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Search Results: 1 - 10 of 195842 matches for " Roy D. Mugerwa "
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Gender and HIV-associated pulmonary tuberculosis: presentation and outcome at one year after beginning antituberculosis treatment in Uganda
Peter Nsubuga, John L Johnson, Alphonse Okwera, Roy D Mugerwa, Jerrold J Ellner, Christopher C Whalen
BMC Pulmonary Medicine , 2002, DOI: 10.1186/1471-2466-2-4
Abstract: We enrolled and followed up a cohort of 105 male and 109 female HIV-infected adults on treatment for initial episodes of culture-confirmed pulmonary tuberculosis between March 1993 and March 1995. A favorable outcome was defined as being cured and alive at one year while an unfavorable outcome was not being cured or dead. Subjects were followed-up by serial medical examinations, complete blood counts, serum β2 microglobulin, CD4+ cell counts, sputum examinations, and chest x-rays.Male patients were older, had higher body mass indices, and lower serum β2 microglobulin levels than female patients at presentation. At one year, there was no difference between male and female patients in the likelihood of experiencing a favorable outcome (RR 1.02, 95% CI 0.89–1.17). This effect persisted after controlling for symptoms, serum β2 microglobulin, CD4+ cell count, and severity of disease on chest x-ray (OR 1.07, 95% CI 0.54–2.13) with a repeated measures model.While differences existed between males and females with HIV-associated pulmonary tuberculosis at presentation, the outcomes at one year after the initiation of tuberculosis treatment were similar in Uganda. Women in areas with a high HIV and tuberculosis prevalence should be encouraged to present for screening at the first sign of tuberculosis symptoms.Tuberculosis is estimated to cause at least three million deaths per year worldwide [1] and also accounts for more than one-quarter of all preventable adult deaths in developing countries [2]. Infection with the human immuno-deficiency virus (HIV) is thought to be the single most important factor that has contributed to the increased incidence of tuberculosis globally in the last decade [2]. Tuberculosis is now the leading cause of death among HIV-infected individuals worldwide and accounts for at least 40% of deaths among HIV-infected persons in Africa [3]. Furthermore, tuberculosis kills more women than any other infectious disease, including malaria and AIDS [4].Repor
Whole Blood Interferon-Gamma Responses to Mycobacterium tuberculosis Antigens in Young Household Contacts of Persons with Tuberculosis in Uganda
Deborah A. Lewinsohn, Sarah Zalwango, Catherine M. Stein, Harriet Mayanja-Kizza, Alphonse Okwera, W. Henry Boom, Roy D. Mugerwa, Christopher C. Whalen
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003407
Abstract: Background Due to immunologic immaturity, IFN-γ-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-γ responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb) would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-γ production in response to mycobacterial antigens between children and adults in Uganda. Methodology/Principal Findings We studied household contacts of persons with culture-positive pulmonary tuberculosis (TB) enrolled in a cohort study conducted in Kampala, Uganda. Whole blood IFN-γ production in response to Mtb culture-filtrate antigens was measured by ELISA and compared between infants (<2 years old, n = 80), young children (2 <5 years old, n = 216), older children (5 <15 years old, n = 443) and adults (≥15 years old, n = 528). We evaluated the relationship between IFN-γ responses and the tuberculin skin test (TST), and between IFN-γ responses and epidemiologic factors that reflect exposure to Mtb, and the effect of prior BCG vaccination on IFN-γ responses. Young household contacts demonstrated robust IFN-γ responses comparable to those of adults that were associated with TST and known risk factors for infection. There was no effect of prior BCG immunization on the IFN-γ response. Conclusions/Significance Young children in a TB endemic setting can mount robust IFN-γ responses generally comparable to those of adults, and as in adults, these responses correlated with the TST and known epidemiologic risk factors for Mtb infection.
Burden of tuberculosis in Kampala, Uganda
Guwatudde,David; Zalwango,Sarah; Kamya,Moses R.; Debanne,Sara M.; Diaz,Mireya I.; Okwera,Alphonse; Mugerwa,Roy D.; King,Charles; Whalen,Christopher C.;
Bulletin of the World Health Organization , 2003, DOI: 10.1590/S0042-96862003001100006
Abstract: objective: to determine the prevalence and incidence of tuberculosis in one of uganda's poor peri-urban areas. methods: multi-stage sampling was used to select a sample of households whose members were evaluated for presence of signs and/or symptoms of active tuberculosis; history of tuberculosis treatment; and relevant demographic, socioeconomic, and household environment characteristics. patients with suspected tuberculosis underwent standardized evaluation for active disease. findings: a sample of 263 households with 1142 individuals was evaluated. nineteen people were classified as having had tuberculosis during the one-year reference period (may 2001-april 2002): nine (47%) cases already had been diagnosed through the health care system, while 10 cases (53%) were diagnosed through the survey. the prevalences for all forms of tuberculosis and for sputum smear-positive tuberculosis were 14.0 (95% confidence interval (ci) 7.8-20.3) and 4.4 (ci = 0.83-7.89) per thousand, respectively. the incidences for all forms of tuberculosis and for sputum smear-positive tuberculosis were 9.2 (ci = 3.97-14.4) and 3.7 (ci = 0.39-6.95) per thousand per year, respectively. conclusion: the rate of tuberculosis in this peri-urban community was exceptionally high and may be underestimated by current surveillance systems. the need for interventions aimed at reducing tuberculosis transmission in this, and other similar communities with high case rates, is urgent.
Low-cost rapid detection of rifampicin resistant tuberculosis using bacteriophage in Kampala, Uganda
Hamidou Traore, Sam Ogwang, Kim Mallard, Moses L Joloba, Francis Mumbowa, Kalpana Narayan, Susan Kayes, Edward C Jones-Lopez, Peter G Smith, Jerrold J Ellner, Roy D Mugerwa, Kathleen D Eisenach, Ruth McNerney
Annals of Clinical Microbiology and Antimicrobials , 2007, DOI: 10.1186/1476-0711-6-1
Abstract: In a blinded study 149 M. tuberculosis isolates were tested for resistance to rifampicin by the phage assay and results compared to those from routine phenotypic testing in BACTEC 460. Three concentrations of drug were used 2, 4 and 10 μg/ml. Isolates found resistant by either assay were subjected to sequence analysis of a 81 bp fragment of the rpoB gene to identify mutations predictive of resistance. Four isolates with discrepant phage and BACTEC results were tested in a second phenotypic assay to determine minimal inhibitory concentrations.Initial analysis suggested a sensitivity and specificity of 100% and 96.5% respectively for the phage assay used at 4 and 10 μg/ml when compared to the BACTEC 460. However, further analysis revealed 4 false negative results from the BACTEC 460 and the phage assay proved the more sensitive and specific of the two tests. Of the 39 isolates found resistant by the phage assay 38 (97.4%) were found to have mutations predictive of resistance in the 81 bp region of the rpoB gene. When used at 2 μg/ml false resistant results were observed from the phage assay. The cost of reagents for testing each isolate was estimated to be 1.3US$ when testing a batch of 20 isolates on a single 96 well plate. Results were obtained in 48 hours.The phage assay can be used for screening of isolates for resistance to rifampicin, with high sensitivity and specificity in Uganda. The test may be useful in poorly resourced laboratories as a rapid screen to differentiate between rifampicin susceptible and potential MDR-TB cases.The emergence of drug resistant strains of Mycobacterium tuberculosis is of growing concern. Multi-drug resistant disease (MDR-TB), where the strain is resistant to both the major anti-tuberculosis drugs rifampicin and isoniazid, has been reported in all regions of the world. Incidences of MDR exceeding 10% of TB caseloads have been reported in parts of Central Asia, China, Eastern Europe, Russia and Africa [1]. The prognosis of patients
Comparison of rapid tests for detection of rifampicin-resistant Mycobacterium tuberculosis in Kampala, Uganda
Sam Ogwang, Benon B Asiimwe, Hamidou Traore, Francis Mumbowa, Alphonse Okwera, Kathleen D Eisenach, Susan Kayes, Edward C Jones-López, Ruth McNerney, William Worodria, Irene Ayakaka, Roy D Mugerwa, Peter G Smith, Jerrold Ellner, Moses L Joloba
BMC Infectious Diseases , 2009, DOI: 10.1186/1471-2334-9-139
Abstract: Sputum specimens from re-treatment TB patients presenting to the Mulago Hospital National TB Treatment Centre in Kampala, Uganda, were examined by conventional methods and simultaneously used in one of the four direct susceptibility tests, namely direct BACTEC 460, Etest, "in-house" phage test, and INNO- Rif.TB. The reference method was the BACTEC 460 indirect culture drug susceptibility testing. Test performance, cost and turn around times were assessed.In comparison with indirect BACTEC 460, the respective sensitivities and specificities for detecting rifampicin resistance were 100% and 100% for direct BACTEC and the Etest, 94% and 95% for the phage test, and 87% and 87% for the Inno-LiPA assay. Turn around times ranged from an average of 3 days for the INNO-LiPA and phage tests, 8 days for the direct BACTEC 460 and 20 days for the Etest. All methods were faster than the indirect BACTEC 460 which had a mean turn around time of 24 days. The cost per test, including labour ranged from $18.60 to $41.92 (USD).All four rapid technologies were shown capable of detecting rifampicin resistance directly from sputum. The LiPA proved rapid, but was the most expensive. It was noted, however, that the LiPA test allows sterilization of samples prior to testing thereby reducing the risk of accidental laboratory transmission. In contrast the Etest was low cost, but slow and would be of limited assistance when treating patients. The phage test was the least reproducible test studied with failure rate of 27%. The test preferred by the laboratory personnel, direct BACTEC 460, requires further study to determine its accuracy in real-time treatment decisions in Uganda.Developing countries account for 95% of active tuberculosis (TB) cases and deaths due to TB worldwide [1,2]. In developing countries, many national TB control programs have low case detection rates and once a case is detected, cure may also be difficult because of poor case holding, high default rates and insufficient co
Tuberculosis Treatment in HIV Infected Ugandans with CD4 Counts >350 Cells/mm3 Reduces Immune Activation with No Effect on HIV Load or CD4 Count
C. Scott Mahan,Maria Walusimbi,Denise F. Johnson,Christina Lancioni,Edwin Charlebois,Joyce Baseke,Keith A. Chervenak,Roy D. Mugerwa,Diane V. Havlir,Harriet Mayanja-Kizza,Christopher C. Whalen,W. Henry Boom
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009138
Abstract: Both HIV and TB cause a state of heightened immune activation. Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no decline in markers of cellular activation in response to TB therapy alone.
Genome Scan of M. tuberculosis Infection and Disease in Ugandans
Catherine M. Stein, Sarah Zalwango, LaShaunda L. Malone, Sungho Won, Harriet Mayanja-Kizza, Roy D. Mugerwa, Dmitry V. Leontiev, Cheryl L. Thompson, Kevin C. Cartier, Robert C. Elston, Sudha K. Iyengar, W. Henry Boom, Christopher C. Whalen
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0004094
Abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is an enduring public health problem globally, particularly in sub-Saharan Africa. Several studies have suggested a role for host genetic susceptibility in increased risk for TB but results across studies have been equivocal. As part of a household contact study of Mtb infection and disease in Kampala, Uganda, we have taken a unique approach to the study of genetic susceptibility to TB, by studying three phenotypes. First, we analyzed culture confirmed TB disease compared to latent Mtb infection (LTBI) or lack of Mtb infection. Second, we analyzed resistance to Mtb infection in the face of continuous exposure, defined by a persistently negative tuberculin skin test (PTST-); this outcome was contrasted to LTBI. Third, we analyzed an intermediate phenotype, tumor necrosis factor-alpha (TNFα) expression in response to soluble Mtb ligands enriched with molecules secreted from Mtb (culture filtrate). We conducted a full microsatellite genome scan, using genotypes generated by the Center for Medical Genetics at Marshfield. Multipoint model-free linkage analysis was conducted using an extension of the Haseman-Elston regression model that includes half sibling pairs, and HIV status was included as a covariate in the model. The analysis included 803 individuals from 193 pedigrees, comprising 258 full sibling pairs and 175 half sibling pairs. Suggestive linkage (p<10?3) was observed on chromosomes 2q21-2q24 and 5p13-5q22 for PTST-, and on chromosome 7p22-7p21 for TB; these findings for PTST- are novel and the chromosome 7 region contains the IL6 gene. In addition, we replicated recent linkage findings on chromosome 20q13 for TB (p = 0.002). We also observed linkage at the nominal α = 0.05 threshold to a number of promising candidate genes, SLC11A1 (PTST- p = 0.02), IL-1 complex (TB p = 0.01), IL12BR2 (TNFα p = 0.006), IL12A (TB p = 0.02) and IFNGR2 (TNFα p = 0.002). These results confirm not only that genetic factors influence the interaction between humans and Mtb but more importantly that they differ according to the outcome of that interaction: exposure but no infection, infection without progression to disease, or progression of infection to disease. Many of the genetic factors for each of these stages are part of the innate immune system.
Effectiveness of the Standard WHO Recommended Retreatment Regimen (Category II) for Tuberculosis in Kampala, Uganda: A Prospective Cohort Study
Edward C. Jones-López equal contributor ,Irene Ayakaka equal contributor,Jonathan Levin,Nancy Reilly,Francis Mumbowa,Scott Dryden-Peterson,Grace Nyakoojo,Kevin Fennelly,Beth Temple,Susan Nakubulwa,Moses L. Joloba,Alphonse Okwera,Kathleen D. Eisenach,Ruth McNerney,Alison M. Elliott,Jerrold J. Ellner,Peter G. Smith,Roy D. Mugerwa
PLOS Medicine , 2011, DOI: 10.1371/journal.pmed.1000427
Abstract: Background Each year, 10%–20% of patients with tuberculosis (TB) in low- and middle-income countries present with previously treated TB and are empirically started on a World Health Organization (WHO)-recommended standardized retreatment regimen. The effectiveness of this retreatment regimen has not been systematically evaluated. Methods and Findings From July 2003 to January 2007, we enrolled smear-positive, pulmonary TB patients into a prospective cohort to study treatment outcomes and mortality during and after treatment with the standardized retreatment regimen. Median time of follow-up was 21 months (interquartile range 12–33 months). A total of 29/148 (20%) HIV-uninfected and 37/140 (26%) HIV-infected patients had an unsuccessful treatment outcome. In a multiple logistic regression analysis to adjust for confounding, factors associated with an unsuccessful treatment outcome were poor adherence (adjusted odds ratio [aOR] associated with missing half or more of scheduled doses 2.39; 95% confidence interval (CI) 1.10–5.22), HIV infection (2.16; 1.01–4.61), age (aOR for 10-year increase 1.59; 1.13–2.25), and duration of TB symptoms (aOR for 1-month increase 1.12; 1.04–1.20). All patients with multidrug-resistant TB had an unsuccessful treatment outcome. HIV-infected individuals were more likely to die than HIV-uninfected individuals (p<0.0001). Multidrug-resistant TB at enrolment was the only common risk factor for death during follow-up for both HIV-infected (adjusted hazard ratio [aHR] 17.9; 6.0–53.4) and HIV-uninfected (14.7; 4.1–52.2) individuals. Other risk factors for death during follow-up among HIV-infected patients were CD4<50 cells/ml and no antiretroviral treatment (aHR 7.4, compared to patients with CD4≥200; 3.0–18.8) and Karnofsky score <70 (2.1; 1.1–4.1); and among HIV-uninfected patients were poor adherence (missing half or more of doses) (3.5; 1.1–10.6) and duration of TB symptoms (aHR for a 1-month increase 1.9; 1.0–3.5). Conclusions The recommended regimen for retreatment TB in Uganda yields an unacceptable proportion of unsuccessful outcomes. There is a need to evaluate new treatment strategies in these patients. Please see later in the article for the Editors' Summary
Treatment Outcomes of New Tuberculosis Patients Hospitalized in Kampala, Uganda: A Prospective Cohort Study
Bruce J. Kirenga, Jonathan Levin, Irene Ayakaka, William Worodria, Nancy Reilly, Francis Mumbowa, Helen Nabanjja, Grace Nyakoojo, Kevin Fennelly, Susan Nakubulwa, Moses Joloba, Alphonse Okwera, Kathleen D. Eisenach, Ruth McNerney, Alison M. Elliott, Roy D. Mugerwa, Peter G. Smith, Jerrold J. Ellner, Edward C. Jones-López
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090614
Abstract: Background In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda Methods and findings Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 – 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/μL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 – 4.01, P = 0.045). Conclusion Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART.
Effect of biotic and abiotic factors on composition and foraging intensity of subterranean termites
S Mugerwa, M Nyangito, D Mpairwe, J Nderitu
African Journal of Environmental Science and Technology , 2011,
Abstract: Elucidating the influence of ecological factors on composition and foraging intensity of subterranean termites is critical in development of sustainable termite management strategies. Our aim was therefore to analyze the effect of selected biotic and abiotic factors on composition and foraging intensity of termites. We used principal component and canonical correspondence analysis to select appropriate factors and to model relationships respectively. Macrotermes species occurred in sites where the quantity of litter was generally above the mean. However, Macrotermes herus (Rambur) and Macrotermes spp.4 occurred in sites where the litter quantity was below the mean. Trinervitermes oeconomous (Tragardh) and Odontoremes spp.1 were noted to occur in the direction of increasing quantity of biomass. Generally, most species occurred in sites where soil pH was above or slightly below the mean (4.8). Majority of the species were also noted to occur in sites where bulk density was below or slightly above the mean (1.55 g/cm3). Highest bait consumption (95%) occurred within a range of 55 to 60% basal cover beyond which the amount of bait consumed reduced. Litter and biomass quantity, pH and bulk density were noted as the most influential environmental variables determining composition of termites while basal cover was the major determinant of foraging intensity.
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