Abstract INTRODUCTION We present a data analysis and review of recent studies regarding the laboratory diagnosis of human T-lymphotropic virus 1 and 2 (HTLV-1/2) infections in Brazil. METHODS Target populations, available diagnostic serological assays (screening and complementary tests), molecular assays (in-house), causes of false-positive and false-negative results, and flowcharts were analyzed. RESULTS A table presents the target populations, two diagnostic flowcharts (depending on laboratory infrastructure and study population), and recent research that may improve how HTLV-1/2 is diagnosed in Brazil. CONCLUSIONS: Our results support the implementation of public policies to reduce HTLV-1/2 transmission and its associated diseases.

ABSTRACT Infection by human T-cell lymphotropic virus type 1 (HTLV-1) occurs in lymphocytes, which travel throughout the body, thus affecting several target organs and causing varied clinical outcomes, particularly in populations that are underserved and do not have access to healthcare. However, the mechanism of pathogenesis is not yet fully understood. The TAX and HTLV-1 basic leucine zipper factor (HBZ) proteins maintain viral persistence and affect pathogenesis through cell proliferation and immune and inflammatory responses that accompany each clinical manifestation. TAX expression leads to inhibition of transcription error control, OX40 overexpression, and cell proliferation in adult T-cell leukemia (ATL). OX40 levels are elevated in the central nervous system (CNS), and the expression of TAX in the CNS causes neuronal damage and loss of immune reactivity among patients with HTLV-1-associated myelopathy (HAM). HBZ reduces viral replication and suppresses the immune response. Its cell compartmentalization has been associated with the pathogenesis of HAM (cytoplasmic localization) and ATL (nuclear localization). TAX and HBZ seem to act antagonistically in immune responses, affecting the pathogenesis of HTLV-1 infection. The progression from HTLV-1 infection to disease is a consequence of HTLV-1 replication in CD4+ T and CD8+ T lymphocytes and the imbalance between proinflammatory and anti-inflammatory cytokines. The compartmentalization of HBZ suggests that this protein may be an additional tool for assessing immune and inflammatory responses, in addition to those already recognized as potential biomarkers associated with progression from infection to disease (including human leukocyte antigen (HLA), killer immunoglobulin-like receptors (KIR), interleukin (IL)-6, IL-10, IL-28, Fas, Fas ligand, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and mannose-binding lectin).

Resumo O artigo aborda a infecção pelo vírus linfotrópico de células T humanas (human T lymphotropic virus, HTLV), tema contemplado no Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil. A infecção pelo HTLV-1/2 é um problema de saúde pública mundial, sendo o Brasil o país a referir o maior número de indivíduos convivendo com o vírus. O HTLV-1 causa diversas manifestações clínicas, de natureza neoplásica, como a leucemia/linfoma de células T do adulto, e de natureza inflamatória, a exemplo da mielopatia associada ao HTLV-1 e outras alterações, como uveíte, artrite e dermatite infecciosa. Estas patologias apresentam elevada morbimortalidade e impactam negativamente a qualidade de vida dos indivíduos infectados. A presente revisão inclui informações relevantes para gestores e profissionais de saúde sobre os mecanismos de transmissão viral, diagnóstico, tratamento e acompanhamento de indivíduos vivendo com o HTLV-1/2 no Brasil.

Resumen El artículo está relacionado con el capítulo sobre virus linfotrópico de células T humanas (human T lymphotropic virus, HTLV) que conforma el Protocolo Clínico y Directrices Terapéuticas para la Atención Integral a Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil. La infección por HTLV-1/2 es un problema de salud pública en el mundo y Brasil tiene el mayor número de personas que viven con el virus. El HTLV-1 causa varias manifestaciones clínicas, de naturaleza neoplásica (leucemia/linfoma de células T adultas), y de naturaleza inflamatoria, como la mielopatía asociada al HTLV-1 y otras manifestaciones como la uveítis, la artritis y la dermatitis infecciosa. Estas patologías tienen una alta morbilidad y mortalidad e impactan negativamente en la calidad de vida de las personas infectadas. Esta revisión incluye información relevante para gerentes y profesionales de la salud sobre los mecanismos de transmisión viral, diagnóstico, tratamiento y monitoreo de personas que viven con HTLV-1 y 2 en Brasil.

Abstract This manuscript is related to the chapter about human T-cell lymphotropic virus (HTLV) that is part of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Health Ministry. HTLV-1/2 infection is a worldwide public health problem and Brazil has the largest number of individuals living with the virus. HTLV-1 causes a variety of clinical manifestations of a neoplastic nature, such as adult leukemia/T-cell lymphoma, and also of an inflammatory nature, such as HTLV-1-associated myelopathy, as well as other manifestations such as uveitis, arthritis and infective dermatitis. These pathologies have high morbidity and mortality and negatively impact the quality of life of infected individuals. This review includes relevant information for health service managers and workers regarding virus transmission modes, diagnosis, treatment and monitoring of individuals living with HTLV-1 and 2 in Brazil.

Resumo O artigo aborda a infecção pelo vírus linfotrópico de células T humanas (human T lymphotropic virus, HTLV), tema contemplado no Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil. A infecção pelo HTLV-1/2 é um problema de saúde pública mundial, sendo o Brasil o país a referir o maior número de indivíduos convivendo com o vírus. O HTLV-1 causa diversas manifestações clínicas, de natureza neoplásica, como a leucemia/linfoma de células T do adulto, e de natureza inflamatória, a exemplo da mielopatia associada ao HTLV-1 e outras alterações, como uveíte, artrite e dermatite infecciosa. Estas patologias apresentam elevada morbimortalidade e impactam negativamente a qualidade de vida dos indivíduos infectados. A presente revisão inclui informações relevantes para gestores e profissionais de saúde sobre os mecanismos de transmissão viral, diagnóstico, tratamento e acompanhamento de indivíduos vivendo com o HTLV-1/2 no Brasil.

Abstract This manuscript is related to the chapter about human T-cell lymphotropic virus (HTLV) that is part of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Health Ministry. HTLV-1/2 infection is a worldwide public health problem and Brazil has the largest number of individuals living with the virus. HTLV-1 causes a variety of clinical manifestations of a neoplastic nature, such as adult leukemia/T-cell lymphoma, and also of an inflammatory nature, such as HTLV-1-associated myelopathy, as well as other manifestations such as uveitis, arthritis and infective dermatitis. These pathologies have high morbidity and mortality and negatively impact the quality of life of infected individuals. This review includes relevant information for health service managers and workers regarding virus transmission modes, diagnosis, treatment and monitoring of individuals living with HTLV-1 and 2 in Brazil.

Resumen El artículo está relacionado con el capítulo sobre virus linfotrópico de células T humanas (human T lymphotropic virus, HTLV) que conforma el Protocolo Clínico y Directrices Terapéuticas para la Atención Integral a Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil. La infección por HTLV-1/2 es un problema de salud pública en el mundo y Brasil tiene el mayor número de personas que viven con el virus. El HTLV-1 causa varias manifestaciones clínicas, de naturaleza neoplásica (leucemia/linfoma de células T adultas), y de naturaleza inflamatoria, como la mielopatía asociada al HTLV-1 y otras manifestaciones como la uveítis, la artritis y la dermatitis infecciosa. Estas patologías tienen una alta morbilidad y mortalidad e impactan negativamente en la calidad de vida de las personas infectadas. Esta revisión incluye información relevante para gerentes y profesionales de la salud sobre los mecanismos de transmisión viral, diagnóstico, tratamiento y monitoreo de personas que viven con HTLV-1 y 2 en Brasil.

Abstract This article addresses the Human T-lymphotropic virus (HTLV). This subject comprises the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health. HTLV-1/2 infection is a public health problem globally, and Brazil has the largest number of individuals living with the virus. HTLV-1 causes several clinical manifestations of neoplasm (adult T-cell leukemia/lymphoma) and inflammatory nature, such as HTLV-1-associated myelopathy and other manifestations such as uveitis, arthritis, and infective dermatitis. These pathologies have high morbidity and mortality and negatively impact the quality of life of infected individuals. This review includes relevant information for health authorities professionals regarding viral transmission, diagnosis, treatment, and monitoring of individuals living with HTLV-1 and 2 in Brazil.

ABSTRACT Background: Tropical spastic paraparesis or HTLV-associated myelopathy (TSP/HAM) may prevent, limit or restrict the performance of daily living activities, and as a consequence, several aspects of life are affected. Objective: The aim of this study was to evaluate activity limitations, risk awareness, social participation, quality of life, and pain in individuals infected with HTLV-1. Methods: This was an observational, descriptive, analytical, cross-sectional study with a quantitative approach. An interview questionnaire, the Screening of Activity Limitation and Safety Awareness (SALSA) scale, the Participation scale, a quality of life questionnaire (SF-36) and the Brief Pain Inventory were used. Results: A total of 55 patients with HTLV-1 were interviewed (62% asymptomatic and 38% symptomatic). In both groups, there was a higher frequency of patients aged 41-50 years old (35.3% asymptomatic and 38.1% symptomatic), with complete secondary education (47.1% asymptomatic and 42.9% symptomatic), and married (64.7% asymptomatic and 52.4% symptomatic). Of the symptomatic patients, 33.3% were retired; among asymptomatic patients, 20.6% performed domestic activities. The majority of patients in both groups had not received blood transfusions. Sexual intercourse was still practiced by patients. After assessment, asymptomatic patients had no activity limitations (64.7%), and symptomatic patients presented limitations (90.5%). None of the groups showed good risk awareness. There was no restriction on social participation in 97.1% of asymptomatic patients and in 52.4% among symptomatics. Both groups complained of pain, being more frequent in the lumbar spine in asymptomatic patients and in the knees in symptomatic patients. Pain was more severe in symptomatic patients and affected aspects of quality of life. Conclusion: The clinical follow-up instruments must be adopted by healthcare professionals to monitor new symptoms so as to avoid the onset of limitations identified in symptomatic patients, in addition to enabling continuous surveillance of asymptomatic patients.

Abstract INTRODUCTION: The present study investigated the association of the rs2794521 polymorphism in the CRP gene in individuals with chronic hepatitis B and C, correlating it with markers of hepatic inflammation, fibrosis scores, viral load, and plasma protein levels. METHODS: The study analyzed 185 blood samples obtained from patients with hepatitis B (n=74) and hepatitis C (n=111) and 300 samples from healthy donors. Genotyping was performed by real-time polymerase chain reaction, and protein levels were quantified using the automated immunoturbidimetric method. RESULTS: The TT genotype was the most frequent in all studied groups and was associated with higher plasma levels of the protein but not with the progression of liver disease. Low levels of C-reactive protein were associated with increased viremia and scores indicative of severe fibrosis and cirrhosis. CONCLUSIONS: The present results demonstrated a close relationship between the ability of the virus to replicate and cause liver damage and low serum concentrations of C-reactive protein. Future research may determine if these results can be interpreted as a possible form of escape for the virus by decreasing its action as an opsonin and decreasing phagocytosis, which are functions of C-reactive protein in the immune response.

Abstract INTRODUCTION: Exposure to human immunodeficiency virus (HIV)-1 during pregnancy is a major risk factor for neurodevelopmental delay and deleterious effects in children. However, limited information about these conditions exists in poor geographical areas in Brazil. Prevention of vertical transmission of HIV-1 is dealt differently in different regions of the country and in poorer areas it is more difficult to evaluate the impact of the prevention methods. The outcomes of the exposure to HIV-1 and the impact of vertical HIV-1 transmission on neuropsychomotor development was evaluated for the first time in children born to HIV-infected mothers in the North region of Brazil, where the majority of the population has poor access to health services. METHODS: Sixty children born to HIV-1-infected mothers (case group) and 58 born to non-infected mothers (control group) were followed for the first 12 months of life in a prospective case-control study. Neuropsychomotor development was assessed using the Denver II test. RESULTS: Suspected neuropsychomotor developmental delays were more frequent in the case group (33.3%), namely in language (38.9%) and gross motor skills (27.8%). These delays were reversed in most children after 12 months of life due to therapeutic intervention. The delays were not reversed in three children, all of whom belonged to the case group. Only one of these was infected with HIV-1, and this child had the poorest neuropsychomotor outcomes. CONCLUSIONS: Maternal HIV-1 infection negatively affected the neuropsychomotor development in children, although other factors may have played a role.

Abstract INTRODUCTION Leprosy often results in sensory and physical limitations. This study aimed to evaluate these limitations using a quantitative approach in leprosy patients in Belém (Pará, Brazil). METHODS This epidemiological, cross-sectional study measured the sensory impairment of smell and taste through the use of a questionnaire and evaluated activity limitations of daily life imposed by leprosy through the Screening of Activity Limitation and Safety Awareness (SALSA) Scale. Data were collected from 84 patients and associations between the degree of disability and clinical and epidemiological characteristics were assessed. RESULTS The majority of patients were men (64.3%), married (52.4%), age 31-40 years old (26.2%), had primary education (50%), and were independent laborers (36.9%). The multibacillary operational classification (81%), borderline clinical form (57.1%), and 0 degrees of physical disability (41.7%) were predominant. SALSA scores ranged from 17 to 59 points, and being without limitations was predominant (53.6%). The risk awareness score ranged from 0 to 8, with a score of 0 (no awareness of risk) being the most common (56%). Evaluation of smell and taste sensory sensitivities revealed that 70.2% did not experience these sensory changes. Patients with leprosy reactions were 7 times more likely to develop activity limitations, and those who had physical disabilities were approximately four times more likely to develop a clinical picture of activity limitations. CONCLUSIONS Most patients showed no sensory changes, but patients with leprosy reactions were significantly more likely to develop activity limitations. Finally, further studies should be performed, assessing a higher number of patients to confirm the present results.

Abstract JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV-1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215 bp) and IG (610 bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4+/TCD8+ lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups.

INTRODUCTION: Chlamydia infection is associated with debilitating human diseases including trachoma, pneumonia, coronary heart disease and urogenital diseases. Serotypes of C. trachomatis show a fair correlation with the group of diseases they cause, and their distribution follows a well-described geographic pattern. Serotype A, a trachoma-associated strain, is known for its limited dissemination in the Middle East and Northern Africa. However, knowledge on the spread of bacteria from the genus Chlamydia as well as the distribution of serotypes in Brazil is quite limited. METHODS: Blood samples of 1,710 individuals from ten human population groups in the Amazon region of Brazil were examined for antibodies to Chlamydia using indirect immunofluorescence and microimmunofluorescence assays. RESULTS: The prevalence of antibodies to Chlamydia ranged from 23.9% (Wayana-Apalai) to 90.7% (Awa-Guaja) with a mean prevalence of 50.2%. Seroreactivity was detected to C. pneumoniae and to all serotypes of C. trachomatis tested; furthermore, we report clear evidence of the as-yet-undescribed occurrence of serotype A of C. trachomatis. CONCLUSIONS: Specific seroreactivity not only accounts for the large extent of dissemination of C. trachomatis in the Amazon region of Brazil but also shows an expanded area of occurrence of serotype A outside the epidemiological settings previously described. Furthermore, these data suggest possible routes of Chlamydia introduction into the Amazon region from the massive human migration that occurred during the 1,700s.

INTRODUCTION: The present study investigated the prevalence of two single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 3 (TLR3) gene in patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: Samples collected from HCV (n = 74) and HBV (n = 35) carriers were subjected to quantitative real-time PCR (qPCR) to detect the presence of the SNPs rs5743305 and rs3775291 in TLR3 and to measure the following biomarkers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and prothrombin time (PT). A healthy control group was investigated and consisted of 299 HCV- and HBV-seronegative individuals. RESULTS: No significant differences in allele, genotype and haplotype frequencies were observed between the investigated groups, and no association was observed between the polymorphisms and histopathological results. Nevertheless, genotypes TA/AA (rs5743305) and GG (rs3775291) appear to be associated with higher levels of ALT (p<0.01), AST (p<0.05) and PT (p<0.05). In addition, genotypes TT (rs5743305; p<0.05) and GG (rs3775291; p<0.05) were associated with higher GGT levels. CONCLUSIONS: This genetic analysis revealed the absence of an association between the polymorphisms investigated and susceptibility to HBV and HCV infection; however, these polymorphisms might be associated with a greater degree of biliary damage during the course of HCV infection.

Introduction This study confirmed the absence of natural infection with Xenotropic murine leukemia virus-related virus (XMRV) or XMRV-related disease in human populations of the Brazilian Amazon basin. We demonstrated that 803 individuals of both sexes, who were residents of Belem in the Brazilian State of Pará, were not infected with XMRV. Methods Individuals were divided into 4 subgroups: healthy individuals, individuals infected with human immunodeficiency virus, type 1 (HIV-1), individuals infected with human T-lymphotrophic virus, types 1 or 2 (HTLV-1/2), and individuals with prostate cancer. XMRV infection was investigated by nested PCR to detect the viral gag gene and by quantitative PCR to detect pol. Results There was no amplification of either gag or pol segments from XRMV in any of the samples examined. Conclusions This study supports the conclusions of the studies that eventually led to the retraction of the original study reporting the association between XMRV and human diseases.

This study evaluated the relative occurrences of BK virus (BKV) and JC virus (JCV) infections in patients with chronic kidney disease (CKD). Urine samples were analysed from CKD patients and from 99 patients without CKD as a control. A total of 100 urine samples were analysed from the experimental (CKD patients) group and 99 from the control group. Following DNA extraction, polymerase chain reaction (PCR) was used to amplify a 173 bp region of the gene encoding the T antigen of the BKV and JCV. JCV and BKV infections were differentiated based on the enzymatic digestion of the amplified products using BamHI endonuclease. The results indicated that none of the patients in either group was infected with the BKV, whereas 11.1% (11/99) of the control group subjects and 4% (4/100) of the kidney patients were infected with the JCV. High levels of urea in the excreted urine, low urinary cellularity, reduced bladder washout and a delay in analysing the samples may have contributed to the low prevalence of infection. The results indicate that there is a need to increase the sensitivity of assays used to detect viruses in patients with CDK, especially given that polyomavirus infections, especially BKV, can lead to a loss of kidney function following transplantation.