Browsing by Author "Peter, Jonny"

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    Comparison of same day diagnostic tools including Gene Xpert and unstimulated IFN-γ for the evaluation of pleural tuberculosis: a prospective cohort study
    (BioMed Central, 2014-04-08) Meldau, Richard; Peter, Jonny; Theron, Grant; Calligaro, Greg; Allwood, Brian; Symons, Greg; Khalfey, Hoosain; Ntombenhle, Gina; Govender, Ureshnie; Binder, Anke; van Zyl-Smit, Richard; Dheda, Keertan
    Background: The accuracy of currently available same-day diagnostic tools (smear microscopy and conventional nucleic acid amplification tests) for pleural tuberculosis (TB) is sub-optimal. Newer technologies may offer improved detection. Methods: Smear-microscopy, adenosine deaminase (ADA), interferon gamma (IFN-γ), and Xpert MTB/RIF [using an unprocessed (1 ml) and centrifuged (~20 ml) sample] test accuracy was evaluated in pleural fluid from 103 consecutive patients with suspected pleural TB. Culture for M.tuberculosis and/or histopathology (pleural biopsy) served as the reference standard. Patients were followed prospectively to determine their diagnostic categorisation. Results: Of 93 evaluable participants, 40 had definite-TB (reference positive), 5 probable-TB (not definite but treated for TB) and 48 non-TB (culture and histology negative, and not treated for TB). Xpert MTB/RIF sensitivity and specificity (95% CI) was 22.5% (12.4 - 37.6) and 98% (89.2 - 99.7), respectively, and centrifugation did not improve sensitivity (23.7%). The Xpert MTB/RIF internal positive control showed no evidence of inhibition. Biomarker specific sensitivity, specificity, PPV, and NPVs were: ADA (48.85 IU/L; rule-in cut-point) 55.3% (39.8 - 69.9), 95.2% (83.9 - 98.7), 91.4 (73.4 - 95.4), 69.7% (56.7 - 80.1); ADA (30 IU/L; clinically used cut-point) 79% (63.7 - 89), 92.7% (80.6 - 97.5), 91.0 (73.4 - 95.4), 82.7% (69.3 - 90.1); and IFN-γ (107.7 pg/ml; rule-in cut-point) 92.5% (80.2 - 97.5), 95.9% (86.1 - 98.9), 94.9% (83.2 - 98.6), 93.9% (83.5 - 97.9), respectively (IFN-γ sensitivity and NPV better than Xpert [p < 0.05] and rule-in ADA [p < 0.05]). Conclusion: The usefulness of Xpert MTB/RIF to diagnose pleural TB is limited by its poor sensitivity. IFN-γ is an excellent rule-in test and, compared to ADA, has significantly better sensitivity and rule-out value in a TB-endemic setting.
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    Correlation of mycobacterium tuberculosis specific and non-specific quantitative Th1 T-cell responses with bacillary load in a high burden setting
    (Public Library of Science, 2012) Theron, Grant; Peter, Jonny; Lenders, Laura; van Zyl-Smit, Richard; Meldau, Richard; Govender, Ureshnie; Dheda, Keertan
    BACKGROUND: Measures of bacillary load in patients with tuberculosis (TB) may be useful for predicting and monitoring response to treatment. The relationship between quantitative T-cell responses and mycobacterial load remains unclear. We hypothesised that, in a HIV-prevalent high burden setting, the magnitude of mycobacterial antigen-specific and non-specific T-cell IFN-γ responses would correlate with (a) bacterial load and (b) culture conversion in patients undergoing treatment. METHODS: We compared baseline (n = 147), 2 (n = 35) and 6 month (n = 13) purified-protein-derivative (PPD) and RD1-specific (TSPOT.TB and QFT-GIT) blood RD1-specific (TSPOT.TB; QFT-GIT) responses with associates of sputum bacillary load in patients with culture-confirmed TB in Cape Town, South Africa. RESULTS: IFN-γ responses were not associated with liquid culture time-to-positivity, smear-grade, Xpert MTB/RIF-generated cycle threshold values or the presence of cavities on the chest radiograph in patients with culture-confirmed TB and irrespective of HIV-status. 2-month IGRA conversion rates (positive-to-negative) were negligible [<11% for TSPOT.TB (3/28) and QFT-GIT (1/29)] and lower compared to culture [60% (21/35); p<0.01]. CONCLUSIONS: In a high burden HIV-prevalent setting T-cell IFN-γ responses to M. tuberculosis- specific and non-specific antigens do not correlate with bacillary load, including Xpert MTB/RIF-generated C T values, and are therefore poorly suited for monitoring treatment and prognostication.
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    High frequency of resistance, lack of clinical benefit, and poor outcomes in capreomycin treated South african patients with extensively drug-resistant tuberculosis
    (Public Library of Science, 2015) Pietersen, Elize; Peter, Jonny; Streicher, Elizabeth; Sirgel, Frik; Rockwood, Neesha; Mastrapa, Barbara; Te Riele, Julian; Davids, Malika; van Helden, Paul; Warren, Robin; Dheda, Keertan
    BACKGROUND: There are limited data about the epidemiology and treatment-related outcomes associated with capreomycin resistance in patients with XDR-TB. Capreomycin achieves high serum concentrations relative to MIC but whether capreomycin has therapeutic benefit despite microbiological resistance remains unclear. METHODS: We reviewed the susceptibility profiles and outcomes associated with capreomycin usage in patients diagnosed with XDR-TB between August 2002 and October 2012 in two provinces of South Africa. Patients whose isolates were genotypically tested for capreomycin resistance were included in the analysis. RESULTS: Of 178 XDR-TB patients 41% were HIV-infected. 87% (154/178) isolates contained a capreomycin resistance-conferring mutation [80% (143/178) rrs A1401G and 6% (11/178) were heteroresistant (containing both the rrs A1401G mutation and wild-type sequences)]. Previous MDR-TB treatment, prior usage of kanamycin, or strain type was not associated with capreomycin resistance. 92% (163/178) of XDR-TB patients were empirically treated with capreomycin. Capreomycin resistance decreased the odds of sputum culture conversion. In capreomycin sensitive and resistant persons combined weight at diagnosis was the only independent predictor for survival (p=<0.001). By contrast, HIV status and use of co-amoxicillin/clavulanic acid were independent predictors of mortality (p=<0.05). Capreomycin usage was not associated with survival or culture conversion when the analysis was restricted to those whose isolates were resistant to capreomycin. CONCLUSION: In South Africa the frequency of capreomycin conferring mutations was extremely high in XDR-TB isolates. In those with capreomycin resistance there appeared to be no therapeutic benefit of using capreomycin. These data inform susceptibility testing and the design of treatment regimens for XDR-TB in TB endemic settings.
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    How Infection and Vaccination Are Linked to Acute and Chronic Urticaria: A Special Focus on COVID-19
    (Multidisciplinary Digital Publishing Institute, 2023-07-20) Kocatürk, Emek; Muñoz, Melba; Elieh-Ali-Komi, Daniel; Criado, Paulo Ricardo; Peter, Jonny; Kolkhir, Pavel; Can, Pelin; Wedi, Bettina; Rudenko, Michael; Gotua, Maia; Ensina, Luis Felipe; Grattan, Clive; Maurer, Marcus
    Since more than a century ago, there has been awareness of the connection between viral infections and the onset and exacerbation of urticaria. Our knowledge about the role of viral infection and vaccination in acute and chronic urticaria improved as a result of the COVID-19 pandemic but it has also highlighted knowledge gaps. Viral infections, especially respiratory tract infections like COVID-19, can trigger the onset of acute urticaria (AU) and the exacerbation of chronic urticaria (CU). Less frequently, vaccination against viruses including SARS-CoV-2 can also lead to new onset urticaria as well as worsening of CU in minority. Here, with a particular focus on COVID-19, we review what is known about the role of viral infections and vaccinations as triggers and causes of acute and chronic urticaria. We also discuss possible mechanistic pathways and outline the unmet needs in our knowledge. Although the underlying mechanisms are not clearly understood, it is believed that viral signals, medications, and stress can activate skin mast cells (MCs). Further studies are needed to fully understand the relevance of viral infections and vaccinations in acute and chronic urticaria and to better clarify causal pathways.
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    Patients with severe cutaneous adverse drug reactions have extremely high hair cortisol concentrations that do not correlate with presence of depression.
    (2024) Zitha, Eddy; Lehloenya, Rannakoe; Khumalo, Nala ; Peter, Jonny
    Background: Hair cortisol concentrations (HCC) +/- DHEA, a depression and stress biomarker has not been studied in severe cutaneous adverse drug reactions (SCAR). Objective: To determine DHEA/HCC correlation with SCAR-associated depression and compare the ratio with published values. Methods: Depression was assessed using M.I.N.I. and DHEA/HCC measured in epidermal necrolysis (EN) and DRESS patients at a South African tertiary hospital. PubMed search was conducted for publications documenting DHEA/HCC. Results: 22/37 participants enrolled were depressed, significantly higher in EN than DRESS. HCC, DHEA or DHEA/HCC were not different between SCAR; depressed versus non-depressed; and presence versus absence of suicidal ideation. DHEA/HCC was unaffected by HIV or TB status. HCC was high in all SCAR patients, regardless of gender. HCC in SCAR was extremely high compared to published healthy controls [309.33 (28.9 - 1835.7) vs. 46.1 (17.7 - 153.2), p = <0.01]; depressed subjects [1349.67 (SD 1935.59) vs. 7.26 (SD 0.47), p = <0.01] and depressed HIV positive males [1479.61 (SD 2313.74) vs. 18.02 (SD 9.37), p =0.0003]. Conclusions: HCC was high and sustained in SCAR irrespective of HIV, TB, or depression status. No association existed between DHEA/HCC ratio and depression. Sustained high cortisol levels potentially impact long-term SCAR-associated outcomes.
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    Patients with severe cutaneous adverse drug reactions have extremely high hair cortisol concentrations that do not correlate with presence of depression.
    (2024) Zitha, Eddy; Lehloenya, Rannakoe; Khumalo Nala &; Peter, Jonny
    Background: Hair cortisol concentrations (HCC) +/- DHEA, a depression and stress biomarker has not been studied in severe cutaneous adverse drug reactions (SCAR). Objective: To determine DHEA/HCC correlation with SCAR-associated depression and compare the ratio with published values. Methods: Depression was assessed using M.I.N.I. and DHEA/HCC measured in epidermal necrolysis (EN) and DRESS patients at a South African tertiary hospital. PubMed search was conducted for publications documenting DHEA/HCC. Results: 22/37 participants enrolled were depressed, significantly higher in EN than DRESS. HCC, DHEA or DHEA/HCC were not different between SCAR; depressed versus non-depressed; and presence versus absence of suicidal ideation. DHEA/HCC was unaffected by HIV or TB status. HCC was high in all SCAR patients, regardless of gender. HCC in SCAR was extremely high compared to published healthy controls [309.33 (28.9 - 1835.7) vs. 46.1 (17.7 - 153.2), p = <0.01]; depressed subjects [1349.67 (SD 1935.59) vs. 7.26 (SD 0.47), p = <0.01] and depressed HIV positive males [1479.61 (SD 2313.74) vs. 18.02 (SD 9.37), p =0.0003]. Conclusions: HCC was high and sustained in SCAR irrespective of HIV, TB, or depression status. No association existed between DHEA/HCC ratio and depression. Sustained high cortisol levels potentially impact long-term SCAR-associated outcomes.
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    Psychological distress and its relationship with non-adherence to TB treatment: a multicentre study
    (Biomed Central Ltd, 2015) Theron, Grant; Peter, Jonny; Zijenah, Lynn; Chanda, Duncan; Mangu, Chacha; Clowes, Petra; Rachow, Andrea; Lesosky, Maia; Hoelscher, Michael; Pym, Alex; Mwaba, Peter; Mason, Peter; Naidoo, Pamela; Pooran, Anil; Sohn, Hojoon; Pai, Madhukar; Stein, Dan
    BACKGROUND:The successful cure of tuberculosis (TB) is dependent on adherence to treatment. Various factors influence adherence, however, few are easily modifiable. There are limited data regarding correlates of psychological distress and their association with non-adherenceto anti-TB treatment. METHODS: In a trial of a new TB test, we measured psychological distress (K-10 score), TB-related health literacy, and morbidity (TBscore), prior to diagnosis in 1502 patients with symptoms of pulmonary TB recruited from clinics in Cape Town (n = 419), Harare (n = 400), Lusaka (n = 400), Durban (n = 200), and Mbeya (n = 83). Socioeconomic, demographic, and alcohol usage-related data were captured. Patients initiated on treatment had their DOTS cards reviewed at two-and six-months. RESULTS: 22 %(95 % CI: 20 %, 25 %) of patients had severe psychological distress (K-10 [greater than or equal to] 30). In a multivariable linear regression model, increased K-10 scorewas independently associated with previous TB [estimate (95 % CI) 0.98(0.09-1.87); p = 0.0304], increased TBscore [1(0.80, 1.20); p <0.0001], and heavy alcohol use [3.08(1.26, 4.91); p = 0.0010], whereas male gender was protective [-1.47(2.28, 0.62); p = 0.0007]. 26 % (95 % CI: 21 %, 32 %) of 261 patients with culture-confirmed TB were non-adherent. In a multivariable logistic regression modelfor non-adherence, reduced TBscore [OR (95 % CI) 0.639 (0.497, 0.797); p = 0.0001], health literacy score [0.798(0.696, 0.906); p = 0.0008], and increased K-10 [1.082(1.033, 1.137); p = 0.0012], and heavy alcohol usage [14.83(2.083, 122.9); p = 0.0002], were independently associated. Culture-positive patients with aK-10 score[greater than or equal to] 30 were more-likely to be non-adherent (OR = 2.290(1.033-5.126); p = 0.0416]. CONCLUSION: Severe psychological distress is frequent amongst TB patients in Southern Africa. Targeted interventions to alleviate psychological distress, alcohol use, and improve health literacy in newly-diagnosed TB patients could reduce non-adherenceto treatment.
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    Test characteristics and potential impact of the urine LAM lateral flow assay in HIV-infected outpatients under investigation for TB and able to self-expectorate sputum for diagnostic testing
    (BioMed Central Ltd, 2015) Peter, Jonny; Theron, Grant; Chanda, Duncan; Clowes, Petra; Rachow, Andrea; Lesosky, Maia; Hoelscher, Michael; Mwaba, Peter; Pym, Alex; Dheda, Keertan; For the TB-NEAT team
    BACKGROUND: The commercially available urine LAM strip test, a point-of-care tuberculosis (TB) assay, requires evaluation in a primary care setting where it is most needed. There is currently inadequate data to guide implementation in TB and HIV-endemic settings. METHODS: Adult HIV-infected outpatients with suspected pulmonary TB able to self-expectorate sputum from four primary clinics in South Africa, Zambia and Tanzania underwent diagnostic evaluation [sputum smear microscopy, Xpert-MTB/RIF, and culture (reference standard)] as part of a prospective parent study. Urine LAM testing (grade-2 cut-point) was performed on archived samples. Performance characteristics of LAM alone or in combination with sputum--based diagnostics were evaluated. Potential impact on 2 and 6-month morbidity (TBscore), patient dropout rates, and prognosis (death/ loss to follow-up) were evaluated. RESULTS: Among 583 participants with suspected TB that were HIV-infected or refused testing, the overall LAM sensitivity (95 % CI; n/N) and in the CD4[less than or equal to]100 cells/mm 3 sub-group was 22.7 % (16.6-28.7; 41/181) and 30.4 % (17.1-43.7; 14/46), respectively. Overall specificity was 93.0 % (90.5-95.6; 361/388). Amongst culture-positive TB cases, adjunctive LAM testing did not improve the sensitivity of either sputum Xpert-MTB/RIF [78.2 % (69.8-86.7; 72/92) versus 76.1 % (67.4-84.8; 70/92), p=0.7] or smear-microscopy [56.2 % (45.9-66.5; 50/89) versus 43.8 % (33.5-54.1; 39/89), p=0.1). Clinic-based LAM, as an adjunct to either smear microscopy or Xpert MTB/RIF same-day testing, would neither have decreased patient dropout, nor increased same-day treatment initiation in this clinical setting where same-day chest radiography was available. LAM positivity was associated with 6-month lost-to-follow-up/death (AOR 4.4; p=0.002) but not TBscore (at baseline or change in TBscore 2-months post-treatment) (p=0.17). CONCLUSIONS: In African HIV-TB co-infected outpatients able to self-expectorate sputum LAM had limited sensitivity even at low CD4 counts, and offered no significant incremental diagnostic yield over Xpert-MTB/RIF or smear microscopy. In primary care clinics with chest radiography and where empiric TB treatment is common, LAM seems unlikely to improve rates of same-day treatment initiation and patient dropout, however, the ability of LAM to identify patients at high risk of death or lost-to-follow-up may offer important prognostic value.
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    The utility of a shortened palliative care screening tool to predict death within 12 months – a prospective observational study in two south African hospitals with a high HIV burden
    (2019-11-13) Raubenheimer, Peter J; Day, Cascia; Abdullah, Faried; Manning, Katherine; Cupido, Clint; Peter, Jonny
    Abstract Background Timely identification of people who are at risk of dying is an important first component of end-of-life care. Clinicians often fail to identify such patients, thus trigger tools have been developed to assist in this process. We aimed to evaluate the performance of a identification tool (based on the Gold Standards Framework Prognostic Indicator Guidance) to predict death at 12 months in a population of hospitalised patients in South Africa. Methods Patients admitted to the acute medical services in two public hospitals in Cape Town, South Africa were enrolled in a prospective observational study. Demographic data were collected from patients and patient notes. Patients were assessed within two days of admission by two trained clinicians who were not the primary care givers, using the identification tool. Outcome mortality data were obtained from patient folders, the hospital electronic patient management system and the Western Cape Provincial death registry which links a unique patient identification number with national death certificate records and system wide electronic records. Results 822 patients (median age of 52 years), admitted with a variety of medical conditions were assessed during their admission. 22% of the cohort were HIV-infected. 218 patients were identified using the screening tool as being in the last year of their lives. Mortality in this group was 56% at 12 months, compared with 7% for those not meeting any criteria. The specific indicator component of the tool performed best in predicting death in both HIV-infected and HIV-uninfected patients, with a sensitivity of 74% (68–81%), specificity of 85% (83–88%), a positive predictive value of 56% (49–63%) and a negative predictive value of 93% (91–95%). The hazard ratio of 12-month mortality for those identified vs not was 11.52 (7.87–16.9, p < 0.001). Conclusions The identification tool is suitable for use in hospitals in low-middle income country setting that have both a high communicable and non-communicable disease burden amongst young patients, the majority under age 60.