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Search Results: 1 - 10 of 183 matches for " Alphonse Okwera "
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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
Aetiology of Pulmonary Symptoms in HIV-Infected Smear Negative Recurrent PTB Suspects in Kampala, Uganda: A Cross-Sectional Study
Alphonse Okwera, Freddie Bwanga, Irene Najjingo, Yusuf Mulumba, David K. Mafigiri, Christopher C. Whalen, Moses L. Joloba
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082257
Abstract: Introduction Previously treated TB patients with pulmonary symptoms are often considered recurrent TB suspects in the resource-limited settings, where investigations are limited to microscopy and chest x-ray. Category II anti-TB drugs may be inappropriate and may expose patients to pill burden, drug toxicities and drug-drug interactions. Objective To determine the causes of pulmonary symptoms in HIV-infected smear negative recurrent pulmonary tuberculosis suspects at Mulago Hospital, Kampala. Methods Between March 2008 and December 2011, induced sputum samples of 178 consented HIV-infected smear negative recurrent TB suspects in Kampala were subjected to MGIT and LJ cultures for mycobacteria at TB Reference Laboratory, Kampala. Processed sputum samples were also tested by PCR to detect 18S rRNA gene of P.jirovecii and cultured for other bacteria. Results Bacteria, M. tuberculosis and Pneumocystis jirovecii were detected in 27%, 18% and 6.7% of patients respectively and 53.4% of the specimens had no microorganisms. S. pneumoniae, M. catarrhalis and H. influenzae were 100% susceptible to chloramphenicol and erythromycin but co-trimoxazole resistant. Conclusion At least 81.5% of participants had no microbiologically-confirmed TB. However our findings call for thorough investigation of HIV-infected smear negative recurrent TB suspects to guide cost effective treatment.
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.
Detection of multiple strains of Mycobacterium tuberculosis using MIRU-VNTR in patients with pulmonary tuberculosis in Kampala, Uganda
Katherine R Dickman, Lydia Nabyonga, David P Kateete, Fred A Katabazi, Benon B Asiimwe, Harriet K Mayanja, Alphonse Okwera, Christopher Whalen, Moses L Joloba
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-349
Abstract: A total of 113 consecutive smear and culture positive patients who previously enrolled in a house-hold contact study were included in this study. To determine whether infection with multiple MTB strains has a clinical impact on the initial presentation of patients, retrospective patient data (baseline clinical, radiological and drug susceptibility profiles) was obtained. To determine presence of infections with multiple MTB strains, MIRU-VNTR (Mycobacterial Interspersed Repetitive Unit-Variable-Number Tandem Repeats) -PCR was performed on genomic DNA extracted from MTB cultures of smear positive sputum samples at baseline, second and fifth months.Of 113 patients, eight (7.1%) had infection with multiple MTB strains, coupled with a high rate of HIV infection (37.5% versus 12.6%, p = 0.049). The remaining patients (105) were infected with single MTB strains. The proportions of patients with MTB smear positive cultures after two and five months of treatment were similar. There was no difference between the two groups for other variables.Infection with multiple MTB strains occurs among patients with first episode of pulmonary tuberculosis in Kampala, in a setting with high TB incidence. Infection with multiple MTB strains had little impact on the clinical course for individual patients. This is the first MIRU-VNTR-based study from in an East African country.Mycobacterium tuberculosis (MTB) is among the most successful human pathogens worldwide and is responsible for extensive morbidity and mortality, with approximately 2 million deaths each year thought to be due to primary infection, endogenous reactivation of primary infection, or exogenous re-infection with a new strain [1]. Molecular epidemiological studies on transmission dynamics [2,3] as well as studies on recurrent tuberculosis (TB) [4,5] have differentiated the MTB complex strains causing disease. Most studies using DNA fingerprinting to differentiate mycobacterial strains have shown single strains in cultures,
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.
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
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
Mycobacterium tuberculosis Specific CD8+ T Cells Rapidly Decline with Antituberculosis Treatment
Melissa R. Nyendak, Byung Park, Megan D. Null, Joy Baseke, Gwendolyn Swarbrick, Harriet Mayanja-Kizza, Mary Nsereko, Denise F. Johnson, Phineas Gitta, Alphonse Okwera, Stefan Goldberg, Lorna Bozeman, John L. Johnson, W. Henry Boom, Deborah A. Lewinsohn, David M. Lewinsohn, for the Tuberculosis Research Unit and the Tuberculosis Trials Consortium
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081564
Abstract: Rationale Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8+ T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy and would decrease during effective antituberculosis treatment. Objectives: We sought to determine the relationship of Mtb specific CD4+ T cells and CD8+ T cells with duration of antituberculosis treatment. Materials and Methods We performed a prospective cohort study, enrolling between June 2008 and August 2010, of HIV-uninfected Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed pulmonary TB at the onset of antituberculosis treatment and the Mtb specific CD4+ and CD8+ T cell responses to ESAT-6 and CFP-10 were measured by IFN-γ ELISPOT at enrollment, week 8 and 24. Results There was a significant difference in the Mtb specific CD8+ T response, but not the CD4+ T cell response, over 24 weeks of antituberculosis treatment (p<0.0001), with an early difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated Mtb specific CD8+ T cell response decreased by 58%. In contrast, there was no significant difference in the Mtb specific CD4+ T cell during the treatment. The Mtb specific CD4+ T cell response, but not the CD8+ response, was negatively impacted by the body mass index. Conclusions Our data provide evidence that the Mtb specific CD8+ T cell response declines with antituberculosis treatment and could be a surrogate marker of response to therapy. Additional research is needed to determine if the Mtb specific CD8+ T cell response can detect early treatment failure, relapse, or to predict disease progression.
Elucidating Emergence and Transmission of Multidrug-Resistant Tuberculosis in Treatment Experienced Patients by Whole Genome Sequencing
Taane G. Clark, Kim Mallard, Francesc Coll, Mark Preston, Samuel Assefa, David Harris, Sam Ogwang, Francis Mumbowa, Bruce Kirenga, Denise M. O’Sullivan, Alphonse Okwera, Kathleen D. Eisenach, Moses Joloba, Stephen D. Bentley, Jerrold J. Ellner, Julian Parkhill, Edward C. Jones-López, Ruth McNerney
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0083012
Abstract: Background Understanding the emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is crucial for its control. MDR-TB in previously treated patients is generally attributed to the selection of drug resistant mutants during inadequate therapy rather than transmission of a resistant strain. Traditional genotyping methods are not sufficient to distinguish strains in populations with a high burden of tuberculosis and it has previously been difficult to assess the degree of transmission in these settings. We have used whole genome analysis to investigate M. tuberculosis strains isolated from treatment experienced patients with MDR-TB in Uganda over a period of four years. Methods and Findings We used high throughput genome sequencing technology to investigate small polymorphisms and large deletions in 51 Mycobacterium tuberculosis samples from 41 treatment-experienced TB patients attending a TB referral and treatment clinic in Kampala. This was a convenience sample representing 69% of MDR-TB cases identified over the four year period. Low polymorphism was observed in longitudinal samples from individual patients (2-15 SNPs). Clusters of samples with less than 50 SNPs variation were examined. Three clusters comprising a total of 8 patients were found with almost identical genetic profiles, including mutations predictive for resistance to rifampicin and isoniazid, suggesting transmission of MDR-TB. Two patients with previous drug susceptible disease were found to have acquired MDR strains, one of which shared its genotype with an isolate from another patient in the cohort. Conclusions Whole genome sequence analysis identified MDR-TB strains that were shared by more than one patient. The transmission of multidrug-resistant disease in this cohort of retreatment patients emphasises the importance of early detection and need for infection control. Consideration should be given to rapid testing for drug resistance in patients undergoing treatment to monitor the emergence of resistance and permit early intervention to avoid onward transmission.
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.
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