Evidence map›Paper›PMID 34494858›Full record

ArticleMicrobiology spectrum2021

Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden.

Emmanuel Musisi, Christian Dide-Agossou, Reem Al Mubarak, Karen Rossmassler, Abdul Wahab Ssesolo, Sylvia Kaswabuli, Patrick Byanyima, Ingvar Sanyu, Josephine Zawedde, William Worodria and 7 more

Open access · goldAbstract read
In one paragraph

Article in Microbiology spectrum, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 25% of its field
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

3 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
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

17 authors at 8 institutions in 3 countries.

Emmanuel Musisi *Infectious Disease Research Collaboration, Kampala, Uganda.
Christian Dide-Agossou *Department of Epidemiology, Colorado School of Public Healthgrid.414594.9, Aurora, Colorado, USA.ORCID 0000-0001-9854-1785
Reem Al MubarakRocky Mountain Regional VA Medical Center, Aurora, Colorado, USA.
Karen RossmasslerRocky Mountain Regional VA Medical Center, Aurora, Colorado, USA.
Abdul Wahab SsesoloInfectious Disease Research Collaboration, Kampala, Uganda.
Sylvia KaswabuliInfectious Disease Research Collaboration, Kampala, Uganda.
Patrick ByanyimaInfectious Disease Research Collaboration, Kampala, Uganda.
Ingvar SanyuInfectious Disease Research Collaboration, Kampala, Uganda.
Josephine ZaweddeInfectious Disease Research Collaboration, Kampala, Uganda.
William WorodriaInfectious Disease Research Collaboration, Kampala, Uganda.
Martin I VoskuilDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Rada M SavicConsortium for Applied Microbial Metrics, Aurora, Colorado, USA.ORCID 0000-0003-3143-5579
Payam NahidConsortium for Applied Microbial Metrics, Aurora, Colorado, USA.
J Lucian DavisDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA.ORCID 0000-0002-8629-9992
Laurence HuangDivision of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, USA.
Camille M MooreDivision of Biostatistics and Bioinformatics, National Jewish Health, Denver, Colorado, USA.
Nicholas D WalterRocky Mountain Regional VA Medical Center, Aurora, Colorado, USA.
Infectious Diseases Research Collaboration · UGUniversity of Colorado Anschutz Medical Campus · USUniversity of California, San Francisco · USColorado School of Public Health · USNational Jewish Health · USSan Francisco General Hospital · USUniversity of St Andrews · GBYale University · US

Funding

Inflammation, Aging, Microbes, Obstructive Lung Disease and Diffusion Abnormalities (I AM OLD-DA) Study - Diversity SupplementR01HL128156 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, LAURENCE, HUNT, PETER W · 2015 to 2024
$7.1M
Sputum Transcriptomic Expression Profiling in Study 31: Express 31R01AI127300 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DAVIS, JOHN LUCIAN, NAHID, PAYAM · 2017 to 2022
$6.2M
International HIV-associated Opportunistic Pneumonias (IHOP) StudyR01HL090335 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, LAURENCE · 2007 to 2011
$4.0M
Lung Microbiome in Cohorts of HIV-Infected Persons (Lung MicroCHIP) StudyU01HL098964 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, LAURENCE · 2009 to 2013
$3.9M
TB and Other Pulmonary Complications of AIDS Research Training ProgramD43TW009607 · FIC · YALE UNIVERSITY · PI DAVIS, JOHN LUCIAN, KATAMBA, ACHILLES · 2013 to 2022
$3.2M
Integrated Analysis of Microbial and Genomic data in Obstructive Lung Disease (I AM GOLD) StudyR01HL143998 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHRISTENSON, STEPHANIE A, HUANG, LAURENCE · 2019 to 2022
$3.2M
Patient-Oriented Research and Mentoring in PneumocystisK24HL087713 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, LAURENCE · 2006 to 2018
$1.8M
Precursor-rRNA profiling as a measure of drug activity in tuberculosisR21AI135652 · NIAID · UNIVERSITY OF COLORADO DENVER · PI VOSKUIL, MARTIN INUA, WALTER, NICHOLAS D · 2018 to 2019
$435k
Blood Expression Profiles as a Biomarker for Responses to Tuberculosis TreatmentIK2CX000914 · VA · VA EASTERN COLORADO HEALTH CARE SYSTEM · PI WALTER, NICHOLAS D · 2014 to 2018
–
Impact of Sterilizing and Non-sterilizing Antibiotics on M. tuberculosis rRNA SynthesisI01BX004527 · VA · VA EASTERN COLORADO HEALTH CARE SYSTEM · PI WALTER, NICHOLAS D · 2020 to 2023
–
BLRD VA I01 BX004527CSRD VA IK2 CX000914FIC NIH HHS D43 TW009607NHLBI NIH HHS K24 HL087713NHLBI NIH HHS R01 HL090335NHLBI NIH HHS R01 HL128156NHLBI NIH HHS R01 HL143998NHLBI NIH HHS U01 HL098964NIAID NIH HHS R01 AI127300NIAID NIH HHS R21 AI135652
6 · The paper itself

Abstract

There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay called the rRNA synthesis (RS) ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. Here, we evaluated RS ratio as a potential pharmacodynamic monitoring tool by testing pretreatment sputa from 38 Ugandan adults with drug-susceptible pulmonary TB. We quantified the RS ratio in paired pretreatment sputa and evaluated the relationship between the RS ratio and microbiologic and molecular markers of M. tuberculosis burden. We found that the RS ratio was highly repeatable and reproducible in sputum samples. The RS ratio was independent of M. tuberculosis burden, confirming that it measures a distinct new property. In contrast, markers of M. tuberculosis burden were strongly associated with each other. These results indicate that the RS ratio is repeatable and reproducible and provides a distinct type of information from markers of M. tuberculosis burden.

Indexed as

AdultBiomarkersFemaleHumansMaleMycobacterium tuberculosisRNA, BacterialRNA, RibosomalSputumTuberculosis, PulmonaryBiomarkersRNA, BacterialRNA, Ribosomalassay developmenthumanMycobacterium tuberculosispharmacodynamicssputum

Identifiers

PMID34494858
PMCPMC8557932
OpenAlexW3197227225

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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.