NRU :: Browsing by Author "Smith, Peter G."

Browsing by Author "Smith, Peter G."

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A Cluster-Randomised Trial to Compare Home-Based with Health Facility- Based Antiretroviral Treatment in Uganda: Study Design and Baseline Findings
(Bentham Science Publishers Ltd., 2007) Amuron, Barbara; Coutinho, Alex; Grosskurth, Heiner; Nabiryo, Christine; Birungi, Josephine; Namara, Geoffrey; Levin, Jonathan; Smith, Peter G.; Jaffar, Shabbar
The scale-up of antiretroviral therapy is progressing rapidly in Africa but with a limited evidence-base. We re- port the baseline results from a large pragmatic cluster-randomised trial comparing different strategies of ART delivery. The trial is integrated in normal health service delivery. 1453 subjects were recruited into the study. Significantly more women (71%) than men (29%) were recruited. The WHO HIV clinical stage at presentation did not differ significantly between men and women: 58% and 53% respectively were at WHO stage III or IV (p=0.9). Median CD4 counts (IQR) x 10 6 cells/l were 98 (28, 160) among men and 111 (36, 166) among women. Sixty-four percent of women and 61% men had plasma viral load 100,000 copies. Baseline characteris- tics did not change over time. Considerably fewer men than women presented for treatment.
Effectiveness of the standard WHO recommended retreatment regimen (Category II) for tuberculosis in Kampala, Uganda
(PLoS medicine, 2011) Jones-López, Edward C.; Ayakaka, Irene; Levin, Jonathan; Reilly, Nancy; Mumbowa, Francis; Dryden-Peterson, Scott; Nyakoojo, Grace; Fennelly, Kevin; Temple, Beth; Nakubulwa, Susan; Joloba, Moses L.; Okwera, Alphonse; Eisenach, Kathleen D.; McNerney, Ruth; Elliott, Alison M.; Ellner, Jerrold J.; Smith, Peter G.; Mugerwa, Roy D.
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 HIVinfected 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.
Rate and Amplification of Drug Resistance among Previously-Treated Patients with Tuberculosis in Kampala, Uganda
(Clinical infectious diseases, 2008) Temple, Beth; Ayakaka, Irene; Ogwang, Sam; Nabanjja, Helen; Kayes, Susan; Nakubulwa, Susan; Worodria, William; Levin, Jonathan; Joloba, Moses; Okwera, Alphonse; Eisenach, Kathleen D.; McNerney, Ruth; Elliott, Alison M.; Smith, Peter G.; Mugerwa, Roy D.; Ellner, Jerrold J.; Jones-Lopez, Edward C.
Drug-resistant Mycobacterium tuberculosis has emerged as a global threat. In resource-constrained settings, patients with a history of tuberculosis (TB) treatment may have drug-resistant disease and may experience poor outcomes. There is a need to measure the extent of and risk factors for drug resistance in such patients. Methods. From July 2003 through November 2006, we enrolled 410 previously treated patients with TB in Kampala, Uganda. We measured the prevalence of resistance to first- and second-line drugs and analyzed risk factors associated with baseline and acquired drug resistance. Results. The prevalence of multidrug-resistant TB was 12.7% (95% confidence interval [95% CI], 9.6%–16.3%). Resistance to second-line drugs was low. Factors associated with multidrug-resistant TB at enrollment included a history of treatment failure (odds ratio, 23.6; 95% CI, 7.7–72.4), multiple previous TB episodes (odds ratio, 15.6; 95% CI, 5.0–49.1), and cavities present on chest radiograph (odds ratio, 5.9; 95% CI, 1.2–29.5). Among a cohort of 250 patients, 5.2% (95% CI, 2.8%–8.7%) were infected with M. tuberculosis that developed additional drug resistance. Amplification of drug resistance was associated with existing drug resistance at baseline (P ! .01) and delayed sputum culture conversion (P ! .01). Conclusions. The burden of drug resistance in previously treated patients with TB in Uganda is sizeable, and the risk of generating additional drug resistance is significant. There is an urgent need to improve the treatment for such patients in low-income countries.
Scale-up of antiretroviral therapy in sub-Saharan Africa – priorities for public health research
(Tropical Medicine and International Health, 2007) Jaffar, Shabbar; Mbidde, Edward; Robb, Alistair; Coutinho, Alex; Muwanga, Moses; Obermeyer, Carla Makhlouf; Weller, Ian; Hart, Graham; Smith, Peter G.; Haines, Andy; Grosskurth, Heiner
The scale-up of antiretroviral therapy (ART) in Africa is the largest health delivery programme ever contemplated on the continent. About 1.3 million people are now on ART and a further 3.5 million are estimated to be in current need of ART. Research is required urgently to identify strategies of scaling-up ART delivery to ensure that it has high coverage, is effective and is available equitably. Furthermore, the number of new infections occurring daily far outstrips the number of patients being placed on ART (World Health Organization, 2007), and to halt the expanding number eligible for treatment, a pressing priority for research is to determine ways of effectively involved in the different components of ART delivery and how should they be trained and supported? What are the costs of ART both to the health services and to the patients? integrating human immunodeficiency virus (HIV) prevention with ART delivery strategies. At present, most government-led ART programmes are based in district or tertiary-level hospitals. This limits the number who can be treated; as hospital services are overburdened, there is a severe shortage of clinical staff, especially physicians, and most hospitals are in urban settings and difficult to access by the majority of people who live in rural areas (Jaffar et al. 2005; Gilks et al. 2006). Home-based care may not be acceptable in many settings because of stigma issues, but it is being evaluated in at least one cluster randomized trial (Jaffar et al., unpublished data). Peripheral health facilities, run by nursing staff or clinical assistants, provide basic primary care in rural communities across Africa. Research is required to determine if ART could be initiated and maintained from such centres. Could the centres monitor patients for side effects from therapy? Could they make referrals to hospitals as and when appropriate? What kind of adherence support and behaviour counselling should the centres provide? How often should patients be followed up and by whom? What should be the minimum cadre of staff
Treatment Outcomes of New Tuberculosis Patients Hospitalized in Kampala, Uganda: A Prospective Cohort Study
(PLoS ONE, 2014) Kirenga, Bruce J.; Levin, Jonathan; Ayakaka, Irene; Worodria, William; Reilly, Nancy; Mumbowa, Francis; Nabanjja, Helen; Nyakoojo, Grace; Fennelly, Kevin; Nakubulwa, Susan; Joloba, Moses; Okwera, Alphonse; Eisenach, Kathleen D.; McNerney, Ruth; Elliott, Alison M.; Mugerwa, Roy D.; Smith, Peter G.; Ellner, Jerrold J.; Jones-Lopez, Edward C.
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/mL 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.
Variability of Infectious Aerosols Produced during Coughing by Patients with Pulmonary Tuberculosis
(American journal of respiratory and critical care medicine, 2012) Fennelly, Kevin P.; Jones-Lopez, Edward C.; Ayakaka, Irene; Kim, Soyeon; Menyha, Harriet; Kirenga, Bruce; Muchwa, Christopher; Joloba, Moses; Dryden-Peterson, Scott; Reilly, Nancy; Okwera, Alphonse; Elliott, Alison M.; Smith, Peter G.; Mugerwa, Roy D.; Eisenach, Kathleen D.; Ellne, Jerrold J.
Mycobacterium tuberculosis is transmitted by infectious aerosols, but assessing infectiousness currently relies on sputum microscopy that does not accurately predict the variability in transmission. Objectives: To evaluate the feasibility of collecting cough aerosols and the risk factors for infectious aerosol production from patients with pulmonary tuberculosis (TB) in a resource-limited setting. Methods: We enrolled subjects with suspected TB in Kampala, Uganda and collected clinical, radiographic, and microbiological data in addition to cough aerosol cultures. A subset of 38 subjects was studied on 2 or 3 consecutive days to assess reproducibility. Measurements and Main Results: M. tuberculosis was cultured from cough aerosols of 28 of 101 (27.7%; 95% confidence interval [CI], 19.9–37.1%) subjects with culture-confirmed TB, with a median 16 aerosol cfu (range, 1–701) in 10 minutes of coughing. Nearly all (96.4%) cultivable particles were 0.65 to 4.7 mm in size. Positive aerosol cultures were associated with higher Karnofsky performance scores (P ¼ 0.016), higher sputum acid-fast bacilli smear microscopy grades (P ¼ 0.007), lower days to positive in liquid culture (P ¼ 0.004), stronger cough (P ¼ 0.016), and fewer days on TB treatment (P ¼ 0.047). In multivariable analyses, cough aerosol cultures were associated with a salivary/mucosalivary (compared with purulent/ mucopurulent) appearance of sputum (odds ratio, 4.42; 95% CI, 1.23–21.43) and low days to positive (per 1-d decrease; odds ratio, 1.17;95%CI, 1.07–1.33). The within-test (kappa, 0.81; 95%CI, 0.68– 0.94) and interday test (kappa, 0.62; 95% CI, 0.43–0.82) reproducibility were high. Conclusions: A minority of patients with TB (28%) produced culturable cough aerosols. Collection of cough aerosol cultures is feasible and reproducible in a resource-limited setting.

Browsing by Author "Smith, Peter G."

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