Imbalanced IL10/TGF-ß production by regulatory T-lymphocytes in patients with HTLV-1-associated myelopathy/ tropical spastic paraparesis.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1), also denominated Human T-cell leukemia virus-1, induces immune activation and secretion of proinflammatory cytokines, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Regulatory T lymphocytes (Tregs) may control of inflammation through the production of regulatory cytokines, including IL10 and TGF-ß. In this study we determined the frequencies of CD4 + and CD8 + Tregs in a HAM/TSP population, compared to asymptomatic carriers and uninfected individuals, as well as investigated the profiles of regulatory and inflammatory cytokines. METHODS: Asymptomatic HTLV-1 carriers and HAM/TSP patients were matched by sex and age. The frequencies of IL10- and/or TGF-ß-producing Tregs were quantified by flow cytometry. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify HTLV-1 proviral load and the mRNA expression of cytokines and cellular receptors in peripheral blood mononuclear cells. RESULTS: Total frequencies of CD4 + Tregs, as well as the IL10-producing CD4 + and CD8 + Treg subsets, were statistically higher in patients with HAM/TSP compared to asymptomatic HTLV-1-infected individuals. In addition, a positive correlation was found between the frequency of CD4 + IL10 + Tregs and proviral load in the HAM/TSP patients evaluated. A positive correlation was also observed between gene expression of proinflammatory versus regulatory cytokines only in HAM / TSP group. CONCLUSIONS: A higher frequencies of IL10-producing Tregs were identified in patients with HAM/TSP. Imbalanced production of IL10 in relation to TGF-ß may contribute to the increased inflammatory response characteristically seen in HAM/TSP patients.

Prevalence and characteristics of HTLV-associated uveitis in patients from Bahia, an endemic area for HTLV - 1 in Brazil.

BACKGROUND: HTLV-1-associated uveitis (HAU) is an inflammatory reaction of the choroid, retina, optic nerve and vitreous that can lead to vision impairment. The worldwide prevalence of HAU varies widely. OBJECTIVE: To determine the prevalence of HAU in patients from Salvador, Bahia-Brazil, and describe uveitis type and associated symptoms. METHODS: Cross-sectional analytical study to determine the prevalence of uveitis in HTLV-1-infected patients recruited in Bahia, Brazil, a region considered endemic for HTLV-1. Patients were enrolled at a local reference center for HTLV (infected) and at an outpatient ophthalmology clinic (noninfected group). All patients were examined by the same ophthalmologist following a single protocol. Prevalence ratios (PR) were calculated. RESULTS: A total of 168 consecutively examined HTLV-1-infected patients and 410 noninfected patients (randomly selected) were included. Females predominated (82.1%) in the HTLV-1-infected group (versus 64.4% in the uninfected group) (p < 0.001). The mean age of infected and uninfected patients was 53.2 and 62.8 years, respectively (p < 0.001). The prevalence of uveitis in HTLV-1+ and HTLV-1- patients was 7.14% and 0.73%, respectively (PR = 9.76; 95CI%:2.79-34.15; p < 0.01). Bilateral intermediate uveitis, associated with symptoms including visual disturbances and floaters, was most commonly identified in the HTLV-1-infected patients, whereas unilateral anterior uveitis, in association with symptoms such as blurring and ocular pain, was more common in the uninfected group. CONCLUSION: The prevalence of uveitis in patients with HTLV-1 was markedly higher than in uninfected subjects. HAU patients were mostly asymptomatic and exhibited bilateral presentation, with uveitis more frequently localized in the intermediate chamber.

HIV/Aids and COVID-19 in Brazil: in four decades, two antithetical approaches to face serious pandemics.

In the space of four decades, Brazil has faced two serious pandemics: human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and Coronavirus disease 2019 (COVID-19). The country's response to HIV/AIDS was coordinated by several stakeholders and recognised the importance of scientific evidence in guiding decision-making, and a network offering monitoring and antiretroviral treatment was provided through coordinated efforts by the country's universal health system. Conversely, the lack of a centrally coordinated strategy and misalignment between government ministries regarding the COVID-19 pandemic response, together with the denial of scientific evidence, promotion of ineffective treatments and insufficient vaccination efforts, have all led to the uncontrolled spread of infection, the near-total collapse of the health system and excess deaths.

Genetic Polymorphisms in Patients With Systemic Lupus Erythematosus and Jaccoud Arthropathy: A Pilot Study.

INTRODUCTION: Jaccoud arthropathy (JA) is a nonerosive and deforming arthropathy experienced frequently by patients with systemic lupus erythematosus (SLE). Although genetic polymorphisms are associated with SLE development, the association between genetic polymorphisms and JA has not been studied to date. The main objective of this study was to evaluate an association between HLA, STAT4, IRF5, and BLK polymorphisms and the presence of JA in Brazilian individuals with SLE. METHODS: Patients were selected from a cohort of individuals with SLE followed at 2 rheumatology reference centers in Salvador, Bahia, Brazil. The JA diagnosis was based on clinical and radiological criteria. The participants were genotyped for rs9271100, rs7574865, rs10488631, and rs13277113 polymorphisms in the HLA, STAT4, IRF5, and BLK genes, respectively, using real-time polymerase chain reaction. The presence of JA was correlated with allele frequencies, and clinical and laboratory data. RESULTS: One hundred forty-four individuals with SLE (38 with JA and 106 with SLE without JA) were studied. The mean age of the patients was 45 ± 12 years; the majority were women and had brown skin. Patients with JA had a longer disease duration than patients without JA. Serositis and neuropsychiatric manifestations were more frequent in the JA population. The A allele of rs13277113 in the BLK gene was associated with the presence of JA. CONCLUSIONS: The rs13277113 polymorphism in the BLK gene was found to be a possible genetic risk for JA development. However, further studies in larger populations should be performed to confirm this finding.

Functional capacity of natural killer cells in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

BACKGROUND: Natural killer (NK) cells are part of the innate immune system and provide surveillance against viruses and cancers. The ability of NK cells to kill virus-infected cells depends on the balance between the effects of inhibitory and activating NK cell receptors. This study aimed to investigate the phenotypic profile and the functional capacity of NK cells in the context of HTLV-1 infection. METHODS: This cross-sectional study sequentially recruited HTLV-1 infected individuals with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-1 (AS) from the Integrated and Multidisciplinary HTLV Center in Salvador, Brazil. Blood samples from healthy blood donors served as controls. NK cell surface receptors (NKG2D, KIR2DL2/KIR2DL3, NKp30, NKG2A, NKp46, TIM-3 and PD-1), intracellular cytolytic (Granzyme B, perforin) and functional markers (CD107a for degranulation, IFN-γ) were assayed by flow cytometry in the presence or absence of standard K562 target cells. In addition, cytotoxicity assays were performed in the presence or absence of anti-NKp30. RESULTS: The frequency of NKp30+ NK cells was significantly decreased in HAM/TSP patients [58%, Interquartile Range (IQR) 30-61] compared to controls (73%, IQR 54-79, p = 0.04). The production of cytolytic (perforin, granzyme B) and functional markers (CD107a and IFN-γ) was higher in unstimulated NK cells from HAM/TSP and AS patients compared to controls. By contrast, stimulation with K562 target cells did not alter the frequency of CD107a+ NK cells in HAM/TSP subjects compared to the other groups. Blockage of the NKp30 receptor was shown to decrease cytotoxic activity (CD107a) and IFN-γ expression only in asymptomatic HTLV-1-infected individuals. CONCLUSIONS: NK cells from individuals with a diagnosis of HAM/TSP present decreased expression of the activating receptor NKp30, in addition to elevated degranulation activity that remained unaffected after blocking the NKp30 receptor.

Performance of Commercially Available Serological Screening Tests for Human T-Cell Lymphotropic Virus Infection in Brazil.

Serological screening for human T-cell lymphotropic virus type 1 (HTLV-1) is usually performed using enzyme-linked immunosorbent assay (ELISA), particle agglutination, or chemiluminescence assay kits. Due to an antigen matrix improvement entailing the use of new HTLV antigens and changes in the format of HTLV screening tests, as well as newly introduced chemiluminescence assays (CLIAs), a systematic evaluation of the accuracy of currently available commercial tests is warranted. We aimed to assess the performance of commercially available screening tests for HTLV infection diagnosis. A diagnostic accuracy study was conducted on a panel of 397 plasma samples: 200 HTLV-negative plasma samples, 170 HTLV-positive plasma samples, and 27 plasma samples indeterminate by Western blotting (WB). WB-indeterminate samples (i.e., those yielding no specific bands for HTLV-1 and/or HTLV-2) were assessed by PCR, and the results were used to compare agreement among the commercially available ELISA screening tests. For performance analysis, WB-indeterminate samples were excluded, resulting in a final study panel of 370 samples. Three ELISA kits (Murex HTLV-1/2 [Murex], anti-HTLV-1/2 SYM Solution [SYM Solution], and Gold ELISA HTLV-1/2 [Gold ELISA]) and one CLIA kit (Architect rHTLV-1/2) were evaluated. All screening tests demonstrated 100% sensitivity. Concerning the HTLV-negative samples, the SYM Solution and Gold ELISA kits had specificity values of >99.5%, while the Architect rHTLV-1/2 test presented 98.1% specificity, followed by Murex, which had a specificity of 92.0%. Regarding the 27 samples with WB-indeterminate results, after PCR confirmation, all ELISA kits showed 100% sensitivity but low specificity. Accuracy findings were corroborated by the use of Cohen's kappa value, which evidenced slight and fair agreement between PCR analysis and ELISAs for HTLV infection diagnosis. Based on the data, we believe that all evaluated tests can be safely used for HTLV infection screening.

Tuberculosis incidence in a cohort of individuals infected with human T-lymphotropic virus type 1 (HTLV-1) in Salvador, Brazil.

BACKGROUND: Few reports have investigated the association between human T-lymphotropic virus type 1 (HTLV-1) and tuberculosis (TB) in countries where both infections are endemic. This study estimates the incidence of TB in a cohort infected with HTLV-1, compared with non-infected individuals, over a ten-year period. METHODS: Retrospective cohort study involving the cross-matching of records of individuals for whom a HTLV serology was performed at a referral center for HTLV (CHTLV) with a database of TB cases from Sinan-the Information System on Diseases of Compulsory Declaration between 2002 and 2012. RESULTS: From a cohort of 6,495 individuals, 1,711 were infected with HTLV-1. A total of 73 TB cases occurred during the study period: 33 HTLV-1-infected patients and 40 uninfected individuals. The incidence density for TB in the HTLV-1 infected group was 3.3 person-years per 1,000 individuals and 1.1 person-years per 1,000 individuals in the group HTLV-1 uninfected group. The relative risk of developing TB in the group of patients infected with HTLV-1 was 2.6 (CI 95 % 1.6-4.2) in comparison with HTLV-1 uninfected group. Compared to individuals with isolated TB, those in the HTLV-1 infected group who had TB were older (p = 0.005) and had lower education levels (p = 0.02). No differences were observed with respect to the clinical/radiological presentation, nor in the outcome of TB and prevalence of HIV infection, when comparing among the HTLV-1-infected and uninfected groups. CONCLUSIONS: Patients infected with HTLV-1 are more susceptible to TB. The epidemiological characteristics of HTLV-1/TB subjects and those infected with TB overlap.

Immune response to Leishmania antigens in an AIDS patient with mucocutaneous leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome (IRIS): a case report.

BACKGROUND: After the onset of HAART, some HIV-infected individuals under treatment present a exacerbated inflammation in response to a latent or a previously treated opportunistic pathogen termed immune reconstitution inflammatory syndrome (IRIS). Few reports of tegumentary leishmaniasis have been described in association with IRIS. Moreover, the immunopathogenesis of IRIS in association with Leishmania is unclear. CASE PRESENTATION: The present study reports on a 29-year-old HIV-infected individual who developed mucocutaneous leishmaniasis associated with immune reconstitution inflammatory syndrome (IRIS) five months following highly active antiretroviral therapy (HAART). Severe lesions resulted in the partial destruction of the nasal septum, with improvement observed 15 days after treatment with Amphotericin B and corticosteroids. The immune response of this patient was evaluated before and after the lesions healed. IRIS was diagnosed in association with high levels of TNF-α and IL-6. Decreased production of IFN-γ and a low IFN-γ/IL-10 ratio were also observed in response to Leishmania antigens. After receiving anti-leishmanial treatment, the individual's specific Th1 immune response was restored. CONCLUSION: The results suggest that the production of inflammatory cytokines by unstimulated T-lymphocytes could contribute to occurrence of leishmaniasis associated with IRIS.

Human T lymphotropic virus type 1 (HTLV-1) proviral load induces activation of T-lymphocytes in asymptomatic carriers.

BACKGROUND: High HTLV-1 proviral load (PVL) is mainly found in infected individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However one third of asymptomatic carriers may have high PVL. This study aimed to evaluate the impact of PVL in the activation of T lymphocytes of asymptomatic individuals infected with HTLV-1. METHODS: Membrane activation markers (CD25+, CD28+, CD45RO+, CD69+, CD62L+, HLA-DR+), FoxP3+ and intracellular IFN-γ expression were evaluated on both CD4+ and CD8+ T-lymphocytes from asymptomatic carriers with PVL ≥ and < 1% of infected cells, using flow cytometry. HTLV-1 proviral load was determined using real-time PCR. RESULTS: Asymptomatic carriers with PVL ≥ 1% presented a higher frequency of CD4+CD25+CD45RO+ (13.2% vs. 4%, p = 0.02), CD4+HLA-DR+ (18% vs. 8.3%, p = 0.01) and CD4+IFN-γ+ (4.5%; 1%, p = 0.01) T-cells, than healthy donors. HTLV-1 PVL was directly correlated with the proportion of CD4+CD25+CD45RO+ T-cells (R = 0.7, p = 0.003). Moreover, a significant increase in the proportion of CD4 + FoxP3+ T-cells was observed in HTLV-1-infected individuals, compared to healthy donors. CONCLUSION: HTLV-1 PVL is associated with activation of both CD4+ and CD8+ T-lymphocytes in asymptomatic individuals. Prospective studies should be conducted to evaluate whether asymptomatic individuals with higher PVL and high immune activation are more prone to developing HTLV-1-associated diseases.

Decreased memory T-cell response and function in human immunodeficiency virus-infected patients with tegumentary leishmaniasis.

The effects of human immunodeficiency virus (HIV) on the immune response in patients with cutaneous leishmaniasis have not yet been fully delineated. This study quantified and evaluated the function of memory T-cell subsets in response to soluble Leishmania antigens (SLA) from patients coinfected with HIV and Leishmania with tegumentary leishmaniasis (TL). Eight TL/HIV coinfected subjects and 10 HIV seronegative subjects with TL were evaluated. The proliferative response of CD4+and CD8+T-cells and naïve, central memory (CM) and effector memory (EM) CD4+T-cells in response to SLA were quantified using flow cytometry. The median cell division indices for CD4+and CD8+T-cells of coinfected patients in response to SLA were significantly lower than those in patients with Leishmania monoinfection (p < 0.05). The proportions of CM and EM CD4+T-cells in response to SLA were similar between the coinfected patients and patients with Leishmania monoinfection. However, the median CM and EM CD4+T-cell counts from coinfected patients were significantly lower (p < 0.05). The reduction in the lymphoproliferative response to Leishmania antigens coincides with the decrease in the absolute numbers of both EM and CM CD4+T-cells in response to Leishmania antigens in patients coinfected with HIV/Leishmania.

Mycobacterium tuberculosis epitope-specific interferon-g production in healthy Brazilians reactive and non-reactive to tuberculin skin test.

The interferon (IFN)-γ response to peptides can be a useful diagnostic marker of Mycobacterium tuberculosis (MTB) latent infection. We identified promiscuous and potentially protective CD4+ T-cell epitopes from the most conserved regions of MTB antigenic proteins by scanning the MTB antigenic proteins GroEL2, phosphate-binding protein 1 precursor and 19 kDa antigen with the TEPITOPE algorithm. Seven peptide sequences predicted to bind to multiple human leukocyte antigen (HLA)-DR molecules were synthesised and tested with IFN-γ enzyme-linked immunospot (ELISPOT) assays using peripheral blood mononuclear cells (PBMCs) from 16 Mantoux tuberculin skin test (TST)-positive and 16 TST-negative healthy donors. Eighty-eight percent of TST-positive donors responded to at least one of the peptides, compared to 25% of TST-negative donors. Each individual peptide induced IFN-γ production by PBMCs from at least 31% of the TST-positive donors. The magnitude of the response against all peptides was 182 ± 230 x 106 IFN-γ spot forming cells (SFC) among TST-positive donors and 36 ± 62 x 106 SFC among TST-negative donors (p = 0.007). The response to GroEL2 (463-477) was only observed in the TST-positive group. This combination of novel MTB CD4 T-cell epitopes should be tested in a larger cohort of individuals with latent tuberculosis (TB) to evaluate its potential to diagnose latent TB and it may be included in ELISPOT-based IFN-γ assays to identify individuals with this condition.

Prevalence of Chlamydia trachomatis endocervical infection in systemic lupus erythematosus patients and evaluation of the risk for HPV-induced lesions.

Chlamydia trachomatis (CT) is the most common bacterial cause of sexually transmitted disease. It has been associated with arthritis and it is a risk factor for human papillomavirus (HPV)-induced lesions. There are few studies on the frequency of CT infection among systemic lupus erythematosus (SLE) patients. The aim of this study was to determine the prevalence of endocervical CT infection among SLE patients and evaluate whether or not CT infection is a risk factor for HPV-induced lesions. A cross-sectional study included a group of patients who fulfilled the American College Rheumatology criteria for a definite diagnosis of SLE and a control group of non-SLE female individuals from Bahia, Brazil. Polymerase chain reaction was used on endocervical swab specimens to test for CT; a gynecological examination including a cervical cytology and biopsy was done for the identification of HPV lesions. A total of 105 SLE patients were studied, and the control group was composed of 104 age-matched apparently normal women. The prevalence of CT endocervical infection was 3.0 % [confidence interval (CI) 95 % = 0.6-8.0 %] in the SLE group and 5.0 % (95 % CI = 2.0-11.0 %) in the control group; the prevalence ratio was 0.60 (95 % CI = 0.1-2.5). The prevalence of vulvar condyloma was higher among SLE patients (11.0 vs. 1.0 %, p < 0.001), as were the prevalences of low-grade lesion (12.0 vs. 1.0 %, p < 0.001) and cervical intraepithelial neoplasia 1 (9.0 vs. 1.0 %, p = 0.02). There was no association between the presence of HPV lesions and CT infections. However, the small number of patients with CT prevents a definite conclusion from being drawn. The prevalence of endocervical CT infection in women with SLE is low and similar to that of the normal population. This suggests that this infection has no role in the pathogenesis of SLE or the development of HPV-induced lesions.

Human T Cell Lymphotropic Virus Type 1 Global Prevalence Associated with the Human Development Index: Systematic Review with Meta-Analysis.

In 2012, the number of people infected with human T cell lymphotropic virus type 1 (HTLV-1) was estimated to be 10 million worldwide. Prevalence varies according to geographic location, ethnic factors, sex, age, populations exposed to risk factors, income, and education, reaching countries with the worst socioeconomic scenarios. There is a need to determine the current global prevalence of HTLV-1 and examine its association with countries' human development index (HDI) to provide data for global health policy. Systematic review with meta-analysis is according to PRISMA 2020 recommendations. It was registered at PROSPERO, CRD42021223146. Prevalence or cross-sectional studies of HTLV-1 infection with at least 100 participants, screening, and confirmatory serologic testing were included. Studies with incomplete or unavailable results or with duplicate information were excluded. Data were selected by two independent investigators and analyzed using R software, a metapackage that generated the forest plots [95% confidence interval (CI)]. Heterogeneity was assessed using the I2 statistic, and funnel plot asymmetry was assessed using Egger's test. Countries were compared using an HDI cutoff ≥0.8. Methodological quality was assessed using Joanna Briggs Institute (JBI) criteria. The overall prevalence of HTLV-1 infection was 0.91% (95% CI: 0.80-1.02, p < .0001) and was higher in low HDI countries [1.18% (95% CI: 1.03-1.34)] than in high HDI countries [0.41% (95% CI: 0.27-0.57)]. Prevalence varied according to the populations studied: it was higher in the general population [1.65% (95% CI: 1.08-2.34)] compared to pregnant women [0.34% (95% CI: 0.17-0.57)] and blood donors [0.04% (95% CI: 0.01-0.08)]. Consistently, prevalence for each population group was higher in low HDI countries than in high HDI countries. The worldwide prevalence of HTLV-1 infection is highly heterogeneous, with a global prevalence of 0.91%. In high HDI countries, the observed prevalence is approximately three times lower than in low HDI countries. In the general population, the observed prevalence is about 5 times higher than in pregnant women and 41 times higher than in blood donors.

HTLV-1 Proviral Load in Vaginal Fluid Correlates with Levels in Peripheral Blood Mononuclear Cells.

BACKGROUND: The prevalence of human T-lymphotropic virus type-1 (HTLV-1) infection is higher in women, and sexual intercourse has been described as an important route of male-to-female transmission. The present study aimed to quantify HTLV-1 proviral load (PVL) in vaginal fluid, and to investigate correlations with PVL in peripheral blood mononuclear cells (PBMCs). In addition, cytopathological alterations and vaginal microbiota were evaluated. METHODS: HTLV-1-infected women were consecutively recruited at a multidisciplinary center for HTLV patients in Salvador, Brazil. All women underwent gynecological examinations to obtain cervicovaginal fluid and venipuncture for blood collection. PVL, as measured by real-time quantitative polymerase chain reaction (RT-qPCR), was expressed as the number of copies of HTLV-1/106 cells in blood and vaginal fluid samples. Light microscopy was used to assess cervicovaginal cytopathology and vaginal microbiota. RESULTS: In the 56 included women (43 asymptomatic carriers and 13 diagnosed with HTLV-1-associated myelopathy/tropical spastic paraparesis-HAM/TSP), mean age was 35.9 (SD ± 7.2) years. PVL was higher in PBMCs (median: 23,264 copies/106 cells; IQR: 6776-60,036) than in vaginal fluid (451.9 copies/106 cells; IQR: 0-2490) (p < 0.0001). PVL in PBMCs was observed to correlate directly with PVL in vaginal fluid (R = 0.37, p = 0.006). PVL was detected in the vaginal fluid of 24 of 43 (55.8%) asymptomatic women compared to 12 of 13 (92.3%) HAM/TSP patients, p = 0.02. Cytopathologic analyses revealed no differences between women with detectable or undetectable PVL. CONCLUSION: HTLV-1 proviral load is detectable in vaginal fluid and correlates directly with proviral load in peripheral blood. This finding suggests that sexual transmission of HTLV-1 from females to males may occur, as well as vertical transmission, particularly in the context of vaginal delivery.

Vaginal dryness in women infected by human T-lymphotropic virus type 1: an exploratory study.

Background: Human T-lymphotropic virus type-1 (HTLV-1) causes a variety of sicca symptoms, including xeroderma, xerostomia, and xerophthalmia. Aim: We sought to evaluate vaginal dryness via the degree of perceived vaginal lubrication, vaginal hormonal cytology, and direct measurements of vaginal wetting. Methods: The research was designed as a cross-sectional study. Vaginal dryness was assessed by scores in the lubrication domain of the Female Sexual Function Index (FSFI) questionnaire and the Vaginal Maturation Index (VMI) determined by vaginal hormonal cytology, as well as the measurement of vaginal lubrication using Schirmer strips placed at the anterior vaginal wall. Medians (25th-75th percentiles) were calculated for each group and compared using a nonparametric Kruskal-Wallis test and the Dunn-Bonferroni post hoc method. Outcomes: Outcomes were detection of the presence of vaginal dryness in women who were infected or noninfected with HTLV-1. Results: HTLV-1-infected women (n = 72, 57 asymptomatic and 15 with HTLV-1-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) and uninfected women (n = 49) were studied. Women with HAM/TSP had significantly lower FSFI lubrication scores than asymptomatic and uninfected women (P = .032). In addition, women with HAM/TSP had significantly lower VMI compared with the asymptomatic and uninfected groups (P = .027 and P = .039, respectively). Clinical Implications: The results of this study show a reduction in vaginal lubrication in HTLV-1-infected women diagnosed with HAM/TSP compared with asymptomatic and uninfected women. Strengths and Limitations: The lack of a gold standard test for the diagnosis of vaginal dryness and the fact that no assessment of vaginal pH was performed were limitations of this study. The strength of the study was the comprehensive assessment of vaginal dryness from several perspectives: subjective (perception of vaginal lubrication according to the vaginal lubrication domain of the FSFI), hormonal (vaginal hormonal cytology to assess local hormone status), and the degree of vaginal moisture (direct measurement of vaginal dryness with an instrument, the Schirmer strip, already used to measure the presence of dry eye). Conclusion: HTLV-1-infected women with HAM/TSP have decreased vaginal lubrication compared with asymptomatic and uninfected women after adjusting for age.

High seroprevalence of Leishmania infantum is linked to immune activation in people with HIV: a two-stage cross-sectional study in Bahia, Brazil.

Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and Leishmania infections is an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by Leishmania infantum and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I, n = 5,346 and CSC-II, n = 317) of treatment-naïve HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble Leishmania infantum Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4+ counts and CD4+/CD8+ ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (p = 0.0076) and a tendency of increased CXCL9 (p = 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with L. infantum seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4+ levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and L. infantum co-infection.

Impact of depression on quality of life in people living with human T cell lymphotropic virus type 1 (HTLV-1) in Salvador, Brazil.

PURPOSE: A previous study found the prevalence of depression in HTLV-1-infected patients to be approximately 30%, but few studies have attempted to correlate depression with quality of life (QOL) in these patients. The present study investigates the association between depression and QOL in people living with HTLV-1. METHODS: A clinical-epidemiological questionnaire, the Mini International Neuropsychiatric Interview and the WHOQOL-Bref were applied to 88 HTLV-1-infected patients (32 with TSP/HAM) at the HTLV Center of the Bahiana School of Medicine and Public Health, Salvador, Brazil. RESULTS: The prevalence of depression among people living with HTLV-1 was 34.1%. Depression was significantly associated with a poor QOL in the physical, psychological, social relationship and environment domains, when controlling for other variables, such as gender, age, time of knowledge of serological diagnosis and presence of tropical spastic paraparesis/HTLV-1associated myelopathy (TSP/HAM). Moreover, patients with TSP/HAM experienced a reduction in their QOL in the physical, psychological and environment domains. CONCLUSION: Our results showed that depression negatively affects the quality of life of people living with HTLV-1, regardless of the presence of TSP/HAM. Since it is possible to improve a patient's QOL by treating depression, psychological evaluations are strongly recommended as a measure to integrate the treatment protocols of HTLV-1 intervention programs.

Prevalence and risk factors for bacterial vaginosis and other vulvovaginitis in a population of sexually active adolescents from Salvador, Bahia, Brazil.

Bacterial vaginosis, trichomoniasis, and genital candidiasis are considered the main etiologies of vulvovaginitis. Few studies estimate the prevalence of vulvovaginitis among adolescents, especially in Brazil. This study aimed to determine the prevalence and main risk factors associated with bacterial vaginosis and genital infection by C. albicans and Trichomonas vaginalis among a group of adolescents from Salvador, Bahia, Brazil. One hundred sexually active adolescents followed at an adolescent gynecology clinic were included. Endocervical and vaginal samples were obtained during gynecological examination. Nugent criteria were applied for the diagnosis of bacterial vaginosis. For Candida albicans and Trichomonas vaginalis detection, culture in Sabouraud agar plates and Papanicolaou cytology were used, respectively. The mean age of participants was 16.6 ± 1.6 years. The prevalence of bacterial vaginosis was 20% (95% CI 12-28) and of genital infection by Candida was 22% (95% CI 14-30). Vaginal cytology detected Trichomonas vaginalis in one patient. Alcohol, tobacco, and illegal drug use (P = 0.02) and multiple lifetime partners were statistically related to bacterial vaginosis (P = 0.01). The prevalence of bacterial vaginosis and genital candidiasis was similar to other studies carried out among adolescents worldwide.

Spatiotemporal distribution analysis of syphilis in Brazil: Cases of congenital and syphilis in pregnant women from 2001-2017.

In Brazil, the notification of congenital (CS) and syphilis in pregnant women (SiP) is compulsory. Notification data provided by the Ministry of Health in combination with the mapping of vulnerable geographic areas is essential to forecasting possible outbreaks and more effectively combating infection through monitoring. We aim to evaluate the spatiotemporal distribution and epidemiological aspects of reported cases of CS and SiP in Brazil. A retrospective ecological study was carried out using secondary surveillance data obtained from the Brazilian National Notifiable Diseases Information System (SINAN) database, considering all reported cases of CS and SiP between 2001 to 2017. Epidemiological characteristics and time trends were analyzed using joinpoint regression models and spatial distribution, considering microregions or states/macroregions as units of analysis. A total of 188,630 (359/100,000 birth lives) CS and 235,895 of SiP (6.3/100,000 inhabitants) were reported during the period studied. In general, the epidemiologic profile of Brazil indicates most reported CS cases occurred in "mixed-race" newborns who were diagnosed within seven days of birth and whose mothers had received prenatal care, but the epidemiologic profile varies by Brazilian macroregion. Regarding SiP, most cases were among women who self-reported 'mixed-race', were aged 20-39 years, had up to eight years of formal education and were diagnosed with primary or latent syphilis. Approximately 549 (98.4%) and 558 (100%) microregions reported at least one case of CS and SiP, respectively. From 2012 to 2016, CS cases increased significantly in almost all Brazilian states, most notably in the South, Southeast, and Central-West macroregions, from 2001-2017 and the relative risk (RR) of SiP increased around 400% (RR: 1,00 to 445,50). Considering the epidemiological scenario of the infection in Brazil, it is necessary to enhance preventive, control and eradication measures.

Efficacy of Corticosteroid Therapy for HTLV-1-Associated Myelopathy: A Randomized Controlled Trial (HAMLET-P).

Corticosteroids are most commonly used to treat HTLV-1-associated myelopathy (HAM); however, their clinical efficacy has not been tested in randomized clinical trials. This randomized controlled trial included 8 and 30 HAM patients with rapidly and slowly progressing walking disabilities, respectively. Rapid progressors were assigned (1:1) to receive or not receive a 3-day course of intravenous methylprednisolone in addition to oral prednisolone therapy. Meanwhile, slow progressors were assigned (1:1) to receive oral prednisolone or placebo. The primary outcomes were a composite of ≥1-grade improvement in the Osame Motor Disability Score or ≥30% improvement in the 10 m walking time (10 mWT) at week 2 for rapid progressors and changes from baseline in 10 mWT at week 24 for slow progressors. In the rapid progressor trial, all four patients with but only one of four without intravenous methylprednisolone achieved the primary outcome (p = 0.14). In the slow progressor trial, the median changes in 10 mWT were -13.8% (95% CI: -20.1--7.1; p < 0.001) and -6.0% (95% CI: -12.8-1.3; p = 0.10) with prednisolone and placebo, respectively (p for between-group difference = 0.12). Whereas statistical significance was not reached for the primary endpoints, the overall data indicated the benefit of corticosteroid therapy. (Registration number: UMIN000023798, UMIN000024085).