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1. Cryptococcal meningoencephalitis: time for action

Author

Stott, KE, Loyse, A, Jarvis, JN, Alufandika, M, Harrison, TS, Mwandumba, HC, Day, JN, Lalloo, DG, Bicanic, T, Perfect, JR, and Hope, W

Subjects
qw180, wl_300
Abstract

Cryptococcal meningoencephalitis was first described over a century ago. This fungal infection is preventable and treatable yet continues to be associated with excessive morbidity and mortality. The largest burden of disease resides in people living with HIV in low-income and middle-income countries. In this group, mortality with the best antifungal induction regimen (7 days of amphotericin B deoxycholate [1·0 mg/kg per day] and flucytosine [100·0 mg/kg per day]) in a clinical trial setting was 24% at 10 weeks. The world is now at an inflection point in terms of recognition, research, and action to address the burden of morbidity and mortality from cryptococcal meningoencephalitis. However, the scope of interventional programmes needs to increase, with particular attention to implementation science that is specific to individual countries. This Review summarises causes of excessive mortality, interventions with proven survival benefit, and gaps in knowledge and practice that contribute to the ongoing high death toll from cryptococcal meningoencephalitis. TRANSLATIONS: For the Vietnamese and Chichewa translations of the abstract see Supplementary Materials section.

Published
2021

2. Very low levels of 25-hydroxyvitamin D are not associated with immunologic changes or clinical outcome in South African patients with HIV-associated cryptococcal meningitis

Author

Jarvis, JN, Bicanic, T, Loyse, A, Meintjes, G, Hogan, L, Roberts, CH, Shoham, S, Perfect, JR, Govender, NP, and Harrison, TS

Abstract

Background. Vitamin D deficiency is associated with impaired immune responses and increased susceptibility to a number of intracellular pathogens in individuals infected with human immunodeficiency virus (HIV). It is not known whether such an association exists with Cryptococcus neoformans.\ud \ud Methods. Levels of 25-hydroxyvitamin D (25[OH]D) were measured in 150 patients with cryptococcal meningitis (CM) and 150 HIV-infected controls in Cape Town, South Africa, and associations between vitamin D deficiency and CM were examined. The 25-hydroxyvitamin D levels and cryptococcal notifications were analyzed for evidence of reciprocal seasonality. Associations between 25(OH)D levels and disease severity, immune responses, and microbiological clearance were investigated in the patients with CM.\ud \ud Results. Vitamin D deficiency (plasma 25[OH]D ≤50 nmol/L) was present in 74% of patients. Vitamin D deficiency was not associated with CM (adjusted odds ratio, 0.93 [95% confidence interval, .6–1.6]; P = .796). Levels of 25(OH)D showed marked seasonality, but no reciprocal seasonality was seen in CM notifications. No significant associations were found between 25(OH)D levels and fungal burden or levels of tumor necrosis factor α, interferon γ, interleukin 6, soluble CD14, or neopterin in cerebrospinal fluid. Rates of fungal clearance did not vary according to vitamin D status.\ud \ud Conclusions. Vitamin D deficiency does not predispose to the development of CM, or lead to impaired immune responses or microbiological clearance in HIV-infected patients with CM.

Published
2014

3. Efficacy of an abbreviated induction regimen of amphotericin B deoxycholate for cryptococcal meningoencephalitis: 3 days of therapy is equivalent to 14 days

Author

Livermore, J, Howard, SJ, Sharp, AD, Goodwin, J, Gregson, L, Felton, T, Schwartz, JA, Walker, C, Moser, B, Müller, W, Harrison, TS, Perfect, JR, and Hope, WW

Abstract

Cryptococcal meningoencephalitis is an urgent global health problem. Induction regimens using 14 days of amphotericin B deoxycholate (dAmB) are considered the standard of care but may not be suitable for resource-poor settings. We investigated the efficacy of conventional and abbreviated regimens of dAmB for cryptococcal meningoencephalitis in both murine and rabbit models of cryptococcal meningoencephalitis. We examined the extent to which immunological effectors contribute to the antifungal effect. We bridged the results to humans as a first critical step to define regimens suitable for further study in clinical trials. There were significant differences in the murine plasma-versus-cerebrum dAmB concentration-time profiles. dAmB was detectable in the cerebrum throughout the experimental period, even following the administration of only three doses of 3 mg/kg. dAmB induced a fungistatic effect in the cerebrum with a 2- to 3-log10 CFU/g reduction compared with controls. The effect of 3 days of therapy was the same as that of daily therapy for 14 days. There was no evidence of increased numbers of CD3(+) CD4(+) or CD3(+) CD8(+) cells in treated mice to account for the persistent antifungal effect of an abbreviated regimen. The administration of dAmB at 1 mg/kg/day for 3 days was the same as daily therapy in rabbits. The bridging studies suggested that a human regimen of 0.7 mg/kg/day for 3 days resulted in nearly maximal antifungal activity in both the cerebrum and cerebrospinal fluid. An abbreviated regimen (3 days of therapy) of dAmB appears to be just as effective as conventional induction therapy for cryptococcal meningoencephalitis. \ud \ud IMPORTANCE: Cryptococcal meningitis is a significant and neglected infection that is associated with excessive morbidity and mortality. In well-resourced health care settings, induction therapy with at least 2 weeks of amphotericin B deoxycholate (dAmB) is advocated. Multiple clinical studies suggest that dAmB is the drug of choice for cryptococcal meningitis. In many parts of the world where the burden of cryptococcal meningitis is highest, it is infeasible to administer dAmB for prolonged periods. This paper provides the experimental basis for the efficacy of abbreviated regimens of dAmB for cryptococcal meningitis. The concept was explored in two well-validated laboratory animal models of cryptococcal meningitis, and the results were bridged to humans by using a range of mathematical modeling techniques. A 3-day regimen is as effective as the standard 14-day course. An abbreviated regimen is significantly more feasible and may enable better antifungal therapy to be administered to many patients with this frequently lethal disease.

Published
2014

4. ACKNOWLEDGEMENT OF REVIEWERS

Author

Adams, NG, Adekambi, T, Afeltra, J, Aguado, J, Aires de Sousa, M, Akiyoshi, K, Al Hasan, M, Ala-Kokko, T, Albert, M, Alfandari, S, Allen, D, Allerberger, F, Almyroudis, N, Alp, E, Amin, R, Anderson-Berry, A, Andes, DR, Andremont, A, Andreu, A, Angelakis, M, Antachopoulos, C, Antoniadou, A, Arabatzis, M, Arlet, G, Arnez, M, Arnold, C, Asensio, A, Asseray, N, Ausiello, C, Avni, T, Ayling, R, Baddour, L, Baguelin, M, Bányai, K, Barbour, A, Basco, LK, Bauer, D, Bayston, R, Beall, B, Becker, K, Behr, M, Bejon, P, Belliot, G, Benito-Fernandez, J, Benjamin, D, Benschop, K, Berencsi, G, Bergeron, MG, Bernard, K, Berner, R, Beyersmann, J, Bille, J, Bizzini, A, Bjarnsholt, T, Blanc, D, Blanco, J, Blot, S, Bohnert, J, Boillat, N, Bonomo, R, Bonten, M, Bordon, JM, Borel, N, Boschiroli, ML, Bosilkovski, M, Bosso, JA, Botelho-Nevers, E, Bou, G, Bretagne, S, Brouqui, P, Brun-Buisson, C, Brunetto, M, Bucher, H, Buchheidt, D, Buckling, A, Bulpa, P, Cambau, E, Canducci, F, Cantón, R, Capobianchi, M, Carattoli, A, Carcopino, X, Cardona-Castro, N, Carling, PC, Carrat, F, Castilla, J, Castilletti, C, Cavaco, L, Cavallo, R, Ceccherini-Silberstein, F, Centrón, D, Chappuis, F, Charrel, R, Chen, M, Chevaliez, S, Chezzi, C, Chomel, B, Chowers, M, Chryssanthou, E, Ciammaruconi, A, Ciccozzi, M, Cid, J, Ciofu, O, Cisneros, D, Ciufolini, MG, Clark, C, Clarke, SC, Clayton, R, Clementi, M, Clemons, K, Cloeckaert, Ael, Cloud, J, Coenye, T, Cohen Bacri, S, Cohen, R, Coia, J, Colombo, A, Colson, P, Concerse, P, Cordonnier, C, Cormican, M, Cornaglia, G, Cornely, O, Costa, S, Cots, F, Craxi, A, Creti, R, Crnich, C, Cuenca Estrella, M, Cusi, MG, d'Ettorre, G, da Cruz Lamas, C, Daikos, G, Dannaoui, E, De Barbeyrac, B, De Grazia, S, de Jager, C, de Lamballerie, X, de Marco, F, del Palacio, A, Delpeyroux, F, Denamur, E, Denis, O, Depaquit, J, Deplano, A, Desenclos, J-C, Desjeux, P, Deutch, S, Di Luca, D, Dianzani, F, Diep, B, Diestra, K, Dignani, C, Dimopoulos, G, Divizia, M, Doi, Y, Dornbusch, HJ, Dotis, J, Drancourt, M, Drevinek, P, Dromer, F, Dryden, M, Dubreuil, L, Dubus, J-C, Dumitrescu, O, Dumke, R, DuPont, H, Edelstein, M, Eggimann, P, Eis-Huebinger, A-M, El Atrouni, WI, Entenza, J, Ergonul, O, Espinel-Ingroff, A, Esteban, J, Etienne, J, Fan, X-G, Fenollar, F, Ferrante, P, Ferrieri, P, Ferry, T, Feuchtinger, T, Finegold, S, Fingerle, V, Fitch, M, Fitzgerald, R, Flori, P, Fluit, A, Fontana, R, Fournier, PE, François, M, Francois, P, Freedman, DO, Friedrich, A, Gallego, L, Gallinella, G, Gangneux, J-P, Gannon, V, Garbarg-Chenon, A, Garbino, J, Garnacho-Montero, J, Gatermann, Soeren, Gautret, P, Gentile, G, Gerlich, W, Ghannoum, M, Ghebremedhin, B, Ghigo, E, Giamarellos-Bourboulis, E, Girgis, R, Giske, C, Glupczynski, Y, Gnarpe, J, Gomez-Barrena, E, Gorwitz, RJ, Gosselin, R, Goubau, P, Gould, E, Gradel, K, Gray, J, Gregson, D, Greub, G, Grijalva, CG, Groll, A, Groschup, M, Gutiérrez, J, Hackam, DG, Hall, WA, Hallett, R, Hansen, S, Harbarth, S, Harf-Monteil, C, Hasanjani, Roushan MR, Hasler, P, Hatchette, T, Hauser, P, He, Q, Hedges, A, Helbig, J, Hennequin, C, Herrmann, B, Hezode, C, Higgins, P, Hoesli, I, Hoiby, N, Hope, W, Houvinen, P, Hsu, LY, Huard, R, Humphreys, H, Icardi, M, Imoehl, M, Ivanova, K, Iwamoto, T, Izopet, J, Jackson, Y, Jacobsen, K, Jang, TN, Jasir, A, Jaulhac, B, Jaureguy, F, Jefferies, JM, Jehl, F, Johnstone, J, Joly-Guillou, M-L, Jonas, M, Jones, M, Joukhadar, C, Kahl, B, Kaier, K, Kaiser, L, Kato, H, Katragkou, A, Kearns, A, Kern, W, Kerr, K, Kessin, R, Kibbler, C, Kimberlin, D, Kittang, B, Klaassen, C, Kluytmans, J, Ko, W-C, Koh, W-J, Kostrzewa, M, Kourbeti, I, Krause, R, Krcmery, V, Krizova, P, Kuijper, E, Kullberg, B-J, Kumar, G, Kunin, CM, La Scola, B, Lagging, M, Lagrou, K, Lamagni, T, Landini, P, Landman, D, Larsen, A, Lass-Floerl, C, Laupland, K, Lavigne, JP, Leblebicioglu, H, Lee, B, Lee, CH, Leggat, P, Lehours, P, Leibovici, Lonard, Leon, L, Leonard, N, Leone, M, Lescure, X, Lesprit, P, Levy, PY, Lew, D, Lexau, CA, Li, S-Y, Li, W, Lieberman, D, Lina, B, Lina, G, Lindsay, JA, Livermore, D, Lorente, L, Lortholary, O, Lucet, J-C, Lund, B, Lütticken, R, MacLeod, C, Madhi, S, Maertens, J, Maggi, F, Maiden, M, Maillard, J-Y, Maira-Litran, T, Maltezou, H, Manian, FA, Mantadakis, E, Maragakis, L, Marcelin, A-G, Marchaim, D, Marchetti, O, Marcos, M, Markotic, A, Martina, B, Martínez, J, Martinez, J-L, Marty, F, Maurin, M, McGee, L, Mediannikov, O, Meersseman, W, Megraud, F, Meletiadis, J, Mellmann, A, Meyer, E, Meyer, W, Meylan, P, Michalopoulos, A, Micol, R, Midulla, F, Mikami, Y, Miller, RF, Miragaia, M, Miriagou, V, Mitchell, TJ, Miyakis, S, Mokrousov, I, Monecke, S, Mönkemüller, K, Monno, L, Monod, M, Morales, G, Moriarty, F, Morosini, I, Mortensen, E, Mubarak, K, Mueller, B, Mühlemann, K, Muñoz Bellido, JL, Murray, P, Muscillo, M, Mylotte, J, Naessens, A, Nagy, E, Nahm, MH, Nassif, X, Navarro, D, Navarro, F, Neofytos, D, Nes, I, Ní Eidhin, D, Nicolle, L, Niederman, MS, Nigro, G, Nimmo, G, Nordmann, P, Nougairède, A, Novais, A, Nygard, K, Oliveira, D, Orth, D, Ortiz, JR, Osherov, N, Österblad, M, Ostrosky-Zeichner, L, Pagano, L, Palamara, AT, Pallares, R, Panagopoulou, P, Pandey, P, Panepinto, J, Pappas, G, Parkins, M, Parola, P, Pasqualotto, A, Pasteran, F, Paul, M, Pawlotsky, J-M, Peeters, M, Peixe, L, Pepin, J, Peralta, G, Pereyre, S, Perfect, JR, Petinaki, E, Petric, M, Pettigrew, M, Pfaller, M, Philipp, M, Phillips, G, Pichichero, M, Pierangeli, A, Pierard, D, Pigrau, C, Pilishvili, T, Pinto, F, Pistello, M, Pitout, J, Poirel, L, Poli, G, Poppert, S, Posfay-Barbe, K, Pothier, P, Poxton, I, Poyart, C, Pozzetto, B, Pujol, M, Pulcini, C, Punyadeera, C, Ramirez, M, Ranque, S, Raoult, D, Rasigade, J-P, Re, MC, Reilly, JS, Reinert, R, Renaud, B, Rice, L, Rich, S, Richet, H, Rigouts, L, Riva, E, Rizzo, C, Robotham, J, Rodicio, MR, Rodriguez, J, Rodriguez-Bano, J, Rogier, C, Roilides, E, Rolain, J-M, Rooijakkers, S, Rooney, P, Rossi, F, Rotimi, V, Rottman, M, Roux, V, Ruhe, J, Russo, G, Sadowy, E, Sagel, U, Said, SI, Saijo, M, Sak, B, Sa-Leao, R, Sanders, EAM, Sanguinetti, M, Sarrazin, C, Savelkoul, P, Scheifele, D, Schmidt, W-P, Schønheyder, H, Schönrich, G, Schrenzel, J, Schubert, S, Schwarz, K, Schwarz, S, Sefton, A, Segondy, M, Seifert, H, Seng, P, Senneville, E, Sexton, D, Shafer, RW, Shalit, I, Shankar, N, Shata, TM, Shields, J, Sibley, C, Sicinschi, L, Siljander, T, Simitsopoulou, M, Simoons-Smit, AM, Sissoko, D, Sjögren, J, Skiada, A, Skoczynska, A, Skov, R, Slack, M, Sogaard, M, Sola, C, Soriano, A, Sotto, A, Sougakoff, W, Souli, M, Spelberg, B, Spelman, D, Spiliopoulou, I, Springer, B, Stefani, S, Stein, A, Steinbach, WJ, Steinbakk, M, Strakova, L, Strenger, V, Sturm, P, Sullivan, P, Sutton, D, Symmons, D, Tacconelli, E, Tamalet, C, Tang, JW, Tang, Y-W, Tattevin, P, Thibault, V, Thomsen, RW, Thuny, F, Tong, S, Torres, C, Townsend, R, Tristan, A, Trouillet, J-L, Tsai, H-C, Tsitsopoulos, P, Tuerlinckx, D, Tulkens, P, Tumbarello, M, Tureen, J, Turnidge, JD, Turriziani, O, Tutuian, R, Uçkay, I, Upton, M, Vabret, A, Vamvakas, EC, van den Boom, D, Van Eldere, J, van Leeuwen, W, van Strijp, J, Van Veen, S, Vandamme, P, Vandenesch, F, Vayssier, M, Velin, D, Venditti, M, Venter, M, Venuti, A, Vergnaud, G, Verheij, T, Verhofstede, C, Viscoli, C, Vizza, CD, Vogel, U, Waller, A, Wang, YF, Warn, P, Warris, A, Wauters, G, Weidmann, M, Weill, F-X, Weinberger, M, Welch, D, Wellinghausen, N, Wheat, J, Widmer, A, Wild, F, Willems, R, Willinger, B, Winstanley, C, Witte, W, Wolff, M, Wong, F, Wootton, M, Wyllie, D, Xu, W, Yamamoto, S, Yaron, S, Yildirim, I, Zaoutis, T, Zazzi, M, Zbinden, R, Zehender, Gianguglielmo G, Zemlickova, H, Zerbini, ML, Zhang, L, Zhang, Y, Zhao, Y-D, Zhu, Z, and Zimmerli, W

Subjects
Microbiology (medical), Infectious Diseases, General Medicine
Published
2011

5. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group

Author

DE PAUW, B, Walsh, Tj, Donnelly, Jp, Stevens, Da, Edwards, Je, Calandra, T, Pappas, Pg, Maertens, J, Lortholary, O, Kauffman, Ca, Denning, Dw, Patterson, Tf, Maschmeyer, G, Bille, J, Dismukes, We, Herbrecht, R, Hope, Ww, Kibbler, Cc, Kullberg, Bj, Marr, Ka, Muñoz, P, Odds, Fc, Perfect, Jr, Restrepo, A, Ruhnke, M, Segal, Bh, Sobel, Jd, Sorrell, Tc, Viscoli, Claudio, Wingard, Jr, Zaoutis, T, Bennett, Je, EUROPEAN ORGANIZATION FOR, RESEARCH AND TREATMENT OF CANCERINVASIVE FUNGAL INFECTIONS COOPERATIVE GROUP, NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES MYCOSES STUDY GROUP, and EORTCMSG CONSENSUS GROUP

Published
2008

6. Clinical research in the lay press: irresponsible journalism raises a huge dose of doubt

Author

Anaissie, Ej, Segal, Bh, Graybill, Jr, Arndt, C, Perfect, Jr, Kleinberg, M, Pappas, P, Benjamin, D, Rubin, R, Aberg, Ja, Adderson, Ee, ADLER SHOHET FC, Akan, H, Akova, M, Almyroudis, Ng, Alexander, Bd, Andes, D, Arrieta, A, Baddley, Jw, Barron, Ma, Belzberg, H, Boucher, Hw, Boyce, Tg, Casadevall, A, Chandrasekar, Ph, Cleary, Jd, Cordonnier, C, Corneli, Oa, CUENCA ESTRELLA, M, Daly, Js, Daoura, N, Denning, Dw, Depauw, B, DE REPENTIGNY, L, Dignani, Mc, Dismukes, Wf, Donnelly, Jp, Donowitz, Gr, Dupont, B, DRUSANO GM ELLIS, M, ESPINEL INGRFF, A, Fishman, Ja, Fleming, R, Forrest, G, Ghannoum, M, Goldman, M, Grazziutti, M, Greene, Jn, Greenberg, Rn, Gubbin, Po, Hadley, S, Herbrecht, R, Hiemenez, Jw, Hope, W, Hopenthal, Dr, Husain, S, Ito, Ji, Jaconson, Rm, Johnson, M, Keating, Mr, Kett, Dh, Knapp, K, Kontoyannis, Dp, Krcmery, Vc, Larsen, R, Laverdiere, M, Ljungman, P, Lortholary, O, Maertens, J, Marriott, D, Mattiuzzi, G, Mcginnins, Mr, Morris, M, Nucci, M, Odds, Fc, Pankey, Ga, Patterson, T, Pfaller, M, Razonable, Rr, Reboli, Ac, Rinaldi, Mg, Roberts, Gd, RODRIGUEZ TUDELA JL, Rotstein, C, Ruhnke, M, Schuster, M, Shoham, S, Sia, Ig, Siebel, N, Silviera, F, Singh, N, Sobel, J, Solomkin, Js, Sorrell, Tc, Steinbach, Wj, Temesgen, Z, Tortorano, A, Vartivarian, S, Verveij, P, Viscoli, Claudio, Viviani, Am, Walker, Rc, Wheat, Jl, Wiley, J, Williamson, P, Wingard, Jr, Yu, Vl, and Zaoutis, T.

Published
2006

8. Preemptive antifungal therapy in critically ill surgical patient

Author

Grenouillet , Frédéric, Millon , Laurence, Blasco , Gilles, Piarroux , Renaud, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Perfect JR, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)

Subjects
[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract

ISBN 978-1-905721-51-1

Published
2009

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