Delirium and pain in patients in the immediate postoperative period of cardiac surgery: prevalence and associated risk factors / Delirium e dor em pacientes no pós-operatório imediato de cirurgia cardíaca: prevalência e fatores de risco associados

ABSTRACT BACKGROUND AND OBJECTIVES: Delirium is an acute mental status change, with fluctuating course and high incidence in cardiac surgery (CS) post-operative (PO) period. Delirium can lead to short and long-term consequences. The aim of this study was to assess the prevalence of delirium and pain and their risk factors on the 1st PO day after CS. METHODS: This was a cross-sectional analytical research. To determine the presence of PO delirium, the Confusion Assessment Method modified for Intensive Care Unit setting (CAM-ICU) and the Richmond Agitation Sedation Scale (RASS) were used. PO pain was analyzed using the Visual Analogue Pain Scale (VAS) and the presence of neuropathic components was analyzed using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale. After bedside analysis, patients were divided into Delirium (D) and Without Delirium (WD) groups. RESULTS: The total number of patients was 79. The prevalence of delirium was 16.5% (95% CI = 9.06 - 26.49%) and the mean number of comorbidities in the preoperative period was a significant risk factor for the occurrence of delirium (D =4.15±2.37 versus WD=2.96±1.78, p: 0.04). Another significant risk factor was the group older than 65 years of age, with the occurrence of delirium 1.45 times higher (PR=1.12-1.88, p: 0.0014). Regarding pain evaluation, 72.15% (95% CI 60.93 - 81.65%) reported it in the 1st PO day. CONCLUSION: The prevalence of delirium was similar to previous studies. The number of previous comorbidities and advanced age were risk factors for delirium. Pain was present predominantly over the sternotomy incision region.

RESUMO JUSTIFICATIVA E OBJETIVOS: Delirium é uma alteração aguda do estado mental, com curso flutuante e alta incidência no pós-operatório (PO) de cirurgia cardíaca (CC). O delirium pode levar a consequências a curto e longo prazo. O objetivo deste estudo foi avaliar a prevalência de delirium e dor e seus fatores de risco no 1º dia PO após CC. MÉTODOS: Trata-se de um estudo transversal analítico. Para determinar delirium no PO, foram utilizados o Confusion Assessment Method modificado para ambiente de Unidade de Terapia Intensiva (CAM-UTI) e a Richmond Agitation Sedation Scale (RASS). A dor PO foi analisada por meio da Escala Analógica Visual (EAV) e a presença de componentes neuropáticos foi analisada por meio da Escala de Avaliação de Sintomas e Sinais Neuropáticos de Leeds (LANSS). Após análise, os pacientes foram divididos nos grupos Delirium (D) e Sem Delirium (SD). RESULTADOS: Foram estudados 79 pacientes. A prevalência de delirium foi de 16,5% (IC 95%=9,06-26,49%) e o número médio de comorbidades no pré-operatório foi um fator de risco significativo para a ocorrência de delirium (D=4,15±2,37 versus SD=2,96±1,78, p: 0,04). Outro fator de risco foi o grupo com mais de 65 anos, com ocorrência de delirium 1,45 vezes maior (RP=1,12-1,88, p: 0,0014). Em relação à avaliação da dor, 72,15% (IC 95% 60,93-81,65%) a relataram no 1º dia PO. CONCLUSÃO: A prevalência de delirium foi semelhante à de estudos anteriores. O número de comorbidades prévias e a idade avançada foram fatores de risco para delirium. A dor estava presente predominantemente na região da incisão da esternotomia.

PREVALENCE OF COMORBIDITIES IN PATIENTS WITH CHAGASIC MEGAESOPHAGUS.

•The study investigated the prevalence of certain comorbidities in patients with Chagas megaoesophagus compared to those without the condition, aiming to determine whether it serves as a protective or risk factor. •In the general group (546 patients), the three most prevalent comorbidities were hypertension (44.3%), dyslipidaemia (17.8%), and heart failure (15.2%). •In the older group (248 patients), similar to that in the general group, the most prevalent comorbidities were hypertension, dyslipidaemia, and heart failure. •The lower prevalence of diabetes mellitus and Alzheimer's disease in the patients with Chagas megaoesophagus suggests the association of enteric nervous system denervation and requires further investigation. Objective - This study aimed to evaluate the prevalence of some epidemiologically important comorbidities in patients with Chagas megaoesophagus in relation to the population without megaoesophagus, and whether this condition would be a protective or a risk factor for the conditions analysed. Methods - This observational descriptive study collected data from the medical records of patients with a previous diagnosis of megaoesophagus (timing: from 2005 to 2020). The patients were divided by age into a general (all ages) and an older group (aged 60 years or more). Associations were searched for four main areas/systems/involvements: cardiovascular, respiratory, endocrine and neurological. Results - The general group included 546 patients and the older group included 248 patients. As for the prevalence of comorbidities in the general group, the three most prevalent diseases were hypertension, with 44.3% (CI95%: 40.21-48.51%); dyslipidaemia, with 17.8% (CI95%: 14.79-21.19%); and heart failure, with 15.2% (CI95%: 12.43-18.45%). Similar to that in the general group, the most prevalent comorbidities in the group of older patients were hypertension, dyslipidaemia, and heart failure. Conclusion - Systemic arterial hypertension, dyslipidaemia, and heart failure were the most prevalent comorbidities in this population. The lower prevalence of diabetes mellitus and Alzheimer's disease suggests the association of enteric nervous system denervation and requires further investigation.

Dual PPRαϒ Agonists for the Management of Dyslipidemia: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Saroglitazar is a novel medication for dyslipidemia, but its specific effects remain unclear. Therefore, we performed a systematic review and meta-analysis to assess the efficacy and safety of saroglitazar for managing dyslipidemia. The PubMed, Scopus, and EMBASE databases were systematically searched for randomized controlled trials (RCTs) comparing 2 and 4 mg of saroglitazar with placebos for treating dyslipidemia. A random-effects model calculated the pooled mean differences for continuous outcomes with 95% confidence intervals. The study included seven RCTs involving 1975 patients. Overall, 340 (31.0%) and 513 (46.8%) participants received 2 and 4 mg of saroglitazar, respectively; 242 (22.11%) received the placebo. The mean ages ranged from 40.2 to 62.6 years, and 436 (39.8%) were women. Compared to the control group, 4 mg of saroglitazar significantly decreased the triglyceride and low-density lipoprotein (LDL) cholesterol levels but did not affect the high-density lipoprotein cholesterol level. Furthermore, the alanine aminotransferase level significantly decreased, the creatine level significantly increased, and body weight did not differ between the groups. Finally, 4 mg of saroglitazar, compared to 2 mg, significantly lowered the triglyceride level. Saroglitazar (4 mg) may be an effective treatment, but safety concerns remain.

Prevalência de comorbidades em pacientes com megaesôfago chagásico / Prevalence of comorbidities in patients with chagasic megaesophagus

ABSTRACT Objective: This study aimed to evaluate the prevalence of some epidemiologically important comorbidities in patients with Chagas megaoesophagus in relation to the population without megaoesophagus, and whether this condition would be a protective or a risk factor for the conditions analysed. Methods: This observational descriptive study collected data from the medical records of patients with a previous diagnosis of megaoesophagus (timing: from 2005 to 2020). The patients were divided by age into a general (all ages) and an older group (aged 60 years or more). Associations were searched for four main areas/systems/involvements: cardiovascular, respiratory, endocrine and neurological. Results: The general group included 546 patients and the older group included 248 patients. As for the prevalence of comorbidities in the general group, the three most prevalent diseases were hypertension, with 44.3% (CI95%: 40.21-48.51%); dyslipidaemia, with 17.8% (CI95%: 14.79-21.19%); and heart failure, with 15.2% (CI95%: 12.43-18.45%). Similar to that in the general group, the most prevalent comorbidities in the group of older patients were hypertension, dyslipidaemia, and heart failure. Conclusion: Systemic arterial hypertension, dyslipidaemia, and heart failure were the most prevalent comorbidities in this population. The lower prevalence of diabetes mellitus and Alzheimer's disease suggests the association of enteric nervous system denervation and requires further investigation.

RESUMO Objetivo: Este estudo teve como objetivo avaliar a prevalência de algumas comorbidades epidemiologicamente importantes em pacientes com megaesôfago chagásico em relação à população sem o megaesôfago e se essa condição seria um fator protetor ou de risco para as condições analisadas. Métodos: Este estudo descritivo observacional coletou dados de prontuários de pacientes com diagnóstico prévio de megaesôfago (período: de 2005 a 2020). Os pacientes foram divididos por idade em um grupo geral (todas as idades) e um grupo idoso (60 anos ou mais). Foram pesquisadas associações para quatro áreas/sistemas/envolvimentos principais: cardiovascular, respiratório, endócrino e neurológico. Resultados: O grupo geral incluiu 546 pacientes e o grupo idosos incluiu 248 pacientes. Quanto à prevalência de comorbidades no grupo geral, as três doenças mais prevalentes foram hipertensão, com 44,3% (IC95%: 40,21-48,51%); dislipidemia, com 17,8% (IC95%: 14,79-21,19%); e insuficiência cardíaca, com 15,2% (IC95%: 12,43-18,45%). Assim como no grupo geral, as comorbidades mais prevalentes no grupo de idosos foram hipertensão, dislipidemia e insuficiência cardíaca. Conclusão: Hipertensão arterial sistêmica, dislipidemia e insuficiência cardíaca foram as comorbidades mais prevalentes nessa população. A menor prevalência de diabetes mellitus e doença de Alzheimer sugere uma associação de denervação do sistema nervoso entérico e requer mais investigação.

Could Cesarean Delivery Help Prevent Mother-to-Child Transmission of Human T-Lymphotropic Virus Type 1?

BACKGROUND: Mother-to-child transmission (MTCT) of human T-lymphotropic virus type 1 (HTLV-1) is an important route of transmission that can cause lifelong infection. There is high morbidity and mortality due to adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy (HAM), and other inflammatory disorders. These conditions develop in nearly 10% of people with HTLV-1 infection, with a higher risk if infection occurs early in life. Identification of risk factors can inform targeted measures to reduce HTLV-1 MTCT. This study aimed to investigate the potential of cesarean delivery to prevent HTLV-1 MTCT. METHODS: We performed a review of the cases of women and their offspring under regular follow-up at the HTLV-1 outpatient clinic at the Institute of Infectious Diseases Emilio Ribas. RESULTS: A total of 177 HTLV-1-infected women and 369 adult offspring were investigated. Overall, 15% of the children were positive for HTLV-1 and 85% were negative. Regarding vertical transmission, we found that a breastfeeding duration of >6 months was associated with MTCT. Moreover, maternal proviral load was not associated with transmission, but high educational level and cesarean delivery were identified as protective factors. CONCLUSIONS: HTLV-1 MTCT was associated with mother's age at delivery of >25 years, low educational level, prolonged breastfeeding, and vaginal delivery.

Is the human T-cell lymphotropic virus type 2 in the process of endogenization into the human genome?

Human T-cell lymphotropic virus type 2 (HTLV-2) infection has been shown to be endemic among intravenous drug users in parts of North America, Europe and Southeast Asia and in a number of Amerindian populations. Despite a 65% genetic similarity and common host humoral response, the human T-cell lymphotropic viruses type 1 (HTLV-1) and 2 display different mechanisms of host interaction and capacity for disease development. While HTLV-1 pathogenicity is well documented, HTLV-2 etiology in human disease is not clearly established. From an evolutionary point of view, its introduction and integration into the germ cell chromosomes of host species could be considered as the final stage of parasitism and evasion from host immunity. The extraordinary abundance of endogenous viral sequences in all vertebrate species genomes, including the hominid family, provides evidence of this invasion. Some of these gene sequences still retain viral characteristics and the ability to replicate and hence are potentially able to elicit responses from the innate and adaptive host immunity, which could result in beneficial or pathogenic effects. Taken together, this data may indicate that HTLV-2 is more likely to progress towards endogenization as has happened to the human endogenous retroviruses millions of years ago. Thus, this intimate association (HTLV-2/human genome) may provide protection from the immune system with better adaptation and low pathogenicity.

Health state utility values in people living with HTLV-1 and in patients with HAM/TSP: The impact of a neglected disease on the quality of life.

BACKGROUND: HTLV-1 is a neglected sexually transmitted infection despite being the cause of disabling neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is no treatment for this infection and public health policies are essential to reduce its transmission. However, there are no data to support adequate cost-effective analysis in this field. The aim of this study was to obtain health state utility values for individuals with HAM/TSP and HTLV-1 asymptomatic carriers (AC). The impact of both states on quality of life (QoL) is described and compared to other diseases. METHODS: A cross-sectional observational study of 141 individuals infected with HTLV-1 (79 with HAM/TSP and 62 AC) from three Brazilian states (Rio de Janeiro, São Paulo and Alagoas) and from the United Kingdom. Participants completed a validated general health questionnaire (EQ-5D, Euroqol) from which country specific health state utility values are generated. Clinical and epidemiological data were collated. PRINCIPAL FINDINGS: Health state utility value for HAM/TSP was 0.2991. QoL for 130 reported clinical conditions ranges from 0.35 to 0.847. 12% reported their quality of life as worse as death. Low QoL was associated with severity rather than duration of disease with a moderate inverse correlation between QoL and Osame's Motor Disability Score (-0.4933) Patients who are wheelchair dependent had lowest QoL whilst those still walking unaided had the highest. AC also reported impaired QoL (0.7121) compared to general population. CONCLUSION: HTLV-1 and its associated neurological disease has a marked impact on QoL. This study provides robust data to support the development of cost-utility analysis of interventions for HTLV-1.

Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load.

Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). METHODS: 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). RESULTS: After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. CONCLUSIONS: We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome.

Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load

Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). METHODS: 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). RESULTS: After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. CONCLUSIONS: We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome

Risk factors associated with HTLV-1 vertical transmission in Brazil: longer breastfeeding, higher maternal proviral load and previous HTLV-1-infected offspring.

HTLV-1 is transmitted primarily either through sexual intercourse or from mother to child. The mother/child pairs were classified as seroconcordant or serodiscordant. We analyzed mother to child transmission (MTCT) according to sociodemographic, clinical and epidemiological characteristics of the mother, child's gender and duration of breastfeeding. Between June 2006 and August 2016 we followed 192 mothers with HTLV-1 infection (mean age 41 years old), resulting in 499 exposed offspring, 288 (57.7%) of whom were tested for HTLV-1, making up the final sample for the study, along with their 134 respective mothers. Among the tested mother/child pairs, 41 (14.2%) were HTLV-1 positive, highlighted that seven of 134 family clusters concentrated 48.8% of positive cases. Variables associated with a positive child: breastfeeding duration ≥12 months, maternal PVL ≥100 copies/104 PBMC, mother's age at delivery >26 years old, and HTLV-1 in more than one child of the same mother. In a multiple logistic regression, breastfeeding ≥12 months, higher maternal PVL and ≥2 previous HTLV-1-infected children remained independently associated with the outcome. Thus, high maternal PVL and breastfeeding beyond 12 months were independently associated with MTCT of the HTLV-1 infection. Our results reinforce the need for both prenatal HTLV screening in endemic areas and for advising mothers on breastfeeding.

Risk factors associated with HTLV-1 vertical transmission in Brazil: longer breastfeeding, higher maternal proviral load and previous HTLV-1-infected offspring

HTLV-1 is transmitted primarily either through sexual intercourse or from mother to child. The mother/child pairs were classified as seroconcordant or serodiscordant. We analyzed mother to child transmission (MTCT) according to sociodemographic, clinical and epidemiological characteristics of the mother, child's gender and duration of breastfeeding. Between June 2006 and August 2016 we followed 192 mothers with HTLV-1 infection (mean age 41 years old), resulting in 499 exposed offspring, 288 (57.7%) of whom were tested for HTLV-1, making up the final sample for the study, along with their 134 respective mothers. Among the tested mother/child pairs, 41 (14.2%) were HTLV-1 positive, highlighted that seven of 134 family clusters concentrated 48.8% of positive cases. Variables associated with a positive child: breastfeeding duration ≥12 months, maternal PVL ≥100 copies/104 PBMC, mother's age at delivery >26 years old, and HTLV-1 in more than one child of the same mother. In a multiple logistic regression, breastfeeding ≥12 months, higher maternal PVL and ≥2 previous HTLV-1-infected children remained independently associated with the outcome. Thus, high maternal PVL and breastfeeding beyond 12 months were independently associated with MTCT of the HTLV-1 infection. Our results reinforce the need for both prenatal HTLV screening in endemic areas and for advising mothers on breastfeeding

In vitro basal T-cell proliferation among asymptomatic Human T cell Leukemia Virus type 1 patients co-infected with hepatitis C and/or Human Immunodeficiency Virus type 1.

BACKGROUND: Infection with Human T cell Leukemia Virus type 1 can be associated with myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory diseases. Lymphocytes from about half of Human T cell Leukemia Virus type 1-infected subjects spontaneously proliferate in vitro, and how this phenomenon relates to symptomatic disease and viral burden is poorly understood. OBJECTIVE: To evaluate T-cell proliferation in vitro among patients co-infected with Human T cell Leukemia Virus type 1/Hepatitis C Virus/Human Immunodeficiency Virus type 1. MATERIAL AND METHODS: From 610 Human T cell Leukemia Virus-infected patients of the Human T cell Leukemia Virus outpatient clinic from Institute of Infectious Diseases "Emilio Ribas" in São Paulo, 273 agreed to participate: 72 had HAM/TSP (excluded from this analysis) and 201 were asymptomatic, a classification performed during a regular neurological appointment. We selected the subgroup made up only by the 201 asymptomatic subjects to avoid bias by the clinical status as a confounder effect, who had laboratory results of Human T cell Leukemia Virus type 1 proviral load and T-cell proliferation assay in our database. They were further grouped according to their serological status in four categories: 121 Human T cell Leukemia Virus type 1 asymptomatic mono-infected carriers; 32 Human T cell Leukemia Virus type 1/Hepatitis C Virus, 29 Human T cell Leukemia Virus type 1/Human Immunodeficiency Virus type 1, and 19 Human T cell Leukemia Virus type 1/Human Immunodeficiency Virus type 1/Hepatitis C Virus co-infected patients. Clinical data were obtained from medical records and interviews. DNA Human T cell Leukemia Virus type 1 proviral load (PVL) and T-cell proliferation (LPA) assay were performed for all samples. RESULTS: From a total of 273 subjects with Human T cell Leukemia Virus type 1, 80 presented co-infections: 29 had Human Immunodeficiency Virus type 1, 32 had Hepatitis C Virus, and 19 had Human Immunodeficiency Virus type 1 and Hepatitis C Virus. Comparing the groups based on their serological status, independently of being asymptomatic carriers, we observed a significant increase of PVL (p<0.001) and LPA (p=0.001). However, when groups were stratified according to their clinical and serological status, there was no significant increase in Human T cell Leukemia Virus type 1 PVL and LPA. CONCLUSION: No significant increase of basal T-cell proliferation among Human T cell Leukemia Virus type 1 co-infected was observed. This interaction may be implicated in liver damage, worsening the prognosis of co-infected patients or, on the contrary, inducing a higher spontaneous clearance of Hepatitis C Virus infection in Human T cell Leukemia Virus type 1 co-infected patients.

In vitro basal T-cell proliferation among asymptomatic Human T cell Leukemia Virus type 1 patients co-infected with hepatitis C and/or Human Immunodeficiency Virus type 1

ABSTRACT Background: Infection with Human T cell Leukemia Virus type 1 can be associated with myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory diseases. Lymphocytes from about half of Human T cell Leukemia Virus type 1-infected subjects spontaneously proliferate in vitro, and how this phenomenon relates to symptomatic disease and viral burden is poorly understood. Objective: To evaluate T-cell proliferation in vitro among patients co-infected with Human T cell Leukemia Virus type 1/Hepatitis C Virus/Human Immunodeficiency Virus type 1. Material and methods: From 610 Human T cell Leukemia Virus-infected patients of the Human T cell Leukemia Virus outpatient clinic from Institute of Infectious Diseases "Emilio Ribas" in São Paulo, 273 agreed to participate: 72 had HAM/TSP (excluded from this analysis) and 201 were asymptomatic, a classification performed during a regular neurological appointment. We selected the subgroup made up only by the 201 asymptomatic subjects to avoid bias by the clinical status as a confounder effect, who had laboratory results of Human T cell Leukemia Virus type 1 proviral load and T-cell proliferation assay in our database. They were further grouped according to their serological status in four categories: 121 Human T cell Leukemia Virus type 1 asymptomatic mono-infected carriers; 32 Human T cell Leukemia Virus type 1/Hepatitis C Virus, 29 Human T cell Leukemia Virus type 1/Human Immunodeficiency Virus type 1, and 19 Human T cell Leukemia Virus type 1/Human Immunodeficiency Virus type 1/Hepatitis C Virus co-infected patients. Clinical data were obtained from medical records and interviews. DNA Human T cell Leukemia Virus type 1 proviral load (PVL) and T-cell proliferation (LPA) assay were performed for all samples. Results: From a total of 273 subjects with Human T cell Leukemia Virus type 1, 80 presented co-infections: 29 had Human Immunodeficiency Virus type 1, 32 had Hepatitis C Virus, and 19 had Human Immunodeficiency Virus type 1 and Hepatitis C Virus. Comparing the groups based on their serological status, independently of being asymptomatic carriers, we observed a significant increase of PVL (p < 0.001) and LPA (p = 0.001). However, when groups were stratified according to their clinical and serological status, there was no significant increase in Human T cell Leukemia Virus type 1 PVL and LPA. Conclusion: No significant increase of basal T-cell proliferation among Human T cell Leukemia Virus type 1 co-infected was observed. This interaction may be implicated in liver damage, worsening the prognosis of co-infected patients or, on the contrary, inducing a higher spontaneous clearance of Hepatitis C Virus infection in Human T cell Leukemia Virus type 1 co-infected patients.

Polymorphisms in HLA-C and KIR alleles are not associated with HAM/TSP risk in HTLV-1-infected subjects

INTRODUCTION: Several genetic polymorphisms may be related to susceptibility or resistance to viral disease outcomes. Immunological or genetic factors may act as major triggers of the immune pathogenesis of HAM/TSP. This study investigated the association of immune related genetic polymorphisms with viral and immunological markers. METHODS: 247 HTLV-1-infected volunteers, drawn from a larger group of HTLV-infected subjects followed at the Institute of Infectious Diseases "Emilio Ribas" (IIER) for up to 19 years, participated in this study, which ran from June 2011 to July 2016. The subjects were classified according to their neurological status into two groups: Group 1 (160 asymptomatic individuals) and Group 2 (87 HAM/TSP patients). Samples were tested for spontaneous lymphocyte proliferation (LPA) and HTLV-1 proviral load (PVL) and for IFN-λ4, HLA-C and KIR genotypes using qPCR. RESULTS: We found associations between LPA (p=0.0001) with HAM/TSP and confirmed the IFN-λ4 polymorphism rs8099917, allele GG, as a protective factor using a recessive model (OR=3.22, CI=1.10-9.47). Polymorphisms in HLA-C and KIR alleles were not associated with risk of developing HAM/TSP. CONCLUSION: We demonstrated that age, LPA and an IFN-λ4 polymorphism were associated with progression to HAM/TSP. Understanding HAM/TSP pathogenesis can provide important markers of prognostic value for clinical management, and contribute to the discovery of new therapeutic interventions in the future

Polymorphisms in HLA-C and KIR alleles are not associated with HAM/TSP risk in HTLV-1-infected subjects.

INTRODUCTION: Several genetic polymorphisms may be related to susceptibility or resistance to viral disease outcomes. Immunological or genetic factors may act as major triggers of the immune pathogenesis of HAM/TSP. This study investigated the association of immune related genetic polymorphisms with viral and immunological markers. METHODS: 247 HTLV-1-infected volunteers, drawn from a larger group of HTLV-infected subjects followed at the Institute of Infectious Diseases "Emilio Ribas" (IIER) for up to 19 years, participated in this study, which ran from June 2011 to July 2016. The subjects were classified according to their neurological status into two groups: Group 1 (160 asymptomatic individuals) and Group 2 (87 HAM/TSP patients). Samples were tested for spontaneous lymphocyte proliferation (LPA) and HTLV-1 proviral load (PVL) and for IFN-λ4, HLA-C and KIR genotypes using qPCR. RESULTS: We found associations between LPA (p=0.0001) with HAM/TSP and confirmed the IFN-λ4 polymorphism rs8099917, allele GG, as a protective factor using a recessive model (OR=3.22, CI=1.10-9.47). Polymorphisms in HLA-C and KIR alleles were not associated with risk of developing HAM/TSP. CONCLUSION: We demonstrated that age, LPA and an IFN-λ4 polymorphism were associated with progression to HAM/TSP. Understanding HAM/TSP pathogenesis can provide important markers of prognostic value for clinical management, and contribute to the discovery of new therapeutic interventions in the future.

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

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.

Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections.

Human T-cell leukemia virus type 1 (HTLV-1), hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are prevalent worldwide, and share similar means of transmission. These infections may influence each other in evolution and outcome, including cancer or immunodeficiency. Many studies have reported the influence of genetic markers on the host immune response against different persistent viral infections, such as HTLV-1 infection, pointing to the importance of the individual genetic background on their outcomes. However, despite recent advances on the knowledge of the pathogenesis of HTLV-1 infection, gaps in the understanding of the role of the individual genetic background on the progress to disease clinically manifested still remain. In this scenario, much less is known regarding the influence of genetic factors in the context of dual or triple infections or their influence on the underlying mechanisms that lead to outcomes that differ from those observed in monoinfection. This review describes the main factors involved in the virus-host balance, especially for some particular human leukocyte antigen (HLA) haplotypes, and other important genetic markers in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other persistent viruses, such as HIV and HCV.