RESUMO
Chimeric antigen receptors (CARs) redirect T cells to recognize a specific target. CAR components play a pivotal role in antigen specificity, structure stability, expression on cell surface, and induction of cellular activation, which together determine the success of CAR T-cell therapy. CAR products targeting B-cell lymphoma encouraged the development of new CAR applications beyond cancer. For example, our group developed a CAR to specifically target glucuronoxylomannan (GXM) in the capsule of Cryptococcus species, called GXMR-CAR or GXMR-IgG4-28ζ. Cryptococcus are fungi that cause the life-threatening disease cryptococcosis, and GXMR-IgG4-28ζ redirected T cells to target yeast and titan cell forms of Cryptococcus spp. Here, we replaced the IgG4-hinge and CD28-transmembrane domains from GXMR-CAR with a CD8α molecule as the hinge/transmembrane and used CD28 or 4-1BB molecules as co-stimulatory domains, creating GXMR-8-28ζ and GXMR-8-BBζ, respectively. Jurkat cells expressing GXMR-CAR containing CD8α as the hinge/transmembrane improved the CAR expression and induced a tonic signaling. GXMR-8-28ζ and GXMR-8-BBζ induced high levels of IL-2 and up-regulation of CD69 expression in the presence of reference strains of C. neoformans and C. gattii. Moreover, GXMR-8-28ζ and GXMR-8-BBζ showed increased strength in response to incubation with clinical isolates of Cryptococcuss spp., and 4-1BB co-stimulatory domain triggered a more pronounced cellular activation. Dasatinib, a tyrosine kinase inhibitor, attenuated the GXMR-CAR signaling cascade's engagement in the presence or absence of its ligand. This study optimized novel second-generation GXMR-CARs containing the CD8-hinge/transmembrane domain that improved CAR expression, antigen recognition, and signal strength in T-cell activation.
Assuntos
Cryptococcus , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos , Humanos , Antígenos CD28/metabolismo , Cryptococcus/imunologia , Cryptococcus/metabolismo , Imunoglobulina G , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/química , Receptores de Antígenos Quiméricos/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto , Polissacarídeos/química , Polissacarídeos/imunologia , Criptococose/imunologia , Criptococose/terapiaRESUMO
La criptococosis es una micosis grave que se manifiesta, en el 90% de los casos, como una meningoencefalitis, especialmente en las personas con VIH. El objetivo de este estudio es describir los casos de criptococosis extrameníngea en personas viviendo con VIH y conocer cuántas de estas padecen compromiso meníngeo concomitante. Además, determinar la relación con el título de antígeno polisacárido capsular de Cryptococcus en suero. Se realizó un estudio retrospectivo, observacional y analítico. Se incluyeron personas viviendo con VIH cuyo diagnóstico inicial de criptococosis se había realizado a partir de muestras extrameníngeas en el período comprendido entre 2012 y 2019. Los pacientes se dividieron en dos grupos. Grupo 1, pacientes sin compromiso meníngeo; Grupo 2, aquellos que finalmente tenían compromiso del SNC. De un total de 531 criptococosis registradas en ese período, se incluyeron 113 pacientes (21%), de los cuales en 58 se comprobó el compromiso meníngeo. No se observaron diferencias significativas en cuanto a la mortalidad entre ambos grupos.Ninguno de los pacientes con antigenemia por LFA (antígeno capsular en suero por inmunocromatografía) positiva, pero con antigenemia por aglutinación de partículas de látex (AL) negativa, tuvo compromiso meníngeo. Se observó que títulos de antígeno para Cryptococcus en suero por AL mayor o igual a 1/100 se correlacionaron con un aumento de 30 veces en la posibilidad de padecer meningitis. En todos los casos se debe descartar el compromiso del SNC. La AL sigue siendo una prueba útil y complementaria, debido a que en los casos con AL negativa no se observó compromiso meníngeo
Cryptococcosis is a serious mycosis that manifests itself, in 90% of cases, as meningoencephalitis, especially in AIDS patients. The objective of this study is to describe the extra-meningeal cases of cryptococcosis in people living with HIV and to know how many of them suffer from concomitant meningeal involvement. Also, to determine its relationship with the Cryptococcus capsular polysaccharide antigen titer in serum.A retrospective, observational and analytical study was carried out. HIV-positive patients whose initial diagnosis had been made from extrameningeal samples in the period between 2012 and 2019 were included. The patients were divided into 2 groups. Group 1: patients without meningeal involvement; group 2: those who finally had CNS involvement.Of a total of 531 cryptococcosis registered in this period, 113 patients (21%) were included, of whom meningeal involvement was confirmed in 58. No significant differences were observed in terms of mortality in both groups.None of the patients with positive LFA antigenemia (Capsular antigen detection by lateral Flow assay) but negative latex particle agglutination (LA) antigenemia had meningeal involvement. LFA was found to be highly sensitive and allows early diagnosis, but it does not replace other diagnostic procedures.Serum Cryptococcus antigen titers for by LA greater than or equal to 1/100 were found to correlate with a 30-fold increase in the likelihood of meningitis.In all cases, CNS involvement must be ruled out. LA continues to be a useful and complementary test, because in cases with negative LA, no meningeal involvement was observed
Assuntos
Humanos , Punção Espinal , Sintomas Concomitantes , Estudos Retrospectivos , Cromatografia de Afinidade/estatística & dados numéricos , HIV/imunologia , Criptococose/diagnóstico , Criptococose/terapia , Testes ImediatosRESUMO
Triatomines are blood-feeding arthropods belonging to the subfamily Triatominae (Hemiptera; Reduviidae), capable of producing immunomodulatory and water-soluble molecules in their hemolymph, such as antimicrobial peptides (AMPs). In this work, we evaluated the antifungal and immunomodulatory activity of the hemolymph of Meccus pallidipennis (MPH) and Rhodnius prolixus (RPH) against Cryptococcus neoformans. Methods: We assessed the activity of the hemolymph of both insects on fungal growth by a minimum inhibitory concentration (MIC) assay. Further, RAW 264.7 macrophages were cultivated with hemolymph and challenged with C. neoformans. Then, their phagocytic and killing activities were assessed. The cytokines MCP-1, IFN-γ, TNF-α, IL-10, IL-12, and IL-6 were measured in culture supernatants 4- and 48-hours post-infection. Results: Both hemolymph samples directly affected the growth rate of the fungus in a dose-dependent manner. Either MPH or RPH was capable of inhibiting fungal growth by at least 70%, using the lowest dilution (1:20). Treatment of RAW 264.7 macrophages with hemolymph of both insects was capable of increasing the production of MCP-I and TNF-α. In addition, when these cells were stimulated with hemolymph in the presence of C. neoformans, a 2- and a 4-fold increase in phagocytic rate was observed with MPH and RPH, respectively, when compared to untreated cells. For the macrophage killing activity, MPH decreased in approximately 30% the number of viable yeasts inside the cells compared to untreated control; however, treatment with RPH could not reduce the total number of viable yeasts. MPH was also capable of increasing MHC-II expression on macrophages. Regarding the cytokine production, MCP-I and TNF-α, were increased in the supernatant of macrophages treated with both hemolymphs, 4 and 48 hours after stimulation. Conclusion: These results suggested that hemolymph of triatomines may represent a source of molecules capable of presenting antifungal and immunomodulatory activity in macrophages during fungal infection.(AU)
Assuntos
Animais , Hemolinfa/química , Triatominae/microbiologia , Criptococose/terapia , Cryptococcus neoformans/imunologia , Antifúngicos/uso terapêutico , Imunomodulação/fisiologiaRESUMO
Background: Cryptococcosis is a serious fungal infection contracted by humans and animals, and the most common systemic mycosis found in cats. This disease is often contracted through inhalation of fungal propagules. The Central Nervous System (CNS) may be infected through local extension (nasal and frontal sinuses) or via hematogenous route. Similarly to CNS bacterial infection, the clinical signs of neurological dysfunction may be attributed to mass effect (gelatinous mass of fungal microorganisms and fungal granuloma formation) or to a more disseminated inflammatory response to invading microorganisms. The objective of this study is to report one case of a patient with cryptococcal granulomas in the central nervous system and one case of a patient with neurological signs associated to a cryptococcosis. Cases: Case 1. A 3-year-old male mixed breed feline was admitted to a veterinary clinic, located in Porto Alegre, RS, Southern Brazil. The patient presented unsourced behavioral changes, vestibular ataxia and dysphagia caused by inability of coordination. The following tests were performed: complete blood count test, biochemical analysis, computed tomography scan (CT scan), fluid analysis, radiography and toxoplasmosis test. The following medicine were administrated for treatment: fluconazole, dexamethasone, mannitol, phenobarbital and levetiracetam. Fluid therapy was also part of the treatment. Immediately after death, the cat was submitted for necropsy, and a fungal granulomatous meningoencephalomyelitis was diagnosed. Cryptococcus sp. was identified as the causal agent through pathological findings, fungal culture and PCR analysis. Case 2. One year later, another feline was admitted to the same clinic (a 2-year-old female mixed breed) presenting hypersalivation, tremors and excessive vocalization. The patient had contact with the deceased feline. The following tests were performed: complete blood count...(AU)
Assuntos
Animais , Gatos , Criptococose/terapia , Criptococose/veterinária , Cryptococcus/isolamento & purificação , Sistema Nervoso Central/microbiologia , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêuticoRESUMO
Background: Cryptococcosis is a serious fungal infection contracted by humans and animals, and the most common systemic mycosis found in cats. This disease is often contracted through inhalation of fungal propagules. The Central Nervous System (CNS) may be infected through local extension (nasal and frontal sinuses) or via hematogenous route. Similarly to CNS bacterial infection, the clinical signs of neurological dysfunction may be attributed to mass effect (gelatinous mass of fungal microorganisms and fungal granuloma formation) or to a more disseminated inflammatory response to invading microorganisms. The objective of this study is to report one case of a patient with cryptococcal granulomas in the central nervous system and one case of a patient with neurological signs associated to a cryptococcosis. Cases: Case 1. A 3-year-old male mixed breed feline was admitted to a veterinary clinic, located in Porto Alegre, RS, Southern Brazil. The patient presented unsourced behavioral changes, vestibular ataxia and dysphagia caused by inability of coordination. The following tests were performed: complete blood count test, biochemical analysis, computed tomography scan (CT scan), fluid analysis, radiography and toxoplasmosis test. The following medicine were administrated for treatment: fluconazole, dexamethasone, mannitol, phenobarbital and levetiracetam. Fluid therapy was also part of the treatment. Immediately after death, the cat was submitted for necropsy, and a fungal granulomatous meningoencephalomyelitis was diagnosed. Cryptococcus sp. was identified as the causal agent through pathological findings, fungal culture and PCR analysis. Case 2. One year later, another feline was admitted to the same clinic (a 2-year-old female mixed breed) presenting hypersalivation, tremors and excessive vocalization. The patient had contact with the deceased feline. The following tests were performed: complete blood count...
Assuntos
Animais , Gatos , Criptococose/terapia , Criptococose/veterinária , Cryptococcus/isolamento & purificação , Sistema Nervoso Central/microbiologia , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêuticoRESUMO
Osteomyelitis due to Cryptococcus neoformans are described in mostly 10% of patients with disseminated cryptococcosis, being direct inoculation even more uncommon. We report the case of an HIV-infected patient with history of recurring itching on his scalp and repetitive local trauma. For eighteen months, he noticed a painful and slow growing lump on his scalp. He was submitted to an excisional biopsy of the lesion but no etiological diagnosis was identified. After this procedure, the post-surgical wound never completely healed. At admission, the patient presented nausea and headache for three days and an open orifice into his skull. Investigations confirmed meningitis and skull osteomyelitis caused by Cryptococcus neoformans. He was treated with bone debridement and combined systemic antifungals, showing good clinical and laboratorial outcome. Cryptococcal disease should be included in the differential diagnoses of chronic osteomyelitis in HIV-infected patients and trauma is a possible source of infection.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Osteomielite/diagnóstico , Crânio/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/terapia , Doença Crônica , Criptococose/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/microbiologia , Osteomielite/terapia , Crânio/cirurgiaRESUMO
La criptococosis es la micosis sistémica más frecuente entre los pacientes con HIV SIDA. Su prevalencia oscila entre el 5% y el 25%, de acuerdo con la región geográfica que se considere. La localización habitual de esta micosis en el paciente VIH es el sistema nervioso central (SNC). La diseminación sanguínea del agente causal ocurre ante defectos de la inmunidad mediada por células, asociándose con frecuencia a linfomas, leucemia, enfermedades del sistema retículo endotelial. A partir de la eclosión del HIV se redujo un aumento significativo del número de casos, transformándose esta última condición en la causa favorecedora más importante.
Cryptococcosis is the most frequent systemic mycosis among patients with HIV AIDS. Its prevalence ranges between 5% and 25%, according to the geographical region considered. The usual location of this mycosis in the HIV patient is the central nervous system (CNS). Blood dissemination of the causative agent occurs due to defects of cell-mediated immunity, frequently associated with lymphomas, leukemia, reticuloendothelial system diseases. From the emergence of HIV, there was a significant increase in the number of cases, with the latter condition becoming the most important favorable cause
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Epidemiologia Descritiva , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Criptococose/imunologia , Criptococose/terapia , Infecções Fúngicas Invasivas/terapiaRESUMO
Cryptococcosis, an invasive fungal infection distributed worldwide that affects both domestic and wild animals, has incredible rates regarding treatment failure, leading to the necessity of the development of new therapies. In this way, we aimed to evaluate the probiotic (Saccharomyces boulardii, Lactobacillus paracasei ST-11, and Lactobacillus rhamnosus GG) and antimicrobial photodynamic alternative therapies against Cryptococcus gattii in a murine model. Although previous studies suggest that these therapies can be promising against cryptococcosis, our experimental conditions for both probiotic and antimicrobial photodynamic therapies (aPDT) were not able to improve the survival of mice with cryptococcosis, even with the treatment combined with fluconazole. Our results may help other researchers to find the best protocol to test alternative therapies against Cryptococcus gattii.
Assuntos
Anti-Infecciosos/farmacologia , Criptococose/terapia , Cryptococcus gattii/efeitos dos fármacos , Probióticos/farmacologia , Animais , Terapias Complementares , Criptococose/microbiologia , Fluconazol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , FotoquimioterapiaRESUMO
A criptococose é uma infecção fúngica bastante encontrada em gatos, trata-se de uma infecção geralmente grave, que também pode acometer cães, humanos e outros mamíferos. A principal forma de contaminação ocorre por inalação das leveduras, acometendo principalmente indivíduos imunodeficientes, como animais muito jovens ou idosos, que foram submetidos a estresse ou tratamento com imunossupressores. A enfermidade pode se apresentar na forma respiratória, nervosa e cutânea, sendo essa última a mais comum. Tem caráter zoonótico e seu agente etiológico, o Cryptococcus neoformans, pode ser encontrado em excretas de aves, principalmente de pombos, o que torna esses animais importantes reservatórios da doença. O tratamento é realizado com triazois como o fluconazol. Objetivou-se relatar um caso de criptococose cutânea em gato, com sucesso terapêutico através do uso do fluconazol, bem como descrever os sinais clínicos apresentados pelo paciente. Iniciou-se a suspeita clinica após exame físico e ao conhecer o histórico do animal que apresentava sinais compatíveis com a patologia, para confirmação foi realizada a técnica de citologia aspirativa por agulha fina e biopsia incisional, diagnosticando a criptococose. Foi instituído o uso do fluconazol e nos primeiros meses já foi constatada a regressão dos sinais clínicos. Conclui-se então a eficácia do fluconazol em animais com criptococose, bem como atenta para os perigos da enfermidade, visto que se trata de uma zoonose.
Cryptococcosis is a very common fungal infection in cats. It is a generally serious infection that can also affect dogs, humans and other mammals. The main form of contamination occurs by inhalation of yeasts, mainly affecting immunodeficient individuals, such as very young or old animals, who have been subjected to stress or treatment with immunosuppressants. The disease can present in the respiratory, nervous and cutaneous form, being the latter the most common. It has a zoonotic character and its etiologic agent, Cryptococcus neoformans, can be found in bird excreta, mainly of pigeons, which makes these animals important reservoirs of the disease. Treatment is performed with triazoles such as fluconazole. The objective of this study was to report a case of cutaneous cryptococcosis in cats with therapeutic success through the use of fluconazole, as well as to describe the clinical signs presented by the patient. Clinical suspicion was initiated after physical examination and the history of the animal showing signs compatible with the pathology was confirmed. A fine needle aspiration cytology and incisional biopsy technique was used to diagnose cryptococcosis. The use of fluconazole was instituted and in the first months the regression of the clinical signs was already verified. The efficacy of fluconazole in animals with cryptococcosis, as well as the risks of the disease, is concluded, since it is a zoonosis.
Criptococosis es una infección por hongos en los gatos bastante encontrado, generalmente es una infección grave, que también puede infectar a los perros, los humanos y otros mamíferos. La forma principal de contaminación se produce por la inhalación de levadura, que afecta principalmente a individuos inmunodeprimidos, como los animales muy jóvenes o viejos, que se sometieron a estrés o el tratamiento con inmunosupresores. La enfermedad puede presentar en forma respiratorio, nervioso y cutánea, siendo esta última la más común. Zoonótica y su agente etiológico, Cryptococcus neoformans, se pueden encontrar en las heces de las aves, especialmente las palomas, lo que hace que estos animales importantes reservorios de la enfermedad. El tratamiento se lleva a cabo con triazol, tales como fluconazol. Este estudio tuvo como objetivo presentar un caso de criptococosis cutánea en gato con éxito terapéutico a través del uso de fluconazol, así como describir los signos clínicos que presenta el paciente. Comenzó la sospecha clínica después de un examen físico y conociendo la historia del animal mostró signos compatibles con la patología para la confirmación se llevó a cabo la técnica de biopsia por aspiración con aguja fina y la biopsia por incisión, el diagnóstico de criptococosis. Se ha instituido el uso de fluconazol y los primeros meses se ha observado regresión de los signos clínicos. En conclusión, entonces la eficacia de fluconazol en criptococosis animal y atento a los peligros de la enfermedad, ya que es una zoonosis.
Assuntos
Animais , Gatos , Criptococose/terapia , Criptococose/veterinária , Cryptococcus neoformans , Dermatomicoses/terapia , Fluconazol/uso terapêutico , Dermatopatias/terapia , Dermatopatias/veterináriaRESUMO
La criptococosis es una de las infecciones oportunistas más frecuentes en pacientes con infección por HIV. La toxicidad de la anfotericina B y el aislamiento de un número creciente de cepas re-sistentes a fluconazol determinan la necesidad de tratamientos alter-nativos y estrategias novedosas. Este artículo presenta un pacien-te HIV positivo con criptococosis meníngea sin negativización de los aislamientos de Cryptococcus neoformans con el tratamiento con-vencional de inducción con anfotericina B más fluconazol, y respues-ta favorable al sustituir éste último antifúngico por voriconazol
Cryptococcosis is one of the most common opportunistic infections in patients with HIV infection. The toxicity of amphotericin B and isolation of an increasing number of strains resistant to fluconazole dictate the need for alternative treatments and novel strategies. This paper presents an HIV positive patient with cryptococcal meningitis without negativisation Cryptococcus neoformans isolates with conventional induction therapy with amphotericin B plus fluconazole, and favorable to the latter replaced by voriconazole antifungal response
Assuntos
Humanos , Masculino , Adulto , Infecções por HIV/terapia , Meningite Criptocócica/terapia , Criptococose/terapia , Voriconazol/uso terapêuticoRESUMO
Paciente feminina, 47 anos, hipertensa e tabagista, em uso crônico de corticoide, apresentou lesões em pele e mucosa nasal, com dor local; tratado empiricamente como sinusite. Houve piora das lesões, com ulceração. Após nove meses do início dos sintomas, foi realizada biópsia da lesão, revelando o anatomopatológico uma micose cutânea sugestiva de criptococose. A paciente foi diagnosticada com infecção pelo vírus da imunodeficiência humana (HIV) e, então, internada em hospital de referência, tendo recebido tratamento com fluconazol 800mg/dia endovenoso, a seguir, fluconazol 800mg/dia oral até completar 12 semanas de tratamento. Houve resolução da lesão ulcerada e posterior fibrose da narina esquerda
A 47-year-old woman, carrier systemic hypertension, tobacco user, and chronic user of corticosteroids, showed skin and nasal mucosa lesions, with local pain; treated empirically as sinusitis. The lesions evolved with increased ulceration. After nine months of symptoms onset, the lesion was biopsied, revealing fungal skin pathology suggestive of cryptococcosis. The patient was diagnosed with an HIV infection. The patient was then hospitalized in a specialized hospital and treated with intravenous fluconazole 800mg/day, followed by fluconazole 800mg daily orally up to 12 weeks of treatment. There was resolution of the ulcerated lesion and subsequent fibrosis of the left nostril
Assuntos
Feminino , Humanos , Adulto , Criptococose , Criptococose/diagnóstico , Criptococose/terapia , Infecções por HIV , Síndrome da Imunodeficiência Adquirida , Fluconazol , Relatos de CasosRESUMO
OBJECTIVE: To investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients. METHOD: 24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied. RESULTS: 15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2 ± 11.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients. CONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Pneumopatias Fúngicas/diagnóstico , Antifúngicos/uso terapêutico , Terapia Combinada , Criptococose/terapia , Fluconazol/uso terapêutico , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/terapia , Prognóstico , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Toracotomia , Tomografia Computadorizada por Raios X , Triazóis/uso terapêuticoRESUMO
OBJECTIVE: To investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients. METHOD: 24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied. RESULTS: 15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2±11.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients. CONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.
Assuntos
Criptococose/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Pneumopatias Fúngicas/diagnóstico , Adulto , Idoso , Antifúngicos/uso terapêutico , Terapia Combinada , Criptococose/terapia , Feminino , Fluconazol/uso terapêutico , Humanos , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Toracotomia , Tomografia Computadorizada por Raios X , Triazóis/uso terapêutico , Voriconazol , Adulto JovemRESUMO
Compared to the incidence in adults, cryptococcosis is rare among children. We report a case of neurocryptococcosis due to Cryptococcus gattii in a five-year-old girl without identified risk factors living in French Guiana. Neurological surgery in combination with long-term antifungal treatment with amphotericin B and 5-flucytosine successfully resolved the cryptococcal infection. Subsequent molecular characterization of the Cryptococcus isolate revealed that the infection was caused by a C. gattii genotype AFLP6B/VGIIb strain.
Assuntos
Infecções Fúngicas do Sistema Nervoso Central/terapia , Criptococose/terapia , Cryptococcus gattii , Pré-Escolar , Feminino , Guiana Francesa , Humanos , Indução de RemissãoRESUMO
Introducción: La criptococosis es una infección micótica oportunista sistémica grave de distribución universal que ha aumentado su incidencia con la aparición de la infección por el Virus de la Inmunodeficiencia Humana (VIH). Objetivos: Determinar la prevalencia, y las características clínicas, de laboratorio y de tratamiento de la criptococosis cutánea en pacientes infectados por el VIH. Diseño: Descriptivo, retrospectivo, y observacional. Lugar: En el Hospital Nacional Dos de Mayo. Participantes: Pacientes con el diagnóstico de criptococosis cutánea infectados por VIH (8 casos). Intervenciones: Identificación y revisión de historias clínicas entre enero del 2000 y diciembre del 2010 (11 años). Se realizó análisis estadístico univariado y bivariado, con un intervalo de confianza del 95 por ciento. Resultados: La prevalencia fue del 0,43 por ciento. La media de la edad de los casos fue de 36,4 años, predominando el sexo masculino con 87,5 por ciento. Las lesiones cutáneas primarias y secundarias más frecuentes fueron: pápula y/o nódulo 85,5 por ciento, umbilical y/o costroso 85,7 por ciento; asociándose a prurito 60 por ciento de casos, con ubicación frecuente en cara y miembros superiores en 100 por ciento y 62,5 por ciento respectivamente. La media de recuento de CD4 en sangre fue de 41,3 células/mm3, con 57,1 por ciento entre 0 y 50. Los casos fueron tratados con Anfoterecina B y Fluconazol 62,5 por ciento de casos, con media de la dosis total de la primera B en 507,2 mg, y de la segunda en 400 mg/24h. Los casos tuvieron evolución clínica favorable, con remisión parcial al primer mes de tratamiento. Conclusiones: Las lesiones cutáneas más frecuentes fueron pápula, umbilicada, y costrosa. Un mes de tratamiento no fue suficiente para la remisión completa de las lesiones cutáneas
Introduction: Cryptococcosis is a mycotic opportunistic systemic serious infection of universal distribution that has raised her incidence with the appearing of the infection for the Human Immunodeficiency Virus (HIV). Objectives: Determining prevalence, and the clinical, laboratory and treatment characteristics of the cutaneous cryptococcosis in patients infected by the HIV. Design: Descriptive, retrospective, and observational. Place: In the Hospital Nacional Dos de Mayo. Participants: Patients with the diagnostic of cutaneous cryptococcosis infected with HIV (8 cases). Interventions: Recognition and revision of case history between January of the 2000 and December of 2010 (11 years). Uni-varied and bi-varied statistical analysis was tested, with 95 per cent confidence intervals. Results: Prevalence was of the 0.43 per cent. The mean age of the cases was of 36,4 years, predominating the masculine sex with 87.5 per cent. The primary and secondary cutaneous lesions more frequent were: Papule and/or nodule 85.5 per cent, and umbilical and/or crusty 85.7 per cent; joining pruritus 60 per cent of cases, with frequent position in face and upper extremities in 100 per cent and 62.5 per cent respectively. The mean of score of CD4 in blood was of 41.3 cell/mm3, with 57.1 per cent between 0 and 50. The cases were treated with Anfoterecine B and Fluconazol 62.5 per cent, with mean of the total of Anfoterecine B of 507.2 mg. Fluconazol's mean dose was of 400 mg/24h. All the cases had clinical favorable evolution, with partial remission to the first month of treatment. Conclusions: The cutaneous lesions more frequent were papule, umbilicate, and crusty. A month of treatment did not suffice to the complete response of the cutaneous injuries
Assuntos
Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Criptococose/epidemiologia , Criptococose/terapia , Infecções Oportunistas , Infecções por HIV/complicações , Manifestações Cutâneas , Síndrome da Imunodeficiência Adquirida , Estudos Observacionais como Assunto , Estudos RetrospectivosAssuntos
Humanos , Masculino , Idoso , Criptococose/diagnóstico , Criptococose/terapia , Soronegatividade para HIVRESUMO
Cryptococcosis is a systemic-opportunistic mycosis caused by two species of the encapsulated yeast-like organism, Cryptococcus neoformans and C. gattii, which cause infection in immunocompromised individuals and in immunologically normal hosts, respectively. Most susceptible to infection are patients with T-cell deficiencies. The spectrum of disease ranges from asymptomatic pulmonary lesions to disseminated infection with meningoencephalitis. After the emergence of AIDS, cryptococcal infections have become much more common. The mycosis occurs less frequently in children than in adults. The purpose of this article is to discuss the aetiology, clinical presentation, predisposing conditions and outcomes in cases of cryptococcosis in children. Emphasis is placed upon paediatric cases occuring in Brazil and in particular to highlight the difference between cases diagnosed in Porto Alegre (South - subtropical climate) and in Belem (North - equatorial climate).
Assuntos
Criptococose , Hospedeiro Imunocomprometido , Brasil/epidemiologia , Criança , Criptococose/diagnóstico , Criptococose/epidemiologia , Criptococose/imunologia , Criptococose/terapia , HumanosRESUMO
Objetivo: relatar um caso de criptococose articular no joelho esquerdo de um paciente residente no município de Benevides, Pará, 2007. Relato do caso: sexo masculino, 37 anos, desenvolveu artrite criptocócica na articulação do joelho, pelo agente etiológico Cryptococcus neoformans. Foi, inicialmente, atendido na Policlínica, em Santa Isabel, apresentando dor articular no joelho esquerdo, náuseas e cefaléia, como principais sintomas. Ao examefisico, verificou-se edema, calor, tumor,flutuação, choque patelar +++ do joelho esquerdo, tinnel-, adenopatia inguinal homolateral, além de palidez e desidratação de primeiro grau. O paciente submetido à punção do joelho e do LCR, na qualfoi diagnosticado o Cryptococcus neoformans. A terapêutica adotada foi a drenagem do joelho esquerdo. Feito isso, o paciente foi conduzido ao serviço público de saúde de referência, para dar continuidade ao tratamento específico. Considerações finais: o acometimento articular pela criptococose é raro. A descrição do caso é alertar uma maior atuação da vigilância sanitária frente à manipulação e manejo das aves nas granjas do estado.
Objective: report a case of articulate cryptococcosis of a lender in the city of Benevides, Pará, 2007. Case report: man, 37 years, developed artrite criptococose in the joint of the knee, by agent Cryptococcus neoformans. Initially he was taken care in clinical Policlinica, Santa Isabel presenting pain articulate in the left knee, nauseas, and chronic headache as main symptoms. To the physical examination edema, heat, tumor, fluctuation, patellar shock + + + of the left knee, tinnel -, homolateral inguinal adenopathy, beyond pallor and dehydration offirst degree were diagnosised. The patient was submitted to a punction of the knee and the lombar, in which Cryptococcus neoformans was diagnosised. The therapeutical adopted was the draining of the left knee. Made this, the patient was lead to the reference publicservice, to give continuity to the specific treatment. Final considerations: the articulate damage for cryptococcosis is rare. The description of the case is to alert to a bigger performance of the sanitary monitoring front the manipulation and handling of the birds in the chickens companies of the state.