Evidence map›Paper›PMID 27798613›Full record

ArticleNature medicine2016

Genomic diversity in autopsy samples reveals within-host dissemination of HIV-associated Mycobacterium tuberculosis.

Tami D Lieberman, Douglas Wilson, Reshma Misra, Lealia L Xiong, Prashini Moodley, Ted Cohen, Roy Kishony

Open access · greenAbstract read
In one paragraph

Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 1 pooled it
12.6field-weighted citation impact, top 1% 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

96 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.

  1. Pooled it
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  7. Article
  8. Heteroresistance inFrontiers in cellular and infection microbiology · 2026
    Review
  9. Review
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  13. Population sequencing for phylogenetic diversity and transmission analyses.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  18. Review
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36 more citing papers are in PubMed but not listed here.

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

7 authors at 4 institutions in 3 countries.

Tami D LiebermanDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
Douglas WilsonDepartment of Internal Medicine, Edendale Hospital, University of KwaZulu-Natal, Pietermaritzburg, South Africa.
Reshma MisraDepartment of Infection Prevention and Control, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.ORCID 0000-0002-5512-9456
Lealia L XiongDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-7636-5936
Prashini MoodleyDepartment of Infection Prevention and Control, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Ted CohenDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA.
Roy KishonyDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA.
Harvard University · USUniversity of KwaZulu-Natal · ZABrigham and Women's Hospital · USEdendale Hospital · ZA

Funding

Understanding and controlling antibiotic resistanceU54GM088558 · NIGMS · HARVARD SCHOOL OF PUBLIC HEALTH · PI LIPSITCH, MARC · 2009 to 2018
$26.4M
The population genetics of antibiotic resistance in multi-drug environmentsR01GM081617 · NIGMS · TECHNION-ISRAEL INSTITUTE OF TECHNOLOGY · PI KISHONY, ROY · 2007 to 2018
$3.7M
Prevalence, risk factors and consequences of complex M. Tuberculosis infectionsDP2OD006663 · OD · BRIGHAM AND WOMEN'S HOSPITAL · PI COHEN, THEODORE H · 2010 to 2010
$2.7M
NIGMS NIH HHS R01 GM081617NIGMS NIH HHS U54 GM088558NIH HHS DP2 OD006663
6 · The paper itself

Abstract

Mycobacterium tuberculosis remains a leading cause of death worldwide, especially among individuals infected with HIV. Whereas phylogenetic analysis has revealed M. tuberculosis spread throughout history and in local outbreaks, much less is understood about its dissemination within the body. Here we report genomic analysis of 2,693 samples collected post mortem from lung and extrapulmonary biopsies of 44 subjects in KwaZulu-Natal, South Africa, who received minimal antitubercular treatment and most of whom were HIV seropositive. We found that purifying selection occurred within individual patients, without the need for patient-to-patient transmission. Despite negative selection, mycobacteria diversified within individuals to form sublineages that co-existed for years. These sublineages, as well as distinct strains from mixed infections, were differentially distributed throughout the lung, suggesting temporary barriers to pathogen migration. As a consequence, samples taken from the upper airway often captured only a fraction of the population diversity, challenging current methods of outbreak tracing and resistance diagnostics. Phylogenetic analysis indicated that dissemination from the lungs to extrapulmonary sites was as frequent as between lung sites, supporting the idea of similar migration routes within and between organs, at least in subjects with HIV. Genomic diversity therefore provides a record of pathogen diversification and repeated dissemination across the body.

Indexed as

AdultAgedAutopsyBacteriological TechniquesCoinfectionDNA, BacterialFemaleGenetic VariationHIV InfectionsHumansLiverLungLymph NodesMaleMiddle AgedMycobacterium tuberculosisDNA, Bacterial

Identifiers

PMID27798613
PMCPMC5508070
OpenAlexW2542326685

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.