Browsing by Author "Andama, Alfred"
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Item C-Reactive Protein Testing for Active Tuberculosis among Inpatients without HIV in Uganda: a Diagnostic Accuracy Study(Journal of Clinical Microbiology, 2020) Meyer, Amanda J.; Ochom, Emmanuel; Turimumahoro, Patricia; Byanyima, Patrick; Sanyu, Ingvar; Lalitha, Rejani; Kaswabuli, Sylvia; Andama, Alfred; Walter, Nicholas D.; Katamba, Achilles; Cattamanchi, Adithya; Worodria, William; Huang, Laurence; Yoon, Christina; Davis, LucianThe objective of this prospective cross-sectional study, conducted at a national referral hospital in Kampala, Uganda, was to determine diagnostic performance of serum C-reactive protein (CRP) as a triage test for tuberculosis (TB) among HIV-seronegative inpatients. We calculated the sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values to determine the diagnostic performance of a CRP enzyme-linked immunosorbent assay (ELISA) (Eurolyser) in comparison to that of a reference standard of Mycobacterium tuberculosis culture on two sputum samples. We constructed receiver operating curves and reported performance in reference to the manufacturer’s cutoff and also to a threshold chosen to achieve sensitivity of 90%, in accordance with the WHO’s targetproduct profile for a triage test. Among 119 HIV-seronegative inpatients, 46 (39%) had culture-positive pulmonary TB. In reference to M. tuberculosis culture, CRP had a sensitivity of 78% (95% confidence interval [CI], 64 to 89%) and a specificity of 52% (95% CI, 40 to 64%) at the manufacturer’s threshold of 10 mg/liter. At a threshold of 1.5 mg/liter, the sensitivity was 91% (95% CI, 79 to 98%) but the specificity was only 21% (95% CI, 12 to 32%). Performance did not differ when stratified by illness severity at either threshold. In conclusion, among HIV-seronegative inpatients, CRP testing performed substantially below targets for a TB triage test. Additional studies among HIV-seronegative individuals in clinics and community settings are needed to assess the utility of CRP for TB screening.Item 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, AdithyaApproaches 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.Item New Manual Quantitative Polymerase Chain Reaction Assay Validated on Tongue Swabs Collected and Processed in Uganda Shows Sensitivity That Rivals Sputum-based Molecular Tuberculosis Diagnostics(Clinical Infectious Diseases, 2024-02-02) Steadman, Amy; Andama, Alfred; Ball, Alexey; Mukwatamundu, Job; Khimani, Khushboo;; Mochizuki, Tessa; Asege, Lucy; Bukirwa, Alice; Kato, John Baptist; Katumba, David; Kisakye, Esther; Mangeni, Wilson; Mwebe, Sandra; Nakaye, Martha; Nassuna, Irene; Nyawere, Justine; Nakaweesa, Annet; Cook, Catherine; Phillips, Patrick; Nalugwa, Talemwa; Bachman, Christine M; Semitala, Fred Collins; Weigl, Bernhard H; Connelly, John; Worodria, William; Cattamanchi, AdithyaBACKGROUNDSputum-based testing is a barrier to increasing access to molecular diagnostics for tuberculosis (TB). Many people with TB are unable to produce sputum, and sputum processing increases assay complexity and cost. Tongue swabs are emerging as an alternative to sputum, but performance limits are uncertain.METHODSFrom June 2022 to July 2023, we enrolled 397 consecutive adults with cough >2 weeks at 2 health centers in Kampala, Uganda. We collected demographic and clinical information, sputum for TB testing (Xpert MTB/RIF Ultra and 2 liquid cultures), and tongue swabs for same-day quantitative polymerase chain reaction (qPCR) testing. We evaluated tongue swab qPCR diagnostic accuracy versus sputum TB test results, quantified TB targets per swab, assessed the impact of serial swabbing, and compared 2 swab types (Copan FLOQSWAB and Steripack spun polyester).RESULTSAmong 397 participants, 43.1% were female, median age was 33 years, 23.5% were diagnosed with human immunodeficiency virus, and 32.0% had confirmed TB. Sputum Xpert Ultra and tongue swab qPCR results were concordant for 98.2% (95% confidence interval [CI]: 96.2-99.1) of participants. Tongue swab qPCR sensitivity was 92.6% (95% CI: 86.5 to 96.0) and specificity was 99.1% (95% CI: 96.9 to 99.8) versus microbiological reference standard. A single tongue swab recovered a 7-log range of TB copies, with a decreasing recovery trend among 4 serial swabs. Swab types performed equivalently.CONCLUSIONSTongue swabs are a promising alternative to sputum for molecular diagnosis of TB, with sensitivity approaching sputum-based molecular tests. Our results provide valuable insights for developing successful tongue swab-based TB diagnostics. MEDLINE - AcademicItem A Prospective Evaluation of Xpert MTB/RIF Ultra for Childhood Pulmonary Tuberculosis in Uganda(Journal of the Pediatric Infectious Diseases Society, 2021) Jaganath, Devan; Wambi, Peter; Reza, Tania F.; Nakafeero, Jascent; Aben, Ernest O.; Kiconco, Emma; Nannyonga, Gertrude; Nsereko, Moses; Sekadde, Moorine P.; Mudiope, Mary; Kato-Maeda, Midori; Starke, Jeffrey; Andama, Alfred; Mohanty, Swomitra; Wobudeya, Eric; Cattamanchi, AdithyaXpert MTB/RIF Ultra (Xpert Ultra) has improved the sensitivity to detect pulmonary tuberculosis (TB) in adults. However, there have been limited prospective evaluations of its diagnostic accuracy in children. Methods. We enrolled children undergoing assessment for pulmonary TB in Kampala, Uganda, over a 12-month period. Children received a complete TB evaluation and were classified as Confirmed, Unconfirmed, or Unlikely TB. We calculated the sensitivity and specificity of Xpert Ultra among children with Confirmed vs Unlikely TB. We also determined the diagnostic accuracy with clinical, microbiological, and extended microbiological reference standards (MRSs). Results. Of the 213 children included, 23 (10.8%) had Confirmed TB, 88 (41.3%) had Unconfirmed TB, and 102 (47.9%) had Unlikely TB. The median age was 3.9 years, 13% were HIV-positive, and 61.5% were underweight. Xpert Ultra sensitivity was 69.6% (95% confidence interval [CI]: 47.1-86.8) among children with Confirmed TB and decreased to 23.4% (95% CI: 15.9-32.4) with the clinical reference standard. Specificity was 100% (95% CI: 96.4-100) among children with Unlikely TB and decreased to 94.7% (95% CI: 90.5-97.4) with a MRS. Sensitivity was 52.9% (95% CI: 35.1-70.2) and specificity 95.5% (95% CI: 91.4-98.1) with the extended MRS. Of the 26 positive Xpert Ultra results, 6 (23.1%) were “Trace-positive,” with most (5/6) occurring in children with Unconfirmed TB. Conclusions. Xpert Ultra is a useful tool for diagnosing pulmonary TB in children, but there remains a need for more sensitive tests to detect culture-negative TB.Item Sputum quality and diagnostic performance of GeneXpert MTB/RIF among smear-negative adults with presumed tuberculosis in Uganda(PLoS ONE, 2017) Meyer, Amanda J.; Atuheire, Collins; Worodria, William; Kizito, Samuel; Katamba, Achilles; Sanyu, Ingvar; Andama, Alfred; Ayakaka, Irene; Cattamanchi, Adithya; Bwanga, Freddie; Huang, Laurence; Davis, J. LucianIntroduction of GeneXpert MTB/RIF (Xpert) assay has constituted a major breakthrough for tuberculosis (TB) diagnostics. Several patient factors may influence diagnostic performance of Xpert including sputum quality. Objective We carried out a prospective, observational, cross-sectional study to determine the effect of sputum quality on diagnostic performance of Xpert among presumed TB patients in Uganda. Methods We collected clinical and demographic information and two sputum samples from participants. Staff recorded sputum quality and performed LED fluorescence microscopy and mycobacterial culture on each sample. If both smear examinations were negative, Xpert testing was performed. We calculated diagnostic yield, sensitivity, specificity, and other indicators for Xpert for each stratum of sputum quality in reference to a standard of mycobacterial culture. Results Patients with salivary sputum showed a trend towards a substantially higher proportion of samples that were Xpert-positive (54/286, 19%, 95% CI 15±24) compared with those with all other sputum sample types (221/1496, 15%, 95% CI 13±17). Blood-stained sputum produced the lowest sensitivity (28%; 95% CI 12±49) and salivary sputum the highest (66%; 95% CI 53±77). Specificity didn't vary meaningfully by sample types. Salivary sputum was significantly more sensitive than mucoid sputum (+13%, 95% CI +1 to +26), while bloodstained sputum was significantly less sensitive (-24%, 95% CI -42 to -5). Conclusions Our findings demonstrate the need to exercise caution in collecting sputum for Xpert and in interpreting results because sputum quality may impact test yield and sensitivity. In particular, it may be wise to pursue additional testing should blood-stained sputum test negative while salivary sputum should be readily accepted for Xpert testing given its higher sensitivity and potentially higher yield than other sample types. These findings challenge conventional recommendations against collecting salivary sputum for TB diagnosis and could inform new standards for sputum quality.