Recurrent trichosporonosis with central nervous system involvement in an allogeneic hematopoietic stem cell transplant recipient.

Trichosporon is an ubiquitous yeast that has emerged as an opportunistic pathogen in the immunocompromised host. We describe a case of invasive trichosporonosis in an allogeneic hematopoietic stem cell transplant (allo-HSCT) recipient while on caspofungin antifungal prophylaxis. She developed disseminated trichosporonosis in the pre-engraftment period and was successfully treated with voriconazole. She later developed 2 further episodes of invasive trichosporonosis involving the central nervous system. This case highlights the challenges of managing trichosporonosis in allo-HSCT recipients and suggests the need for lifelong therapy in some patients.

[Meningitis due to Listeria monocytogenes in adults]. / Meningitis por Listeria monocytogenes en adultos.

INTRODUCTION: Listeria monocytogenes is the third most common cause of community-acquired bacterial meningitis in adults. AIMS: To describe the characteristics of meningitis caused by Listeria (LM) in adults and to compare them with those of meningitis due to other causations (nLM). PATIENTS AND METHODS: A retrospective analysis of a series of hospital cases was conducted, including patients aged between ≥ 14 years diagnosed with LM in a referral hospital between 1982 and 2011. RESULTS: The study involves 16 cases of LM, 12.1% of the cases of community-acquired meningitis with an identified aetiology. Predisposing factors were age (mean of 65 versus 52 years; p = 0.019) and immunosuppression/comorbidity (62.5% versus 3.4%; p < 0.001), treatment with corticoids (37.5%) and chronic liver disease (25%) being the most frequent. The classical triads of acute bacterial meningitis, clinical features and analysis of the cerebrospinal fluid (CSF) were observed in 50 and 75% of the cases, respectively. Patients with LM presented lower leukocyte counts in CSF, a lower percentage of neutrophils, a greater frequency of lymphocytic pleocytosis and a lower frequency of Gram stain positive than those with nLM. The mortality rate was 12.5%, similar to that of patients with nLM. CONCLUSIONS: LM mainly affects patients who are immunosuppressed or with comorbidity, as well as elderly patients, although it may occur in the absence of risk factors. Clinically it does not differ from other causes of meningitis, but the initial CSF study may suggest it. Its mortality rate is similar to that of meningitis due to other aetiologies.

Two rare cases of central nervous system opportunistic mycoses.

This article presents two cases of opportunistic mycoses (OMs) of the central nervous system (CNS) caused by Cryptococcus neoformans and Aspergillus nidulans, respectively. The patients were hospitalised in local hospitals between 2009 and 2011 because of unspecific symptoms (fever, headache, and/or weight lost). Duration of symptoms varied from 4 days to over 2 weeks. The patients were treated with antibiotics and symptomatically. OM was not suspected in any of them. The patients became critically ill with symptoms of CNS involvement and were transferred to the Intensive Care Unit (ICU) of the University Hospital for Infectious diseases (UHID) in Zagreb. None of the patients belonged to the high-risk population for developing OMs. They were not HIV-infected, had no transplantation of bone marrow or solid organ, and were not on severe immunosuppressive chemotherapy. Fungi were isolated from cerebrospinal fluid (CSF) samples and, in one patient, from aspirate of cerebral abscess. Isolation and mycological identification of all fungal isolates and in vitro antifungal susceptibility testing of these isolates were done at the Reference Centre for Mycological Diagnostics of Systemic and Disseminated Infections (RCMDSDI) in Zagreb. The patient with cryptococcal meningitis was treated with amphotericin B and fluconazole and the patient with cerebral aspergilloma with voriconazole.

Cryptococcal meningitis in patients with glioma: a report of two cases.

OBJECTIVE AND IMPORTANCE: We describe two patients with high-grade glioma undergoing treatment with corticosteroids and chemotherapy who presented with cryptococcal meningitis and sepsis. This report of two cases highlights the importance of examining the efficacy of prophylactic antibiotic and/or antifungal regimens in this patient population due to their increased risk of opportunistic infections. CLINICAL PRESENTATION: A 73-year-old man with a history of glioblastoma multiforme (GBM), on dexamethasone and status post radiation therapy and two cycles of temozolamide, presented with decreased level of consciousness for 24 h and was found to have cerebrospinal fluid (CSF) and blood cultures positive for Cryptococcus neoformans. A 33-year-old man with a history of anaplastic astrocytoma, on dexamethasone and status post radiation therapy, four cycles of temozolomide and two cycles of Lomustine (CCNU), presented with headache, dizziness and photophobia and was found to have CSF and blood cultures positive for Cryptococcus neoformans. INTERVENTION: Both patients were treated with an initial regimen of amphotericin B and flucytosine for a minimum of two weeks and switched to fluconazole for 6 months to 1 year of treatment. CONCLUSION: Patients with high-grade glioma treated with long-term corticosteroid therapy and chemotherapy are at increased risk of developing opportunistic infections. The two patients reported here developed cryptococcal meningitis and sepsis. Prophylactic regimens with either fluconazole or itraconazole currently exist that effectively decrease the incidence of both cryptococcal infections. Further investigations into the risk:benefit ratio of primary prophylactic therapy in this patient population may prove beneficial.

[Cryptococcosis in renal transplant recipients]. / Criptococosis en pacientes con trasplante renal.

This article presented the case of a 64 years-old renal transplant recipient, who was a poultry farm worker and had suffered meningoencephalitis six months after receiving immunosuppressive therapy. Rapid diagnosis was based on a cerebrospinal fluid sample analyzed with latex particles for Cryptococcus spp antigen detection. Culture of the clinical sample in agar-Sabouraund-chloramphenicol medium confirmed the initial diagnosis whereas biochemical identification was made with the API 20C AUX system. Amphotericin B treatment was immediately applied to the patient and later fluconazole until microbiological tests yielded negative results. After 5 months, the patient relapsed and restarted the specific treatment. He was followed up on outpatient service and two year after the organ transplantation, his recovery was favourable.

Contrast enhancement of cerebrospinal fluid on delayed MRI in a patient with an epidural abscess and renal failure.

Cerebrospinal fluid (CSF) is normally of low signal intensity on T1 weighted MRI. The case of a patient with renal failure who developed an epidural abscess, and in whom the CSF appeared of high signal intensity on delayed T1 weighted MRI is presented. Possible mechanisms for this are discussed.

Tuberculous meningitis in a renal transplant recipient.

Tuberculous meningitis is a very rare, but serious extrapulmonary complication of mycobacterial infections in immunocompromised patients, such as organ transplant recipients. We describe here a 66-year-old Turkish woman without any history of tuberculosis, who received a renal allograft transplant in 1994. After a pilgrimage to an endemic area for tuberculosis, she presented with fever and headache in August 1998. Clinical examination revealed positive meningism and hyperreflexia. Lymphocytosis was noted in her cerebrospinal fluid (CSF) and Mycobacterium tuberculosis infection was detected by PCR within the CSF. Despite immediate triple antituberculosis therapy, the patient's clinical condition deteriorated rapidly, with the development of septic shock syndrome, and she died three weeks after admission due to cardiovascular and respiratory failure. Mycobacterial infections, including extrapulmonary manifestations, should thus be considered in all renal transplant recipients presenting with unexplained fever. Preventive therapy, i.e. isoniazid prophylaxis, may also be recommended for patients risking exposure in areas endemic for tuberculosis.

Cytologic detection of Toxoplasma gondii tachyzoites in cerebrospinal fluid.

We reviewed our case records to see how often Toxoplasma gondii organisms were identified by cytologic evaluation of cerebrospinal fluid (CSF). During a 12-year period, 6,090 CSF specimens were examined, and 2 cases (0.03%) showed tachyzoites. Both patients were immunocompromised. One patient underwent lumbar and ventricular taps, and the other underwent only ventricular tap. Organisms were identified in the ventricular specimens but not in the lumbar sample. Both patients were treated, and subsequent ventricular CSF samples were negative. Toxoplasma gondii can be identified by cytologic examination of CSF. Our results confirm prior observations that in patients with obstructive hydrocephalus, tachyzoites are more likely to be found in ventricular rather than lumbar specimens.

Cryptococcosis in Hodgkin's disease: description of two cases and review of the literature.

Systemic mycosis caused by Cryptococcus neoformans frequently becomes life threatening in patients with cellular immunodeficiencies. In contrast to AIDS patients, there are only a few reports of concurrent systemic cryptococcosis in patients with Hodgkin's disease (HD). Only two of 75 (2.7%) patients with HD who were consecutively admitted to our hospital in the past decade developed Cryptococcus neoformans infection. Both had stage IVB (Ann Arbor) HD with bone marrow involvement and absolute lymphopenia (< 1/nl). We have reviewed the literature and analyzed the data of 54 cases with concurrent cryptococcosis and HD. Presence of HD for > or = 12 months, stage IV disease, absolute lymphopenia (< 1/nl), and extensive pretreatment were the most common features among these patients and must be regarded as predisposing for acquiring a cryptococcal infection. In our patients antimycotic therapy was successful using liposomal amphotericin B (lipAmB) simultaneously with cytotoxic therapy for HD. Drug level measurements performed in one patient revealed a higher level of amphotericin B in CSF when the liposomal formulation was administered as compared with the level in CSF after administration of conventional amphotericin B. To our knowledge, this is the first report on antimycotic treatment of cryptococcosis with lipAmB in patients with HD. Regarding the favorable therapeutic index of lipAmB as compared with conventional amphotericin B, the drug should be considered as a less toxic and perhaps more effective alternative in the therapy of acute cryptococcosis, especially when cytotoxic treatment is administered simultaneously.

[Cerebrospinal fluid in 50 AIDS patients]. / Líquido cefalorraqueano em 50 pacientes com AIDS.

Fifty AIDS patients were studied. All patients had anti-HIV antibodies (ELISA) present and met OPAS/Caracas punctuation criteria for AIDS cases in adults. Cerebrospinal fluid (CSF) analysis included pressure, cytology (number of cytomorphological aspects), total protein and electrophoresis, glucose and chloride concentration. Bacteriological and mycological investigations were performed as well as agglutination tests for Cryptococcus. Complement fixation, indirect immunoflorescence, passive hemagglutination and/or ELISA tests were performed for syphilis, toxoplasmosis, viral and fungal infections. All CSF analysis were made in the same laboratory following the same methodology. CSF was altered in 45 cases (90.0%) of the 50 patients studied. The most important alterations observed were: gammaglobulin (55.5%) and total protein (51.1%) increase, hypercytosis (48.9%) and decrease of chloride concentration (40.0%). HIV antibodies were detected in 42 patients (93.3%). Toxomoplamosis, isolated or associated to other agents, was the most frequent opportunistic infection (57.7%). Cerebrospinal fluid should always be examined in AIDS patients with or without neurological symptoms.

Líquido cefalorraqueano em 50 pacientes com AIDS / Cerebrospinal fluid in 50 AIDS patients

Foram estudados 50 pacientes com AIDS, todos estes pacientes apresentavam anticorpos ant-HIV1 (ELISA) e preenchiam os critérios de pontuaçao OPAS/Caracas de definiçao de casos de AIDS em adultos. A análise do liquido cefalorraqueano (LCR) incluiu: pressao; citologia (número de células e aspectos citomorfológicos); proteína total e eletroforese; concentraçoes de glicose, cloretos e testes imunológicos para sífilis, toxoplasmose e infecçoes virais (citomegalovírus, varicela-zoster, Herpes simplex, e HIV1). Investigaçoes bacteriológicas e micológicas (pesquisa direta e cultura), além de teste de aglutinaçao (látex) paracryptococcus foram também realizados. Os testes imunológicos usados foram fixaçao do complemento, imunofluorescência indireta, hemaglutinaçao passiva e/ou ELISA. Todos os LCR foram analisados no mesmo laboratório seguindo sempre a mesma metodologia. O LCR esteve alterado em 45 pacientes (90,0 por cento) dos 50 pacientes estudados. As principais alteraçoes encontradas no LCR foram: aumento de gamaglobulina em 25 casos (55,5 por cento); aumento da proteína total em 23 (51,1 por cento); hipercitose em 22 (48,9 por cento) e diminuiçao dos cloretos em 18(40,0 por cento). A detecçao de anticorpos anti- HIV1 estiveram presentes em 42 pacientes (93,3 por cento). Toxoplasmose isolada ou associada a outros agentes foi a infecçao oportunista mais frequente, detectada em 26 casos (57,7 por cento). O LCR deverá ser sempre analisado em todos os pacientes com AIDS, com ou sem sintomas neurológicos.

Tumour necrosis factor (TNF-alpha) and neurological disorders in HIV infection.

Tumour necrosis factor (TNF-alpha) concentrations were determined in the CSF from 42 HIV-infected patients, with or without CNS involvement. In addition, 14 subjects with various neurological disorders but without HIV antibodies were included as controls. Raised CSF concentrations of TNF-alpha (greater than 40 ng/l) were detected both in patients with AIDS dementia complex (ADC) (6/9) and with CNS opportunistic infections (10/19) and, less commonly, in HIV infected subjects without CNS diseases (2/14) and in anti-HIV negative controls (1/14). The highest CSF concentrations of TNF-alpha (greater than 100 ng/l), however, were found in seven out of eight patients with cryptococcal meningitis. Although a role for TNF-alpha in demyelinating lesions associated with ADC has been suggested, our results indicate that a clear elevation of TNF-alpha in the CSF from HIV positive patients mostly occurs in acute inflammatory disorders, such as cryptococcal meningitis.

[Cryptococcosis: presentation of 26 cases]. / Criptococosis: presentación de 26 casos.

BACKGROUND: Cryptococcosis is more frequently observed since the appearance of the acquired immunodeficiency syndrome (AIDS). AIDS has modified the clinical and evolutive forms of the disease. This study reviews the changes produced in the infection from the context of AIDS. METHODS: The present is a retrospective study (1985-1990) including patients presenting: 1) a positive latex agglutination test (serum or spinal fluid) or 2) a Sabouraud culture positive for cryptococcus. Clinical histories were revised collecting clinical, radiologic, analytic, therapeutic and evolutive data. RESULTS: Twenty-six patients (21 males) were included in the study. Twenty patients had the human immunodeficiency virus. The clinical picture was: 22 cases with cryptococcal meningitis (13 with hematogenous participation), 3 with pulmonary cryptococcosis and one with disseminated cryptococcosis without meningeal involvement. The patients with AIDS had: greater frequency of positive hemocultures, higher serologic titers and fewer with the meningeal syndrome. The number of T4 lymphocytes was lower than 150 elements/ml in AIDS patients. In 17 patients treatment with amphotericin B and 5-fluorocytosine was administered, 5 received amphotericin B and two fluconazole and two did not receive the above since they had not been diagnosed alive. There were 6 deaths and 10 relapses in 6 AIDS patients and none in the remaining patients. CONCLUSIONS: The incidence of cryptococcosis has increased as a consequence of AIDS. In these patients the disease occurs in advanced stages of immunodeficiency and frequently in disseminated, severe and paucisymptomatic forms. Treatment is usually effective although a maintenance therapy is required to avoid relapse.

AIDS: a CSF laboratory experience on 470 cases in a 7 year time period

Durante o período de 7 anos (Julho 1984 a Junho 1991) foram estudados em laboratório de LCR 36.216 novos pacientes, 470 com AIDS. O número de pacientes com AIDS representa 1,30% de todos os casos novos no período; para os primeiros 6 meses de 1991 esse número atingiu 2,8%. LCR normal foi observado apenas em 16 casos (3,4%). Patologias associadas foram observadas em 66% dos casos. Infecçöes oportunistas predominaram entre elas (227 casos). Esses dados justificam indicar o exame de LCR em pacientes infectados pelo HIV, devendo o exame ser o mais completo possível

[Cryptococcal meningitis and AIDS. Clinical description of 10 patients]. / Meningitis criptocócica y SIDA. Descripción clínica de 10 pacientes.

We have studied 10 patients with cryptococcal meningitis and AIDS. Nine of them were intravenous drug users and four have been previously diagnosed of AIDS. In 60% of them cryptococcal meningitis was the first opportunistic infection, and as group represented only 6.3% of our 158 patients with AIDS on the same period. The most common symptoms were: malaise (100%), headache (80%), fever (60%), meningeal signs (50%). Two of them had focal neurological disease. CSF culture and serum cryptococcal antigen test were positive in 90%, the Indian ink in 77% and blood cultures in 30% of the cases, while indian ink preparation did it in 77%. MRI showed bilateral small lesions, deeply located, in 3 cases; it was also useful to prove optical tract lesions in a patient with blindness as a result of cryptococcal meningitis. We had treatment successes in 80% of the cases, all patients being treated with amphotericin B, alone in 4 and amphotericin B plus fluorocytosine in 6. Two patients died within the first 2 weeks. Maintenance therapy with fluconazole was effective and well tolerated, with 3 patients dying from causes other than cryptococcal meningitis. We recorded a survival rate over 12 months in 33% of patients.

Review of the central nervous system cytopathology in human immunodeficiency virus infection.

The human immunodeficiency virus (HIV) is a neurotropic retrovirus capable of producing a wide spectrum of central nervous system changes. Nearly 40% of HIV-infected patients demonstrate neuropathy ranging from dementia to the opportunistic infections and neoplasia seen in the acquired immunodeficiency syndrome (AIDS). Dramatic increases in the numbers of AIDS cases have allowed for the cytotechnologist and cytopathologist to become acquainted with the various pathologic manifestations of HIV infection. In this review, we are reporting the HIV-related diseases in the central nervous system and the role of diagnostic cytology.

Calprotectin in cerebrospinal fluid of the HIV infected: a diagnostic marker of opportunistic central nervous system infection?

The calprotectin level in the cerebrospinal fluid (CSF) of 15 HIV positive patients with symptoms from the central nervous system (CNS) was measured. All 5 patients with opportunistic infections had levels above the reference range and all 10 patients with HIV associated encephalopathy had levels within the reference range. Thus, the calprotectin level in CSF can be of diagnostic value in differentiating between HIV associated encephalopathy and opportunistic infection in the HIV positive patient with symptoms from the CNS.

Correlation of early MRI with CT scan, EEG, and CSF: analyses in a case of biopsy-proven herpes simplex encephalitis.

Herpes simplex encephalitis (HSE) carries a high mortality rate. Therefore, an early diagnosis and institution of acyclovir are essential. We report a case of biopsy-proven HSE with 2 negative cerebrospinal fluid (CSF) analyses and 2 normal CT scans. However, MRI together with EEG were abnormal early in the disease stressing their significant role in any suspected case of HSE. Although brain biopsy remains controversial, CSF herpes simplex antigen detection offers hope in providing an early or retrospective diagnosis while specific antiviral therapy with acyclovir is initiated. Overdependency on routine CSF analysis or head CT scan can result in unnecessary delays in diagnosis and treatment.