Evidence map›Paper›PMID 37952096›Full record

ArticleMedical mycology2023

Genetic diversity and microevolution in clinical Cryptococcus isolates from Cameroon.

Poppy Sephton-Clark, Elvis Temfack, Jennifer L Tenor, Dena L Toffaletti, Angela Loyse, Síle F Molloy, John R Perfect, Tihana Bicanic, Thomas S Harrison, Olivier Lortholary and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Medical mycology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 32% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Pathogenic diversity ofCell surface (Amsterdam, Netherlands) · 2025
    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

12 authors at 6 institutions in 4 countries.

Poppy Sephton-ClarkInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000-0003-1103-6028
Elvis TemfackInternal Medicine Unit, Douala General Hospital, Douala, Cameroon.ORCID 0000-0001-8189-6555
Jennifer L TenorDivision of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Dena L ToffalettiDivision of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Angela LoyseInstitute of Infection and Immunity, St George's University of London, London, UK.ORCID 0000-0001-7853-1344
Síle F MolloyInstitute of Infection and Immunity, St George's University of London, London, UK.
John R PerfectDivision of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Tihana BicanicInstitute of Infection and Immunity, St George's University of London, London, UK.
Thomas S HarrisonInstitute of Infection and Immunity, St George's University of London, London, UK.
Olivier LortholaryDepartment of Infectious Diseases and Tropical Medicine, Paris Cité University, Necker-Enfants Malades Hospital, AP-HP, IHU Imagine, Paris, France.
Charles KouanfackDepartment of Public Health, Faculty of Medicine and Pharmaceutical Sciences, University of Dschang, Dschang, Cameroon.
Christina A CuomoInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.ORCID 0000-0002-5778-960X
St George's, University of London · GBDuke University · USBroad Institute · USCentre National de la Recherche Scientifique · FRInstitut Pasteur · FRUniversité de Dschang · CM

Funding

Viral Genomics: evolution, spread, and host interactionsU19AI110818 · NIAID · BROAD INSTITUTE, INC. · PI BIRREN, BRUCE W., NEAFSEY, DANIEL E · 2014 to 2024
$66.5M
Pathobiology of C. neoformans in the Central Nervous SystemR01AI073896 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 2008 to 2018
$4.4M
Evolution of Cryptococcus neoformans Strains from Patients with HIV/AIDSR01AI093257 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 2011 to 2022
$3.8M
Medical Research Council MR/V033417/1NIAID NIH HHS R01 AI073896NIAID NIH HHS R01 AI093257NIAID NIH HHS U19 AI110818NIAID NIH HHS U19AI110818
6 · The paper itself

Abstract

Cryptococcal meningitis is the second most common cause of death in people living with HIV/AIDS, yet we have a limited understanding of how cryptococcal isolates change over the course of infection. Cryptococcal infections are environmentally acquired, and the genetic diversity of these infecting isolates can also be geographically linked. Here, we employ whole genome sequences for 372 clinical Cryptococcus isolates from 341 patients with HIV-associated cryptococcal meningitis obtained via a large clinical trial, across both Malawi and Cameroon, to enable population genetic comparisons of isolates between countries. We see that isolates from Cameroon are highly clonal, when compared to those from Malawi, with differential rates of disruptive variants in genes with roles in DNA binding and energy use. For a subset of patients (22) from Cameroon, we leverage longitudinal sampling, with samples taken at days 7 and 14 post-enrollment, to interrogate the genetic changes that arise over the course of infection, and the genetic diversity of isolates within patients. We see disruptive variants arising over the course of infection in several genes, including the phagocytosis-regulating transcription factor GAT204. In addition, in 13% of patients sampled longitudinally, we see evidence for mixed infections. This approach identifies geographically linked genetic variation, signatures of microevolution, and evidence for mixed infections across a clinical cohort of patients affected by cryptococcal meningitis in Central Africa.

Indexed as

Acquired Immunodeficiency SyndromeCoinfectionCryptococcusCryptococcus neoformansHIV InfectionsMeningitis, CryptococcalCameroonGenetic VariationHumansCryptococcusgenome sequencingGWASintrahost diversityphylogeography

Identifiers

PMID37952096
PMCPMC10709296
OpenAlexW4388604174

What OpenQuestion holds

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LicenceCC BY
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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.