Search Results (113)

Eosinophils are innate immune cells that infiltrate tissues in response to cell proliferation and necrosis, which occurs during normal injury repair, parasitic infections, allergies, and cancer. Their involvement in cancer is controversial particularly with regard to tumor-associated tissue eosinophilia (TATE) and a recently defined mechanism of extracellular trap cell death (ETosis), a particular type of eosinophil cell death that is distinct from both apoptosis and necrosis. This narrative review synthesizes the literature regarding the prognostic significance of TATE, focusing on eosinophil ETosis and the important role of transmission electron microscopy (TEM) in its detection and morphological characterization. The prognostic role of TATE is contradictory: in certain tumors, it is a favorable prognostic marker, while in others, it is unfavorable. However, recent research reveals that TATE is associated with a better prognosis in non-viral neoplasms, but it may correlate with a poor prognosis in virus-related neoplasms, such as human T-lymphotropic virus type 1 (HTLV-1)-associated lymphomas and HPV-positive carcinomas. Our ultrastructural investigations revealed distinct phases of eosinophil ETosis in gastric cancer, which were defined by chromatin decondensation, plasma membrane disruption, granule discharge, and development of extracellular traps. We observed synapse-like interactions between eosinophils, exhibiting ETosis or compound exocytosis, and tumor cells, which showed various degrees of cellular damage, ultimately leading to colloid-osmotic tumor cell death. TEM provides important insights into eosinophil-mediated cytotoxicity, requiring further investigation as potential immune effector mechanisms in non-viral tumors. TATE evaluation, together with the viral status of the neoplasia, may be useful to confirm its prognostic significance and consequently its therapeutic implication in specific cancers. Full article

Organ transplantation significantly enhances the survival and quality of life for recipients. However, multiple dependent and independent variables can adversely affect life expectancy after transplantation. Cancer is one of the most common causes of morbidity and mortality for long-term organ transplant recipients. The incidence of cancer in transplanted tissues can be twice as high in approximately 32 distinct cancer types. Oncogenic viruses present in graft tissues may contribute to the etiology of various cancers in transplant recipients. Such oncogenic viruses include hepatitis viruses, papillomaviruses, Epstein–Barr virus, Kaposi’s sarcoma, Merkel cell virus, JC virus, BK virus, and human T-lymphotropic virus type 1, all of which have been associated with various malignancies in these patients. To mitigate this risk, a comprehensive viral screening protocol should be integrated into the transplantation process. Depending on the type of graft, diagnostic methods, control strategies, and post-transplantation care may vary considerably. To efficiently implement any strategy to inhibit viral oncogenicity, a comprehensive understanding of viral–host interactions involving oncogenic viruses within graft tissue is essential. The current view of tumor biology is that changes in the tumor microenvironment and immune signaling influence evolutionary selection pressures. Such interactions ultimately promote conditions that favor uncontrolled host–cell proliferation and malignant transformation. This review examines these viral–host interactions and their role in cancer development among transplant recipients. Full article

HTLV-1/2 in people with HIV (PWH) has been little studied in the Peruvian Amazon, an endemic area for both viruses. We aimed to estimate its prevalence and describe the main clinical and epidemiological features of individuals with HTLV-HIV co-existence. We conducted a cross-sectional study (October–December 2023) at the Division of Infectious Diseases and Tropical Medicine at the Regional Hospital of Loreto in Iquitos. We performed a screening test (recombinant HTLV I+II ELISA) and confirmed the results with INNO-LIA. Among 293 PWH analyzed, 14 (4.8%) were HTLV-positive: 1/293 was HTLV-1-positive (0.3%; 95% CI 0.06–0.9), 11/293 were HTLV-2-positive (3.8%; 95% CI 2.1–6.8), and 2/293 were non-typeable (0.7%; 95% CI 0.1–2.7). Compared with HIV-monoinfected individuals, superinfected patients were older (55 vs. 39 years; p = 0.001). Low education was more frequent in the univariate analysis (35.7% vs. 15.4%; p = 0.05) but was not retained in the multivariable model. In conclusion, HIV–HTLV-2 co-existence is relatively common (~4%) in the Peruvian Amazon, particularly among older individuals, highlighting the need for targeted screening and prevention strategies. Integrating HTLV testing into routine HIV clinic workflows, along with brief and focused counseling for superinfected patients, may help optimize follow-up and care. Full article

Human T-cell lymphotropic virus (HTLV), a retrovirus associated with severe conditions such as leukemia/lymphoma and myelopathy, exhibits variable global prevalence, with higher rates observed in regions such as northeastern Brazil and sub-Saharan Africa. While intrauterine transmission can occur via viral expression in placental tissue and contact with umbilical cord blood, the predominant route is vertical transmission through breastfeeding. Diagnostic testing, particularly serological screening with ELISA and confirmatory methods such as Western blot and PCR, is essential for early detection during pregnancy. The implementation of prenatal screening programs, as seen in Japan and Brazil, has proven effective in reducing vertical transmission by guiding interventions such as breastfeeding cessation in infected mothers. Beyond clinical implications, the psychosocial impact on affected pregnant women highlights the need for an interdisciplinary approach. Although the association between HTLV infection and adverse obstetric outcomes remains controversial, studies suggest increased risks of preterm birth, low birth weight, and other neonatal complications. Given the importance of early diagnosis and prevention, universal prenatal screening protocols represent a critical strategy to reduce viral transmission and its long-term consequences. Full article

Human T-lymphotropic virus 1 (HTLV-1) infection has been associated with inflammatory, autoimmune, and lymphoproliferative diseases with a wide spectrum of clinical manifestations. Among patients with inflammatory rheumatological disease manifestations, cases of rheumatoid arthritis, Sjögren’s syndrome, polymyositis, and fibromyalgia, among others, have been reported. Another common feature of rheumatological diseases is the presence of joint manifestations, such as arthralgia and arthritis. In the present study, we sought to determine the laboratory profile and clinical rheumatological manifestations of people living with HTLV-1/2 residing in a metropolitan area in the Brazilian Amazon. A total of 957 individuals were screened for HTLV-1/2 infection by enzyme-linked immunosorbent assay (ELISA), and samples from seropositive individuals were subjected to infection confirmation by Western blotting or quantitative polymerase chain reaction (qPCR). Individuals with confirmed HTLV-1 and HTLV-2 infection were clinically evaluated for signs and symptoms of rheumatological diseases. Of the 957 individuals tested, 69 were positive for HTLV-1/2 infection, with 56 confirmed cases of HTLV-1 infection (5.9%), 12 of HTLV-2 infection (1.2%), and 1 classified as undetermined (0.1%). After clinical screening, 15 infected individuals with complaints suggestive of rheumatological disease were selected for evaluation by a rheumatologist (11 with HTLV-1 infection (1.1%) and 4 with HTLV-2 infection (0.4%)). The predominant pain pattern was symmetrical polyarthralgia, with large joints predominantly being affected. The diseases diagnosed were psoriatic arthritis, osteoarthritis, fibromyalgia, and regional pain syndromes. Antinuclear antibody (ANA) positivity was observed in two patients. Our findings confirm that HTLV-1 infection is associated with rheumatological disease manifestations and highlight the novel finding of cases of HTLV-2 infection in patients with rheumatoid arthritis symptoms. Full article

Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types. HTLV-1 is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while HTLV-2 shows a lower pathogenic potential, with occasional links to neurological disorders. HTLV-3 and HTLV-4, identified in Central Africa, remain poorly characterized but are genetically close to their simian counterparts, indicating recent zoonotic transmission events. HTLVs replicate through a complex cycle involving cell-to-cell transmission and clonal expansion of infected lymphocytes. Viral persistence is mediated by regulatory and accessory proteins, notably Tax and HBZ in HTLV-1, which alter host cell signaling, immune responses, and genomic stability. Integration of proviral DNA into transcriptionally active regions of the host genome may contribute to oncogenesis and long-term viral latency. Differences in viral protein function and intracellular localization contribute to the distinct pathogenesis observed between HTLV-1 and HTLV-2. Geographically, HTLV-1 shows endemic clusters in southwestern Japan, sub-Saharan Africa, the Caribbean, South America, and parts of the Middle East and Oceania. HTLV-2 is concentrated among Indigenous populations in the Americas and people who inject drugs in Europe and North America. Transmission occurs primarily via breastfeeding, sexual contact, contaminated blood products, and, in some regions, zoonotic spillover. Diagnostic approaches include serological screening (ELISA, Western blot, LIA) and molecular assays (PCR, qPCR), with novel biosensor and AI-based methods under development. Despite advances in understanding viral biology, therapeutic options remain limited, and preventive strategies focus on transmission control. The long latency period, lack of effective treatments, and global neglect complicate public health responses, underscoring the need for increased awareness, research investment, and targeted interventions. Full article

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. Full article

The human T-cell lymphotropic viruses of type 1 and 2 (HTLV 1/2) are retroviruses with estimations of 10 million people infected worldwide. HTLV 1/2 viruses are endemic in South America where Indigenous and Afro American populations are considered of high risk. Although several case reports of HTLV 1/2 associated pathologies and some prevalence studies have been reported in Ecuador, the country lacks a national surveillance and control program, and no screening of blood or organ donors is currently done. We discuss the problems associated to HTLV 1/2 in Ecuador and propose a strategy to improve a surveillance and control program. Full article

Background: Flower-shaped nuclei in plasma cells are rare in multiple myeloma. Case presentation: We report on an 88-year-old male who presented with a mass lesion in the clavicular region. A biopsy of the mass revealed an increase in mature plasma cells with round nuclei. In contrast, a bone marrow examination showed increased plasma cells with flower-shaped nuclei. The patient tested negative for human T-lymphotropic virus type-1 and was diagnosed with multiple myeloma. Conclusions: While multiple myeloma is known for intra-tumor heterogeneity, reports of morphological heterogeneity based on the site of tumor sampling are limited. In this case, the presence of plasma cells with flower-shaped nuclei enabled the identification of site-dependent morphological tumor heterogeneity. Full article

Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic to Brazil, and there is still no specific treatment for these patients. The literature shows that few studies have described the cognitive impairment associated with an HTLV-1 infection, with none of them examining the population of Salvador, where there are approximately forty thousand people infected with the virus. Objectives: To determine the prevalence of cognitive impairment among individuals with HTLV-1. In addition, investigate whether sociodemographic aspects, time since the diagnosis of infection, and the diagnosis of HTLV-Associated Myelopatia/Tropical Spastic Paraparesis (HAM/TSP) or depression are associated with cognitive impairment in this population. Methods: This was an observational, cross-sectional study that consisted of consecutively approaching 100 HTLV-1 patients during outpatient care at a referral center followed by the administration of three questionnaires— the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and Beck’s Depression Inventory. Results: The prevalence of cognitive impairment found was 71% using the MMSE and 82% using the MoCA. There was a statistically significant association between the cognitive dysfunction and the variables of age and education according to the MoCA analysis but not the MMSE data. Diagnosis of HAM/TSP was correlated with cognitive impairment using the MMSE but not the MoCA. The prevalence of depression was 20%, and there was no association between cognitive impairment and depressive symptoms in these patients. Conclusions: The findings of this study demonstrate a correlation between cognitive dysfunction and HTVL-1 infection, with a more evident involvement of executive functions and memory. Larger studies are needed to clarify the association between cognitive dysfunction, age, education, and the diagnosis of HAM/TSP. Full article

This is the first systematic review and meta-analysis to estimate the prevalence of human T-lymphotropic virus 1 and 2 (HTLV-1 and 2) infections among immigrants and refugees worldwide. PubMed/MEDLINE, Scopus, EMBASE, Web of Science, and Virtual Health Library (VHL) databases were searched for studies published from their inception to 6 January 2023. A meta-analysis using a generalized linear mixed model with a random effect was performed for HTLV-1 and HTLV-2. Subgroup analyses were performed based on the decade of study, sample size, confirmatory methods, region of study, risk group, and region of origin. Of the 381 studies initially identified, 21 were included. The pooled prevalence of HTLV-1 and HTLV-2 was 1.28% (95% CI: 0.58, 2.81) and 0.11% (95% CI: 0.04, 0.33), respectively. HTLV-1 prevalence differed significantly by region of origin, with the highest prevalence among those from the Western Pacific Region (7.27%; 95% CI: 2.94, 16.83). The subgroup analysis also showed significant differences between the estimates of HTLV-1 considering the decade of study, sample size, and region of study. For HTLV-2, significant differences were shown in relation to sample size, confirmatory methods, and risk group. The higher HTLV-1 prevalence found deserves public health attention in immigrant and refugee-receiving non-endemic countries. Full article

Adult T-cell Leukemia/Lymphoma (ATLL) is a rare but aggressive malignancy associated with the human T-cell lymphotropic virus type 1 (HTLV-1). ATLL is a challenging malignancy characterized by its aggressive nature and poor prognosis. Despite advancements in treatment, relapse rates remain high. Donor lymphocyte infusion (DLI) is a promising therapeutic option post-hematopoietic stem cell transplantation (HSCT) to prevent relapse. However, the prophylactic use of DLI in ATLL patients remains underexplored. We report the case of a 45-year-old female diagnosed with ATLL. Following induction chemotherapy and successful HSCT, a modified prophylactic DLI regimen was administered, consisting of gradually increasing doses of donor lymphocytes. The patient demonstrated a favorable response with no significant graft-versus-host disease (GVHD) and maintained remission over a 40-month follow-up period, suggesting a potential benefit of this approach. This case highlights the potential efficacy and safety of modified prophylactic DLI in ATLL patients, warranting further investigation. Our findings suggest that modified prophylactic DLI is a viable option for ATLL patients post-HSCT, offering a balance between efficacy and safety. Future research should focus on optimizing DLI protocols and exploring biomarkers for response prediction. Full article

HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a progressive non-remitting and incapacitating disease more frequently seen in women and with a patchy worldwide distribution. HAM/TSP develops in a small percentage of HTLV-1-infected individuals during their lifetime and etiologic factors for disease progression are still unclear. This study aims to describe the first case series of the progression of HAM/TSP in relation to pregnancy. Between January and March of 2012, we reviewed medical charts of women with HAM/TSP currently enrolled in the HTLV-1 cohort at the institute of tropical medicine of Cayetano Heredia University. Inclusion criteria included having a diagnosis of HAM/TSP according to the WHO guidelines and self-reported initial symptoms of HAM/TSP during pregnancy or within six months of delivery. Fifteen women reported having had symptoms compatible with HAM/TSP within four months of delivery. Among them, ten women had no symptoms before pregnancy and reported gait impairment after delivery. Five women with mild gait impairment before pregnancy noticed a worsening of their symptoms after delivery. Symptoms worsened after successive pregnancies. Recent studies have shown that HTLV-1 infection induces a strong T cell-mediated response and that the quality of this response plays a role in HAM/TSP pathogenesis. The relative immunosuppression during pregnancy, including blunting of the T-cell response, might allowed in certain women enhanced replication of HTLV-1 and disease progression in the postpartum. This is the first study looking specifically at HAM/TSP and pregnancy and the number of cases is remarkable. Further prospective studies of HTLV-1-infected women assessing immune markers during pregnancy are warranted. Breastfeeding was the main route of transmission. Strategies to prevent vertical transmission need to be evaluated in HTLV-1 endemic countries of Latin America. Full article

Human T-cell lymphotropic virus (HTLV) infection affects over ten million people worldwide, but there is no effective treatment so far. This review describes the virological, immunological, and clinical outcomes of antiretroviral therapy (ART) in people with HTLV infection. This systematic review followed PRISMA reporting guidelines and was registered in PROSPERO: CRD42022350076. The Newcastle–Ottawa Scale, adapted for cross-sectional studies, and Rob-2 were used to assess the methodological quality of these studies. Systematic searches were conducted in the Medline (PubMed), Scopus (Elsevier), Cochrane Library, and Web of Science (Clarivate Analytics) databases. We retrieved data from eight methodologically diverse articles on treatment of patients infected by HTLV-1 or HTLV-2 alone, or coinfected by HIV-1, who received Raltegravir, Tenofovir, Lamivudine, or Zidovudine. The proviral load decreased in three out of seven studies over 4 to 48 weeks of antiretroviral use. Cellular immune response (CD4, CD8, CD25, CD69, and CD71 cells) was evaluated in six studies. While no significant clinical improvement was observed, all studies reported clinical stability during treatment. Despite the demonstrated antiviral activity of ART, in vitro, clinical improvement was not proven. Most studies showed disease stability during ART use, suggesting potential clinical benefits. There is a need of larger, well-controlled trials to define the role of ART in the treatment of HTLV infection. Full article

Human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects lymphocytes and causes severe diseases. HTLV-1 proviral load (PVL), i.e., the number of host cells that carry HTLV-1 proviral DNA integrated into their genome, can be measured in peripheral blood mononuclear cells (PBMCs) using quantitative polymerase chain reaction. In this narrative review, we discuss the usefulness of HTLV-1 PVL quantification and share our experience acquired during more than 30 years of follow-up of people living with HTLV-1 in the UK. Patients with HTLV-1-associated myelopathy have higher PVL than those with asymptomatic infection. This is consistent across studies in different countries. High PVL predates symptom onset for both inflammatory and proliferative diseases. High PVL is essential but not sufficient for the development of HTLV-1-associated diseases. Therefore, PVL quantification can be used to support the care of people living with HTLV-1 by identifying those most at risk of HTLV-1-associated diseases. Full article