Rita Catarina Medeiros Sousa

Familial Transmission of Human T-cell Lymphotrophic Virus: Silent Dissemination of an Emerging but Neglected Infection

Background HTLV-1 is a retrovirus that causes lymphoproliferative disorders and inflammatory and degenerative diseases of the central nervous system in humans. The prevalence of this infection is high in parts of Brazil and there is a general lack of public health care programs. As a consequence, official data on the transmission routes of this virus are scarce. Objective To demonstrate familial aggregation of HTLV infections in the metropolitan region of Belém, Pará, Brazil. Method A cross-sectional study involving 85 HTLV carriers treated at an outpatient clinic and other family members. The subjects were tested by ELISA and molecular methods between February 2007 and December 2010. Results The prevalence of HTLV was 43.5% (37/85) for families and 25.6% (58/227) for the family members tested (95% CI: 1.33 to 3.79, P = 0.0033). Sexual and vertical transmission was likely in 38.3% (23/60) and 20.4% (29/142) of pairs, respectively (95% CI: 1.25 to 4.69, P = 0.0130). Positivity was 51.3% (20/39) and 14.3% (3/21) in wives and husbands, respectively (95% CI: 0.04 to 0.63, P = 0.0057). By age group, seropositivity was 8.0% (7/88) in subjects <30 years of age and 36.7% (51/139) in those of over 30 years (95% CI: 0.06 to 0.34, P<0.0001). Positivity was 24.1% (7/29) in the children of patients infected with HTLV-2, as against only 5.8% (4/69) of those infected with HTLV-1 (95% CI: 0.05 to 0.72, P = 0.0143). Conclusion The results of this study indicate the existence of familial aggregations of HTLV characterized by a higher prevalence of infection among wives and subjects older than 30 years. Horizontal transmission between spouses was more frequent than vertical transmission. The higher rate of infection in children of HTLV-2 carriers suggests an increase in the prevalence of this virus type in the metropolitan region of Belém.

FAS −670A/G single nucleotide polymorphism may be associated with human T lymphotropic virus-1 infection and clinical evolution to TSP/HAM

FAS and FASLG genes are closely linked to the apoptosis mechanism of the immune system and several polymorphisms in these genes have been associated with susceptibility to diseases. The present study investigated the polymorphisms at positions -670 in the FAS gene, and -169 and -124 in the FASLG gene, among HTLV-1 infected subjects. Blood samples from HTLV infected subjects and seronegative individuals were collected, and polymorphisms were analyzed using a polymerase chain reaction (PCR) followed by RFLP analysis using restriction endonucleases. The genotype frequencies of the FAS -670 polymorphism was the only one that showed a higher and significant prevalence of genotype -670GG among HTLV-1 infected subjects as compared to the control group (p=0.0160), but the genotype -670AA was more frequent among TSP/HAM patients as compared to the asymptomatic individuals (p=0.0005). TCD4(+) and TCD8(+) lymphocyte counts from HTLV infected and seronegative subjects, as well as the proviral load values, according to the status of symptomatic and asymptomatic infection carrying different genotypes were compared but showed no statistical significance. The present results suggest that FAS -670 polymorphism seems to be associated with susceptibility to HTLV-1 and may increase the chance to develop TSP/HAM among HTLV-1 infected persons.

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-β (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-β 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.

Correction: CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon

The aim of this study was to compare computed tomography (CT) scans of chest and lung function among patients with Human T-Lymphotropic Virus Type 1 (HTLV) with and without HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this cross-sectional study performed between January 2013 and June 2016, we included 48 patients with HAM/TSP (19 women and 11 men) and without HAM/TSP (12 women and 6 men). We compared CT findings and lung functions of these groups. Patients who had HAM/TSP had abnormal CT findings (P = 0.000), including more frequent bronchiectasis (P = 0.049), parenchymal bands (P = 0.007), interlobular septal thickening (P = 0.035), and pleural thickening (P = 0.009). In addition, neither patients with HAM/TSP (9/30; 30%) nor the controls (0/18; 0%) had obstructive or restrictive lung disease (P = 0.009). HTLV diagnosis should be considered in all patients with abnormal CT findings in whom no other cause is apparent. It is important to remember that lung disease increases the rates of morbidity and mortality in developing countries.

Association between histological findings, aminotransferase levels and viral genotype in chronic hepatitis C infection

INTRODUCTION The genomic heterogeneity of hepatitis C virus (HCV) influences liver disorders. This study aimed to determine the prevalence of HCV genotypes and to investigate the influence of these genotypes on disease progression. METHODS Blood samples and liver biopsies were collected from HCV-seropositive patients for serological analysis, biochemical marker measurements, HCV genotyping and histopathological evaluation. RESULTS Hepatitis C virus-ribonucleic acid (HCV-RNA) was detected in 107 patients (90.6% with genotype 1 and 9.4% with genotype 3). Patients infected with genotype 1 exhibited higher mean necroinflammatory activity and fibrosis. CONCLUSIONS HCV genotype 1 was the most prevalent and was associated with greater liver dysfunction.

Ocorrência de Bocavírus Humano associado às infecções respiratórias agudas em crianças de 0 a 2 anos de idade na Cidade de Belém, Pará, Brasil

INTRODUCTION: Acute Respiratory Infections (ARI) are one of the main public health problems in the world. Most of these infections are associated with several pathogens, and viruses are the most prevalent agents. Recently, a new parvovirus named Human Bocavirus (HBoV) has been described. Investigations on the relationship between this new agent and cases of ARI in individuals are still scarce. Herein, we review a study of HBoV in a population segment in the Amazon. MATERIALS AND METHODS: In this study, samples of nasopharyngeal aspirates from patients with ARI treated in Health Care Units in Belem, Brazil, were analyzed. Identification of the virus was carried out by polymerase chain reaction using pairs of specific oligonucleotides, followed by phylogenetic analysis of the nucleotide sequences obtained. RESULTS: Of the 397 samples studied, three specimens were HBoV-positive, and one presented as a co-infection with the respiratory syncytial virus. DISCUSSION: The positivity rate obtained in this investigation was lower than that described in other studies; however, previous studies involved hospitalized patients, which constitute a different population group. The phylogenetic analyses revealed a significant similarity between the virus strains found and those previously described. CONCLUSION: This is the first report associating HBoV with ARI in the Amazon.INTRODUCTION: Acute Respiratory Infections (ARI) are one of the main public health problems in the world. Most of these infections are associated with several pathogens, and viruses are the most prevalent agents. Recently, a new parvovirus named Human Bocavirus (HBoV) has been described. Investigations on the relationship between this new agent and cases of ARI in individuals are still scarce. Herein, we review a study of HBoV in a population segment in the Amazon. MATERIALS AND METHODS: In this study, samples of nasopharyngeal aspirates from patients with ARI treated in Health Care Units in Belém, Brazil, were analyzed. Identification of the virus was carried out by polymerase chain reaction using pairs of specific oligonucleotides, followed by phylogenetic analysis of the nucleotide sequences obtained. RESULTS: Of the 397 samples studied, three specimens were HBoV-positive, and one presented as a co-infection with the respiratory syncytial virus. DISCUSSION: The positivity rate obtained in this investigation was lower than that described in other studies; however, previous studies involved hospitalized patients, which constitute a different population group. The phylogenetic analyses revealed a significant similarity between the virus strains found and those previously described. CONCLUSION: This is the first report associating HBoV with ARI in the Amazon.

Barefoot Plantar Pressure Indicates Progressive Neurological Damage in Patients with Human T-Cell Lymphotropic Virus Type 1 Infection

Background The human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is a retrovirus associated with neurological alterations; individuals with HTLV-1 infection may develop HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). Frequent neurological complaints include foot numbness and leg weakness. In this study, we compared the distribution of the body weight on different areas of the foot in HTLV-1 patients with HAM/TSP, asymptomatic HTLV-1 patients, and healthy individuals. Methodology We studied 36 HTLV-1 infected patients, who were divided in two groups of 18 patients each based on whether or not they had been diagnosed with HAM/TSP, and 17 control subjects. The evaluation included an interview on the patient’s clinical history and examinations of the patient’s reflexes, foot skin tactile sensitivity, and risk of falling. The pressure distribution on different areas of the foot was measured with baropodometry, using a pressure platform, while the patients had their eyes open or closed. Main Findings The prevalence of neurological disturbances—altered reflexes and skin tactile sensitivity and increased risk of falling—was higher in HTLV-1 HAM/TSP patients than in HTLV-1 asymptomatic patients. The medium and maximum pressure values were higher in the forefoot than in the midfoot and hindfoot in both HTLV-1 groups. In addition, the pressure on the hindfoot was lower in HAM/TSP patients compared to control subjects. Conclusions The neurological disturbances associated with HTLV-1 infection gradually worsened from HTLV-1 asymptomatic patients to HAM/TSP patients. Baropodometry is a valuable tool to establish the extent of neurological damage in patients suffering from HTLV-1 infection.

Distribution of HIV-1 subtypes in patients with HAART therapeutic failure in the States of Pará and Amazonas, Brazil: 2002 to 2006

The aim of this study was to determine the distribution of HIV-1 subtypes in patients undergoing highly active antiretroviral therapy (HAART) therapeutic failure in Amazonas and Para, two States in northern Brazil, from 2002 to 2006. This study was performed using plasma collected from individuals with human immunodeficiency virus-1 (HIV-1) and/or acquired immunodeficiency syndrome (AIDS) who were selected from the National Genotyping Network (Rede Nacional de Genotipagem – RENAGENO). From 2002 to 2006, a total of 127 plasma samples from the States of Amazonas and Para, in northern Brazil, were obtained from AIDS and/or HIV-positive patients and subjected to genotyping and resistance testing TM using the ViroSeq Genotyping System kit. Using the genetic information obtained from the HIV-1 protease and/or reverse transcriptase regions, HIV-1 subtype B was identified in 85% of the cases, followed by subtype F1 (4.6%) and the recombinant forms BF1 (4.6%) and CF1 (0.8%). The results of this study were similar to the results of other studies conducted in other regions of Brazil, with the exception of the detection of recombinant CF1, which was described for the first time in the Amazon Region.

Data Mining Applied to Diagnose Diseases Caused by Lymphotropic Virus: a Performance Analysis

This paper proposes a new methodology to diagnose the rheumatology manifestations and HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis, or HAM/TSP, in patients who have Lymphotropic virus of T cells in Humans or HTLV of type I and II. Computational intelligence algorithms are used to classify HTLV patient carriers with or without the presence of rheumatology manifestations and of HAM / TSP. A benchmarking is performed among artificial neural intelligence, naive bayes, Bayesian networks and decision tree to evaluate the most suitable technique for solving this application issue. The obtained results demonstrate the potential of the methodology on the helping non-specialist doctors to classify the patient with the disease suspicion.