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. 2010 Jun;100(6):378-82.
doi: 10.7196/samj.3515.

Symptomatic relapse of HIV-associated cryptococcal meningitis in South Africa: the role of inadequate secondary prophylaxis

Joseph N Jarvis  1 , Graeme Meintjes, Zomzi Williams, Kevin Rebe, Thomas S Harrison
Affiliations

Symptomatic relapse of HIV-associated cryptococcal meningitis in South Africa: the role of inadequate secondary prophylaxis

Joseph N Jarvis et al. S Afr Med J. 2010 Jun.

Abstract

Objectives: 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.

Design: 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.

Outcome measures: 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.

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Figures

Figure 1
Figure 1. Causes of Symptomatic Relapse
Causes of symptomatic relapse of cryptococcal meningitis, divided in to immune reconstitution inflammatory syndrome (IRIS) in patients taking ART, absence of fluconazole secondary prophylaxis (subdivided into patient non-adherence and not given - either not prescribed, not dispensed, or not continued at primary care level), and relapses in patients taking fluconazole prior to starting ART.
See this image and copyright information in PMC

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