Maria Fernanda Rios Grassi

INTRODUCTION: Human T-cell lymphotropic virus 1 (HTLV-1) is associated with significant health challenges, including a high prevalence of depression and a reduced quality of life (QoL). We aimed to investigate associations between HTLV-1 infection status (uninfected, asymptomatic, or HAM/TSP), depression, and different QoL domains across the QoL. METHODS: This cross-sectional study included 171 participants: 26 uninfected controls, 91 HTLV-1-infected asymptomatic individuals, and 54 individuals diagnosed with HAM/TSP. Depression and QoL were assessed using the Mini-International Neuropsychiatric Interview and the WHOQOL-BREF, respectively. Functional capacity was determined using the Expanded Disability Status Scale (EDSS) and Osame’s Motor Disability Score (OMDS). RESULTS: The overall prevalence of depression was 33.9%, varying significantly according to infection status (19.2% - uninfected individuals, 29.7% - asymptomatic HTLV-1, 48.1% - HAM/TSP). Multivariate analysis revealed that depression had a profoundly negative impact across all QoL domains, particularly the psychological health domain (average -3.58 - point reduction). Individuals with HAM/TSP reported the lowest QoL scores, while asymptomatic individuals also exhibited reduced scores in the physical health domain compared to uninfected controls. CONCLUSIONS: Our findings highlight the urgent need for comprehensive mental health and QoL interventions tailored to HTLV-1-infected populations. This study provides novel insights into the multidimensional effects of HTLV-1 on well-being, emphasizing the importance of addressing both physical and psychological dimensions to improve outcomes for this neglected tropical disease.

Background: Conventional autopsy is the gold standard for postmortem examination, but its use is constrained by biosafety, infrastructure, and acceptability concerns. Ultrasound-guided minimally invasive autopsy and ultrasound-guided minimally invasive tissue sampling (US-MITS) offer practical alternatives for tissue sampling in infectious diseases. The aim of this study was to present a standardized protocol for multiorgan US-MITS and evaluate its performance in terms of success rates, accuracy, and sample quality. Methods: An observational study was conducted on 13 decedents with reverse transcription-polymerase chain reaction (RT-PCR)-confirmed coronavirus disease 2019 in Salvador, Brazil. Using a portable ultrasound machine and 14G semi-automatic Tru-Cut needles, samples were collected from the skin, liver, spleen, kidneys, pancreas, lungs (four-quadrant bilateral sampling), heart, brain, and skeletal muscle. The workflow included routine histological examinations (hematoxylin and eosin, and special stains), electron microscopy, and molecular testing via Ion Torrent sequencing for severe acute respiratory syndrome coronavirus 2 variant calling. Performance was evaluated by measuring the success rates and accuracy (ratio of target tissue to contaminants) using high-resolution slide scanning and digital morphometry. Results: Sampling success ranged from 77% to 100% across the heart, lungs, liver, spleen, and kidneys. Four-quadrant lung sampling yielded comprehensive histological representation. Contamination was generally low, except in the pancreas and lower medial lung quadrant. Tissue suitable for electron microscopy was obtained from most organs; severe acute respiratory syndrome coronavirus 2 was detected in all 13 lungs, and variants were assigned in 10 cases. Conclusion: With minimal training, teams can perform US-MITS. Using a traceable, standardized workflow accelerates proficiency while enabling diagnostic-grade samples to be produced for histological examinations, ultrastructural analysis, and molecular testing in resource-limited and outbreak settings.

To estimate the global prevalence of keratoconjunctivitis sicca (KCS) among Human T‑cell lymphotropic virus type 1 (HTLV‑1)-infected individuals and to evaluate diagnostic methods and research gaps within ocular immunology. A systematic review and meta‑analysis were performed per PRISMA. We searched PubMed/MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, SciELO, LILACS, DOAJ, OpenGrey, and CAPES through December 2023. Eligible studies were cross‑sectional or cohort investigations reporting KCS prevalence in confirmed HTLV‑1-seropositive adults (ELISA or Western blot). Two independent reviewers screened 289 records, with discrepancies resolved by a third. Eight studies met the inclusion criteria. The random‑effects pooled prevalence of KCS in HTLV‑1 infection was 34.6% (95% CI: 19.8%-51.0%; I² = 97.2%). Patients with HTLV‑1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) exhibited a higher prevalence (prevalence ratio [PR]: 2.01; 95% CI: 1.73-2.31). Diagnostic approaches in six studies employed Rose Bengal staining, Schirmer I test, and tear film breakup time. Approximately one in three HTLV‑1-infected patients develop KCS, with elevated risk in those with HAM/TSP. Persistent heterogeneity-driven by diagnostic variability, geographic factors, and demographic differences-underscores the need for standardized criteria, inclusion of diverse populations, and further research on proviral load, gender, and ethnicity to inform ocular practice, including immunology.

Human T-cell lymphotropic virus type 1 (HTLV-1) infection poses significant challenges to maternal and neonatal health, particularly in endemic regions. Vertical transmission, which occurs most commonly through prolonged breastfeeding and rarely during pregnancy, or childbirth, perpetuates the virus within families. This observational, retrospective study analyzed HTLV-1-infected and uninfected pregnant women admitted for delivery at a university maternity hospital in Salvador, Brazil (2020–2022). Medical records provided sociodemographic, clinical, and laboratory data. The HTLV-1 infection rate was 4.61 per 1000 deliveries. The sociodemographic characteristics were similar between infected (n = 17) and uninfected (n = 34) women. HTLV-1-positive women had higher rates of unplanned and undesired pregnancies. Adverse pregnancy outcomes were frequent in both groups (94.1% vs. 91.2%), but metabolic disorders and hypertension/eclampsia were more common among the infected women. Preterm birth and postpartum complications were also more frequent (17.6% vs. 5.9%, respectively), although the difference was not statistically significant. Breastfeeding initiation within the first hours of life was lower among exposed newborns (28.6% vs. 70%; p = 0.013). Neonatal characteristics did not differ significantly between the groups. These findings highlight critical gaps in reproductive health awareness and barriers to accessing preventive interventions. Further research on therapeutic strategies is urgently needed to support the World Health Organization’s (WHO) goal of eliminating HTLV-1 vertical transmission by 2030.

Persistent oncogenic HPV infection is strongly associated with cervical cancer. Studies have suggested a higher prevalence of HPV in women living with HTLV-1. This study aimed to determine whether HTLV-1 infection is associated with cervicovaginal HPV infection and to characterize HPV types according to oncogenic risk. Vaginal fluid samples were subjected to HPV diagnosis via PCR, and positive samples were subjected to Sanger sequencing and massive sequencing. Papanicolaou smears were examined using light microscopy to identify cell abnormalities. Among the 155 women screened, 79 were HTLV-1-infected and 76 were uninfected. HPV PCR identified 23 positive samples (15/79 vs. 8/76; p = 0.13). Twenty-three HPV types were identified, of which only types 31, 54, and 58 were present in both groups. When the number of HPV58 infections in each group was compared, women with HTLV-1 had a higher prevalence (8/79 versus 1/76; p = 0.03). In total, 61.9% of HTLV-1-infected women had at least one high-risk or probable high-risk HPV type (p = 0.12). Cytopathological findings were not significantly different between the groups. Further research is needed to determine whether HTLV-1 infection affects HPV progression and cervical cancer development and to assess the potential benefits of vaccination for women living with HTLV-1.

Human T-cell leukemia virus type 1 (HTLV-1) is associated with an increased risk of tuberculosis (TB). This study aimed to evaluate the performance of the QuantiFERON-TB Gold (QFT) test for the diagnosis of Mycobacterium tuberculosis (MTB) infection in HTLV-1-infected individuals. HTLV-1-infected participants were divided into four groups: HTLV-1-infected individuals with a history of tuberculosis (HTLV/TB), individuals with positive HTLV and tuberculin skin tests (HTLV/TST+) or negative TST (HTLV/TST−), and HTLV-1-negative individuals with positive TST results (HN/TST+). We compared the diagnostic performance of the QFT assay with that of the TST as a reference and evaluated test sensitivity, specificity, accuracy, likelihood ratio, and diagnostic odds ratio. The results showed a higher frequency of positive TST results and induration diameter ≥10 mm in HTLV-1-infected individuals than in the controls. The QFT test was more frequently positive in the HTLV/TB group than in the other groups, while a combined analysis of HTLV/TB and HTLV/TST+ indicated a QFT sensitivity of 57.5%. No significant differences were found in the other diagnostic performance measures, as QFT test results were in agreement with TST results, particularly in TST-negative individuals. Given the low sensitivity of QFT for LTBI in individuals infected with HTLV-1, the TST may be preferable in regions where both infections are endemic.

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-β. 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-β-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-β may contribute to the increased inflammatory response characteristically seen in HAM/TSP patients.

Background: In most cases, Zika virus (ZIKV) causes a self-limited acute illness in adults, characterized by mild clinical symptoms that resolve within a few days. Immune responses, both innate and adaptive, play a central role in controlling and eliminating virus-infected cells during the early stages of infection. Aim: To test the hypothesis that circulating T cells exhibit phenotypic and functional activation characteristics during the viremic phase of ZIKV infection. Methods: A comprehensive analysis using mass cytometry was performed on peripheral blood mononuclear cells obtained from patients with acute ZIKV infection (as confirmed by RT-PCR) and compared with that from healthy donors (HD). The frequency of IFN-γ-producing T cells in response to peptide pools covering immunogenic regions of structural and nonstructural ZIKV proteins was quantified using an ELISpot assay. Results: Circulating CD4⁺ and CD8⁺ T lymphocytes from ZIKV-infected patients expressed higher levels of IFN-γ and pSTAT-5, as well as cell surface markers associated with proliferation (Ki-67), activation ((HLA-DR, CD38) or exhaustion (PD1 and CTLA-4), compared to those from HD. Activation of CD4⁺ and CD8⁺ memory T cell subsets, including Transitional Memory T Cells (TTM), Effector Memory T cells (TEM), and Effector Memory T cells Re-expressing CD45RA (TEMRA), was prominent among CD4⁺ T cell subset of ZIKV-infected patients and was associated with increased levels of IFN-γ, pSTAT-5, Ki-67, CTLA-4, and PD1, as compared to HD. Additionally, approximately 30% of ZIKV-infected patients exhibited a T cell response primarily directed against the ZIKV NS5 protein. Conclusion: Circulating T lymphocytes spontaneously produce IFN-γ and express elevated levels of pSTAT-5 during the early phase of ZIKV infection whereas recognition of ZIKV antigen results in the generation of virus-specific IFN-γ-producing T cells.

Introduction: Familial clustering of HTLV-1 and related diseases has been reported in Brazil. However, intrafamilial transmission of HTLV-1 based on molecular analysis has been studied only in a few communities of Japanese immigrants and African-Brazilians. Objective: To investigate the familial clustering of HTLV-1 infection and to determine the likely routes of transmission through epidemiological and genetic analyzes. Methods: Medical records of 1,759 HTLV-1+ patients from de the Center for HTLV in Salvador, Brazil, were evaluated to identify first-degree relatives previously tested for HTLV-1. Familial clustering was assumed if more than one member of the same family was HTLV-1+. LTR regions of HTLV-1 sequences were analyzed for the presence of intrafamilial polymorphisms. Family pedigrees were constructed and analyzed to infer the likely transmission routes of HTLV-1. Results: In 154 patients at least one other family member had tested positive for HTLV-1 (a total of 182 first-degree relatives). Of the 91 couples (182 individuals), 51.6% were breastfed, and 67.4% reported never using a condom. Of the 42 mother-child pairs, 23.8% had a child aged 13 years or younger; all mothers reported breastfeeding their babies. Pedigrees of families with 4 or more members suggests that vertical transmission is a likely mode of transmission in three families. Three families may have had both vertical and sexual transmission routes for HTLV-1. The genetic signatures of the LTR region of 8 families revealed 3 families with evidence of vertical transmission, another 3 families (spouses) with sexual transmission, and one family with both transmission routes. HTLV-1 sequences belonged to Cosmopolitan subtype HTLV-1a Transcontinental subgroup A. Conclusion: Sexual and vertical transmission routes contribute to the intrafamilial spread of HTLV-1 in the state of Bahia.