Browsing by Author "Loyse, Angela"

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    Correction to: AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial
    (2019-01-14) Lawrence, David S; Youssouf, Nabila; Molloy, Síle F; Alanio, Alexandre; Alufandika, Melanie; Boulware, David R; Boyer-Chammard, Timothée; Chen, Tao; Dromer, Francoise; Hlupeni, Admire; Hope, William; Hosseinipour, Mina C; Kanyama, Cecilia; Lortholary, Oliver; Loyse, Angela; Meya, David B; Mosepele, Mosepele; Muzoora, Conrad; Mwandumba, Henry C; Ndhlovu, Chiratidzo E; Niessen, Louis; Schutz, Charlotte; Stott, Katharine E; Wang, Duolao; Lalloo, David G; Meintjes, Graeme; Jaffar, Shabbar; Harrison, Thomas S; Jarvis, Joseph N
    Following publication of the original article [1], we have been notified that one of the author names was listed incorrectly. Both incorrect and correct author names are presented below. The original publication has been corrected.
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    Genotypic diversity is associated with clinical outcome and phenotype in cryptococcal meningitis across Southern Africa
    (Public Library of Science, 2015) Beale, Mathew A; Sabiiti, Wilber; Robertson, Emma J; Fuentes-Cabrejo, Karen M; O'Hanlon, Simon J; Jarvis, Joseph N; Loyse, Angela; Meintjes, Graeme; Harrison, Thomas S; May, Robin C
    Cryptococcal meningitis is a major cause of mortality throughout the developing world, yet little is known about the genetic markers underlying Cryptococcal virulence and patient outcome. We studied a cohort of 230 Cryptococcus neoformans (Cn) isolates from HIV-positive South African clinical trial patients with detailed clinical follow-up using multi-locus sequence typing and in vitro phenotypic virulence assays, correlating these data with clinical and fungal markers of disease in the patient. South African Cn displayed high levels of genetic diversity and locus variability compared to globally distributed types, and we identified 50 sequence types grouped within the main molecular types VNI, VNII and VNB, with 72% of isolates typed into one of seven 'high frequency' sequence types. Spatial analysis of patients' cryptococcal genotype was not shown to be clustered geographically, which might argue against recent local acquisition and in favour of reactivation of latent infection. Through comparison of MLST genotyping data with clinical parameters, we found a relationship between genetic lineage and clinical outcome, with patients infected with the VNB lineage having significantly worse survival (n=8, HR 3.35, CI 1.51-7.20, p=0.003), and this was maintained even after adjustment for known prognostic indicators and treatment regimen. Comparison of fungal genotype with in vitro phenotype (phagocytosis, laccase activity and CSF survival) performed on a subset of 89 isolates revealed evidence of lineage-associated virulence phenotype, with the VNII lineage displaying increased laccase activity (p=0.001) and ex vivo CSF survival (p=0.0001). These findings show that Cryptococcus neoformans is a phenotypically heterogeneous pathogen, and that lineage plays an important role in cryptococcal virulence during human infection. Furthermore, a detailed understanding of the genetic diversity in Southern Africa will support further investigation into how genetic diversity is structured across African environments, allowing assessment of the risks different ecotypes pose to infection.
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    Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures
    (2009) Bicanic, Tihana; Brouwer, Annemarie E; Meintjes, Graeme; Rebe, Kevin; Limmathurotsakul, Direk; Chierakul, Wirongrong; Teparrakkul, Praprit; Loyse, Angela; White, Nicholas J; Wood, Robin; Jaffar, Shabbar; Harrison, Thomas
    Objectives: To assess impact of serial lumbar punctures on association between cerebrospinal fluid (CSF) opening pressure and prognosis in HIV-associated cryptococcal meningitis; to explore time course and relationship of opening pressure with neurological findings, CSF fungal burden, immune response, and CD4 cell count. Design: Evaluation of 163 HIV-positive ART-naive patients enrolled in three trials of amphotericin B-based therapy for cryptococcal meningitis in Thailand and South Africa. Methods: Study protocols required four lumbar punctures with measurements of opening pressure over the first 2 weeks of treatment and additional lumbar punctures if opening pressure raised. Fungal burden and clearance, CSF immune parameters, CD4 cell count, neurological symptoms and signs, and outcome at 2 and 10 weeks were compared between groups categorized by opening pressure at cryptococcal meningitis diagnosis. Results: Patients with higher baseline fungal burden had higher baseline opening pressure. High fungal burden appeared necessary but not sufficient for development of high pressure. Baseline opening pressure was not associated with CD4 cell count, CSF pro-inflammatory cytokines, or altered mental status. Day 14 opening pressure was associated with day 14 fungal burden. Overall mortality was 12% (20/162) at 2 weeks and 26% (42/160) at 10 weeks, with no significant differences between opening pressure groups. Conclusion: Studies are needed to define factors, in addition to fungal burden, associated with raised opening pressure. Aggressive management of raised opening pressure through repeated CSF drainage appeared to prevent any adverse impact of raised opening pressure on outcome in patients with cryptococcal meningitis. The results support increasing access to manometers in resource-poor settings and routine management of opening pressure in patients with cryptococcal meningitis.