and control subjects were similar with regard to age, sex, race, previous opportunistic infection, and use of antiretroviral therapy, but they were more likely than control subjects to have a history of intravenous drug use (49 versus 19%). The mean CD4+ counts were similar for cases and control subjects (154 versus 153 cells/microliters, respectively). The incidence rate of new AIDS-defining opportunistic infections in cases was 4.0 infections per 100 person-months compared with 2.8 in...

557 citations

Journal ArticleDOI
David Lanier1, Neil Schram2, Ellen C. Cooper3, Kenneth A. Freedberg4, Kenneth H. Mayer5, Richard Blinkhorn6, Jerrold J. Ellner6, Fred Angulo2, Ruth L. Berkelman2, Robert F. Breiman2, Ralph T. Bryan2, James W. Buehler2, Blake Caldwell2, Kenneth G. Castro2, James E. Childs2, Susan Chu2, Carol A. Ciesielski2, D. Peter Drotman2, Brian R. Edlin2, Tedd V. Ellerbrock2, Patricia L. Fleming2, Larry Geiter2, Rana A. Hajjeh2, Debra L. Hanson2, Scott D. Holmberg2, James M. Hughes2, Harold W. Jaffe2, Jeffrey L. Jones2, Dennis D. Juranek2, Jonathan E. Kaplan2, David W. Keller2, William J. Martone2, Michael M. Mc Neil2, Bess Miller2, Thomas R. Navin2, Verla S. Neslund2, Stephen M. Ostroff2, Philip E. Pellett2, Robert W. Pinner2, Susan E. Reef2, William C. Reeves2, Russell L. Regnery2, Frank O. Richards2, Martha F. Rogers2, Lawrence B. Schonberger2, R. J. Simonds2, Patricia M. Simone2, Dawn K. Smith2, Steven L. Solomon2, Richard A. Spiegel2, John A. Stewart2, David L. Swerdlow2, Suzanne D. Vernon2, John W. Ward2, Joyce J. Neal7, Walter F. Schlech8, Catherine M. Wilfert9, Robert Horsburgh10, John Mc Gowan10, David Rimland10, Mark Goldberger11, Carol Braun Trapnell11, David Barr12, Gabriel Torres12, Harrison C. Stetler, Peter A. Gross13, Wafaa El-Sadr14, Deborah J. Cotton15, Wayne L. Greaves16, John Bartlett17, Richard E. Chaisson17, Judith Feinberg17, Thomas C. Quinn17, Joseph Horman18, Kristine Mac Donald, Mary E. Wilson19, Rhoda S. Sperling20, Alberto Avandano, A. Cornelius Baker, Anthony R. Kalica21, Joseph A. Kovacs21, Henry Masur21, Michael A. Polis21, Steven M. Schnittman21, Charles Nelson, John P. Phair22, Constance A. Benson23, Bob Wood, Walter T. Hughes24, Benjamin J. Luft25, Newton E. Hyslop26, Richard J. Whitley27, Neil M. Ampel28, W. Lawrence Drew29, Jane E. Koehler29, Constance B. Wofsy29, James D. Neaton30, Fred R. Sattler31, Sharon A. Baker32, Lawrence Corey32, King K. Holmes32, William G. Powderly33 

422 citations

Journal ArticleDOI
TL;DR: A six-month course of isoniazid confers short-term protection against tuberculosis among PPD-positive, HIV-infected adults and multidrug regimens with isoniaZid and rifampin taken for three months also reduce the risk of tuberculosis.
Abstract: Background Infection with the human immunodeficiency virus (HIV) greatly increases the risk of reactivation tuberculosis. We evaluated the safety and efficacy of three preventive-therapy regimens in a setting where exposure to tuberculosis is common. Methods We performed a randomized, placebo-controlled trial in 2736 HIV-infected adults recruited in Kampala, Uganda. Subjects with positive tuberculin skin tests (induration, >5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462). Subjects with anergy (0 mm induration in reaction to PPD and candida antigens) were randomly assigned to receive either placebo (323 subjects) or six months of isoniazid (395). The medications were dispensed monthly and were self-administered. Results Among the PPD-positive subjects, the incidence of tuberculosi...

410 citations

Journal ArticleDOI
TL;DR: For tuberculosis case detection, sensitivity ofXpert Ultra was superior to that of Xpert in Patients with paucibacillary disease and in patients with HIV, however, this increase in sensitivity came at the expense of a decrease in specificity.
Abstract: Summary Background The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. Methods In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Findings Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (−2·7%, −3·9 to −1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. Interpretation For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. Funding Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases.

391 citations

Journal ArticleDOI
TL;DR: The data indicate that the immunosuppression of TB is not only immediate and apparently dependent (at least in part) on Immunosuppressive cytokines early during the course of Mycobacterium TB infection but is also long lasting, presumably relating to a primary abnormality in T-cell function.
Abstract: Immunological and clinical profiles were evaluated in 2 groups: human immunodeficiency virus (HIV)-uninfected and HIV-infected patients, with newly diagnosed pulmonary tuberculosis (TB), and tuberculin-skin-test-reactive healthy control subjects. HIV-uninfected patients with TB were also followed up longitudinally during and after chemotherapy. At the time of diagnosis, purified protein derivative (PPD)-stimulated production of interferon (IFN)-gamma by peripheral blood mononuclear cells from TB patients was depressed, compared with that of healthy control subjects, whereas levels of transforming growth factor (TGF)-beta and interleukin (IL)-10 were increased. In longitudinal studies, PPD stimulated production of IL-10 and TGF-beta returned to baseline by 3 months, whereas IFN-gamma production remained depressed for at least 12 months. These data indicate that the immunosuppression of TB is not only immediate and apparently dependent (at least in part) on immunosuppressive cytokines early during the course of Mycobacterium TB infection but is also long lasting, presumably relating to a primary abnormality in T-cell function.

313 citations


Cited by
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Journal ArticleDOI
TL;DR: These Guidelines were developed by the Panel* on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services and the Henry J. Kaiser Family Foundation.
Abstract: SUMMARY The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents. This report recommends that care should be supervised by an expert, and makes recommendations for laboratory monitoring including plasma HIV RNA, CD4 cell counts and HIV drug resistance testing. The report also provides guidelines for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy, and therapeutic options when changing therapy. Special considerations are provided for adolescents and pregnant women. As with treatment of other chronic conditions, therapeutic decisions require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Antiretroviral regimens are complex, have major side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance due to non-adherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic

4,321 citations

Journal ArticleDOI
TL;DR: The technical aspects involved are discussed, conventional and kinetic RT-PCR methods for quantitating gene expression are contrasted, and the usefulness of these assays are illustrated by demonstrating the significantly different levels of transcription between individuals of the housekeeping gene family, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH).
Abstract: The reverse transcription polymerase chain reaction (RT-PCR) is the most sensitive method for the detection of low-abundance mRNA, often obtained from limited tissue samples. However, it is a complex technique, there are substantial problems associated with its true sensitivity, reproducibility and specificity and, as a quantitative method, it suffers from the problems inherent in PCR. The recent introduction of fluorescence-based kinetic RT-PCR procedures significantly simplifies the process of producing reproducible quantification of mRNAs and promises to overcome these limitations. Nevertheless, their successful application depends on a clear understanding of the practical problems, and careful experimental design, application and validation remain essential for accurate quantitative measurements of transcription. This review discusses the technical aspects involved, contrasts conventional and kinetic RT-PCR methods for quantitating gene expression and compares the different kinetic RT-PCR systems. It illustrates the usefulness of these assays by demonstrating the significantly different levels of transcription between individuals of the housekeeping gene family, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH).

4,100 citations

Journal ArticleDOI
18 Aug 1999-JAMA
TL;DR: The global burden of tuberculosis remains enormous, mainly because of poor control in Southeast Asia, sub-Saharan Africa, and eastern Europe, and because of high rates of M tuberculosis and HIV coinfection in some African countries.
Abstract: Objective To estimate the risk and prevalence of Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB) incidence, prevalence, and mortality, including disease attributable to human immunodeficiency virus (HIV), for 212 countries in 1997. Participants A panel of 86 TB experts and epidemiologists from more than 40 countries was chosen by the World Health Organization (WHO), with final agreement being reached between country experts and WHO staff. Evidence Incidence of TB and mortality in each country was determined by (1) case notification to the WHO, (2) annual risk of infection data from tuberculin surveys, and (3) data on prevalence of smear-positive pulmonary disease from prevalence surveys. Estimates derived from relatively poor data were strongly influenced by panel member opinion. Objective estimates were derived from high-quality data collected recently by approved procedures. Consensus Process Agreement was reached by (1) participants reviewing methods and data and making provisional estimates in closed workshops held at WHO's 6 regional offices, (2) principal authors refining estimates using standard methods and all available data, and (3) country experts reviewing and adjusting these estimates and reaching final agreement with WHO staff. Conclusions In 1997, new cases of TB totaled an estimated 7.96 million (range, 6.3 million–11.1 million), including 3.52 million (2.8 million–4.9 million) cases (44%) of infectious pulmonary disease (smear-positive), and there were 16.2 million (12.1 million–22.5 million) existing cases of disease. An estimated 1.87 million (1.4 million–2.8 million) people died of TB and the global case fatality rate was 23% but exceeded 50% in some African countries with high HIV rates. Global prevalence of MTB infection was 32% (1.86 billion people). Eighty percent of all incident TB cases were found in 22 countries, with more than half the cases occurring in 5 Southeast Asian countries. Nine of 10 countries with the highest incidence rates per capita were in Africa. Prevalence of MTB/HIV coinfection worldwide was 0.18% and 640,000 incident TB cases (8%) had HIV infection. The global burden of tuberculosis remains enormous, mainly because of poor control in Southeast Asia, sub-Saharan Africa, and eastern Europe, and because of high rates of M tuberculosis and HIV coinfection in some African countries.

3,035 citations

Book ChapterDOI
TL;DR: The existence of NK cells has prompted a reinterpretation of both the studies of specific cytotoxicity against spontaneous human tumors and the theory of immune surveillance, at least in its most restrictive interpretation.
Abstract: Publisher Summary Studies of cytotoxicity by human lymphocytes revealed not only that both allogeneic and syngeneic tumor cells were lysed in a non-MHC-restricted fashion, but also that lymphocytes from normal donors were often cytotoxic. Lymphocytes from any healthy donor, as well as peripheral blood and spleen lymphocytes from several experimental animals, in the absence of known or deliberate sensitization, were found to be spontaneously cytotoxic in vitro for some normal fresh cells, most cultured cell lines, immature hematopoietic cells, and tumor cells. This type of nonadaptive, non-MHC-restricted cellmediated cytotoxicity was defined as “natural” cytotoxicity, and the effector cells mediating natural cytotoxicity were functionally defined as natural killer (NK) cells. The existence of NK cells has prompted a reinterpretation of both the studies of specific cytotoxicity against spontaneous human tumors and the theory of immune surveillance, at least in its most restrictive interpretation. Unlike cytotoxic T cells, NK cells cannot be demonstrated to have clonally distributed specificity, restriction for MHC products at the target cell surface, or immunological memory. NK cells cannot yet be formally assigned to a single lineage based on the definitive identification of a stem cell, a distinct anatomical location of maturation, or unique genotypic rearrangements.

2,982 citations

Journal ArticleDOI
TL;DR: Its striking inter- and intracellular signaling capacity makes it extremely difficult to predict the effect of NOS inhibitors and NO donors, which still hampers therapeutic applications.
Abstract: During the past two decades, nitric oxide (NO) has been recognized as one of the most versatile players in the immune system. It is involved in the pathogenesis and control of infectious diseases, tumors, autoimmune processes and chronic degenerative diseases. Because of its variety of reaction partners (DNA, proteins, low–molecular weight thiols, prosthetic groups, reactive oxygen intermediates), its widespread production (by three different NO synthases (NOS) and the fact that its activity is strongly influenced by its concentration, NO continues to surprise and perplex immunologists. Today, there is no simple, uniform picture of the function of NO in the immune system. Protective and toxic effects of NO are frequently seen in parallel. Its striking inter- and intracellular signaling capacity makes it extremely difficult to predict the effect of NOS inhibitors and NO donors, which still hampers therapeutic applications.

2,944 citations