Performance of cryptococcal antigen lateral flow assay in serum, cerebrospinal fluid, whole blood, and urine in HIV-infected patients with culture-proven cryptococcal meningitis admitted at a Brazilian referral center.

Cryptococcal meningitis is the most common cause of opportunistic meningitis in HIV-infected patients in Brazil and causes unacceptable high mortality rates. In this study, HIV-infected patients with a first episode of culture-proven cryptococcal meningitis in cerebrospinal fluid (CSF) were prospectively included in order to evaluate sensitivity of cryptococcal antigen (CrAg) lateral flow assay (LFA) in serum, CSF, whole blood (fingerstick), and fresh urine. In addition, HIV-infected patients with other neurological confirmed diseases were included in order to evaluate the specificity of CrAg LFA in serum. Twenty patients with cryptococcal meningitis were included and in 19 of them, CrAg LFA in CSF, serum, and whole blood were positive (95% sensitivity). In 18 patients, India ink test was positive in CSF (90% sensitivity), and in 16 cases, CrAg LFA was positive in urine (80% sensitivity). Thirty-six HIV-infected patients with other neurological diseases had negative results of CrAg LFA in serum (100% specificity). In conclusion, CrAg LFA in serum, CSF, and whole blood showed high sensitivity and specificity. Whole blood CrAg LFA seems to be a good and reliable strategy to improve AIDS-related cryptococcal meningitis diagnosis in Brazil.

High risk of heterosexual transmission of human T-cell lymphotropic virus type 1 infection in Brazil

Human T-cell lymphotropic virus type 1 is transmitted primarily either through sexual intercourse or from mother to child. The current study investigated sexual transmission and compared the HTLV-1 proviral load between seroconcordant and serodiscordant couples by examining both men and women among the index partners without using subjective criteria to establish the direction of sexual transmission. Between January 2013 and May 2015, 178 HTLV-1-positive patients had spouses, 107 of which had tested partners, thus increasing the initial sample size (46 men and 61 women). Individuals co-infected with HTLV-2 or human immunodeficiency virus were not included in the analysis. From among the included participants, 26 men and 26 women were paired with each other, resulting in 26 seroconcordant couples; 12 seroconcordant couples were formed from another four men and eight women. Forty-three serodiscordant couples were formed from 16 men and 27 women. The rate of seroconcordance was 46.9%. The HTLV-1 proviral load was compared between 19 and 37 seroconcordant and serodiscondant couples, respectively, and the concordant couples showed higher proviral loads (P = 0.03). There were no differences between the groups according to age, relationship length, having a mother or sibling with HTLV-1, race, ethnicity, nationality, education, history of blood transfusion, HAM/TSP, ALT, or hepatitis C virus status. In multivariate analysis, relationship time was shown associated with ocurrence of seroconcordance status. The apparent association between high circulating levels of provirus and seroconcordance rate among couples suggests that proviral loads contribute markedly to the risk of sexual transmission, regardless of gender index

Polyomavirus detection in multiple sclerosis patients under natalizumab therapy: Profile and frequency of urinary shedding

Patients undergoing Natalizumab (NTZ) therapy are at risk of progressive multifocal leukoencephalopathy (PML). Besides John Cunningham virus (JCV), BK polyomavirus might represent an additional concern for such patients since it can also infect CNS cells. Currently, data regarding the presence of anti-JCV antibodies added to previous immunosuppressive therapy and prolonged NTZ therapy has been used to classify patients at risk of developing PML. Here, we investigated the profile shedding of JCV and BKV in multiple sclerosis (MS) patients during treatment with NTZ. Serial blood and urine samples from 97 MS patients receiving either NTZ or ß-interferon were investigated for polyomavirus shedding. While all blood samples tested negative, 36% of the patients shed polyomavirus in the urine in at least one time point. From these, 21.7%, 9.3%, and 5.1% shed JCV, BKV, and both polyomavirus, respectively. No difference was observed between the rates of urinary shedding of patients treated with NTZ (38.9%) and patients treated with other drugs (34.5%), also no PML event was diagnosed during the follow-up. Therefore, urinary shedding might not be interfered by therapy condition. In our study, we also observed 14/27 (52%) of anti-JCV antibodies prevalence, and nearly half of them (42%) did not present any event of urinary shedding during the follow-up

Strategies to reduce mortality and morbidity due to AIDS-related cryptococcal meningitis in Latin America

Latin America is the region with the third most AIDS-related cryptococcal meningitis infections globally. Highly active antiretroviral therapy (HAART) has reduced the number of infections; however, the number of deaths and the case-fatality rate continues to be unacceptable. In this review, we focus on the burden of AIDS-related cryptococcosis in Latin America and discuss potential strategies to reduce early mortality from Cryptococcus. In this review, we highlight the importance of: (1) earlier HIV diagnosis and HAART initiation with retention-in-care to avoid AIDS; (2) pre-HAART cryptococcal antigen (CRAG) screening with preemptive fluconazole treatment; (3) better diagnostics (e.g. CRAG testing); and (4) optimal treatment with aggressive management of intracranial pressure and induction therapy with antifungal combination. Implementation of these strategies can reduce cryptococcal-related deaths, improve care, and reduce healthcare costs.

JC virus-associated central nervous system diseases in HIV-infected patients in Brazil: clinical presentations, associated factors with mortality and outcome.

INTRODUCTION: Several presentations of neurologic complications caused by JC virus (JCV) in human immunodeficiency virus (HIV)-infected patients have been described and need to be distinguished from the "classic" form of progressive multifocal leukoencephalopathy (PMl). The objectives of this study were: 1) to describe the spectrum and frequency of presentations of JCV-associated central nervous system (CNS) diseases; 2) identify factors associated with in-hospital mortality of patients with JCV-associated CNS disease; and 3) to estimate the overall mortality of this population. MATERIAL AND METHODS: This was a retrospective study of HIV-infected patients admitted consecutively for JCVassociated CNS diseases in a referral teaching center in São Paulo, Brazil, from 2002 to 2007. All patients with laboratory confirmed JCV-associated CNS diseases were included using the following criteria: compatible clinical and radiological features associated with the presence of JCV DNA in the cerebrospinal fluid. JCV-associated CNS diseases were classified as follows: 1) classic PMl; 2) inflammatory PMl; and 3) JC virus granule cell neuronopathy (GCN). RESULTS: We included 47 cases. JCV-associated CNS diseases were classified as follows: 1) classic PMl: 42 (89%); 2) inflammatory PMl: three (6%); and 3) JC virus GCN: four (9%). Nosocomial pneumonia (p = 0.003), previous diagnosis of HIV infection (p = 0.03), and imaging showing cerebellar and/or brainstem involvement (p = 0.02) were associated with in-hospital mortality. overall mortality during hospitalization was 34%. CONCLUSIONS: Novel presentations of JCV-associated CNS diseases were observed in our setting; nosocomial pneumonia, previous diagnosis of HIV infection, and cerebellar and/or brainstem involvement were associated with in-hospital mortality; and overall mortality was high.

JC virus-associated central nervous system diseases in HIV-infected patients in Brazil: clinical presentations, associated factors with mortality and outcome

INTRODUCTION: Several presentations of neurologic complications caused by JC virus (JCV) in human immunodeficiency virus (HIV)-infected patients have been described and need to be distinguished from the "classic" form of progressive multifocal leukoencephalopathy (PMl). The objectives of this study were: 1) to describe the spectrum and frequency of presentations of JCV-associated central nervous system (CNS) diseases; 2) identify factors associated with in-hospital mortality of patients with JCV-associated CNS disease; and 3) to estimate the overall mortality of this population. MATERIAL AND METHODS: This was a retrospective study of HIV-infected patients admitted consecutively for JCVassociated CNS diseases in a referral teaching center in São Paulo, Brazil, from 2002 to 2007. All patients with laboratory confirmed JCV-associated CNS diseases were included using the following criteria: compatible clinical and radiological features associated with the presence of JCV DNA in the cerebrospinal fluid. JCV-associated CNS diseases were classified as follows: 1) classic PMl; 2) inflammatory PMl; and 3) JC virus granule cell neuronopathy (GCN). RESULTS: We included 47 cases. JCV-associated CNS diseases were classified as follows: 1) classic PMl: 42 (89%); 2) inflammatory PMl: three (6%); and 3) JC virus GCN: four (9%). Nosocomial pneumonia (p = 0.003), previous diagnosis of HIV infection (p = 0.03), and imaging showing cerebellar and/or brainstem involvement (p = 0.02) were associated with in-hospital mortality. overall mortality during hospitalization was 34%. CONCLUSIONS: Novel presentations of JCV-associated CNS diseases were observed in our setting; nosocomial pneumonia, previous diagnosis of HIV infection, and cerebellar and/or brainstem involvement were associated with in-hospital mortality; and overall mortality was high.

Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature / Complicações neurológicas causadas pelo citomegalovírus em pacientes com AIDS: estudo retrospectivo de 13 casos e revisão da literatura

Neurological disorders caused by Cytomegalovirus (CMV) in patients with Acquired Immunodeficiency Syndrome (AIDS) are rarely reported in the Highly Active Antiretroviral Therapy (HAART) period. The objective of this study was to describe the main clinical and laboratory features of patients with CMV-related neurological complications in HIV-infected patients admitted to a referral center in São Paulo, Brazil. CMV disease requires the identification of the virus in the cerebrospinal fluid (CSF) using Polymerase Chain Reaction (PCR). Thirteen cases were identified between January, 2004 and December, 2008. The median age of patients was 38 years and nine (69 percent) were men. At admission all patients were aware of their HIV status and only four (31 percent) patients were on HAART. Patients who were not on antiretroviral therapy before admission received HAART while inpatients. CMV disease was the first AIDS-defining illness in eight (62 percent) patients. The neurologic syndromes identified were diffuse encephalitis (n = 7; 62 percent), polyradiculopathy (n = 7; 54 percent), focal encephalitis (rhombencephalitis) (n = 1; 8 percent), and ventriculo-encephalitis (n = 1; 8 percent). Seven (54 percent) patients presented extra-neural CMV disease and four (31 percent) had retinitis. The median of CD4+ T-cell count was 13 cells/µL (range: 1-124 cells/µL). Overall in-hospital mortality was 38 percent. Eight patients used ganciclovir or foscarnet (in-hospital mortality: 50 percent) and five patients used ganciclovir and foscarnet (in-hospital mortality: 20 percent). None of the patients fulfilled the diagnosis criteria of immune reconstitution inflammatory syndrome. Four patients were lost to follow-up, and three patients presented immune recovery and discontinued secondary prophylaxis. Although infrequent, distinct neurological syndromes caused by CMV continue to cause high mortality among AIDS patients. Survival depends upon the use of effective antiviral therapy against CMV and the early introduction of HAART.

As complicações neurológicas causadas pelo Citomegalovírus (CMV) em pacientes com aids são raramente relatadas na era HAART. O objetivo deste estudo foi descrever as principais características clínicas e laboratoriais de pacientes com complicações neurológicas associadas ao CMV em pacientes com aids admitidos em centro de referência em Sao Paulo, Brasil. A doença citomegálica precisou da identificação do vírus no líquor mediante a reação em cadeia da polimerase (PCR). Treze casos foram identificados entre janeiro de 2004 e dezembro de 2008. A mediana da idade foi 38 anos e nove (69 por cento) eram homens. Na admissão, todos os pacientes sabiam do seu status sorológico para o HIV e apenas quatro (31 por cento) pacientes usavam HAART. A doença citomegálica foi a primeira doença definidora de aids em oito (62 por cento) pacientes. As síndromes neurológicas identificadas foram: encefalite difusa (n = 7; 62 por cento), polirradiculopatia (n = 7; 54 por cento), encefalite focal (romboencefalite) (n = 1; 8 por cento), e ventrículo-encefalite (n = 1; 8 por cento). Sete (54 por cento) pacientes apresentaram doença citomegálica fora do sistema nervoso e quatro (31 por cento) tiveram retinite. A mediana da contagem de células CD4+ foi 13 células/µL. A mortalidade global durante a internação foi 38 por cento. Oito pacientes usaram ganciclovir ou foscarnet (mortalidade: 50 por cento) e cinco pacientes usaram ganciclovir e foscarnet (mortalidade: 20 por cento). Nenhum paciente apresentou critérios diagnósticos da síndrome inflamatória de reconstituição imunológica. Quatro pacientes foram perdidos do acompanhamento ambulatorial e três pacientes apresentaram reconstituição imunológica e descontinuaram as profilaxias secundárias. Embora raras, as particulares síndromes neurológicas causadas pelo CMV continuam causando elevada mortalidade em pacientes com aids. A sobrevida depende do uso de terapia antiviral efetiva contra o CMV e a introdução oportuna do HAART.

Ring enhancing intracranial lesion responding to antituberculous treatment in an HIV-infected patient.

Cerebral tuberculomas constitute a major differential diagnosis of cerebral toxoplasmosis in human immunodeficiency virus (HIV)-infected patients in developing countries. We report the case of a 34-year old woman co-infected with HIV and possible disseminated tuberculosis (hepatitis, lymphadenopathy, and pleural effusion) who presented a large and solitary intracranial mass lesion. Despite extensive diagnostic efforts, including brain, ganglionar, and liver biopsies, no definitive diagnosis was reached. However, a trial with first-line antituberculous drugs led to a significant clinical and radiological improvement. Atypical presentations of cerebral tuberculomas should always be considered in the differential diagnosis of intracranial mass lesions in HIV-infected patients and a trial with antituberculous drugs is a valuable strategy to infer the diagnosis in a subset of patients.

Ring enhancing intracranial lesion responding to antituberculous treatment in an HIV-infected patient / Lesão intracraniana que respondeu ao tratamento anti-tuberculoso em paciente infectado pelo HIV

Cerebral tuberculomas constitute a major differential diagnosis of cerebral toxoplasmosis in human immunodeficiency virus (HIV)-infected patients in developing countries. We report the case of a 34-year old woman co-infected with HIV and possible disseminated tuberculosis (hepatitis, lymphadenopathy, and pleural effusion) who presented a large and solitary intracranial mass lesion. Despite extensive diagnostic efforts, including brain, ganglionar, and liver biopsies, no definitive diagnosis was reached. However, a trial with first-line antituberculous drugs led to a significant clinical and radiological improvement. Atypical presentations of cerebral tuberculomas should always be considered in the differential diagnosis of intracranial mass lesions in HIV-infected patients and a trial with antituberculous drugs is a valuable strategy to infer the diagnosis in a subset of patients.

Os tuberculomas cerebrais constituem diagnóstico diferencial importante da toxoplasmose cerebral em pacientes infectados pelo vírus da imunodeficiência humana (HIV) de países em desenvolvimento. Os autores relatam o caso de uma mulher HIV positiva de 34 anos de idade, que apresentou provável tuberculose disseminada (hepatite, adenomegalia, e derrame pleural) associada à lesão expansiva cerebral única e gigante. Apesar dos esforços diagnósticos realizados, incluindo biópsia cerebral, ganglionar e hepática, o diagnóstico etiológico não foi confirmado. Porém, a resposta clínico-radiológica ao tratamento tuberculostático permitiu definir o diagnóstico de tuberculoma cerebral e a paciente teve alta hospitalar. Apresentações atípicas de tuberculomas cerebrais devem ser sempre consideradas no diagnóstico diferencial das lesões expansivas cerebrais em pacientes infectados pelo HIV e o uso do tratamento tuberculostático constitui ferramenta útil na definição diagnóstica em um sub-grupo de pacientes.

Neurologic cytomegalovirus complications in patients with AIDS: retrospective review of 13 cases and review of the literature.

Neurological disorders caused by Cytomegalovirus (CMV) in patients with Acquired Immunodeficiency Syndrome (AIDS) are rarely reported in the Highly Active Antiretroviral Therapy (HAART) period. The objective of this study was to describe the main clinical and laboratory features of patients with CMV-related neurological complications in HIV-infected patients admitted to a referral center in São Paulo, Brazil. CMV disease requires the identification of the virus in the cerebrospinal fluid (CSF) using Polymerase Chain Reaction (PCR). Thirteen cases were identified between January, 2004 and December, 2008. The median age of patients was 38 years and nine (69%) were men. At admission all patients were aware of their HIV status and only four (31%) patients were on HAART. Patients who were not on antiretroviral therapy before admission received HAART while inpatients. CMV disease was the first AIDS-defining illness in eight (62%) patients. The neurologic syndromes identified were diffuse encephalitis (n = 7; 62%), polyradiculopathy (n = 7; 54%), focal encephalitis (rhombencephalitis) (n = 1; 8%), and ventriculo-encephalitis (n = 1; 8%). Seven (54%) patients presented extra-neural CMV disease and four (31%) had retinitis. The median of CD4+ T-cell count was 13 cells/µL (range: 1-124 cells/µL). Overall in-hospital mortality was 38%. Eight patients used ganciclovir or foscarnet (in-hospital mortality: 50%) and five patients used ganciclovir and foscarnet (in-hospital mortality: 20%). None of the patients fulfilled the diagnosis criteria of immune reconstitution inflammatory syndrome. Four patients were lost to follow-up, and three patients presented immune recovery and discontinued secondary prophylaxis. Although infrequent, distinct neurological syndromes caused by CMV continue to cause high mortality among AIDS patients. Survival depends upon the use of effective antiviral therapy against CMV and the early introduction of HAART.

Aids-related progressive multifocal leukoencephalopathy: a retrospective study in a referral center in São Paulo, Brazil / Leucoencefalopatia multifocal progressiva em pacientes com aids: estudo retrospectivo em um centro de referência de São Paulo, Brasil

Few data are available about progressive multifocal leukoencephalopathy (PML) in patients with acquired immunodeficiency syndrome (AIDS) from Brazil. The objectives of this study were to describe the main features of patients with PML and estimate its frequency among AIDS patients with central nervous system (CNS) opportunistic diseases admitted to the Instituto de Infectologia Emílio Ribas, São Paulo, Brazil, from April 2003 to April 2004. A retrospective and descriptive study was performed. Twelve (6 percent) cases of PML were identified among 219 patients with neurological diseases. The median age of patients with PML was 36 years and nine (75 percent) were men. Nine (75 percent) patients were not on antiretroviral therapy at admission. The most common clinical manifestations were: focal weakness (75 percent), speech disturbances (58 percent), visual disturbances (42 percent), cognitive dysfunction (42 percent), and impaired coordination (42 percent). The median CD4+ T-cell count was 45 cells/µL. Eight (67 percent) of 12 patients were laboratory-confirmed with PML and four (33 percent) were possible cases. Eleven (92 percent) presented classic PML and only one case had immune reconstitution inflammatory syndrome (IRIS)-related PML. In four (33 percent) patients, PML was the first AIDS-defining illness. During hospitalization, three patients (25 percent) died as a result of nosocomial pneumonia and nine (75 percent) were discharged to home. Cases of PML were only exceeded by cases of cerebral toxoplasmosis, cryptococcal meningoencephalitis, and CNS tuberculosis, the three more frequent neurologic opportunistic infections in Brazil. The results of this study suggest that PML is not an uncommon HIV-related neurologic disorder in a referral center in Brazil.

Existe informação limitada sobre a presença da leucoencefalopatia multifocal progressiva (LEMP) em pacientes com aids no Brasil. Os objetivos do presente estudo foram descrever as principais características dos pacientes com LEMP e estimar a freqüência desta doença em pacientes com aids e doenças oportunistas do sistema nervoso central (SNC) internados em um centro de referência de São Paulo, Brasil. Neste estudo retrospectivo e descritivo, identificamos 12 (6 por cento) casos de LEMP entre 219 pacientes com doenças neurológicas oportunistas do SNC. A idade média dos pacientes com LEMP foi 36 anos e 9 (75 por cento) eram do sexo masculino. As manifestações clínicas mais freqüentes foram: déficits focais (75 por cento), alterações da fala (58 por cento), alterações visuais (42 por cento), alterações cognitivas (42 por cento), e problemas de coordenação (42 por cento). A média da contagem de células T-CD4+ foi 45 células/µL. Oito (67 por cento) dos 12 pacientes com LEMP tiveram diagnóstico confirmado laboratorialmente e em quatro (33 por cento) casos o diagnóstico foi possível. Onze (92 por cento) pacientes apresentaram LEMP clássica e um caso teve LEMP associada à síndrome de reconstituição imune. Em quatro (33 por cento) pacientes, a LEMP foi a primeira doença definidora de aids. Durante a internação, três pacientes (25 por cento) faleceram devido a pneumonia hospitalar e nove (75 por cento) tiveram alta. A LEMP foi apenas ultrapassada em freqüência pela toxoplasmose cerebral, a meningoencefalite criptococócica e a neurotuberculose, as três mais freqüentes doenças neurológicas oportunistas no Brasil. Os resultados deste estudo sugerem que a LEMP não é uma complicação neurológica incomum em pacientes com infecção pelo HIV no nosso meio.

HIV-associated neuromuscular weakness syndrome in Brazil: report of the two first cases.

We describe two Brazilian patients with HIV-associated neuromuscular weakness syndrome (HANWS), a unique clinical toxic syndrome that was recently reported in developed countries. Both patients were women, used stavudine and had hyperlactatemia, one of them with lactic acidosis. Electrophysiological studies were consistent with axonal neuropathy. After discontinuation of antiretroviral therapy the patients had significant improvement in neurologic manifestations, and normalization of lactate levels. To our knowledge, this is the first report of HANWS in developing countries. Growing use of antiretroviral therapy in this setting, particularly stavudine, make it likely that similar cases will be observed.

HIV-associated neuromuscular weakness syndrome in Brazil: report of the two first cases

We describe two Brazilian patients with HIV-associated neuromuscular weakness syndrome (HANWS), a unique clinical toxic syndrome that was recently reported in developed countries. Both patients were women, used stavudine and had hyperlactatemia, one of them with lactic acidosis. Eletrophysiological studies were consistent with axonal neuropathy. After discontinuation of antiretroviral therapy the patients had significant improvement in neurologic manifestations, and normalization of lactate levels. To our knowledge, this is the first report of HANWS in developing countries. Growing use of antiretroviral therapy in this setting, particularly stavudine, make it likely that similar cases will be observed.

Os autores descrevem dois pacientes brasileiros com a síndrome da fraqueza neuromuscular associada ao HIV, uma síndrome tóxica, clínicamente particular, que foi recentemente relatada em países desenvolvidos. Ambas pacientes eram do sexo feminino, usavam estavudina e apresentaram hiperlactatemia, uma delas com acidose láctica. Os exames electrofisiológicos foram consistentes com neuropatia axonal. As pacientes melhoraram significativamente das alterações neurológicas, assim como normalizaram os níveis de lactato, após descontinuar o uso dos antiretrovirais. Até onde sabemos, este é o primeiro relato da síndrome de fraqueza neuromuscular associada ao HIV em países em desenvolvimento. Nesse contexto, o uso crescente de antiretrovirais, particularmente a estavudina, possibilitarão que casos similares sejam observados.