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Search Results: 1 - 10 of 14064 matches for " William Worodria "
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Abdominal Sonographic Findings in Severely Immunosuppressed Human Immunodeficiency Virus-Infected Patients Treated for Tuberculosis  [PDF]
Harriet Nalubega Kisembo, Michael Grace Kawooya, Chris Kenyon, William Worodria, Robert Colebunders
Journal of Tuberculosis Research (JTR) , 2014, DOI: 10.4236/jtr.2014.22008
Abstract: Objective: We describe the abdominal sonographic findings among patients with HIV-tuberculosis (TB) co-infection with advanced immune suppression before initiation of ART and relate these findings to the patients’ abdominal symptoms and CD4 T-cell count. Methods: Consecutive HIV-TB co-infected patients, qualifying for ART, were prospectively enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Programme clinic in Kampala, Uganda. An abdominal ultrasound was performed at enrolment. Results: A total of 209 HIV-TB co-infected patients (76% with pulmonary, 19% with extrapulmonary TB and 5% with extrapulmonary and pulmonary TB) underwent an abdominal ultrasound scan. Only 49 patients (23.4%) had a normal abdominal ultrasound. The following sonographic abnormalities were found: multiple lymphadenopathy (38%), splenomegaly (18%), renal abnormalities (14%), gastro-intestinal tract abnormalities (thickened bowel loops, appendicitis) (13%), splenic abscesses (13%) and ascites (6%). The commonest groups of enlarged lymph nodes were in the porta-hepatis (19%) and peripancreatic (17%) area and 80% of the enlarged lymph nodes were hypoechoic. Conclusion: Most patients with advanced immune suppression and HIV-TB co-infection have sonographic evidence of generalized TB with abdominal involvement, therefore Ultrasound may assist in the early diagnosis of disseminated TB.
Performance of Frontloading for Smear Microscopy in the Diagnosis of Pulmonary Tuberculosis: A Cross-Sectional Study at a Referral Hospital in Uganda
Penelope Miremba, Joan N. Kalyango, William Worodria, Henry Mugerwa, Ethel Nakakawa, Benon B. Asiimwe
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048531
Abstract: Objective To compare the performance of frontloading and the standard WHO method for diagnosis of pulmonary TB at Mulago Hospital in order to validate the technique in this setting. Methods This was a cross-sectional study in which 229 adult (≥18 years) TB suspects were consecutively enrolled. Suspects submitted three sputum samples as follows: at initial presentation, one hour after the first sample, and the next morning. The first and next morning samples formed the standard WHO method, while the first and the one hour later samples formed the frontloading method. Sample processing was by the standard N-acetyl L-cystein (NALC)-NaOH method, and fluorescent microscopy was done for both methods, while cultures of the first sample on Lowenstein-Jensen slants acted as a gold standard. The sensitivity, specificity and predictive values for the WHO standard and frontloading methods were compared. Results The sensitivity of both the frontloading and standard schemes was 91.1% while their specificities were 86.2% and 91.7% respectively. There was excellent agreement between the diagnostic capacity of the two methods (kappa statistic = 0.87, P<0.0001). The positive predictive value for the frontloading scheme was 87.2% and that for the standard approach was 91.9%, while the negative predictive values were 90.4% and 90.9%, respectively. Among the HIV positive patients, frontloading identified 59/79 (74.7%) culture positive samples while the standard approach identified 55/79 (69.6%). In the HIV sero-negative category, on the other hand, front-loading identified 48/110 (43.6%) culture positive samples compared to 45/110 (40.9%) by the standard approach. Conclusion Frontloading based on smear examination of two same-day sputum samples has a similar performance to the current standard method and would not be associated with any significant missed diagnosis. It may therefore be advocated for use in our setting so as to reduce time to completion of diagnosis and patient loss to follow-up.
Antiretroviral Treatment-Associated Tuberculosis in a Prospective Cohort of HIV-Infected Patients Starting ART
William Worodria,Marguerite Massinga-Loembe,Harriet Mayanja-Kizza,Jane Namaganda,Andrew Kambugu,Yukari C. Manabe,Luc Kestens,Robert Colebunders
Clinical and Developmental Immunology , 2011, DOI: 10.1155/2011/758350
Abstract: Commencement of antiretroviral treatment (ART) in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB) disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI) consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4%) patients were diagnosed with TB during followup. Eight (3.8%) patients had ART-associated TB (incidence rate of 4.3 per 100 person years); of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years). A body mass index of less than 18.5 kg/m2 BMI (HR 5.85 95% CI 1.24–27.46, =.025) and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36–38.33, =.020) were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray), the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence.
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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