RESUMO
Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurological and clinical manifestations that do not meet diagnostic criteria for HAM. These conditions may later progress to HAM or constitute an intermediate clinical form: intermediate syndrome (IS), a mid-point between asymptomatic HTLV-1 carriers and those with full myelopathy. Thus, we determined the incidence of HAM cases in the HTLV-1-asymptomatic and IS patients, and the clinical/laboratory associated markers. A total of 204 HTLV-1-positive patients were included in this study, divided into two groups: Group 1, including 145 asymptomatic HTLV-1 subjects (ASY), and Group 2, including 59 patients with inflammatory clinical symptoms in more than three systems and a high proviral load (PVL). During a 60-month follow-up time, with the age ranging from 47 to 79 years, ten patients of the fifty-nine initially diagnosed as IS developed HAM (iHAM), and two patients of the initial 145 ASY developed HAM directly. Women were more prevalent in all groups. For the iHAM patients, the age ranged from 20 to 72 years, with a mean of 53 (±15 SD). Older age was associated with the development of HAM, higher PVL and IS; however, there was no any specific symptom or clinical sign, that was associated with risk for iHAM. In conclusion, IS cases could be an early phase of development of HAM. These findings show the presence of higher incidence probabilities in our cohort than previously reported.
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Perilesional edema, associated or not with neurological manifestations, is a well-characterized finding in cases of calcified neurocysticercosis. There are no previous reports of HIV-related calcified toxoplasmosis that mimics this presentation of neurocysticercosis. We report on five patients, four of them with new-onset neurological manifestations, who showed brain calcifications associated with perilesional edema. All cases had a history of HIV-related toxoplasmosis and current virological and immunological control of HIV infection. Similar to neurocysticercosis, brain calcified toxoplasmosis may cause perilesional edema and symptoms in people living with HIV/AIDS.
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BACKGROUND: Cryptococcal meningitis remains a common cause of mortality in low- and middle-income countries, where amphotericin B deoxycholate (amphotericin) plus fluconazole is the most common treatment. Flucytosine is almost uniformly absent as is outcome data on flucytosine use in routine care. The main goal of this study was identified the cumulative mortality at 2, 4, and 10 weeks after hospital admission. METHODS: We conducted a retrospective, observational cohort study among HIV-infected adults with cryptococcal meningitis receiving amphotericin plus flucytosine as induction therapy in Brazil. We assessed cumulative mortality at 2, 4, and 10 weeks and the cumulative proportion discontinuating amphotericin or flucytosine due to toxicity at 2 weeks. We performed multiple logistic regression to identify variables associated with in-hospital mortality. RESULTS: In total, 77 individuals (n = 66 men) were included with median baseline CD4 of 29 (IQR, 9-68) cells/mcL. Twenty (26%) had at least one concurrent neurological disease diagnosed. Sixty (78%) patients received at least 14 days of amphotericin plus flucytosine. Cumulative mortality was 5% (4/77) at 2 weeks, 8% (6/77) at 4 weeks, and 19% (15/77) at 10 weeks. Cumulative proportion of patients that discontinuated amphotericin or flucytosine due to toxicity was 20% (16/77) at 2 weeks. In addition, in-hospital mortality was associated with receiving ≤ 10 days of induction therapy (odds ratio = 4.5, 95% CI 1.2-17.1, P = 0.028) or positive cerebrospinal fluid fungal culture after 2 weeks (odds ratio = 3.8, 95% CI 1.1-13.5, P = 0.035). CONCLUSION: In this "real-world" study, amphotericin plus flucytosine shows low early mortality of patients with HIV-associated cryptococcal meningitis. Early discontinuation due to adverse events was moderate. More effective and safe antifungals are needed in order to improve the outcome of cryptococcal meningitis.
Assuntos
Infecções por HIV , Meningite Criptocócica , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Brasil , Ácido Desoxicólico , Combinação de Medicamentos , Quimioterapia Combinada , Fluconazol/uso terapêutico , Flucitosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Meningite Criptocócica/tratamento farmacológico , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
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.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Antígenos de Fungos/análise , Cryptococcus/imunologia , Imunoensaio/métodos , Meningite Criptocócica/diagnóstico , Adulto , Antígenos de Fungos/imunologia , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
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
Assuntos
Humanos , Masculino , Feminino , Brasil/epidemiologia , Infecções por HTLV-I/transmissão , Infecções Sexualmente TransmissíveisRESUMO
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
Assuntos
Humanos , Polyomavirus , Natalizumab/uso terapêutico , Esclerose Múltipla/tratamento farmacológicoRESUMO
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. J. Med. Virol. 89:528-534, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos
Vírus BK/isolamento & purificação , Fatores Imunológicos/administração & dosagem , Esclerose Múltipla/tratamento farmacológico , Natalizumab/administração & dosagem , Infecções por Polyomavirus/virologia , Eliminação de Partículas Virais , Sangue/virologia , Humanos , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla/complicações , Natalizumab/efeitos adversos , Urina/virologiaRESUMO
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.
Assuntos
Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/transmissão , Vírus Linfotrópico T Tipo 1 Humano , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Adulto , Western Blotting , Brasil/epidemiologia , Coinfecção/epidemiologia , Coinfecção/virologia , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Infecções por HTLV-I/virologia , Heterossexualidade , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Vírus Linfotrópico T Tipo 2 Humano , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Provírus/genética , Fatores de Risco , Parceiros Sexuais , Doenças Virais Sexualmente Transmissíveis/transmissão , Cônjuges , Carga Viral , Adulto JovemRESUMO
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.