Transmission dynamics of SARS-CoV-2 variants in the Brazilian state of Pará.

Introduction: After three years since the beginning of the pandemic, the new coronavirus continues to raise several questions regarding its infectious process and host response. Several mutations occurred in different regions of the SARS-CoV-2 genome, such as in the spike gene, causing the emergence of variants of concern and interest (VOCs and VOIs), of which some present higher transmissibility and virulence, especially among patients with previous comorbidities. It is essential to understand its spread dynamics to prevent and control new biological threats that may occur in the future. In this population_based retrospective observational study, we generated data and used public databases to understand SARS-CoV-2 dynamics. Methods: We sequenced 1,003 SARS-CoV-2 genomes from naso-oropharyngeal swabs and saliva samples from Pará from May 2020 to October 2022. To gather epidemiological data from Brazil and the world, we used FIOCRUZ and GISAID databases. Results: Regarding our samples, 496 (49.45%) were derived from female participants and 507 (50.55%) from male participants, and the average age was 43 years old. The Gamma variant presented the highest number of cases, with 290 (28.91%) cases, followed by delta with 53 (5.28%). Moreover, we found seven (0.69%) Omicron cases and 651 (64.9%) non-VOC cases. A significant association was observed between sex and the clinical condition (female, p = 8.65e-08; male, p = 0.008961) and age (p = 3.6e-10). Discussion: Although gamma had been officially identified only in December 2020/January 2021, we identified a gamma case from Belém (capital of Pará State) dated May 2020 and three other cases in October 2020. This indicates that this variant was circulating in the North region of Brazil several months before its formal identification and that Gamma demonstrated its actual transmission capacity only at the end of 2020. Furthermore, the public data analysis showed that SARS-CoV-2 dispersion dynamics differed in Brazil as Gamma played an important role here, while most other countries reported a new infection caused by the Delta variant. The genetic and epidemiological information of this study reinforces the relevance of having a robust genomic surveillance service that allows better management of the pandemic and that provides efficient solutions to possible new disease-causing agents.

Comparison of Static Balance Control in Infected Htlv-1 Subjects with Different Tsp/Ham Diagnosis.

(1) Background: Tropical spastic paraparesis (TSP/HAM) associated with the T cell lymphotropic virus in type I humans (HTLV-1) is a slow, chronic, and progressive disease that causes balance changes. TSP/HAM diagnosis can be classified as probable, possible, and definite. We compared the static balance control of HTLV-1-infected patients with different TSP/HAM diagnosis. (2) Methods: Our sample consisted of 13 participants infected with HTLV-1 and 16 healthy participants. The center of pressure was recorded using a force platform with open and closed eyes. We divided the recordings into three intervals, period T1 (corresponds to the first 10 s); period T2 (from 10 to 45 s); period T3 (from 45 to 55 s). (3) Results: Eight participants infected with HTLV-1 were classified as probable TSP/HAM and five participants infected with HTLV-1 were classified as definite TSP/HAM. There was a significant increase in postural instability in patients with definite PET/MAH considering the structural and global variables of body sway compared to the control and the probable TSP/HAM. (4) Conclusions: We concluded that the severity of balance is directly related to the degree of signs and symptoms of TSP/HAM.

Chest Computed Tomography Is an Efficient Method for Initial Diagnosis of COVID-19: An Observational Study.

Coronavirus disease (COVID-19) is an infectious disease that can lead to pneumonia, pulmonary oedema, acute respiratory distress syndrome, multiple organ and system dysfunction, and death. This study aimed to verify the efficacy of chest computed tomography (CT) for the initial diagnosis of COVID-19. This observational, retrospective, cross-sectional study included 259 individuals who underwent clinical evaluation, blood collection, chest CT, and a reverse transcription polymerase chain reaction (RT-PCR) diagnostic test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during their course of treatment at a reference hospital in Belém, Pará, Brazil between April and June 2020. Inclusion criteria were flu-like symptoms in adults of both sexes. Individuals with an inconclusive COVID-19 molecular test or who had artifacts in the chest CT images were excluded. Parametric data were analyzed using Student-t-test and non-parametric data were analyzed using average test and Fisher exact test. Participants were divided into two groups: Group 1 (COVID-19 positive), n = 211 (124 males, 87 females), 51.8 ± 17.9 years old and Group 2 (COVID-19 negative), n = 48 (22 males, 26 females), 47.6 ± 18.6 years old. Most frequent symptoms were cough [Group 1 n = 199 (94%)/Group 2 n = 46 (95%)], fever [Group 1 n = 154 (72%)/Group 2 n = 28 (58%)], myalgia [Group 1 n = 172 (81%)/Group 2 n = 38 (79%)], dyspnoea [Group 1 n = 169 (80%) / Group 2 n = 37 (77%)], headache [Group 1 n = 163 (77%)/Group 2 n = 32 (66%)], and anosmia [Group 1 n = 154 (73%)/Group 2 n = 29 (60%)]. Group 1 had a higher proportion of ground-glass opacity [Group 1 n = 175 (83%)/Group 2 n = 24 (50%), 0.00], vascular enhancement sign [Group 1 n = 128 (60%)/Group 2 n = 15 (31%), 0.00], septal thickening [Group 1 n = 99 (47%)/Group 2 n = 13 (27%), 0.01], crazy-paving pattern [Group 1 n = 98 (46%) / Group 2 n = 13 (27%), 0.01], consolidations [Group 1 n = 92 (43%)/Group 2 n = 8 (16%), 0.00], and CO-RADS 4 and 5 [Group 1 n = 163 (77.25%)/Group 2 n = 24 (50%), 0.00] categories in chest CT. Chest CT, when available, was found to be an efficient method for the initial diagnosis and better management of individuals with COVID-19.

HLA-B*13, B*35 and B*39 Alleles Are Closely Associated With the Lack of Response to ART in HIV Infection: A Cohort Study in a Population of Northern Brazil.

Introduction: Immune reconstitution failure after HIV treatment is a multifactorial phenomenon that may also be associated with a single polymorphism of human leukocyte antigen (HLA); however, few reports include patients from the Brazilian Amazon. Our objective was to evaluate the association of the immunogenic profile of the "classical" HLA-I and HLA-II loci with treatment nonresponse in a regional cohort monitored over 24 months since HIV diagnosis. Materials and Methods: Treatment-free participants from reference centers in the state of Pará, Brazil, were enrolled. Infection screening was performed using enzyme immunoassays (Murex AG/AB Combination DiaSorin, UK) and confirmed by immunoblots (Bio-Manguinhos, FIOCRUZ). Plasma viral load was quantified by real-time PCR (ABBOTT, Chicago, Illinois, USA). CD4+/CD8+ T lymphocyte quantification was performed by immunophenotyping and flow cytometry (BD Biosciences, San Jose, CA, USA). Infection was monitored via test and logistics platforms (SISCEL and SICLOM). Therapeutic response failure was inferred based on CD4+ T lymphocyte quantification after 1 year of therapy. Loci A, B and DRB1 were genotyped using PCR-SSO (One Lambda Inc., Canoga Park, CA, USA). Statistical tests were applied using GENEPOP, GraphPad Prism 8.4.3 and BioEstat 5.3. Results: Of the 270 patients monitored, 134 responded to treatment (CD4+ ≥ 500 cells/µL), and 136 did not respond to treatment (CD4+ < 500 cells/µL). The allele frequencies of the loci were similar to heterogeneous populations. The allelic profile of locus B was statistically associated with treatment nonresponse, and the B*13, B*35 and B*39 alleles had the greatest probabilistic influence. The B*13 allele had the highest risk of treatment nonresponse, and carriers of the allele had a detectable viral load and a CD4+ T lymphocyte count less than 400 cells/µL with up to 2 years of therapy. The B*13 allele was associated with a switch in treatment regimens, preferably to efavirenz (EFZ)-based regimens, and among those who switched regimens, half had a history of coinfection with tuberculosis. Conclusions: The allelic variants of the B locus are more associated with non-response to therapy in people living with HIV (PLHIV) from a heterogeneous population in the Brazilian Amazon.

Epstein-Barr Virus (EBV) Genotypes Associated with the Immunopathological Profile of People Living with HIV-1: Immunological Aspects of Primary EBV Infection.

BACKGROUND: The aim of the present study was to evaluate the immunological profile of adult HIV-1+ patients coinfected with primary Epstein-Barr virus (EBV) infection who were free of antiretroviral drugs and inhabitants of the Brazilian Amazon region. MATERIALS AND METHODS: Primary EBV infection was screened by the semiquantitative detection of IgM and IgG anti-VCA. Genotypes were determined by conventional PCR. EBV and HIV viral load (VL) were quantified by real-time PCR. Cytokine dosage and cell quantification were performed by cytometry. RESULTS: Only HIV-1+ individuals had primary EBV infection (7.12%). The EBV-1 genotype was the most prevalent (47.37%). The VL of HIV-1 was lower in the HIV/EBV-2 group. CD4+ T lymphocytes were inversely proportional to the VL of EBV in HIV/EBV-1/2 multi-infected patients. The HIV/EBV-2 group had the lowest cytokine levels, especially IFN-γ and IL-4. Different correlations were proposed for each coinfection. The late search for specific care related to HIV infection directly affected the cytokine profile and the number of CD8+ T lymphocytes. Symptoms were associated with the increase in VL of both viruses and cytokine profile. CONCLUSIONS: Different immunological profiles were associated with EBV genotypes in primary infection, with EBV-2 being more frequent in patients with low levels of HIV viral load. With late infection monitoring and consequent delay in the initiation of HAART, clinical changes and effects on the maintenance of the immune response were observed.

Computed tomography with 6-year follow-up demonstrates the evolution of HTLV-1 related lung injuries: A cohort study.

Previous observational studies have demonstrated the development of pulmonary impairments in human T-lymphotropic virus type 1 (HTLV-1) infected individuals. The main observed lesions due to chronic inflammation of viral infection in situ are bronchiectasis and lung-scarring injuries. This lung inflammation may be the causal agent of restrictive and obstructive lung diseases, primarily in tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP-HAM) patients. We conducted a prospective cohort study to compare spirometry and high-resolution computed tomography (HRCT) findings among 28 HTLV-1-carrier patients over the course of 6 years (2014-2019) (male/female: 7/21; mean age: 54.7 ± 9.5, range: 41-68 years). Chest HRCT exams revealed the development and evolution of lung lesions related to TSP-HAM: including centrilobular nodules, parenchymal bands, lung cysts, bronchiectasis, ground-glass opacity, mosaic attenuation, and pleural thickening. Spirometry exams showed maintenance of respiratory function, with few alterations in parameters suggestive of obstructive and restrictive disorders primarily in individuals with lung lesions and TSP-HAM. The findings of the present study indicate that pulmonary disease related to HTLV-1 is a progressive disease, with development of new lung lesions, mainly in individuals with TSP-HAM. To improve clinical management of these individuals, we recommend that individuals diagnosed with PET-MAH undergo pulmonary evaluation.

Epidemiological risk factors associated with primary infection by Epstein-Barr virus in HIV-1-positive subjects in the Brazilian Amazon region.

To identify the prevalence and risk factors for primary Epstein-Barr virus (EBV) infection in human immunodeficiency virus (HIV)-1-positive adult treatment-naïve patients between January 2018 and December 2019 in a state of the Brazilian Amazon region. A total of 268 HIV-1 positive patients and 65 blood donors participated in the study. Epidemiological data were obtained from medical records and through a designed questionnaire. EBV infection was screened by the semiquantitative detection of anti-viral capsid antigen (VCA) EBV IgM and IgG, followed by molecular detection of the EBNA-3C gene. The plasma viral loads of HIV-1 and EBV were quantified using a commercial kit. The prevalence of primary coinfection was 7.12%. The associated risk factors were education level, family income, history of illicit drug use and sexually transmitted infections, homosexual contact and condom nonuse. Approximately 58.5% had late initiation of highly active antiretroviral therapy, which influenced the risk of HIV-EBV 1/2 multiple infection (odds ratio (OR): 4.76; 95% CI 1.51-15.04) and symptom development (p = 0.004). HIV viral load was associated with patient age (OR: 2.04; 95% CI 2.01-2.07; p = 0.026) and duration of illicit drug use (OR: 1.57; 95% CI 1.12-2.22; p = 0.0548). EBV viral load was associated with younger age (OR: 0.82; 95% CI 0.79-1.03; p = 0.0579). The replication of both viruses was associated with symptom development (HIV = OR: 2.06; 95% CI 1.22-3.50; p = 0.0073; EBV = OR: 8.81; 95% CI 1-10; p = 0.0447). The prevalence of HIV/EBV coinfection was lower than that observed in other studies, and social vulnerability and promiscuous sexual behavior were associated risk factors. A long time of HIV-1 infection, without therapy, influenced the risk of coinfection and disease progression. The viral loads of both viruses may be associated with some epidemiological aspects of the population.

Decrease in naïve T cell production due to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development.

Human T-lymphocytic virus 1 (HTLV-1) is mainly associated with adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP exhibit significant changes in their immune response, and HTLV-1 infection can interfere in cytokine production and perhaps in T cell production. The aims of this study were to evaluate thymic function in HAM/TSP patients and HTLV-1 healthy carriers (HCs) and correlate it to age and interleukin 7 (IL-7) gene expression. Thymic function in 21 HAM/TSP patients and 12 HCs was evaluated by quantifying T cell receptor rearrangement excision circle (TREC) particles and IL-7 gene expression, both measured by quantitative polymerase chain reaction. HAM/TSP patients presented lower TREC particle counts (p = 0.0112) and lower IL-7 expression (p = 0.0102) than HCs. Both TREC particles and IL-7 gene expression were separately analyzed in two age groups: ≤ 59 years and ≥60 years, The ≤59-year-old HAM/TSP patients had a lower TREC count compared with the ≤59-year-old HCs (p = 0.0476). In conclusion, HAM/TSP development could interfere with thymic function because the results showed TREC particle reduction in HAM/TSP patients in relation to HCs, and it could be associated with a concomitant reduction in IL-7 expression.

Genotypes of Epstein-Barr virus (EBV1/EBV2) in individuals with infectious mononucleosis in the metropolitan area of Belém, Brazil, between 2005 and 2016.

Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans. Although their genomes are similar, the regions containing the EBNA genes differ. This study aimed to characterize the EBV genotypes of infectious mononucleosis (IM) cases in the metropolitan region of Belém, Brazil, from 2005 to 2016. A total of 8295 suspected cases with symptoms/signs of IM were investigated by infectious disease physicians at Evandro Chagas Institute, Health Care Service, from January 2005 to December 2016. Out of the total, 1645 (19.8%) samples had positive results for EBV by enzyme immunoassay and 251 (15.3%) were submitted to polymerase chain reaction (PCR) technique, using the EBNA3C region, in order to determine the type of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were also performed. EBV type was identified by PCR in 30.3% (76/251) of individuals; of those, 71.1% (54/76) were classified as EBV1, 17.1% (13/76) as EBV2, and 11.8% (9/76) as EBV1 + EBV2. The main symptoms/signs observed with EBV1 infection were cervical lymphadenopathy (64.8%, 35/54), fever (63%, 34/54), headache (20.4%, 11/54), arthralgia (20.4%, 11/54), and exanthema (18.5%, 10/54). EBV2 infection was detected in all but two age groups, with an average age of 24 years. The most common signs/symptoms of EBV2 were fever (76.9%, 10/13), average duration of 18 days, and lymphadenopathy (69.2%, 9/13). In contrast, EBV1 + EBV2 coinfections were more frequent in those aged five years or less (20.0%, 2/10). The symptoms of EBV1 + EBV2 coinfection included fever (66.7%, 6/9), and cervical lymphadenopathy and headache (33.3%, 3/9) each. The mean values of hepatic enzymes according to type of EBV was significantly different (p < 0.05) in those EBV1 infected over 14 years of age. Thus, this pioneering study, using molecular methods, identified the EBV genotypes in 30.3% of the samples, with circulation of EBV1, EBV2, and EBV1 + EBV2 co-infection in cases of infectious mononucleosis in the northern region of Brazil.

HTLV-I induces lesions in the pulmonary system: A systematic review.

This study analyzed the relationship between infection by human T-cell lymphotropic virus type 1 (HTLV-1) and changes in the pulmonary system. Cohort and case-control study models that analyzed a causal association between HTLV-1 and changes in the pulmonary system were considered. There were no restrictions on language and publication period. The study was registered in the PROSPERO systematic analysis database (Protocol No. CRD42017078236) and was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The following databases were used: PubMed, BVS Regional Portal, Embase, CINAHL and Web of Science. We utilized the Newcastle-Ottawa Scale to assess the methodological quality of published studies and the Kappa coefficient to assess the agreement level between two reviewers. Of the total 1156 studies retrieved by the search strategy, 28 were considered potentially eligible (Kappa test = 0.928). Of the 28 studies, three fully met the inclusion criteria. These indicated that pulmonary lesions, such as bronchiectasis and bronchitis/bronchiolitis, were observed in patients with HTLV-1, with high-resolution computed tomography of the chest being the main method of diagnostic investigation. The analyzed cohort and case-control studies indicated an etiological relationship between HTLV-1 infection and the presence of lung lesions, with emphasis on bronchiectasis in the presence of high viral loads, as well as a higher mortality in these individuals compared with the general population.

HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil.

INTRODUCTION: Human cytomegalovirus is one of the causes of opportunist infections in immunocompromised patients, and is triggered by factors such as state of viral latency, weakened immune responses, and development of antiviral resistance to ganciclovir, the only drug offered by the public health system in Brazil to treat the infection. The goal of this study was to identify mutations that may be associated with antiviral resistance in immunocompromised patients. METHODS: Molecular analysis was performed in 82 blood samples and subjected to genomic DNA extraction by a silica-based method. Three sequences of the HCMV UL97 gene, which encodes a phosphotransferase protein required for activation of ganciclovir, were amplified by polymerase chain reaction. Pyrosequencing methods were applied to one external 2096-bp segment DNA and two internal sequences between nucleotides 1087 to 1828 to detect mutations in this gene. RESULTS: Approximately 10% of sequences contained mutations between nucleotides 377 and 594, in conserved regions of the UL97 gene, leading to amino acid changes. Eleven coding mutations were identified, including changes leading to amino acid substitutions, E596K and S604F, which were observed in 100% of samples and are described for the first time in Brazil. In addition, one mutation (A594V) that is associated with ganciclovir resistance was detected in a kidney transplant patient. CONCLUSIONS: Further studies to detect mutations associated with HCMV resistance to antiviral drugs are required to demonstrate the need to increase the variety and availability of drugs used to treat viral infections in the public health care system in Brazil.

HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil

Abstract INTRODUCTION: Human cytomegalovirus is one of the causes of opportunist infections in immunocompromised patients, and is triggered by factors such as state of viral latency, weakened immune responses, and development of antiviral resistance to ganciclovir, the only drug offered by the public health system in Brazil to treat the infection. The goal of this study was to identify mutations that may be associated with antiviral resistance in immunocompromised patients. METHODS: Molecular analysis was performed in 82 blood samples and subjected to genomic DNA extraction by a silica-based method. Three sequences of the HCMV UL97 gene, which encodes a phosphotransferase protein required for activation of ganciclovir, were amplified by polymerase chain reaction. Pyrosequencing methods were applied to one external 2096-bp segment DNA and two internal sequences between nucleotides 1087 to 1828 to detect mutations in this gene. RESULTS: Approximately 10% of sequences contained mutations between nucleotides 377 and 594, in conserved regions of the UL97 gene, leading to amino acid changes. Eleven coding mutations were identified, including changes leading to amino acid substitutions, E596K and S604F, which were observed in 100% of samples and are described for the first time in Brazil. In addition, one mutation (A594V) that is associated with ganciclovir resistance was detected in a kidney transplant patient. CONCLUSIONS: Further studies to detect mutations associated with HCMV resistance to antiviral drugs are required to demonstrate the need to increase the variety and availability of drugs used to treat viral infections in the public health care system in Brazil.

Low genetic diversity of the Human T-cell Lymphotropic Virus (HTLV-1) in an endemic area of the Brazilian Amazon basin.

The Human T-cell Lymphotropic Virus (HTLV-1) is a Deltaretrovírus that was first isolated in the 1970s, and associated with Adult T-cell Leucemia-Lymphoma (ATLL), and subsequently to Tropical Spastic Paraparesis-Myelopathy (TSP/HAM). The genetic diversity of the virus varies among geographic regions, although its mutation rate is very low (approximately 1% per thousand years) in comparison with other viruses. The present study determined the genetic diversity of HTLV-1 in the metropolitan region of Belém, in northern Brazil. Blood samples were obtained from patients at the UFPA Tropical Medicine Nucleus between January 2010 and December 2013. The DNA was extracted and the PX region of the HTLV was amplified using nested PCR. The positive samples were then digested using the Taq1 enzyme for the identification and differentiation of the HTLV-1 and HTLV-2. The 5'LTR region of the positive HTLV-1 samples were amplified by nested PCR, and then sequenced genetically. The phylogenetic analysis of the samples was based on the maximum likelihood method and the evolutionary profile was analyzed by the Bayesian approach. Overall, 78 samples tested positive for HTLV-1, and 44 were analyzed here. The aA (cosmopolitan-transcontinental) subtype was recorded in all the samples. The following evolutionary rates were recorded for the different subtypes-a: 2.10-3, b: 2.69. 10-2, c: 6.23. 10-2, d: 3.08. 10-2, e: 6. 10-2, f: 1.78. 10-3, g: 2.2. 10-2 mutations per site per year. The positive HTLV-1 samples tested in the present study were characterized by their low genetic diversity and high degree of stability.

The His131Arg substitution in the FCGR2A gene (rs1801274) is not associated with the severity of influenza A(H1N1)pdm09 infection.

BACKGROUND: The virulence and pathogenicity of different influenza strains are responsible for a more or less severe disease. Recent studies have attempted to understand how host genetic factors may influence the clinical presentation of the disease. In the present study, the His131Arg (rs1801274) polymorphism was investigated in individuals from a Brazilian admixed population with a diagnosis of influenza A(H1N1)pdm09 infection. METHODS: In the present study, the influence of the His131Arg (rs1801274) polymorphism, a variant of the FCGR2A gene, was investigated in 436 patients with a diagnosis of influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010. Patients were divided into a group of non-hospitalized patients (n = 192) and a group of hospitalized patients (n = 244; 100 of them died). RESULTS: No significant difference in the allele or genotype frequencies of the rs1801274 polymorphism was observed between groups (p = 0.952 and p = 0.388). Multinomial logistic regression showed no effect of the rs1801274 polymorphism on severity or death of patients from the Brazilian admixed population (p = 0.368 and p = 0.469). CONCLUSIONS: The rs1801274 polymorphism is not associated with severe disease in patients infected with influenza A(H1N1)pdm09.

IL28B gene polymorphisms and Th1/Th2 cytokine levels might be associated with HTLV-associated arthropathy.

The present study is the first investigation of the association between single nucleotide polymorphisms (SNPs - rs8099917, rs12979860 and rs8103142) of the IL28B gene and the development of human T-lymphotropic virus (HTLV)-associated arthropathy (HAA). Individuals with HAA exhibited low interleukin (IL) 6 (p<0.05) and high IL-10 (p<0.05) levels compared with asymptomatic patients. TNF-α/CD4(+) T cell count, TNF-α/CD8(+) T cell count and IFN-γ/proviral load positively correlated in asymptomatic patients. The allelic and genotypic frequencies did not differ between patients with HAA and asymptomatic patients. Seven haplotypes were detected in the investigated population, with haplotype CCT (p<0.05) being the most frequent among the HTLV-infected individuals, while haplotype TTG (p<0.05) was detected in the group with HAA only. Compared with asymptomatic patients, individuals with HAA and genotype TT (rs8099917) exhibited larger numbers of CD8(+) T cells (p<0.05) and higher proviral load levels (p<0.05). Those patients with HAA and genotypes CC (rs12979860) and TT (rs8103142) exhibited high TNF-ß (p<0.05) and IFN-γ (p<0.05) levels. Those patients with HAA and genotype CT/TT (rs12979860) exhibited high IL-10 levels (p<0.05). These results suggest that haplotypes CCT and TTG might be associated with susceptibility to HTLV infection and progression to HAA, respectively. Genotype TT (rs8099917) might be a risk factor for elevation of the proviral load and CD8(+) T cell count. In addition, genotypes CC (rs12979860) and TT (rs8103142) seem to be associated with increased TNF-ß and IFN-γ levels.

Correlation between clinical symptoms and peripheral immune response in HAM/TSP.

HTLV-1 infects principally CD4+ T cells that are the main reservoirs of the virus in vivo, which play an important role in the immunological response. Most of the infected patients are asymptomatic. However, 2-3% of patients will develop HAM/TSP or Adult T lymphoma. HAM/TSP is a chronic inflammatory disease of the central nervous system, which is characterized by unremitting myelopathic symptoms. Studies have shown that cytokines levels alterations (IFN-γ and TNF-α) were associated with tissue injury in HAM/TSP. The aims of this study were to compare the gene expression of IFN-γ, IL-4 and IL-10 of asymptomatic and HAM/TSP HTLV-1 infected patients, and to correlate the gene expression with those of clinical symptoms. 28 subjects were included, 20 asymptomatic HTLV-1 and 8 with HAM/TSP. Spasticity was evaluated using the Modified Ashworth Scale and the degree of walking aid was classified on a progressive scale. The relative gene expression of IFN-γ, IL-4, and IL-10 was measured by Real-Time PCR. Results showed high gene expression of IFN-γ for all patients, but it was higher among HAM/TSP. A significant correlation was observed between IFN-γ gene expression and the degree of walking aid, and IFN-γ gene expression was higher among wheelchair users compared to non-wheelchair users. No association was found with IL-4 and IL-10. These findings indicate that HAM/TSP patients express higher amounts of IFN-γ than asymptomatic patients, and more importantly, the expression of this cytokine was strongly correlated with the need of walking aid.

Siaα2-3Galß1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity.

Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galß1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D' = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus.

The CCR5Δ32 (rs333) polymorphism is not a predisposing factor for severe pandemic influenza in the Brazilian admixed population.

BACKGROUND: Recent studies have tried to identify host genetic variants that could explain severe cases and deaths in infection with Influenza A(H1N1)pdm09, especially among children and young adults. CCR5 is a chemokine receptor expressed on T cells, macrophages and dendritic cells, which is an important mediator of leukocyte chemotaxis during the immune response. A deletion mutation (Δ32) in this gene interferes with the response of immune cells, impairing viral clearance. We evaluated the CCR5Δ32 polymorphism (rs333) in individuals of the Brazilian admixed population with a diagnosis of Influenza A(H1N1)pdm09 infection. METHODS: A total of 330 subjects with a diagnosis of Influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010, were genotyped for the Δ32 deletion (rs333). The cases were classified according to the progression of infection into a group of hospitalized patients (n = 156) and a group of non-hospitalized patients (n = 174). RESULTS: No significant differences in the allele or genotype frequencies of the CCR5Δ32 polymorphism were observed between non-hospitalized and hospitalized patients (p = 0.289 and p = 0.431, respectively). CONCLUSION: The Δ32 deletion in the CCR5 gene is not associated with an unfavorable outcome in patients infected with Influenza A(H1N1)pdm09 in the Brazilian admixed population.

Myocarditis associated with Plasmodium vivax malaria: a case report

Malaria remains a major public health problem in Brazil where Plasmodium vivax is the predominant species, responsible for 82% of registered cases in 2013. Though benign, P. vivax infection may sometimes evolve with complications and a fatal outcome. Here, we report a severe case of P. vivax malaria in a 35-year-old Brazilian man from a malaria endemic area, who presented with reversible myocarditis.