Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study.
BACKGROUND
Cryptococcosis is a life-threatening opportunistic fungal infection in both HIV-positive and -negative patients. Information on clinical presentation and therapeutic guidelines, derived mostly from clinical trials performed before introduction of highly active antiretroviral therapy in patients with cryptococcal meningoencephalitis, is missing data on extrameningeal involvement and infections by serotype D as opposed to serotype A of Cryptococcus neoformans.


RESULTS
The prospective multicenter study CryptoA/D was designed in France (1997-2001) to analyse the factors influencing clinical presentation and outcome without the bias of inclusion into therapeutic trials. Of the 230 patients enrolled, 177 (77%) were HIV-positive, 50 (22%) were female, and 161 (72.5%) were infected with serotype A. Based on culture results at baseline, cryptococcosis was more severe in men, in HIV-positive patients, and in patients infected with serotype A. Factors independently associated with mycological failure at week 2 independent of HIV status were initial dissemination (OR, 2.4 [95% confidence interval (CI), 1.2-4.9]), high (>1:512) serum antigen titre (OR, 2.6 [1.3-5.4]), and lack of flucytosine during induction therapy (OR, 3.8 [1.9-7.8]). The three-month survival was shorter in patients with abnormal neurology or brain imaging at baseline, and in those with haematological malignancy.


CONCLUSIONS
Thus sex, HIV status, and infecting serotype are major determinants of presentation and outcome during cryptococcosis. We propose a modification of current guidelines for the initial management of cryptococcosis based on systematic fungal burden evaluation.
Dromer
Françoise
F
Unité de Mycologie Moléculaire, Centre National de Référence Mycologie et Antifongiques, CNRS URA3042, Institut Pasteur, Paris, France. dromer@pasteur.fr
Mathoulin-Pélissier
Simone
S
Launay
Odile
O
Lortholary
Olivier
O
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000666:Amphotericin B / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use; D003453:Cryptococcosis / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000401:mortality; D003455:Cryptococcus neoformans / Q000145:classification; D005260:Female; D005437:Flucytosine / Q000627:therapeutic use; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D008590:Meningoencephalitis / Q000188:drug therapy / Q000453:epidemiology; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000935:Antifungal Agents; D000666:Amphotericin B; D005437:Flucytosine