Imperial College London

ProfessorMichaelLevin

Faculty of MedicineDepartment of Medicine

Chair in Paediatrics & International Child Health
 
 
 
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Contact

 

+44 (0)20 7594 3760m.levin

 
 
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Location

 

233Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

214 results found

Brent AJ, Mugo D, Musyimi R, Mutiso A, Morpeth S, Levin M, Scott JAGet al., 2017, Bacteriological diagnosis of childhood TB: a prospective observational study, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

JOURNAL ARTICLE

Dietz SM, van Stijn D, Burgner D, Levin M, Kuipers IM, Hutten BA, Kuijpers TWet al., 2017, Dissecting Kawasaki disease: a state-of-the-art review, EUROPEAN JOURNAL OF PEDIATRICS, Vol: 176, Pages: 995-1009, ISSN: 0340-6199

JOURNAL ARTICLE

Gliddon HD, Herberg JA, Levin M, Kaforou Met al., 2017, Genome-wide host RNA signatures of infectious diseases: discovery and clinical translation., Immunology

The use of whole blood gene expression to derive diagnostic biomarkers capable of distinguishing between phenotypically similar diseases holds great promise but remains a challenge. Differential gene expression analysis is used to identify the key genes that undergo changes in expression relative to healthy individuals, as well as to patients with other diseases. These key genes can act as diagnostic, prognostic and predictive markers of disease. Gene expression 'signatures' in the blood hold the potential to be used for the diagnosis of infectious diseases, where current diagnostics are unreliable, ineffective or of limited potential. For diagnostic tests based on RNA signatures to be useful clinically, the first step is to identify the minimum set of gene transcripts that accurately identify the disease in question. The second requirement is rapid and cost-effective detection of the gene expression levels. Signatures have been described for a number of infectious diseases, but 'clinic-ready' technologies for RNA detection from clinical samples are limited, though existing methods such as RT-PCR are likely to be superseded by a number of emerging technologies, which may form the basis of the translation of gene expression signatures into routine diagnostic tests for a range of disease states.

JOURNAL ARTICLE

Hemingway C, Berk M, Anderson ST, Wright VJ, Hamilton S, Eleftherohorinou H, Kaforou M, Goldgof GM, Hickman K, Kampmann B, Schoeman J, Eley B, Beatty D, Pienaar S, Nicol MP, Griffiths MJ, Waddell SJ, Newton SM, Coin LJ, Relman DA, Montana G, Levin Met al., 2017, Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function., PLoS One, Vol: 12

The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies.

JOURNAL ARTICLE

Israel L, Wang Y, Bulek K, Della Mina E, Zhang Z, Pedergnana V, Chrabieh M, Lemmens NA, Sancho-Shimizu V, Descatoire M, Lasseau T, Israelsson E, Lorenzo L, Yun L, Belkadi A, Moran A, Weisman LE, Vandenesch F, Batteux F, Weller S, Levin M, Herberg J, Abhyankar A, Prando C, Itan Y, van Wamel WJB, Picard C, Abel L, Chaussabel D, Li X, Beutler B, Arkwright PD, Casanova J-L, Puel Aet al., 2017, Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity, CELL, Vol: 168, Pages: 789-+, ISSN: 0092-8674

JOURNAL ARTICLE

Kaforou M, Herberg JA, Wright VJ, Coin LJM, Levin Met al., 2017, Diagnosis of Bacterial Infection Using a 2-Transcript Host RNA Signature in Febrile Infants 60 Days or Younger, JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, Vol: 317, Pages: 1577-1578, ISSN: 0098-7484

JOURNAL ARTICLE

Shimizu C, Kim J, Eleftherohorinou H, Wright V, Hoang L, Tremoulet A, Franco A, Hibberd M, Takahashi A, Kubo M, Ito K, Tanaka T, Onouchi Y, Coin L, Levin M, Burns J, Shike Het al., 2017, Genetic Variants in HLA-C and Class I Pathway Genes Influence Susceptibility to Kawasaki Disease, Publisher: WILEY, ISSN: 2326-5191

CONFERENCE PAPER

Gliddon HD, Howes PD, Kaforou M, Levin M, Stevens MMet al., 2016, A nucleic acid strand displacement system for the multiplexed detection of tuberculosis-specific mRNA using quantum dots, NANOSCALE, Vol: 8, Pages: 10087-10095, ISSN: 2040-3364

JOURNAL ARTICLE

Herberg JA, Kaforou M, Wright VJ, Shailes H, Eleftherohorinou H, Hoggart CJ, Cebey-Lopez M, Carter MJ, Janes VA, Gormley S, Shimizu C, Tremoulet AH, Barendregt AM, Salas A, Kanegaye J, Pollard AJ, Faust SN, Patel S, Kuijpers T, Martinon-Torres F, Burns JC, Coin LJM, Levin Met al., 2016, Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children, JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, Vol: 316, Pages: 835-845, ISSN: 0098-7484

JOURNAL ARTICLE

Levin M, Kaforou M, 2016, Predicting active tuberculosis progression by RNA analysis, LANCET, Vol: 387, Pages: 2268-2270, ISSN: 0140-6736

JOURNAL ARTICLE

Martinon-Torres F, Png E, Khor CC, Davila S, Wright VJ, Sim KS, Vega A, Fachal L, Inwald D, Nadel S, Carrol ED, Martinon-Torres N, Marcos Alonso S, Carracedo A, Morteruel E, Lopez-Bayon J, Concha Torre A, Calvo Monge C, Gonzalez de Aguilar PA, Esteban Torne E, del Carmen Martinez-Padilla M, Maria Martinon-Sanchez J, Levin M, Hibberd ML, Salas Aet al., 2016, Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322

JOURNAL ARTICLE

McDonald JU, Kaforou M, Clare S, Hale C, Ivanova M, Huntley D, Dorner M, Wright VJ, Levin M, Martinon-Torres F, Herberg JA, Tregoning JSet al., 2016, A Simple Screening Approach To Prioritize Genes for Functional Analysis Identifies a Role for Interferon Regulatory Factor 7 in the Control of Respiratory Syncytial Virus Disease, MSYSTEMS, Vol: 1, ISSN: 2379-5077

JOURNAL ARTICLE

Seaby EG, Wright VJ, Levin M, 2016, Genome-wide Association Studies in Infectious Diseases, PEDIATRIC INFECTIOUS DISEASE JOURNAL, Vol: 35, Pages: 802-804, ISSN: 0891-3668

JOURNAL ARTICLE

Shimizu C, Eleftherohorinou H, Wright VJ, Kim J, Alphonse MP, Perry JC, Cimaz R, Burgner D, Dahdah N, Hoang LT, Khor CC, Salgado A, Tremoulet AH, Davila S, Kuijpers TW, Hibberd ML, Johnson TA, Takahashi A, Tsunoda T, Kubo M, Tanaka T, Onouchi Y, Yeung RSM, Coin LJM, Levin M, Burns JCet al., 2016, Genetic Variation in the SLC8A1 Calcium Signaling Pathway Is Associated With Susceptibility to Kawasaki Disease and Coronary Artery Abnormalities, CIRCULATION-CARDIOVASCULAR GENETICS, Vol: 9, Pages: 559-+, ISSN: 1942-325X

JOURNAL ARTICLE

Davies S, Sutton N, Blackstock S, Gormley S, Hoggart CJ, Levin M, Herberg JAet al., 2015, Predicting IVIG resistance in UK Kawasaki disease, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 100, Pages: 366-368, ISSN: 0003-9888

JOURNAL ARTICLE

Eleftheriou D, Levin M, Shingadia D, Tulloh R, Klein N, Brogan Pet al., 2015, Authors' response to 'Aspirin dose for treatment of Kawasaki disease', ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 100, ISSN: 0003-9888

JOURNAL ARTICLE

Evans C, Orf K, Horvath E, Levin M, De La Fuente J, Chakravorty S, Cunnington AJet al., 2015, Impairment of neutrophil oxidative burst in children with sickle cell disease is associated with heme oxygenase-1, HAEMATOLOGICA, Vol: 100, Pages: 1508-1516, ISSN: 0390-6078

JOURNAL ARTICLE

George EC, Walker AS, Kiguli S, Olupot-Olupot P, Opoka RO, Engoru C, Akech SO, Nyeko R, Mtove G, Reyburn H, Berkley JA, Mpoya A, Levin M, Crawley J, Gibb DM, Maitland K, Babiker AGet al., 2015, Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) Score, BMC MEDICINE, Vol: 13, ISSN: 1741-7015

JOURNAL ARTICLE

Kiguli S, Maitland K, George EC, Olupot-Olupot P, Opoka RO, Engoru C, Akech SO, Nyeko R, Mtove G, Reyburn H, Levin M, Babiker AG, Gibb DM, Crawley Jet al., 2015, Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness, BMC MEDICINE, Vol: 13, ISSN: 1741-7015

JOURNAL ARTICLE

Nicol MP, Gnanashanmugam D, Browning R, Click ES, Cuevas LE, Detjen A, Graham SM, Levin M, Makhene M, Nahid P, Perez-Velez CM, Reither K, Song R, Spiegel HML, Worrell C, Zar HJ, Walzl Get al., 2015, A Blueprint to Address Research Gaps in the Development of Biomarkers for Pediatric Tuberculosis, CLINICAL INFECTIOUS DISEASES, Vol: 61, Pages: S164-S172, ISSN: 1058-4838

JOURNAL ARTICLE

Shah V, Christov G, Mukasa T, Brogan KS, Wade A, Eleftheriou D, Levin M, Tulloh RM, Almeida B, Dillon MJ, Marek J, Klein N, Brogan PAet al., 2015, Cardiovascular status after Kawasaki disease in the UK, HEART, Vol: 101, Pages: 1646-1655, ISSN: 1355-6037

JOURNAL ARTICLE

Stevens J, Herberg JA, Levin M, 2015, Infectious diseases and the kidney in children, Pediatric Nephrology, Seventh Edition, Pages: 1609-1654, ISBN: 9783662435960

© Springer-Verlag Berlin Heidelberg 2009, 2016. The kidney is involved in a wide range of bacterial, viral, fungal, and parasitic diseases. In most systemic infections, renal involvement is a minor component of the illness, but in some, renal failure may be the presenting feature and the major problem in management. Although individual infectious processes may have a predilection to involve the renal vasculature, glomeruli, interstitium, or collecting systems, a purely anatomic approach to the classification of infectious diseases affecting the kidney is rarely helpful because most infections may involve several different aspects of renal function. In this chapter, a microbiological classification of the organisms affecting the kidney is adopted. Although they are important causes of renal dysfunction in infectious diseases, urinary tract infections and hemolytic uremic syndrome (HUS) are not discussed in detail because they are considered separately in chapters XX and XX, respectively. The kidney is involved in a wide range of bacterial, viral, fungal, and parasitic diseases. In most systemic infections, renal involvement is a minor component of the illness, but in some, renal failure may be the presenting feature and the major problem in management. Although individual infectious processes may have a predilection to involve the renal vasculature, glomeruli, interstitium, or collecting systems, a purely anatomic approach to the classification of infectious diseases affecting the kidney is rarely helpful because most infections may involve several different aspects of renal function. In this chapter, a microbiological classification of the organisms affecting the kidney is adopted. Although they are important causes of renal dysfunction in infectious diseases, urinary tract infections and hemolytic uremic syndrome (HUS) are not discussed in detail because they are considered separately in Chaps.‚Äč 47, “Renal Involvement in Children with HUS,” and 53

BOOK CHAPTER

von Both U, Kaforou M, Levin M, Newton SMet al., 2015, Understanding immune protection against tuberculosis using RNA expression profiling, VACCINE, Vol: 33, Pages: 5289-5293, ISSN: 0264-410X

JOURNAL ARTICLE

Anderson ST, Kaforou M, Brent AJ, Wright VJ, Banwell CM, Chagaluka G, Crampin AC, Dockrell HM, French N, Hamilton MS, Hibberd ML, Kern F, Langford PR, Ling L, Mlotha R, Ottenhoff THM, Pienaar S, Pillay V, Scott JAG, Twahir H, Wilkinson RJ, Coin LJ, Heyderman RS, Levin M, Eley Bet al., 2014, Diagnosis of Childhood Tuberculosis and Host RNA Expression in Africa, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 370, Pages: 1712-1723, ISSN: 0028-4793

JOURNAL ARTICLE

Carpenter D, Taype C, Goulding J, Levin M, Eley B, Anderson S, Shaw M-A, Armour JALet al., 2014, CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis, BMC MEDICAL GENETICS, Vol: 15, ISSN: 1471-2350

JOURNAL ARTICLE

Eleftheriou D, Levin M, Shingadia D, Tulloh R, Klein NJ, Brogan PAet al., 2014, Management of Kawasaki disease, ARCHIVES OF DISEASE IN CHILDHOOD, Vol: 99, Pages: 74-83, ISSN: 0003-9888

JOURNAL ARTICLE

Eleftheriou D, Levin M, Shingadia D, Tulloh R, Klein NJ, Brogan PAet al., 2014, Management of Kawasaki disease, ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, Vol: 99, Pages: 74-83, ISSN: 1359-2998

JOURNAL ARTICLE

Hoang LT, Shimizu C, Ling L, Naim ANM, Khor CC, Tremoulet AH, Wright V, Levin M, Hibberd ML, Burns JCet al., 2014, Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease, GENOME MEDICINE, Vol: 6, ISSN: 1756-994X

JOURNAL ARTICLE

Kaforou M, Wright VJ, Levin M, 2014, Host RNA signatures for diagnostics: An example from paediatric tuberculosis in Africa, JOURNAL OF INFECTION, Vol: 69, Pages: S28-S31, ISSN: 0163-4453

JOURNAL ARTICLE

Kiguli S, Akech SO, Mtove G, Opoka RO, Engoru C, Olupot-Olupot P, Nyeko R, Evans J, Crawley J, Prevatt N, Reyburn H, Levin M, George EC, South A, Babiker AG, Gibb DM, Maitland Ket al., 2014, WHO guidelines on fluid resuscitation in children: missing the FEAST data, BMJ-BRITISH MEDICAL JOURNAL, Vol: 348, ISSN: 1756-1833

JOURNAL ARTICLE

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