Abdominal ultrasound for diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV‐positive individuals
Information
- DOI:
- https://doi.org/10.1002/14651858.CD012777.pub2Copy DOI
- Database:
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- Cochrane Database of Systematic Reviews
- Version published:
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- 30 September 2019see what's new
- Type:
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- Diagnostic
- Stage:
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- Review
- Cochrane Editorial Group:
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Cochrane Infectious Diseases Group
- Classified:
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- Up to date
All studies incorporated from most recent search
All studies identified during the most recent search (4 Apr, 2019) have been incorporated in the review, and one ongoing study identifiedAssessed: 26 September 2019
- Up to date
- Copyright:
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- Copyright © 2019 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.
- This is an open access article under the terms of the Creative Commons Attribution‐Non‐Commercial Licence, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Authors
Contributions of authors
Daniël J van Hoving and Eleanor A Ochodo wrote the protocol with input from Yemisi Takwoingi, Rulan Griesel, Graeme Meintjes, and Gary Maartens. Daniël J van Hoving and Rulan Griesel reviewed articles for inclusion and extracted data. Discrepancies were resolved by Graeme Meintjes. Eleanor A Ochodo analysed the data with input from Yemisi Takwoingi. Daniël J van Hoving and Eleanor A Ochodo interpreted the analyses and drafted the manuscript. Graeme Meintjes, Gary Maartens and Yemisi Takwoingi provided critical revisions to the manuscript. All review authors read and approved the final manuscript draft.
Sources of support
Internal sources
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South African Medical Research Council, South Africa.
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Liverpool School of Tropical Medicine, UK.
External sources
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Department for International Development, UK.
Project number 300342‐104
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Wellcome Trust Foundation, UK.
Grant: 109939
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Wellcome Trust Foundation, UK.
Grant: 098316
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South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation, South Africa.
Grant: 64787
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National Research Foundation incentive funding, South Africa.
UID: 85858
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TB and HIV Collaborating Centres Programme, South African Medical Research Council, South Africa.
RFA# SAMRC‐RFA‐CC: TB/HIV/AIDS‐01‐2014
Declarations of interest
Daniël J van Hoving has no conflicts of interest to declare.
Graeme Meintjes has no conflicts of interest to declare.
Yemisi Takwoingi has no conflicts of interest to declare.
Rulan Griesel has no conflicts of interest to declare.
Gary Maartens has no conflicts of interest to declare.
Eleanor A Ochodo has no conflicts of interest to declare.
Acknowledgements
We acknowledge Vittoria Lutje and Joy Oliver for their assistance with the MEDLINE draft search strategy. Dr Karen R Steingart was the academic editor for this review.
Eleanor A Ochodo is supported by a grant from the Wellcome Trust Foundation (grant number: 109939). The Wellcome Trust has no role in the design, conduct, and interpretation of this review.
Graeme Meintjes is supported by the Wellcome Trust (098316), the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (Grant No 64787), NRF incentive funding (UID: 85858) and the South African Medical Research Council through its TB and HIV Collaborating Centres Programme with funds received from the National Department of Health (RFA# SAMRC‐RFA‐CC: TB/HIV/AIDS‐01‐2014).
Yemisi Takwoingi is supported by the UK National Institute for Health Research (NIHR) through a postdoctoral fellowship award (PDF‐2017‐10‐059) and the NIHR Birmingham Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
The editorial base of the Cochrane Infectious Diseases Group is funded by UK aid from the UK government for the benefit of low‐ and middle‐income countries (project number 300342‐104). The views expressed do not necessarily reflect the UK government’s official policies.
Version history
| Published | Title | Stage | Authors | Version |
| 2019 Sep 30 | Abdominal ultrasound for diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV‐positive individuals | Review | Daniel J Van Hoving, Rulan Griesel, Graeme Meintjes, Yemisi Takwoingi, Gary Maartens, Eleanor A Ochodo | |
| 2017 Aug 31 | Abdominal ultrasound for diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV‐positive adults | Protocol | Daniel J Van Hoving, Graeme Meintjes, Yemisi Takwoingi, Rulan Griesel, Gary Maartens, Eleanor A Ochodo | |
Differences between protocol and review
We amended the protocol title from Abdominal ultrasound for diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV‐positive adults to Abdominal ultrasound for diagnosing abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV‐positive individuals.
Our review differed from the Cochrane protocol in several ways (Van Hoving 2017). In the protocol we stated a secondary objective to determine the diagnostic accuracy of combinations of abdominal ultrasound and existing tests (chest radiograph, full blood count) for detecting abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV‐positive individuals. However, we could not find any study that evaluated abdominal ultrasound as an add‐on test or in combination with other tests, and we therefore did not report on this.
The MEDION database is not active anymore and has not been searched.
In the protocol, we stated that we would have one primary meta‐analysis at individual patient level. However we decided to have two sets of primary meta‐analyses; one with 2 x 2 tables generated with a higher‐quality reference standard and the other with a lower‐quality reference standard. As stated in the analysis section, some studies produced two data points (with higher‐quality and lower‐quality reference standards). Because we did not want to lose information by only selecting one data point for each study and also to produce meaningful results, we present two sets of meta‐analyses. We used Stata instead of SAS for all analyses.
Due to insufficient data we did not investigate all potential sources of heterogeneity as stated in the protocol (including clinical setting, and ultrasound training level).
We defined adults in the protocol as participants aged 18 years or older. Two studies included participants under 18 years (older than 15 years) (Sculier 2010‐h; Weber 2018‐h; Weber 2018‐l). We included the studies as i) the number of paediatric cases was low, ii) many countries manage 15‐year‐old patients as adults, and iii) the results would be valuable for policy making. However, we have downgraded the certainty of the evidence for applicability concerns due to indirectness.
We judged publication bias using three criteria: for‐profit interest, only studies detected that produce precise estimates of high accuracy despite small sample size, and knowledge about studies that were conducted but are not published.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
Medical Subject Headings Check Words
Humans;
Diagnostic workup of HIV‐positive individuals with suspected abdominal tuberculosis or disseminated tuberculosis with abdominal involvement
Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study. Suffix (h) indicates higher quality reference standard; suffix (l) indicates lower quality reference standard.
Forest plot of abdominal ultrasound for detecting abdominal TB or disseminated TB with abdominal involvement. TP = true positive; FP = false positive; FN = false negative; TN = true negative. Suffix (h) indicates higher quality reference standard; suffix (l) indicates lower quality reference standard.
Forest plot of individual findings on ultrasound for detecting abdominal TB or disseminated TB with abdominal involvement. TP = true positive; FP = false positive; FN = false negative; TN = true negative. Suffix (h) indicates higher quality reference standard; suffix (l) indicates lower quality reference standard.
Flow diagram summarizing the main results in hypothetical cohort with TB prevalence 20%
Abnormal abdominal ultrasound (higher quality).
Abnormal abdominal ultrasound (lower quality).
| Review question: Should abdominal ultrasound be used to diagnose abdominal tuberculosis or disseminated tuberculosis with abdominal involvement in HIV‐positive individuals? Patient or population: HIV‐positive individuals Setting: Healthcare facility Index test: Abdominal ultrasound Reference standard: We considered two reference standards. The higher‐quality reference standard was bacteriological confirmation of M tuberculosis (any clinical specimen including (i) at least one specimen culture positive for M tuberculosis, (ii) microscopic identification of acid‐fast bacilli on stained sputum smears, lymph node aspirate, or any other specimen; or iii) Xpert MTB/RIF positive). The lower‐quality reference standard was clinical diagnosis of TB without microbiological confirmation (including cases diagnosed on the basis of: i) suggestive histology (necrotizing granulomatous inflammation), ii) x‐ray abnormalities, iii) extrapulmonary cases without laboratory confirmation, and iv) anti‐tuberculosis therapy initiated by a healthcare practitioner for cases with a high suspicion of tuberculosis). Threshold: Any abnormality found on abdominal ultrasound Study design: Cross‐sectional and cohort Limitations: A small number of studies and participants were included in the analyses. Risks of bias were generally high in the patient selection domain | ||||||
| Test result | Number of results per 1000 HIV‐positive individuals tested (95% CI) | Number of studies | Number of participants | Certainty of the evidence (GRADE) | ||
| Prevalence 10% | Prevalence 20% | Prevalence 40% | ||||
| Bacteriological confirmation as reference standard: pooled sensitivity = 63% (95% CI 43% to 79%) and pooled specificity = 68% (95% CI 42% to 87%) | ||||||
| True positives (participants correctly classified as having tuberculosis) | 63 (43 to 79) | 126 (86 to 158) | 252 (172 to 316) | 5 | 368 | ⊕⊝⊝⊝ |
| False negatives (participants incorrectly classified as not having tuberculosis) | 37 (21 to 57) | 74 (42 to 114) | 148 (84 to 228) | |||
| True negatives (participants correctly classified as not having tuberculosis) | 612 (378 to 783) | 544 (336 to 696) | 408 (252 to 522) | 5 | 511 | ⊕⊝⊝⊝ |
| False positives (participants incorrectly classified as having tuberculosis) | 288 (117 to 522) | 256 (104 to 464) | 192 (78 to 348) | |||
| Abbreviations: CI: confidence interval GRADE certainty of evidence (GRADEpro GDT 2015; Schünemann 2016) The table displays normalized frequencies within a hypothetical cohort of 1000 people at three different tuberculosis prevalences (pre‐test probabilities): 10%, 20% and 40%. We selected prevalence values based on the range of prevalence observed across the included studies. We estimated confidence intervals based on those around the point estimates for pooled sensitivity and specificity. Explanations aRisk of bias: We rated one study at high risk for participant selection since it excluded people unable to produce sputum (Griesel 2019‐h). We downgraded the certainty of the evidence by one level. | ||||||
| Author (publication year) | Study design | Country | Clinical setting | Target condition definition | Qualification of person performing index test | Sample size | Tuberculosisproportion in study |
| Case‐control | Germany | Not reported | Gastro‐intestinal tuberculosis | Not reported | 25a (7 cases, 18 pulmonary tuberculosis controls) | ‐ | |
| Cross‐sectional | South Sudan | Referral hospital | Extra‐pulmonary tuberculosis | Trained non‐radiologist | 100 | 24% | |
| Cross‐sectional | Spain | Not reported | Extra‐pulmonary tuberculosis | Sonographer | 116 | 55% (higher) 58% (lower) | |
| Cross‐sectional | South Africa | Non‐tertiary hospital | Culture‐positive tuberculosis | Sonographer | 377 | 53% | |
| Case‐control | India | Not reported | Pulmonary tuberculosis, extra‐pulmonary tuberculosis, disseminated tuberculosis | Not reported | 90 (45 cases, 45 HIV‐positive controls without any pathology) | ‐ | |
| Case‐control | Spain | Not reported | Disseminated tuberculosis | Not reported | 152 (76 cases, 76 HIV‐positive controls without any pathology) | ‐ | |
| Cohort | Tanzania | Referral hospital | Pulmonary tuberculosis, extra‐pulmonary tuberculosis, disseminated tuberculosis | Board‐certified sonographers | 100 (191 original study sample) | 46% (higher) 64% (lower) | |
| Cross‐sectional | South Africa | Non‐tertiary hospital | Disseminated tuberculosis | Radiologist | 35 (44 original study sample) | 34% | |
| Cross‐sectional | Cambodia | Referral hospital | Disseminated tuberculosis | Radiologist | 212 | 18% | |
| Cross‐sectional | Zambia | Tertiary hospital | Abdominal tuberculosis | Not reported | 31 | 71% | |
| Cohort | India | Tertiary hospital | Disseminated tuberculosis | Trained non‐radiologist | 81 (425 original study sample) | 30% (higher) 49% (lower) | |
| aIncludes five HIV‐negative participants. Suffix (h) indicates higher‐quality reference standard; suffix (l) indicates lower‐quality reference standard. | |||||||
| Author (publication year) | Index test variable included (threshold) | Reference standard quality and definition |
| Ascites (any) Lymphadenopathy (abdominal and perihepatic nodes with longitudinal diameter > 20 mm) Splenomegaly (> 135 mm) | Lower: Clinical, endoscopic, histologic, radiologic and operative findings including microbiology and polymerase chain reaction of biopsies taken during endoscopy | |
| Any abnormality (Presence of ≥ 1: i) pericardial effusion, ii) periportal/para‐aortic lymph nodes (> 15 mm diameter), iii) focal splenic lesions, iv) pleural effusion or consolidation of the lung, v) ascites without alternative explanation) | Lower: Sputum microscopy OR clinical reasons OR Focused Assessment with Sonography in HIV‐associated tuberculosis (FASH) | |
| Any abnormality (presence of ≥ 1: i) multiple hypoechoic splenic lesions (< 10 mm), ii) any abdominal adenopathy, iii) hypo‐ or hyperechoic liver lesions) | Higher: Microscopy OR culture | |
| Any abnormality (presence of ≥ 1: i) abdominal lymph nodes (any size), ii) splenic hypoechoic lesions, iii) splenomegaly (≥ 110 mm), iv) any one of abdominal, pleural, or pericardial effusions) Ascites (any) Lymphadenopathy (any size) Splenic lesions (hypoechoic) Splenomegaly (≥ 110 mm) | Higher: Positive culture for M tuberculosis from any site | |
| Ascites (any) Hepatomegaly (not defined) Lymphadenopathy (diameter > 15 mm) Splenic lesions (multiple, hypoechoic, 5 mm to 10 mm diameter) Splenomegaly (not defined) | Lower: Lymphocytic predominance and elevated adenosine deaminase (ADA) levels in pleural or ascitic fluid OR granulomatous lymphadenitis and acid‐fast bacilli in lymph node OR sputum microscopy | |
| Ascites (any) Hepatomegaly (not defined) Lymphadenopathy (> 15 mm diameter) Splenic lesions (hypoechoic nodes) Splenomegaly (long axis > 120 mm or subjective impression) | Lower: Blood culture positive for M tuberculosis OR medullary bone or liver biopsy with granulomatous inflammation or culture positive for M tuberculosis OR microbiological or histopathological confirmation in ≥ 2 non‐contiguous extra‐pulmonary sites | |
| Any abnormality (presence of ≥ 1: i) pleural or pericardial effusion, ii) ascites, iii) abdominal lymph nodes > 15 mm, iv) hypoechogenic lesions in the liver or spleen, v) ileum wall thickening > 4 mm or destructed ileum wall architecture) Ascites (any) Hepatomegaly (not defined) Lymphadenopathy (> 15 mm diameter) Splenomegaly (not defined) | Higher: Xpert MTB/RIF assay and/or bacteriologic culture (growth of M tuberculosis) | |
| Ascites (any) Lymphadenopathy (not defined) | Higher: Positive mycobacterial blood or bone marrow cultures OR positive mycobacterial cultures from 2 or more other sites OR post mortem evidence | |
| Any abnormality (presence of ≥ 1: i) any lymph nodes ≥ 12 mm, ii) ascites, iii) hepatomegaly, iv) splenomegaly, v) hepatic or splenic hypoechoic lesions with or without organ enlargement) | Higher: Positive culture for M tuberculosis from any site | |
| Ascites (any) Hepatomegaly (not defined) Lymphadenopathy (not defined) Splenomegaly (not defined) | Lower: Positive bacteriological culture OR granulomatous inflammation with positive Ziehl‐Neelsen (ZN) staining on microscopy OR granulomatous inflammation on microscopy OR visual inspection on laparoscopy consistent with tuberculosis (presence of tubercles, fibro‐adhesive peritonitis, or caseating lymphadenopathy) and favourable response to anti‐tuberculous treatment | |
| Any abnormality (presence of ≥ 1: i) pericardial or pleural effusion, ii) focal liver or splenic lesions, iii) abdominal lymphadenopathy) Ascites (any) Hepatomegaly (not defined) Lymphadenopathy (≥ 15 mm diameter) Splenic lesions (multiple, hypoechoic, 2 mm to 5 mm diameter) | Higher: Positive fluorescent microscopy, polymerase chain reaction, or tuberculosis culture | |
| Suffix (h) indicates higher quality reference standard; suffix (l) indicates lower quality reference standard | ||
| Abdominal ultrasound finding | Number of studies | Number of participants (tuberculosiscases) | Pooled sensitivity (95% CI) % | Pooled specificity (95% CI) % | Range of sensitivity % | Range of specificity % |
| Any abnormality (higher‐quality reference standard) | 5 | 879 (368) | 63 (43 to 79) | 68 (72 to 87) | 35 to 82 | 20 to 92 |
| Any abnormality (lower‐quality reference standard) | 4 | 397 (149) | 68 (45 to 85) | 73 (41 to 91) | 37 to 88 | 22 to 92 |
| Splenic lesions | 6 | 916 (477) | Not calculated | Not calculated | 13 to 62 | 86 to 100 |
| Intra‐abdominal lymph nodes | 8 | 917 (455) | Not calculated | Not calculated | 22 to 86 | 56 to 100 |
| Ascites | 8 | 891 (433) | Not calculated | Not calculated | 4 to 73 | 33 to 100 |
| Splenomegaly | 6 | 775 (397 | Not calculated | Not calculated | 5 to 62 | 45 to 89 |
| Hepatomegaly | 4 | 373 (189) | Not calculated | Not calculated | 24 to 76 | 20 to 78 |
| Test | No. of studies | No. of participants |
| 1 Abnormal abdominal ultrasound (higher quality) Show forest plot | 5 | 879 |
| 2 Abnormal abdominal ultrasound (lower quality) Show forest plot | 4 | 397 |
| 3 Ascites Show forest plot | 8 | 891 |
| 4 Splenic lesions Show forest plot | 6 | 916 |
| 5 Abdominal lymph nodes Show forest plot | 8 | 917 |
| 6 Splenomegaly Show forest plot | 6 | 775 |
| 7 Hepatomegaly Show forest plot | 4 | 373 |
