Browsing by Author "Zawedde, Josephine"

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    Accuracy of GenoQuick MTB Test in Detection of Mycobacterium tuberculosis in Sputum from TB
    (SAGE Open Medicine, 2022) Kaswabuli, Sylvia; Musisi, Emmanuel; Byanyima, Patrick; Sessolo, Abdul; Sanyu, Ingvar; Zawedde, Josephine; Worodria, William; Okeng, Alfred; Bwanga, Freddie
    The objective of the study was to determine the diagnostic performance of the GenoQuick MTB test on heated sputum against the conventional Lowenstein–Jensen Mycobacterium tuberculosis culture as the reference method for tuberculosis diagnosis. Fast, reliable, and easy-to-use tests for tuberculosis diagnosis are essential to achieving the Sustainable Development Goal of diagnosing and treating 90% of tuberculosis patients by 2030. We evaluated the diagnostic performance of the GenoQuick MTB, a polymerase chain reaction–lateral flow test, in Uganda, a resource-constrained, high tuberculosisand HIV-burden setting. Fresh sputum samples from presumptive tuberculosis patients at Mulago Hospital were tested for M. tuberculosis using smear microscopy, GenoQuick MTB test, and Lowenstein–Jensen culture. For the GenoQuick MTB test, mycobacterial DNA was extracted by heating sputum at 95°C for 30min while DNA amplification and detection were done following the manufacturer’s protocol (Hain Lifescience, Nehren, Germany). Sensitivity, specificity, and kappa agreements were calculated against Lowenstein–Jensen M. tuberculosis culture as a reference test using STATA V12. Of the 86 tested samples, 30.2% had culture-confirmed pulmonary tuberculosis. Overall, sensitivity was higher for GenoQuick MTB (81%, 95% confidence interval: 60%−93%) than for smear microscopy (69%, 95% confidence interval: 48%−86%). Among people living with HIV, sensitivity was identical for GenoQuick MTB and smear tests (75%, 95% confidence interval: 42%−95%). Contrastingly, smear had a higher overall specificity (98%, 95% confidence interval: 91%−100%) than for GenoQuick MTB (92%, 95% confidence interval: 81%−97%). A similar trend of specificity was observed among the people living with HIV for smear microscopy (100%, 95% CI: 87%−100%) and for GenoQuick MTB (96%, 95% confidence interval: 81%−100%). The GenoQuick MTB test could be a potential tuberculosis diagnostic test given its higher sensitivity. Evaluation of this test in larger studies is recommended.
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    Accuracy of the tuberculosis molecular bacterial load assay to diagnose and monitor response to anti-tuberculosis therapy: a longitudinal comparative study with standard-of-care smear microscopy, Xpert MTB/RIF Ultra, and culture in Uganda
    (Elsevier Ltd, 2024-03) Musisi, Emmanuel; Wamutu, Samuel; Ssengooba, Willy; Kasiinga, Sharifah; Sessolo, Abdulwahab; Sanyu, Ingvar; Kaswabuli, Sylvia; Zawedde, Josephine; Byanyima, Patrick; Kia, Praiscillia; Muwambi, William; Toskin, Divine Tracy; Kigozi, Edgar; Walbaum, Natasha; Dombay, Evelin; Legrady, Mate Bonifac; Ssemambo, Kizza David-Martin; Joloba, Moses; Kuchaka, Davis; Worodria, William; Huang, Laurence; Gillespie, Stephen H; Sabiiti, Wilber
    Abstract In 2018, the tuberculosis molecular bacterial load assay (TB-MBLA), a ribosomal RNA-based test, was acknowledged by WHO as a molecular assay that could replace smear microscopy and culture for monitoring tuberculosis treatment response. In this study, we evaluated the accuracy of TB-MBLA for diagnosis and monitoring of treatment response in comparison with standard-of-care tests. For this longitudinal prospective study, patients aged 18 years or older with presumptive tuberculosis (coughing for at least 2 weeks, night sweats, and weight loss) were enrolled at China-Uganda Friendship Hospital Naguru (Kampala, Uganda). Participants were evaluated for tuberculosis by TB-MBLA in comparison with Xpert MTB/RIF Ultra (Xpert-Ultra) and smear microscopy, with Mycobacteria Growth Indicator Tube (MGIT) culture as a reference test. Participants who were positive on Xpert-Ultra were enrolled on a standard 6-month anti-tuberculosis regimen, and monitored for treatment response at weeks 2, 8, 17, and 26 after initiation of treatment and then 3 months after treatment. Between Nov 15, 2019, and June 15, 2022, 210 participants (median age 35 years [IQR 27–44]) were enrolled. 135 (64%) participants were male and 72 (34%) were HIV positive. The pretreatment diagnostic sensitivities of TB-MBLA and Xpert-Ultra were similar (both 99% [95% CI 95–100]) but the specificity was higher for TB-MBLA (90% [83–96]) than for Xpert-Ultra (78% [68–86]). Ten participants were Xpert-Ultra trace positive, eight (80%) of whom were negative by TB-MBLA and MGIT culture. Smear microscopy had lower diagnostic sensitivity (75% [65–83]) but higher specificity (98% [93–100]) than TB-MBLA and Xpert-Ultra. Among participants who were smear microscopy negative, the sensitivity of TB-MBLA was 96% (95 CI 80–100) and was 100% (95% CI 86–100) in those who were HIV positive. 129 (61%) participants were identified as tuberculosis positive by Xpert-Ultra and these individuals were enrolled in the treatment group and monitored for treatment response. According to TB-MBLA, 19 of these patients cleared bacillary load to zero by week 2 of treatment and remained negative throughout the 6-month treatment follow-up. Positivity for tuberculosis decreased with treatment as measured by all tests, but the rate was slower with Xpert-Ultra. Consequently, 31 (33%) of 95 participants were still Xpert-Ultra positive at the end of treatment but were clinically well and negative on TB-MBLA and culture at 6 months of treatment. Two patients were still Xpert-Ultra positive with a further 3 months of post-treatment follow-up. The rate of conversion to negative of the DNA-based Xpert-Ultra was 3·3-times slower than that of the rRNA-based TB-MBLA. Consequently for the same patient, it would take 13 weeks and 52 weeks to reach complete tuberculosis negativity by TB-MBLA and Xpert-Ultra, respectively. Participants who were positive on smear microscopy at 8 weeks, who received an extra month of intensive treatment, had a similar TB-MBLA-measured bacillary load at 8 weeks to those who were smear microscopy negative. TB-MBLA has a similar performance to Xpert-Ultra for pretreatment diagnosis of tuberculosis, but is more accurate at detecting and characterising the response to treatment than Xpert-Ultra and standard-of-care smear microscopy. European and Developing Countries Clinical Trials Partnership, Makerere University Research and Innovation Fund, US National Institutes of Health.
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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.
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    Sex and HIV Differences in Preserved Ratio Impaired Spirometry (PRISm) Among Ugandans Postpneumonia
    (Oxford University Press, 2024-03) Abelman, Rebecca A; Fitzpatrick, Jessica; Byanova, Katerina L; Zawedde, Josephine; Sanyu, Ingvar; Byanyima, Patrick; Musisi, Emmanuel; Hsieh, Jenny; Zhang, Michelle; Branchini, Jake; Sessolo, Abdul; Hunt, Peter W; Lalitha, Rejani; Davis, J Lucian; Crothers, Kristina; Worodria, William; Huang, Laurence
    Preserved ratio impaired spirometry (PRISm), defined as a normal ratio of forced expiratory volume in 1 second (FEV ) to forced vital capacity (≥0.70) with low FEV (<80% predicted), has been associated with increased mortality in the general population. Female sex has been associated with increased odds of PRISm in people without HIV. People with HIV (PWH) are at increased risk for lung function abnormalities, but whether HIV modifies the effect of sex on PRISm development is largely unknown. Adults with and without HIV underwent baseline followed by serial spirometry after completing therapy for pneumonia, predominantly tuberculosis (TB), in Kampala, Uganda. Using generalized estimating equations adjusted for age, body mass index, smoking, biomass fuel exposure, HIV, and TB status, we compared individuals with PRISm with those with normal spirometry. These models were stratified by HIV status. Of 339 baseline participants, 153 (45%) were women; 129 (38%) had HIV, of whom 53% were women. Overall, 105/339 participants (31%) had PRISm at baseline. HIV was associated with lower odds of PRISm (adjusted odds ratio [aOR], 0.38; 95% CI, 0.21-0.68; = .001). Female sex trended toward increased odds of PRISm among all participants (aOR, 1.65; 95% CI, 0.99-2.75; = .052). The association between female sex and PRISm tended to be stronger among PWH (aOR, 3.16; 95% CI, 1.14-8.76; = .03) than among those without HIV (aOR, 1.34; 95% CI, 0.73-2.45; = .34); this study was underpowered to detect an HIV-sex interaction of this magnitude ( = .30). Among Ugandan adults who recovered from pneumonia, female sex was associated with increased odds and HIV with decreased odds of PRISm, suggesting independent sex and HIV effects on PRISm pathogenesis.