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IntroductionTLR7 detects the presence of single-stranded RNA (ssRNA) viruses, including human T-lymphotropic virus 1 (HTLV-1), and triggers antiviral and inflammatory responses that are responsible for infection control. Genetic variations in the TLR7 gene may alter cytokine production and influence the course of HTLV-1 infection. In the present study, the associations of TLR7 gene polymorphisms with HTLV-1-related symptoms, receptor expression levels, IFN-α and TNF-α levels and the proviral load were investigated.MethodsBlood samples from 159 individuals with HTLV-1 infection (66 with inflammatory diseases and 93 asymptomatic individuals) and 159 controls were collected. The genotyping of polymorphisms, TLR7 gene expression analysis and the quantification of the proviral load were performed by real-time PCR, and cytokine measurement was performed by enzyme-linked immunosorbent assay (ELISA).ResultsCarriers of the polymorphic allele for TLR7 rs179008 (A/T) had lower levels of IFN-α, while carriers of the polymorphic allele for TLR7 rs3853839 (C/G) had higher levels of TLR7 and IFN-α expression. The polymorphisms were not associated with symptoms of diseases related to HTLV-1 infection. The combination of A/G alleles for the TLR7 rs179008 (A/T) and TLR7 rs3853839 (C/G) polymorphisms was associated with increased IFN-α levels and a decreased proviral load.DiscussionAlthough the polymorphisms did not influence the presence of symptoms of diseases caused by HTLV-1, carriers of the wild-type alleles for TLR7 rs179008 (A/T) and the polymorphism for TLR7 rs3853839 (C/G) appears to have a stronger antiviral response and increased infection control.

Human T-limphotropic virus 1 infection has a global distribution, with a high prevalence in some regions of Brazil and the world, while HTLV-2 infection is endemic mainly among indigenous people and drug users. To analyze intrafamilial transmission of HTLV-1/2 in five Kayapó indigenous peoples (Gorotire, Kararaô, Kokraimoro, Kubenkokre, and Xikrin do Bacajá), we investigated 1452 individuals who underwent serological and molecular tests. Among the 276 indigenous people with positive results, we identified intrafamily transmission in 42.7% of cases, representing 38 families. It was possible to suggest horizontal and vertical transmissions in 15.8% (6/38) and 47.4% (18/38) of the family groups, respectively. In 15.8%, it was not possible to suggest the route, which indicated that the transmission may have occurred through both vertical and horizontal routes. Through phylogenetic analyses, 35 samples positive for HTLV-2 were sequenced and classified as subtype 2c, and the two samples that tested positive for HTLV-1 were shown to belong to the cosmopolitan subtype, transcontinental subgroup (HTLV-1aA). This study confirms the intrafamilial transmission of HTLV-1/2 infection in indigenous people of the Brazilian Amazon, highlighting the importance of the sexual and mother-to-child transmission routes in maintaining the virus in these people.

This study aimed to describe the prevalence of HTLV-1/2 in quilombola communities in the state of Pará and investigate the possible sociodemographic risk factors associated with the infection, as well as to trace the occurrence of the familial transmission of the virus. A total of 310 individuals living in eight quilombos located in the state of Pará (northern Brazil) were investigated for the presence of anti-HTLV-1/2 antibodies using an enzyme-linked immunosorbent assay (ELISA), and positive samples were confirmed using Western blot and/or real-time quantitative polymerase chain reaction (qPCR). Participants answered a questionnaire about sociodemographic aspects and risk factors for infection. Anti-HTLV-1/2 antibodies were detected in two individuals (one man and one woman), for an overall seroprevalence of 0.65%. Both individuals belonged to the community of São José de Icatú. The search for intrafamilial infection identified two other infected women, which increased the general prevalence of HTLV-1 among the Icatú to 6.25% (4/64). Western blot and qPCR confirmed their HTLV-1 infection, and phylogenetic analysis demonstrated that the isolates were of the cosmopolitan subtype and transcontinental subgroup. Epidemiological investigation of the cases revealed that the three women, at some point in their lives, had a relationship with the infected male individual. HTLV-1 is transmitted silently between individuals in the community of São José de Icatú with a present or past family relationship, stressing the need for screening and laboratory diagnosis to prevent further dissemination of the virus and surveillance of disease emergence.

Sexually transmitted infections (STIs) represent a worldwide public health burden, but many infections and diseases continue to be neglected. Areas with a low human development index, including the northern areas of Brazil, particularly the immense geographic Amazon region, present a high frequency of STIs because of variables that contribute to disseminate the infection, including lack of access to education, prevention measures and treatment to these vulnerable population groups. This review describes the chronological investigation of the etiology of pathologies associated with infection by Chlamydia trachomatis, including its prevalence, distribution, and clinical, descriptive and molecular epidemiology in regard to STIs, trachoma and heart disease. Long-term investigations among urban and nonurban populations are discussed and show the need for and effects of continuous surveillance to diminish the burden among vulnerable populations (female sex workers, quilombos and indigenous peoples) and to define new etiological associations of diseases with infections by C. trachomatis.

TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated.

IntroductionHuman T-lymphotropic virus 2 (HTLV-2) has been described for more than 30 years as an endemic infection in Brazilian indigenous populations, with its occurrence varying by age and sex, maintained mainly by sexual intercourse and mother-to-child transmission, favoring intrafamilial aggregation.MethodsThe epidemiological scenario of HTLV-2 infection has been described among communities of the Amazon region of Brazil (ARB), with the number of retrospective positive blood samples increasing for more than 50 years.ResultsFive publications were selected that showed the presence of HTLV-2 in 24 of 41 communities; the prevalence of infection was described among 5,429 individuals at five points in time. Among the Kayapó villages, the prevalence rates were described according to age and sex and reached up to 41.2%. Three communities (Asurini, Araweté, and Kaapor) were kept virus free for 27 to 38 years of surveillance. Low, medium and high prevalence levels of infection were defined, and two pockets of high endemicity were shown in the state of Pará, pointing to the Kikretum and Kubenkokrê Kayapó villages as the epicenter of HTLV-2 in the ARB.DiscussionThe prevalence rates over the years have shown a decline among the Kayapó (from 37.8 to 18.4%) and an apparent change to a higher prevalence among females, but not during the first decade of life, usually associated with transmission from mother to child. Sociocultural and behavioral aspects, as well as public health policies directed toward sexually transmitted infections, might have positively influenced the decline in HTLV-2 infections.

Abstract Background Genetic changes may induce dysregulated cytokine production and affect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-inflammatory cytokines determines the outcome of infection. This study evaluated the TNFA -308G>A and IL10 -1082A>G polymorphisms in the susceptibility and progress of chronic hepatitis C. Method The study included 101 samples from patients with chronic hepatitis C and 300 samples from healthy donors. Polymorphisms were typed by real-time PCR and were analyzed for associations with histopathological parameters (according to METAVIR classification) and HCV viral load. Results The polymorphic genotype for the TNFA -308G>A variant was not present in the group of patients with chronic hepatitis C and its absence could be associated with protection against HCV infection (p = 0.0477). Patients with the polymorphic genotype of the IL10 -1082A>G polymorphism had higher HCV viral load than wild-type patients (p = 0.0428). Neither polymorphism was associated with different levels of necroinflammatory activity or fibrosis scores. Conclusion Our results suggest the polymorphic genotype at TNFA -308G>A as protective against chronic HCV infection, and the polymorphic genotype at the IL10 -1082A>G variant associated with higher HCV viral load. Further studies must be performed in order to confirm these associations.

Some genetic variations in cytokine genes can alter their expression and influence the evolution of Mycobacterium tuberculosis (Mtb) infection. This study aimed to investigate the association of polymorphisms in cytokine genes and variability in plasma levels of cytokines with the development of tuberculosis (TB) and latent tuberculosis infection (LTBI). Blood samples from 245 patients with TB, 80 with LTBI, and healthy controls (n = 100) were included. Genotyping of the IFNG +874A/T, IL6 -174G/C, IL4 -590C/T, and IL10 -1082A/G polymorphisms was performed by real-time PCR, and cytokine levels were determined by flow cytometry. Higher frequencies of genotypes AA (IFNG +874A/T), GG (IL6 -174G/C), TT (IL4 -590C/T), and GG (IL10 -1082A/G) were associated with an increased risk of TB compared to that of LTBI (p = 0.0027; p = 0.0557; p = 0.0286; p = 0.0361, respectively) and the control (p = p = 0.0021; p = 0.01655; p = 0.0132, respectively). In combination, the A allele for IFNG +874A/T and the T allele for IL4 -590C/T were associated with a higher chance of TB (p = 0.0080; OR = 2.753 and p < 0.0001; OR = 3.273, respectively). The TB group had lower levels of IFN-γ and higher concentrations of IL-6, IL-4, and IL-10. Cytokine levels were different between the genotypes based on the polymorphisms investigated (p < 0.05). The genotype and wild-type allele for IFNG +874A/T and the genotype and polymorphic allele for IL4 -590C/T appear to be more relevant in the context of Mtb infection, which has been associated with the development of TB among individuals infected by the bacillus and with susceptibility to active infection but not with susceptibility to latent infection.

Abstract Background The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. Methods This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p

Abstract Background Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients. Methods This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA). Results ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p

Human T-lymphotropic virus 1 (HTLV-1) is endemic worldwide and the infection results in severe diseases, including Adult T-cell Leukemia (ATL) and HTLV-1 associated myelopathy (HAM). There are some limitations of employing the present commercial serological assays for both diagnostic and epidemiological purposes in different geographical areas of the Brazil, such as the Amazon Region. Currently, methods for diagnosis are usually expensive to adapt for routine use. The aim of this work was to identify and characterize specific ligands to IgG that mimic HTLV-1 epitopes through the Phage Display technique, which could be used for diagnosis and as future vaccine candidates. Initially, IgG from 10 patients with HTLV-1 and 20 negative controls were covalently coupled to protein G-magnetic beads. After biopanning, genetic sequencing, bioinformatics analysis and Phage-ELISA were performed. The technique allowed the identification of 4 clones with HTLV-1 mimetic peptides, three aligned with gp46, A6 (SPYW), B6 (SQLP) and D7 (PLIL), and one with the protease and Tax, A8 (SPPR). Clones A6 and B6 showed higher values of accessibility, antigenicity and hydrophilicity. The reactivity of the clones evaluated by the Receiver Operating Characteristic (ROC) curve showed that the B6 clone had the highest Area Under Curve (0.83) and sensitivity and specificity values (both were 77.27 %; p < 0.001). The study showed that the Phage Display technique is effective for the identification of HTLV-1-related peptides. Clone B6 indicated to be a good marker for bioprospecting diagnostic test for HTLV-1 infection and could be used as a possible vaccine candidate for future studies.

The human T-lymphotropic virus 1 (HTLV-1) and 2 (HTLV-2) can be transmitted between humans by mechanisms associated with horizontal and vertical routes. Recently, high prevalence rates and levels of genetic diversity for HTLV-1 and HTLV-2 were detected among people who use illicit drugs (PWUDs) in the Brazilian state of Pará. None of the PWUDs with HTLV-1 or HTLV-2 were aware of their carrier condition of the retrovirus, and they ability to spread it to their family group, sexual partners, and other contacts. Thus, this study evaluated the presence of HTLV-1 and HTLV-2 in families of PWUDs in the state of Pará, in Northern Brazil. This descriptive study used convenience sampling and accessed 37 PWUDs and their respective families (n = 97) in 18 municipalities in the state of Pará, northern Brazil. All participants provided personal data and were tested for the presence of HTLV-1 and HTLV-2 using enzyme-linked immunosorbent assay and western blotting. HTLV positive samples were selected for Nested-PCR, and viral genotyping by nucleotide sequencing and phylogenetic analysis. HTLV-1 or HTLV-2 infections were detected in 15 families of PWUDs: 27 family members of PWUDs were infected with HTLV-1 (27.8%) and another 20 of them with HTLV-2 (20.6%). Subtypes 1a [subgroup A (54.5%)], 2b (20.5%), and 2c (25.0%) were detected. High horizontal (76.9%) and vertical (61.4%) transmission rates of HTLV were ascertained. Factors that facilitate the acquisition and transmission of HTLV-1 and HTLV-2 were reported by the participants, such as long-term relationships, unprotected sex, breastfeeding, and lack of knowledge about the condition of being a carrier of the retrovirus. Evidence indicates intrafamilial transmission of HTLV from PWUDs to members of their respective families. Key interventions should urgently be employed for the control and prevention of HTLV-1 and HTLV-2 to reduce the spread of this retrovirus in PWUDs and the general population in Northern Brazil and elsewhere.

A multi-epitope protein expressed in a prokaryotic system, including epitopes of Env, Gag, and Tax proteins of both HTLV-1 and HTLV-2 was characterized for HTLV-1/2 serological screening. This tool can contribute to support the implementation of public policies to reduce HTLV-1/2 transmission in Brazil, the country with the highest absolute numbers of HTLV-1/2 infected individuals. The chimeric protein was tested in EIA using serum/plasma of HTLV-infected individuals and non-infected ones from four Brazilian states, including the North and Northeast regions (that present high prevalence of HTLV-1/2) and Southeast region (that presents intermediate prevalence rates) depicting different epidemiological context of HTLV-1/2 infection in our country. We enrolled samples from Pará (n = 114), Maranhão (n = 153), Minas Gerais (n = 225) and São Paulo (n = 59) states; they are from blood donors' candidates (Pará and Minas Gerais), pregnant women (Maranhão) and HIV+/high risk for sexually transmitted infection (STI; São Paulo). Among the HTLV-1/2 positive sera, there were co-infections with viral (HTLV-1 + HTLV-2, HIV, HCV, and HBV), bacterial (Treponema pallidum) and parasitic (Trypanosoma cruzi, Schistosma mansoni, Strongyloides stercoralis, Entamoeba coli, E. histolytica, and Endolimax nana) pathogens related to HTLV-1/2 co-morbidities that can contribute to inconclusive diagnostic results. Sera positive for HIV were included among the HTLV-1/2 negative samples. Considering both HTLV-1 and HTLV-2-infected samples from all states and different groups (blood donor candidates, pregnant women, and individuals with high risk for STI), mono or co-infected and HTLV-/HIV+, the test specificity ranged from 90.09 to 95.19% and the sensitivity from 82.41 to 92.36% with high accuracy (ROC AUC = 0.9552). This multi-epitope protein showed great potential to be used in serological screening of HTLV-1 and HTLV-2 in different platforms, even taking into account the great regional variation and different profile of HTLV-1 and HTLV-2 mono or co-infected individuals.

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 Background The forkhead box protein 3 (FOXP3) transcription factor is one of the main markers of immunological suppression in different pathological profiles, and the presence of polymorphic variants may alter the gene expression of this factor. Despite descriptions of an association between the presence of the rs2232365 polymorphism and chronic diseases, the role of the sex variant in this context has not yet been elucidated, as the FOXP3 gene is located on the human sex chromosome X. Results To contribute to this topic, 323 women and 373 men were enrolled in the study, of which 101 were diagnosed with chronic viral liver diseases (39 women and 62 men), 67 with HTLV-1 infection (44 women and 23 men), 230 with coronary artery disease (91 women and 139 men) and 298 healthy and uninfected blood donors (149 women and men). They were genotyped for the rs2232365 polymorphism. The rs2232365 polymorphism was associated with clinical and pathological aspects and biomarkers of viral infections only in men, with functional differences between different infections. Conclusions A relationship is suggested between sex and FOXP3 rs2232365 polymorphism, resulting in different biological repercussions.

Abstract Background Human immunodeficiency virus (HIV-1) infection is characterized by high viral replication and a decrease in CD4+ T cells (CD4+TC), resulting in AIDS, which can lead to death. In elite controllers and viremia controllers, viral replication is naturally controlled, with maintenance of CD4+TC levels without the use of antiretroviral therapy (ART). Methods The aim of the present study was to describe virological and immunological risk factors among HIV-1-infected individuals according to characteristics of progression to AIDS. The sample included 30 treatment-naive patients classified into three groups based on infection duration (> 6 years), CD4+TC count and viral load: (i) 2 elite controllers (ECs), (ii) 7 viremia controllers (VCs) and (iii) 21 nonviremia controllers (NVCs). Nested PCR was employed to amplify the virus genome, which was later sequenced using the Ion PGM platform for subtyping and analysis of immune escape mutations. Results Viral samples were classified as HIV-1 subtypes B and F. Greater selection pressure on mutations was observed in the group of viremia controllers, with a higher frequency of immunological escape mutations in the genes investigated, including two new mutations in gag. The viral sequences of viremia controllers and nonviremia controllers did not differ significantly regarding the presence of immune escape mutations. Conclusion The results suggest that progression to AIDS is not dependent on a single variable but rather on a set of characteristics and pressures exerted by virus biology and interactions with immunogenetic host factors.

Yellow fever has been recently described in nonurban areas of Brazil despite 80 years of commercial vaccine use. Although the disease does not spread fear in the general population as it did in the past, yellow fever virus continues to cause many cases of severe disease. Persistence of the virus in the host is a new mechanism to be considered in the pathology of the disease. Immunization with a fractional dose of vaccine during emergency situations needs to be evaluated for antibody duration, and new and improved vaccines should be considered.

Abstract Background Syphilis is a sexually transmitted infection (STI) transmitted from person to person mainly by sexual intercourse or through vertical transmission during pregnancy. Female sex workers (FSWs) are exposed especially to syphilis infection, and besides all the efforts to control the spread of STIs, syphilis prevalence is still rising, mainly occurring in low-income countries. This study aimed to investigate the syphilis prevalence, demographic characteristics and sexual habits among FSWs in the Amazon region of Brazil. Methods A cross-sectional study was carried out including 184 FSWs from 3 countryside cities of the state of Pará, Amazon region of Brazil. A venereal disease research laboratory test and an indirect immunoenzyme assay to test antibodies against Treponema pallidum were used for screening syphilis infection, while sexual habits and demographic data information were collected through a semi-structured questionnaire. Data was analyzed comparing groups with/without syphilis. Poisson regression models were used to estimate the reasons of prevalence (RP). Results The overall prevalence of syphilis was 14.1% (95% CI = 9.8–17.8). FSWs had between 15 and 56 years of age, most were unmarried (65.7%), had attended less than 8 years of formal education (64.1%), had between 10 and 20 partners per week (64.1%), and reported no previous history of STIs (76.1%) and regular use of condom (52.7%). Low level of education attending up to the primary school (RP adjusted = 3.8; 95% CI = 1.4–9.2) and high frequency of anal sex during the past year (RP adjusted = 9.3; 95% CI = 3.5–28.7) were associated with a higher prevalence of syphilis. Conclusions A high prevalence of syphilis among FSWs in the Brazilian Amazon region was identified, showing that syphilis is more likely to be transmitted in FSW working in low-income areas, which is attributed to the low level of education. Anal intercourse was found as a risk factor associated with syphilis. Health programs focused on risk populations appear as a rational way to control syphilis spread, which is a rising problem in Brazil and in other several countries.

Abstract HTLV-1 was the first described human retrovirus and was soon found to be associated with severe clinical diseases, including a devastating lymphoma/leukemia and other inflammatory diseases. Although HTLV-2 is not usually pathogenic, it is widely distributed among native Indian populations in Brazil, particularly in the Amazon region of the country. Presently, HTLV spreads mainly by the sexual route and from mother to child, and virus persistence is an active biological factor aiding its transmission. Recently, the use of illicit drugs has been shown to be an additional risk factor, showing the influence of new habits on the epidemiology of HTLV in the region. Despite the detection of the virus in several different populations in the Amazon region of Brazil for almost 30 years, the exact prevalence of HTLV-1/2 is not well defined. The original biases in sampling and the selection of epidemiologically unsuitable populations were commonly repeated in most prevalence studies, generating unreliable and conflicting figures that do not represent the actual prevalence of HTLV. The improvements in clinical and laboratory facilities have resulted in the description of several clinical manifestations that were previously unknown in the region. The extent of the spread of the virus must be defined in this region, which is the largest geographical area of the country. As prophylaxis advances toward the use of vaccines against HTLV-1, it is important to determine who is at risk of being infected and developing a disease to successfully implement preventive measures, particularly as proposals are made to eradicate the virus among humans.

Human T lymphotropic virus 1 (HTLV-1) is a public health issue for most countries and imposes important consequences on patients' health and socioeconomic status. Brazil is one of the global leaders of the public health response to these viruses. The country has challenges to overcome to implement meaningful policies aiming to eliminate HTLV-1/2. An analysis of strengths, weaknesses, opportunities, and threats (SWOT) for the implementation of public health policies on HTLV-1/2 was performed. The strengths identified were the Brazilian Unified Health System (SUS); Brazilian expertise in public health programs successfully implemented; currently available policies targeting HTLV; and strong collaboration with researchers and patient's representative. Lack of awareness about HTLV, insufficient epidemiological data, lack of reference centers for patient care, insufficient availability of confirmatory tests, lack of universal antenatal screening, and absence of cost-effectiveness studies were identified as weaknesses. Some interesting opportunities included the increased interest from international organizations on HTLV, possibility of integrating HTLV into other programs, external funding for research, available online platforms, opportunity to acquire data from HTLV-1/2 surveillance to gather epidemiological information, and HTLV policies that were implemented independently by states and municipalities. In addition to the COVID-19 pandemic, existing demands from different diseases, the country's demography and its marked sociocultural diversity and the volatility of the technical team working with HTLV-1/2 at the Brazilian Ministry of Health are threats to the implementation of public policies on HTLV-1/2. This SWOT analysis will facilitate strategic planning to allow continuous progress of the Brazilian response to HTLV-1/2 infection.

Introdução: O sistema Fas-FasL de membrana celular é um importante mediador de apoptose de células infectadas. A apoptose de macrófagos infectados pelo Mycobacterium tuberculosis é uma estratégia imunológica de proteção contra a tuberculose (TB). Objetivo: Investigar a influência dos níveis de expressão dos genes FAS e FASL no estabelecimento da TB em 20 amostras de pacientes diagnosticados com TB e 22 amostras controle. Material e métodos: Foram coletadas amostras de sangue, as quais foram submetidas à extração de mRNA e transcrição reversa, para obtenção de cDNA, utilizado para a quantificação relativa (RQ) da expressão gênica por meio de PCR em tempo real (RT-PCR). A avaliação dos níveis de expressão de FAS e FASL, entre pacientes e controles, foi realizada pelos testes não paramétricos Mann-Whitney e correlação de Spearman. O estudo foi aprovado pelo Comitê de Ética em Pesquisa com Seres Humanos do Instituto de Ciências da Saúde da Universidade Federal do Pará (CAAE no. 31446920.0.3001.0017). Resultados: O grupo controle apresentou níveis de expressão de FAS significativamente mais elevados (mediana = 1,806 RQ) do que no grupo com diagnóstico de TB (mediana = 0,2725 RQ) (p = 0,0171), o que também foi observado na comparação da expressão gênica de FASL entre controles (mediana = 0,325 RQ) e pacientes (mediana = 0,0265 RQ) (p = 0,0193). Houve correlação positiva entre a expressão de FAS e a de FASL no grupo com TB (p = 0,0011). Conclusão: A expressão gênica reduzida de FAS e FASL nos pacientes com TB pode ser o resultado da evasão do M. tuberculosis das respostas imunes do hospedeiro, induzindo a diminuição da ativação da apoptose pela via Fas-FasL de maneira a favorecer sua sobrevivência e persistência no interior dos macrófagos. A expressão deficiente de FAS e FASL pode prejudicar as sinalizações de apoptose celular e favorecer o desenvolvimento da TB.

Introdução/Objetivo: A infecção pelo HTLV-2 é endêmica em povos indígenas das Américas, tendo sua origem no continente atribuída ao fluxo migratório dos povos ancestrais dos ameríndios. O presente estudo teve como objetivo investigar a prevalência da infecção pelos HTLV-1/2 em indígenas da etnia Kayapó. Método: A prevalência da infecção pelo HTLV-1/2 foi investigada em 661 indígenas (371 mulheres e 290 homens), com a idades variando entre 3 meses a 94 anos (média igual a 29 anos), pertencentes do povo Kayapó, subgrupos Xikrin do Bacajá (n = 216), Kararaô (n = 44), Gorotite (n = 261) e Kokraimoro (n = 140), localizados no estado do Pará, região Norte do Brasil. Após consentimento das lideranças indígenas, amostras de sangue venoso foram coletas em tubos de EDTA e o plasma foi utilizado na triagem realizada por meio de ensaio de imunoabsorção enzimática - ELISA (Murex HTLV-I+II, DiaSorin, Dartford, UK) para pesquisa de anticorpos contra os HTLV-1/2. Resultados: Do total de indivíduos testados, 111 (16,8%) foram reagentes no ELISA, sendo 37,8% (42/111) homens e 62,2% (69/111) mulheres. A distribuição da prevalência da infecção pelo HTLV foi bastante heterogênea entre as populações: Xikrin (17,6%), Gorotire (21,1%) e Kokraimoro (12,9%). Não foi encontrada infecção no povo Kararaô. A média de idade dos positivos foi de 48,6 anos, variando entre 2 e 86 anos. A infecção foi mais prevalente em indivíduos acima de 61 anos (61,1%), sendo as mulheres mais acometidas. Conclusão: Descrevemos aqui uma infecção hiperendêmica de HTLV-1/2 entre três subgrupos do povo Kayapó e a ausência de infecção observada apenas no subgrupo Kararaô. A alta prevalência de infecção nesses subgrupos deve ser reflexo de diferentes perfis epidemiológicos observados nestes povos, tais como a transmissão sexual com múltiplos parceiros e o aleitamento materno, especialmente em casos de amamentação cruzada. Ademais, o efeito de fundador, o isolamento sócio-geográfico e o número amostral reduzido podem explicar a ausência de infecção e proteção à emergência do HTLV no subgrupo Kararaô.

Background: Most of the countries facing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic are still trying to understand the dynamics of the behavior of the virus and dissemination of the new agent. Objectives: A retrospective descriptive epidemiological study of the 26 state capitals of Brazil and its capital, Brasilia, was performed to investigate the behavior of the infection and disease caused by SARS-CoV-2. Study design: The data presented were obtained from the State Health Departments and the Brazilian Ministry of Health. Seven epidemiological markers (including the incidence, mortality and case fatality rates and the growth of the epidemic measured by the ratios observed on days 30, 60 and 90) were compared for the initial 90 days of the epidemic for each city. Results: The epidemic spread to the country within 25 days, and deaths occurred as early as nine days from initiation. The incidence and mortality rates ranged from 70 to almost 1,599/100,000 and less than 1 to 1,171/1,000,000, respectively, at the end of the 90-day period of observation. The CFR was less than two up to 12.31%. The magnitude of each marker clustered the cities in different groups. The epidemic was managed differently in each city, with differences in qualified medical services and medical preparedness to face the emergency situation. Conclusions: Although modeling the epidemic has been a constant task, epidemiological data should be pursued to define actual information, such as the prevalence and incidence rates, to understand the unpredictable nature of this emerging infection, including the present policy of vaccination campaigns.

Apoptosis of macrophages infected by Mycobacterium tuberculosis via Fas-FasL is an important immune mechanism against infection. This study investigated the association of tuberculosis (TB) with the presence of the polymorphisms FAS -670A/G and FASL -124A/G, the levels of sFas and sFasL, and the gene expression of FASL and cytokines. Samples of 200 individuals diagnosed with TB and 200 healthy controls were evaluated. Real-time PCR (genotyping and gene expression) and ELISA (dosages of sFas, sFasL, IFN-γ, and IL-10) tests were performed. There was no association of FAS -670A/G and FASL -124A/G polymorphisms with TB. The TB group exhibited high plasma levels of sFas and reduced plasma levels of sFasL (p < 0.05). The correlation analysis between these markers revealed a positive correlation between the levels of sFas and sFasL, sFasL and FASL expression, and between sFas and FASL expression (p < 0.05). In the TB group, there was a positive correlation between FASL expression and IFN-γ levels and higher levels of IL-10 compared to IFN-γ (p < 0.05). High levels of sFas and reduced levels of sFasL and FASL expression may contribute to the inhibition of apoptosis in infected cells and represent a possible bacterial resistance resource to maintain the infection.

HTLV-1/2 infection is endemic in Indigenous peoples of the Americas. Its origin is attributed to the migratory flow of Amerindian ancestral peoples. The present study aimed to investigate the seroprevalence of HTLV-1/2 infection in Indigenous peoples of the Brazilian Amazon. A total of 3350 Indigenous people belonging to 15 communities were investigated. The investigation was performed using serological (ELISA), molecular (qPCR) and confirmatory (Western blot and/or Inno-Lia) tests to detect and differentiate the infection. The seroprevalence was 8.3% for HTLV-1/2 infection, with 0.1% of individuals seropositive for HTLV-1 and 8.1% for HTLV-2. The prevalence of infection was statistically higher in women (10.1%) than in men (6.5%) (p = 0.0002). This female predominance was observed in all age groups; in females the prevalence was significant from 41 years old (p < 0.0001) and in males from 51 years old (p < 0.0001). Here, we present a prevalence of HTLV-1/2 among Indigenous peoples of the Brazilian Amazon. The endemic infection in these groups must reflect the different epidemiological profiles observed in these peoples, such as sexual transmission through rejection of condom use, breastfeeding, especially in cases of cross-breastfeeding, and the high rate of pregnancy in the villages.

Antiretroviral therapy (ART) improves the quality of life of people living with HIV-1 (PLHIV) and reduces the mortality rate, but some individuals may develop metabolic abnormalities. This study evaluated changes in the nutritional status and biochemistry of PLHIV on antiretroviral therapy in a cohort that had not previously received ART and to follow up these individuals for 24 months after starting treatment. The initial cohort consisted of 110 individuals and ended with 42 people, assessed by a physical examination. A biochemical assay was performed using the colorimetric enzyme reaction technique, the proviral load was detected by qPCR and the quantification of the CD4/CD8 T lymphocytes was conducted by flow cytometry. PLHIV had increased levels of total cholesterol, LDL, triglycerides, ALT, urea and creatinine after 24 months of ART use (p < 0.05). In the assessment of the nutritional status, PLHIV had increased measures of Triciptal Skinfold, body mass index and arm circumference after the use of ART (p < 0.05). The viral load levels decreased and the CD4 levels increased after 24 months of ART use (p < 0.05). The change in the nutritional status in PLHIV on antiretroviral therapy seems to be a slow process, occurring in the long term, therefore, there is the need for a constant evaluation of these people to identify patients who need a nutritional intervention.

Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed.

The Marajo Archipelago, located in the rural area of ​​the state of Para (Amazon region of Brazil), is the region with the lowest index of human development in the country, presenting poor health services, which makes adequate epidemiological surveillance of HIV-1 infection difficult. After a serological screening enrolling 1,877 samples, three samples were diagnosed with HIV-1 and the pro gene was sequenced to evaluate the presence of resistance mutations to protease inhibitors. Molecular analyses revealed, for the first time in the region of Marajo Island, the occurrence of HIV-1 subtypes B and D, as well as the presence of transmitted high and intermediate protease inhibitors resistance mutations. The results emphasize the importance of ongoing molecular epidemiological surveillance studies in the Brazilian Amazon region because antiretroviral (ARV) resistance mutations may limit treatment options, and the presence of certain subtypes seems to influence the progression to AIDS, particularly in areas where the entry and spread of the virus can be facilitated by socio-demographic problems that expose the population to sexually transmitted infections.

Abstract Backgrounds Neural growth factor (NGF) is a neurotrophin that can interact with the p75NTR receptor and initiate a cascade of reactions that determines cell survival or death, and both are associated with the physiology of liver tissue. Single nucleotide polymorphisms (SNPs) in the NGF and p75NTR genes have been investigated in different pathologies; however, there are no studies that have analyzed their biological roles in the hepatic microenvironment. In the present study, we evaluated the impact of SNPs in these genes on the maintenance of liver function at different stages of inflammation and fibrosis in patients with chronic viral liver disease in the Brazilian Amazon. Methods The SNPs -198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala and Ser205Leu were genotyped by real-time PCR in samples from patients with chronic viral hepatitis stratified by stage of inflammation and liver fibrosis. Histopathological, viral load (VL), liver enzyme and comorbidities data were obtained from updated medical records. Other aspects were highlighted by applied epidemiological questionnaires. Results The -198C/T and Ala35Val polymorphisms in NGF were associated with changes in histopathological profiles, VL and liver enzymes. Ser205Leu polymorphism in p75NTR was associated only with changes in VL and liver enzymes. Polymorphic frequencies were variable among different ethnic populations, mainly for biologically relevant polymorphisms. A multifactorial network of interactions has been established based on genetic, virological, behavioral and biochemical aspects. Conclusion Mutations in the NGF (−198C > T, Ala35Val) and p75NTR (Ser205Leu) genes, within the list of multifactorial aspects, are associated with liver function in different histopathological profiles of patients with chronic viral liver disease in the Brazilian Amazon.

Abstract Arawete and Asurini Indian tribes were revisited after a 36-year follow-up in search of HTLV infections. 46 persons (23 from each tribe) were tested for HTLV-1/2 antibodies and viral DNA. None were positive; this was probably because of their social/cultural isolation from neighboring tribes where HTLV-2c is hyperendemic.

Abstract Background Studies have shown that the human T-lymphotropic virus 2 (HTLV-2) is endemic in several indigenous populations of the Brazilian Amazon and molecular analyses have shown the exclusive presence of HTLV-2 subtype 2c among the indigenous groups of this geographical region. Methods The present study characterizes the prevalence of HTLV-2 infection in three new villages of the Xikrin tribe, in the Kayapo group, according to their distribution by sex and age. The study included 263 samples from individuals from the Kateté, Djujeko and Oodjã villages. Plasma samples were tested for the presence of anti-HTLV-1/2 antibodies using enzyme-linked immunosorbent assays (ELISA). Seropositive samples were confirmed using real-time PCR, nested PCR and sequencing. Results The serological and molecular results confirmed the sole presence of HTLV-2 in 77 (29%) samples, with a prevalence of 38% among women and 18% among men. In these communities, it was found that the prevalence of HTLV-2 infection increased with age. Nucleotide sequences (642 bp, 5’LTR) from eight samples were subjected to phylogenetic analysis by the neighbor-joining method to determine the viral subtype, which confirmed the presence of HTLV-2c. Conclusions The results of the present study establish the presence of HTLV-2 infection in three new villages of the Xikrin tribe and confirm the high endemicity of the infection in the Kayapo indigenous group of the Brazilian Amazon.

Several factors are associated with the development of different clinical forms of tuberculosis (TB). The present study evaluated epidemiological variables and cytokine levels in samples from 89 patients with TB (75 with pulmonary TB and 14 with extrapulmonary TB) and 45 controls. Cytokines were measured by flow cytometry (Human Th1/Th2/Th17 Cytometric Bead Array kit). The TB group had a higher frequency of individuals who were 39 years of age or older, married, with primary education or illiterate and had a lower family income (p < 0.05). All individuals with extrapulmonary TB reported that they were not working, and the main reasons were related to disease symptoms or treatment. The levels of IFN-γ (OR = 4.06) and IL-4 (OR = 2.62) were more likely to be elevated in the TB group (p = 0.05), and IFN-γ levels were lower in patients with extrapulmonary TB compared to those with pulmonary TB (OR = 0.11; p = 0.0050). The ROC curve was applied to investigate the diagnostic accuracy of IFN-γ levels between the different clinical forms of tuberculosis, resulting in high AUC (0.8661; p < 0.0001), sensitivity (93.85%) and specificity median (65.90%), suggesting that IFN-γ levels are useful to differentiate pulmonary TB from extrapulmonary TB. The dysregulation of pro- and anti-inflammatory cytokine levels represent a risk for the development of TB and contribute to the pathogenesis of the disease, especially variation in IFN-γ levels, which may determine protection or risk for extrapulmonary TB.

Chlamydia trachomatis is one of the most prevalent sexually transmitted bacteria worldwide and may increase the risk of other sexually transmitted infections (STIs) including the human immunodeficiency virus (HIV). This study describes the seroprevalence of C. trachomatis infection among antiretroviral-naïve patients who are newly diagnosed with HIV in the city of Belém, Pará, in the Amazon region of Brazil. A cross-sectional study was carried out between January 2018 and January 2019 in 141 people living with HIV/AIDS (PLHA) who were followed up in a specialized unit of the public health network of Pará. The investigation of IgG antibodies against C. trachomatis was performed by enzyme immunoassay. Sociodemographic and sexual behavior information were obtained through a questionnaire. The prevalence of IgG anti-C. trachomatis antibodies was 64.8% (92/141). The majority of individuals were young, heterosexual, single men who did not use condoms during sexual intercourse and had no history of STIs. No significant differences were found when comparing any clinical or demographic data between groups. Our results demonstrated a high rate of exposure to C. trachomatis in newly diagnosed HIV-infected individuals in the Amazon region of Brazil, and all PLHA should be screened for C. trachomatis to decrease transmission of the bacteria and prevent the clinical manifestations of chronic infection.

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.

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).

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.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the world. Several studies have shown a higher prevalence of HPV infection in HIV-infected women. The aim of this study was to determine the prevalence and the genotype diversity of HPV infection in HIV-infected women. From April 2010 to December 2012 cervical specimens were collected from 169 HIV-infected women who screening for cervical cancer at Reference Unit in Belém. The detection of HPV infection was performed by nested PCR and HPV type was performed using a commercial system. The prevalence of HPV infection was 63.3%. Of the 47 genotyped samples, 40.4% was found positive for high risk-HPV 16 and 12.8% for high risk-HPV 52. HPV infection was predominant in the group of women with no incidence of cytological abnormalities and more prevalent in women of reproductive age, unmarried, low education level, and who reported use condoms during sexual intercourse. It was observed an association between HPV infection and independent variables, such as condom use, multiple sexual partners, and history of sexually transmitted diseases. High-risk types of HPV infection were prevalent in our study. Infection with multiple high-risk HPV genotypes may potentiate the development of cervical cancer in HIV-infected women.

Genetic variations in components of the immune response seem to be an important factor that contributes to the manifestation of symptoms of some diseases related to HTLV-1 infection. Nerve growth factor (NGF) and the p75 neurotrophin receptor (p75NTR) are related to the maintenance of neurons and the activation of the immune response. In this study, we evaluated the association of the NGF -198C/T, NGF Ala35Val, and p75NTR Ser205Leu polymorphisms with HTLV-1 infection and plasma cytokine levels in 166 samples from individuals infected with HTLV-1 (59 symptomatic and 107 asymptomatic). The genotyping and quantification of the proviral load were performed by real-time PCR, and cytokine levels were measured by ELISA. The NGF -198C/T and NGF Ala35Val polymorphisms were not associated with HTLV-1 infection. The frequency of the Ser/Leu genotype of p75NTR Ser205Leu was more frequent in the control group (p = 0.0385), and the Ser/Leu genotype and allele Leu were more frequent among the asymptomatic (p < 0.05), especially with respect to the HTLV-1-associated myelopathy (HAM) group (p < 0.05). The symptomatic showed a higher proviral load and higher TNF-α and IL-10 levels (p < 0.05). Asymptomatic carriers of the Ser/Leu genotype (p = 0.0797) had lower levels of proviral load and higher levels of TNF-α (p = 0.0507). Based on the results obtained, we conclude that the p75NTR Ser205Leu polymorphism may be associated with reduced susceptibility to HTLV-1 infection, a lower risk of developing symptoms, including HAM, and better infection control.

Female sex workers (FSWs) represent a key population for the acquisition of sexually transmitted infections (STI) due to their social vulnerability and the risks associated with their occupation. This study was conducted to describe the sociodemographic characteristics and sexual behavior among FSWs in cities in northern Brazil, to determine the prevalence of human immunodeficiency virus 1 (HIV-1) and human T-cell lymphotropic virus (HTLV-1/2) infections and to identify the circulating subtypes of these agents in this key population. A cross-sectional study using the Time Location Sampling (TLS) method was conducted among 339 FSWs in cities in the state of Pará from 2005 to 2006. Serological and molecular tests were performed to identify infections and viral subtypes, and bivariate and multivariate analyses were conducted to identify risk factors. Most FSWs were young, single, less educated and had at least one child. The prevalence of antibodies against HIV-1 and HTLV-1 was 2.3 and 1.7%, respectively. HIV-1 subtypes B (87.5%) and F1 (12.5%) were identified among FSWs, as were Cosmopolitan subtype (1a) and Transcontinental subgroup (A). Unprotected sex and illicit drug use were associated with HIV-1 and HTLV-1 infections using bivariate and multivariate analyses, and age ≥27 years was associated only with HIV. The important information highlighted here clearly indicates that the lack of actions to control and prevent pathogens in FSWs and the lack of strategies for health promotion in key populations can further aggravate the epidemiological scenario of viral infections in remote areas with low human development indices. Neglecting these facts may be causing the spread of these two viruses and their respective subtypes in the general population of northern Brazil.

Chronic infection with Hepacivirus C (HCV) can lead to the occurrence of antinuclear antibodies (ANAs) and changes in cytokine profiles that can be similar to autoimmune diseases. The aim of the study was to identify polymorphisms in important mediators of the immune response in association with ANAs, which could contribute to the development of autoimmunity in hepatitis C. The study included 87 patients with chronic hepatitis C who were evaluated for the presence of ANA (indirect immunofluorescence) and for polymorphisms in the FOXP3, IFNG, IL6, IL8, IL10, MBL2, CRP, TGFΒ1 and TNFA genes (real-time PCR). Of the patients evaluated, 17 (19.54%) had ANA reactivity. The G allele of the FOXP3 rs2232365 polymorphism was more frequent in ANA-positive women (p = 0.0231; OR = 3,285). The C allele of the TGFΒ1 rs1800469 polymorphism was associated with ANA production (p = 0.0169; OR = 2.88). The results suggest that polymorphisms in genes related to immunological regulation may be associated with mechanisms that lead to the emergence of autoantibodies in the context of chronic Hepacivirus C infection.

SAMHD1, a host dNTPase, acts as a retroviral restriction factor by degrading the pool of nucleotides available for the initial reverse transcription of retroviruses, including HTLV-1. Polymorphisms in the SAMDH1 gene may alter the enzymatic expression and influence the course of infection by the virus. The present study investigated the effect of polymorphisms on HTLV-1 infection susceptibility and on progression to disease in 108 individuals infected by HTLV-1 (47 symptomatic and 61 asymptomatic) and 100 individuals in a control group. SAMHD1 rs6029941 (G/A) genotyping and HTLV-1 proviral load measurements were performed using real-time PCR and plasma IFN-α was measured by ELISA. Polymorphism frequency was not associated with HTLV-1 infection susceptibility or with the presence of symptoms. The proviral load was significantly higher in symptomatic individuals with the G allele (p = 0.0143), which presented lower levels of IFN-α (p = 0.0383). SAMHD1 polymorphism is associated with increased proviral load and reduced levels of IFN-α in symptomatic patients, and may be a factor that contributes to the appearance of disease symptoms.

The dysregulation of cytokine production can lead to an inefficient immune response, promoting viral persistence that induces the progression of chronic viral hepatitis. The study investigated the association of the IL6-174G/C polymorphism with changes in cytokine levels and its influence on the persistence and progression of chronic hepatitis caused by HBV and HCV in 72 patients with chronic hepatitis B (HBV), 100 patients with hepatitis C (HCV), and a control group of 300 individuals. The genotyping of the IL6-174G/C polymorphism was performed by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). HCV patients with the wild-type genotype (GG) had a higher viral load (p = 0.0230). The plasma levels of IL-6 were higher among patients infected with HBV and HCV than among the control group (p < 0.0001). Patients with HCV were associated with increased inflammatory activity (A2–A3; p < 0.0001). In hepatitis C, carriers of the GG genotype had higher levels of IL-6 (p = 0.0286), which were associated with A2–A3 inflammatory activity (p = 0.0097). Patients with A2–A3 inflammatory activity and GG genotype had higher levels of IL-6 than those with the GC/CC genotype (p = 0.0127). In conclusion, the wild-type genotype for the IL6-174G/C polymorphism was associated with high levels of IL-6 and HCV viral load and inflammatory activity, suggesting that this genotype may be a contributing factor to virus-induced chronic infection.

The present study evaluated the IL8-251 A/T polymorphism in samples from 74 patients with chronic hepatitis B (HBV), 100 patients with chronic hepatitis C (HCV), and 300 healthy donors (CG). The correlations of this polymorphism with plasma IL-8 and disease stage were calculated. Polymorphisms were identified by real-time PCR. IL-8 was measured by enzyme-linked immunosorbent assay. The IL8-251 A/T genotype was not associated with susceptibility to infection by HBV or HCV. The wild-type allele (A) was associated with higher levels of inflammation (p = 0.0464) and fibrosis scores (p = 0.0016) in the HBV group, representing an increased risk for increased inflammatory activity (OR = 1.84; p = 0.0464) and for high fibrosis scores (OR = 2.63; p = 0.0016). Viral load was higher in HBV patients with polymorphic genotypes (TA and TT) at the IL8-251 A/T polymorphism than in those with the wild-type genotype (p = 0.0272 and p = 0.0464, respectively). Plasma IL-8 was higher among patients infected with HBV or HCV than in the control group (p = 0.0445 and p = 0.0001, respectively). The polymorphic genotype was associated with lower IL-8 than the wild-type genotype in the HBV group (p = 0.0239) and the HCV group (p = 0.0372). The wild-type genotype for IL8-251 A/T and high IL-8 were associated with a worse prognosis for infections; therefore, they may contribute to viral persistence and the development of more severe forms of chronic viral liver diseases.

The present study evaluated the frequency of seropositivity for anti-SARS-CoV-2 (S1 and S2) total antibodies and anti-SARS-CoV-2 (receptor binding domain-RBD-S1) neutralizing antibodies in individuals vaccinated with the immunizing agent Coronavac. This was a cross-sectional study involving 358 individuals divided into two groups. Group 1 consisted of 205 volunteers who were tested for anti-SARS-CoV-2 total antibodies; group 2 consisted of 153 individuals tested for the presence of anti-SARS-CoV-2 neutralizing antibodies. Seropositivity was greater than 70% in both groups, although 17.6% and 20.9% of individuals showed no neutralizing or total antibody reactivity, respectively. The frequency of anti-SARS-CoV-2 total antibodies displayed a significantly different distribution between the sexes but not according to age. The frequency of anti-SARS-CoV-2 neutralizing antibodies was 93.3% (95% CI 68.1–99.8) in the age group from 21 to 40 years but significantly decreased with advancing age, and was 76.2% (95% CI 52.8–91.8) for 41 to 60 years, 72.5% (95% CI 62.8–80.9) for 61 to 80 years, and 46.7% (95% CI 21.3–73.4) for >80 years. Our results reveal a high prevalence of anti-SARS-CoV-2 total antibodies and anti-SARS-CoV-2 neutralizing antibodies in individuals who received both doses of the Coronavac vaccine, suggesting a lower effectiveness of the humoral immune response among those older than 60 years of age, which might be associated with senescence of the immune system.

Objectives: This study investigated the association of alpha-1-antrypsin deficiency (A1AT; S and Z polymorphisms) with HIV-1 and HTLV-1 infection. Methods: Blood samples from 201 HIV-1-infected and 115 HTLV-1-infected individuals were examined and compared with those from 300 healthy controls. Genotyping of A1AT (S and Z) and quantification of plasma viral load were performed using RT-PCR, and the CD4+/CD8+ T-cell count was determined by flow cytometry. Results: The wild-type MM genotype showed the highest frequency in each of the three groups investigated. SS and ZZ homozygous genotypes (variants) were observed only among HTLV-1 patients and controls, respectively. Genotype MS was significantly less frequent in HTLV-1-positive persons than in controls. Statistically significant differences were observed when comparing genotype frequencies between symptomatic and asymptomatic HTLV-1-infected persons. The distribution of plasma HIV-1 viral load among individuals with different genotypes of A1AT polymorphism also differed significantly. Conclusions: The results suggest that A1AT polymorphisms may be associated with human retrovirus infections when dealing with an ethnically mixed population from the Amazon region of Brazil. Keywords: A1T1, Polymorphisms, HIV-1, HTLV-1