Browsing by Subject "Diagnosis"

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    A cost-effective strategy for primary prevention of acute rheumatic fever and rheumatic heart disease in children with pharyngitis
    (2013) Irlam, James H; Mayosi, Bongani M; Engel, Mark E; Gaziano, Thomas A
    Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in children depends on prompt and effective diagnosis and treatment of pharyngitis at the primary level of care. Cost-effectiveness modeling shows that the most cost-effective strategy for primary prevention in South Africa (SA) is to use a simple symptomatic clinical decision rule (CDR) to diagnose pharyngitis in children presenting at the primary level of care and then to treat them with a single dose of intramuscular penicillin. Treat All and CDR2+ strategies are affordable and simple and miss few cases of streptococcal pharyngitis at the primary level of care. The CDR2+ strategy is the most cost-effective for primary prevention of ARF and RHD in urban SA and should complement primordial and secondary prevention efforts.
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    Culture-confirmed childhood tuberculosis in Cape Town, South Africa: a review of 596 cases
    (Biomed Central Ltd, 2007) Schaaf, H Simon; Marais, Ben; Whitelaw, Andrew; Hesseling, Anneke; Eley, Brian; Hussey, Gregory; Donald, Peter
    BACKGROUND:The clinical, radiological and microbiological features of culture-confirmed childhood tuberculosis diagnosed at two referral hospitals are described. METHODS: Cultures of Mycobacterium tuberculosis from children less than 13 years of age at Tygerberg and Red Cross Children's Hospitals, Cape Town, South Africa, were collected from March 2003 through February 2005. Folder review and chest radiography were performed and drug susceptibility tests done. RESULTS: Of 596 children (median age 31 months), 330 (55.4%) were males. Of all children, 281 (47.1%) were HIV-uninfected, 133 (22.3%) HIV-infected and 182 (30.5%) not tested. Contact with infectious tuberculosis adults was recorded in 295 (49.5%) children. Missed opportunities for chemoprophylaxis were present in 117/182 (64.3%) children less than 5 years of age.Extrathoracic TB was less common in HIV-infected than in HIV-uninfected children (49/133 vs. 156/281; odds ratio 0.50, 95% confidence interval 0.32-0.78). Alveolar opacification (84/126 vs. 128/274; OR 1.85, 95%CI 1.08-3.19) and cavitation (33/126 vs. 44/274; OR 2.28, 95%CI 1.44-3.63) were more common in HIV-infected than in HIV-uninfected children. Microscopy for acid-fast bacilli on gastric aspirates and sputum was positive in 29/142 (20.4%) and 40/125 (32.0%) children, respectively. Sixty-seven of 592 (11.3%) children's isolates showed resistance to isoniazid and/or rifampicin; 43 (7.3%) were isoniazid-monoresistant, 2 (0.3%) rifampicin-monoresistant and 22 (3.7%) multidrug-resistant. Death in 41 children (6.9%) was more common in HIV-infected children and very young infants. CONCLUSION: HIV infection and missed opportunities for chemoprophylaxis were common in children with culture-confirmed TB. With cavitating disease and sputum or gastric aspirates positive for acid-fast bacilli, children may be infectious. Transmission of drug-resistant TB is high in this setting.
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    Current challenges and opportunities in the care of patients with fibrodysplasia ossificans progressiva (FOP): an international, multi-stakeholder perspective
    (2022-04-18) Pignolo, Robert J; Bedford-Gay, Christopher; Cali, Amanda; Davis, Michelle; Delai, Patricia L R; Gonzales, Kristi; Hixson, Candace; Kent, Alastair; Newport, Hope; Robert, Manuel; Scott, Christiaan; Kaplan, Frederick S
    Background Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, disabling genetic disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification of soft and connective tissues. Assiduous attention to the unmet needs of this patient community is crucial to prevent potential iatrogenic harm and optimize care for individuals with FOP. Objective To gather international expert opinion and real-world experience on the key challenges for individuals with FOP and their families, highlight critical gaps in care, communication, and research, and provide recommendations for improvement. Methods An international group of expert clinicians, patients and patient advocates, caregivers and representatives from the international FOP community participated in a virtual, half-day meeting on 22 March 2021 to discuss the key unmet needs of individuals with FOP. Results Individuals with FOP often face the frustration of long diagnostic journeys, the burden of self-advocacy and the navigation of novel care pathways. Globally, patients with FOP are also confronted with inequities in access to diagnosis and specialist care, and consequently, unequal access to registries, clinical trials, and essential support from patient associations. Organizations such as the International FOP Association, the International Clinical Council on FOP, and national FOP organizations work to provide information, facilitate access to expert clinical guidance, nurture patient empowerment, fund FOP research and/or foster meaningful collaborations with the research community. The non-profit Tin Soldiers Global FOP Patient Search program aims to identify and provide a pathway to diagnosis and care for individuals with FOP, particularly in underserved communities. Such global initiatives and the increasingly widespread use of telemedicine and digital platforms offer opportunities to improve vital access to care and research. Conclusions This multi-stakeholder perspective highlights some of the unmet needs of individuals with FOP and their families. Regional and international organizations play an important role in improving the quality of life of those they reach in the global FOP community. However, globally, fundamental issues remain around raising awareness of FOP among healthcare professionals, identifying individuals with FOP, reducing time to diagnosis, and ensuring access to best practice in care, support, and clinical research. Medical writing support was industry-sponsored.
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    Delivery of health care for cardiovascular and metabolic diseases among people living with HIV/AIDS in African countries: a systematic review protocol
    (BioMed Central, 2016) Watkins, David A; Tulloch, Nathaniel L; Anderson, Molly E; Barnhart, Scott; Steyn, Krisela; Levitt, Naomi S
    Background: People living with HIV (PLHIV) in African countries are living longer due to the rollout of antiretroviral drug therapy programs, but they are at increasing risk of non-communicable diseases (NCDs). However, there remain many gaps in detecting and treating NCDs in African health systems, and little is known about how NCDs are being managed among PLHIV. Developing integrated chronic care models that effectively prevent and treat NCDs among PLHIV requires an understanding of the current patterns of care delivery and the major barriers and facilitators to health care. We present a systematic review protocol to synthesize studies of healthcare delivery for an important subset of NCDs, cardiovascular and metabolic diseases (CMDs), among African PLHIV. Methods/design: We plan to search electronic databases and reference lists of relevant studies published in African settings from January 2003 to the present. Studies will be considered if they address one or both of our major objectives and focus on health care for one or more of six interrelated CMDs (ischemic heart disease, stroke, heart failure, hypertension, diabetes, and hyperlipidemia) in PLHIV. Our first objective will be to estimate proportions of CMD patients along the “cascade of care”—i.e., screened, diagnosed, aware of the diagnosis, initiated on treatment, adherent to treatment, and with controlled disease. Our second objective will be to identify unique barriers and facilitators to health care faced by PLHIV in African countries. For studies deemed eligible for inclusion, we will assess study quality and risk of bias using previously published criteria. We will extract study data using standardized instruments. We will meta-analyze quantitative data at each level of the cascade of care for each CMD (first objective). We will use meta-synthesis techniques to understand and integrate qualitative data on health-related behaviors (second objective). Discussion: CMDs and other NCDs are becoming major health concerns for African PLHIV. The results of our review will inform the development of research into chronic care models that integrate care for HIV/AIDS and CMDs among PLHIV. Our findings will be highly relevant to health policymakers, administrators, and practitioners in African settings.
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    Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort
    (2017) Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; Boulle, Andrew; Vogt, Monica; Gupta-Wright, Ankur; Nicol, Mark P; Meintjes, Graeme
    Abstract Background We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB. Methods Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions. Results Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and LAM assay specificity (using a grade-2 cut-off) was 98.9% (274/277; 95% confidence interval [CI] 96.9–99.8). Among TB cases, positive urine-LAM status was strongly associated with mortality at 90 days (adjusted hazard ratio 4.20; 95% CI 1.50–11.75). Conclusions Routine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis.
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    HIV-associated tuberculosis: relationship between disease severity and the sensitivity of new sputum-based and urine-based diagnostic assays
    (BioMed Central Ltd, 2013) Lawn, Stephen; Kerkhoff, Andrew; Vogt, Monica; Wood, Robin
    BACKGROUND: Reducing mortality from HIV-associated tuberculosis (TB) requires diagnostic tools that are rapid and have high sensitivity among patients with poor prognosis. We determined the relationship between disease severity and the sensitivity of new sputum-based and urine-based diagnostic assays. METHODS: Consecutive ambulatory patients enrolling for antiretroviral treatment in South Africa were screened for TB regardless of symptoms using diagnostic assays prospectively applied to sputum (fluorescence smear microscopy, Xpert MTB/RIF and liquid culture (reference standard)) and retrospectively applied to stored urine samples (Determine TB-LAM and Xpert MTB/RIF). Assay sensitivities were calculated stratified according to pre-defined indices of disease severity: CD4 count, symptom intensity, serum C-reactive protein (CRP), hemoglobin concentration and vital status at 90 days. RESULTS: Sputum culture-positive TB was diagnosed in 15% (89/602) of patients screened and data from 86 patients were analyzed (median CD4 count, 131 cells/muL) including 6 (7%) who died. The sensitivity of sputum microscopy was 26.7% overall and varied relatively little with disease severity. In marked contrast, the sensitivities of urine-based and sputum-based diagnosis using Determine TB-LAM and Xpert MTB/RIF assays were substantially greater in sub-groups with poorer prognosis. Rapid diagnosis from sputum and/or urine samples was possible in >80% of patients in sub-groups with poor prognosis as defined by either CD4 counts <100 cells/muL, advanced symptoms, CRP concentrations >200 mg/L or hemoglobin <8.0 g/dl. Retrospective testing of urine samples with Determine TB-LAM correctly identified all those with TB who died. CONCLUSIONS: The sensitivities of Xpert MTB/RIF and Determine TB-LAM for HIV-associated TB were highest among HIV-infected patients with the most advanced disease and poorest prognostic characteristics. These data provide strong justification for large-scale intervention studies that assess the impact on survival of screening using these new sputum-based and urine-based diagnostic approaches.
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    Hyperthyroidism - an unusual feature of thyroid carcinoma
    (MedPharm Publications, 2006) Ekpebegh, Chukwuma O; Ross, Ian L; Levitt, Naomi S
    A 53-year-old woman presented with thyrotoxicosis, which is an unusual manifestation of thyroid carcinoma. Hyperthyroidism associated with malignancy usually occurs with well-differentiated follicular thyroid carcinoma. We show that extensive disease burden contributed to the development of hyperthyroidism, the occurrence of the Jod-Basedow phenomenon and the subsequent death of the patient. This diagnosis and treatment can be challenging.
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    Mental, behavioral and neurodevelopmental disorders in the ICD-11: an international perspective on key changes and controversies
    (2020-01-27) Stein, Dan J; Szatmari, Peter; Gaebel, Wolfgang; Berk, Michael; Vieta, Eduard; Maj, Mario; de Vries, Ymkje A; Roest, Annelieke M; de Jonge, Peter; Maercker, Andreas; Brewin, Chris R; Pike, Kathleen M; Grilo, Carlos M; Fineberg, Naomi A; Briken, Peer; Cohen-Kettenis, Peggy T; Reed, Geoffrey M
    Abstract An update of the chapter on Mental, Behavioral and Neurodevelopmental Disorders in the International Classification of Diseases and Related Health Problems (ICD) is of great interest around the world. The recent approval of the 11th Revision of the ICD (ICD-11) by the World Health Organization (WHO) raises broad questions about the status of nosology of mental disorders as a whole as well as more focused questions regarding changes to the diagnostic guidelines for specific conditions and the implications of these changes for practice and research. This Forum brings together a broad range of experts to reflect on key changes and controversies in the ICD-11 classification of mental disorders. Taken together, there is consensus that the WHO’s focus on global applicability and clinical utility in developing the diagnostic guidelines for this chapter will maximize the likelihood that it will be adopted by mental health professionals and administrators. This focus is also expected to enhance the application of the guidelines in non-specialist settings and their usefulness for scaling up evidence-based interventions. The new mental disorders classification in ICD-11 and its accompanying diagnostic guidelines therefore represent an important, albeit iterative, advance for the field.
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    Neurocysticercosis : experience at the teaching hospitals of the University of Cape Town
    (1993) Thomson, AJG
    In the 15 years 1975-1989, 239 patients attending the associated teaching hospitals of the University of Cape Town have been identified retrospectively as having neurocysticercosis. One hundred and twenty-three (51,46%) were children 12 years of age or younger, 14 (5,86%) were adolescents aged 13-19 years, and 102 (42,68%) were adults 20 years of age or older. Two hundred and twelve (88,7%) of these patients were black, almost exclusively Xhosa-speakers originating from the eastern Cape homeland regions of Transkei and Ciskei. Although the clinical features of neurocysticercosis are protean, these patients could be divided into three clinicoradiological groups - a group with seizures, a group with raised intracranial pressure, and an asymptomatic group.In the 15 years 1975-1989, 239 patients attending the associated teaching hospitals of the University of Cape Town have been identified retrospectively as having neurocysticercosis. One hundred and twenty-three (51,46%) were children 12 years of age or younger, 14 (5,86%) were adolescents aged 13-19 years, and 102 (42,68%) were adults 20 years of age or older. Two hundred and twelve (88,7%) of these patients were black, almost exclusively Xhosa-speakers originating from the eastern Cape homeland regions of Transkei and Ciskei. Although the clinical features of neurocysticercosis are protean, these patients could be divided into three clinicoradiological groups - a group with seizures, a group with raised intracranial pressure, and an asymptomatic group.
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    Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review
    (BioMed Central Ltd, 2012) Lawn, Stephen
    Detection of Mycobacterium tuberculosis antigens in urine is attractive as a potential means of diagnosing tuberculosis (TB) regardless of the anatomical site of disease. The most promising candidate antigen is the cell wall lipopolysaccharide antigen lipoarabinomannan (LAM), which has been used to develop commercially available enzyme-linked immunosorbent assays. Although highly variable diagnostic accuracy has been observed in different clinical populations, it is now clear that this assay has useful sensitivity for diagnosis of HIV-associated TB in patients with advanced immunodeficiency and low CD4 cell counts. Thus, this assay is particularly useful when selectively used among patients enrolling in antiretroviral treatment services or in HIV-infected patients requiring admission to hospital medical wards. These are the very patients who have the highest mortality risk and who stand to gain the most from rapid diagnosis, permitting immediate initiation of TB treatment. A recently developed low-cost, lateral-flow (urine 'dip-stick') format of the assay provides a result within 30 minutes and is potentially a major step forward as it can be used at the point-of-care, making the possibility of immediate diagnosis and treatment a reality. This paper discusses the likely utility of this point-of-care assay and how it might best be used in combination with other diagnostic assays for TB. The many further research studies that are needed on this assay are described. Consideration is particularly given to potential reasons for the variable specificity observed in existing field evaluations of LAM ELISAs. Whether this might be related to the assay itself or to the challenges associated with study design is discussed.
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    Pre-operative diagnosis of thyroid cancer: Clinical, radiological and pathological correlation
    (2013) Cairncross, Lydia; Panieri, Eugenio
    AIM: Ultrasonography and fine-needle aspiration biopsy (FNAB) are the mainstays of diagnosing thyroid cancer accurately and reducing the number of diagnostic lobectomies. No benchmark for diagnostic accuracy has been published in the South African context. This single-institution study addresses this deficit. METHODS: The oncology, pathology and surgical records of all patients diagnosed with thyroid carcinoma from 2004 to 2010 at Groote Schuur Hospital, Cape Town, South Africa, were reviewed and data were recorded on a standardised confidential proforma. The findings on pre-operative clinical assessment, ultrasound and FNAB were correlated with the histopathology results. Diagnostic accuracy for thyroid cancer was determined by correlating pre-operative investigations with the final diagnosis. Sensitivity of ultrasound and FNAB were calculated. RESULTS: A total of 109 patients, 79 female and 30 male, were identified. The majority (99, 90.8%) had well-differentiated thyroid cancers (56 papillary, 30 follicular, 10 mixed and 3 Hurtle cell carcinomas). There were 6 anaplastic and 4 medullary carcinomas. Of the 109 patients 38 had a definite pre-operative diagnosis, in 61 a malignant tumour was suspected, and 10 had surgery for benign disease. FNAB was inadequate in 11 cases and the findings indicated a benign lesion in 47, a suspicious lesion in 13 and a malignant lesion in 38 patients diagnosed with thyroid carcinoma. FNAB diagnosed all patients with medullary and anaplastic carcinoma but less than half of those with well-differentiated thyroid carcinoma. Ultrasound scans detected at least one suspicious feature in 44 patients. Microcalcification was the most common sign. CONCLUSION: The rate of pre-operative diagnosis of well-differentiated thyroid carcinomas in this unit is under 50%, well below international norms. Our standard practice needs to change to include ultrasound-guided FNAB and standardised reporting of high-resolution ultrasound and cytology, before reassessment of our diagnostic accuracy.
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    Rapid microbiological screening for tuberculosis in HIV-positive patients on the first day of acute hospital admission by systematic testing of urine samples using Xpert MTB/RIF: a prospective cohort in South Africa
    (2015-08-14) Lawn, Stephen D; Kerkhoff, Andrew D; Burton, Rosie; Schutz, Charlotte; van Wyk, Gavin; Vogt, Monica; Pahlana, Pearl; Nicol, Mark P; Meintjes, Graeme
    Abstract Background Autopsy studies of HIV/AIDS-related hospital deaths in sub-Saharan Africa reveal frequent failure of pre-mortem diagnosis of tuberculosis (TB), which is found in 34–64 % of adult cadavers. We determined the overall prevalence and predictors of TB among consecutive unselected HIV-positive adults requiring acute hospital admission and the comparative diagnostic yield obtained by screening urine and sputum samples obtained on day 1 of admission with Xpert MTB/RIF (Xpert). Methods To determine overall TB prevalence accurately, comprehensive clinical sampling (sputum, urine, blood plus other relevant samples) was done and TB was defined by detection of Mycobacterium tuberculosis in any sample using Xpert and/or mycobacterial liquid culture. To evaluate a rapid screening strategy, we compared the diagnostic yield of Xpert testing sputum samples and urine samples obtained with assistance from a respiratory study nurse in the first 24 h of admission. Results Unselected HIV-positive acute adult new medical admissions (n = 427) who were not receiving TB treatment were enrolled irrespective of clinical presentation or symptom profile. From 2,391 cultures and Xpert tests done (mean, 5.6 tests/patient) on 1,745 samples (mean, 4.1 samples/patient), TB was diagnosed in 139 patients (median CD4 cell count, 80 cells/μL). TB prevalence was very high (32.6 %; 95 % CI, 28.1–37.2 %; 139/427). However, patient symptoms and risk factors were poorly predictive for TB. Overall, ≥1 non-respiratory sample(s) tested positive in 115/139 (83 %) of all TB cases, including positive blood cultures in 41/139 (29.5 %) of TB cases. In the first 24 h of admission, sputum (spot and/or induced samples) and urine were obtainable from 37.0 % and 99.5 % of patients, respectively (P <0.001). From these, the proportions of total TB cases (n = 139) that were diagnosed by Xpert testing sputum, urine or both sputum and urine combined within the first 24 h were 39/139 (28.1 %), 89/139 (64.0 %) and 108/139 (77.7 %) cases, respectively (P <0.001). Conclusions The very high prevalence of active TB and its non-specific presentation strongly suggest the need for routine microbiological screening for TB in all HIV-positive medical admissions in high-burden settings. The incremental diagnostic yield from Xpert testing urine was very high and this strategy might be used to rapidly screen new admissions, especially if sputum is difficult to obtain.
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    A study to evaluate immunodiagnostic tests for tuberculosis infection and determinants of TB infection in a population of health care workers in the Western Cape of South Africa
    (2015) Adams, Shahieda; Dheda, Keertan; Ehrlich, Rodney
    Background: Health care workers are at increased risk of acquiring latent tuberculosis infection (LTBI). The emergence of interferon - gamma release assays (IGRAs) for the diagnosis of LTBI, presents an opportunity for improved estimation of TB infection prevalence and incidence. Their utility in settings with high background prevalence TB and HIV infection is unknown. Major aims of the study were to: * Evaluate the prevalence and factors associated with TB infection using both tuberculin skin test (TST) and IGRA assays in a sample of health care workers. * Evaluate change in interval test response over one year to determine annual risk of infection and determinants associated with test conversion. Methods: Participants completed a questionnaire on occupational and environmental characteristics including a TB symptom screen and underwent chest radiograph and rapid HIV test. Three tests for latent TB infection were administered: TST, QuantiFERON - TB Gold In - Tube (QFT - GIT) and a T - SPOT.TB test. All tests were repeated one year later. Results: The prevalence of TB infection at baseline was 84%, 65% and 60% as measured by TST, QFT - GIT and T - SPOT.TB. There was only fair agreement between TST and IGRAs. HIV positive status was significantly associated with having a TST negative / T - SPOT.TB positive discordant test response (OR=4.72). TST had superior sensitivity than IGRAs for the diagnosis of LTBI. In primary level staff a positive TST outcome, was negatively associated with HIV positive status (OR=0.41). Long employment duration was positively associated with TST (OR=4.17) and QFT - GIT (OR= 2.42) positivity. Involvement in sputum collection (OR=3.25) and home - based care of TB patients (OR= 4.14) was associated with a positive IGRA test. The conversion rate for TST and IGRAs was 38% and 22%, respectively. Reversion rates ranged from 1 % - 16 % and was lowest for TST. Factors associated with conversion (for IGRAs) included employment sector, counselling of TB patients and a baseline positive TST. Conclusion: The annual rate of TB infection was very high pointing to occupational exposure as a contributory factor. TST had superior sensitivity than IGRAs for LTBI diagnosis but poor uptake on serial testing. IGRAs had excellent uptake but its clinical utility was negatively influenced by high rates of reversion.
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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 immunological response to syphilis differs by HIV status; a prospective observational cohort study
    (2017) Kenyon, Chris; Osbak, Kara Krista; Crucitti, Tania; Kestens, Luc
    BACKGROUND: It is not known if there is a difference in the immune response to syphilis between HIV-infected and uninfected individuals. METHODS: We prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for IFNα, IFNγ, IL-1β, IL-12p40, IL-12p70, IP-10, MCP-1, MIP-1α, MIP-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10 and IL-17A at baseline pre-treatment and 6 months following therapy. RESULTS: A total of 79 HIV-infected [44 primary/secondary syphilis (PSS) and 35 latent syphilis (LS)] and 12 HIV-uninfected (10 PSS and 2 LS) cases of syphilis and 30 HIV-infected controls were included in the study. At the baseline visit, compared to the control group, concentrations of IL-10 were significantly elevated in the HIV-infected and uninfected groups. The level of IL-10 was significantly higher in the HIV-infected compared to the HIV-uninfected PSS group (25.3 pg/mL (IQR, 4.56-41.76) vs 2.73 pg/mL (IQR, 1.55-9.02), P = 0.0192). In the HIV-infected PSS group (but not the HIV-infected LS or HIV-uninfected PSS groups) the IP-10, MIP-1b, IL-6 and IL-8 were raised compared to the controls. IL-10 levels decreased but did not return to control baseline values by 6 months in HIV infected PSS and LS and HIV uninfected PSS. CONCLUSION: PSS and LS in HIV-infected individuals is characterized by an increase in inflammatory and anti-inflammatory cytokines such as IL-10. The increase of IL-10 is greater in HIV-infected than uninfected individuals. Further work is required to ascertain if this is part of an immunological profile that correlates with adverse outcomes such as serofast syphilis and neurosyphilis, in HIV-infected individuals.
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    The international WAO/EAACI guideline for the management of hereditary angioedema – the 2017 revision and update
    (BioMed Central, 2018-02-27) Maurer, Marcus; Magerl, Markus; Ansotegui, Ignacio; Aygören-Pürsün, Emel; Betschel, Stephen; Bork, Konrad; Bowen, Tom; Boysen, Henrik B; Farkas, Henriette; Grumach, Anete S; Hide, Michihiro; Katelaris, Constance; Lockey, Richard; Longhurst, Hilary; Lumry, William R.; Martinez-Saguer, Inmaculada; Moldovan, Dumitru; Nast, Alexander; Pawankar, Ruby; Potter, Paul; Riedl, Marc; Ritchie, Bruce; Rosenwasser, Lanny; Sánchez-Borges, Mario; Zhi, Yuxiang; Zuraw, Bruce; Craig, Timothy
    Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: 1) How should HAE-1/2 be defined and classified?, 2) How should HAE-1/2 be diagnosed?, 3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, 4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and 5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures? This article is co-published with permission in Allergy and the World Allergy Organization Journal.
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    Utility of interferon-gamma ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africa
    (Biomed Central Ltd, 2007) Lawn, Stephen; Bangani, Nonzwakazi; Vogt, Monica; Bekker, Linda-Gail; Badri, Motasim; Ntobongwana, Marjorie; Dockrell, Hazel; Wilkinson, Robert; Wood, Robin
    BACKGROUND:Interferon-gamma (IFN-gamma) ELISPOT assays incorporating Mycobacterium tuberculosis-specific antigens are useful in the diagnosis of tuberculosis (TB) or latent infection. However, their utility in patients with advanced HIV is unknown. We studied determinants of ELISPOT responses among patients with advanced HIV infection (but without active TB) living in a South African community with very high TB notification rates. METHODS: IFN-gamma responses to ESAT-6 and CFP-10 in overnight ELISPOT assays and in 7-day whole blood assays (WBA) were compared in HIV-infected patients (HIV+, n = 40) and healthy HIV-negative controls (HIV-, n = 30) without active TB. Tuberculin skin tests (TSTs) were also done. RESULTS: ELISPOTs, WBAs and TSTs were each positive in >70% of HIV- controls, reflecting very high community exposure to M. tuberculosis. Among HIV+ patients, quantitative WBA responses and TSTs (but not the proportion of positive ELISPOT responses) were significantly impaired in those with CD4 cell counts <100 cells/mul compared to those with higher counts. In contrast, ELISPOT responses (but not WBA or TST) were strongly related to history of TB treatment; a much lower proportion of HIV+ patients who had recently completed treatment for TB (n = 19) had positive responses compared to those who had not been treated (11% versus 62%, respectively; P < 0.001). Multivariate analysis confirmed that ELISPOT responses had a strong inverse association with a history of recent TB treatment (adjusted OR = 0.06, 95%CI = 0.10-0.40, P < 0.01) and that they were independent of CD4 cell count and viral load. Among HIV+ individuals who had not received TB treatment both the magnitude and proportion of positive ELISPOT responses (but not TST or WBA) were similar to those of HIV-negative controls. CONCLUSION: The proportion of positive ELISPOT responses in patients with advanced HIV infection was independent of CD4 cell count but had a strong inverse association with history of TB treatment. This concurs with the previously documented low TB risk among patients in this cohort with a history of recent treatment for TB. These data suggest ELISPOT assays may be useful for patient assessment and as an immuno-epidemiological research tool among patients with advanced HIV and warrant larger scale prospective evaluation.
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    Xpert MTB/RIF Ultra and mycobacterial culture in routine clinical practice at a Tertiary Paediatric Hospital
    (2021) Enimil, Anthony Kwame; Eley, Brian; Nuttall, James
    Introduction World Health Organization approved the use of Xpert MTB/RIF Ultra (Ultra) in children due to quick turn-around time, improved yield over smear microscopy, and ability to detect rifampicin resistance despite culture being the “gold standard”. This study reviewed published literature on current childhood tuberculosis diagnostic modalities. It also retrospectively compared demographic, clinical, and radiological features of children with confirmed and unconfirmed PTB, reviewed criteria for microbiologically unconfirmed PTB, and assessed incremental microbiological yield on second and third Ultra and/or mycobacterial culture results in routine clinical care at a tertiary paediatric hospital. Method For the review on childhood TB diagnostic modalities, PubMed was searched using Boolean terms OR/AND between childhood tuberculosis and words such as diagnosis, polymerase chain reaction, molecular, histology, imaging, and cultures. All abstracts were read after which selected articles that met the objectives of the thesis were fully reviewed and referenced appropriately. The retrospective study was conducted in children (0 to 13 years) treated for Pulmonary TB (PTB) between 1 February 2018 and 31 January 2019 and who had at least one respiratory specimen investigated by Ultra and/or mycobacterial culture before TB treatment was commenced. Relevant demographic, clinical information, tuberculin skin test results and laboratory results were abstracted from paper-based medical records and electronic database. Baseline chest radiographic findings were obtained from the radiology digital imaging database. All data was entered anonymously into a Microsoft Excel spreadsheet and exported to R-statistical software for statistical analysis. Descriptive and inferential statistics were used in the analysis. Incremental yield of Ultra and/or mycobacterial cultures on sequential respiratory specimens was determined. Results Ultra is an important diagnostic method for confirming TB in children even though mycobacterial culture, molecular, and histology tests are also available. Other modalities such as imaging and immunologic tests support the diagnosis of microbiologically unconfirmed TB. 174 children with PTB ± EPTB were included in the retrospective study. The median age was 2.5 years. Tuberculosis was microbiologically confirmed in 93 (53.4%). Yield on Ultra in first respiratory specimens was 39.1%. When the results of Ultra and mycobacterial culture on first respiratory specimens were combined, 47.1% (82/174) had microbiologically confirmed TB. Microcytic anaemia and pulmonary pathology were more common in confirmed TB. Of 81 children with microbiologically unconfirmed TB, 31 (38.3%) met a consensus definition of unconfirmed intrathoracic TB formulated by an international expert committee. In the subset of children (n=70) who were screened by Ultra on two sequential respiratory specimens, the incremental yield was 30.3%. When the results of Ultra and mycobacterial culture were combined the incremental yield in children who had 2 sequential respiratory specimens tested was 24.4% and 3.1% on Ultra and mycobacterial culture, respectively. Conclusion Ultra and/or mycobacterial culture on single respiratory specimens resulted in high microbiological yield. Ultra on second sequential respiratory specimens increased microbiological confirmation. The value of additional Ultra and/or mycobacterial culture testing in routine clinical practice requires further study.