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Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study.

Dromer F, Mathoulin-Pélissier S, Launay O, Lortholary O, French Cryptococcosis Study Gro - PLoS Med. (2007)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Unité de Mycologie Moléculaire, Centre National de Référence Mycologie et Antifongiques, CNRS URA3042, Institut Pasteur, Paris, France. dromer@pasteur.fr

ABSTRACT

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.

Methods and findings: 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.

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Related in: MedlinePlus

Overall Survival at Three Months after the Diagnosis of Cryptococcosis(A) Patients presenting with and without abnormal neurology at baseline.(B) Patients with and without haematological malignancies.(C) Patients presenting with and without abnormal brain imaging at baseline (data missing for 39 patients).
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pmed-0040021-g002: Overall Survival at Three Months after the Diagnosis of Cryptococcosis(A) Patients presenting with and without abnormal neurology at baseline.(B) Patients with and without haematological malignancies.(C) Patients presenting with and without abnormal brain imaging at baseline (data missing for 39 patients).

Mentions: The survival probability at Mo3 was thus lower in patients with abnormal neurology at baseline (survival probability 0.71 [95% CI, 0.60–0.80]) compared to those without (0.90 [95% CI, 0.84–0.94], p = 0.0008), in patients with haematological malignancies (0.54 [95% CI, 0.29–0.74]) compared to those without (0.85 [95% CI, 0.79–0.90], p = 0.011), and in patients with abnormal brain imaging at baseline (0.74 [95% CI, 0.53–0.83]) compared to those with normal brain imaging (0.88 [95% CI, 0.81–0.93], p = 0.0274) (Figure 2). Abnormal neurology and abnormal brain imaging still influenced survival probability when patients with concomitant or past cerebral toxoplasmosis were excluded (unpublished data).


Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study.

Dromer F, Mathoulin-Pélissier S, Launay O, Lortholary O, French Cryptococcosis Study Gro - PLoS Med. (2007)

Overall Survival at Three Months after the Diagnosis of Cryptococcosis(A) Patients presenting with and without abnormal neurology at baseline.(B) Patients with and without haematological malignancies.(C) Patients presenting with and without abnormal brain imaging at baseline (data missing for 39 patients).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1808080&req=5

pmed-0040021-g002: Overall Survival at Three Months after the Diagnosis of Cryptococcosis(A) Patients presenting with and without abnormal neurology at baseline.(B) Patients with and without haematological malignancies.(C) Patients presenting with and without abnormal brain imaging at baseline (data missing for 39 patients).
Mentions: The survival probability at Mo3 was thus lower in patients with abnormal neurology at baseline (survival probability 0.71 [95% CI, 0.60–0.80]) compared to those without (0.90 [95% CI, 0.84–0.94], p = 0.0008), in patients with haematological malignancies (0.54 [95% CI, 0.29–0.74]) compared to those without (0.85 [95% CI, 0.79–0.90], p = 0.011), and in patients with abnormal brain imaging at baseline (0.74 [95% CI, 0.53–0.83]) compared to those with normal brain imaging (0.88 [95% CI, 0.81–0.93], p = 0.0274) (Figure 2). Abnormal neurology and abnormal brain imaging still influenced survival probability when patients with concomitant or past cerebral toxoplasmosis were excluded (unpublished data).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Unité de Mycologie Moléculaire, Centre National de Référence Mycologie et Antifongiques, CNRS URA3042, Institut Pasteur, Paris, France. dromer@pasteur.fr

ABSTRACT

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.

Methods and findings: 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.

Show MeSH
Related in: MedlinePlus