Browsing by Author "Verburgh, Estelle"

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    A comparative cost analysis of the pathway to diagnosing lymphoma in a tertiary hospital, Western Cape, South Africa
    (2022) Fareed-Brey, Waarisa; Cunnama, Lucy; Verburgh, Estelle; Antel, Katherine
    Cancer is one of the leading causes of death before the age of 70 in 91 countries (out of 172) with a noted increasing incidence of cancer and mortality (Bray et al., 2018). In tuberculosis (TB) endemic areas, a fine needle aspirate (FNA) is often used as the diagnostic tool of choice when trying to understand the underlying cause of lymphadenopathy (LAP), which can lead to delayed diagnosis of lymphoma (Antel et al., 2019). A significant gap exists in the lack of costing of the diagnostic pathway to diagnosing lymphoma. The study aimed to cost the diagnostic pathways, namely FNA, core-needle biopsy (CNB), and surgical excision biopsy (SEB) using secondary data collected in 2018 (February until October) at Groote Schuur Hospital (GSH), within the tertiary level hospital outpatient clinics to informed the patient pathways. The overall purpose of the study was to inform policy-making decisions and process guidelines. A cost analysis study was conducted using a combination of ingredients-based costing and top-down costing from a provider's perspective. Annual costs were calculated and inflated to 2021 South African Rands using the consumer price index (CPI) and converted to United States American Dollars. More CNBs are currently being performed than SEBs at GSH, and when pathways were followed, CNB initiated pathways (US $567) were less costly compared to FNA initiated pathways (US$ 877). The cost of the CNB procedure varied with the use of a single-use biopsy gun and the multi-use Magnum BARD gun. CNB provides an alternate choice to SEB and based on the study conducted, CNB pathways are less costly. The main cost driver for all three procedures was personnel and this could be decreased by task shifting and training of medical officers and interns.
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    CD68-positive tumour associated macrophages, PD-L1 expression, and EBV latent infection in a high HIV-prevalent South African cohort of Hodgkin lymphoma patients
    (2021) Antel, Katherine Rae; Verburgh, Estelle
    Background and aims A higher proportion of CD68-positive tumour associated macrophages (TAMs) has been associated with poorer outcomes in HIV-negative patients with Hodgkin lymphoma (HL), but whether this is true in HIV positive patients with HL is not known. In this study, we investigated the number of CD68-positive TAMs and expression of programmed cell death-ligand 1 (PD-L1) in lymph node specimens from HL patients and correlated expression with clinical features (HIV status, disease severity and survival) and histopathological features (EBV latent positivity and subtype of HL). Methods We stained archived lymph node specimens from 77 patients diagnosed with HL for CD68 and PD-L1. Stains were graded as: CD68 low (≤25%), CD68 high (>25%), PD-L1 low (≤50%), and PD-L1 high (>50%). Expression levels were correlated with the clinical and histopathological features using bivariate and multivariate analyses. Survival was analysed by overall and progression-free survival. Results Thirty-four of the 77 included patients (44%) were HIV-positive. EBV latency was detected in 97% of HIV positive HL patients and in 14% of HIV-negative HL patients. A high CD68 score was associated with lower median haemoglobin levels (9.4 vs 11.4 g/dL; p=0.02), platelet numbers (262 vs 424 cells ×109 /L; p=0.01), and lymphocyte numbers (0.99 vs 1.70 cells ×109 /L, p=0.01) and a trend towards advanced disease (international prognostic score ≥4; hazard ratio 2.4; confidence interval 0.89–6.47; p=0.08). HIV status did not affect CD68 or PD-L1 expression. A higher proportion of CD68-positive TAMs was found in samples that were EBV-positive. HIV positivity and EBV negativity correlated with poorer survival. CD68 and PD-L1 expression were not predictive of survival. Conclusions High CD68 expression was associated with EBV positivity but not HIV positivity and did not predict adverse outcomes. PD-L1 expression was unaffected by HIV status or EBV positivity and did predict adverse outcomes.
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    Correction to: Diagnostic accuracy of the Xpert MTB/Rif Ultra for tuberculosis adenitis
    (2020-03-02) Antel, Katherine; Oosthuizen, Jenna; Malherbe, Francois; Louw, Vernon J; Nicol, Mark P; Maartens, Gary; Verburgh, Estelle
    After publication of the original article [1], we were notified that there is a mistake in the article note.
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    Developing a validated framework for a Patient Blood Management (PBM) toolkit appropriate for the South African healthcare context
    (2025) Rambiritch, Vanitha; Louw, Vernon; Verburgh, Estelle
    Patient blood management (PBM) is a patient-centred, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood while promoting patient safety and empowerment. The historic inappropriate use of risk-associated blood transfusions in treating anaemia and blood loss needs to be replaced with evidence-based PBM practices. This study was aimed at developing a validated framework of cost- effective, feasible, evidence-based PBM measures to guide the development of a toolkit that can support PBM implementation in hospitals, and assist clinicians in optimising the care of patients and minimising inappropriate blood transfusions. A mixed-methods research design was applied. One-on-one semi-structured interviews with PBM champion participants in the qualitative phase provided insight into the challenges and barriers to PBM implementation in South Africa, and the educational and clinical practice guiding tools needed to support implementation. The thematically analysed data from the literature and the interviews were used to develop statements that were subsequently rated by a panel of PBM experts in a three-round Delphi survey in the semi-quantitative phase of the study. Consensus was gained on the tools deemed essential for primary, secondary, and tertiary-level hospitals in South Africa, including the educational needs and overall barriers that need to be addressed. The findings revealed four broad categories of tools: (i) definitional tools to contextualise PBM and frame the importance of its implementation in South Africa; (ii) policy and procedural tools to guide evidence-based clinical practices, taking into account resource and infrastructure capabilities in the various levels of hospitals; (iii) education and training tools directed at bridging PBM educational gaps among doctors, nurses, healthcare leadership stakeholders, and patients; and (iv) planning, assessment and evaluation tools to assist hospitals with planning and implementing PBM interventions. The framework for a PBM toolkit as the outcome of this research contributes significant value by proposing an actionable, evidence-based model that adapts international PBM principles to resource-limited settings, promoting safer and more effective patient care while minimising inappropriate blood transfusions. Education supported by the right mix of clinical practice guiding tools informed by the PBM toolkit framework can make PBM implementation possible in South Africa and beyond.
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    Diagnostic accuracy of the Xpert MTB/Rif Ultra for tuberculosis adenitis
    (2020-01-13) Antel, Katherine; Oosthuizen, Jenna; Malherbe, Francois; Louw, Vernon J; Nicol, Mark P; Maartens, Gary; Verburgh, Estelle
    Abstract Background The WHO recently recommended the new Xpert MTB/RIF Ultra assay (Ultra) instead of the Xpert MTB/RIF assay because Ultra has improved sensitivity. We report the diagnostic accuracy of Ultra for tuberculous adenitis in a tuberculosis and HIV endemic setting. Methods We obtained fine-needle aspirates (FNA) and lymph node tissue by core-needle biopsy in adult patients with peripheral lymphadenopathy of >20 mm. Ultra and mycobacterial culture were performed on FNA and tissue specimens, with histological examination of tissue specimens. We assessed the diagnostic accuracy of Ultra against a composite reference standard of ‘definite tuberculosis’ (microbiological criteria) or ‘probable tuberculosis’ (histological and clinical criteria). Results We prospectively evaluated 99 participants of whom 50 were HIV positive: 21 had ‘definite tuberculosis’, 15 ‘probable tuberculosis’ and 63 did not have tuberculosis (of whom 38% had lymphoma and 19% disseminated malignancy). Using the composite reference standard the Ultra sensitivity on FNA was 70% (95% CI 51–85; 21 of 30), and on tissue was 67% (45–84; 16/24) these were far superior to the detection of acid-fast bacilli on an FNA (26%; 7/27); AFB on tissue (33%; 8/24); or tissue culture (39%; 9/23). The detection of granulomas on histology had high senstivity (83%) but the lowest specficity. When compared with culture the Ultra on FNA had a sensitvity of 78% (40-97; 7/9) and tissue 90% (55-100; 9/10). Conclusions Ultra performed on FNA or tissue of a lymph node had good sensitivity and high specificity. Ultra had a higher yield than culture and has the advantage of being a rapid test. Ultra on FNA would be an appropriate initial investigation for lymphadenopathy in tuberculosis endemic areas followed by a core biopsy for histopathology with a repeat Ultra on tissue if granulomas are present.
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    Evaluation of prognostic risk factors at diagnosis and treatment outcomes in adult patients with early-stage hodgkin lymphoma in Cape Town, South Africa
    (2024) Dawood, Shakira; Verburgh, Estelle; Mohamed, Zainab
    The National Comprehensive Cancer Network (NCCN) Guidelines are a recognized standard for prognostic staging in Hodgkin Lymphoma (HL). We aimed to determine if the NCCN staging system and its individual risk factors correlated with patient treatment outcomes in early-stage adult classical HL (cHL) patients. This retrospective study included 70 patients diagnosed with and treated for early-stage (stage I and II) cHL from 2010 to 2022, at Groote Schuur Hospital Radiation Oncology and Clinical Haematology Units. NCCN unfavourable risk factors assessed were mediastinal mass ratio, presence of bulky disease, B-symptoms, number of nodal regions involved and erythrocyte sedimentation rate. Patients were divided into early-stage favourable (no unfavourable factors) and early-stage unfavourable (any unfavourable factors). Kaplan-Meier curves and log-rank tests were used to compare treatment outcomes between groups. The median age at diagnosis was 35 years and 50% of the patients were male. Most patients had stage II disease (86%) and were classified as unfavourable (76%). During the study period, 6 patients died (9%) all of whom had stage II unfavourable disease. The 5-year overall survival for the favorable and unfavourable groups was similar (94% vs. 90%, P=0.599). Progression free survival at 5 years was also similar (83% vs. 88%, P=0.984). This study demonstrates excellent 5-year survival outcomes in early-stage cHL patients. These findings are comparable with those in higher income countries and were not affected by HIV status or unfavourable risk factors. This highlights the importance of early diagnosis and treatment while patients still have early-stage disease
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    Feature detection in ultrasound images for computer aided diagnosis of Hodgkin's Lymphoma
    (2021) Dawood, Tareen; Mutsvangwa, Tinashe; Verburgh, Estelle
    The varying clinical presentation of Hodgkin's lymphoma (HL) poses a diagnostic challenge in South Africa, as the clinical picture of this lymphoma overlaps with prevalent comorbidities such as tuberculosis (TB) and the Human Immuno-Deficiency Virus (HIV). HIV infection additionally increases the risk of developing HL. These factors motivate for the need to investigate the role of imaging modalities in the diagnostic pathway of HL. The goal of this project was to develop and evaluate an automated framework for improving diagnostic imaging interpretability of ultrasound for HL diagnosis in a HIV TB endemic environment. To achieve this, a precise abdominal ultrasound protocol was developed with clinical guidance. The specific frames in the protocol were used to detect several image biomarkers of clinical interest: splenic enlargement (splenomegaly), splenic lesions, splenic microabscesses, abdominal lymph node enlargement, ascites, and effusions (pleural and pericardial). The developed protocol provided a novel guideline to identify an abnormality from the available ultrasound images. A secondary outcome of the protocol was the development of a prospective guide to image Hodgkin's lymphoma patients using ultrasound, however further testing and evaluation is required to validate its use. Image processing techniques were then applied to identified frames, and geometrical and textural features extracted, to develop an automated abnormality characterisation framework. A total of 36 features were extracted and used to characterise each abnormality. Thereafter, an automated algorithm was used to characterise and classify Hodgkin's lymphoma. A support vector machine model was built, with two experiments performed to evaluate the model. The model achieved a maximum training accuracy of 83%, similar in performance to support vector machine classification models used in medical applications. Noticeably the classification accuracy increased favourably when specific abnormalities were assessed: an enlarged spleen, splenic micro abscesses, ascites, pleural effusions, and pericardial effusions. This may indicate that these specific abnormalities are sufficient to differentiate patients with and without Hodgkin's lymphoma but understanding the reasoning for the decision taken by the system requires further investigation. In this study we show how image processing and automated classification techniques when applied to ultrasound images, have the potential to improve the differential diagnostic pathway of HL. Further evaluation using a larger dataset is planned, to validate and implement these findings in a strained healthcare setting.
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    Implementation of the JAK2V617F mutation analysis in the pathway of suspected myeloproliferative neoplasms in Groote Schuur Hospital
    (2016) Poulet, Erma; Verburgh, Estelle
    We studied the implementation of JAK2 mutation analysis in conjunction with the World Health Organisation (WHO) guidelines in the pathway to MPN diagnosis in 279 patients presenting with one of three clinical scenarios: erythrocytosis, OR leukocytosis and/or thrombocytosis and/or splenomegaly; OR patients with thrombosis without cytoses. Patients were investigated for MPN and managed in the haematology clinic of Groote Schuur Hospital. We studied the association of clinical and laboratory variables with clonal vs non-clonal diagnoses. In 120/297 patients MPN was confirmed: Polycythemia vera (PV), (n=51, 100% JAK2 mutated); essential thrombocytosis, (n=41, 42% JAK2 mutated); primary myelofibrosis (n=28, 57% JAK2 mutated). The 2016 WHO haemoglobin/haematocrit thresholds in PV were validated. Idiopathic erythrocytosis (IE) found in 44 patients. Bone marrow histology, but not serum EPO level, was essential to differentiate between clonal and non-clonal erythrocytosis. Both PV and IE patients complied with the criteria of absolute erythrocytosis on peripheral blood, yet nuclear red cell mass identified critical differences between clonal and non-clonal erythrocytosis. No patient venesected for nonclonal erythropoiesis developed thrombocytosis. JAK2 mutation analysis applied with the WHO diagnostic algorithm efficiently differentiated true clonal myeloproliferation from reactive cytoses. Lifestyle and metabolic factors such as smoking and thrombosis were not associated with either clonal or non-clonal erythrocytosis, and were equally present in mutated and unmutated essential thrombocytosis.
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    Lymphoma: Understanding the diagnostic challenges and improving outcomes in a TBand HIV-endemic area
    (2021) Antel, Katherine Rae; Verburgh, Estelle; Maartens, Gary; Louw, Vernon
    Background and aims Diagnosing lymphoma can be challenging: even in the best-resourced settings, lymphoma diagnosis may be delayed owing to the insidious onset of symptoms and/or difficulties in obtaining lymph node biopsy for diagnosis. In TB-endemic countries the diagnostic challenges in lymphoma may be further compounded by symptoms overlapping with those of TB and by resource limitations that may impede obtaining a diagnostic biopsy. New lymphoma diagnostic modalities, including the use of nextgeneration sequencing, are evolving rapidly and informing both prognosis and therapy in the field of lymphoma. These modalities of testing are likely to mean that less tissue is needed for assessment, or even that diagnosis can be made from peripheral blood. In this thesis we identify and describe local barriers in the diagnosis of lymphoma; and describe methods used to decrease the time-to-diagnosis of lymphoma and to subtype the most common lymphoma, diffuse large B-cell lymphoma (DLBCL). Our four main aims have been to: (i) Describe the pathway to a diagnosis of lymphoma in South Africa, with emphasis on the examination of local barriers to diagnosis (including overlapping symptomatology with TB) by retrospectively studying a cohort of patients with lymphoma. (ii) Investigate the diagnostic utility of the newest TB diagnostic test (the Xpert MTB/RIF Ultra); and apply this test in a diagnostic algorithm for lymphadenopathy of unknown aetiology, both on a fine-needle aspirate (FNA) from a lymph node and on tissue obtained by corebiopsy. (iii) Investigate whether a rapid-access lymph node biopsy clinic that used a core-biopsy method for lymph node biopsy was able to reduce the time-to-diagnosis of lymphoma, and to subtype accurately lymphomas for which subtyping is clinically relevant. (iv) Describe the subtype of DLBCL by HIV status using an immunohistochemical algorithm, in order both to describe the pattern of DLBCL by the most current diagnostic classification and to lay the foundations for further genetic work potentially capable of identifying mutations that could be used for genetic testing in DLBCL locally. Methods Four cohorts were analysed: (i) In the first, a group of 163 patients with lymphoma, the time-to-diagnosis and factors causing a delay in diagnosis were analysed. (ii) In the second, 99 patients with lymphadenopathy of unknown cause were recruited and the sensitivity and specificity of the Ultra were analysed using both fine-needle aspirate (FNA) and a core-biopsy technique. (iii) In the third cohort (n = 130), which included the second cohort of n = 99), outcomes from a rapid-access lymph node biopsy clinic – which used the core-biopsy method for the diagnosis of lymphoma – were analysed. (iv) In the fourth cohort (n = 182), the tissue of patients with DLBCL was analysed based on further immunohistochemical stains using the Hans algorithm in order to determine the molecular subtypes of DLBCL and determine their effect on prognosis. Results (i) In the first cohort ((n = 163), 29% HIV-infected), which was studied retrospectively, it took a median of 7 weeks for the diagnosis of lymphoma to be made from the time the patient sought medical attention. The longest time delay was in the healthcare practitioner interval (time from first healthcare visit to diagnostic biopsy). On multivariable logistic regression analysis, diagnostic delay > 6 weeks was associated with late-stage disease at presentation (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.1–5.2) and a diagnosis of Hodgkin lymphoma (OR 3.0, 95% CI 1.1–8.0). HIV status was not associated with diagnostic delay (OR 0.9, 95% CI 0.3–2.2). The median time to diagnosis for patients on TB treatment was a month longer than for patients not on TB treatment. However, this was not statistically significant owing likely to a small sample size (n = 16, p = 0.28). (ii) In the second cohort, the diagnostic utility of the Ultra on lymph node aspirate and tissue were prospectively evaluated. The Ultra was found to be a sensitive and specific test for diagnosing TB of the lymph node. When compared with culture, the Ultra on aspirate had a sensitivity of 78% (40–97; 7/9) and on tissue 90% (55–100; 9/10). When using a composite reference score that combined both ‘definite TB' (culture positive) and ‘probable TB' (histological and clinical criteria), the Ultra was superior to currently used methods of diagnosing TB of the lymph node, including the detection of AFBs from an aspirate or on tissue biopsy or tissue culture (which had sensitivities of 26%, 33% and 39% respectively). The detection of granulomas on histology had high sensitivity (83%) but the lowest specificity. (iii) In the third cohort, which was studied prospectively, we obtained two important outcomes. Firstly, we showed that a rapid-access lymph node biopsy clinic was able to decrease the time-to-diagnosis of lymphoma when compared with that of cohort one (the historical cohort) to a diagnostic interval of 13.5 days compared with 48 days (p = 0.002). Secondly, the core-biopsy was able to detect lymphoma with a high rate of accuracy. The first-attempt core-biopsy was able to diagnose lymphoma in 84% of cases, and provided sufficient tissue to subtype lymphoma in a high proportion of the lymphoma cases (27/30, 90%). (iv) In the fourth, retrospectively evaluated cohort of patients with DLBCL (n = 181, 51 HIVpositive), there was a similar distribution of germinal centre (GC) and activated B cell (ABC) subtypes in the HIV-infected and HIV-uninfected groups. In contrast to what is reported in HIV-negative DLBCL literature, there were no statistically significant differences in overall survival by DLBCL subtype. Moreover, no significant difference in 5-year overall survival was demonstrated between the GCB and ABC subtypes (HR 1.2, 95% CI 0.8–1.9). Patients with HIV infection with a CD4 count of < 150 CD4 cells/mm3 had significantly poorer survival than those with no HIV infection (HR 2.4, 95% CI 1.3–4.1). Conclusions Making a diagnosis of lymphoma in South Africa is challenging. Two of the greatest challenges are overlapping symptomatology with TB and obtaining an adequate lymph node sample. The Ultra test on lymph node tissue is rapid, sensitive and specific; and can be performed on both FNA and tissue obtained through core-biopsy. Making an accurate diagnosis of TB is of critical importance, as TB is the most common cause for enlarged lymph nodes in TB-endemic areas. A reliable TB test on lymph node tissue will enable both an accurate TB diagnosis and the identification of patients who are negative for TB. The latter will require further investigation with a lymph node biopsy (via core needle or excision). As diagnostic testing and methods evolve in the direction of next-generation platforms, it is important to understand the tumour biology in our local setting, and in HIV-lymphoma, in order to be able to apply these new methods. This thesis describes the subtypes and outcomes seen in HIV DLBCL – knowledge that will be important in developing genetic next-generation sequencing methods that are specific to the type of lymphoma to be found in our context (and which may include genetic mutations induced by the Epstein–Barr virus). A clear diagnostic algorithm for the investigation of lymphadenopathy is presented, pulling together the four aims presented at the start of this section. Considering the prevalence of TB in South Africa, the goal is, in the first instance, to diagnose or exclude TB adenitis. In patients who test negative for TB, the goal then becomes to proceed with a diagnostic biopsy and, from our findings, to support the use of core-biopsy. This method, we have demonstrated, is able to provide sufficient tissue for the diagnosis and subtyping of lymphoma.
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    Response and remission after first line corticosteroid therapy in primary ITP
    (2023) Mapimhidze, Danai; Verburgh, Estelle; Bailly, Jenique
    Background: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by an isolated thrombocytopenia of <100 x 109/L in the absence of identifiable secondary causes. Treatment is indicated when the platelet count is <20-30 x 109/L but may be commenced at higher platelet counts when the risk of bleeding is high. Corticosteroids are the backbone of initial treatment of ITP. There is a paucity of data in South Africa on the outcomes of newly diagnosed ITP patients treated with corticosteroids. Objectives: To describe the response, remission and clinical outcomes of newly diagnosed primary ITP patients on first-line corticosteroids. Methods: This was a retrospective cohort study of 68 patients with a new diagnosis of ITP, seen at the Clinical Haematology unit at Groote Schuur Hospital, over a 5-year period (20162020). Demographic and clinical data were obtained from paper and electronic record systems. All participants with secondary causes were excluded. The initial platelet responses to corticosteroids and the final outcomes at last follow up were determined. Initial platelet responses were classified into no response (NR), partial response (PR) and complete response (CR) in accordance with consensus definitions. Remission was defined as maintenance of a CR after being off corticosteroids for at least 6 months. Variables were described by frequencies and percentages or medians and interquartile ranges, as appropriate. Results: The majority of patients were females (88.2%) and the median age at diagnosis was 36 years (IQR 23.0-55.5). Most patients responded to corticosteroids (92.4%) with 74.2% achieving a CR and 18.2% achieving a PR. Only 5 patients failed to respond (7.6%). The median time to achieve CR was 15 (IQR: 8-25) days and the median time to achieve PR was 10.5 days (IQR 8-22). Half of the patients went into remission. Following remission, two patients (6.1%) subsequently relapsed at day 344 and day 777, respectively. Hypertension and/or diabetes were newly diagnosed in 10.6 % of patients. Conclusion: Corticosteroids are effective first line therapy for ITP but are not remission inducing in all patients. For those patients progressing to chronic ITP, there is a need to investigate cost effective treatment. Some patients are at high risk of developing new hypertension and diabetes mellitus on corticosteroids and should be monitored.
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    The determinants and impact of diagnostic delay in lymphoma in a TB and HIV endemic setting
    (2019-04-25) Antel, Katherine; Levetan, Carly; Mohamed, Zainab; Louw, Vernon J; Oosthuizen, Jenna; Maartens, Gary; Verburgh, Estelle
    Background Little is known about the pathway to diagnosis of lymphoma in Sub-Saharan Africa, despite the increased risk of lymphoma in people living with HIV (PLHIV). The challenges of diagnosis in this setting include diagnostic confusion with extrapulmonary tuberculosis (EPTB), which commonly causes lymphadenopathy in PLHIV. Methods We analysed the time to diagnosis and treatment in patients using predetermined time intervals. Univariate and multivariable analyses were performed to determine the relationship between patient and disease-specific variables with delays to diagnosis. We were particularly interested in the impact of HIV, empiric tuberculosis therapy and fine-needle aspirate for cytology (FNAC) in contributing to delay. Results Patients (n = 163), 29% HIV-infected, waited a median of 4 weeks before seeking medical attention. It took a median of 7 weeks for the diagnosis of lymphoma to be made from the time the patient sought medical attention, termed the healthcare practitioner interval. In multivariable logistic regression analysis, diagnostic delay > 6 weeks was associated with late-stage disease (OR 2.3, 95% CI 1.1–5.2) and Hodgkin lymphoma (HL) (OR 3.0, 95% CI 1.1–8.0). HIV status was not associated with diagnostic delay (OR 0.9, 95% CI 0.3–2.2). The median time to diagnosis was a median of 4 weeks longer for patients on tuberculous (TB) therapy (n = 16, p = 0.28) and patients who underwent an FNAC (n = 63, p = 0.04). Where FNAC was performed, it was diagnostic for lymphoma in only 11%. Diagnostic delay was not associated with overall survival. Conclusions Time-to-diagnosis of lymphoma in South Africa was similar to that reported from high-income countries and shows significant periods of delay between the onset of symptoms to diagnosis and treatment. The longest period of delay was in the health practitioner interval. Education regarding the significance of lymphadenopathy for both patients and health care practitioners and appropriate investigative steps preferably by best-practice algorithms specific to TB-endemic areas are needed to shorten the time-to-diagnosis of lymphoma.
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    The diagnostic accuracy of abdominal ultrasound findings in patients evaluated for peripheral lymphadenopathy in a high HIV TB endemic population
    (2023) Adams, Ellouise; Verburgh, Estelle; Antel Katherine
    Background: Extrapulmonary tuberculosis (EPTB) is common among people living with HIV (PLWH). The abdominal ultrasound is an accessible investigation frequently employed to support the diagnosis of EPTB but may lead to misdiagnoses of diseases with overlapping clinical features, such as lymphoma. Objectives: To describe the abdominal ultrasound features and confirmed diagnoses of patients referred to a biopsy clinic with unexplained lymphadenopathy. Method: This was a retrospective descriptive study of patients attending the peripheral lymph node biopsy clinic at Groote Schuur Hospital (GSH) between 2017 and 2020 who had abdominal ultrasound examination while being investigated for unexplained lymphadenopathy. Ultrasound features were compared to the final diagnosis made on the lymph node biopsy. Results: Thirty-four patients were included, most of whom were HIV-infected (59.0%). Approximately one third had a confirmed diagnosis of lymphoma (29%) and approximately one third had a confirmed diagnosis of tuberculosis (32%). Splenic hypoechoic lesions were more common in patients with lymphoma (63.6%) than patients with tuberculosis (45.5%) and malignancy (16.7%). Ascites was equally distributed between patients with tuberculosis (36.4%) and lymphoma (36.4%). The ultrasound report and confirmed diagnoses were in agreement in 40.0% of patients with tuberculosis. Additionally, 36.4% of patients with confirmed lymphoma were suspected to have tuberculosis based on the abdominal ultrasound. Conclusion: Abdominal ultrasound detection of abnormalities such as splenic hypoechoic lesions, lymphadenopathy and ascites/pleural effusion have a differential diagnosis including both tuberculosis and lymphoma, and should be interpreted in conjunction with equally focused diagnostic tests.
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    The diagnostic pathway to a surgical lymph node excision biopsy service in a HIV and TB endemic region in a Western Cape Tertiary Institution
    (2025) Potelwa, Tennis Tomo Camagu; Verburgh, Estelle; Malherbe, Francois
    In the HIV/TB endemic public care setting of the Western Cape, diagnostic consideration of patients with persistent lymphadenopathy is focused towards extra- pulmonary tuberculosis (EPTB), more than other infectious or malignant causes of lymphadenopathy. We investigated patients consecutively referred for lymph node excision at Groote Schuur Hospital for selection of, and results of, laboratory tests performed during the diagnostic pathway and possible impact on diagnostic delay. Eighty-six patients were included, 61 patients (71%) had no previous diagnosis to explain the lymphadenopathy, while 25 patients had a previous diagnosis of a haematological malignancy, cancer or tuberculosis. In the new patient group, EPTB was the commonest diagnostic outcome (24.6%, 15/61), followed by lymphoma (21.3%, 13/61) and cancer (14.8%, 9/61). HIV positive patients constituted 41% (n=25). Median time from presentation with lymphadenopathy to first excision biopsy was 55 days (IQR 22-106). Fine needle aspiration (FNA) cytology of lymphadenopathy was performed in 30/61 (49%) of patients and repeated in a third of these, while smear for AFBs and culture for M. tuberculosis were infrequently performed and GeneXpert MTB/RIF assay on FNA never performed. Furthermore, in the seven patients with a final diagnosis of lymphoma in whom FNA cytology was performed, cytology was not diagnostic of lymphoma. In patients with persistent lymphadenopathy, this study demonstrates how poorly structured diagnostic pathways contribute to unnecessary health care utilisation and diagnostic delay in readily treatable conditions. We need to implement accurate diagnostic pathways for patients with lymphadenopathy in South Africa's healthcare system, thus improving early diagnosis of both EPTB and lymphoma, potentially improving patient outcomes.
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    The international prognostic score and HIV status predict red cell concentrate transfusion needs in Hodgkin lymphoma
    (2025) Simba, Kudakwashe; Verburgh, Estelle
    Despite the burden of anaemia among Hodgkin Lymphoma (HL) patients, data evaluating red cell concentrate transfusion is limited. We retrospectively studied 285 newly diagnosed HL patients who received first-line ABVD treatment at Groote Schuur Hospital, Cape Town. HIV prevalence in the cohort was 39.5% and 74.2% of patients had advanced stage HL. Patient prognosis was scored using the HL International Prognostic Score (IPS-7) and HL IPS-3. Seventy (24.6%) patients were transfused with a median of 2(IQR 1-5) units per patient. Compared to HIV-negative patients, more HIV-positive patients were transfused (14.1% vs 40.4%, P<0.001) and received more units, median 2(IQR 1-3) vs. 3(IQR 2-5), P=0.035. HL IPS-7 (OR 2.1, P<0.001) and HL IPS-3 (OR 2.6, P<0.001) were independently associated with transfusion. HL IPS-7, HL IPS-3 and HIV positivity remained associated with transfusion after adjusting for covariates. For patients with newly diagnosed HL, HL IPS-7, HL IPS-3 and HIV status predicted transfusion.
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    Trends in clinical presentation and treatment outcomes in a South African TTP cohort
    (2024) Vundla, Nokubonga; Verburgh, Estelle; Bailly, Jenique
    Background: HIV is the most common cause of secondary thrombotic thrombocytopenic purpura (TTP) in South Africa. Objectives: To assess the clinical presentations and outcomes of patients treated for HIV-associated and idiopathic TTP. Methods: We conducted a retrospective cohort study of patients consecutively diagnosed with TTP from 2010 to 2020 at Groote Schuur Hospital. Study participants were identified by reviewing patient files and Western Cape Blood Services records. Kaplan-Meier curves and log-rank tests were used to evaluate remission rates overall and, by HIV status and treatment group. Logistic regression models were used to identify predictors of remission and relapse. Results: 139 patients were included, 85.6% of whom were HIV positive. There were no significant differences in the TTP pentad features by HIV status. Most patients achieved remission (71.9%) with an overall median time of 8 days. Remission occurred significantly earlier in those treated with FFPs only, suggesting less severe disease (median=8 days [IQR 6-10]), compared to those requiring the addition of plasma exchange suggesting more severe disease (median=12 days [IQR 8-22]). The overall mortality in the 10-year period was 38.9%, with 10.8% of the surviving patients relapsing after a median of 169 days (IQR 146-281) following the initial TTP event. There were no significant differences in remission status, time to remission, mortality or relapse by HIV status. All HIV positive patients who relapsed had defaulted their antiretroviral therapy (ART). Conclusion: HIV status did not affect patient outcomes in our cohort. ART is important in preventing HIV-associated TTP and relapse. What this study adds: A well-defined demographic of patients with TTP in the ART era in South Africa. Key words: Thrombotic thrombocytopenic purpura, haemolytic anaemia, thrombotic microangiopathy, HIV-associated TTP, ADAMTS13, treatment outcomes, plasma infusion, plasma exchange.