Browsing by Author "Schutz, Charlotte"
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- ItemOpen AccessA systematic review: the role of neuroinflammation as a pathway to injury in traumatic brain injury(2025) Vermeulen, Marcia; Schutz, Charlotte; Meintjes, GraemeBackground: HIV-associated tuberculosis has a high mortality. Chest x-rays are an adjunct diagnostic tool for tuberculosis but has high inter-reader variability, which may be reduced with chest x-ray scoring systems. We analysed and scored chest x-rays of hospitalised patients with HIV-associated tuberculosis and assessed the relationship of these chest x-ray scores with 12-week mortality and biomarkers of tuberculosis dissemination. Methods: In this cohort study, the chest x-rays of adult patients, admitted with a new diagnosis of microbiologically confirmed HIV-associated tuberculosis were scored using the Timika scoring system. We excluded patients without a valid test result for the 3 biomarkers of tuberculosis dissemination (urine lipoarabinomannan, TB blood culture and urine Xpert); valid chest x-ray; or who were lost to follow up. Results: Amongst 364 included participants, 73 (20%) died and 291 (80%) survived. Median age was 36 years and median CD4 count 57cells/mm3. 25% of participants had normal chest x-rays. No association was found between chest x-ray score and dissemination score. Higher chest x-ray score was associated with higher hazards of death using a multivariate analysis: every 10-point increase in chest x-ray score resulted in 9% increased hazards of death. Conclusion: In this cohort, a higher Timika chest x-ray score was associated with higher hazards of death at 12-weeks.
- ItemOpen AccessBurden of antituberculosis and antiretroviral drug-induced liver injury at a secondary hospital in South Africa(2012) Schutz, Charlotte; Meintjies, GraemeAims : 1. To determine the proportion of patients who present with TB treatment and or ART-associated drug-induced liver injury (DILI) amongst all patients presenting with significant liver injury to GF Jooste Hospital during the study period. 2. To describe base line clinical characteristics and management of TB treatment and or ART-associated DILI patients. 3. To describe the in-patient and 3-month mortality of TB treatment and or ART-associated DILI patients. Background and Rationale : GF Jooste Hospital is a public sector referral hospital and serves a densely populated area with a high burden of HIV and tuberculosis (TB). ART rollout in the Western Cape started in 2001/2002 at two pilot clinics and is now well established (1). Many patients are on concomitant TB treatment and ART. At ART clinics in the referral area 25 - 40% of patients are on TB treatment when they start ART (2, 3) . At GF Jooste hospital many HIV positive patients are seen who are on TB treatment and or ART, and present with symptomatic liver dysfunction. Patients are on multiple hepatotoxic drugs, may have multiple opportunistic infections, systemic sepsis and hepatic TB immune reconstitution disease also plays a role. Anecdotally, these patients are complex to manage, require frequent specialist input, spend a long time in hospital and have high mortality. Management guidelines are based on expert opinion and is not evidence based. In practice management relies heavily on the attending clinicians’ experience and clinical judgment and management often differ widely between clinicians. Mortality could be due to progression of TB and or HIV because of interruption of effective therapy, other opportunistic infections or hospital acquired infections. Few early liver biopsies are done and it is not known if early liver biopsies would aid by guiding management of these patients. Prospective studies are urgently needed to guide management in these patients. The burden of TB treatment and or ART-associated drug induced liver injury in this setting has not been described to our knowledge, neither has management, outcome or mortality. This study was performed to aid planning of prospective studies in this field.
- ItemOpen AccessComplications of antiretroviral therapy initiation in hospitalised patients with HIV-associated tuberculosis(Public Library of Science, 2013) van der Plas, Helen; Meintjes, Graeme; Schutz, Charlotte; Goliath, Rene; Myer, Landon; Baatjie, Dorothea; Wilkinson, Robert J; Maartens, Gary; Mendelson, MarcBACKGROUND: HIV-associated tuberculosis is a common coinfection in Sub-Saharan Africa, which causes high morbidity and mortality. A sub-set of HIV-associated tuberculosis patients require prolonged hospital admission, during which antiretroviral therapy initiation may be required. The aim of this study was to document the causes of clinical deterioration of hospitalised patients with HIV-associated tuberculosis starting antiretroviral therapy in order to inform healthcare practice in low- to middle-income countries. METHODS: Prospective, observational cohort study of adult inpatients with HIV-associated tuberculosis starting antiretroviral therapy in a dedicated tuberculosis hospital in Cape Town, South Africa. Causes of clinical deterioration and outcome were recorded in the first 12 weeks of antiretroviral therapy. Patients with rifampicin-resistant tuberculosis were excluded. RESULTS: Between May 2009 and November 2010, 112 patients (60% female), with a median age of 32 years were enrolled. At baseline the median CD4 count was 55 cells/mm 3 (IQR 31-106) and HIV viral load 5.6 log copies/mL. All patients had significant comorbidity: 82% were bed-bound, 65% had disseminated tuberculosis and 27% had central nervous system tuberculosis. Seventy six patients (68%) developed 144 clinical events after starting antiretroviral therapy. TB-IRIS, hospital-acquired infections and significant drug toxicities occurred in 42%, 20.5% and 15% of patients respectively. A new opportunistic disease occurred in 15% of patients and a thromboembolic event in 8%. Mortality during the 12 week period was 10.6%. CONCLUSIONS: High rates of TB-IRIS, hospital-acquired infections and drug toxicities complicate the course of patients with HIV-associated tuberculosis starting antiretroviral therapy in hospital. Despite the high morbidity, mortality was relatively low. Careful clinical management and adequate resources are needed in hospitalised HIV-TB patients in the 1 st three months following ART initiation.
- ItemOpen AccessCorrection to: AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial(2019-01-14) Lawrence, David S; Youssouf, Nabila; Molloy, Síle F; Alanio, Alexandre; Alufandika, Melanie; Boulware, David R; Boyer-Chammard, Timothée; Chen, Tao; Dromer, Francoise; Hlupeni, Admire; Hope, William; Hosseinipour, Mina C; Kanyama, Cecilia; Lortholary, Oliver; Loyse, Angela; Meya, David B; Mosepele, Mosepele; Muzoora, Conrad; Mwandumba, Henry C; Ndhlovu, Chiratidzo E; Niessen, Louis; Schutz, Charlotte; Stott, Katharine E; Wang, Duolao; Lalloo, David G; Meintjes, Graeme; Jaffar, Shabbar; Harrison, Thomas S; Jarvis, Joseph NFollowing publication of the original article [1], we have been notified that one of the author names was listed incorrectly. Both incorrect and correct author names are presented below. The original publication has been corrected.
- ItemOpen AccessPresentation and outcome of tuberculous meningitis in a high HIV prevalence setting(Public Library of Science, 2011) Marais, Suzaan; Pepper, Dominique J; Schutz, Charlotte; Wilkinson, Robert J; Meintjes, GraemeBACKGROUND: Mycobacterium tuberculosis is a common, devastating cause of meningitis in HIV-infected persons. Due to international rollout programs, access to antiretroviral therapy (ART) is increasing globally. Starting patients with HIV-associated tuberculous meningitis (TBM) on ART during tuberculosis (TB) treatment may increase survival in these patients. We undertook this study to describe causes of meningitis at a secondary-level hospital in a high HIV/TB co-infection setting and to determine predictors of mortality in patients with TBM. METHODS: A retrospective review of cerebrospinal fluid findings and clinical records over a six-month period (March 2009-August 2009). Definite, probable and possible TBM were diagnosed according to published case definitions. RESULTS: TBM was diagnosed in 120/211 patients (57%) with meningitis. In 106 HIV-infected patients with TBM, six-month all-cause mortality was lower in those who received antiretroviral therapy (ART) during TB treatment; hazard ratio = 0.30 (95% CI = 0.08-0.82). Factors associated with inpatient mortality in HIV-infected patients were 1) low CD4 + count at presentation; adjusted odds ratio (AOR) = 1.4 (95% confidence interval [CI] = 1.03-1.96) per 50 cells/µL drop in CD4 + count and, 2) higher British Medical Research Council TBM disease grade (2 or 3 versus 1); AOR = 4.8 (95% CI = 1.45-15.87). Interpretation Starting ART prior to or during TB treatment may be associated with lower mortality in patients with HIV-associated TBM. Advanced HIV and worse stage of TBM disease predict in-hospital mortality in patients presenting with TBM.
- ItemOpen AccessProlonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors(BioMed Central, 2016-09-27) Bana, Tasnim M; Lesosky, Maia; Pepper, Dominique J; van der Plas, Helen; Schutz, Charlotte; Goliath, Rene; Morroni, Chelsea; Mendelson, Marc; Maartens, Gary; Wilkinson, Robert J; Meintjes, GraemeBackground: In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. Prolonged TB-IRIS has not been prospectively studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS. Methods: We pooled data from two prospective observational studies and a randomized controlled trial conducted in Cape Town, South Africa, that enrolled patients with paradoxical TB-IRIS. We used the same diagnostic approach and clinical case definitions for TB-IRIS in the 3 studies. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for prolonged TB-IRIS were analysed using Wilcoxon rank sum test, Fisher’s exact test, multivariate logistic regression and Cox proportional hazards models. Results: Two-hundred and sixteen patients with TB-IRIS were included. The median duration of TB-IRIS symptoms was 71.0 days (IQR 41.0–113.2). In 73/181 patients (40.3 %) with adequate follow-up data, IRIS duration was > 90 days. Six patients (3.3 %), mainly with lymph node involvement, had IRIS duration > 1 year. In univariate logistic regression analysis the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis, drug-resistant TB, lymph node TB-IRIS, and not being hospitalised at time of TB-IRIS diagnosis. In our multivariate logistic regression model lymph node TB-IRIS (aOR 2.27, 95 % CI 1.13–4.59) and not being hospitalised at time of TB-IRIS diagnosis (aOR for being hospitalised 0.5, 95 % CI 0.25-0.99) remained significantly associated with prolonged TB-IRIS, and drug-resistant TB was of borderline significance (aOR 3.26, 95 % CI 0.97–12.99). The association of not being hospitalised with longer duration of IRIS might be related to 1 of the 3 cohorts in which all patients were hospitalised at ART initiation with close inpatient follow-up. This could have resulted in diagnosis of milder cases and earlier IRIS treatment potentially resulting in shorter TB-IRIS duration in these hospitalised patients. Conclusions: Around 40 % of patients with TB-IRIS have symptoms for more than 90 days. Involvement of lymph nodes at time of TB-IRIS is an independent risk factor for prolonged TB-IRIS. Future studies should address whether more prompt anti-inflammatory treatment of lymph node TB-IRIS reduces the risk of prolonged TB-IRIS. Trial registration: The randomized controlled trial was registered with Current Controlled Trials ISRCTN21322548 on 17 August 2005.
- ItemOpen AccessRapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa(2015-08-14) Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; van Wyk, Gavin; Vogt, Monica; Pahlana, Pearl; Nicol, Mark P; Meintjes, GraemeAbstract Background Autopsy studies of HIV/AIDS-related hospital deaths in sub-Saharan Africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (TB), which is found in 34–64 % of adult cadavers. We determined the overall prevalence and predictors of TB among consecutive unselected HIV-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with Xpert MTB/RIF (Xpert). Methods To determine overall TB prevalence accurately, comprehensive clinical sampling (sputum, urine, blood plus other relevant samples) was done and TB was defined by detection of Mycobacterium tuberculosis in any sample using Xpert and/or mycobacterial liquid culture. To evaluate a rapid screening strategy, we compared the diagnostic yield of Xpert testing sputum samples and urine samples obtained with assistance from a respiratory study nurse in the first 24 h of admission. Results Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/μL). TB prevalence was very high (32.6 %; 95 % CI, 28.1–37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, ≥1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases, respectively (P <0.001). Conclusions The very high prevalence of active TB and its non-specific presentation strongly suggest the need for routine microbiological screening for TB in all HIV-positive medical admissions in high-burden settings. The incremental diagnostic yield from Xpert testing urine was very high and this strategy might be used to rapidly screen new admissions, especially if sputum is difficult to obtain.
- ItemOpen AccessReduced referral and case fatality rates for severe symptomatic hyperlactataemia in a South African public sector antiretroviral programme: a retrospective observational study(BioMed Central Ltd, 2010) Schutz, Charlotte; Boulle, Andrew; Stead, Dave; Rebe, Kevin; Osler, Meg; Meintjes, GraemeBACKGROUND: Interventions to promote prevention and earlier diagnosis of severe symptomatic hyperlactataemia (SHL) were implemented in the Western Cape provincial antiretroviral programme (South Africa) from 2004. Interventions included clinician education, point-of-care lactate meters, switch from stavudine to zidovudine in high risk patients and stavudine dose reduction. This study assessed trends in referral rate, severity at presentation and case fatality rate for severe SHL. METHODS: Retrospective study of severe SHL cases diagnosed at a referral facility from 1 January 2003 to 31 December 2008. Severe SHL was defined as patients with compatible symptoms and serum lactate [greater than or equal to] 5 mmol/l attributable to antiretroviral therapy (ART). Cumulative ART exposure at referring ART clinics was used to calculate referral rates. RESULTS: There were 254 severe SHL cases. The referral rate (per thousand patient years [py] ART exposure) peaked in 2005 (20.4/1000py), but fell to 1.3/1000py by 2008 (incidence rate ratio [IRR] = 0.07, 95%CI 0.04-0.11). In 2003, 66.7% of cases presented with a standard bicarbonate (SHCO3) level <15 mmol/l, but this fell to 12.5% by 2008 (p for trend < 0.001). Case fatality rate fell from a peak of 33.3% in 2004 to 0% in 2008 (p for trend = 0.002). CONCLUSIONS: These trends suggest the interventions were associated with reduced referral, less severe metabolic acidosis at presentation and improved survival.