Symptomatic relapse of HIV-associated cryptococcal meningitis in South Africa: the role of inadequate secondary prophylaxis.
OBJECTIVE
Cryptococcal meningitis is the commonest cause of adult meningitis in Southern Africa. A sizeable proportion of this disease burden is thought to be due to symptomatic relapse of previously treated infection. We carried out a study to examine the contribution of inadequate secondary fluconazole prophylaxis to symptomatic relapses of cryptococcal meningitis.


METHODS
A prospective observational study of patients presenting with laboratory-confirmed symptomatic relapse of HIV-associated cryptococcal meningitis between January 2007 and December 2008 at GF Jooste Hospital, a public sector adult referral hospital in Cape Town.


METHODS
Relapse episodes were categorized into 1) patients not taking fluconazole prophylaxis, 2) immune reconstitution inflammatory syndrome (IRIS) and 3) relapses occurring prior to ART in patients taking fluconazole. In-hospital mortality was recorded.


RESULTS
There were 69 relapse episodes, accounting for 23% of all cases of cryptococcal meningitis. 43%(n=30) of relapse episodes were in patients not taking fluconazole prophylaxis, 45%(31) were due to IRIS and 12%(8) were in patients pre-ART taking fluconazole. Patients developing relapse due to inadequate secondary prophylaxis had severe disease and high in-hospital mortality (33%). Of the 30 patients not taking fluconazole, 47% (14) had not been prescribed secondary prophylaxis by their healthcare providers. Importantly, we documented no relapses due to fluconazole resistance in this cohort of patients who has received amphotericin B as initial therapy.


CONCLUSIONS
Large numbers of relapses of cryptococcal meningitis are due to failed prescription, dispensing, referral for or adherence to secondary fluconazole prophylaxis. Interventions to improve the use of secondary fluconazole prophylaxis are essential.
Jarvis
Joseph N
JN
Infectious Diseases Unit, GF Jooste Hospital, Cape Town, South Africa. joejarvis@doctors.net.uk
Meintjes
Graeme
G
Williams
Zomzi
Z
Rebe
Kevin
K
Harrison
Thomas S
TS
D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000517:prevention & control* / Q000821:virology*; D011446:Prospective Studies; D012008:Recurrence; D013019:South Africa; D017211:Treatment Failure
D000935:Antifungal Agents; D015725:Fluconazole