A prospective longitudinal study of the clinical outcomes from cryptococcal meningitis following treatment induction with 800 mg oral fluconazole in Blantyre, Malawi
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A prospective longitudinal study of the clinical outcomes from cryptococcal meningitis following treatment induction with 800 mg oral fluconazole in Blantyre, Malawi. / Rothe, Camilla; Sloan, Derek J; Goodson, Patrick; Chikafa, Jean; Mukaka, Mavuto; Denis, Brigitte; Harrison, Tom; van Oosterhout, Joep J; Heyderman, Robert S; Lalloo, David G; Allain, Theresa; Feasey, Nicholas A.
In: PLOS ONE, Vol. 8, No. 6, 01.01.2013, p. e67311.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - A prospective longitudinal study of the clinical outcomes from cryptococcal meningitis following treatment induction with 800 mg oral fluconazole in Blantyre, Malawi
AU - Rothe, Camilla
AU - Sloan, Derek J
AU - Goodson, Patrick
AU - Chikafa, Jean
AU - Mukaka, Mavuto
AU - Denis, Brigitte
AU - Harrison, Tom
AU - van Oosterhout, Joep J
AU - Heyderman, Robert S
AU - Lalloo, David G
AU - Allain, Theresa
AU - Feasey, Nicholas A
PY - 2013/1/1
Y1 - 2013/1/1
N2 - INTRODUCTION: Cryptococcal meningitis is the most common neurological infection in HIV infected patients in Sub Saharan Africa, where gold standard treatment with intravenous amphotericin B and 5 flucytosine is often unavailable or difficult to administer. Fluconazole monotherapy is frequently recommended in national guidelines but is a fungistatic drug compromised by uncertainty over optimal dosing and a paucity of clinical end-point outcome data.METHODS: From July 2010 until March 2011, HIV infected adults with a first episode of cryptococcal meningitis were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients were treated with oral fluconazole monotherapy 800 mg daily, as per national guidelines. ART was started at 4 weeks. Outcomes and factors associated with treatment failure were assessed 4, 10 and 52 weeks after fluconazole initiation.RESULTS: Sixty patients were recruited. 26/60 (43%) died by 4 weeks. 35/60 (58.0%) and 43/56 (77%) died or failed treatment by 10 or 52 weeks respectively. Reduced consciousness (Glasgow Coma Score <14 of 15), moderate/severe neurological disability (modified Rankin Score >3 of 5) and confusion (Abbreviated Mental Test Score <8 of 10) were all common at baseline and associated with death or treatment failure. ART prior to recruitment was not associated with better outcomes.CONCLUSIONS: Mortality and treatment failure from cryptococcal meningitis following initiation of treatment with 800 mg oral fluconazole is unacceptably high. To improve outcomes, there is an urgent need for better therapeutic strategies and point-of-care diagnostics, allowing earlier diagnosis before development of neurological deficit.
AB - INTRODUCTION: Cryptococcal meningitis is the most common neurological infection in HIV infected patients in Sub Saharan Africa, where gold standard treatment with intravenous amphotericin B and 5 flucytosine is often unavailable or difficult to administer. Fluconazole monotherapy is frequently recommended in national guidelines but is a fungistatic drug compromised by uncertainty over optimal dosing and a paucity of clinical end-point outcome data.METHODS: From July 2010 until March 2011, HIV infected adults with a first episode of cryptococcal meningitis were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients were treated with oral fluconazole monotherapy 800 mg daily, as per national guidelines. ART was started at 4 weeks. Outcomes and factors associated with treatment failure were assessed 4, 10 and 52 weeks after fluconazole initiation.RESULTS: Sixty patients were recruited. 26/60 (43%) died by 4 weeks. 35/60 (58.0%) and 43/56 (77%) died or failed treatment by 10 or 52 weeks respectively. Reduced consciousness (Glasgow Coma Score <14 of 15), moderate/severe neurological disability (modified Rankin Score >3 of 5) and confusion (Abbreviated Mental Test Score <8 of 10) were all common at baseline and associated with death or treatment failure. ART prior to recruitment was not associated with better outcomes.CONCLUSIONS: Mortality and treatment failure from cryptococcal meningitis following initiation of treatment with 800 mg oral fluconazole is unacceptably high. To improve outcomes, there is an urgent need for better therapeutic strategies and point-of-care diagnostics, allowing earlier diagnosis before development of neurological deficit.
KW - Adolescent
KW - Adult
KW - Antifungal Agents
KW - Female
KW - Fluconazole
KW - HIV Infections
KW - Humans
KW - Induction Chemotherapy
KW - Kaplan-Meier Estimate
KW - Longitudinal Studies
KW - Malawi
KW - Male
KW - Meningitis, Cryptococcal
KW - Middle Aged
KW - Multivariate Analysis
KW - Proportional Hazards Models
KW - Prospective Studies
KW - Treatment Failure
KW - Young Adult
U2 - 10.1371/journal.pone.0067311
DO - 10.1371/journal.pone.0067311
M3 - SCORING: Journal article
C2 - 23840659
VL - 8
SP - e67311
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 6
ER -