Browsing by Author "Kalema, Nelson"

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    Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
    (PLoS ONE, 2018) Farr, Katherine; Ravindran, Resmi; Strnad, Luke; Chang, Emily; Chaisson, Lelia H.; Yoon, Christina; Worodria, William; Andama, Alfred; Ayakaka, Irene; Bbosa Nalwanga, Priscilla; Byanyima, Patrick; Kalema, Nelson; Kaswabuli, Sylvia; Katagira, Winceslaus; Denise Aman, Kyomugisha; Musisi, Emmanuel; Tumwine, Nuwagaba Wallen; Sanyu, Ingvar; Ssebunya, Robert; Davis, J. Lucian; Huang, Laurence; Khan, Imran H.; Cattamanchi, Adithya
    Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy. Methods Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough � 2 weeks were enrolled. Patients underwent extensive evaluation for pulmonary TB. Concentrations of 43 cytokines/chemokines were measured at the same time point as C-reactive protein (CRP) in banked plasma samples using commercially-available multiplex kits. Advanced classification algorithms were used to rank cytokines/chemokines for their ability to identify TB, and to model the specificity of the top-ranked cytokines/chemokines individually and in combination with sensitivity constrained to � 90% as recommended for TB screening. Results The median plasma level of 5 biomarkers (IL-6, INF-γ, MIG, CRP, IL-18) was significantly different between patients with and without TB. With sensitivity constrained to 90%, all had low specificity with IL-6 showing the highest specificity (44%; 95% CI 37.4–49.5). Biomarker panels were found to be more valuable than any biomarker alone. A panel combining IFN-γ and IL-6 had the highest specificity (50%; 95% CI 46.7–53.3). Sensitivity remained high (>85%) for all panels among sputum smear-negative TB patients. Conclusions Direct measurement of unstimulated plasma cytokines/chemokines in peripheral blood is a promising approach to TB screening. Cytokine/chemokine panels retained high sensitivity for smear-negative TB and achieved improved specificity compared to individual cytokines/ chemokines. These markers should be further evaluated in outpatient settings where most TB screening occurs and where other illnesses associated with systematic inflammation are less common.
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    Predictors and short-term outcomes of recurrent pulmonary tuberculosis, Uganda: a cohort study
    (South African respiratory journal, 2017) Kalema, Nelson; Lindan, Christina; Glidden, Dave; Yoo, Samuel D.; atamba, Achilles K; Alfred, Andama; Katagira, Winceslaus; Byanyima, Patrick; Musisi, Emmanuel; Kaswabuli, Sylvia; Ingvar, Sanyu; Zawedde, Josephine; Yoon, Christina; Ayakaka, Irene; Lucian Davis, J.; Huang, Laurence; Worodria, William; Cattamanchi, Adithya
    Recurrent tuberculosis (TB) occurring >2 years after completing treatment for a prior TB episode is most often due to reinfection with a new strain of M. tuberculosis. Objectives—We determined the prevalence and outcome of late recurrent TB among hospitalized patients in Kampala, Uganda. Methods—We conducted a retrospective analysis of patients admitted to Mulago Hospital who had cough of >2 weeks’ duration and completed TB treatment >2 years prior to admission. All patients had mycobacterial culture performed on two sputum specimens and vital status ascertained 2-months post-enrollment. We performed logistic regression and Cox proportional hazards modelling to identify predictors of recurrent TB and survival, respectively. Results—Among 234 patients, 84 (36%) had recurrent TB. Independent predictors included younger age (aOR=0.64, 95% CI=0.42-0.97, p=0.04), chest pain >2 weeks (aOR=3.32, 95% CI=1.38-8.02, p=0.007), severe weight loss ≥5 kilograms (aOR=4.88, 95% CI=1.66-14.29, p=0.004) and presence of ≥1 WHO danger sign of severe illness (aOR=3.55, 95% CI=1.36-9.29, p=0.01). Two-month mortality was 17.8% (95% CI=10.5-29.2%), and was higher among patients who were not initiated on TB treatment (aHR=16.67, 95% CI=1.18-200, p=0.04), those who were HIV-positive and not on antiretroviral treatment (aHR=16.99, 95% CI=1.17-246.47, p=0.04) and those with a history of smoking (aHR=1.20, 95% CI=1.03-1.40, p=0.02). Conclusion—The high prevalence of late recurrent TB likely reflects high levels of TB transmission in Kampala. Increased use of empiric TB treatment and early ART treatment initiation if HIV-positive should be considered in patients with a prior history of TB, particularly if they are young, with weight loss ≥5kgs, chest pain >2 weeks or ≥1 WHO danger sign of severe illness.