Browsing by Author "Peter, Jonathan"

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    Acute cognitive dysfunction, short and long-term outcomes and the impact of medical follow-up following hospitalisation for general medical illness in Cape Town, South Africa
    (2023) Abdullah, Mohamed; Peter, Jonathan; Raubenheimer Peter
    Background. Delirium is an important and common general medical condition with a high morbidity and mortality rate independently associated with increases in the length of hospital stay, the requirement for institutional care, persistent cognitive deficits, and functional decline. The Gold standard for testing delirium continues to evolve but requires lengthy bedside cognitive testing by trained specialists. In a busy acute general medical setting, the use of these tools is impractical. Many alternatives and shorter tools have been developed for screening, diagnosis, and assessing the severity of delirium, but the majority have only been validated for use in geriatric populations or intensive care settings in developed countries. Objective. In this study, we validate the simple ‘RACY' 4-question delirium screening tool for use in general medical tertiary hospital admissions. Methods. This was a prospective observational cohort study conducted amongst acute general medical admissions at Groote Schuur Hospital, in Cape Town, South Africa, admitted between 30 September 2013 and 30 January 2014. ROC characteristics and diagnostic accuracy of the ‘RACY' 4-question delirium screening tool, sensitivity analysis of factors influencing RACY performance, and interrater agreement were obtained. Reference delirium testing was performed by neuropsychologists, using the Confusion Assessment Method. Results. A total of 609 medical in-patients were included. The prevalence of delirium was 16.9% (95% CI: 13.7-20.6, 82/485), and the median (IQR) age of admissions was 50 (36-65) years. The AUROC for RACY was 0.859. A cut-point of RACY ≤ 2 offered the best overall diagnostic utility classifying 8 out of 10 patients correctly with sensitivity, specificity, positive and negative likelihood ratios (+LR, -LR) of 74.4% (95% CI: 63.6-83.4, n/N: 61/82); 83.6% (95% CI: 79.6-87.5, n/N: 337/403); 4.5 (95% CI: 3.5-5.9); and 0.3 (95% CI: 0.2-0.4) respectively. Alternatively, a cut-point of RACY ≤ 3 optimised rule-out utility with a sensitivity and NPV of 94.0% (95% CI: 86.3-98.0, n/N: 77/82) and 97.6% (95% CI: 94.4-99.2, n/N: 201/206). RACY testing could be performed in less than a minute. Overall interrater agreement was 70% with a kappa of 0.55. Conclusions. The rapid RACY tool is a simple valid and reliable method to screen for delirium amongst new general medical admissions in a developing country setting.
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    Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples
    (Public Library of Science, 2010) Dheda, Keertan; Davids, Virginia; Lenders, Laura; Roberts, Teri; Meldau, Richard; Ling, Daphne; Brunet, Laurence; Smit, Richard van Zyl; Peter, Jonathan; Green, Clare; Badri, Motasim; Sechi, Leonardo; Sharma, Surendra; Hoelscher, Michael; Dawson, Rodney
    BACKGROUND: The accurate diagnosis of TB in HIV-infected patients, particularly with advanced immunosuppression, is difficult. Recent studies indicate that a lipoarabinomannan (LAM) assay (Clearview-TB®-ELISA) may have some utility for the diagnosis of TB in HIV-infected patients; however, the precise subgroup that may benefit from this technology requires clarification. The utility of LAM in sputum samples has, hitherto, not been evaluated. METHODS: LAM was measured in sputum and urine samples obtained from 500 consecutively recruited ambulant patients, with suspected TB, from 2 primary care clinics in South Africa. Culture positivity for M. tuberculosis was used as the reference standard for TB diagnosis. RESULTS: Of 440 evaluable patients 120/387 (31%) were HIV-infected. Urine-LAM positivity was associated with HIV positivity (p = 0.007) and test sensitivity, although low, was significantly higher in HIV-infected compared to uninfected patients (21% versus 6%; p<0.001), and also in HIV-infected participants with a CD4 <200 versus >200 cells/mm 3 (37% versus 0%; p = 0.003). Urine-LAM remained highly specific in all 3 subgroups (95%-100%). 25% of smear-negative but culture-positive HIV-infected patients with a CD4 <200 cells/mm 3 were positive for urine-LAM. Sputum-LAM had good sensitivity (86%) but poor specificity (15%) likely due to test cross-reactivity with several mouth-residing organisms including actinomycetes and nocardia species. CONCLUSIONS: These preliminary data indicate that in a high burden primary care setting the diagnostic usefulness of urine-LAM is limited, as a rule-in test, to a specific patient subgroup i.e. smear-negative HIV-infected TB patients with a CD4 count <200 cells/mm 3 , who would otherwise have required further investigation. However, even in this group sensitivity was modest. Future and adequately powered studies in a primary care setting should now specifically target patients with suspected TB who have advanced HIV infection.
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    Comparison of quantitative techniques including Xpert MTB/RIF to evaluate mycobacterial burden
    (Public Library of Science, 2011) van Zyl-Smit, Richard N; Binder, Anke; Meldau, Richard; Mishra, Hridesh; Semple, Patricia L; Theron, Grant; Peter, Jonathan; Whitelaw, Andrew; Sharma, Suren K; Warren, Robin; Bateman, Eric D; Dheda, Keertan
    Introduction: Accurate quantification of mycobacterial load is important for the evaluation of patient infectiousness, disease severity and monitoring treatment response in human and in-vitro laboratory models of disease. We hypothesized that newer techniques would perform as well as solid media culture to quantify mycobacterial burden in laboratory specimens. METHODS: We compared the turn-around-time, detection-threshold, dynamic range, reproducibility, relative discriminative ability, of 4 mycobacterial load determination techniques: automated liquid culture (BACTEC-MGIT-960), [ 3 H]-uracil incorporation assays, luciferase-reporter construct bioluminescence, and quantitative PCR(Xpert -MTB/RIF) using serial dilutions of Mycobacterium bovis and Mycobacterium tuberculosis H37RV. Mycobacterial colony-forming-units(CFU) using 7H10-Middlebrook solid media served as the reference standard. RESULTS: All 4 assays correlated well with the reference standard, however, bioluminescence and uracil assays had a detection threshold ≥1×10 3 organisms. By contrast, BACTEC-MGIT-960 liquid culture, although only providing results in days, was user-friendly, had the lowest detection threshold (<10 organisms), the greatest discriminative ability (1 vs. 10 organisms; p = 0.02), and the best reproducibility (coefficient of variance of 2% vs. 38% compared to uracil incorporation; p = 0.02). Xpert-MTB/RIF correlated well with mycobacterial load, had a rapid turn-around-time (<2 hours), was user friendly, but had a detection limit of ∼100 organisms. CONCLUSIONS: Choosing a technique to quantify mycobacterial burden for laboratory or clinical research depends on availability of resources and the question being addressed. Automated liquid culture has good discriminative ability and low detection threshold but results are only obtained in days. Xpert MTB/RIF provides rapid quantification of mycobacterial burden, but has a poorer discrimination and detection threshold.
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    Delirium amongst HIV-infected general medical admissions in Cape Town, South Africa
    (2021) Day, Cascia; Peter, Jonathan; Raubenheimer, Peter
    Background Delirium is associated with increased mortality and hospital length of stay. Limited data are available from HIV-infected acute hospital admissions in developing countries. We conducted a prospective study of delirium amongst acute medical admissions in South Africa - a developing country with universal ART access and high burdens of TB and noncommunicable disease. Methods Three cohorts of adult acute medical admissions to Groote Schuur and Victoria Hospitals, Cape Town, South Africa were evaluated for prevalent delirium within 24 hours of admission. Reference delirium testing was performed by either consultant physicians or neuropsychologists, using the Confusion Assessment Method (CAM). Findings The study included 1182 acute medical admissions; with 318 (26·9%) HIV-infected Median(IQR) age and CD4 count was 35(30-43) years and 132(61-256) cells/mm3 respectively, with 140/318(44%) using ART on admission. Delirium prevalence was 17·6%(95% CI 13·7-22·1%) amongst HIV-infected patients and was an independent risk factor for inpatient mortality. In multivariable logistic regression, factors associated with delirium were age ≥55 years(AOR 6·95[2·03-23·67], p=0·002) and urea ≥15(AOR 4·83[1·7- 13·44], p=0·003), while ART use reduced risk (p=0·014). Low CD4 count, unsuppressed viral load, and active TB were not predictors of delirium; nor were other traditional risk factors such as non-opportunistic, acute infections or polypharmacy. Interpretation Delirium is common and predicts poor outcome in HIV-infected acute medical admissions in endemic settings despite increased ART use. Older HIV-infected patients with renal dysfunction are at high risk for inpatient delirium while those using ART on admission are protected.
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    Determine TB-LAM lateral flow urine antigen assay for HIV-associated tuberculosis: recommendations on the design and reporting of clinical studies
    (BioMed Central Ltd, 2013) Lawn, Stephen; Dheda, Keertan; Kerkhoff, Andrew; Peter, Jonathan; Dorman, Susan; Boehme, Catharina; Nicol, Mark
    Detection of the Mycobacterium tuberculosis cell wall antigen lipoarabinomannan (LAM) in urine permits diagnoses of tuberculosis (TB) to be made in HIV-infected patients with advanced immunodeficiency. This can be achieved at the point-of-care within just 30 minutes using the Determine TB-LAM, which is a commercially available, lateral-flow urine 'strip test' assay. The assay has been shown to have useful diagnostic accuracy in patients enrolling in antiretroviral treatment services or in HIV-infected patients requiring admission to hospital medical wards in sub-Saharan Africa. Such patients have high mortality risk and have most to gain from rapid diagnosis of TB and immediate initiation of treatment. However, few studies using this assay have yet been reported and many questions remain concerning the correct use of the assay, interpretation of results, the role of the assay as an add-on test within existing diagnostic algorithms and the types of further studies needed. In this paper we address a series of questions with the aim of informing the design, conduct and interpretation of future studies. Specifically, we clarify which clinical populations are most likely to derive benefit from use of this assay and how patients enrolled in such studies might best be characterised. We describe the importance of employing a rigorous microbiological diagnostic reference standard in studies of diagnostic accuracy and discuss issues surrounding the specificity of the assay in different geographical areas and potential cross-reactivity with non-tuberculous mycobacteria and other organisms. We highlight the importance of careful procedures for urine collection and storage and the critical issue of how to read and interpret the test strips. Finally, we consider how the assay could be used in combination with other assays and outline the types of studies that are required to build the evidence base concerning its use.
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    Development of a simple reliable radiographic scoring system to aid the diagnosis of pulmonary tuberculosis
    (Public Library of Science, 2013) Pinto, Lancelot M; Dheda, Keertan; Theron, Grant; Allwood, Brian; Calligaro, Gregory; van Zyl-Smit, Richard; Peter, Jonathan; Schwartzman, Kevin; Menzies, Dick; Bateman, Eric; Pai, Madhukar; Dawson, Rodney
    Rationale: Chest radiography is sometimes the only method available for investigating patients with possible pulmonary tuberculosis (PTB) with negative sputum smears. However, interpretation of chest radiographs in this context lacks specificity for PTB, is subjective and is neither standardized nor reproducible. Efforts to improve the interpretation of chest radiography are warranted. Objectives To develop a scoring system to aid the diagnosis of PTB, using features recorded with the Chest Radiograph Reading and Recording System (CRRS). METHODS: Chest radiographs of outpatients with possible PTB, recruited over 3 years at clinics in South Africa were read by two independent readers using the CRRS method. Multivariate analysis was used to identify features significantly associated with culture-positive PTB. These were weighted and used to generate a score. RESULTS: 473 patients were included in the analysis. Large upper lobe opacities, cavities, unilateral pleural effusion and adenopathy were significantly associated with PTB, had high inter-reader reliability, and received 2, 2, 1 and 2 points, respectively in the final score. Using a cut-off of 2, scores below this threshold had a high negative predictive value (91.5%, 95%CI 87.1,94.7), but low positive predictive value (49.4%, 95%CI 42.9,55.9). Among the 382 TB suspects with negative sputum smears, 229 patients had scores <2; the score correctly ruled out active PTB in 214 of these patients (NPV 93.4%; 95%CI 89.4,96.3). The score had a suboptimal negative predictive value in HIV-infected patients (NPV 86.4, 95% CI 75,94). CONCLUSIONS: The proposed scoring system is simple, and reliably ruled out active PTB in smear-negative HIV-uninfected patients, thus potentially reducing the need for further tests in high burden settings. Validation studies are now required.
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    Immunological evaluation of HIV-negative invasive fungal disease at Groote Schuur Hospital, Cape Town, South Africa
    (2019) Onyango, Vonwicks Czelestakov; Peter, Jonathan; Dlamini, Sipho
    Background The majority of invasive fungal disease in South African hospitals is HIV-related or associated with another secondary immunodeficiency e.g. haematopoietic stem cell transplant. After excluding secondary immunodeficiency, a detailed immune work-up can lead to a diagnosis of primary immunodeficiency. Objective To detail an appropriate step-wise immunological work-up for a series of patients with invasive fungal diseases and possible underlying primary immune deficiency. Methods Detailed review of all culture- or histologically confirmed cases of invasive fungal disease (IFD) at Groote Schuur Hospital between 2007-2017. Step-wise immunological work-up of IFD patients with no secondary immunodeficiency. Clinical characteristics and step-wise immunological profiles were evaluated. Results Sixty-seven adults with IFD were identified; 72% (48/67) were HIV-related. 8/19 HIVnegative cases were either deceased (4) or lost-to-follow-up (4). Work-up of the remaining 11 cases found five with non-HIV secondary immunodeficiencies (Lupus, liver transplant, endstage renal failure and haematological malignancy). A primary immunodeficiency was suspected in six cases, but 1 case of cutaneous sporotrichosis was excluded; with five cases (4 with disseminated Cryptococcus neoformans and 1 with cerebral aspergillosis) undergoing detailed immune work-up. A case of idiopathic CD4 lymphopenia was diagnosed; but all other cases had no evidence of neutrophil or a cell-mediated immune defect; including investigations of naïve and memory T-cell subsets and cytokine responses to PHA and candida. All cases were noted to have low baseline vaccine responses and Vitamin D deficiency. Conclusion Invasive fungal disease is predominantly associated with HIV and secondary immunodeficiency in South Africa. Known primary immunodeficiencies can be identified with basic immune work-up; but no obvious functional immune defect is evident in the majority of these cases.
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    Immunoproteome of anti-TB drug associated DRESS in HIV TB co-infection
    (2022) Buck, Chloe; Peter, Jonathan
    Introduction: A greater incidence of severe cutaneous adverse drug reaction (SCAR) such as Drug Reaction with Eosinophilia Systemic Symptoms (DRESS) occur among HIV-infected patients. We sought to characterize the immunoproteomic profile of DRESS to first-line TB drugs in HIV infected cases. We hypothesize that differentially regulated proteins would be found interindividually and with disease evolution that may provide a mechanistic understanding of DRESS underlying pathways. Participants and Methods: HIV cases with DRESS (probable or definite) and confirmed reactions to either one or many first-line anti-TB (FLTB) drugs were chosen (n=8). Discovery High Performance Liquid Chromatography Mass Spectrometry (HPLC-MS) (data independent proteomic) analysis was carried out on plasma samples with downstream protein identification and quantification analysis done on Spectronaut â„¢. (https://biognosys.com/resources/spectronaut-15-expand-biological-insights-with-diaproteomics/) Data and statistical analysis was carried out using Perseus and R programming language. Results: Overall protein clustering suggested greater plasma proteome differences between individuals than intraindividually between DRESS disease states and drug rechallenge reactions. Acute phase proteins and immunoglobulin kappa variable chains dominate the serum proteome of acute DRESS in TB/HIV co-infected patients, with CRP having the highest fold change (q = 2.5) in acute versus early recovery samples. LRG and L-Selectin (q < 0.05, FC > 1.5), both proteins involved in maintenance and regulation of the immune system especially at endothelia, were found to be upregulated in acute compared to recovery samples. Multiple non-immune related proteins, linked to actin-binding and thus cell structure, morphology, and functioning, were also upregulated (p < 0.05, FC > 1.5) in acute samples (including (ACTB) Actin, cytoplasmic 1, (ACTC1) Actin, alpha cardiac muscle 1, (VCL) Viculin). (MPO) Positive drug reaction samples from single versus multiple drug reactors had differentially regulated immune proteins: myeloperoxidase (p = 0.04, FC = 1.4), CRP (p = 0.04, FC = 5.2) and (LYST) Lysosomal-trafficking regulator (p = 0.04, FC > 2.7), proteins linked to polymorphonuclear cell inflammation, acute phase response and antiviral lymphocyte responses respectively. Conclusion: Acute phase proteins and non-discriminatory hypergammaglobulinemia dominated the plasma proteome of HIV/TB co-infection and DRESS to FLTD, with drivers including TB disease burden and acute DRESS being hard to discriminate. A few differentially regulated immune proteins, particularly when comparing single versus multiple drug reactors, highlight roles for polymorphonuclear cell inflammation, and antiviral lymphocyte responses beyond the exaggerate innate acute phase response. Further work with increased sample size is warranted to confirm these preliminary findings.
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    Long-term HIV and tuberculosis outcomes in co-infected patients with treatment limiting severe cutaneous adverse reactions
    (2023) Veenstra, Simon; Peter, Jonathan
    Background Treatment-limiting severe cutaneous adverse reactions (SCAR) occur more commonly amongst persons co-infected with tuberculosis (TB) and advanced HIV. The impact of SCAR on long-term HIV and TB outcomes is unknown. Methods Patients with active TB and/or HIV admitted to Groote Schuur Hospital, Cape Town, South Africa with SCAR between 1/10/2018 and 30/09/2021 were eligible. Clinical and laboratory follow-up data was collected for 6 and 12-month outcomes: mortality, TB and antiretroviral therapy (ART) regimen changes, TB treatment completion, and CD4 count recovery. Results Forty-eight SCAR admissions included: 34, 11, and 3 HIV-associated TB, HIV-only and TB-only patients with 32, 13 and 3 cases of drug reaction with eosinophilia and systemic symptoms, StevensJohnson syndrome/toxic epidermal necrolysis and generalised bullous fixed drug eruption respectively. Nine (19%), all HIV-positive, were deceased at 12-months, and 12 (25%) were lost to all care levels. Amongst TB-SCAR patients, seven (21%) were discharged on all four first-line anti-TB drugs (FLTD), while 12 (33%) had discharge regimens with no FLTDs; 24/37 (65%) completed TB treatment. Amongst HIV-SCAR patients, 10/31 (32%) changed ART regimen. If retained in care (24/36), median (IQR) CD4 counts increased by 12-months post-SCAR (115 (62-175) vs. 319 (134-439) cells/uL). Conclusion SCAR admission amongst patients with HIV-associated TB results in substantial mortality, and considerable treatment complexity. However, if retained in care, TB regimens are successfully completed, and immune recovery is good despite SCAR.
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    Neuropsychological sequelae of paediatric posterior fossa brain tumours : the effect on quality of life
    (2002) Leng, Jeanette Anne; Hemp, Frances; Peter, Jonathan; Oxtoby, Richard
    Bibliography: leaves 248-285.
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    Prevalence and outcome of delirium amongst acute general medical inpatients in Cape Town, South Africa
    (2019) Du Plooy, Daniël Francois; Raubenheimer, Peter; Peter, Jonathan
    Objectives Delirium is a common, serious, underdiagnosed condition in acute medical and surgical inpatients. It is associated with increased risk of mortality and morbidity. Data are largely limited to developed countries in geriatric cohorts. Here we describe prevalence, risk factors and outcomes of delirium amongst general medical patients admitted to two hospitals in Cape Town, South Africa. Design and Setting Prospective cohort study of patients admitted acutely to a general medical inpatient service, in a secondary and tertiary-level public hospital serving the Metro West area of Cape Town, South Africa. Participants Patients ≥ 18 years old were recruited daily from all acute medical admissions. Patients were excluded if they were aphasic or had Glasgow Coma Scale < 12/15. In total, 808 patients were included. Main outcome measures Delirium was diagnosed using the validated confusion assessment method (CAM) tool performed by trained neuropsychologists. Demographic data was collected by a clinical team and short and long-term mortality data were obtained using linkage analysis of hospitalised patients to routinely collected provincial death certification records. Results: The median age of inpatients was 51 (36-65) years. Twenty nine percent were proven HIV-infected. The overall prevalence of delirium was 12.3%. Multivariate predictors of delirium included: the presence of an indwelling urinary catheter (OR 4.37, CI 2.36-8.03), admission with a central nervous system disease (OR 4.37, CI 2.39-7.98), pre-existing cognitive impairment (OR 2.72, CI 1.11-6.64) and admission with a terminal disease (OR 3.11, CI 1.09-8.89). HIV infection was not associated with increased risk of delirium. Delirium was associated with an increased risk for in-hospital (delirium vs. no delirium: 29% vs 12%; p<0.01) and 12-month mortality (30% vs 20%; p < 0.01), as well as increased length of hospital stay (7 days vs 5 days, p < 0 .01). Conclusion: In this cohort of medical in-patients (with a relative young age and high HIV prevalence,) one in eight (12.3%) are delirious.. Delirium was associated with adverse outcomes. Delirium risk factors in this young cohort are similar to those in geriatric cohorts in developed countries, and neither HIV nor opportunistic infections increased risk.
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    Spinal compression in childhood : the University of Cape Town experience
    (1996) Buwembo, Joseph E; Peter, Jonathan
    Aim: A retrospective study of cases of childhood spinal compression over a 30-year period (1963-1992) was undertaken in order to determine the trend in incidence, aetiology, diagnosis, treatment and prognosis. Patients and Methods: The study includes children less than 15 years of age who were treated for spinal compression at the Red Cross War Memorial Children's Hospital, Maitland Cottage Hospital and Groote Schuur Hospital. Children who had tuberculosis of the spine without a neurological deficit, were excluded. The study also excludes dysraphism and non-compressive causes of paraplegia, such as Guillain-Barre Syndrome and poliomyelitis.
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    The Dandy-Walker syndrome
    (1992) Domingo, Zayne; Peter, Jonathan
    The Dandy-Walker syndrome (DWS) has been defined as a congenital malformation of the structures of the posterior fossa characterised by cystic dilatation of the fourth ventricle, hypoplasia of the cerebellar vermis, enlargement of the posterior fossa, atresia of the foramina of Luschke and Magendie and associated hydrocephalus. Since its initial description definitions have been modified to include findings encountered in a particular case or series of cases. This lack of uniformity of the diagnostic criteria has made the objective assessment of management and outcome difficult. It has also resulted in terms such as DandyWalker variant, mega cisterna pouch and prominent cisterna posterior fossa cysts which magna, magna, do not persistent Blake's being applied to fit in with the particular criteria used for the series described.
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    The immunopathogenic mechanism of severe cutaneous adverse reactions to first line anti-tuberculosis drugs
    (2024) Choshi, Phuti; Peter, Jonathan
    Background and hypothesis In HIV-TB endemic settings like South Africa, first line anti-tuberculosis drugs (FLTD) are the commonest cause of severe immune mediated adverse drug reactions, including Stevens Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). The mechanisms of these treatment-limiting, life-threatening reactions, particular in persons living with HIV (PLHV) is poorly understood, making diagnosis and treatment challenging in patients who can ill-afford suboptimal and prolonged anti-TB treatment interruptions. We hypothesize that polymorphisms in Human Leukocyte Antigen (HLA), Endoplasmic Reticulum Aminopeptidase (ERAP) and Killer Immunoglobulin Receptor (KIR) genes along with HIV-related immune dysregulation during drug exposure might confer susceptibility. In this thesis, we aimed to identify genetic markers in African populations for FLTD-induced SJS/TEN and DRESS, and using single-cell proteomic and transcriptomic analyses, we aimed to immunophenotype different stages of the reactions. Methods We selected three groups of participants from the IMARI in Africa registry: i) HIV+ FLTD SCAR cases, ii) HIV- FLTD SCAR cases and iii) HIV+/- FLTD tolerant controls (>8 weeks on treatment without any adverse events). We collected saliva and blood at baseline and in SCAR cases, we collected blood at different stages of the reaction including pre sequential drug challenge (SDC), on positive reaction to any FLTD (post SDC) and during recovery (at least three months from an acute reaction). We used RegiSCAR phenotype validation, Naranjo drug causality and ELISpot assay to identify offending drugs and precision phenotype cases. We isolated DNA from saliva for HLA, ERAP and KIR typing. In a well-defined subset of patients, we used an integrated single-cell approach involving: i) mass cytometry by time of flight (n=8), and ii) single cell RNA sequencing (scRNA-seq) (n=3) to characterise immune cells activated by drug. Results Forty-one RegiSCAR validated SCAR cases that reacted to one or more FLTD on rechallenge were included, Rifampicin-associated DRESS was commonest (n=18). IFN-gamma ELISpot, optimised for FLTDs, was most sensitive (75%) for Rifampicin-DRESS cases. Rifampicin-DRESS/SJS/TEN (with positive ELISpot) was associated with HLA-B*44:03 (OR:28.8; 95%CI: 5.6-107.7; P=
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    Utility of novel diagnostic tests for tuberculosis using human urine
    (2012) Muchinga, Tapuwa Enwell; Dheda, Keertan; Peter, Jonathan; Govender, Ureshnie
    Two thirds of new TB cases in sub-Saharan Africa are HIV coinfected. HIV-TB co-infection increases the incidence of extra-pulmonary, sputum smear-negative and sputum-scarce TB. In these vulnerable patientgroups with high mortality rates, sputum-based diagnostic tools are unhelpful. Urine-based diagnostics offer an attractive, easily available alternative for rapid diagnosis. We evaluated the point-of-care urine LAM strip test (Determine TB LAM Ag test, Alere) and urine-based Xpert MTB/RIF for TB diagnosis in two patient cohorts with high HIV prevalence. A spot urine sample was collected from two cohorts of persons with suspected TB. The first cohort consisted of ambulatory primary care clinic patients suspected of having TB (group 1) whilst the second comprised hospitalised patients with suspected HIV co-infection (group 2). The urine LAM ELISA, LAM strip test and Xpert MTB/RIF were performed according to the manufacturer’s instructions. In addition, the effects of using an alternative ‘rulein’ cut-point for the urine LAM strip test and a pelleted (2-10ml) urine sample for Xpert MTB/RIF testing on diagnostic accuracy and inter-reader reliability was assessed. The diagnostic reference standard was M. tuberculosis culture positivity.
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    Variations in pollen and fungal spore air spora: an analysis of 30 years of monitoring for the clinical assessment of patients in the Western Cape
    (2018) Berman, Dilys Melanie; Potter, Paul; Peter, Jonathan
    Background and aims: Pollen and fungal spore concentrations in the atmosphere of Cape Town have been monitored since 1984 in two areas of Cape Town. Volumetric spore traps were used to monitor the air spora that trigger allergic disease in susceptible individuals. A pollen count was produced for the diagnosis and treatment of patients attending respiratory clinics at the academic hospitals but the findings of the different aerobiological monitoring areas have never been compared. We considered that more than one aerobiological area should be monitored to produce a representative pollen count for the most densely populated areas of Cape Town. Methods: The pollen taxa and fungal spore genera collected from the two aerobiological zones, now named the West Coast and Valkenberg Aerobiomes were defined. Eight of the air spora were selected for detailed comparison. The relative abundance and seasons of Poaceae, or grasses, the tree pollen taxa Cupressaceae, Platanus and Quercus and the fungal spores: Alternaria, Cladosporium, Epicoccum and Pleospora were evaluated and compared in each aerobiome. Differences in the annual distribution and seasonal limits of the air spora in the two aerobiomes were found using statistical techniques. Results: Significant differences were found between the tree pollen loads in the different aerobiomes. Spring pollinating trees were the most prevalent pollen taxa in the Valkenberg Aerobiome with short flowering seasons that spanned six weeks (August-September) for Platanus and Quercus but eight weeks (July-September) for Cupressaceae. The grass season was longer (September- March) in both aerobiomes and grasses flowered earlier at the inland site. Poaceae dominated the annual pollen catch at the coastal aerobiological zone. Parietaria was the only weed taxon with significant concentrations. Pleospora showed a seasonal trend peaking in mid to late winter at the West Coast. No comparable peaks for Pleospora were seen from the Valkenberg sites. Cladosporium concentrations were low and seldom breached the significant threshold of 3,000 spores/m-3 in either of the aerobiomes. The influence of meteorological parameters on Cladosporium and temperature on Poaceae was explored. A table was designed that clarified the ranges for Cladosporium and a formula was adapted for predicting the start of the grass season. Significant decreases in the Poaceae concentrations in both aerobiomes were observed and discussed with reference to Global Warming. Conclusions: The differences in the pollen spectra and seasonality of the selected allergenic air spora indicate that both aerobiomes should be monitored concurrently for patients who live and work in these different microclimates. Pollen profiles for skin, blood and specific IgE testing panels should be reassessed to include Cupressaceae, Parietaria, Myrica, Pleospora and basidiospores. When patients are recruited for clinical drug trials, their place of residence or work should be within the realm of the aerobiome that is being monitored. Current pollen monitoring programmes should be consulted for immunisation regimes to grass and tree pollen. These findings will be applied to the diagnosis and prescription of immunotherapy in clinical practice.