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Search Results: 1 - 10 of 299936 matches for " J. Lucian Davis "
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A Transcriptional Signature for Active TB: Have We Found the Needle in the Haystack?
Adithya Cattamanchi ,Nicholas D. Walter,John Z. Metcalfe,J. Lucian Davis
PLOS Medicine , 2013, DOI: 10.1371/journal.pmed.1001539
Abstract:
Population-Level Impact of Same-Day Microscopy and Xpert MTB/RIF for Tuberculosis Diagnosis in Africa
David W. Dowdy, J. Lucian Davis, Saskia den Boon, Nicholas D. Walter, Achilles Katamba, Adithya Cattamanchi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070485
Abstract: Objective To compare the population-level impact of two World Health Organization-endorsed strategies for improving the diagnosis of tuberculosis (TB): same-day microscopy and Xpert MTB/RIF (Cepheid, USA). Methods We created a compartmental transmission model of TB in a representative African community, fit to the regional incidence and mortality of TB and HIV. We compared the population-level reduction in TB burden over ten years achievable with implementation over two years of same-day microscopy, Xpert MTB/RIF testing, and the combination of both approaches. Findings Same-day microscopy averted an estimated 11.0% of TB incidence over ten years (95% uncertainty range, UR: 3.3%–22.5%), and prevented 11.8% of all TB deaths (95% UR: 7.7%–27.1%). Scaling up Xpert MTB/RIF to all centralized laboratories to achieve 75% population coverage had similar impact on incidence (9.3% reduction, 95% UR: 1.9%–21.5%) and greater effect on mortality (23.8% reduction, 95% UR: 8.6%–33.4%). Combining the two strategies (i.e., same-day microscopy plus Xpert MTB/RIF) generated synergistic effects: an 18.7% reduction in incidence (95% UR: 5.6%–39.2%) and 33.1% reduction in TB mortality (95% UR: 18.1%–50.2%). By the end of year ten, combining same-day microscopy and Xpert MTB/RIF could reduce annual TB mortality by 44% relative to the current standard of care. Conclusion Scaling up novel diagnostic tests for TB and optimizing existing ones are complementary strategies that, when combined, may have substantial impact on TB epidemics in Africa.
Rapid Molecular Testing for TB to Guide Respiratory Isolation in the U.S.: A Cost-Benefit Analysis
Alexander J. Millman, David W. Dowdy, Cecily R. Miller, Robert Brownell, John Z. Metcalfe, Adithya Cattamanchi, J. Lucian Davis
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079669
Abstract: Background Respiratory isolation of inpatients during evaluation for TB is a slow and costly process in low-burden settings. Xpert MTB/RIF (Xpert) is a novel molecular test for tuberculosis (TB) that is faster and more sensitive but substantially more expensive than smear microscopy. No previous studies have examined the costs of molecular testing as a replacement for smear microscopy in this setting. Methods We conducted an incremental cost–benefit analysis comparing the use of a single negative Xpert versus two negative sputum smears to release consecutive adult inpatients with presumed TB from respiratory isolation at an urban public hospital in the United States. We estimated all health-system costs and patient outcomes related to Xpert implementation, diagnostic evaluation, isolation, hospitalization, and treatment. We performed sensitivity and probabilistic uncertainty analyses to determine at what threshold the Xpert strategy would become cost-saving. Results Among a hypothetical cohort of 234 individuals undergoing evaluation for presumed active TB annually, 6.4% had culture-positive TB. Compared to smear microscopy, Xpert reduced isolation bed utilization from an average of 2.7 to 1.4 days per patient, leading to a 48% reduction in total annual isolation bed usage from 632 to 328 bed-days. Xpert saved an average of $2,278 (95% uncertainty range $1582–4570) per admission, or $533,520 per year, compared with smear microscopy. Conclusions Molecular testing for TB could provide substantial savings to hospitals in high-income countries by reducing respiratory isolation usage and overall length of stay.
Nucleic Acid Amplification Tests for Diagnosis of Smear-Negative TB in a High HIV-Prevalence Setting: A Prospective Cohort Study
J. Lucian Davis,Laurence Huang,William Worodria,Henry Masur,Adithya Cattamanchi,Charles Huber,Cecily Miller,Patricia S. Conville,Patrick Murray,Joseph A. Kovacs
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016321
Abstract: Nucleic acid amplification tests are sensitive for identifying Mycobacterium tuberculosis in populations with positive sputum smears for acid-fast bacilli, but less sensitive in sputum-smear-negative populations. Few studies have evaluated the clinical impact of these tests in low-income countries with high burdens of TB and HIV.
Bronchoalveolar Lavage Enzyme-Linked Immunospot for Diagnosis of Smear-Negative Tuberculosis in HIV-Infected Patients
Adithya Cattamanchi, Isaac Ssewenyana, Rose Nabatanzi, Cecily R. Miller, Saskia Den Boon, J. Lucian Davis, Alfred Andama, William Worodria, Samuel D. Yoo, Huyen Cao, Laurence Huang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039838
Abstract: Background Peripheral blood interferon-gamma release assays (IGRAs) have sub-optimal sensitivity and specificity for diagnosis of active pulmonary tuberculosis (TB). However, assessment of local immune responses has been reported to improve the accuracy of TB diagnosis. Methods We enrolled HIV-infected adults with cough ≥2 weeks’ duration admitted to Mulago Hospital in Kampala, Uganda and referred for bronchoscopy following two negative sputum acid-fast bacillus smears. We performed an ELISPOT-based IGRA (T-SPOT.TB?, Oxford Immunotec, Oxford, UK) using peripheral blood and bronchoalveolar lavage (BAL) fluid mononuclear cells, and determined the accuracy of IGRAs using mycobacterial culture results as a reference standard. Results 94 HIV-infected patients with paired peripheral blood and BAL IGRA results were included. The study population was young (median age 34 years [IQR 28–40 years]) and had advanced HIV/AIDS (median CD4+ T-lymphocyte count 60 cells/μl [IQR 22–200 cells/μl]). The proportion of indeterminate IGRA results was higher in BAL fluid than in peripheral blood specimens (34% vs. 14%, difference 20%, 95% CI 7–33%, p = 0.002). BAL IGRA had moderate sensitivity (73%, 95% CI 50–89%) but poor specificity (48%, 95% CI 32–64%) for TB diagnosis. Sensitivity was similar (75%, 95% CI 57–89%) and specificity was higher (78%, 95% CI 63–88%) when IGRA was performed on peripheral blood. Conclusions BAL IGRA performed poorly for the diagnosis of smear-negative TB in a high HIV/TB burden setting. Further studies are needed to examine reasons for the large proportion of indeterminate results and low specificity of BAL IGRA for active TB in high HIV/TB burden settings.
Oral Antimicrobial Rinse to Reduce Mycobacterial Culture Contamination among Tuberculosis Suspects in Uganda: A Prospective Study
Nelson Kalema, Saskia Den Boon, Adithya Cattamanchi, J. Lucian Davis, Alfred Andama, Winceslaus Katagira, Charles Everett, Nicholas Walter, Patrick Byanyima, Sylvia Kaswabuli, William Worodria, Laurence Huang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038888
Abstract: Rationale Contamination by bacterial or fungal organisms reduces the effectiveness of mycobacterial culture for diagnosis of pulmonary tuberculosis (TB). We evaluated the effect of an anti-microbial and an anti-fungal oral rinse prior to expectoration on culture-contamination rates. Methods We enrolled a consecutive random sample of adults with cough for ≥2 weeks and suspected TB admitted to Mulago Hospital (Kampala, Uganda) between October 2008 and June 2009. We randomly assigned patients to oral rinse (60 seconds with chlorhexidine followed by 60 seconds with nystatin) vs. no oral rinse prior to initial sputum collection. Uganda National Tuberculosis Reference Laboratory technicians blinded to the method of sputum collection (with or without oral rinse) processed all sputum specimens for smear microscopy (direct Ziehl-Neelsen) and mycobacterial culture (Lowenstein-Jensen media). Results Of 220 patients enrolled, 177 (80%) were HIV-seropositive (median CD4-count 37 cells/uL, IQR 13–171 cells/uL). Baseline characteristics were similar between patients in the oral-rinse (N = 110) and no oral-rinse (N = 110) groups. The proportion of contaminated cultures was significantly lower in the oral-rinse group compared to the no oral-rinse group (4% vs. 15%, risk difference ?11%, 95% CI ?18 to ?3%, p = 0.005). Oral rinse significantly reduced the proportion of contaminated cultures among HIV-infected patients (3% vs. 18%, risk difference ?14%, 95% CI ?23 to ?6%, p = 0.002) but not HIV-uninfected (6% vs. 4%, risk difference 2%, 95% CI ?12 to +15%, p = 0.81) patients. However, the proportion of smear-positive specimens (25% vs. 35%, p = 0.10) and culture-positive specimens (48% vs. 56%, p = 0.24) were lower in the oral-rinse compared to the no oral-rinse group, although the differences were not statistically significant. Conclusions Oral rinse prior to sputum expectoration is a promising strategy to reduce mycobacterial culture contamination in areas with high HIV prevalence, if strategies can be devised to reduce the adverse impact of oral rinse on smear- and culture-positivity.
The Role of Speciation in Positive Lowenstein-Jensen Culture Isolates from a High Tuberculosis Burden Country
William Worodria, Jillian Anderson, Adithya Cattamanchi, J. Lucian Davis, Saskia den Boon, Alfred Andama, Samuel D. Yoo, Moses Joloba, Laurence Huang, Midori Kato-Maeda
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027017
Abstract: Objective To determine the need for routine speciation of positive Lowenstein-Jensen mycobacterial cultures in HIV-infected patients suspected of having pulmonary tuberculosis at Mulago Hospital in Kampala, Uganda. Methods Sputum and bronchoalveolar lavage Lowenstein-Jensen mycobacterial culture isolates from consecutive, HIV-infected patients admitted to Mulago Hospital with 2 weeks or more of cough were subjected to IS6110 PCR and rpoB genetic analysis to determine the presence of Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM). Results Eighty (100%) mycobacterial cultures from 65 patients were confirmed to be members of MTBC. Subsequent analysis of the cultures from 54 patients by PCR and sequence analyses to identify co-infection with NTM confirmed the presence of MTBC as well as the presence of Micrococcus luteus (n = 4), Janibacter spp. (n = 1) and six cultures had organisms that could not be identified. Conclusions Presumptive diagnosis of tuberculosis on the basis of a positive Lowenstein-Jensen culture is sufficient in HIV-infected Ugandans suspected of having tuberculosis. Routine molecular confirmation of positive Lowenstein-Jensen cultures is unnecessary in this low resource setting.
Clinical and Radiographic Factors Do Not Accurately Diagnose Smear-Negative Tuberculosis in HIV-infected Inpatients in Uganda: A Cross-Sectional Study
J. Lucian Davis,William Worodria,Harriet Kisembo,John Z. Metcalfe,Adithya Cattamanchi,Michael Kawooya,Rachel Kyeyune,Saskia den Boon,Krista Powell,Richard Okello,Samuel Yoo,Laurence Huang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009859
Abstract: Although World Health Organization guidelines recommend clinical judgment and chest radiography for diagnosing tuberculosis in HIV-infected adults with unexplained cough and negative sputum smears for acid-fast bacilli, the diagnostic performance of this approach is unknown. Therefore, we sought to assess the accuracy of symptoms, physical signs, and radiographic findings for diagnosing tuberculosis in this population in a low-income country with a high incidence of tuberculosis.
Role of interferon-gamma release assays in the diagnosis of pulmonary tuberculosis in patients with advanced HIV infection
Adithya Cattamanchi, Isaac Ssewenyana, J Lucian Davis, Laurence Huang, William Worodria, Saskia den Boon, Samuel Yoo, Alfred Andama, Philip C Hopewell, Huyen Cao
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-75
Abstract: We enrolled HIV-infected patients admitted to Mulago Hospital in Kampala, Uganda with cough ≥ 2 weeks. All patients underwent standard medical evaluation. We collected peripheral blood specimens at enrollment and performed a commercial, ELISPOT-based IGRA according to the manufacturer's recommendations. IGRA sensitivity and specificity were determined using mycobacterial culture results as the reference standard.Overall, 236 patients were enrolled. The median CD4+ T-lymphocyte count was 49 cells/μl and 126 (53%) patients were diagnosed with active pulmonary tuberculosis. IGRAs were not performed in 24 (10%) patients due to insufficient mononuclear cell counts. In the remaining 212 patients, results were indeterminate in 54 (25%). IGRAs were positive in 95 of 158 (60%) patients with interpretable results. The proportion of positive test results was similar across CD4+ count strata. IGRA sensitivity was 73% and specificity 54%. IGRA results did not meaningfully alter the probability of active tuberculosis in patients with negative sputum smears.An ELISPOT-based IGRA detected a high prevalence of latent tuberculosis infection in a hospitalized population of tuberculosis suspects with advanced HIV/AIDS but had limited utility for diagnosis of active tuberculosis in a high prevalence setting. Further research is needed to identify stronger and more specific immune responses in patients with active tuberculosis.T-cell interferon-gamma release assays (IGRAs) measure interferon-gamma release by sensitized T-lymphocytes stimulated with Mycobacterium tuberculosis (M. TB)-specific antigens. Though IGRAs are highly accurate for diagnosis of latent tuberculosis infection (LTBI) [1], their use as a diagnostic tool for active tuberculosis (TB) poses several challenges. IGRAs measure the host immune response to M. TB rather than the presence or absence of the organism in clinical specimens. In addition, IGRAs cannot distinguish an immune response to current active TB from an immune
Sensitivity of direct versus concentrated sputum smear microscopy in HIV-infected patients suspected of having pulmonary tuberculosis
Adithya Cattamanchi, David W Dowdy, J Lucian Davis, William Worodria, Samuel Yoo, Moses Joloba, John Matovu, Philip C Hopewell, Laurence Huang
BMC Infectious Diseases , 2009, DOI: 10.1186/1471-2334-9-53
Abstract: We performed a prospective, blinded evaluation of direct and concentrated Ziehl-Neelsen smear microscopy on a single early-morning sputum sample in HIV-infected patients with > 2 weeks of cough hospitalized in Kampala, Uganda. Direct and concentrated smear results were compared with results of Lowenstein-Jensen culture.Of 279 participants, 170 (61%) had culture-confirmed TB. The sensitivity of direct and concentrated smear microscopy was not significantly different (51% vs. 52%, difference 1%, 95% confidence interval (CI): [-7%, 10%], p = 0.88). However, when results of both direct and concentrated smears were considered together, sensitivity was significantly increased compared with either method alone (64%, 95% CI: [56%, 72%], p < 0.01 for both comparisons) and was similar to that of direct smear results from consecutive (spot and early-morning) specimens (64% vs. 63%, difference 1%, 95% CI: [-6%, 8%], p = 0.85). Among 109 patients with negative cultures, one had a positive direct smear and 12 had positive concentrated smears (specificity 99% vs. 89%, difference 10%, 95% CI: [2%, 18%], p = 0.003). Of these 13 patients, 5 (38%) had improved on TB therapy after two months.Sputum concentration did not increase the sensitivity of light microscopy for TB diagnosis in this HIV-infected population. Given the resource requirements for sputum concentration, additional studies using maximal blinding, high-quality direct microscopy, and a rigorous gold standard should be conducted before universally recommending this technique.Direct sputum smear microscopy is the cornerstone of tuberculosis (TB) diagnosis worldwide [1]. Direct smear microscopy is rapid, inexpensive [2-4], highly specific [5-7], and capable of identifying the most infectious cases of TB [7-9], but its sensitivity is limited, particularly in those with human immunodeficiency virus (HIV) co-infection [10-13]. Processing of sputum with subsequent concentration by centrifugation or sedimentation may increase the
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