Publications by authors named "Eliza Gil"

12 Publications

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Acute bacterial meningitis.

Curr Opin Neurol 2021 Mar 26. Epub 2021 Mar 26.

Francis Crick Institute NIHR Mucosal Pathogens Research Unit, Department of Infection, Division of Infection and Immunity, University College London, London, UK.

Purpose Of Review: Community-acquired bacterial meningitis is a continually changing disease. This review summarises both dynamic epidemiology and emerging data on pathogenesis. Updated clinical guidelines are discussed, new agents undergoing clinical trials intended to reduce secondary brain damage are presented.

Recent Findings: Conjugate vaccines are effective against serotype/serogroup-specific meningitis but vaccine escape variants are rising in prevalence. Meningitis occurs when bacteria evade mucosal and circulating immune responses and invade the brain: directly, or across the blood-brain barrier. Tissue damage is caused when host genetic susceptibility is exploited by bacterial virulence. The classical clinical triad of fever, neck stiffness and headache has poor diagnostic sensitivity, all guidelines reflect the necessity for a low index of suspicion and early Lumbar puncture. Unnecessary cranial imaging causes diagnostic delays. cerebrospinal fluid (CSF) culture and PCR are diagnostic, direct next-generation sequencing of CSF may revolutionise diagnostics. Administration of early antibiotics is essential to improve survival. Dexamethasone partially mitigates central nervous system inflammation in high-income settings. New agents in clinical trials include C5 inhibitors and daptomycin, data are expected in 2025.

Summary: Clinicians must remain vigilant for bacterial meningitis. Constantly changing epidemiology and emerging pathogenesis data are increasing the understanding of meningitis. Prospects for better treatments are forthcoming.
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http://dx.doi.org/10.1097/WCO.0000000000000934DOI Listing
March 2021

Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV.

Emerg Infect Dis 2021 Mar;27(3):944-948

Nontuberculous mycobacteria can cause disseminated infections in immunocompromised patients and are challenging to treat because of antimicrobial resistance and adverse effects of prolonged multidrug treatment. We report successful treatment with bedaquiline, a novel antimycobacterial drug, as part of combination therapy for 2 patients with disseminated nontuberculous mycobacteria co-infected with HIV.
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http://dx.doi.org/10.3201/eid2703.202359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920675PMC
March 2021

Bacterial and Fungal Co-Infection.

Clin Infect Dis 2020 Aug 6. Epub 2020 Aug 6.

Department of Infection and Microbiology, North Middlesex University Hospital, London, UK.

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http://dx.doi.org/10.1093/cid/ciaa1120DOI Listing
August 2020

Blood transcriptomic discrimination of bacterial and viral infections in the emergency department: a multi-cohort observational validation study.

BMC Med 2020 07 21;18(1):185. Epub 2020 Jul 21.

Division of Infection and Immunity, University College London, London, UK.

Background: There is an urgent need to develop biomarkers that stratify risk of bacterial infection in order to support antimicrobial stewardship in emergency hospital admissions.

Methods: We used computational machine learning to derive a rule-out blood transcriptomic signature of bacterial infection (SeptiCyte™ TRIAGE) from eight published case-control studies. We then validated this signature by itself in independent case-control data from more than 1500 samples in total, and in combination with our previously published signature for viral infections (SeptiCyte™ VIRUS) using pooled data from a further 1088 samples. Finally, we tested the performance of these signatures in a prospective observational cohort of emergency department (ED) patients with fever, and we used the combined SeptiCyte™ signature in a mixture modelling approach to estimate the prevalence of bacterial and viral infections in febrile ED patients without microbiological diagnoses.

Results: The combination of SeptiCyte™ TRIAGE with our published signature for viral infections (SeptiCyte™ VIRUS) discriminated bacterial and viral infections in febrile ED patients, with a receiver operating characteristic area under the curve of 0.95 (95% confidence interval 0.90-1), compared to 0.79 (0.68-0.91) for WCC and 0.73 (0.61-0.86) for CRP. At pre-test probabilities 0.35 and 0.72, the combined SeptiCyte™ score achieved a negative predictive value for bacterial infection of 0.97 (0.90-0.99) and 0.86 (0.64-0.96), compared to 0.90 (0.80-0.94) and 0.66 (0.48-0.79) for WCC and 0.88 (0.69-0.95) and 0.60 (0.31-0.72) for CRP. In a mixture modelling approach, the combined SeptiCyte™ score estimated that 24% of febrile ED cases receiving antibacterials without a microbiological diagnosis were due to viral infections. Our analysis also suggested that a proportion of patients with bacterial infection recovered without antibacterials.

Conclusions: Blood transcriptional biomarkers offer exciting opportunities to support precision antibacterial prescribing in ED and improve diagnostic classification of patients without microbiologically confirmed infections.
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http://dx.doi.org/10.1186/s12916-020-01653-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372897PMC
July 2020

Analysis tools to quantify dissemination of pathology in zebrafish larvae.

Sci Rep 2020 02 21;10(1):3149. Epub 2020 Feb 21.

Infection and Immunity, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, United Kingdom.

We describe new open source software called QuantiFish for rapid quantitation of fluorescent foci in zebrafish larvae, to support infection research in this animal model. QuantiFish extends the conventional measurements of bacterial load and number of bacterial foci to include measures for dissemination of infection. These are represented by the proportions of bacteria between foci and their spatial distribution. We showcase these measures by comparison of intravenous and hindbrain routes of Mycobacterium marinum infection, which are indistinguishable by measurement of bacterial load and not consistently differentiated by the number of bacterial foci. The intravenous route showed dose dependent dissemination of infection, reflected by increased spatial dispersion of bacteria and lower proportions of bacteria distributed across many foci. In contrast, hindbrain infection resulted in localised disease, limited to a smaller area and higher proportions of bacteria distributed across fewer foci. The application of QuantiFish may extend beyond models of infection, to study other pathologies such as metastatic cancer.
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http://dx.doi.org/10.1038/s41598-020-59932-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035342PMC
February 2020

Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis.

JCI Insight 2016 Oct 6;1(16):e87238. Epub 2016 Oct 6.

Division of Infection and Immunity, University College London, London, United Kingdom.

Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. We identified and validated elevated blood basic leucine zipper transcription factor 2 () transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1-negative individuals, and 0.85 in HIV-1-infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. Elevated blood transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR.
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http://dx.doi.org/10.1172/jci.insight.87238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053151PMC
October 2016

Case report: passive transfer of hepatitis B antibodies from intravenous immunoglobulin.

BMC Infect Dis 2014 Feb 22;14:99. Epub 2014 Feb 22.

Flat 19, 3 St Pancras Way, London NW1 0PB, UK.

Background: Prior to initiating immunosuppressive therapy in the treatment of autoimmune inflammatory conditions, it is a requirement to screen for certain viral serology, including hepatitis B (HBV). A positive result may indicate the need for antiviral therapy, or contraindicate immunosuppression all together. An accurate interpretation of serological markers is therefore imperative in order to treat patients appropriately. We present a case of passive anti-HBV antibody transfer following intravenous immunoglobulin (IVIg) infusion, in which misinterpretation of serology results almost led to inappropriate treatment with antiviral therapy and the withholding of immunosuppressive agents. This phenomenon has been previously reported, but awareness remains limited.

Case Presentation: A 50 year old Caucasian gentleman with a history of allogeneic haematopoietic stem cell transplant for transformed follicular lymphoma was admitted to hospital with recurrent respiratory tract infections. Investigation found him to be hypogammaglobulinaemic, and he was thus given 1 g/kg of intravenous immunoglobulin. The patient also disclosed a 3-week history of painful, swollen joints, leading to a diagnosis of seronegative inflammatory polyarthritis. Prior to initiating long term immunosuppression, viral screening found hepatitis B serology suggestive of past infection, with positive results for both anti-HBc and anti-HBs antibody, but negative HBV DNA. In response, prednisolone was weaned and the local hepatology team recommended commencement of lamivudine. Having been unable to identify a source of infection, the case was reported to the local blood centre, who tested a remaining vial from the same batch of IVIg and found it to be anti-HBc and anti-HBs positive. Fortunately the blood products were identified and tested prior to the patient initiating HBV treatment, and the effect of a delay in starting disease-modifying therapy was inconsequential in light of an excellent response to first-line therapies.

Conclusion: Misinterpretation of serology results following IVIg infusion may lead to significant patient harm, including unnecessary antiviral administration, the withholding of treatments, and psychosocial damage. This is especially pertinent at a time when we have an ever increasing number of patients being treated with IVIg for a wide array of immune-mediated disease. Passive antibody transfer should be considered wherever unexpected serological changes are identified.
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http://dx.doi.org/10.1186/1471-2334-14-99DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937526PMC
February 2014

The clinical and ecological impact of childhood pneumococcal vaccination.

Br J Hosp Med (Lond) 2013 Apr;74(4):212-6

Respiratory Medicine Department, University College, London, UK.

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http://dx.doi.org/10.12968/hmed.2013.74.4.212DOI Listing
April 2013

Systemic vasculitis: a dual diagnosis?

BMJ Case Rep 2011 Dec 2;2011. Epub 2011 Dec 2.

Care of the elderly, University College Hospital, London, UK.

The authors describe a 25-year-old male with systemic vasculitis fulfilling the American College of Rheumatology classification criteria for both granulomatosis with polyangiitis (Wegener's granulomatosis) and polyarteritis nodosa. The patient was diagnosed with granulomatosis with polyangiitis following a mediastinal biopsy which revealed necrotising granulomas of the large airways, a positive cytoplasmic antineutrophil cytoplasmic antibodies and high antiproteinase 3 antibody titre. He then developed acute right-sided abdominal and testicular pain as well as areas of hyperaesthesia and parasthesiae on both lower limbs. He was found to have focal crescentic glomerulonephritis and mononeuritis multiplex, in keeping with his diagnosis of granulomatosis with polyangiitis, as well as two areas of infarction in his right testicle and multiple aneurysms of his hepatic and right renal arteries, more typical of polyarteritis nodosa. His symptoms developed 6 weeks after hepatitis B vaccination, which may have played an aetiological role.
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http://dx.doi.org/10.1136/bcr.10.2011.4968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233918PMC
December 2011