Cryptococcosis by Cryptococcus neoformans/Cryptococcus gattii Species Complexes in non-HIV-Infected Patients in Southeastern Brazil

Abstract INTRODUCTION: The clinical manifestations of cryptococcosis are usually associated with the infecting agents Cryptococcus neoformans (CN) and C. gattii (CG) species complexes and the host. In this study, non-HIV-infected patients, at a university hospital in southeastern Brazil, had epidemiological and clinical data associated with cryptococcal disease and isolated Cryptococcus species: CN - 24 patients and CG - 12 patients. METHODS: The comparison was comprised of demographic data, predisposing factors, clinical and laboratory manifestations, and outcomes of cryptococcosis patients treated between 2000 and 2016. Immunocompetent and immunosuppressed patients were also compared, irrespective of the infecting species. Cryptococcus spp. were genotyped by PCR-RFLP analysis of the URA5 gene. RESULTS: Infections by the CN species complex (100% VNI genotype) were associated with drug immunosuppression and fungemia, and patients infected with the CG species complex (83% VG II and 17% VGI genotypes) had more evident environmental exposure and higher humoral response. CN and CG affected patients with or without comorbidities. CONCLUSIONS: Diabetes mellitus, other chronic non-infectious diseases, and alcoholism were likely predisposing factors for infection by both CN and CG species. Immunocompetent patients, independent of the infecting Cryptococcus species complexes, showed a higher occurrence of meningitis and a trend toward less fungal dissemination and longer survival than immunosuppressed hosts.

Frequency and geographical distribution of genotypes and mating types of Cryptococcus neoformans and Cryptococcus gattii species complexes in Argentina / Frecuencia y distribución geográfica de genotipos y tipos sexuales de los complejos de especies Cryptococcus neoformans y Cryptococcus gattii en Argentina

Abstract The aim of this work was to know the frequency and geographical distribution of genotypes and mating types of Cryptococcus neoformans and Cryptococcus gattii species complexes isolated from human infections in Argentina during the period from April 2009 to April 2011. A multicenter study was conducted, in which 372 isolates were obtained from 61 laboratories throughout the country. Of those, 98.8% of the isolates belonged to the C. neoformans species complex and 1.1% to the C. gattii species complex. Genotype VNI (MATa) was the most frequently isolated (n = 326, 87.6%), followed by VNII (MATa) (n = 22, 5.9%), the recently described VNII-VNIV (aADa) hybrid (n = 14, 3.8%), VNIV (MATa) (n=4, 1.1%), VNIII (aADa) hybrid (n = 1, 0.3%), and VNIII (aADa) hybrid (n = 1, 0.3%). The Argentine Central region showed the greatest number of cases and genotype diversity. Interestingly, a relative high frequency was observed in genotype VNII (MATa) in the Cuyo, Northeast and Northwest regions and, also in VNII-VNIV (aADa) hybrids in the Northwest region. C. gattii species complex was isolated at a low rate; 3 VGI (MATa) and 1 VGII (MATa) isolates were obtained from the Northwest and Central regions. In conclusion, this study shows that genotype frequencies seem to vary among regions in Argentina and reveals a relatively high frequency of rare hybrids in the Northwest region. Further regional clinical and environmental studies may help to elucidate if those varia-tions in frequencies are associated with the existence of regional ecological niches or any other regional factors.

Resumen El objetivo de! trabajo fue conocer la frecuencia y la distribución geográfica de genotipos y tipos sexuales de aislados pertenecientes a los complejos de especies Cryptococcus neoformansy Cryptococcus gattii obtenidos de infecciones humanas en Argentina. Entre abril de 2009 y abril de 2011 se realizó un estudio multicéntrico del que se obtuvieron 372 aislados de 61 laboratorios de diferentes zonas del país. El 98,8% de los aislados pertenecieron al complejo C. neoformansy el 1,1% al complejo C. gattii. El genotipo VNI (MATa) fue el más frecuente (n = 326; 87,6%), le siguieron VNII (MATa) (n = 22; 5,9%), el híbrido VNII-VNIV (aADa) (n = 14; 3,8%), VNIV (MATa) (n =4; 1,1%) y los híbridos VNIII (aADa) (n = 1; 0,3%) y VNIII (aADa) (n = 1; 0,3%). La región Centro mostró el mayor número de casos y la mayor diversidad de genotipos. Cabe destacar que el genotipo VNII (MATa) tuvo una frecuencia relativamente alta en las regiones de Cuyo, Noreste y Noroeste. En esta última región, también fue alta la frecuencia del híbrido VNII-VNIV (aADa). La frecuencia de aislamiento de miembros del complejo C. gattii fue baja: se obtuvieron 3 aislados VGI (MATa) y 1 VGII (MATa) de las regiones Centro y Noroeste. En conclusión, este estudio muestra que las frecuencias de genotipos varían entre las distintas regiones de Argentina y señala la presencia de híbridos poco comunes en una frecuencia relativamente alta dentro de la región Noroeste. Contar con mayor número de estudios clínicos y ambientales regionales podría ayudar a elucidar si tales variaciones están asociadas a la existencia de nichos ecológicos particulares o a algún otro factor regional.

Clinical and microbiological characteristics of cryptococcosis at an university hospital in China from 2013 to 2017

ABSTRACT Background: This study aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis from 2013 to 2017 in a major teaching hospital in China. Methods: Trends in antifungal drug susceptibility of 217 consecutive non-repetitive cryptococcal isolates collected from patients of an university hospital in China were analyzed between 2013 and 2017. Of those, 98 isolates were conserved for identification by internal transcribed spacer (ITS) sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Multilocus sequence typing (MLST) was used to designate molecular types. Clinical characteristics of the 98 patients with cryptococcosis during the period of 2013-2017 were retrospectively evaluated. Results: There was a trend for gradual increase in the MIC range of fluconazole was from 2013 to 2017. The conserved 98 clinical cryptococcal isolates included 97 C. neoformans and one C. gattii, and 90 (91.8%) isolates belonged to ST5 genotype VNI. Out of the 98 patients with cryptococcosis, 28 (28.6%) were HIV-infected and 32 (32.7%) had no underlying diseases. HIV-infected patients had higher mortality than HIV-uninfected patients (28.6% vs 14.3%, p = 0.147). Conclusions: Most of the patients with cryptococcosis were not HIV-infected in this study, while patients with HIV had a higher mortality. Reduced susceptibility to fluconazole was observed among C. neoformans isolates, most of them belonged to ST5 genotype VNI having an impact on the effective dose of fluconazole.

Asymptomatic cryptococcal antigenemia in HIV-infected patients: a review of recent studies / 中华医学杂志(英文版)

The prevalence of asymptomatic cryptococcal antigenemia (ACA) in human immunodeficiency virus (HIV) infected individuals has been observed to be elevated. The prevalence of ACA ranges from 1.3% to 13%, with different rates of prevalence in various regions of the world. We reviewed studies conducted internationally, and also referred to two established expert consensus guideline documents published in China, and we have concluded that Chinese HIV-infected patients should undergo cryptococcal antigen screening when CD4 T-cell counts fall below 200 cells/μL and that the recommended treatment regimen for these patients follow current World Health Organization guidelines, although it is likely that this recommendation may change in the future. Early screening and optimized preemptive treatment for ACA is likely to help decrease the incidence of cryptococcosis, and is lifesaving. Further studies are warranted to explore issues related to the optimal management of ACA.

Boletim epidemiológico: perfil de pacientes com micoses sistêmicas notificados de 2013 a 2018 em hospital de referência do estado de Goiás / Epidemiological bulletin: profile of patients with systemic mycoses notified from 2013 to 2018 in a reference hospital in the state of Goiás

Micoses Sistêmicas são infecções fúngicas causadas por patógenos primários cujo trato respiratório é utilizado como porta de entrada, mas ocasionalmente se disseminam para todo o organismo. As micoses sistêmicas consideradas endêmicas no Brasil são: paracoccidioidomicose, histoplasmose, coccidioidomicose e criptococose. Por se tratarem de doenças fúngicas emergentes constata-se a necessidade de implantação de uma vigilância epidemiológica eficaz, que tenha impacto positivo na saúde pública no que diz respeito à elaboração de diretrizes e execuções de ações para prevenção, tratamento, e controle dessas micoses. Desta forma, este boletim tem como objetivo descrever o perfil de pacientes com micoses sistemas notificados em hospital de referência de Goiás. Trata-se de um estudo transversal descrito, quantitativo, com dados obtidos do Sistema de Informação de Agravos de Notificação (SINAN-NET) de um Núcleo Hospitalar de Vigilância Epidemiológica do estado de Goiás no período de 2013 a 2018

Systemic mycoses are fungal infections caused by primary pathogens whose respiratory tract is used as a gateway, but occasionally disseminate throughout the body. The systemic mycoses considered endemic in Brazil are: paracoccidioidomycosis, histoplasmosis, coccidioidomycosis and cryptococcosis. As they are emerging fungal diseases, there is a need to implement effective epidemiological surveillance, which has a positive impact on public health with regard to the elaboration of guidelines and execution of actions for the prevention, treatment, and control of these mycoses. Thus, this bulletin aims to describe the profile of patients with systemic mycoses reported in a referral hospital in Goiás. This is a descriptive, quantitative, cross-sectional study with data obtained from the Notifiable Diseases Information System (SINAN-NET) of a Hospital Center for Epidemiological Surveillance in the state of Goiás from 2013 to 2018

Prevalence of cryptococcosis in Atlántico, department of Colombia assessed with an active epidemiological search

Abstract INTRODUCTION Cryptococcosis is the second most frequent cause of opportunistic infections in human immunodeficiency virus (HIV) patients in Colombia. We aimed to determine the prevalence of cryptococcosis in the Colombian department of Atlántico. METHODS An active search for cryptococcosis cases was conducted between 2015 and 2017 in health institutions by distributing surveys to clinicians and characterizing samples phenotypically and genotypically. RESULTS Thirty-eight cryptococcosis cases were identified (81.6% men, 76.3% HIV patients). The calculated annual prevalence was 5.08/1 million inhabitants. Cryptococcus neoformans var. grubii VNI was isolated in 34 cases. CONCLUSIONS These results provide the basis for passive surveillance of cryptococcosis.

Antifungal susceptibility of clinical and environmental Cryptococcus neoformans and Cryptococcus gattii isolates in Jabalpur, a city of Madhya Pradesh in Central India

In this study, we present antifungal susceptibility data of clinical and environmental isolates of Central Indian Cryptococcus neoformans (Serotype A, n = 8 and n = 50 respectively) and Cryptococcus gattii (Serotype B, n = 01 and n = 04 respectively). Susceptibilities to fluconazole, itraconazole and ketoconazole were determined by using NCCLS broth micro-dilution methodology. The total number of resistant strains for fluconazole in case of C. neoformans and C. gattii showed a significant difference by using chi-square test (p < 0.05*), while considering fisher's exact p value was nonsignificant (p > 0.05). However, the total number of resistant strains for itraconazole and ketoconazole was not found statistically significant. A comparison of geometric means of clinical and environmental strains of C. gattii and C. neoformans was not found statistically significant using student ‘t’ test (p value > 0.05 NS). Though less, the antifungal data obtained in this study suggests that primary resistance among environmental and clinical isolates of C. neoformans and C. gattii against tested antifungal was present and C. gattii comparatively was less susceptible than C. neoformans var. grubii isolates to fluconazole than to itraconazole and ketoconazole. A continuous surveillance of antifungal susceptibility of clinical and environmental isolates of C. neoformans and C. gattii is desirable to monitor the emergence of any resistant strains for better management of cryptococcosis patients.

Cryptococcosis in Atlántico, Colombia: an approximation of the prevalence of this mycosis and the distribution of the etiological agent in the environment

ABSTRACTINTRODUCTION:Cryptococcosis is an invasive disease acquired by inhalation of infectious propagules from the environment. Currently, compulsory notification of the spread of this disease is not required in Colombia. However, reporting of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome cases to the National Surveillance System has suggested that there is a growing population at risk of contracting cryptococcosis. Few studies have described the occurrence of cryptococcosis in Colombia. Therefore, in this study, we examined the pathology of this disease in Atlántico, Colombia and determined the distributions of Cryptococcus neoformans and Cryptococcus gattii in the environment.METHODS:Clinical samples/isolates were gathered from cases of cryptococcosis previously diagnosed at health institutions in Atlántico, and surveys were completed by clinicians. The environmental study considered 32 sampling points and three tree species, i.e., Quickstick ( Gliricidia sepium ), Almond ( Terminalia catappa ), and Pink trumpet ( Tabebuia rosea ). Environmental and clinical samples/isolates were analyzed for phenotypic and genotypic confirmation.RESULTS:From 1997-2014, 41 cases of cryptococcosis were reported. The mean patient age was 40.5 years (range: 18-63 years); 76% were men, and 78% were HIV positive. Isolation was possible in 38 cases ( C. neoformans , molecular type VNI in 37 cases and C. gattii , molecular type VGI in one case). In 2012-2014, 2,068 environmental samples were analyzed with a positivity of 0.4% ( C. neoformans , molecular type VNI) in Almond and Pink trumpet trees.CONCLUSIONS:Cryptococcus neoformans , molecular type VNI had a higher prevalence than C. gattii and was associated with human exposure and the pathogenesis of cryptococcosis in this geographical region.

Epidemiological characterization and prognostic factors in patients with confirmed cerebral cryptococcosis in central Taiwan

Background Cryptococcal meningitis is a deadly fungal infection. This study aimed to characterize the epidemiology of cerebral cryptococcosis and to define its prognostic factors. Methods This cross-sectional study collected clinical information from cryptococcal meningitis patients with confirmed cerebral cryptococcosis from 2006 to 2012 at the Changhua Christian Healthcare System to access prognostic factors. Result Fifty-nine adult cryptococcal meningitis patients were studied. The incidence at Changhua Christian Healthcare System was approximately 170 episodes per 100,000 patients within the studied period. Forty-one of 59 cryptococcal meningitis patients developed complications. Overall, 12 of 59 patients died, for a three-month mortality rate of 20.3 %. Prognostic factors positively associated with the three-month mortality included age (>55 years), patient delay, prolonged delay by the doctor in administering antifungal agent therapy, duration of intensive care unit stay, chronic lung disease, cryptococcemia, headache, altered mental status, positive blood cultures, and high cerebrospinal fluid opening pressure (>250 mm H2O). Conclusions We strongly recommend early administration of an antifungal agent to each suspected cryptococcal meningitis patient to decrease both the delay by doctors in administering therapy and the mortality risk. Aggressive and supportive care for severe cryptococcal meningitis patients is critical to decrease overall mortality from this infection.

Cryptococcosis in Colombian children and literature review

Cryptococcosis is reported in adults and is often acquired immune deficiency syndrome (AIDS)-associated; however, its frequency in children is low. Based on the National Survey on Cryptococcosis conducted in Colombia, an epidemiological and clinical analysis was performed on cases of the disease observed in children less than 16 years old between 1993-2010. We found 41 affected children (2.6% prevalence) from the 1,578 surveys received. The country mean annual incidence rate was 0.017 cases/100,000 children under 16 years, while in Norte de Santander the incidence rate was 0.122 cases/100,000 (p < 0.0001). The average age of infected children was 8.4 and 58.5% were male. In 46.3% of cases, a risk factor was not identified, while 24.4% had AIDS. The most frequent clinical manifestations were headache (78.1%), fever (68.8%), nausea and vomiting (65.6%), confusion (50%) and meningeal signs (37.5%). Meningitis was the most frequent clinical presentation (87.8%). Amphotericin B was given to 93.5% of patients as an initial treatment. Positive microbiological identification was accomplished by India ink (94.7%), latex in cerebrospinal fluid (100%) and culture (89.5%). Out of 34 isolates studied, Cryptococcus neoformans var. grubii (VNI 85.3%, VNII 8.8%) was isolated in 94.1% of cases and Cryptococcus gattii (VGII) was isolated in 5.9% of cases. These data are complemented by a literature review, which overall suggests that cryptococcosis in children is an unusual event worldwide.

Análise da variabilidade do genótipo vgii de cryptococcus gattii em isolados clínicos e ambientais do Brasil / Analysis of the variability of vgii genotype of cryptococcus gattii in environmental and clinical isolates from Brazil

A criptococose é causada por duas espécies distintas de leveduras capsuladas da divisão dos basidiomicetos, Cryptococcus neoformans e Cryptococccus gattii, as quais causam infecções invasivas emergentes de significativa letalidade, seja em imunodeprimidos ou imunocompetentes. No Brasil, a criptococose por C. gattii tem caráter endêmico, ocorrendo principalmente em indivíduos HIV negativos. O caráter epidêmico deste agente tem sido evidenciado por surtos em animais, sendo o mais significativo a epidemia ocorrida em Vancouver, Canadá, atingindo humanos e animais desde 1999...

Cryptococcosis is caused by two distinct species of capsulated basidiomycetes yeasts, Cryptococcus neoformans and Cryptococccus gattii, which are responsible for invasive infections with significant lethality, either in immunocompetent or immunocompromised individuals. In Brazil, cryptococcosis by C. gattii is endemic, occurring mainly in HIV negative individuals. The epidemic nature of this agent has been reported by outbreaks in animals and human in Vancouver, Canada, which is the most significant outbreak and started in 1999...

Contribución al estudio de la criptococosis infantil en Cuba / Contribution to the study of infant cryptococosis in Cuba

Introducción: a partir de 1998 en el laboratorio de micología del Instituto Pedro Kourí se observó un incremento del número de aislamientos de Cryptococcus obtenidos de niños seronegativos al VIH con meningoencefalitis. Los reportes de criptococosis infantil a nivel mundial son infrecuentes y generalmente se encuentran asociados al sida. Objetivo: estudiar la criptococosis infantil en Cuba a través de la evaluación integral de 7 casos. Métodos: se realizó un estudio retrospectivo integral, se revisaron las historias clínicas de 7 pacientes pediátricos afectados por criptococosis menigoencefálica y se caracterizaron los aislamientos obtenidos (uno de cada paciente). A estos se les determinó la especie, variedad, serotipo, patogenicidad en un modelo murino y susceptibilidad a la anfotericina B. Resultados: la edad media de los niños fue de 5,8 años, con ligero predominio del sexo femenino (4:3). Los síntomas más frecuentes resultaron la cefalea, fotofobia, fiebre y los vómitos. En 6 pacientes el estudio citoquímico del líquido cefalorraquídeo y el examen imaginológico de cráneo evidenciaron anomalías. El diagnóstico microbiológico se realizó mediante examen directo y cultivo. Todos los aislamientos correspondieron con Cryptococcus neoformans serotipo A y la anfotericina B mostró una concentración mínima inhibitoria menor o igual que 0,125 mg/mL. El 85,7 porciento mostró actividad fenoloxidasa y elevada letalidad en los animales infectados (71,4-100 porciento). Conclusiones: el pronóstico de la meningoencefalitis por Cryptococcus está estrechamente ligado a un diagnóstico precoz. Esta realidad hace que deba tenerse siempre presente, por lo que los datos aportados bien pudieran servir de alerta a los médicos de asistencia

Introduction: since 1998, an increasing number of Cryptococcus isolates obtained from HIV-negative children with meningoencephalitis was observed in the mycology laboratory at Pedro Kourí Institute. The global reports of child cryptococcosis are rare and usually associated with AIDS. Objectives: to study child cryptococosis in Cuba through the comprehensive evaluation of 7 cases. Methods: the clinical histories of seven pediatric patients with cryptococcal meningoencephalitis were examined and the obtained isolates (one per patient) were characterized. The species, variety, serotype, pathogenicity in a mouse model and amphotericin B susceptibility of the isolates were determined. Results: average age of the children was 5.8 years, with a slight female predominance (4:3). The most common symptoms were headache, photophobia, fever and vomiting. The cytochemical study of cerebral spinal fluid and skull imaging test showed abnormalities in 6 patients. The microbiological diagnosis was made through direct examination and culture. All the isolates were from Cryptococcus neoformans serotype A and amphotericin B showed a minimum inhibitory concentration £ 0.125 mg/mL. In the group, 85.7 percent showed phenoloxidase activity and high lethality rate in infected animals (71.4 to 100 percent). Conclusions: the prognosis of cryptococcal meningoencephalitis is closely linked to early diagnosis, therefore, this should be always kept in mind and the provided data from this study may serve as warning to attending physicians

Suscetibilidade in vitro e resistência a antifúngicos - estudo comparativo entre os tipos moleculares vni de cryptococcus neoformans e vgi, vgii de cryptococcus gattii pela citometria de fluxo / In vitro susceptibility and resistance to antifungal drugs - a comparative study of the molecular types of cryptococcus neoformans vni, cryptococcus gattii vgi and vgii by flow cytometry

A criptococose é uma micose sistêmica adquirida pela inalação de basidiosporos ou leveduras desidratadas de Cryptococus neoformans e Cryptococus gattii, estas duas espécies podem causar criptococose oportunista e primária respectivamente. C. neoformans está constituído de tipos moleculares VNI-VNIV e C. gattii de VGI-VGIV que apresentam distribuição geográfica diferenciada, como por exemplo, o tipo VNI é cosmopolita e está associado a AIDS e VGI predominando na Austrália e EUA, o tipo VGII predominando no Brasil e America Latina. Este trabalho tem por objetivo realizar estudo comparado dos tipos moleculares VNI de C. neoformans, VGI e VGII de C. gattii analisando diferentes aspectos tais como: 1- Determinar o perfil da suscetibilidade in vitro da concentração inibitória mínima (CIM) de fluconazol (FLZ), itraconazol (ITZ), 5-fluorocitosina (5FC) e anfotericina B (AMB), isoladamente e de forma combinada de AMB com 5FC e AMB com Voriconazol (VRZ); 2- Determinar CIM pela citometria de fluxo (CMF) frente a FLZ, ITZ e AMB; 3- Definir a concentração mínima letal (CML) de AMB e 5FC, isoladamente e em combinação; 4- Avaliar a ação da melanina frente a 5FC e AMB na forma combinada e isolada de 5FC; 5- Induzir a resistência in vitro para FLZ e padronizar os fluorocromos: acetoximetil - calceína (calceina-AM), acetoximetil - 2’, 7’ -bis-(2-carboxietil)-5-(e -6)- carboxifluoresceína (BCECF-AM), rodamina 123 (Rh123) e iodeto de 3, 3’ –dipentiloxacarbocianina (DiOC5) na CMF para verificar a expressão de bombas de efluxo; 6- Comparar a expressão de bombas de efluxo...

Cryptococcosis is a systemic mycosis acquired by inhalation of dried yeasts or basidiospores of Cryptococus neoformans and Cryptococus gattii, these species can cause cryptococcosis opportunistic and primary respectively. C. neoformans is composed of molecular types VNI - VNIV and C. gattii VGI - VGIV they have different geographical distribution, the VNI type is cosmopolitan and is associated with AIDS, VGI type is predominant in Australia and the USA; while VGII type occurs in Brazil and Latin America. This paper aims to conduct a comparative study of the molecular types VNI C. neoformans and VGI, VGII C. gattii analyzing different aspects such as: 1 – The susceptibility profile in vitro of fluconazole ( FLZ ), itraconazole ( ITZ ), 5 - fluorocytosine ( 5FC ) and amphotericin B ( AMB ) alone and in combination with 5FC and AMB with voriconazole ( VRZ ) 2 – The minimum inhibitory concentration ( MIC ) by flow cytometry ( FCM ) comparing MIC of FLZ, ITZ and AMB with CLSI; 3 - The minimum lethal concentration ( MLC ) of AMB and 5FC, alone and in combination; 4 - The action of melanin against 5FC and AMB alone and combined 5FC, 5 – The induced resistance in vitro to FLZ and standardize the fluorochromes: acetoximetil - calceína (calceina-AM), acetoximetil - 2’, 7’ -bis-(2-carboxietil)-5-(e -6)- carboxifluoresceína (BCECF-AM), rodamina 123 (Rh123) e iodeto de 3, 3’ – dipentiloxacarbocianina (DiOC5) in FCM to verify expression of efflux pumps; 6 - The compare the expression of efflux pumps...

Cryptococcosis in Colombia: Results of the national surveillance program for the years 2006-2010 / Criptococosis en Colombia: resultados de la encuesta nacional, 2006-2010

Introduction: A survey on cryptococcosis is being conducted regularly in Colombia since 1997. We present hereby the results corresponding to patients diagnosed from 2006 to 2010. Objective: To analyze the data obtained during this period. Materials and methods: Retrospective analysis of the corresponding surveys. Results: A total of 526 surveys originating from 72% of the Colombian political divisions were received during the 5-year period. Most patients (76.6%) were males and 74.9% were 21-50 years old. The most prevalent risk factor was HIV infection (83.5%) with cryptococcosis defining AIDS in 23% of the cases. In the general population the estimated mean annual incidence rate for cryptococcosis was 2.4 x 106 inhabitants while in AIDS patients this rate rose to 3.3 x 103. In 474 surveys stating clinical features, most frequent complaints were headache 84.5%, fever 63.4%, nausea and vomiting 57.5%, mental alterations 46.3%, meningeal signs 33.0%, cough 26.4% and visual alterations 24.5%. Neurocryptococcosis was recorded in 81.8% of the cases. Laboratory diagnosis was based on direct examination, culture and latex in 29.3% cases. From 413 Cryptococcus isolates analyzed, 95.6% were identified as C. neoformans var. grubii, 1% C. neoformans var. neoformans, and 3.4% C. gattii. Treatment was reported for 71.6% of the cases with amphotericin B alone or in combination with fluconazole prescribed in 28%. Conclusions: Surveys done through passive surveillance continue to be sentinel markers for HIV infection and represent a systematic approach to the study of opportunistic problems regularly afflicting AIDS patients since cryptococcosis requires no compulsory notification in Colombia.

Introducción. Desde 1997 se viene realizando un programa nacional de vigilancia sobre la criptococosis en Colombia. Se presentan los resultados correspondientes a los pacientes diagnosticados entre el 2006 y el 2010. Objetivo. Analizar los datos obtenidos durante este periodo. Materiales y métodos. Análisis retrospectivo de las encuestas. Resultados. Durante los cinco años mencionados se recibieron 526 encuestas representativas del 72 % de la división política colombiana. La mayoría de pacientes (76,6 %) eran hombres y 74,9 % estaban entre los 21 y los 50 años. El factor de riesgo prevalente fue la infección por VIH (83,5 %), y la criptococosis definió el sida en 23 % de los casos. La incidencia anual promedio en la población general fue de 2,4 por un millón de habitantes mientras que, en pacientes con sida, aumentó a 3,3 por 1.000. En 474 encuestas se informaron manifestaciones clínicas; las más frecuentes fueron: cefalea (84,5 %), fiebre (63,4 %), náuseas y vómito (57,5 %), alteraciones mentales (46,3 %), signos meníngeos (33 %), tos (26,4 %) y alteraciones visuales (24,5 %). La neurocriptococosis se reportó en 81,8 % de los casos. El diagnóstico se hizo por examen directo, cultivo y antigenemia en 29,3 % de los casos. De 413 aislamientos recuperados, 95,6 % fueron C. neoformans var. grubii, 1 % C. neoformans var. neoformans, y 3,4 % C. gattii. En 71,6 % de los casos para el tratamiento se administró anfotericina B y en 28 % se combinó con fluconazol. Conclusiones. La vigilancia pasiva continúa siendo un marcador centinela para la infección por VIH, y constituye una aproximación sistemática al estudio de infecciones oportunistas en pacientes con sida, debido a que la criptococosis no es de notificación obligatoria en Colombia.

Estudio clínico-epidemiológico de la criptococosis en Venezuela: años 1994-2003 / Clinical-epidemological study of cryptococcosis in Venezuela: 1994-2003

La criptococosis es una enfermedad oportunista de distribución mundial. Frecuentemente es una infección definitoria de SIDA. El tratamiento antirretroviral ha disminuido su frecuencia. El impacto de esta entidad en Venezuela es desconocido. El objetivo de este trabajo es describir las características más relevantes de la criptococosis en nuestro país. Se revisaron 110 historias clínicas de pacientes hospitalizados con el diagnostico de criptococosis, entre 1994 y 2003, en 6 hospitales. Los datos recolectados incluyeron: características demográficas, clínicas, diagnósticas, terapéuticas y la evolución de los pacientes. Para el análisis se utilizaron los programas SPSS 10.0 y EpiInfo 6.04 (2001). Dentro de los 110 pacientes evaluados se incluyeron 17 protocolos de autopsia. Uno solo de los pacientes tenia 8 años de edad, el resto era mayor de 15 años. 91 eran del sexo masculino y 19 femenino. 91 (82,73 por ciento) tenían SIDA y 19 (17,27 por ciento) eran VIH negativo. En los pacientes con SIDA el valor promedio de CD4+ fue < 200 cel/mm³ y la carga viral era > 30000 copias/mL; 52 (57,14 por ciento) de los casos no tenían otra infección oportunista y 39 (42,86 por ciento) tenían otras condiciones asociadas, tales como tuberculosis (30,97 por ciento), neumocistosis (28,21 por ciento), y toxoplasmosis (20,51 por ciento). En los pacientes VIH negativo, el uso de esteroides (25 por ciento) fue el factor de riesgo predominante. Dos pacientes eran embarazadas. En 107 (57,27 por ciento) se encontró infección del SNC. 12 (13,19 por ciento) de los pacientes con SIDA tenían alteración de pares craneales. Se encontró afectación pulmonar en 4 (3,77 por ciento) pacientes, 1 de ellos con SIDA. La criptococosis fue la enfermedad definitoria de SIDA en el 61,54 por ciento de los casos. 33 (30 por ciento) de los pacientes fallecieron. En la mayoría de los pacientes la criptococosis se asoció a SIDA. A pesar de la eficacia del tratamiento antirretrovial, esta micosis es todavia ...

Cryptococcosis is an opportunistic disease of worldwide distribution. It is frequently an AIDS-defining infection. Antiretroviral treatment has reduced its occurrence. In Venezuela, the impact of this disease is unknown. The aim of this study is to describe the most relevant features of cryptococcosis in our country. 110 clinical records with a diagnosis of cryptococcosis hospitalized between 1994 and 2003 in 6 Venezuelan hospitals were analyzed. Data collected included demographic, clinical, diagnostic, therapeutic and outcome information. SPSS 10.0 software and EpiInfo 6, version 6.04 (2001) were used. 110 patients with cryptococcosis were enrolled, including 17 autopsy protocols. One was 8 years old, the rest were over 15. Nineteen were female and 91 male; 91 (82.73 percent) had AIDS, 19 (17.27 percent) were HIV negative. Among the AIDS patients, average CD4+ count was < 200 cel/mm3 and viral load was > 30000 copies/ml; 52 (57.14 percent) did not have other opportunistic infections or AIDS-related disease, and 39 (42.86 percent) had other associated conditions, such as tuberculosis (30.97 percent), PCP (28.21 percent) and toxoplasmosis (20.51 percent). In HIV negative patients, use of steroids (25 percent) was the predominant risk factor. Two patients were pregnant. 107 (57.27 percent) presented CNS infection; 12 (13.19 percent) with AIDS had cranial nerve alterations. Pulmonary disease was found in 4 (3.77 percent), of which one had AIDS. Cryptococcosis was an AIDS-defining infection in 61.54 percent of cases; 33 (30 percent) of the patients died. In most of the patients, cryptococcosis was associated with AIDS. In spite of the efficacy of antiretroviral treatment, this mycosis is still significant in Venezuela, perhaps due to late HIV infection diagnosis

Primary endemic Cryptococcosis gattii by molecular type VGII in the state of Pará, Brazil

In order to study the infectious agents causing human disseminated cryptococcosis in the state of Pará, North Brazil, 56 isolates of Cryptococcusspp. (54 isolated from cerebral spinal fluid and two from blood cultures) from 43 cases diagnosed between 2003-2007 were analysed. The species were determined through morphological and physiological tests and genotypes were determined by URA5-RFLP and PCR-fingerprinting (wild-type phage M13). The following species and genotypes were identified: Cryptococcus neoformans VNI (28/56, 50 percent), Cryptococcus gattii VGII (25/56, 44.64 percent) and C. gattii VGI (3/56, 5.26 percent). The genotype VNI occurred in 12 out of 14 HIV-positive adults, whereas the genotype VGII occurred in 11 out of 21 HIV-negative adults (p < 0.02, OR = 6.6 IC95 percent 0.98-56.0). All patients less than 12 years old were HIV negative and six cases were caused by the VGII genotype, one by the VGI and one by VNI. Therefore, endemic primary mycosis in HIV-negative individuals, including an unexpectedly high number of children, caused by the VGII genotype deserves further study and suggests the need for surveillance on cryptococcal infection in the state of Pará, Eastern Amazon.

Clinical and epidemiological features of 123 cases of cryptococcosis in Mato Grosso do Sul, Brazil

To identify the clinical and epidemiological profile of cryptococcosis diagnosed at the University Hospital of the Federal University of Mato Grosso do Sul, Brazil, medical records of 123 patients admitted from January 1995 to December 2005 were analyzed. One hundred and four cases (84.5 percent) had HIV infection, six (4.9 percent) had other predisposing conditions and 13 (10.6 percent) were immunocompetent. Male patients predominated (68.3 percent) and their age ranged from 19 to 69 years (mean: 35.9). Most patients (73.2 percent) were born and lived lifelong in the state of Mato Grosso do Sul. Involvement of the central nervous system occurred in 103 patients (83.7 percent) and headache and vomiting were the most frequent symptoms. In 77 cases it was possible to identify the Cryptococcus species: 69 (89.6 percent) C. neoformans and eight (10.4 percent) C. gattii. Amphotericin B was the drug of choice for treatment (106/123), followed by fluconazole in 60 percent of cases. The overall lethality rate was 49.6 percent, being 51 percent among the HIV infected patients and 41.2 percent among the non-HIV infected (p > 0.05). Although cryptococcosis exhibited in our region a similar behavior to that described in the literature, the detection of an important rate of immunocompetent individuals and five C. gattii cryptococcosis in HIV-infected patients is noteworthy.

O perfil clínico-epidemiológico de 123 casos de criptococose diagnosticados no Hospital Universitário da Universidade Federal de Mato Grosso do Sul, no período de janeiro de 1995 até dezembro de 2005, foi estudado retrospectivamente. Cento e quatro (84,9 por cento) casos tinham associação com HIV, seis (4,9 por cento) tinham outra condição predisponente e 13 (10,6 por cento) eram imunocompetentes. Houve predomínio do sexo masculino (68,3 por cento) e a idade variou de 19 a 69 anos (média de 35,9 anos). A maioria (73,2 por cento) era natural e procedente de Mato Grosso do Sul. O envolvimento do sistema nervoso central ocorreu em 103 (83,7 por cento) pacientes e os sintomas mais freqüentes foram cefaléia e vômitos. Em 77 casos foi possível identificar a espécie do agente, sendo 69 (89,6 por cento) C. neoformans e oito (10,4 por cento) C. gattii. O antifúngico mais utilizado foi anfotericina B (106/123) seguido de fluconazol em aproximadamente 60 por cento dos casos. A taxa de letalidade foi de 49,6 por cento, sendo 51 por cento entre os pacientes infectados pelo HIV e 41,2 por cento entre os não infectados pelo HIV (p > 0,005). Apesar da criptococose observada em nossa região apresentar comportamento semelhante ao descrito na literatura, chama a atenção a importante taxa da micose em imunocompetentes e cinco casos de infecção por C. gattii em pacientes HIV-positivos.

Estudio clínico y epidemiológico de la criptococosis en Colombia: resultados de nueve años de la encuesta nacional, 1997-2005 / Results of nine years of the clinical and epidemiological survey on cryptococcosis in Colombia, 1997-2005

Introducción. Con el fin de conocer la situación de la criptococosis en Colombia se ha llevado a cabo una encuesta nacional. El presente estudio analiza la información recogida de 1997 a 2005. Materiales y métodos. Se utilizó el formato de encuesta de la Confederación Europea de Micología Médica. Resultados. Se recibieron 931 encuestas de 76 centros. Se identificaron 891 (95,7 por ciento) casos de neurocriptococosis, 27 (2,9 por ciento) de formas pulmonares, cinco (0,5 por ciento) de lesiones cutáneas, dos (0,2 por ciento) de ganglionares, dos (0,2 por ciento) de úlceras orofaríngeas y un caso (0,1 por ciento) de cada una de las siguientes formas clínicas: peritonitis, lesión hepática, celulitis de los miembros inferiores e infección de las vías urinarias. El 82,7 por ciento fueron hombres con predominio de los adultos jóvenes. Sin embargo, se reportaron 25 (2,7 por ciento) niños. La infección por el virus de la inmunodeficiencia humana se encontró en el 78,1 por ciento de los casos. La incidencia promedio anual de criptococosis en la población general fue de 2,4 casos x106, pero en los pacientes con sida se elevó a 3,0 casos x 103. Las manifestaciones clínicas más frecuentes fueron: cefalea (85,2 por ciento), náuseas y vómito (59,1 por ciento), fiebre (59 por ciento), cambios mentales (46,2 por ciento) y signos meníngeos (33,4 por ciento). El examen directo de líquido cefalorraquídeo fue positivo en el 92,8 por ciento de los casos y el hongo se recuperó en el 90,3 por ciento. El antígeno capsular tuvo una positividad del 98,9 por ciento en el líquido cefalorraquídeo y del 93,7 por ciento en el suero. De 788 aislamientos remitidos, 95,9 por ciento fueron Cryptococcus neoformans var. grubii serotipo A, 0,3 por ciento, var. neoformans serotipo D, 3,3 por ciento, C. gattii serotipo B y 0,5 por ciento, C. gattii serotipo C. La mayoría de los pacientes fueron tratados inicialmente con anfotericina B. Conclusión: La criptococosis es una enfermedad cuya incidencia a...

Introduction. A national survey on cryptococcosis has been conducted in Colombia since 1997. The survey data recorded over a 9-year period, 1997 to 2005, was summarized. Materials and methods. The format provided by the European Confederation of Medical Mycology was adapted with the correspondent permission. Results. Over the 9 year period, 931 surveys were received from 76 centers. The associated disease syndromes were as follows: 891 (95.7%) were neurocryptococosis cases, 27 (2.9%) pulmonary disease, 5 (0.5%) cutaneous lesions, 2 (0.2%) ganglionar forms, 2 (0.2%) oropharyngeal lesions and one case (0.1%) each from peritonitis, liver lesion, cellulitis and urinary tract infection. Demographic data indicated 82.7% of the subjects were males, and 59.4% were between 20-39 years old; 25 children less than 16 years old were reported. The prevalent risk factor was HIV infection (78.1%). The mean annual incidence rate of cryptococcosis in the general population was 2.4 X 106 inhabitants, but in AIDS patients the rate rose to one in 3 X 103. The most frequent clinical features were headache (85.2%), nausea and vomiting (59.1%), fever (59.0%), mental changes (46.2%), meningeal signs (33.4%), cough (23.6%) and visual alterations or loss of vision (20.9%). Laboratory data showed that direct examination of cerebrospinal fluid (CSF) was positive in 92.8% cases and Cryptococcus was recovered in 90.3% of the cases. Cryptococcal antigen reactivity was 98.9% in CSF and 93.7% in serum samples. From 788 isolates submitted, 95.9% were C. neoformans var. grubii serotype A, 0.3% var. neoformans serotype D, 3.3% C. gattii serotype B and 0.5% C. gattii serotype C. The majority of patients were treated initially with amphotericin B. Conclusion. Cryptococcosis incidence has increased dramatically in Colombia with the AIDS pandemic and it can be considered as a sentinel marker for HIV infection.

Estudio epidemiológico de la Criptococosis / Crytococosis epidemiologic study

En este trabajo, se realizó un estudio clínico-epidemiológico de la criptococosis, de tipo mixto, dividido en 3 secciones: SECCIÓN I: Los pacientes con criptococosis, estudio descriptivo. Se evaluaron 110 historias clínicas cuyo diagnóstico se realizó entre los años de 1994-2003, en 4 centros de referencia asistencial del país. Se tomaron en cuenta caracteres demográficos, clínicos y paraclínicos. Un 82,7 por ciento tenía SIDA y un 17,3 por ciento eran VIH seronegativos. La clínica más frecuentemente observada fue la encefalitis o meningoencefalitis (98,2 por ciento). La mortalidad fue de un 30,00 por ciento, predominantemente en pacientes con SIDA, a razón de 7.3:1. Entre los indicadores de mal pronóstico de la población evaluada, la alteración del estado de conciencia fue la que ejerció el mayor peso. SECCIÓN II: Los aislados de Cryptococcus spp, estudio experimental. Se evaluó la utilidad del medio agar cerebro-corazón con sangre, para el aislamiento de las cepas a partir de las muestras clínicas, entre los años 2001-2003. Se estudiaron un total de 132 cepas de cryptococcus spp, unas aisladas de muestras clínicas y otras conservadas en micotecas en los últimos 10 años. En este trabajo se introdujo la prueba de auxanograma por la técnica de Beijerinck modificada por Araujo, la cual resultó tener una elevada sensibilidad y especificidad. Se comprobó la utilidad del Caldo Urea de Stuart para la realización de la prueba de la ureasa a levaduras de este género. SECCIÓN III: La cepa de crytococcus spp y el paciente, estudio descriptivo. Se evaluó la relación existente entre la variedad de C. neoformans aislado y el patrón genotípico del mismo con repsecto a caracteres demográficos, clínica, paraclínica y evolución, entre otros presentadores por el paciente al cual se le aisló la cepa. Se encontró una diferencia estadísticamente significativa en la asociación entre C. neoformans var gattii y la presencia de alteración de los pares craneales.