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.

Acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome: prevalence, main characteristics, and outcomes in a Brazilian center / Síndrome inflamatória de reconstituição imune da leucoencefalopatia multifocal progressiva associada à síndrome da imunodeficiência adquirida: prevalência, principais características e desfecho em um hospital brasileiro

Abstract 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.

Resumo 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 (27-50) 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 (30-70) 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.

Subacute Cognitive Impairment in Individuals With Mild and Moderate COVID-19: A Case Series.

Background: Previous reported neurologic sequelae associated with SARS-CoV-2 infection have mainly been confined to hospital-based patients in which viral detection was restricted to nasal/throat swabs or to IgM/IgG peripheral blood serology. Here we describe seven cases from Brazil of outpatients with previous mild or moderate COVID-19 who developed subacute cognitive disturbances. Methods: From June 1 to August 15, 2020, seven individuals 18 to 60 years old, with confirmed mild/moderate COVID-19 and findings consistent with encephalopathy who were observed >7 days after respiratory symptom initiation, were screened for cognitive dysfunction. Paired sera and CSF were tested for SARS-CoV-2 (IgA, IgG ELISA, and RT-PCR). Serum and intrathecal antibody dynamics were evaluated with oligoclonal bands and IgG index. Cognitive dysfunction was assessed by the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Clock Drawing Test (CDT). Results: All but one of our patients were female, and the mean age was 42.6 years. Neurologic symptoms were first reported a median of 16 days (IQR 15-33) after initial COVID-19 symptoms. All patients had headache and altered behavior. Cognitive dysfunction was observed mainly in phonemic verbal fluency (MoCA) with a median of six words/min (IQR 5.25-10.75) and altered visuospatial construction with a median of four points (IQR 4-9) (CDT). CSF pleocytosis was not detected, and only one patient was positive for SARS-Co Conclusions: A subacute cognitive syndrome suggestive of SARS-CoV-2-initiated damage to cortico-subcortical associative pathways that could not be attributed solely to inflammation and hypoxia was present in seven individuals with mild/moderate COVID-19.

Air pollution and its impact on the concentration of airborne fungi in the megacity of São Paulo, Brazil.

In the context of megacities in an urban environment, air quality is an important issue, due to the direct correlation to population's health. The biomonitoring of pollutants can indicate subtle environmental alterations, for that, anemophilous fungi can be monitored for changes in atmospheric conditions related to pollution. In the present study, the concentration of fungi and bacteria in the atmosphere was measured during a specific vehicle fleet reduction in the city of São Paulo, Brazil, from May 24 to 30, 2018, using impactor air samplers. The number of isolated developed colonies was related to atmospheric conditions and the concentration of other air pollutants constantly monitored. Aspergillus, Curvularia, Penicillium, Neurospora, Rhizopus and Trichoderma were identified. The number of colony-forming units increased by approximately 80% during the sampling period in response to environmental changes favored by the fleet reduction. This result implies the relation between fuel emissions, concentration of atmospheric pollutants, and the presence of viable fungal spores in the urban environment, which highlights the importance of combined public policies for air quality in large cities.

Cognitive assessment in patients with Hepatitis C submitted to treatment with Sofosbuvir and Simeprevir or Daclatasvir.

BACKGROUND: Hepatitis C can be defined as an infectious disease that develops an inflammatory activity, which may cause an impairment in the central nervous system, may cause cognitive impairments and symptoms of depression. OBJECTIVE: The objective of this study was to verify the cognitive performance of patients with chronic hepatitis C before and after treatment with simeprevir, sofosbuvir, and daclatasvir. METHODS: A prospective study was carried out in three stages: before, right after treatment, and six months after. Fifty-eight patients under clinical follow-up were evaluated at the Emílio Ribas Infectology Institute, in São Paulo, Brazil. The following instruments were used: sociodemographic questionnaire, Lawton's Scale, Beck's Depression Inventory, and a battery of neuropsychological tests that evaluated: intellectual function, memory, attention, executive function, and motor and processing speed). For statistical analysis, the analyses described (mean, frequency, and standard deviation), chi-square, and ANOVA were used. RESULTS: Most of the participants were male (n=30, 51.7%), with a mean of 58.23±8.79 years, mean schooling of 9.75±4.43 years. Comparing the results of neuropsychological evaluations (before, just after completion of drugs, and six months), a significant improvement was observed in relation to the acquisition of new knowledge (p=0.03), late visual memory (p=0.01), and tendency towards alternate attention (p=0.07). CONCLUSION: The treatment of the hepatitis C virus improved cognitive performance, especially in relation to memory.

Cognitive assessment in patients with Hepatitis C submitted to treatment with Sofosbuvir and Simeprevir or Daclatasvir

BACKGROUND: Hepatitis C can be defined as an infectious disease that develops an inflammatory activity, which may cause an impairment in the central nervous system, may cause cognitive impairments and symptoms of depression. OBJECTIVE: The objective of this study was to verify the cognitive performance of patients with chronic hepatitis C before and after treatment with simeprevir, sofosbuvir, and daclatasvir. METHODS: A prospective study was carried out in three stages: before, right after treatment, and six months after. Fifty-eight patients under clinical follow-up were evaluated at the Emílio Ribas Infectology Institute, in São Paulo, Brazil. The following instruments were used: sociodemographic questionnaire, Lawton's Scale, Beck's Depression Inventory, and a battery of neuropsychological tests that evaluated: intellectual function, memory, attention, executive function, and motor and processing speed). For statistical analysis, the analyses described (mean, frequency, and standard deviation), chi-square, and ANOVA were used. RESULTS: Most of the participants were male (n=30, 51.7%), with a mean of 58.23±8.79 years, mean schooling of 9.75±4.43 years. Comparing the results of neuropsychological evaluations (before, just after completion of drugs, and six months), a significant improvement was observed in relation to the acquisition of new knowledge (p=0.03), late visual memory (p=0.01), and tendency towards alternate attention (p=0.07). CONCLUSION: The treatment of the hepatitis C virus improved cognitive performance, especially in relation to memory

INTRODUÇÃO: A hepatite C pode ser definida como uma doença infecciosa, que se desenvolve por uma atividade inflamatória, que pode gerar um comprometimento no Sistema Nervoso Central, podendo ocasionar prejuízos cognitivos e sintomas de depressão. OBJETIVO: O objetivo deste estudo foi verificar o desempenho cognitivo de pacientes com hepatite C crônica antes e após o tratamento com simeprevir, sofosbuvir e daclatasvir. MÉTODOS: Foi realizado um estudo prospectivo em três etapas: antes, logo após o tratamento e seis meses depois. Foram avaliados 58 pacientes em acompanhamento clínico no Instituto de Infectologia Emílio Ribas, em São Paulo, Brasil. Foram utilizados os seguintes instrumentos: questionário sociodemográfico, Escala de Lawton, Inventário de Depressão de Beck e uma bateria de testes neuropsicológicos que avaliaram: função intelectual, memória, atenção, função executiva e velocidade motora e de processamento). Para análise estatística, foram utilizadas as análises descritas (média, frequência e desvio padrão), qui-quadrado e ANOVA. RESULTADOS: A maioria dos participantes era do sexo masculino (n=30, 51,7%), com média de 58,23±8,79 anos, escolaridade média de 9,75±4,43 anos. Comparando os resultados das avaliações neuropsicológicas (antes, logo após a finalização dos medicamentos e seis meses), observou-se melhora significativa em relação à aquisição de novos conhecimentos (p=0,03), memória visual tardia (p=0,01) e tendência em relação a atenção alternada (p=0,07). CONCLUSÃO: O tratamento do vírus da hepatite C melhorou o desempenho cognitivo, principalmente em relação à memória

The reasons to include the serology of human T-lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) in the clinical follow-up of patients with viral hepatitis B and C in Brazil.

BACKGROUND: The WHO established targets for 2030 to globally reduce new viral hepatitis B and C infections by 90% and deaths by 65% and recommends searching for coinfections that increase the progression of chronic liver infections towards cirrhosis and hepatocellular carcinoma. AIMS AND METHODOLOGY: This study aimed to add information concerning the influence of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) infections in hepatitis B and C, since in Brazil, these human retroviruses are endemic but neglected. Serum samples from 1,910 patients with hepatitis B and 1,315 with hepatitis C from São Paulo, southeast Brazil, that were previously tested and grouped for HIV and HTLV-1/-2 coinfections were analyzed for hepatitis B virus (HBV) and hepatitis C virus (HCV) loads measurements and subsequent clearance using data from laboratory records. KEY RESULTS: Briefly, the lowest HBV viral load (VL) was detected in HBV/HTLV-2 coinfected patients, regardless of whether they were infected with HIV (all comparisons p<0.05). In contrast, higher HCV VL was detected in HCV/HIV, HCV/HIV/HTLV-1/-2 coinfected patients (all p<0.05), and the lowest HCV VL was detected in HCV/HTLV-2 coinfected patients. Curiously, 61.1% of the patients with HBV/HTLV-2 coinfection had an undetectable HBV VL at the beginning of the study versus 21.4% in the patients with HBV/HTLV-1 coinfection. Although the percentages of undetectable HCV loads in HCV/HTLV-1 and HCV/HTLV-2 coinfected patients were quite similar, during follow-up, more HCV clearance was detected in patients with HCV/HTLV-2 coinfection [OR 2.65; 95% IC (1.17-5.99)]. MAJOR CONCLUSIONS: HTLV-2 positively impacts HBV and HCV viral loads and HCV clearance, while HIV and/or HTLV-1 negatively impacts HCV viral load. Thus, the search for HTLV-1/-2 in viral hepatitis B and C infected patients has virological prognostic value, which is a strong reason to suggest including HTLV serology in the follow-up of patients.

The reasons to include the serology of human T-lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) in the clinical follow-up of patients with viral hepatitis B and C in Brazil

BACKGROUND: The WHO established targets for 2030 to globally reduce new viral hepatitis B and C infections by 90% and deaths by 65% and recommends searching for coinfections that increase the progression of chronic liver infections towards cirrhosis and hepatocellular carcinoma. AIMS AND METHODOLOGY: This study aimed to add information concerning the influence of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) infections in hepatitis B and C, since in Brazil, these human retroviruses are endemic but neglected. Serum samples from 1,910 patients with hepatitis B and 1,315 with hepatitis C from São Paulo, southeast Brazil, that were previously tested and grouped for HIV and HTLV-1/-2 coinfections were analyzed for hepatitis B virus (HBV) and hepatitis C virus (HCV) loads measurements and subsequent clearance using data from laboratory records. KEY RESULTS: Briefly, the lowest HBV viral load (VL) was detected in HBV/HTLV-2 coinfected patients, regardless of whether they were infected with HIV (all comparisons p<0.05). In contrast, higher HCV VL was detected in HCV/HIV, HCV/HIV/HTLV-1/-2 coinfected patients (all p<0.05), and the lowest HCV VL was detected in HCV/HTLV-2 coinfected patients. Curiously, 61.1% of the patients with HBV/HTLV-2 coinfection had an undetectable HBV VL at the beginning of the study versus 21.4% in the patients with HBV/HTLV-1 coinfection. Although the percentages of undetectable HCV loads in HCV/HTLV-1 and HCV/HTLV-2 coinfected patients were quite similar, during follow-up, more HCV clearance was detected in patients with HCV/HTLV-2 coinfection [OR 2.65; 95% IC (1.17­5.99)]. MAJOR CONCLUSIONS: HTLV-2 positively impacts HBV and HCV viral loads and HCV clearance, while HIV and/or HTLV-1 negatively impacts HCV viral load. Thus, the search for HTLV-1/-2 in viral hepatitis B and C infected patients has virological prognostic value, which is a strong reason to suggest including HTLV serology in the follow-up of patients

Neuropsychological Assessment of 412 HIV-Infected Individuals in São Paulo, Brazil.

HIV-associated neurocognitive disorders (HAND) remain frequent even among individuals receiving combined antiretroviral therapy (cART). In addition, HAND may adversely affect the quality of life and adherence to cART. There is scarce epidemiological information about HAND in Latin America. This cross-sectional study recruited HIV-infected patients from a tertiary teaching institution in São Paulo, Brazil, between May 2013 and February 2015. The patients were adults with at least 4 years of education and patients with current neurological or psychiatric diseases were excluded. HAND remain frequent even among individuals receiving cART, use of psychoactive substance, or inability to understand the content for neuropsychological evaluation. We used standardized tools to evaluate depression, use of psychoactive substances, and daily life activities, and we performed a comprehensive neuropsychological examination. HAND was classified using the Frascati criteria. Prevalence of HAND was estimated, and an associated variable of symptomatic HAND was identified by logistic regression. Four-hundred twelve HIV-infected patients were included [male: 281 (68%), mean age of 45.3 years]. Most of them [n = 340 (83.7%)] had an undetectable viral load. The prevalence of HAND was 73.6% (n = 303): 210 (50.9%) had asymptomatic neurocognitive involvement (ANI), 67 (16.2%) had mild neurocognitive disorder (MND), and 26 (6.3%) had HIV-associated dementia (HAD). The univariate logistic regression analysis showed that female gender, age older than 50 years, <11 years of schooling, CD4 count below 200 cells/mm3, presence of previous illnesses (e.g., diabetes, hypertension), opportunistic disease history, and a Beck Depression Inventory (BDI) score between 13 and 19 points were factors associated with symptomatic HAND (MND and HAD). However, a BDI score between 13 and 19 points was the single independent variable associated with symptomatic HAND. HAND was highly prevalent in São Paulo, Brazil, and ANI was the more frequent category of HAND. However, 22.5% of participants had symptomatic HAND. This finding constitutes a challenge in clinical practice. A BDI score between 13 and 19 points was the single independent variable associated with symptomatic HAND.

Neuropsychological Assessment of 412 HIV-Infected Individuals in Sao Paulo, Brazil

HIV-associated neurocognitive disorders (HAND) remain frequent even among individuals receiving combined antiretroviral therapy (cART). In addition, HAND may adversely affect the quality of life and adherence to cART. There is scarce epidemiological information about HAND in Latin America. This cross-sectional study recruited HIV-infected patients from a tertiary teaching institution in São Paulo, Brazil, between May 2013 and February 2015. The patients were adults with at least 4 years of education and patients with current neurological or psychiatric diseases were excluded. HAND remain frequent even among individuals receiving cART, use of psychoactive substance, or inability to understand the content for neuropsychological evaluation. We used standardized tools to evaluate depression, use of psychoactive substances, and daily life activities, and we performed a comprehensive neuropsychological examination. HAND was classified using the Frascati criteria. Prevalence of HAND was estimated, and an associated variable of symptomatic HAND was identified by logistic regression. Four-hundred twelve HIV-infected patients were included [male: 281 (68%), mean age of 45.3 years]. Most of them [n = 340 (83.7%)] had an undetectable viral load. The prevalence of HAND was 73.6% (n = 303): 210 (50.9%) had asymptomatic neurocognitive involvement (ANI), 67 (16.2%) had mild neurocognitive disorder (MND), and 26 (6.3%) had HIV-associated dementia (HAD). The univariate logistic regression analysis showed that female gender, age older than 50 years, <11 years of schooling, CD4 count below 200 cells/mm3, presence of previous illnesses (e.g., diabetes, hypertension), opportunistic disease history, and a Beck Depression Inventory (BDI) score between 13 and 19 points were factors associated with symptomatic HAND (MND and HAD). However, a BDI score between 13 and 19 points was the single independent variable associated with symptomatic HAND. HAND was highly prevalent in São Paulo, Brazil, and ANI was the more frequent category of HAND. However, 22.5% of participants had symptomatic HAND. This finding constitutes a challenge in clinical practice. A BDI score between 13 and 19 points was the single independent variable associated with symptomatic HAND