Treatment of severe forms of paracoccidioidomycosis: is there a role for corticosteroids?

Despite their immunosuppressive effects, corticosteroids have long been used as adjunct therapy (aCST) in the treatment of infectious diseases. The rationale is that in certain infections it is necessary to decrease the exacerbated host's inflammatory response, which can otherwise result in tissue damage and organ dysfunction. In fact, a major concern in treating paracoccidioidomycosis (PCM) is the host's intense inflammatory response to Paracoccidioides brasiliensis, which can be further intensified by antifungal therapy. Depending on its localization, this immunological phenomenon may be life threatening or result in permanent sequels, as is the case for some patients with cerebral or laryngeal involvement. However, the literature on aCST in paracoccidioidomycosis treatment is scarce and as a result we present our recent experience in the management of four patients with severe PCM manifestations, i.e., cerebral paracoccidioidal granuloma, laryngeal stenosis, compressive abdominal mass, and exacerbated inflammatory response with tissue destruction. In addition to the antifungal therapy, these patients required aCST, which probably promoted their clinical improvement and/or prevented serious complications. We suggest that aCST: (a) can potentially help in the management of selected cases of severe forms of PCM, particularly when there is a risk of acute complications, and (b) that it can be used safely provided that the risk-benefit ratio is carefully weighed. Well-controlled, prospective studies of aCST in the treatment of severe cases of paracoccidioidomycosis are needed to better define its role in the management of PCM.

Application of synthetic 8-kD and recombinant GP50 antigens in the diagnosis of neurocysticercosis by enzyme-linked immunosorbent assay.

The gold standard serodiagnostic assay for cysticercosis and neurocysticercosis, diseases caused by the metacestode of Taenia solium, uses lentil lectin-purified glycoprotein (LLGP) in a Western blot assay. We tested two antigens derived from LLGP, synthetic TS18var1 (sTS18var1) and recombinant GP50 antigen (rGP50), in an enzyme-linked immunosorbent assay (ELISA) using serum and cerebrospinal fluid (CSF) samples. The sensitivity for serum and CSF was 94.7% and 100% for rGP50 and 90.4% and 90.2% for sTS18var1, respectively. The specificity for serum and CSF samples was 93.8% and 100% for rGP50 and 90.3% and 98.0% for sTS18var1, respectively. The use of these antigens individually or combined as a diagnostic antigen cocktail eliminates the need for purification of antigens from parasite material and offers the advantage of using a simple and quantitative ELISA format.

Evaluation of an antigen from Taenia crassiceps cysticercus for the serodiagnosis of neurocysticercosis.

We report here the evaluation of an antigen from Taenia crassiceps cysticercus as a potential reagent in an enzyme-immunoelectrotransfer blotting assay (EITB) and an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of neurocysticercosis (NC) using clinical specimens obtained from patients in different phases of the disease. Serum and cerebrospinal fluid (CSF) samples from 64 patients suspected of having NC according to clinical manifestation and brain computed tomography were tested by ELISA with Taenia solium total saline antigen (ELISA-Tso) and by immunoblotting with T. crassiceps glycoproteins antigen (EITB-gpTcra). Forty-five serum samples were also tested immunoblotting with T. solium glycoproteins antigen (EITB-gpTso) and 30 were tested by ELISA with T. crassiceps 14 kDa glycoprotein (ELISA-gp14Tcra). Serum samples from apparently healthy individuals without any parasitic disease and from patients with other parasitic diseases were included as controls. The results of ELISA-Tso analysis with CSF obtained from 64 patients with NC showed that 53 (83%) were reactive. EITB-gpTcra analysis with serum from the same group of patients showed a sensitivity of 91%. Results of EITB-gpTso and EITB-gpTcra analysis with serum samples demonstrated an agreement of 100% between both tests. ELISA-gp14Tcra was positive in 23 (77%) sera, 22 with paired CSF positive. When ELISA-gp14Tcra results were compared to EITB-Tso results, a relative sensitivity of 95% was observed. All serum samples from the control group were negative in ELISA-gp14Tcra and only one serum from an individual with Taenia saginata was reactive in this assay, showing a specificity of 99% for ELISA-gp14Tcra. This fraction was purified in only one step with a good yield for use in immunoassays. We suggest that the gp14Tcra antigen can be used for detecting anti-cysticercus antibodies in serum samples for epidemiological investigation purposes and also for diagnostic screening of NC patients.

IgG intrathecal synthesis and specific antibody index in patients with neurocysticercosis.

UNLABELLED: We analyzed cerebrospinal fluid (CSF) and blood serum from 55 patients with neurocysticercosis (NC) at different clinical stages. According to inflammatory activity in the CSF, three stages were identified: (1) reactive, when there was at least an increase in the number of cells; (2) weakly reactive, when significant alterations were found in the CSF, including an increase in gamma globulins, albeit without hypercytosis; (3) non-reactive, when there was neither hypercytosis nor increase in gamma globulins. Nineteen patients had the reactive form; 18 had the weakly reactive form; 18 displayed the non-reactive form. Local immunoproduction was intense in the reactive group, moderate in the weakly reactive group, and absent in the non-reactive group. The specific antibody index was raised in approximately 2/3 of patients with the reactive form, 2/3 in those with the weakly reactive form, and 1/3 in those with the non-reactive form. IN CONCLUSION: (1) the classical CSF syndrome in NC can present both in complete and partial modes; (2) local immunoproduction can occur in weakly reactive forms; (3) a raised specific antibody index can occur in the absence of an inflammatory reaction in the CSF.

Neuroinfection survey at a neurological ward in a Brazilian tertiary teaching hospital.

OBJECTIVES: This study was undertaken to characterize the neuroinfection profile in a tertiary neurological ward. INTRODUCTION: Neuroinfection is a worldwide concern and bacterial meningitis, tetanus and cerebral malaria have been reported as the commonest causes in developing countries. METHODS: From 1999 to 2007, all patients admitted to the Neurology Ward of Hospital das Clínicas, São Paulo University School of Medicine because of neuroinfection had their medical records reviewed. Age, gender, immunological status, neurological syndrome at presentation, infectious agent and clinical outcome were recorded. RESULTS: Three hundred and seventy four cases of neuroinfectious diseases accounted for 4.2% of ward admissions and the identification of infectious agent was successful in 81% of cases. Mean age was 40.5 + 13.4 years, 63.8% were male, 19.7% were immunocompromised patients and meningoencephalitis was the most common clinical presentation despite infectious agent. Viruses and bacteria were equally responsible for 29.4% of neuroinfectious diseases; parasitic, fungal and prion infections accounted for 28%, 9.6% and 3.5% respectively. Human immunodeficiency virus (HIV), herpes simplex virus 1 (HSV1), Mycobacterium tuberculosis, Treponema pallidum, Taenia solium, Schistosoma mansoni, Cryptococcus neoformans and Histoplasma capsulatum were the more common infectious pathogens in the patients. Infection mortality rate was 14.2%, of which 62.3% occurred in immunocompetent patients. CONCLUSION: Our institution appeared to share some results with developed and developing countries. Comparison with literature may be considered as quality control to health assistance.

Neuroinfection survey at a neurological ward in a Brazilian tertiary teaching hospital

OBJECTIVES: This study was undertaken to characterize the neuroinfection profile in a tertiary neurological ward. INTRODUCTION: Neuroinfection is a worldwide concern and bacterial meningitis, tetanus and cerebral malaria have been reported as the commonest causes in developing countries. METHODS: From 1999 to 2007, all patients admitted to the Neurology Ward of Hospital das Clínicas, São Paulo University School of Medicine because of neuroinfection had their medical records reviewed. Age, gender, immunological status, neurological syndrome at presentation, infectious agent and clinical outcome were recorded. RESULTS: Three hundred and seventy four cases of neuroinfectious diseases accounted for 4.2 percent of ward admissions and the identification of infectious agent was successful in 81 percent of cases. Mean age was 40.5 + 13.4 years, 63.8 percent were male, 19.7 percent were immunocompromised patients and meningoencephalitis was the most common clinical presentation despite infectious agent. Viruses and bacteria were equally responsible for 29.4 percent of neuroinfectious diseases; parasitic, fungal and prion infections accounted for 28 percent, 9.6 percent and 3.5 percent respectively. Human immunodeficiency virus (HIV), herpes simplex virus 1 (HSV1), Mycobacterium tuberculosis, Treponema pallidum, Taenia solium, Schistosoma mansoni, Cryptococcus neoformans and Histoplasma capsulatum were the more common infectious pathogens in the patients. Infection mortality rate was 14.2 percent, of which 62.3 percent occurred in immunocompetent patients. CONCLUSION: Our institution appeared to share some results with developed and developing countries. Comparison with literature may be considered as quality control to health assistance.

Taenia solium DNA is present in the cerebrospinal fluid of neurocysticercosis patients and can be used for diagnosis.

Neurocysticercosis is the most frequent parasitic infection of the CNS and the main cause of acquired epilepsy worldwide. Seizures are the most common symptoms of the disease, together with headache, involuntary movements, psychosis and a global mental deterioration. Absolute diagnostic criteria include the identification of cysticerci, with scolex, in the brain by MRI imaging. We demonstrate here, for the first time, that T. solium DNA is present in the cerebrospinal fluid of patients. The PCR amplification of the parasite DNA in the CSF enabled the correct identification of 29/30 cases (96.7 %). The PCR diagnosis of parasite DNA in the CSF may be a strong support for the diagnosis of neurocysticercosis.

Urological manifestations of chronic schistosomal myeloradiculopathy.

OBJECTIVE: To describe the clinical and urodynamic features of patients with chronic voiding dysfunction secondary to schistosomal myeloradiculopathy (SM), as the clinical involvement of the spinal cord is a well recognized complication of Schistosomiasis mansoni infection. PATIENTS AND METHODS: We reviewed the records and urodynamic studies of 26 consecutive patients (17 males and nine females, aged 8-58 years) with chronic neurological and urinary symptoms secondary to SM. The voiding function history, radiological and urodynamic findings and therapeutic approaches were reviewed. Patients with and without upper urinary tract complications were compared in terms of age, duration of voiding dysfunction and urodynamic pattern. RESULTS: The most common urinary symptoms were difficulty in emptying the bladder (17 patients, 65%), urinary incontinence (14, 54%), and urgency and frequency (13, 50%). Laboratory and radiographic evaluation showed urinary tract infection in eight (30%) patients, bilateral hydronephrosis in five (19%) and bladder calculi in five (19%). Urodynamics showed detrusor overactivity with detrusor-external sphincter dyssynergia (DESD) in 14 patients (54%), detrusor arreflexia in six (23%), detrusor overactivity with no dyssynergia in four (15%), and detrusor underactivity in two (8%). Comparing patients with and without upper tract complications showed no differences in age and duration of urinary symptoms, but there was a significant association of detrusor overactivity with DESD and upper urinary tract complications (P = 0.04). Urological management consisted of antibiotics, clean intermittent catheterization, anticholinergic medication and stone removal, as appropriate. Conservative treatment failed in three patients and they required an injection with botulinum-A toxin into the detrusor (two) or ileocystoplasty (one). CONCLUSION: Patients with chronic SM behave clinically like those with other causes of spinal cord disease and neurogenic bladder dysfunction requiring lifelong surveillance. The severity of illness in these patients should re-emphasize the need for early recognition and treatment of this condition, to prevent or reverse the neurological deficits.

Sinalizaçäo do líquido cefalorraqueano em doenças inflamatórias crônicas do sistema nervoso central / Cerebrospinal fluid signalization in chronic inflammatory diseases of the central nervous system

Foi estudado o comportamento do dual citoproteico do LCR em processos inflamatórios do sistema nervoso central (SNC). Do ponto de vista neuroimunológico e levando em conta a sinalizaçäo observada mediante o estudo do líquido cefalorraqueano (LCR) podem ser considerados três grupos de modelos: o agudo, o crônico e o intermediário. Cada um deles pode apresentar subtipos. Foram avaliadas as características de comportamento do dual em dois modelos do tipo intermediário (criptococose do SNC e esquistossomose do SNC) e em 4 crônicos: dois de tipo contínuo (neurossífilis e panencefalite esclerosante subaguda) e dois de tipo repetitivo (neurocisticercose e esclerose múltipla). Os dados analisados permitem visäo quanto ao comportamento do dual citoproteico do LCR (número de células, perfil citomorfológico, subpopulaçöes linfocitárias, estudo proteico, fraçöes proteicas e suas relaçöes) nos modelos inflamatórios considerados. As diferenças observadas entre os modelos intermediários e os crônicos, tanto o contínuo como o repetitivo, säo evidentes independentemente do agente etiológico considerado

Síndrome de calcificaçöes dos gânglios da base, leucodistrofia e pleocitose linfomonocitária crônica do líquido cefalorraqueano / Syndrome of calcifications of basal ganglia leukodystrophy and chronic lymphomonocytic pleocytosis of the cerebrospinal fluid: report of a case

Em 1966 Norman e Tingey descreveram síndrome de micrencefalia, calcificaçöes estrio-cerebelares e leucodistrofia, síndrome esta que, em 1968, acrescida de nanismo, Lyon e col. tornaram a relatar. Esses autores näo descreveram alteraçöes do LCR. Em 1984, Aicardi e Goutièrres descreveram 8 crianças pertencentes a 5 famílias, com a síndrome antes referida, porém com a diferença de as calcificaçöes serem dos gânglios de base, além de haver pleocitose do LCR crônica linfomonoclear. Todos os pacientes tiveram evoluçäo progressiva e caráter familiar, com provável herança autossômica recessiva. É propósito deste registro relatar caso semelhante, num paciente branco do sexo masculino, com 6 meses e meio de idade e que apresentou quadro semelhante, diagnosticado aos 3 meses de idade: nanismo e microcefalia limiares, calcificaçöes dos gânglios de base e leucodistrofia à TC. Seis exames de LCR sucessivos mostraram pleocitose de predomínio linfomononuclear. Fez-se estudo das subpopulaçöes de linfócitos T-ativos e T-ávidos, o qual sugeriu sinalizaçäo local no sistema do LCR. Säo discutidos o diagnóstico diferencial e a estranha combinaçäo de provável etiologia genética associada a mecanismo imunitário, revelando processo inflamatório local. Processaram-se pesquisas no intuito de afastar etiologia a vírus, as quais se revelaram negativas, o que näo afasta esta hipótese

Líquido cefalorraqueano na síndrome de imunodeficiência adquirida: análise de 50 casos / Cerebrospinal fluid in the acquired immunodeficiency syndrome: analysis of 50 cases

Foi estudado sistematizadamente o LCR de 50 pacientes com AIDS que apresentavam sintomatologia passível de ser atribuída a comprometimento do SNC. Somente 5 apresentavam o quadro do LCR dentro dos limites normais. Em um, ocorriam células neoplásicas (linfoma); em 10, Cryprococcus neoformans; reaçöes imunológicas foram positivas para sífilis em três e para toxoplasmose em 4. Um dos casos de criptococose apresentava simultaneamente toxoplasmose e desenvolveu sífilis, anteriormente. Em outro dos casos de criptococose durante a evoluçäo surgiram leveduras de gênero Candida. Considerando os achados, säo discutidos quanto ao LCR aspectos: da reaçäo inflamatória na vigência de imunodeficiência; do comprometimento da BHE; do comprometimento do SNC; de efeitos de massa que podem ocorrer, como aqueles provocados por tumores e granulomas

Diffusion-weighted MR imaging of cystic lesions of neurocysticercosis: a preliminary study

Neurocysticercosis is an endemic disease in some developing countries. It has pleomorfic clinical and imaging findings, which are variable from patient to patient. In this preliminary note, we studied the magnetic resonance (MR) diffusion-weighted images (DWI) of sixteen patients presenting with cystic lesions of this disease diagnosed by clinical and laboratorial findings. All the lesions had hypointense signal and the similar apparent diffusion coeficient (ADC) values as the cerebrospinal fluid (CSF)

Líquido cefalorraqueano e neurocysticercoses: aspectos evolutivos da resposta inflamatória celular / Cerebrospinal fluid and neurocysticercosis: evolutive aspects of the inflammatory response

Foram estudadas 357 amostras de LCR de 40 pacientes com neurocisticercose, submetidos a tratamento medicamentoso com praziquantel associado a dexametasona. No sentido de avaliar aspectos evolutivos do componente celular da resposta, inflamatória, foram programadas, para cada paciente, avaliaçöes do exame de LCR em 13 oportunidades: por ocasiäo do diagnóstico; durante o tratamento; e posteriormente, a intervalos prefixados até completar dois anos de evoluçäo. Foi utilizada metodologia adequada ao estudo citológico e citomorfológico, bem como à quantificaçäo de linfócitos B e T. Para determinaçäo de subpopulaçöes T-ativa, T-sensibilizada e T-ávidas foram utilizados, como marcadores supoerfície, receptores para hemácias de carneiro. O grupo controle é constituido de 50 pacientes com cefaléia crônica e que näo apresentavam alteraçöes ao exame físico e ao exame neurológico. Em todos, o exame de LCR estava dentro dos limites normais. Linfócitos B e T näo apresentavam alteraçöes no exame inicial de LCR; näo houve modificaçöes no seu comportamento durante toda a evoluçäo. Os elementos da resposta inflamatória celular capazes de fornecer informaçöes significativas acerca do perfil evolutivo em estudo foram: o número de células, a presença e o número de polimorfonucleares neutrófilos e de células eosinófilas e a quantificaçäo de subpopulaçöes T-ativa e T-sensibilizada. A presença de polimorfonucleares neutrófilos embora influenciada pela açäo dos corticosteróides e pela presença de sistema de derivaçäo do trânsito do LCR, pode constitui-se em elemento qualitativo sugestivo de atividade inflamatória. Os valores percentuais para linfócitos T-ativos, diminuídos na primeira amostra, e T-sensibilizados, aumentados na primeira amostra, podem ser indicadores quantitativos e qualitativos adequados a reconhecer a vigência de atividade inflamatória local no sistema LCR; estas subpopulaçöes linfocitárias, com alteraçöes significativas em 63,2% dos pacientes no exame inicial, näo säo influenciadas significativamente pelo uso de corticosteróides. Os valores de eosinófilos e de linfócitos T-sensibilizados estäo significativamente aumentados em pacientes que apresentaram complicaçöes clínicas durante o período de acompanhamento após o tratamento; subpopulaçäo e linfócitos T-ativos estava significativamente diminuída nestes casos...

Imunoglobulinas do líquido cefalorraqueano no recém-nascido / Immunoglobulins in the cerebrospinal fluid of neroborn infants

Foram estudadas as imunoglobulinas IgG, IgA e IgM no soro e no LCR de 36 recém-nacidos no segundo dia de vida. Para caracterizaçäo prévia da normalidade, tanto para as amostras de soro, como para as amostras de LCR, foram realizados estudos comparativos com dados já estabelecidos anteriormente no nosso meio. O estudo das imunoglobulinas no soro e no LCR foram realizados por dois métodos: imunodifusäo radial e nefelometria. Os valores encontrados (média + ou - desvio padräo) säo os que se seguem (mg/dl). Para o soro: pelo método de IDR IgG 1346 + ou - 299,1; IgM 10,4 + ou - 2,26; IgA 1,1 + ou - 1,06; pelo método de nefelometria IgG 1372 + ou - 319,7; IgM 10,6 + ou - 4,10; IgA 1,5 + ou - 0,31. Nas amostras de LCR ambos os métodos näo permitiram detectar IgA e IgM; IgG foi detectada por ambos e os valores observados (média + ou - desvio padräo) foram (mg/dl): por imunodifusäo radial 11,1 + ou - 2,52; por nefelometria 9,6 + ou - 7,04. Foram estudadas também as relaçöes e o índice de IgG; deles, salienta-se que o indice de IgG, apresenta valores normais de 0,5 + ou - 0,14

Proteína básica de Mielina no líquido cefalorragueano na neurocisticercose / Myelin basic protein in cerebrospinal fluid in neurocysticercosis

Foram estudadas 133 amostras de LCR provenientes de 115 pacientes para verificar o teor da PBM, fragmento P1 43-88. Os casos foram subdivididos em subgrupos de acordo com o diagnóstico nosológico. No grupo controle (50 casos de pacientes com cefaléia crônica) näo houve detecçäo de PBM em qualquer das amostras; dos casos de neurocisticercose (44), em 4 havia presença da PBM; nos de esclerose múltipla (8) em três havia PBM; em um caso de neuroesquistossomose, forma medular, também foi detectada a presença da PBM. Consideraçöes de ordem neuroimunológica säo tecidas sobre os resultados encontrados

ELISA (IgG e IgM) No LCR e soro na neurocisticercose em tratamento com praziquantel: comparaçäo com reaçöes de fixaçäo do complemento e imunofluorescência / ELISA (IgG and IgM) in CSF and serum in neurocysticercosis under treatment with praziquantel: comparation with complement fixation reactions and immunofluoréscence

Foram estudados amostras de LCR e soro de 10 pacientes com neurocisticercose submetidos a tratamento com praziquantel visando a comparaçäo de reaçöes imunológicas. As reaçöes estudadas foram ELISA-G, ELISA-M, imunofluorescência-G, imunofluorescência-M e fixaçäo do complemento. As alteraçöes e a variabilidade verificadas nesta série comprovam a natureza dos fenômenos neuroimunológicos descritos na afcçäo. Fenômenos da fase aguda foram verificados pelas reaçöes ELISA-M e RIF-M em 6 caso pelo estudo do LCR e em apenas um caso pelo estudo do soro. Maior sensibilidade tanto para o diagnóstico como para o acompanhamento evolutivo foi observado para a reaçäo ELISA-G quando comparada às demais reaçöes imunológicas, tanto no LCR como no soro. É salientada a importância da realizaçäo das várias reaçöes imunológicas em pacientes com neurocisticercose

Síndrome do líquido cefalorraqueano na neuroesquistossomose / Cerebrospinal fluid syndrome in neuroschistosomiasis

Foram estudados 220 amostras de LCR de pacientes com afecçöes diversas do sistema nervoso, nas quais de maneira sistematizada, foram realizadas reaçöes de imunofluorescência para esquistossomose. Estas foram realizadas com cortes de vermes adultos e com cortes de fígado de hamster infectados por Schistosoma mansoni em que havia formaçäo de granulomas, ambas por técnica indireta antiglobulínica. Säo analisados as características do LCR dos 16 casos em que essas duas reaçöes foram reagentes. Discute-se a introduçäo e pesquisa sistematizada dessas reaçöes no LCR de pacientes com moléstias inflamatórias do sistema nervoso central. De acordo com o quadro do LCR observado nesses pacientes configura-se a introduçäo do conceito de "síndrome do LCR na neuroesquistossomose" a exemplo do que já ocorre em outras afecçöes inflamatórias do sistema nervoso, como a neurocisticercose e a neurossífilis

Teste de hemaglutinação para o diagnóstico da neurocisticercose humana: desenvolvimento de reagente estável utilizando antígeno heterólogo / Hemmagglutination test for the diagnosis of human neurocysticercosis: development of a stable reagent using heterologous antigens

Foi padronizado o teste de hemaglutinação (HA) empregando hemácias de ganso formolizadas, taninizadas e sensibilizadas com extrato antigênico de líquido vesicular de C. longicollis (HA-CI) e extrato salino total de C. cellulosae (HA-Cc). Foram ensaiados 61LCR de dois grupos: 41 de pacientes com neurocisticercose e 20 de grupo controle, respectivamente, reativos e não-reativos no teste ELISA empregando C. cellulosae. Nos LCR do grupo controle não foi observada reatividade e 34 (82,9%) e 35 (85,4%) LCR de doentes foram reativos, respectivamente, nos testes HA-CI e HA-Cc. O estudo da estabilidade dos reagentes pronto para uso mostrou vantagens para o armazenamento a 4°C, em glicerol a 50%, por até 6 meses. Os resultados obtidos indicam que o reagente utilizando Cysticercus longicollis e estabilizado com glicerol pode ser empregado como alternativa no diagnóstico imunológico da neutocisticercose