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  1. Home
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Browsing by Author "Marais, Suzaan"

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    Assessment at antiretroviral clinics during TB treatment reduces loss to follow-up among HIV-infected patients
    (Public Library of Science, 2012) Pepper, Dominique J; Marais, Suzaan; Bhaijee, Feriyl; Wilkinson, Robert J; De Azevedo, Virginia; Meintjes, Graeme
    Setting: A South African township clinic where loss to follow-up during TB treatment may prevent HIV-infected TB patients from receiving life-saving ART. Objective: To determine factors associated with loss to follow-up during TB treatment. Design: Regression analyses of a cohort of ART-eligible TB patients who commenced TB treatment and were followed for 24 weeks. RESULTS: Of 111 ART-eligible TB patients, 15 (14%) died in the ensuing 24 weeks. Of the remaining 96 TB patients, 11 (11%) were lost to follow-up. All TB patients lost to follow-up did not initiate ART. Of 85 TB patients in follow-up, 62 (73%) initiated ART 56 days after TB diagnosis (median, IQR 33-77 days) and 31 days after initial assessment at an ART clinic (median, IQR: 18-55 days). The median duration from TB diagnosis to initial assessment at an ART clinic was 19 days (IQR: 7-48 days). At 24 weeks, 6 of 85 (7%) TB patients who presented to an ART clinic for assessment were lost to follow-up, compared to 5 of 11 (45%) TB patients who did not present to an ART clinic for assessment. Logistic regression analysis (adjusted odds ratio  = 0.1, 95% confidence interval [95% CI]: 0.03-0.66) and our Cox proportional hazards model (hazard ratio  = 0.2, 95% CI: 0.04-0.68) confirmed that assessment at an ART clinic during TB treatment reduced loss to follow-up. CONCLUSION: Assessment at antiretroviral clinics for HIV care by trained health-care providers reduces loss to follow-up among HIV-infected patients with TB.
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    Barriers to initiation of antiretrovirals during antituberculosis therapy in Africa
    (Public Library of Science, 2011) Pepper, Dominique J; Marais, Suzaan; Wilkinson, Robert J; Bhaijee, Feriyl; De Azevedo, Virginia; Meintjes, Graeme
    BACKGROUND: In the developing world, the principal cause of death among HIV-infected patients is tuberculosis (TB). The initiation of antiretroviral therapy (ART) during TB therapy significantly improves survival, however it is not known which barriers prevent eligible TB patients from initiating life-saving ART. Method Setting. A South African township clinic with integrated tuberculosis and HIV services. Design. Logistic regression analyses of a prospective cohort of HIV-1 infected adults (≥18 years) who commenced TB therapy, were eligible for ART, and were followed for 6 months. FINDINGS: Of 100 HIV-1 infected adults eligible for ART during TB therapy, 90 TB patients presented to an ART clinic for assessment, 66 TB patients initiated ART, and 15 TB patients died. 34% of eligible TB patients (95%CI: 25-43%) did not initiate ART. Male gender and younger age (<36 years) were associated with failure to initiate ART (adjusted odds ratios of 3.7 [95%CI: 1.25-10.95] and 3.3 [95%CI: 1.12-9.69], respectively). Death during TB therapy was associated with a CD4+ count <100 cells/µL. CONCLUSION: In a clinic with integrated services for tuberculosis and HIV, one-third of eligible TB patients - particularly young men - did not initiate ART. Strategies are needed to promote ART initiation during TB therapy, especially among young men.
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    Central nervous system disorders afrer starting antiretroviral therapy in South Africa
    (Lippincott, Williams & Wilkins, 2010) Asselman, Valerie; Thienemann, Fredrich; Pepper, Dominique J; Boulle, Andrew; Wilkinson, Robert J; Graeme Meintjes; Marais, Suzaan
    Objective: To describe the spectrum of central nervous system (CNS) disease during the first year of antiretroviral therapy (ART), and to determine the contribution of neurological immune reconstitution inflammatory syndrome (IRIS). Design: A prospective observational cohort study conducted over a 12-month period at a public sector referral hospital in South Africa. Methods: HIV seropositive patients who developed new or recurrent neurological or psychiatric symptom(s) or sign(s) within the first year of starting ART were enrolled. We used the number of patients starting ART in the referral area in the preceding year as the denominator to calculate the incidence of referral for neurological deterioration. Patients with delirium and peripheral neuropathy were excluded. Outcome at six months was recorded. Results: Seventy-five patients were enrolled. The median nadir CD4+ count was 64 cells/μL. 59% of patients were receiving antituberculosis treatment. The incidence of referral for CNS deterioration in the first year of ART was 23.3 cases (95% CI, 18.3–29.2) per 1000 patient years at risk. CNS tuberculosis (n=27, 36%), cryptococcal meningitis (n=18, 24%), intracerebral space occupying lesions (other than tuberculoma) (n=10, 13%) and psychosis (n=9, 12%) were the most frequent diagnoses. Paradoxical neurological IRIS was diagnosed in 21 patients (28%), related to tuberculosis in 16 and cryptococcosis in 5. At 6 months, 23% of patients had died and 20% were lost to follow-up. Conclusion: Opportunistic infections, notably tuberculosis and cryptococcosis, were the most frequent causes for neurological deterioration after starting ART. Neurological IRIS occurred in over a quarter of patients.
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    Clinical deterioration during antituberculosis treatment in Africa: Incidence, causes and risk factors
    (BioMed Central Ltd, 2010) Pepper, Dominique; Marais, Suzaan; Wilkinson, Robert; Bhaijee, Feriyl; Maartens, Gary; McIlleron, Helen; De Azevedo, Virginia; Cox, Helen; McDermid, Cheryl; Sokhela, Simiso; Patel, Janisha; Meintjes, Graeme
    BACKGROUND:HIV-1 and Mycobacterium tuberculosis cause substantial morbidity and mortality. Despite the availability of antiretroviral and antituberculosis treatment in Africa, clinical deterioration during antituberculosis treatment remains a frequent reason for hospital admission. We therefore determined the incidence, causes and risk factors for clinical deterioration. METHODS: Prospective cohort study of 292 adults who initiated antituberculosis treatment during a 3-month period. We evaluated those with clinical deterioration over the following 24 weeks of treatment. RESULTS: Seventy-one percent (209/292) of patients were HIV-1 infected (median CD4+: 129 cells/muL [IQR:62-277]). At tuberculosis diagnosis, 23% (34/145) of HIV-1 infected patients qualifying for antiretroviral treatment (ART) were receiving ART; 6 months later, 75% (109/145) had received ART. Within 24 weeks of initiating antituberculosis treatment, 40% (117/292) of patients experienced clinical deterioration due to co-morbid illness (n = 70), tuberculosis related illness (n = 47), non AIDS-defining HIV-1 related infection (n = 25) and AIDS-defining illness (n = 21). Using HIV-1 uninfected patients as the referent group, HIV-1 infected patients had an increasing risk of clinical deterioration as CD4+ counts decreased [CD4+>350 cells/muL: RR = 1.4, 95% CI = 0.7-2.9; CD4+:200-350 cells/muL: RR = 2.0, 95% CI = 1.1-3.6; CD4+<200 cells/muL: RR = 3.0, 95% CI = 1.9-4.7]. During follow-up, 26% (30/117) of patients with clinical deterioration required hospital admission and 15% (17/117) died. Fifteen deaths were in HIV-1 infected patients with a CD4+<200 cells/muL. CONCLUSIONS: In multivariate analysis, HIV-1 infection and a low CD4+ count at tuberculosis diagnosis were significant risk factors for clinical deterioration and death. The initiation of ART at a CD4+ count of <350 cells/muL will likely reduce the high burden of clinical deterioration.
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    Cognitive outcomes in adults with HIV-associated Tuberculous Meningitis
    (2017) Albertyn, Christine Herculine; Solms, Mark; Marais, Suzaan; Gouse, Theta; Bateman, Kathleen
    Tuberculous meningitis (TBM) is a common cause of meningitis in adults in South Africa (1-3), second only to cryptococcal meningitis in studies of microbiologically confirmed meningitis, and accounting for 28% of cases in one (1). Conventional diagnostic tests for TBM are, however, relatively insensitive, and the true incidence is likely to be underreported. When both microbiological and clinical diagnostic criteria (4) are used in the same setting, the incidence of TBM rose to 57% (3), emerging as the most common cause of meningitis in adults in a district level hospital in the Western Cape. In the setting of high human immunodeficiency virus (HIV) and tuberculosis (TB) prevalence, approximately 88% of patients with definite or probable TBM are co-infected with HIV (3, 5) and six-month mortality in this group approaches 50% (3). Survivors may be left with long-term disability secondary to hydrocephalus, cranial neuropathies, seizures and strokes (6).
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    Investigations into HIV-associated tuberculous meningitis
    (2014) Marais, Suzaan; Wilkinson, Robert J; Meintjes, Graeme; Wilkinson, Katalin
    [Background] Tuberculous meningitis (TBM) is a common form of tuberculosis in high TB incidence settings. However, the burden of disease and outcome in affected adults is unknown in Cape Town. The diagnosis of TBM is often challenging, particularly in HIV co-infected patients and no standardized clinical case definition exists. An emerging complication that contributes to poor outcome in HIV-associated TBM is neurological TB immune reconstitution inflammatory syndrome (TB-IRIS). [Methods] A consensus clinical TBM case definition was developed following a TBM meeting that I co-ordinated. I led two observational studies that determined the burden of HIV-associated TBM and neurological TB-IRIS at a district-level hospital in Cape Town. Patients with HIV-associated TBM were prospectively enrolled in a third cohort study to determine the clinical and immunological characteristics of paradoxical TBM-IRIS. [Results] TBM accounted for 57% of meningitis cases over a 6-months period; 88% of these patients were HIV-infected. At six months follow-up, mortality in HIV-associated TBM patients was 48%. Neurological TB-IRIS accounted for 21% of patients who presented with central nervous system (CNS) deterioration during the first year of antiretroviral therapy (ART) over a one-year period. TBM-IRIS developed in 47% of HIV-associated TBM patients and associated with extensive cerebrospinal fluid (CSF) inflammation both at TBM diagnosis and at TBM-IRIS presentation. Patients who did not develop TBM-IRIS, but who were culture-positive for Mycobacterium tuberculosis from CSF at TBM diagnosis, showed an immunological phenotype similar to TBM-IRIS patients; however neutrophils were increased in TBM-IRIS patients compared to culture-positive TBM-non-IRIS patients, both at TBM diagnosis and two weeks after ART initiation. [Conclusions] HIV-associated TBM is a common cause of meningitis with a poor outcome in Cape Town. TBM-IRIS is a frequent complication of ART in HIV-associated TBM patients. CSF Mycobacterium tuberculosis culture positivity drives an inflammatory response that manifests as TBM-IRIS in most, but not all TBM patients. Neutrophils associate closely with the CNS inflammation that characterizes TBM-IRIS. An intensified TB treatment regimen with increased CSF penetration early during TB treatment may lead to improved mycobacterial clearance from the CNS, which may result in improved outcome during TBM treatment and a reduced frequency of TBM-IRIS. We aim to test this hypothesis in future studies.
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    Overt hypoadrenalism is uncommon in patients with stage 3 and 4 bronchogenic carcinoma
    (Health & Medical Publishing Group, 2003) Ross, Ian L; Marais, Suzaan; Raubenheimer, Peter; Abratt, Raymond; Isaacs, Sedick; Soule, Steven
    Introduction. Lung cancer is the leading cause of cancer mortality in most countries. The adrenal glands are common sites of metastatic lung cancer as approximately 40% of subjects with stage 4 bronchogenic carcinoma have adrenal metastases. The prevalence of biochemical hypoadrenalism is, however, remarkably poorly documented. Objectives. Our study aimed to determine the prevalence of primary hypoadrenalism, as defined by a subnormal cortisol response to the 250 µg adrenocorticotrophic hormone (ACTH) stimulation test, in patients with stage 3 and 4 lung cancer. Methods. Thirty patients with stage 3 and 4 bronchogenic carcinoma were prospectively recruited from the bronchus clinic. Demographic data and electrolytes were recorded and each patient had a 250 µg ACTH stimulation test to determine the prevalence of overt adrenal insufficiency, defined as a +30 minute cortisol of less than 550 nmol/l. Results. The median age and quartile deviation was 62 (10) years and the median basal cortisol was 429.5 (321) nmol/l. The median peak cortisol was 828.5 (342) nmol/l (range 536 - 1 675 nmol/l). Twenty-eight patients (93.3%) had an appropriate rise of cortisol to greater than 550 nmol/l following 250 µg ACTH stimulation. Two patients (6.7%) had mild primary adrenal failure with a peak cortisol between 500 and 550 nmol/l associated with a raised plasma ACTH concentration (131.4 and 10.5 pmol/l, normal 2.2 - 10 pmol/l). Twenty-eight patients (92.9%) were normonatraemic, while the two hyponatraemic patients had biochemical evidence of the syndrome of inappropriate antidiuretic hormone secretion. Conclusion. In conclusion, despite evidence that the adrenal glands of patients with disseminated bronchogenic carcinoma are frequently affected by metastatic disease, biochemical evidence of clinically significant hypoadrenalism is relatively uncommon and is not accurately predicted by electrolyte abnormalities.
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    Presentation 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, Graeme
    BACKGROUND: 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.
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    The neuroinfec-ous diseases profile in a specialist neurology centre in South Africa
    (2024) Oosthuizen, Katryn Nell Cobie; Marais, Suzaan
    Objective: This study aimed to assess the burden of neuroinfectious diseases and describe the causes and presentation of neurological infections to a tertiary level hospital neurology service in South Africa. Methods: A retrospective electronic search of medical discharge records was conducted for adult patients admitted to the neurology ward over a two-year period, and patients with neuroinfectious diseases were identified. Diagnostic criteria were applied to classify patients according to the certainty of their neuroinfectious disease diagnosis. Results: Neuroinfectious diseases accounted for 15% of the 802 admissions to the neurology ward. The most common infectious aetiologies were tuberculosis (27%), syphilis (21%), neurological diseases related to HIV itself (19%), and HIV-associated opportunistic infections (10%). Diagnostic challenges were observed, with only 17% of cases having a definite diagnosis. The majority of patients with neuroinfectious diseases were young, with a median age of 38 years (IQR: 32-46), and 56% were HIV-positive. Morbidity was high, with prolonged hospitalisation (>2 weeks) and limited full recovery at discharge in 56% and 98% of patients, respectively. Conclusions: This study provides important insights into the burden and characteristics of neuroinfectious diseases encountered at an inpatient South African neurology service. The findings highlight the need for earlier testing for, and treatment of, infections such as HIV, tuberculosis, and syphilis. Increased investment in neurological services should be a health care priority, to enhance the management of neuroinfectious diseases and ultimately improve patient outcomes.
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