Characteristics, mortality, associated variables with death, and therapeutic response among HIV-positive, solid organ transplant (SOT), and non-HIV-positive/non-transplant (NHNT) patients with cryptococcosis: First multicenter cohort study in Brazil.

Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. A total of 384 patients were included; the median age was 39 years and 283 (73.7%) were men. In all, 304 HIV-positive were hosts (79.2%), 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplant (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). A total of 271 (70.6%) patients were discharged and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional amphotericin B (AMB) mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Most patients who died belong to the CNS cryptococcosis category (83/113; 73.4%) when compared with the others (P = .017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .008 and OR, 1.84; 95% CI, 1.01-3.53; P = .048, respectively). Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.

This multicenter cohort study included 384 hospitalized individuals with cryptococcosis in Brazil. Most individuals were men (74%), HIV-positive (79%), had central nervous system involvement (82%), and received conventional amphotericin plus fluconazole (84%). In-hospital mortality was high (29%).

Early clinical and microbiological predictors of outcome in hospitalized patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis causes high mortality in immunocompromised and immunocompetent patients. The objective of this study was to identify early predictors of clinical outcome, available at the first days of hospitalization, in patients with cryptococcal meningitis in a tertiary center in Brazil. METHODS: Ninety-six cases of cryptococcal meningitis with clinical, epidemiological and laboratory data, and identification and antifungal susceptibility of the strains were analyzed. Quantitative CSF yeast counts were performed by direct microscopic exam with a Fuchs-Rosenthal cell counting chamber using an institutional protocol. Univariable and multiple analyses using logistic regression were performed to identify predictors, available at the beginning of hospitalization, of in-hospital mortality. Moreover, we performed a secondary analysis for a composite outcome defined by hospital mortality and intensive care unit transfer. RESULTS: The species and the antifungal susceptibility were not associated with the outcomes evaluated. The variables significantly associated with the mortality were age (OR = 1.08, 95% CI 1.02-1.15), the cerebrospinal fluid (CSF) yeasts count (OR = 1.65, 95% CI 1.20-2.27), systemic arterial hypertension (OR = 22.63, 95% CI 1.64-312.91) and neurological impairment identified by computed tomography (OR = 41.73, 95% CI 3.10-561.65). At the secondary analysis, CSF yeast count was also associated with the composite outcome, in addition to the culture of Cryptococcus spp. from bloodstream and cerebral toxoplasmosis. The associations were consistent with survival models evaluated. CONCLUSIONS: Age and CSF yeast count were independently associated with in-hospital mortality of patients with cryptococcal meningitis but Cryptococcus species identification and antifungal susceptibility were not associated with the outcomes. Quantitative CSF yeast counts used in this study can be evaluated and implemented in other low and middle-income settings.

High prevalence of Cryptococcal antigenemia using a finger-prick lateral flow assay in individuals with advanced HIV disease in Santarém Municipality, Brazilian Amazon Basin.

There is scarce information about HIV-related cryptococcosis in the Brazilian Amazon basin where laboratory infrastructure is limited. The serum cryptococcal antigen (CrAg) lateral flow assay (LFA) has simplified diagnosis of cryptococcosis and is recommended for screening in advanced HIV disease. We evaluated the prevalence of cryptococcal antigenemia using finger-prick CrAg LFA in the Brazilian Amazon basin. We enrolled a prospective cohort of outpatients and hospitalized individuals with advanced HIV disease at two centers in Santarém Municipality, Northern Brazil. All individuals were > 18 years old with advanced HIV disease, regardless of antiretroviral therapy (ART) status and with no prior or current history of confirmed cryptococcal meningitis. We tested CrAg LFA on finger-prick whole blood using an exact volume transfer pipette. From August 2018 to October 2019, 104 individuals were enrolled (outpatients 62 [60%] and hospitalized 42 [40%]). Median age was 38 years (interquartile range [IQR] 30-46), and 84 (81%) were male. Sixty-five (63%) individuals were ART-naïve. Prevalence of finger-prick CrAg LFA-positive was 10.6%; 95% CI, 5.4 to 18.1%. Prevalence of finger-prick CrAg LFA-positive among individuals without neurological symptoms was 6.0%; 95% CI, 1.7-14.6%. The number needed to test to detect one CrAg-positive individual was 9.4 persons (95% CI, 5.5-18.5). Prevalence of cryptococcal antigenemia using finger-prick whole blood CrAg LFA was high. Point-of-care approach was important for the diagnosis and screening of cryptococcosis in resource-limited settings. Screening and preemptive therapy strategy should be urgently implemented in individuals with advanced HIV disease in the Brazilian Amazon basin.

This prospective cohort study was carried-out in the Brazilian Amazon basin. We used a cryptococcal rapid test in patients with AIDS. We included 104 participants, and 11 (10.6%) of them had positive results showing a high prevalence of cryptococcal antigenemia.

Plasma extracellular microRNAs are related to AIDS/cerebral toxoplasmosis co-infection.

This study investigated the potential of five miRNA candidates for cerebral toxoplasmosis/HIV co-infection (CT/HIV) biomarkers. miR-155-5p, miR-146a-5p, miR-21-5p, miR-125b-5p and miR-29c-3p were tested in 79 plasma divided into groups: 32 CT/HIV patients; 27 individuals with asymptomatic toxoplasmosis (AT); and 20 individuals seronegative for toxoplasmosis (NC). From each was collected peripheral blood/EDTA for laboratory diagnosis. Blood cells for DNA extractions (molecular diagnosis), plasma for RNA extractions (gene expression) and ELISA (serological diagnosis). miRNA expression was performed by qPCR, and values were expressed in Relative Quantification (RQ). Among the five miRNAs, miR-21-5p and miR-146a-5p were up-expressed in CT/HIV group when compared with AT and NC groups. RQ means for miR-21-5p and miR-146a-5p in CT/HIV group were 3.829 and 2.500, while in AT group, were 1.815 and 1.661, respectively. Differences between 3 groups were statistically significant (Kruskal-Wallis ANOVA test), as well as CT/HIV and AT groups (Mann-Whitney test). Plasma of CT/HIV and AT groups expressed similar levels of miR-29c-3p, miR-155-5p and miR-125b-5p. As NC group was different of CT/HIV and AT groups, differences between three groups were statistically significant (Kruskal-Wallis ANOVA test). No difference was shown between CT/HIV and AT groups (Mann-Whitney test). These results suggest the host miRNAs modulation by Toxoplasma gondii.

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. J. Med. Virol. 89:528-534, 2017. © 2016 Wiley Periodicals, Inc.

Genotyping of Toxoplasma gondii: DNA extraction from formalin-fixed paraffin-embedded autopsy tissues from AIDS patients who died by severe disseminated toxoplasmosis.

This study investigated the genetic features of Toxoplasma gondii isolated directly in autopsies of HIV-infected patients who died with severe disseminated toxoplasmosis. This retrospective analysis was conducted in a cohort of 15 HIV-infected patients with clinical and laboratory data. They had previous cerebral toxoplasmosis at least 6 months before the disseminated toxoplasmosis episode. The hypothesis was that they were infected with highly virulent parasites due to the condition in which they died. T. gondii genotyping was done directly in DNA extracted from 30 autopsy brain and lung samples (2 per patient) and mutilocus PCR-RFLP genotyping was done using 12 molecular markers. The 30 clinical samples were genotyped successfully in 8 or more loci and six suggestive genotypes were identified. One of them was Toxo DB #11, previously identified in different domestic animals and virulent in experimental animals. The other five suggestive genotypes identified in 14 patients were not described. TgHuDis1 was the most frequent and was determined in 8 patients. TgHuDis3 and TgHuDis5 were identified in two patients each. TgHuDis2 and TgHuDis4 have been identified in one patient each. These suggestive genotypes could be considered as virulent, since they caused severe tissue damage and had similar characteristics as Toxo # DB 11.

High frequency of dolutegravir resistance in patients failing a raltegravir-containing salvage regimen.

OBJECTIVES: Dolutegravir is a second-generation integrase strand transfer inhibitor (InSTI) that has been recently approved by the FDA to treat antiretroviral therapy-naive as well as treatment-experienced HIV-infected individuals, including those already exposed to the first-generation InSTI. Despite having a different mutational profile, some cross-resistance mutations may influence its susceptibility. The aim of this study was to evaluate the impact of a raltegravir-containing salvage regimen on dolutegravir activity. PATIENTS AND METHODS: Blood samples of 92 HIV-infected individuals with virological failure (two or more viral loads >50 copies/mL after 6 months of treatment) using raltegravir with optimized background therapy were sequenced and evaluated according to the Stanford University HIV Drug Resistance Database algorithm. RESULTS: Among the 92 patients analysed, 32 (35%) showed resistance to dolutegravir, in most cases associated with the combination of Q148H/R/K with G140S/A mutations. At genotyping, patients with resistance to dolutegravir had viral load values closer to the highest previously documented viral load. CONCLUSIONS: Changes in viraemia during virological failure may indicate the evolution of raltegravir resistance and may predict the emergence of secondary mutations that are associated with a decrease in dolutegravir susceptibility. Early discontinuation of raltegravir from failing regimens might favour subsequent salvage with dolutegravir, but further studies are necessary to evaluate this issue.

Calcified cerebral toxoplasmosis associated with recurrent perilesional edema causing neurological manifestations in an HIV-infected individual: case report with a decade-long follow-up.

Four cases of people living with HIV/AIDS (PLWHA) with calcified cerebral toxoplasmosis associated with perilesional edema causing a single episode of neurological manifestations have recently been reported. Here, we describe the first detailed description of perilesional edema associated with calcified cerebral toxoplasmosis causing three episodes of neurological manifestations in a PLWHA, including seizures in two of them. These recurrences occurred over approximately a decade. Throughout this period, the patient showed immunological and virological control of the HIV infection, while using antiretroviral therapy regularly. This case broadens the spectrum of an emerging presentation of calcified cerebral toxoplasmosis, mimicking a well-described finding of neurocysticercosis in immunocompetent hosts.

AIDS-related gastrointestinal cytomegalovirus end-organ disease: A retrospective cohort study at a tertiary center in São Paulo, Brazil.

BACKGROUND: Current information about AIDS-related gastrointestinal cytomegalovirus end-organ disease (CMV-EOD) is scarce. The objectives of this study were to identify the prevalence and main features of gastrointestinal CMV-EOD in patients with advanced HIV disease. METHODS: Retrospective cohort study carried-out at a tertiary-care center in São Paulo, Brazil, from January to December 2019. We included hospitalized people living with HIV with gastrointestinal CMV-EOD, CD4 + count ≤100 cells/µL, and ≥ one quantitative detection of CMV DNA in plasma. RESULTS: Ten (3.8%) of 261 cases had gastrointestinal CMV-EOD. Nine (90%) cases were men, age median (IQR) was 44 (38-54) years, and CD4 + cell count median (IQR) was 6 (7-39) cells/µL. The 10 cases had positive quantitative detection of CMV DNA in plasma with median (IQR) of 572 (103-2 981) IU/mL. The main presenting condition was esophagitis (n = 7, 2.7% cases). Eight (80%) cases received anti-CMV treatment, and one case died due to nosocomial pneumonia. CONCLUSIONS: The prevalence of gastrointestinal CMV-EOD was 3.8%, similar to described in pre-combined antiretroviral therapy studies. Among cases with gastrointestinal CMV-EOD, all had positive quantitative detection of CMV-DNA in plasma but the values varied; esophagitis was the most common presentation, and all but one were discharged from the hospital.

Effectiveness, Tolerability, and Safety of Different Amphotericin B Formulations in Invasive Fungal Infections: A Multicenter, Retrospective, Observational Study.

PURPOSE: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. METHODS: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. FINDINGS: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. IMPLICATIONS: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.

Cerebral toxoplasmosis with neurological co-infection in people living with AIDS/HIV: results of a prospective cohort in São Paulo, Brazil.

BACKGROUND: Concomitant neurological diseases in people living with HIV/AIDS (PLWHA) is a challenging subject that has been insufficiently evaluated by prospective clinical studies. The goal of the present study was to identify the clinical characteristics and outcomes of PLWHA with cerebral toxoplasmosis and neurological co-infections. METHODS: We conducted a prospective observational cohort study at a tertiary teaching center in São Paulo, Brazil, from January to July 2017. Hospitalized PLWHA aged ≥ 18 years with cerebral toxoplasmosis were consecutively enrolled. A standardized neurological examination was performed at admission and weekly until discharge or death. Diagnosis and treatment followed institutional routines; neuroradiology, molecular diagnosis, neurosurgery, and the intensive care unit (ICU) were available. The main outcomes were neurological coinfections and in-hospital death. RESULTS: We included 44 (4.3%) cases among 1,032 hospitalized patients. The median age was 44 (interquartile range [IQR]: 35-50) years, and 50% (n = 22) of the patients were male. The median CD4+ T lymphocyte count was of 50 (IQR: 15-94) cells/mm3. Multiple lesions on computed tomography were present in 59% of the cases. Neurological coinfections were diagnosed in 20% (n = 9) of the cases, and cytomegalovirus was the most common etiology (encephalitis: n = 3; polyradiculopathy: n = 2). Longer hospital stays (30 versus 62 days; p = 0.021) and a higher rate of ICU admissions (14% versus 44%; p = 0.045) were observed among PLWHA with neurological coinfections in comparison to those without them. The rate of in-hospital mortality was of 13.6% (n = 6) (coinfection group: 33%; no coinfection group: 8.6%; p = 0.054). CONCLUSION: Neurological c-infections were common among PLWHA with cerebral toxoplasmosis, and cytomegalovirus was the main copathogen. The group of PLWHA with neurological co-infections underwent longer hospital stays and more frequent intensive care unit admissions. Additionally, this group of patients tended to have higher in-hospital mortality rate.

ANTECEDENTES: Coinfecções neurológicas em pessoas que vivem com HIV/AIDS (PVHA) é um tema que não foi suficientemente avaliado em estudos clínicos prospectivos. Nosso objetivo foi identificar as características clínicas e os desfechos de PVHA com toxoplasmose cerebral e coinfecções neurológicas. MéTODOS: Estudo prospectivo de coorte observacional conduzido em um centro de ensino terciário de São Paulo, Brasil, entre janeiro e julho de 2017. Foram incluídos consecutivamente PVHA internadas com ≥ 18 anos e toxoplasmose cerebral. Realizou-se exame neurológico padronizado na admissão e semanalmente até a alta/óbito. Tanto o diagnóstico quanto o tratamento seguiram a rotina institucional; neurorradiologia, diagnóstico molecular, neurocirurgia e Unidade de Terapia Intensiva (UTI) estavam disponíveis. Os principais desfechos foram coinfecções neurológicas e óbitos hospitalares. RESULTADOS: Incluímos 44 (4,3%) casos entre 1.032 pacientes internados. A idade mediana foi de 44 (intervalo interquartil [IIQ]: : 35­50) anos, e 50% (n = 22) dos pacientes eram do sexo masculino. A contagem mediana de linfócitos T CD4+ foi de 50 (IIQ:15­94) células/mm3. Múltiplas lesões na tomografia computadorizada foram observadas em 59% dos casos. Coinfecções neurológicas foram diagnosticadas em 20% (n = 9) dos casos, sendo o citomegalovírus a etiologia mais comum (encefalite: n = 3; polirradiculopatia: n = 2). Observou-se maior tempo de internação (26 versus 62 dias; p = 0,021) e uma taxa mais alta de admissão à UTI (14% versus 44%; p = 0,045) em PVHA com coinfecções neurológicas em comparação àquelas sem coinfecção. A mortalidade intra-hospitalar foi de 13,6% (n = 6) (grupo com coinfecções: 33% versus grupo sem coinfecção: 8,6%; p = 0,054). CONCLUSãO: Coinfecções neurológicas foram comuns em PVHA com toxoplasmose cerebral, sendo o citomegalovírus o principal copatógeno. O grupo de PVHA com coinfecções neurológicas apresentou maior tempo de internação, maior taxa de internações na UTI, e tendência a maior taxa de mortalidade intra-hospitalar.

Lumbar puncture for neurosyphilis investigation in asymptomatic patients with HIV-syphilis coinfection: a cross-sectional study among infectious disease specialists.

BACKGROUND: Syphilis is a major public health issue worldwide. In people living with human immunodeficiency virus (PLHIV), there are higher incidences of both syphilis and neurosyphilis. The criteria for referring PLHIV with syphilis for lumbar puncture is controversial, and the diagnosis of neurosyphilis is challenging. OBJECTIVE: To describe the knowledge, attitudes, and practices of infectious disease specialists and residents in the context of care for asymptomatic HIV-syphilis coinfection using close-ended questions and case vignettes. DESIGN AND SETTING: Cross-sectional study conducted in three public health institutions in São Paulo (SP), Brazil. METHODS: In this cross-sectional study, we invited infectious disease specialists and residents at three academic healthcare institutions to answer a self-completion questionnaire available online or in paper form. RESULTS: Of 98 participants, only 23.5% provided answers that were in line with the current Brazilian recommendation. Most participants believed that the criteria for lumbar puncture should be extended for people living with HIV with low CD4+ cell counts (52.0%); in addition, participants also believed that late latent syphilis (29.6%) and Venereal Disease Research Laboratory (VDRL) titers ≥ 1:32 (22.4%) should be conditions for lumbar puncture in PLHIV with no neurologic symptoms. CONCLUSION: This study highlights heterogeneities in the clinical management of HIV-syphilis coinfection. Most infectious disease specialists still consider syphilis stage, VDRL titers and CD4+ cell counts as important parameters when deciding which patients need lumbar puncture for investigating neurosyphilis.

Cytomegalovirus retinitis in hospitalized people living with HIV in the late antiretroviral therapy era in São Paulo, Brazil.

BACKGROUND: There is scarce information on AIDS-related cytomegalovirus (CMV) retinitis in middle-income countries. The objectives of this study were to identify the prevalence of active CMV retinitis in severely immunosuppressed people living with HIV (PLWHIV) and to describe its main features. METHODS: This retrospective cohort study was carried out at a tertiary center in São Paulo, Brazil. We included hospitalized adults PLWHIV with CD4 count ≤100 cells/µL, ≥ one quantitation of CMV DNA in plasma, and indirect ophthalmoscopy evaluation. RESULTS: Thirty-eight (21.6%) of 176 participants had at least an ophthalmoscopy diagnosis and only 3 (1.7%) individuals presented active CMV retinitis. All these participants were male, and retinitis was asymptomatic in 2 cases. Two participants had extraocular end-organ CMV disease and detectable CMV DNA in plasma. CONCLUSIONS: These results show a low prevalence of active CMV retinitis in the evaluated population. However, 2 of 3 participants had asymptomatic active CMV retinitis and a fifth of participants had at least one ophthalmoscopy diagnosis, suggesting the need for routine ophthalmologic evaluation in hospitalized severely immunosuppressed PLWHIV. The profile of participants with active CMV retinitis was similar to that described in the pre-ART era and quantitation of CMV DNA in plasma was variable.

AIDS-related cytomegalovirus encephalitis in the late ART era: A retrospective cohort study at a referral center in Brazil.

BACKGROUND: AIDS-related cytomegalovirus (CMV) encephalitis has declined in the combined antiretroviral therapy (ART) era in high-income countries. However, there is scarce information on CMV encephalitis in low- and middle-income countries. The objectives of this study were to identify the prevalence of AIDS-related CMV encephalitis and describe its main features. METHODS: This was a retrospective cohort study carried out at a referral center in São Paulo, Brazil. We included adult people living with HIV/AIDS (PLWHA), hospitalized in 2019, with a CD4 cell count ≤100/mm3 and quantitation CMV DNA results in plasma. Cases with compatible neurological manifestations and detection of CMV DNA by polymerase chain reaction (PCR) in cerebrospinal fluid samples were defined as CMV encephalitis. RESULTS: Among 761 PLWHA hospitalized, 248 (32.5%) cases were included in this study. Prevalence of CMV encephalitis was 2.4% (6/248) among all included cases and 7.7% (6/78) among individuals with neurological opportunistic diseases. The six patients with CMV encephalitis were males and had CD4 cell count <50/mm3. Five (83%) cases had CMV encephalitis as AIDS-defining disease and showed CMV DNA detection by PCR >50,000 UI/mL plasma. All six cases received anti-CMV therapy (ganciclovir, n = 4; ganciclovir plus foscarnet, n = 2) and five were discharged to home. CMV encephalitis was not uncommon among hospitalized PLWHA with neurological opportunistic diseases. CONCLUSIONS: The epidemiological and immunological profile of individuals with CMV encephalitis was similar to that described in the pre-ART era, but in contrast, most cases were treated and discharged from the hospital.

Septic shock, hyperferritinemic syndrome, and multiple organ dysfunction without respiratory failure in a patient with disseminated histoplasmosis and advanced HIV disease.

AIDS-related disseminated histoplasmosis (DH) can cause septic shock and multiorgan dysfunction with mortality rates of up to 80%. A 41-year-old male presented with fever, fatigue, weight loss, disseminated skin lesions, low urine output, and mental confusion. Three weeks before admission, the patient was diagnosed with HIV infection, but antiretroviral therapy (ART) was not initiated. On day 1 of admission, sepsis with multiorgan dysfunction (acute renal failure, metabolic acidosis, hepatic failure, and coagulopathy) was identified. A chest computed tomography showed unspecific findings. Yeasts suggestive of Histoplasma spp. were observed in a routine peripheral blood smear. On day 2, the patient was transferred to the ICU, where his clinical condition progressed with reduced level of consciousness, hyperferritinemia, and refractory septic shock, requiring high doses of vasopressors, corticosteroids, mechanical ventilation, and hemodialysis. Amphotericin B deoxycholate was initiated. On day 3, yeasts suggestive of Histoplasma spp. were observed in the bone marrow. On day 10, ART was initiated. On day 28, samples of peripheral blood and bone marrow cultures revealed Histoplasma spp. The patient stayed in the ICU for 32 days, completing three weeks of intravenous antifungal therapy. After progressive clinical and laboratory improvement, the patient was discharged from the hospital on oral itraconazole, trimethoprim-sulfamethoxazole, and ART. This case highlights the inclusion of DH in the differential diagnosis of patients with advanced HIV disease, septic shock and multiorgan dysfunction but without respiratory failure. In addition, it provides early in-hospital diagnosis and treatment and comprehensive management in the ICU as determining factors for a good outcome.

Acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome: prevalence, main characteristics, and outcomes in a Brazilian center.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) - immune reconstitution inflammatory syndrome (IRIS) in people living with HIV/AIDS (PLWHA) has been rarely described in low- and middle-income countries. OBJECTIVE: To describe the prevalence of PML-IRIS among PLWHA with PML and its main features in a tertiary hospital in Brazil. METHODS: We performed a retrospective cohort study. We included PLWHA with PML-IRIS patients admitted at Instituto de Infectologia Emílio Ribas, São Paulo, Brazil, between 2011 and 2021. We retrieved information on neurological manifestations, neuroimaging findings, treatments, and outcomes. RESULTS: We identified 11 (11.8%) PML-IRIS cases among 93 patients with definite PML. Eight (73%) cases were men and had a median (IQR) age of 41 (27-50) years. Seven (63.6%) patients developed unmasking PML-IRIS and 4 (36.4%) had paradoxical PML-IRIS. The median (IQR) time from initiation of combined antiretroviral therapy (cART) to IRIS diagnosis was 49 (30-70) days. Ten (90.9%) patients received corticosteroids. There were 4 (36%) in-hospital deaths and 3 were associated with hospital-acquired pneumonia. Among the 7 (64%) patients who survived, 5 (71.5%) had sequelae at discharge. One year after the PML-IRIS diagnosis, 6 (54.5%) patients were alive. CONCLUSION: The prevalence of PML-IRIS was 11.8%. Most patients had unmasking PML-IRIS. In-hospital mortality and morbidity were high. One-year survival was similar to that described in some high-income countries.

ANTECEDENTES: A síndrome inflamatória de reconstituição imune (SIRI) da leucoencefalopatia multifocal progressiva (LEMP) em pessoas vivendo com HIV/Aids (PVHA) foi raramente descrita em países de baixa e média renda. OBJETIVO: Descrever a prevalência da SIRI-LEMP- em PVHA com LEMP e suas principais características em um hospital no Brasil. MéTODOS: Foi realizado um estudo de coorte retrospectivo. Incluímos PVHA com SIRI-LEMP admitidos no Instituto de Infectologia Emílio Ribas, São Paulo, Brasil, entre 2011 e 2021. Recuperamos informações sobre manifestações neurológicas, neuroimagem, tratamento e desfecho. RESULTADOS: Identificamos 11 (11,8%) casos de SIRI-LEMP entre 93 pacientes com LEMP definitiva. Oito (73%) casos eram homens e a mediana de idade (amplitude interquartile - AIQ) foi de 41 (27­50) anos. Sete (63,6%) pacientes desenvolveram SIRI-LEMP "desmascarada" e 4 (36,4%) casos apresentaram SIRI-LEMP "paradoxal". A mediana de tempo (AIQ) desde o início da terapia antirretroviral combinada (cART) até o diagnóstico de SIRI foi de 49 (30­70) dias. Dez (90,9%) pacientes receberam corticoide. Houve 4 (36%) óbitos intra-hospitalares e 3 foram associados à pneumonia hospitalar. Dos 7 (64%) pacientes que sobreviveram, 5 (71,5%) ficaram com sequelas na alta. Um ano após o diagnóstico de SIRI-LEMP, 6 (54,5%) pacientes estavam vivos. CONCLUSãO: A prevalência de SIRI-LEMP foi de 11,8%. A maioria dos pacientes apresentava SIRI-LEMP "desmascarada". A mortalidade e morbidade hospitalar foram altas. A sobrevida em 1 ano foi semelhante à descrita em alguns países de alta renda.

Chronic disseminated cryptococcosis without meningeal involvement in a severely immunosuppressed HIV-infected patient successfully treated with fluconazole.

A 43-year-old female with advanced HIV infection presented with two chronic skin lesions. Cutaneous cryptococcosis was confirmed and pulmonary cryptococcosis was suspected. The patient was neurologically asymptomatic and the cerebrospinal fluid cryptococcal antigen lateral flow assay was negative. She received oral fluconazole and had resolution of the skin lesions and significant improvement of the lung lesions. We report a person with AIDS with chronic disseminated cryptococcosis without meningeal involvement successfully treated with oral fluconazole.

Diagnostic and therapeutic approach to chronic meningitis in Brazil: a narrative review.

BACKGROUND: Chronic meningitis (CM) is characterized by neurological symptoms associated with the evidence of cerebrospinal fluid pleocytosis lasting > 4 weeks. Studies on the management of CM in Brazil are scarce. OBJECTIVE: To critically review the literature on CM and propose a rational approach in the Brazilian scenario. METHODS: Narrative literature review discussing the epidemiology, clinical evaluation, basic and advanced diagnostic testing, and empirical and targeted therapy for the most relevant causes of CM. The present review was contextualized with the local experience of the authors. In addition, we propose an algorithm for the management of CM in Brazil. RESULTS: In Brazil, tuberculosis and cryptococcosis are endemic and should always be considered in CM patients. In addition to these diseases, neurosyphilis and other endemic conditions should be included in the differential diagnosis, including neurocysticercosis, Baggio-Yoshinari syndrome, and endemic mycosis. After infectious etiologies, meningeal carcinomatosis and autoimmune diseases should be considered. Unbiased and targeted methods should be used based on availability and clinical and epidemiological data. CONCLUSION: We propose a rational approach to CM in Brazil, considering the epidemiological scenario, systematizing the etiological investigation, and evaluating the timely use of empirical therapies.

ANTECEDENTES: A meningite crônica (MC) é caracterizada por sintomas neurológicos associados à evidência de pleiocitose do líquido cefalorraquidiano por > 4 semanas. Os estudos sobre o manejo da MC no Brasil são escassos. OBJETIVO: Rever criticamente a literatura sobre MC e propor uma abordagem racional no cenário brasileiro. MéTODOS: Revisão da literatura narrativa discutindo a epidemiologia, avaliação clínica, testes diagnósticos básicos e avançados, além da terapia empírica e direcionada para as causas mais relevantes do MC. A presente revisão foi contextualizada com a experiência local dos autores. Além disso, propomos um algoritmo para o manejo da MC no Brasil. RESULTADOS: No Brasil, a tuberculose e a criptococose são endêmicas e devem ser sempre consideradas em pacientes com MC. Além destas doenças, a neurossífilis e outras condições endêmicas devem ser incluídas no diagnóstico diferencial, incluindo: neurocisticercose, síndrome de Baggio-Yoshinari e micoses endêmicas. Após etiologias infecciosas, devem ser consideradas a carcinomatose meningeal e doenças autoimunes sistêmicas. Métodos diagnósticos devem ser utilizados com base na disponibilidade, nos dados clínicos e nos dados epidemiológicos. CONCLUSãO: Propomos uma abordagem racional para a MC no Brasil, considerando o cenário epidemiológico, sistematizando a investigação etiológica e avaliando o uso oportuno de terapias empíricas.

Prevalence of cognitive impairment in HIV patients: vertical and horizontal transmission.

Antiretroviral treatment has significantly increased the survival of patients infected with HIV-1. However, with increased survival, cognitive changes associated with HIV are frequently observed in this population. The clinical manifestations of HIV changes can vary as a result of several aspects, including the virus transmission route. Several studies have pointed out premature neurological changes in vertically infected patients, while the manifestation of cognitive damage in adults may take a longer time. Objective: The aim of this study was to verify the prevalence of cognitive changes in patients with HIV via vertical transmission after the highly active antiretroviral therapy and the cognitive performance of these patients compared to a group of sexually infected patients. Methods: A total of 48 patients were evaluated, 25 with vertical transmission and 23 with sexual transmission, between May 2013 and February 2015 at the Institute of infectology Emilio Ribas. Neuropsychological tests were applied to assess cognitive performance, scales to assess symptoms of anxiety and depression, and sociodemographic questionnaire. Results: The results demonstrate that the frequency of cognitive impairment in vertically transmitted patients was higher than in sexually transmitted patients. Conclusions: These findings suggest that the deleterious effects of the HIV virus on the development of the central nervous system reverberate more strongly than in patients who acquire it after adulthood.

O tratamento antirretroviral tem aumentado significativamente a sobrevida de pacientes contaminados pelo HIV-1. Entretanto, com o aumento da sobrevida, observam-se frequentemente alterações cognitivas associadas ao HIV nessa população. As manifestações clínicas das alterações do HIV podem variar em decorrência de diversos aspectos, entre eles a via de transmissão do vírus. Diversos estudos têm apontado alterações neurológicas prematuras em pacientes contaminados por via vertical, enquanto a manifestação de danos cognitivos em adultos pode levar um tempo maior. Objetivo: O objetivo deste estudo foi verificar a prevalência das alterações cognitivas em pacientes com HIV via transmissão vertical após a era da terapia antirretroviral altamente ativa e o desempenho cognitivo desses pacientes comparado ao de um grupo de pacientes contaminados por via sexual. Métodos: Foram avaliados 48 pacientes, sendo 25 com transmissão vertical e 23 com transmissão sexual no período entre maio de 2013 e fevereiro de 2015, no Instituto de Infectologia Emílio Ribas. Foram aplicados testes neuropsicológicos para avaliar o desempenho cognitivo, escalas para avaliar sintomas de ansiedade e depressão e questionário sociodemográfico. Resultados: Os resultados demonstraram que a frequência de comprometimento cognitivo em pacientes contaminados via transmissão vertical foi maior do que naqueles contaminados via transmissão sexual. Conclusões: Essas descobertas sugerem que os efeitos deletérios do vírus HIV na formação do sistema nervoso central repercutem de forma mais acentuada do que em pacientes que o adquiriram após a vida adulta.