Evidence map›Paper›PMID 35325781›Full record

ArticleEBioMedicine2022

Serial measurement of M. tuberculosis in blood from critically-ill patients with HIV-associated tuberculosis.

David A Barr, Charlotte Schutz, Avuyonke Balfour, Muki Shey, Mireille Kamariza, Carolyn R Bertozzi, Timothy J de Wet, Ryan Dinkele, Amy Ward, Kathryn A Haigh and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
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  5. Implant-associatedJournal of clinical orthopaedics and trauma · 2024
    Article
  6. Review
  7. Article
  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

David A BarrWellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa; Institute of Infection and Global Health, University of Liverpool, Liverpool L7 3EA, UK. Electronic address: david.barr@liverpool.ac.uk.
Charlotte SchutzWellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa; Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
Avuyonke BalfourWellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa.
Muki SheyWellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa; Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
Mireille KamarizaDepartment of Biology, Stanford University, Stanford, CA 94305, USA.
Carolyn R BertozziDepartment of Chemistry, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Timothy J de WetSAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, University of Cape Town, Observatory 7925, South Africa.
Ryan DinkeleSAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, University of Cape Town, Observatory 7925, South Africa.
Amy WardWellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa; Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
Kathryn A HaighInstitute of Infection and Global Health, University of Liverpool, Liverpool L7 3EA, UK.
Jean-Paul KanyikWellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa; Khayelitsha Hospital, Department of Medicine, Cape Town, South Africa.
Valerie MizrahiWellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa; SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, University of Cape Town, Observatory 7925, South Africa.
Mark P NicolDivision of Infection and Immunity School of Biomedical Sciences, University of Western Australia, Perth, Australia,; Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
Robert J WilkinsonWellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa; Department of Medicine, University of Cape Town, Observatory 7925, South Africa; The Francis Crick Institute, London NW1 1AT, UK; Department of Infectious Disease, Imperial College, London W12 0NN, United Kingdom.
David G LallooLiverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
Digby F WarnerWellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa; SAMRC/NHLS/UCT Molecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, University of Cape Town, Observatory 7925, South Africa.
Graeme MeintjesWellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa; Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
Gerry DaviesInstitute of Infection and Global Health, University of Liverpool, Liverpool L7 3EA, UK.

Funding

Mycobacterial Sulfation PathwaysR01AI051622 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI BERTOZZI, CAROLYN · 2002 to 2015
$6.0M
Chemical MycobateriologyR37AI051622 · NIAID · STANFORD UNIVERSITY · PI BERTOZZI, CAROLYN · 2016 to 2025
$4.7M
Inflammatory determinants of disease severity and treatment outcome in TB patientsU01AI115940 · NIAID · UNIVERSITY OF CAPE TOWN · PI SHER, ALAN, WILKINSON, ROBERT JOHN · 2015 to 2019
$1.1M
Investigating a fluorogenic DMN-trehalose conjugate as a novel detection tool for Mycobacterium tuberculosisF31AI129359 · NIAID · STANFORD UNIVERSITY · PI KAMARIZA, MIREILLE · 2017 to 2018
$89k
NIAID NIH HHS F31 AI129359NIAID NIH HHS R01 AI051622NIAID NIH HHS R37 AI051622NIAID NIH HHS U01 AI115940Wellcome Trust
6 · The paper itself

Abstract

backgroundDespite being highly prevalent in hospitalised patients with severe HIV-associated tuberculosis (TB) and sepsis, little is known about the mycobacteriology of Mycobacterium tuberculosis bloodstream infection (MTBBSI). We developed methods to serially measure bacillary load in blood and used these to characterise MTBBSI response to anti-TB therapy (ATT) and relationship with mortality.

methodsWe established a microscopy method for direct visualisation of M. tuberculosis bacilli in blood using a novel lysis-concentration protocol and the fluorescent probe, 4-N,N-dimethylaminonaphthalimide-trehalose (DMN-Tre). We tested blood using GeneXpert® MTB/RIF-Ultra (Xpert-ultra) and Myco/F lytic culture after processing blood through lysis-wash steps to remove PCR inhibitors and anti-microbial drug carry-over. HIV-positive patients predicted to have MTBBSI gave blood samples 0, 4, 24, 48 and 72 h after ATT initiation. Bacillary loads were quantified using microscopy, Xpert-ultra cycle threshold, and culture time-to-positivity. Pharmacodynamics were modelled using these measures combined on an ordinal scale, including association with 12-week mortality.

findingsM. tuberculosis was detected in 27 of 28 recruited participants; 25 (89%) by blood Xpert-ultra, 22 (79%) by DMN-Tre microscopy, and 21 (75%) by Myco/F lytic blood culture. Eight (29%) participants died by 12-week follow-up. In a combined pharmacodynamic model, predicted probabilities of negative DMN-Tre microscopy, blood Xpert-ultra, or blood culture after 72 h treatment were 0·64, 0·27, and 0·94, respectively, in those who survived, compared with 0·23, 0·06, and 0·71 in those who died (posterior probability of slower clearance of MTBBSI in those that died >0·99). DMN-Tre microscopy of blood demonstrated heterogenous bacillary morphologies, including microcolonies and clumps. Bacillary cell-length varied significantly with ATT exposure (mean cell-length increase 0·13 log-µm/day; 95%CrI 0·10-0·16).

interpretationPharmacodynamics of MTBBSI treatment can be captured using DMN-Tre microscopy, blood Xpert-ultra and culture. This could facilitate interventional trials in severe HIV-associated TB.

fundingWellcome Trust, NIH Fogarty International Center, South African MRC, NIHR(UK), National Research Foundation of South Africa.

Indexed as

HIV InfectionsMycobacterium tuberculosisTuberculosisTuberculosis, PulmonaryCritical IllnessHumansSensitivity and SpecificitySputumBlood stream infectionCritical-illnessHIV-associated tuberculosisPharmacodynamicsSepsis

Identifiers

PMID35325781
PMCPMC8938880

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.