A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru

Most cases of pediatric HIV were acquired via perinatal transmission; few mothers were diagnosed before delivery; and among mothers with known HIV status, PMTCT was suboptimal even after national PMTCT policy was implemented. Most children were diagnosed with advanced disease. These findings underscore the need for improving early pediatric HIV diagnosis and treatment, as well as PMTCT strategies.

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“…As has been shown in other studies, diagnosis of pediatric tuberculosis, especially with HIV co-infection, is very challenging. 34,35…”

Section: Discussionmentioning

confidence: 99%

Morbidity and Mortality of a Cohort of Peruvian HIV-infected Children 2003–2012

Baker

Bayer

Viani

et al. 2018

Pediatric Infectious Disease Journal

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“…Sputum culture is considered the gold standard for ATB diagnosis but takes 6–7 days for a positive diagnosis and up to 42 days for a confirmed negative diagnosis. Current sputum-based tests in clinical practice (e.g., smear microscopy, culture, and PCR-based assays) do not meet the desired target product profiles (TPPs), lack the sensitivity to reliably distinguish ATB from LTBI, and are prone to producing false negative results because sufficient bacilli-containing sputum samples can be difficult to obtain, especially from children and from individuals co-infected with HIV [3–12]. Sputum-bacilli tests cannot be used to identify patients with a high risk of progression because diagnosis with ATB is defined by the presence of bacilli in sputum [12].…”

Section: Introductionmentioning

confidence: 99%

Host-response-based gene signatures for tuberculosis diagnosis: A systematic comparison of 16 signatures

2019

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Background The World Health Organization (WHO) and Foundation for Innovative New Diagnostics (FIND) have published target product profiles (TPPs) calling for non-sputum-based diagnostic tests for the diagnosis of active tuberculosis (ATB) disease and for predicting the progression from latent tuberculosis infection (LTBI) to ATB. A large number of host-derived blood-based gene-expression biomarkers for diagnosis of patients with ATB have been proposed to date, but none have been implemented in clinical settings. The focus of this study is to directly compare published gene signatures for diagnosis of patients with ATB across a large, diverse list of publicly available gene expression datasets, and evaluate their performance against the WHO/FIND TPPs. Methods and findings We searched PubMed, Gene Expression Omnibus (GEO), and ArrayExpress in June 2018. We included all studies irrespective of study design and enrollment criteria. We found 16 gene signatures for the diagnosis of ATB compared to other clinical conditions in PubMed. For each signature, we implemented a classification model as described in the corresponding original publication of the signature. We identified 24 datasets containing 3,083 transcriptome profiles from whole blood or peripheral blood mononuclear cell samples of healthy controls or patients with ATB, LTBI, or other diseases from 14 countries in GEO. Using these datasets, we calculated weighted mean area under the receiver operating characteristic curve (AUROC), specificity at 90% sensitivity, and negative predictive value (NPV) for each gene signature across all datasets. We also compared the diagnostic odds ratio (DOR), heterogeneity in DOR, and false positive rate (FPR) for each signature using bivariate meta-analysis. Across 9 datasets of patients with culture-confirmed diagnosis of ATB, 11 signatures had weighted mean AUROC > 0.8, and 2 signatures had weighted mean AUROC ≤ 0.6. All but 2 signatures had high NPV (>98% at 2% prevalence). Two gene signatures achieved the minimal WHO TPP for a non-sputum-based triage test. When including datasets with clinical diagnosis of ATB, there was minimal reduction in the weighted mean AUROC and specificity of all but 3 signatures compared to when using only culture-confirmed ATB data. Only 4 signatures had homogeneous DOR and lower FPR when datasets with clinical diagnosis of ATB were included; other signatures either had heterogeneous DOR or higher FPR or both. Finally, 7 of 16 gene signatures predicted progression from LTBI to ATB 6 months prior to sputum conversion with positive predictive value > 6% at 2% prevalence. Our analyses may have under- or overestimated the performance of certain ATB diagnostic signatures because our implementation may be different from the published models for those signatures. We re-implemented published models because the exact models were not publicly available. Conclusions We found that host-response-based diagnostics could accurately iden...

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“…We excluded children younger than 12 years because both expectoration of sputum and laboratory confirmation of tuberculosis are uncommon in this age group. 14 …”

Section: Introductionmentioning

confidence: 99%

Comparison of sputum collection methods for tuberculosis diagnosis: a systematic review and pairwise and network meta-analysis

Datta

Shah

Gilman

et al. 2017

The Lancet Global Health

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SummaryBackgroundThe performance of laboratory tests to diagnose pulmonary tuberculosis is dependent on the quality of the sputum sample tested. The relative merits of sputum collection methods to improve tuberculosis diagnosis are poorly characterised. We therefore aimed to investigate the effects of sputum collection methods on tuberculosis diagnosis.MethodsWe did a systematic review and meta-analysis to investigate whether non-invasive sputum collection methods in people aged at least 12 years improve the diagnostic performance of laboratory testing for pulmonary tuberculosis. We searched PubMed, Google Scholar, ProQuest, Web of Science, CINAHL, and Embase up to April 14, 2017, to identify relevant experimental, case-control, or cohort studies. We analysed data by pairwise meta-analyses with a random-effects model and by network meta-analysis. All diagnostic performance data were calculated at the sputum-sample level, except where authors only reported data at the individual patient-level. Heterogeneity was assessed, with potential causes identified by logistic meta-regression.FindingsWe identified 23 eligible studies published between 1959 and 2017, involving 8967 participants who provided 19 252 sputum samples. Brief, on-demand spot sputum collection was the main reference standard. Pooled sputum collection increased tuberculosis diagnosis by microscopy (odds ratio [OR] 1·6, 95% CI 1·3–1·9, p<0·0001) or culture (1·7, 1·2–2·4, p=0·01). Providing instructions to the patient before sputum collection, during observed collection, or together with physiotherapy assistance increased diagnostic performance by microscopy (OR 1·6, 95% CI 1·3–2·0, p<0·0001). Collecting early morning sputum did not significantly increase diagnostic performance of microscopy (OR 1·5, 95% CI 0·9–2·6, p=0·2) or culture (1·4, 0·9–2·4, p=0·2). Network meta-analysis confirmed these findings, and revealed that both pooled and instructed spot sputum collections were similarly effective techniques for increasing the diagnostic performance of microscopy.InterpretationTuberculosis diagnoses were substantially increased by either pooled collection or by providing instruction on how to produce a sputum sample taken at any time of the day. Both interventions had a similar effect to that reported for the introduction of new, expensive laboratory tests, and therefore warrant further exploration in the drive to end the global tuberculosis epidemic.FundingWellcome Trust, Joint Global Health Trials consortium, Innovation For Health and Development, and Bill & Melinda Gates Foundation.

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A Controlled Study of Tuberculosis Diagnosis in HIV-Infected and Uninfected Children in Peru

Cited by 14 publications

References 26 publications

Morbidity and Mortality of a Cohort of Peruvian HIV-infected Children 2003–2012

Morbidity and Mortality of a Cohort of Peruvian HIV-infected Children 2003–2012

Host-response-based gene signatures for tuberculosis diagnosis: A systematic comparison of 16 signatures

Comparison of sputum collection methods for tuberculosis diagnosis: a systematic review and pairwise and network meta-analysis

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