Evidence map›Paper›PMID 24040170›Full record

ArticlePloS one2013

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

Jayne S Sutherland, Maeve K Lalor, Gillian F Black, Lyn R Ambrose, Andre G Loxton, Novel N Chegou, Desta Kassa, Adane Mihret, Rawleigh Howe, Harriet Mayanja-Kizza and 15 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 2 pooled it
3.6field-weighted citation impact, top 6% 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

35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. A Systematic Review on NovelFrontiers in immunology · 2018
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  19. An adjuvant-modulated vaccine response in human whole blood.Human vaccines & immunotherapeutics · 2017
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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

25 authors at 11 institutions in 9 countries.

Jayne S SutherlandVaccinology Theme, Medical Research Council Unit, Fajara, The Gambia.
Maeve K Lalor
Gillian F Black
Lyn R Ambrose
Andre G Loxton
Novel N Chegou
Desta Kassa
Adane Mihret
Rawleigh Howe
Harriet Mayanja-Kizza
Marie P Gomez
Simon Donkor
Kees Franken
Willem Hanekom
Michel R Klein
Shreemanta K Parida
W Henry Boom
Bonnie A Thiel
Amelia C Crampin
Martin Ota
Gerhard Walzl
Tom H M Ottenhoff
Hazel M Dockrell
Stefan H E Kaufmann
GCGH Biomarkers for TB consortium
MRC Unit the Gambia · GMStellenbosch University · ZALeiden University Medical Center · NLLondon School of Hygiene & Tropical Medicine · GBArmauer Hansen Research Institute · ETCase Western Reserve University · USMax Planck Institute for Infection Biology · DEEthiopian Public Health Institute · ETMakerere University · UGMalawi Epidemiology and Intervention Research Unit · MWUniversity of Cape Town · ZA

Funding

Medical Research Council MC_U190071468Medical Research Council MC_U190074190Medical Research Council MC_U190081991Medical Research Council MC_UP_A900_1122Wellcome Trust 098610
6 · The paper itself

Abstract

backgroundTuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas.

methodsWe analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens.

resultsThere was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen.

conclusionsOur multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials.

Indexed as

CoinfectionAdultAfrica South of the SaharaAntigens, BacterialCD4 Lymphocyte CountCluster AnalysisFemaleHIV InfectionsHumansInterferon-gammaMaleMiddle AgedMycobacterium tuberculosisTuberculosisYoung AdultAntigens, BacterialInterferon-gamma

Identifiers

PMID24040170
PMCPMC3769366
OpenAlexW2105219899

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.