Browsing by Author "Meintjes, Graeme"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Abdominal ultrasound for diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV-positive adults
    (John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration, 2017) Van Hoving, Daniel J.; Meintjes, Graeme; Takwoingi, Yemisi; Griesel, Rulan; Maartens, Gary; Ochodo, Eleanor A.
    This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To determine the diagnostic accuracy of abdominal ultrasound as a standalone test for detecting abdominal TB or disseminated TB with abdominal involvement in HIV-positive adults. • To determine the diagnostic accuracy of combinations of abdominal ultrasound and existing tests (chest radiograph, full blood count) for detecting abdominal TB or disseminated TB with abdominal involvement in HIV-positive adults. • To investigate potential sources of heterogeneity in test accuracy, including clinical setting, ultrasound training level, and type of reference standard.
  • Thumbnail Image
    Item
    Abdominal ultrasound for diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV-positive individuals
    (John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration, 2019) Van Hoving, Daniel J.; Griesel, Rulan; Meintjes, Graeme; Takwoingi, Yemisi; Maartens, Gary; Ochodo, Eleanor A.
    Background: Accurate diagnosis of tuberculosis in people living with HIV is difficult. HIV‐positive individuals have higher rates of extrapulmonary tuberculosis and the diagnosis of tuberculosis is often limited to imaging results. Ultrasound is such an imaging test that is widely used as a diagnostic tool (including point‐of‐care) in people suspected of having abdominal tuberculosis or disseminated tuberculosis with abdominal involvement. Objectives: To determine the diagnostic accuracy of abdominal ultrasound for detecting abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV‐positive individuals. To investigate potential sources of heterogeneity in test accuracy, including clinical setting, ultrasound training level, and type of reference standard. Search methods: We searched for publications in any language up to 4 April 2019 in the following databases: MEDLINE, Embase, BIOSIS, Science Citation Index Expanded (SCI‐EXPANDED), Social Sciences Citation Index (SSCI), Conference Proceedings Citation Index‐ Science (CPCI‐S), and also ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform to identify ongoing trials. Selection criteria: We included cross‐sectional, cohort, and diagnostic case‐control studies (prospective and retrospective) that compared the result of the index test (abdominal ultrasound) with one of the reference standards. We only included studies that allowed for extraction of numbers of true positives (TPs), true negatives (TNs), false positives (FPs), and false negatives (FNs). Participants were HIV‐positive individuals aged 15 years and older. A higher‐quality reference standard was the bacteriological confirmation of Mycobacterium tuberculosis from any clinical specimen, and a lower‐quality reference standard was a clinical diagnosis of tuberculosis without microbiological confirmation. We excluded genitourinary tuberculosis. Data collection and analysis: For each study, two review authors independently extracted data using a standardized form. We assessed the quality of studies using a tailored Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool. We used the bivariate model to estimate pooled sensitivity and specificity. When studies were few we simplified the bivariate model to separate univariate random‐effects logistic regression models for sensitivity and specificity. We explored the influence of the type of reference standard on the accuracy estimates by conducting separate analyses for each type of reference standard. We assessed the certainty of the evidence using the GRADE approach. Main results: We included 11 studies. The risks of bias and concern about applicability were often high or unclear in all domains. We included six studies in the main analyses of any abnormal finding on abdominal ultrasound; five studies reported only individual lesions. The six studies of any abnormal finding were cross‐sectional or cohort studies. Five of these (83%) were conducted in low‐ or middle‐income countries, and one in a high‐income country. The proportion of participants on antiretroviral therapy was none (1 study), fewer then 50% (4 studies), more than 50% (1 study), and not reported (5 studies). The first main analysis, studies using a higher‐quality reference standard (bacteriological confirmation), had a pooled sensitivity of 63% (95% confidence interval (CI) 43% to 79%; 5 studies, 368 participants; very low‐certainty evidence) and a pooled specificity of 68% (95% CI 42% to 87%; 5 studies, 511 participants; very low‐certainty evidence). If the results were to be applied to a hypothetical cohort of 1000 people with HIV where 200 (20%) have tuberculosis then: ‐ About 382 individuals would have an ultrasound result indicating tuberculosis; of these, 256 (67%) would be incorrectly classified as having tuberculosis (false positives). ‐ Of the 618 individuals with a result indicating that tuberculosis is not present, 74 (12%) would be incorrectly classified as not having tuberculosis (false negatives). In the second main analysis involving studies using a lower‐quality reference standard (clinical diagnosis), the pooled sensitivity was 68% (95% CI 45% to 85%; 4 studies, 195 participants; very low‐certainty evidence) and the pooled specificity was 73% (95% CI 41% to 91%; 4 studies, 202 participants; very low‐certainty evidence). Authors' conclusions: In HIV‐positive individuals thought to have abdominal tuberculosis or disseminated tuberculosis with abdominal involvement, abdominal ultrasound appears to have 63% sensitivity and 68% specificity when tuberculosis was bacteriologically confirmed. These estimates are based on data that is limited, varied, and low‐certainty. The low sensitivity of abdominal ultrasound means clinicians should not use a negative test result to rule out the disease, but rather consider the result in combination with other diagnostic strategies (including clinical signs, chest x‐ray, lateral flow urine lipoarabinomannan assay (LF‐LAM), and Xpert MTB/RIF). Research incorporating the test into tuberculosis diagnostic algorithms will help in delineating more precisely its value in diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement.
  • Thumbnail Image
    Item
    Management of intracranial tuberculous mass lesions : how long should we treat for? [version 3; peer review: 3 approved]
    (F1000Research, 2019) Marais, Suzaan; Van Toorn, Ronald; Chow, Felicia C.; Manesh, Abi; Siddiqi, Omar K.; Figaji, Anthony; Schoeman, Johan F.; Meintjes, Graeme; Tuberculous Meningitis International Research Consortium
    ENGLISH ABSTRACT: Tuberculous intracranial mass lesions are common in settings with high tuberculosis (TB) incidence and HIV prevalence. The diagnosis such lesions, which include tuberculoma and tuberculous abscesses, is often presumptive and based on radiological features, supportive evidence of TB elsewhere and response to TB treatment. However, the treatment response is unpredictable, with lesions frequently enlarging paradoxically or persisting for many years despite appropriate TB treatment and corticosteroid therapy. Most international guidelines recommend a 9-12 month course of TB treatment for central nervous system TB when the infecting Mycobacterium tuberculosis (M.tb) strain is sensitive to first-line drugs. However, there is variation in opinion and practice with respect to the duration of TB treatment in patients with tuberculomas or tuberculous abscesses. A major reason for this is the lack of prospective clinical trial evidence. Some experts suggest continuing treatment until radiological resolution of enhancing lesions has been achieved, but this may unnecessarily expose patients to prolonged periods of potentially toxic drugs. It is currently unknown whether persistent radiological enhancement of intracranial tuberculomas after 9-12 months of treatment represents active disease, inflammatory response in a sterilized lesion or merely revascularization. The consequences of stopping TB treatment prior to resolution of lesional enhancement have rarely been explored. These important issues were discussed at the 3rd International Tuberculous Meningitis Consortium meeting. Most clinicians were of the opinion that continued enhancement does not necessarily represent treatment failure and that prolonged TB therapy was not warranted in patients presumably infected with M.tb strains susceptible to first-line drugs. In this manuscript we highlight current medical treatment practices, benefits and disadvantages of different TB treatment durations and the need for evidence-based guidelines regarding the treatment duration of patients with intracranial tuberculous mass lesions.
  • Thumbnail Image
    Item
    A multi-parameter diagnostic clinical decision tree for the rapid diagnosis of tuberculosis in HIV-positive patients presenting to an emergency centre
    (Wellcome Trust, 2020-04) Van Hoving, Daniël Jacobus; Meintjes, Graeme; Maartens, Gary; Kengne, Andre Pascal
    Background: Early diagnosis is essential to reduce the morbidity and mortality of HIV-associated tuberculosis. We developed a multi-parameter clinical decision tree to facilitate rapid diagnosis of tuberculosis using point-of-care diagnostic tests in HIV-positive patients presenting to an emergency centre. Methods: A cross-sectional study was performed in a district hospital emergency centre in a high-HIV-prevalence community in South Africa. Consecutive HIV-positive adults with ≥1 WHO tuberculosis symptoms were enrolled over a 16-month period. Point-of-care ultrasound (PoCUS) and urine lateral flow lipoarabinomannan (LF-LAM) assay were done according to standardized protocols. Participants also received a chest X-ray. Reference standard was the detection of Mycobacterium tuberculosis using Xpert MTB/RIF or culture. Logistic regressions models were used to investigate the independent association between prevalent microbiologically confirmed tuberculosis and clinical and biological variables of interest. A decision tree model to predict tuberculosis was developed using the classification and regression tree algorithm. Results: There were 414 participants enrolled: 171 male, median age 36 years, median CD4 cell count 86 cells/mm3. Tuberculosis prevalence was 42% (n=172). Significant variables used to build the classification tree included ≥2 WHO symptoms, antiretroviral therapy use, LF-LAM, PoCUS independent features (pericardial effusion, ascites, intra-abdominal lymphadenopathy) and chest X-ray. LF-LAM was positioned after WHO symptoms (75% true positive rate, representing 17% of study population). Chest X-ray should be performed next if LF-LAM is negative. The presence of ≤1 PoCUS independent feature in those with ‘possible or unlikely tuberculosis’ on chest x-ray represented 47% of non-tuberculosis participants (true negative rate 83%). In a prediction tree which only included true point-of-care tests, a negative LF-LAM and the presence of ≤2 independent PoCUS features had a 71% true negative rate (representing 53% of sample). Conclusions: LF-LAM should be performed in all adults with suspected HIV-associated tuberculosis (regardless of CD4 cell count) presenting to the emergency centre.
  • Thumbnail Image
    Item
    Rapid diagnosis of cryptococcal meningitis by use of lateral flow assay on cerebrospinal fluid samples : influence of the high-dose “hook” effect
    (American Society for Microbiology, 2014) Lourens, Adre; Jarvis, Joseph N.; Meintjes, Graeme; Samuel, Catherine M.
    Cryptococcal meningitis is the most frequent cause of meningitis and a major cause of mortality in HIV-infected adults in Africa. This study evaluated the performance of the lateral flow assay (LFA) on cerebrospinal fluid (CSF) samples for the diagnosis of cryptococcal meningitis against that of existing diagnostic tests. LFA performed on 465 undiluted CSF samples had a sensitivity of 91%. When the LFA was paired with Gram staining, a sensitivity of 100% was achieved after implementation of a dilution step for samples with negative LFA results and the presence of yeasts on microscopy. Microscopy is essential for preventing the reporting of false-negative results due to the high-dose “hook” effect.