Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 165
Filter
1.
Int J Tuberc Lung Dis ; 28(6): 266-272, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822483

ABSTRACT

BACKGROUNDCurrent metrics for TB transmission include TB notifications, disease mortality, and prevalence surveys. These metrics are helpful to national TB programs to assess the burden of disease, but they do not directly measure incident infection in the community.METHODSTo estimate incidence of Mycobacterium tuberculosis infection in Kampala, Uganda, we performed a prospective cohort study between 2014 and 2017 which enrolled of 1,275 adult residents without signs of tuberculous infection (tuberculin skin test [TST] <5 mm and no signs of TB disease) and followed them for conversion of TST at 1 year.RESULTSDuring follow-up, 194 participants converted the TST and 158 converted by one year. The incidence density of TST conversion was 13.2 conversions/100 person-year (95% CI 11.6-15.1), which corresponds to an annual cumulative incidence of tuberculous infection of 12.4% (95% CI 10.7-14.3). Cumulative incidence was greater among older participants and among men. Among participants who reported prior exposure to TB cases, the cumulative risk was highest among those reporting exposure during follow-up.CONCLUSIONSThe high annual incidence of infection suggests that residents of Kampala have adequate contact for infection with undetected, infectious cases of TB as they go about their daily lives..


Subject(s)
Tuberculin Test , Tuberculosis , Humans , Incidence , Male , Uganda/epidemiology , Adult , Female , Prospective Studies , Tuberculosis/epidemiology , Young Adult , Middle Aged , Adolescent , Mycobacterium tuberculosis/isolation & purification , Prevalence , Endemic Diseases , Cohort Studies
3.
Ann Oncol ; 30(4): 551-557, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30753272

ABSTRACT

BACKGROUND: Olaparib is a poly(ADP-ribose) polymerase inhibitor and cediranib is an oral anti-angiogenic. In the primary analysis of this phase II study, combination cediranib/olaparib improved progression-free survival (PFS) compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. This updated analysis was conducted to characterize overall survival (OS) and update PFS outcomes. PATIENTS AND METHODS: Ninety patients were enrolled to this randomized, open-label, phase II study between October 2011 and June 2013 across nine United States-based academic centers. Data cut-off was 21 December 2016, with a median follow-up of 46 months. Participants had relapsed platinum-sensitive ovarian cancer of high-grade serous or endometrioid histology or had a deleterious germline BRCA1/2 mutation (gBRCAm). Participants were randomized to receive olaparib capsules 400 mg twice daily or cediranib 30 mg daily and olaparib capsules 200 mg twice daily until disease progression. RESULTS: In this updated analysis, median PFS remained significantly longer with cediranib/olaparib compared with olaparib alone (16.5 versus 8.2 months, hazard ratio 0.50; P = 0.007). Subset analyses within stratum defined by BRCA status demonstrated statistically significant improvement in PFS (23.7 versus 5.7 months, P = 0.002) and OS (37.8 versus 23.0 months, P = 0.047) in gBRCA wild-type/unknown patients, although OS was not statistically different in the overall study population (44.2 versus 33.3 months, hazard ratio 0.64; P = 0.11). PFS and OS appeared similar between the two arms in gBRCAm patients. The most common CTCAE grade 3/4 adverse events with cediranib/olaparib remained fatigue, diarrhea, and hypertension. CONCLUSIONS: Combination cediranib/olaparib significantly extends PFS compared with olaparib alone in relapsed platinum-sensitive ovarian cancer. Subset analyses suggest this margin of benefit is driven by PFS prolongation in patients without gBRCAm. OS was also significantly increased by the cediranib/olaparib combination in this subset of patients. Additional studies of this combination are ongoing and should incorporate analyses based upon BRCA status. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT0111648.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Phthalazines/administration & dosage , Piperazines/administration & dosage , Quinazolines/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Diarrhea/chemically induced , Diarrhea/epidemiology , Drug Administration Schedule , Drug Resistance, Neoplasm/genetics , Fatigue/chemically induced , Fatigue/epidemiology , Female , Follow-Up Studies , Germ-Line Mutation , Humans , Hypertension/chemically induced , Hypertension/epidemiology , Kaplan-Meier Estimate , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Phthalazines/adverse effects , Piperazines/adverse effects , Platinum Compounds/pharmacology , Platinum Compounds/therapeutic use , Progression-Free Survival , Quinazolines/adverse effects , Response Evaluation Criteria in Solid Tumors , Time Factors
4.
Int J Tuberc Lung Dis ; 23(12): 1286-1292, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31931913

ABSTRACT

BACKGROUND: It is very difficult to observe tuberculosis (TB) transmission chains and thus, identify superspreaders. We investigate cough duration as a proxy measure of transmission to assess the presence of potential TB superspreaders.DESIGN: We analyzed six studies from China, Peru, The Gambia and Uganda, and determined the distribution of cough duration and compared it with several theoretical distributions. To determine factors associated with cough duration, we used linear regression and boosted regression trees to examine the predictive power of patient, clinical and environmental characteristics.RESULTS: We found within-study heterogeneity in cough duration and strong similarities across studies. Approximately 20% of patients contributed 50% of total cough days, and around 50% of patients contributed 80% of total cough days. The cough duration distribution suggested an initially increasing, and subsequently, decreasing hazard of diagnosis. While some of the exposure variables showed statistically significant associations with cough duration, none of them had a strong effect. Multivariate analyses of different model types did not produce a model that had good predictive power.CONCLUSION: We found consistent evidence for the presence of supercoughers, but no characteristics predictive of such individuals.


Subject(s)
Cough/physiopathology , Tuberculosis, Pulmonary/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , China/epidemiology , Cohort Studies , Cough/etiology , Female , Gambia/epidemiology , Humans , Male , Middle Aged , Peru/epidemiology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/transmission , Uganda/epidemiology , Young Adult
5.
Int J Tuberc Lung Dis ; 22(9): 1000-1006, 2018 09 01.
Article in English | MEDLINE | ID: mdl-30092864

ABSTRACT

OBJECTIVE: To investigate diagnostic agreement of the QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in adult tuberculin skin test (TST) converters in a high tuberculosis (TB) burden setting. SETTING AND DESIGN: We performed a case-cohort study from 2014 to 2016 in Uganda among residents who were not infected with Mycobacterium tuberculosis. Participants were followed up for 1 year, when they were retested to determine TST conversion. All TST converters and a random sample of participants from baseline were offered QFT-GIT testing. RESULTS: Of 368 enrolled participants, 61 (17%) converted their TST by 1 year. Among 61 converters, 42 were tested using QFT-GIT, 64% of whom were QFT-GIT-positive. Of 307 participants with a persistent negative TST, 48 were tested using QFT-GIT, 83% of whom were QFT-negative. Overall concordance of TST and QFT-GIT was moderate (κ = 0.48, 95%CI 0.30-0.66). Converters with a conversion of 15 mm had a higher proportion of concordant QFT-GIT results (79%) than converters with increments of 10-14.9 mm (52%). CONCLUSION: Concordance between TST and QFT-GIT was moderate among TST converters in this urban African population. These findings call for improved tests that more accurately measure conversion to tuberculous infection.


Subject(s)
HIV Infections/microbiology , Interferon-gamma Release Tests/methods , Tuberculosis/diagnosis , Adolescent , Adult , CD4 Lymphocyte Count , Female , HIV Infections/complications , Humans , Male , Mycobacterium tuberculosis/immunology , Prospective Studies , Risk Factors , Tuberculin Test/methods , Tuberculosis/epidemiology , Uganda/epidemiology , Young Adult
6.
Ann Oncol ; 28(3): 512-518, 2017 03 01.
Article in English | MEDLINE | ID: mdl-27993796

ABSTRACT

Background: Based upon preclinical synergy in murine models, we carried out a phase I trial to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and biomarkers of response for the combination of BKM120, a PI3K inhibitor, and olaparib, a PARP inhibitor. Patients and methods: Olaparib was administered twice daily (tablet formulation) and BKM120 daily on a 28-day cycle, both orally. A 3 + 3 dose-escalation design was employed with the primary objective of defining the combination MTD, and secondary objectives were to define toxicities, activity, and pharmacokinetic profiles. Eligibility included recurrent breast (BC) or ovarian cancer (OC); dose-expansion cohorts at the MTD were enrolled for each cancer. Results: In total, 69 of 70 patients enrolled received study treatment; one patient never received study treatment because of ineligibility. Twenty-four patients had BC; 46 patients had OC. Thirty-five patients had a germline BRCA mutation (gBRCAm). Two DLTs (grade 3 transaminitis and hyperglycemia) were observed at DL0 (BKM120 60 mg/olaparib and 100 mg b.i.d.). The MTD was determined to be BKM120 50 mg q.d. and olaparib 300 mg b.i.d. (DL8). Additional DLTs included grade 3 depression and transaminitis, occurring early in cycle 2 (DL7). Anticancer activity was observed in BC and OC and in gBRCAm and gBRCA wild-type (gBRCAwt) patients. Conclusions: BKM120 and olaparib can be co-administered, but the combination requires attenuation of the BKM120 dose. Clinical benefit was observed in both gBRCAm and gBRCAwt pts. Randomized phase II studies will be needed to further define the efficacy of PI3K/PARP-inhibitor combinations as compared with a PARP inhibitor alone.


Subject(s)
Aminopyridines/administration & dosage , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/drug therapy , Morpholines/administration & dosage , Ovarian Neoplasms/drug therapy , Phthalazines/administration & dosage , Piperazines/administration & dosage , Adult , Aged , Aminopyridines/pharmacokinetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Dose-Response Relationship, Drug , Female , Germ-Line Mutation , Humans , Middle Aged , Morpholines/pharmacokinetics , Neoplasm Grading , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Phosphoinositide-3 Kinase Inhibitors , Phthalazines/pharmacokinetics , Piperazines/pharmacokinetics , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , Poly(ADP-ribose) Polymerases/genetics
8.
Int J Tuberc Lung Dis ; 18(1): 13-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24365547

ABSTRACT

OBJECTIVES: To determine the yield of undetected active tuberculosis (TB), TB and human immunodeficiency virus (HIV) coinfection and the number needed to screen (NNS) to detect a case using active case finding (ACF) in an urban community in Kampala, Uganda. METHODS: In a door-to-door survey conducted in Rubaga community from January 2008 to June 2009, residents aged ≥15 years were screened for chronic cough (≥2 weeks) and tested for TB disease using smear microscopy and/or culture. Rapid testing was used to screen for HIV infection. The NNS to detect one case was calculated based on population screened and undetected cases found. RESULTS: Of 5102 participants, 3868 (75.8%) were females; the median age was 24 years (IQR 20-30). Of 199 (4%) with chronic cough, 160 (80.4%) submitted sputum, of whom 39 (24.4%, 95%CI 17.4-31.5) had undetected active TB and 13 (8.1%, 95%CI 6.7-22.9) were TB-HIV co-infected. The NNS to detect one TB case was 131 in the whole study population, but only five among the subgroup with chronic cough. CONCLUSION: ACF obtained a high yield of previously undetected active TB and TB-HIV cases. The NNS in the general population was 131, but the number needed to test in persons with chronic cough was five. These findings suggest that boosting the identification of persons with chronic cough may increase the overall efficiency of TB case detection at a community level.


Subject(s)
Coinfection , HIV Infections/diagnosis , Tuberculosis, Pulmonary/diagnosis , Adolescent , Adult , Chronic Disease , Cough/diagnosis , Cough/epidemiology , Cough/microbiology , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Humans , Male , Middle Aged , Mycobacterium tuberculosis/isolation & purification , Predictive Value of Tests , Sputum/microbiology , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/microbiology , Uganda/epidemiology , Urban Health , Young Adult
9.
Am J Surg ; 205(4): 441-6, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23375760

ABSTRACT

BACKGROUND: Transjugular intrahepatic portosystemic stent shunt (TIPS) has become the modality of choice for complicated portal decompression. This study was undertaken to determine outcomes after TIPS and the usefulness of TIPS as a "bridge" to transplantation. METHODS: Patients undergoing TIPS from 2001 to 2010 at a teaching hospital with a transplant program were studied. The median data are presented. RESULTS: TIPS was undertaken in 256 patients. TIPS decreased portal vein-inferior vena cava (IVC) gradients from 17 to 5 mm Hg (P < .001). Reinterventions were undertaken in 54 patients (21%). Survival after TIPS was 26 months; liver transplantation was undertaken in 35 (14%) patients. CONCLUSIONS: TIPS effectively decompresses portal hypertension but leads to frequent reinterventions and short survival. After TIPS, liver transplantation is uncommonly undertaken. TIPS is a "bridge" to transplantation that is seldom "crossed," and TIPS continues to be plagued by frequent reinterventions. Outcomes after TIPS and the infrequency of transplantation after TIPS make it difficult to recommend on merit.


Subject(s)
Hypertension, Portal/surgery , Portasystemic Shunt, Transjugular Intrahepatic , Adult , Aged , Female , Follow-Up Studies , Humans , Hypertension, Portal/etiology , Hypertension, Portal/mortality , Kaplan-Meier Estimate , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Liver Cirrhosis/surgery , Liver Transplantation , Male , Middle Aged , Portasystemic Shunt, Transjugular Intrahepatic/mortality , Reoperation/statistics & numerical data , Treatment Outcome
10.
Int J Tuberc Lung Dis ; 17(3): 361-7, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23407224

ABSTRACT

OBJECTIVE: To determine the proportion of recurrent tuberculosis (TB) due to relapse with the patient's initial strain or reinfection with a new strain of Mycobacterium tuberculosis 1-2 years after anti-tuberculosis treatment in Uganda, a sub-Saharan TB-endemic country. DESIGN: Records of patients with culture-confirmed TB who completed treatment at an urban Ugandan clinic were reviewed. Restriction fragment length polymorphism (RFLP) patterns were used to determine relapse or reinfection. Associations between human immunodeficiency virus (HIV) positivity and type of TB recurrence were determined. RESULTS: Of 1701 patients cured of their initial TB episode with a median follow-up of 1.24 years, 171 (10%) had TB recurrence (8.4 per 100 person-years). Rate and risk factors for recurrence were similar to other studies from sub-Saharan Africa. Insertion sequence (IS) 6110-based RFLP of paired isolates from 98 recurrences identified 80 relapses and 18 reinfections. Relapses among HIV-positive and -negative patients were respectively 79% and 85% of recurrences. CONCLUSIONS: Relapse was more common and presented earlier than reinfection in both HIV-positive and -negative TB patients 1-2 years after completing treatment. These findings impact both the choice of retreatment drug regimen, as relapsing patients are at higher risk for acquired drug resistance, and clinical trials of new TB regimens with relapse as clinical endpoint.


Subject(s)
Antitubercular Agents/therapeutic use , Endemic Diseases , Mycobacterium tuberculosis/pathogenicity , Rifampin/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Urban Health , Adult , Amplified Fragment Length Polymorphism Analysis , Coinfection , Female , Genotype , HIV Infections/epidemiology , Humans , Incidence , Kaplan-Meier Estimate , Male , Multivariate Analysis , Mycobacterium tuberculosis/genetics , Phenotype , Polymorphism, Restriction Fragment Length , Proportional Hazards Models , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Sputum/microbiology , Time Factors , Treatment Outcome , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/microbiology , Uganda/epidemiology
11.
Gynecol Oncol ; 123(3): 499-504, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21955480

ABSTRACT

OBJECTIVE: This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). METHODS: Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan (phase I) and response rate (phase II). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. Eligibility included recurrent platinum-resistant OC or PPC, <3 prior regimens, normal end-organ function. 3+3 dose escalation was used for phase I, sorafenib being tested at 400mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m(2) to 3.5mg/m(2) IV weekly. The phase II regimen was sorafenib 400mg daily and topotecan 3.5mg/m(2) weekly on days 1, 8, 15 of a 28 days cycle. RESULTS: 16 patients were enrolled in phase I and 14 patients in phase II. Median age was 52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7%), and 14 patients (46.7%) with stable disease (SD). Four PRs were recorded during phase I and 1 during phase II. One of those PRs occurred in a patient with platinum-sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 hand-foot syndrome was recorded. CONCLUSIONS: The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Benzenesulfonates/administration & dosage , Benzenesulfonates/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Middle Aged , Niacinamide/analogs & derivatives , Peritoneal Neoplasms/drug therapy , Phenylurea Compounds , Pyridines/administration & dosage , Pyridines/adverse effects , Sorafenib , Topotecan/administration & dosage , Topotecan/adverse effects
12.
J Infect Dis ; 204(6): 884-92, 2011 Sep 15.
Article in English | MEDLINE | ID: mdl-21849285

ABSTRACT

BACKGROUND: Optimal treatment of human immunodeficiency virus (HIV)-associated tuberculosis in patients with high CD4⁺ T-cell counts is unknown. Suppression of viral replication during therapy for tuberculosis may block effects of immune activation on T cells and slow HIV disease progression. METHODS: We conducted a randomized trial in 214 HIV-infected patients with active tuberculosis and CD4⁺ T-cell counts of ≥ 350 cells/µL to determine whether 6 months of antiretroviral therapy given during tuberculosis treatment would improve clinical outcomes. Subjects were randomized to receive 6 months of abacavir-lamivudine-zidovudine concurrent with tuberculosis therapy or delayed antiretroviral therapy. Endpoints were CD4⁺ T-cell counts of < 250 cells/µL, AIDS, or death. RESULTS: Intervention and comparison arms had similar median CD4⁺ counts (517 and 534 cells/µL, respectively) and HIV RNA levels (4.6 and 4.7 log10 copies/µL, respectively). Viral suppression was achieved in 86% of patients allocated to intervention. Seventeen subjects (15.6%) in the intervention arm developed study outcome compared to 25 subjects (22.8%) in the comparison arm (P = .17). Grade 3 or 4 adverse events were less frequent in the intervention arm. By 2 months, 90% of subjects in both arms were culture-negative for tuberculosis. CONCLUSIONS: Short-term antiretroviral therapy during tuberculosis treatment in patients with CD4⁺T-cell counts of >350 cells/µL was safe and associated with clinical benefits.


Subject(s)
Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , Antitubercular Agents/administration & dosage , CD4-Positive T-Lymphocytes/immunology , HIV Infections/drug therapy , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Antitubercular Agents/adverse effects , CD4 Lymphocyte Count , Dideoxynucleosides/administration & dosage , Female , HIV Infections/complications , HIV Infections/mortality , Humans , Lamivudine/administration & dosage , Male , Middle Aged , Survival Analysis , Treatment Outcome , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/mortality , Uganda , Young Adult , Zidovudine/administration & dosage
13.
Int J STD AIDS ; 21(9): 611-6, 2010 Sep.
Article in English | MEDLINE | ID: mdl-21097732

ABSTRACT

Herpes simplex virus type 2 (HSV-2) is a risk factor for HIV-1 infection. We characterized HSV-2 serology assay performance in HIV-positive and HIV-negative Africans. Serostatus for HSV-2 and HIV-1 was determined in 493 serum specimens stored from a community HSV-2 prevalence survey in Kampala, Uganda. HSV-2 serology by Focus HerpeSelect ELISA, Biokit HSV-2 rapid assay and Kalon HSV-2 was compared with HSV-2 Western blot (WB) according to HIV-1 serostatus. Sensitivity/specificity was: 99.5%/70.2% for Focus, 97.0%/86.4% for Biokit and 97.5%/96.2% for Kalon. Focus with Biokit confirmation improved sensitivity/specificity (99.4%/96.8%, respectively). Use of a higher Focus index value cut-off of 2.2 instead of 1.1 increased specificity from 70.2% to 92.4%. Kalon had higher specificity than Focus (P < 0.001). Of commercially available HSV-2 serological assays, Kalon alone, or Focus ELISA followed by Biokit confirmation perform best. Improved HSV-2 assays are needed for HSV-2 and HIV-1 public health activities in Africa.


Subject(s)
Antibodies, Viral/blood , Herpes Simplex/diagnosis , Herpesvirus 2, Human/immunology , Virology/methods , Adult , Female , HIV Infections/diagnosis , Herpes Simplex/complications , Herpesvirus 2, Human/isolation & purification , Humans , Immunoassay/methods , Male , Reagent Kits, Diagnostic , Sensitivity and Specificity , Uganda
14.
Int J Tuberc Lung Dis ; 14(10): 1295-302, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20843421

ABSTRACT

BACKGROUND: The human immunodeficiency virus (HIV) alters the presentation of pulmonary tuberculosis (PTB), but it remains unclear whether alterations occur at a CD4 cell threshold or throughout HIV infection. OBJECTIVE: To better understand the relationship between CD4 count and clinical and radiographic presentation of PTB. SETTING AND DESIGN: Initial presentations of culture-confirmed PTB patients evaluated at a Ugandan national TB referral center and an affiliated research unit were compared by HIV status and across 11 CD4 cell count strata: 0-50 to >500 cells/µl. RESULTS: A total of 873 HIV-infected PTB cases were identified. Among HIV-infected PTB cases with CD4 < 50, 21% had a normal chest X-ray (CXR) vs. 2% with CD4 > 500, with a continuous trend across CD4 strata (test for trend, P < 0.001). All radiographic manifestations of PTB displayed significant trends across CD4 strata. HIV-infected vs. non-HIV-infected patients had no significant difference in CXR findings of miliary patterns or pleural effusion at CD4 > 100, normal CXR or fibrosis at CD4 > 150, adenopathy at CD4 > 250, and cavitation or upper lung disease at CD4 > 300. Twenty-three per cent of co-infected cases with CD4 < 50 and 1% with CD4 > 500 had negative acid-fast bacilli (AFB) smears, with a significant trend between (P < 0.001). CONCLUSION: Variations in CXR appearance and AFB smear correlate with CD4 decline in significant, continuous trends.


Subject(s)
CD4 Lymphocyte Count , HIV Infections/immunology , Tuberculosis, Pulmonary/diagnosis , Bacteriological Techniques , Chi-Square Distribution , HIV Infections/complications , HIV Infections/virology , Humans , Logistic Models , Mycobacterium tuberculosis/isolation & purification , Predictive Value of Tests , Radiography, Thoracic , Retrospective Studies , Sputum/microbiology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnostic imaging , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/microbiology , Uganda
15.
Ann Oncol ; 20(12): 1971-6, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19605506

ABSTRACT

BACKGROUND: No standard therapy exists for post-docetaxel castrate-resistant prostate cancer (CRPC) patients. This trial aimed to determine the safety and efficacy of pemetrexed in post-docetaxel CRPC patients. MATERIALS AND METHODS: CRPC patients with progression after docetaxel (Taxotere) therapy received pemetrexed (500 mg/m2) i.v. every 3 weeks. The primary end point was prostate-specific antigen (PSA) response. A pharmacogenetic analysis of the reduced folate carrier-1 gene (RFC1) G80A polymorphism was also carried out. RESULTS: Forty-nine patients were enrolled: median age 68 years, median baseline PSA 72 ng/ml, and median Karnofsky performance status of 90. Grade 3 or 4 toxicity occurred in 20 (43%) and four patients (8%), respectively. Confirmed >50% PSA decline occurred in four patients (8%), stable PSA lasting at least 12 weeks in 10 patients (20%). A significant relationship was observed between time from prior docetaxel therapy and overall survival. Pharmacogenetic analyses of RFC1 G80A genotype frequencies showed no relationship between genotypes and clinical efficacy. CONCLUSIONS: Pemetrexed treatment of CRPC patients after docetaxel therapy was associated with only modest clinical activity. Further investigation of pemetrexed as a single agent in a nonenriched CRPC population is unlikely to add significant clinical benefit over that seen with traditional second-line chemotherapy agents such as mitoxantrone.


Subject(s)
Antineoplastic Agents/therapeutic use , Glutamates/therapeutic use , Guanine/analogs & derivatives , Orchiectomy , Prostatic Neoplasms/drug therapy , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Glutamates/adverse effects , Guanine/adverse effects , Guanine/therapeutic use , Humans , Male , Membrane Transport Proteins/genetics , Middle Aged , Mutation , Neoplasm Metastasis , Pemetrexed , Pharmacogenetics , Polymorphism, Genetic , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Survival Analysis
16.
Int J Tuberc Lung Dis ; 13(4): 508-13, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19335958

ABSTRACT

SETTING: Kisenyi slum in peri-urban Kampala, Uganda. OBJECTIVES: Using chronic cough (> or = 2 weeks) inquiry as a screening tool to identify undetected smear-positive tuberculosis (TB) cases and to describe the characteristics of smear-positive TB cases detected by active case finding. DESIGN: A house-to-house survey was conducted in five randomly selected villages in Kampala between June and August 2005. A sample of households was visited; adults aged > or = 15 years were consecutively interviewed to identify those with chronic cough. Three sputum specimens were collected and examined by smear microscopy. RESULTS: Among 930 individuals, we identified 189 (20%) chronic coughers. Of these, we found 33 (18%) undiagnosed smear-positive cases. The newly detected cases had an even sex distribution (P = 0.47), a median age of 30 years, a median cough duration of 1 month and 55% had acid-fast bacilli 1+ sputum smear grade. CONCLUSION: These findings suggest that active case finding could supplement DOTS to yield additional smear-positive TB cases, lead to early diagnosis and thus shorten the duration of infectiousness before effective chemotherapy is initiated. In communities such as Kisenyi, this is a feasible strategy that may prove useful for TB control, but its cost-effectiveness needs to be evaluated. Early health care seeking for cough should be emphasized.


Subject(s)
Cough/diagnosis , Poverty Areas , Tuberculosis/diagnosis , Adolescent , Adult , Chronic Disease , Female , Humans , Male , Middle Aged , Mycobacterium tuberculosis/isolation & purification , Tuberculosis/microbiology , Uganda
17.
Int J Tuberc Lung Dis ; 11(8): 854-9, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17705950

ABSTRACT

SETTING: Zomba and Blantyre, Malawi, Africa. OBJECTIVES: To determine whether daily micronutrient supplementation reduces the mortality of human immunodeficiency virus (HIV) infected adults with pulmonary tuberculosis (TB). DESIGN: A randomised, controlled clinical trial of micronutrient supplementation for HIV-positive and HIV-negative adults with pulmonary TB. Participants were enrolled at the commencement of chemotherapy for sputum smear-positive pulmonary TB and followed up for 24 months. RESULTS: A total of 829 HIV-positive and 573 HIV-negative adults were enrolled. During follow-up, 328 HIV-positive and 17 HIV-negative participants died. The proportion of HIV-positive participants who died in the micronutrient and placebo groups was 38.7% and 40.4%, respectively (P = 0.49). Micronutrient supplementation did not reduce mortality (hazard ratio [HR] 0.93, 95%CI 0.75-1.15) among HIV-positive adults. CONCLUSIONS: Micronutrient supplementation at the doses used in this study does not reduce mortality in HIV-positive adults with pulmonary TB in Malawi.


Subject(s)
HIV Infections , Tuberculosis, Pulmonary , Adult , HIV Infections/drug therapy , HIV Seropositivity , Humans , Micronutrients , Sputum , Tuberculosis, Pulmonary/drug therapy
18.
Microb Drug Resist ; 13(1): 21-8, 2007.
Article in English | MEDLINE | ID: mdl-17536930

ABSTRACT

There are little data on the genetic relatedness between antibiotic-resistant pneumococcal isolates colonizing the Ugandan population. Penicillin-intermediate pneumococci of serogroups or serotypes rarely or not previously reported as being penicillin nonsusceptible were selected out of 166 isolates representing 26 capsular serogroups or serotypes isolated from Ugandan children in 1995 and human immunodeficiency virus (HIV) infected Ugandan adults in 2004-2005. Pairs of penicillin-intermediate pneumococci of the same serogroup or serotype present in both patient populations were characterized further by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Seven such pairs of isolates were found and included serogroups 7, 11, 15B/C, and 16 as well as serotypes 13, 21, and 35B. PFGE of these seven pairs showed no clonality between serogroups or serotypes, and clonality only within serogroup 11 and serotype 13. MLST of the 14 individual isolates revealed 13 different sequence types (STs), 11 of which had not previously been recorded. Comparisons with all known STs revealed that most of these strains were related only to strains of the same serotype in other countries, with these related strains frequently also being penicillin intermediate. These findings suggest that penicillin nonsusceptibility in Uganda is likely due to the introduction of antibiotic-resistant pneumococcal clones into Uganda rather than development of resistance within the country.


Subject(s)
Anti-Bacterial Agents/pharmacology , Carrier State , HIV Infections/microbiology , Penicillins/pharmacology , Pneumococcal Infections/microbiology , Streptococcus pneumoniae/genetics , Adult , Child, Preschool , Electrophoresis, Gel, Pulsed-Field , HIV Infections/complications , HIV Infections/epidemiology , Humans , Infant , Infant, Newborn , Penicillin Resistance , Pneumococcal Infections/complications , Pneumococcal Infections/epidemiology , Prevalence , Serotyping , Streptococcus pneumoniae/isolation & purification , Uganda/epidemiology
19.
J Med Virol ; 79(6): 758-65, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17457908

ABSTRACT

Human papillomavirus (HPV) infection is associated with almost all cases of cervical cancer, and cervical cancer is a common malignancy in women living in developing countries. A cross-sectional study was conducted to determine the prevalence of HPV infection, human immunodeficiency virus (HIV) infection, and cervical cytologic abnormalities in women presenting to a sexually transmitted infections clinic in Kampala, Uganda. In June and July, 2002, 135 women underwent complete physical exams including Papanicolaou (Pap) smears. HIV status was evaluated by serology. Cervical and vaginal swabs were obtained by clinicians and tested for HPV genotypes by PCR/reverse blot strip assay. Of the 106 women with cervical swabs adequate for HPV testing, the HPV prevalence was 46.2% (49/106). HIV prevalence was 34.9% (37/106). High risk genotypes 52, 58, and 16 were the genotypes detected most commonly. Eighteen percent (9/49) of women infected with HPV were found to have genotypes 16 and/or 18. Seventy-three percent (27/37) of HIV-positive women versus 16% (10/63) of HIV-negative women had abnormal Pap smears (P < 0.0001). Among HIV-positive women, abnormal Pap smears were associated with the presence of high risk HPV genotypes (P < 0.001). The majority of women infected with HPV attending this sexually transmitted infections clinic in Uganda were infected with high risk HPV genotypes other than 16 and 18. Future studies should focus on whether current HPV vaccine formulations, that are limited to high risk genotypes 16 and 18, would be effective at decreasing the burden of cervical cancer in this population.


Subject(s)
HIV Infections/complications , Papillomaviridae/classification , Papillomaviridae/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Uterine Cervical Dysplasia/complications , Adolescent , Adult , Cervix Uteri/virology , Cross-Sectional Studies , Female , HIV Antibodies/blood , HIV Infections/epidemiology , HIV Infections/virology , Humans , Middle Aged , Papanicolaou Test , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Polymerase Chain Reaction/methods , Prevalence , Uganda , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/virology , Vagina/virology , Vaginal Smears
20.
Int J Tuberc Lung Dis ; 11(2): 168-74, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17263287

ABSTRACT

OBJECTIVES: Voluntary counseling and testing (VCT) for the human immunodeficiency virus (HIV) is recommended for persons treated for tuberculosis (TB). Opportunities to diagnose HIV may be missed by limiting HIV testing to only persons diagnosed with TB. Among TB suspects in Uganda, we determined HIV prevalence, risk behaviors, and willingness to refer family for VCT. METHODS: Consenting adult patients presenting for evaluation at a referral TB clinic received same-day VCT. TB diagnosis data were abstracted from clinical records. RESULTS: Among 665 eligible patients, 565 (85%) consented to VCT. Among these, 238 (42%) were HIV-positive. Of the HIV-infected patients, 37% had received a non-TB diagnosis. HIV seroprevalence was higher in patients with a non-TB diagnosis (49%) than those diagnosed with TB (39%) (P = 0.02). Fewer than 6% of HIV-infected patients reported always using condoms with sexual partners. The majority of patients (86%) reported being 'very willing' to refer family members for VCT. CONCLUSIONS: Over 35% of HIV-infected cases in our population would have been undetected if HIV testing was limited to cases with diagnosed TB. The high HIV seroprevalence in both TB and non-TB cases merits HIV testing for all patients evaluated at TB clinics. HIV-infected TB suspects reporting high-risk behavior are at risk for HIV transmission, and should receive risk-reduction counseling.


Subject(s)
HIV Infections/epidemiology , HIV Seroprevalence , Tuberculosis, Pulmonary/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Comorbidity , Counseling , Female , HIV Infections/prevention & control , Humans , Male , Mass Screening/methods , Middle Aged , Risk-Taking , Uganda/epidemiology
SELECTION OF CITATIONS
SEARCH DETAIL
...