Prevalence and Risk Factors for HTLV-1/2 Infection inRiverside and Rural Populations of the State of Pará.

Human T-lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) infection has been described in several Amazonian populations; however, there is still a lack of data on the prevalence of the virus in riparian populations living in rural areas of the state of Pará. The present study aimed to evaluate the prevalence of HTLV-1/2 infection in four riverine communities and one rural area in the state of Pará and to describe the possible risk factors for infection. A total of 907 individuals responded to an epidemiological survey and gave blood samples collected for anti-HTLV-1/2 antibodies by immunoenzymatic assay (EIA). The serum-reactive samples were subjected to confirmation by an in-line assay (Inno-Lia) and by proviral DNA screening using real-time PCR (qPCR). The total prevalence was 0.8% (7/907) for HTLV-1/2 (CI: 0.2-1.3%), with 0.66% HTLV-1 and 0.11% HTLV-2. The prevalence by sex was 0.7% in women (4/565) and 0.9% in men (3/342). Among seropositive patients, 83.3% (5/7) reported being sexually active, and 57.1% (4/7) reported not having the habit of using condoms during their sexual relations. Intrafamily infection was also observed. The results reinforce the need for public policies to prevent and block the spread of HTLV, especially in riparian communities that are subject to difficulties in accessing the Unified Health System (Sistema Único de Saúde/SUS) because infected individuals need clinical monitoring for surveillance and early diagnosis of symptoms associated with HTLV-1.

Association of the p75NTR Ser205Leu Polymorphism with Asymptomatic HTLV-1 Infection.

Genetic variations in components of the immune response seem to be an important factor that contributes to the manifestation of symptoms of some diseases related to HTLV-1 infection. Nerve growth factor (NGF) and the p75 neurotrophin receptor (p75NTR) are related to the maintenance of neurons and the activation of the immune response. In this study, we evaluated the association of the NGF -198C/T, NGF Ala35Val, and p75NTR Ser205Leu polymorphisms with HTLV-1 infection and plasma cytokine levels in 166 samples from individuals infected with HTLV-1 (59 symptomatic and 107 asymptomatic). The genotyping and quantification of the proviral load were performed by real-time PCR, and cytokine levels were measured by ELISA. The NGF -198C/T and NGF Ala35Val polymorphisms were not associated with HTLV-1 infection. The frequency of the Ser/Leu genotype of p75NTR Ser205Leu was more frequent in the control group (p = 0.0385), and the Ser/Leu genotype and allele Leu were more frequent among the asymptomatic (p < 0.05), especially with respect to the HTLV-1-associated myelopathy (HAM) group (p < 0.05). The symptomatic showed a higher proviral load and higher TNF-α and IL-10 levels (p < 0.05). Asymptomatic carriers of the Ser/Leu genotype (p = 0.0797) had lower levels of proviral load and higher levels of TNF-α (p = 0.0507). Based on the results obtained, we conclude that the p75NTR Ser205Leu polymorphism may be associated with reduced susceptibility to HTLV-1 infection, a lower risk of developing symptoms, including HAM, and better infection control.

Prevalence and Risk Factors for HTLV-1/2 Infection in Quilombo Remnant Communities Living in the Brazilian Amazon.

Human T-lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) are retroviruses that originated on the African continent and dispersed throughout other continents through human migratory flows. This study describes the prevalence of HTLV-1 and HTLV-2 infection in residents of 11 quilombo remnant communities in the state of Pará, Brazil, and the associated risk factors. A total of 859 individuals (334 men and 525 women), aged between 7 and 91 years, participated in the study. All subjects answered a questionnaire with questions on sociodemographic characteristics and on risk factors associated with HTLV infection, and blood samples were collected and separated into plasma and leukocytes. An immunoenzymatic assay (ELISA; Murex HTLV-I+II, DiaSorin, Dartford, UK) was used as a screening test, and positive samples were subjected to line immunoassay confirmatory tests (Inno-LIA HTLV I/II Score FUJIREBIO) and DNA extraction for subsequent real-time PCR to differentiate the viral type. Four of the 859 individuals were seropositive for HTLV. HTLV-1 infection was confirmed in one individual from the Itamoari community (0.92%), and HTLV-2 infection was confirmed in two individuals from São Benedito (3.17%) and in one individual from Arimandeua (2.22%). Blood transfusion was the only risk factor associated with HTLV infection in this study. This study reports the occurrence of HTLV-1 and HTLV-2 in quilombo remnant communities in the state of Pará. Considering the African origin of the virus and its introduction into Brazil from the slave trade, the continued evaluation of quilombola communities in the state of Pará is essential to better characterize the distribution of infections in these populations and to create public health policies for the control of the spread of the virus and associated diseases.

The Relevance of a Diagnostic and Counseling Service for People Living With HTLV-1/2 in a Metropolis of the Brazilian Amazon.

Introduction: To identify the prevalence of infection in the urban area of the capital city of Belém, Brazil, the Laboratory of Virology of the Federal University of Pará implemented, as a public service, serological screening for human T-lymphotropic viruses 1 and 2 (HTLV-1/2) infection and, if necessary, counseling service and referral to specialized medical care. The project is funded by the National Council of Science and Technology, the Ministry of Health of Brazil and the Pan American Health Organization. Methods: From January 2020 to June 2021, 1,572 individuals of both sexes were approached to answer a questionnaire and were tested using an enzyme immunoassay (Murex HTLV-I+II, DiaSorin, Dartford, UK). Seropositive samples were confirmed as HTLV-1 and HTLV-2 infection by line immunoassay (INNO-LIA® HTLV I/II Score, Fujirebio, Japan) and/or by real-time polymerase chain reaction. G and Fisher's exact tests were applied to identify the association between epidemiological characteristics and HTLV-1/2 infection. Results: Of the 1,572 screened individuals, 63.74% were females between the ages of 30 and 59 years (49.04%). Infection was confirmed in six individuals (0.38%), among whom three (0.19%) were infected with HTLV-1 and three with HTLV-2 (0.19%). Blood transfusion before 1993 was the main risk factor associated with the route of exposure to the virus (p = 0.0442). The infected individuals were referred to a counseling session with a nursing professional, and two patients who manifested signs and symptoms suggestive of myelopathy associated with HTLV were referred to a neurologist. Conclusion: The implementation of the screening service revealed the occurrence of moderate endemicity of HTLV-1/2 in Belém, reinforcing the importance of continuing the service as a means of establishing an early diagnosis and providing counseling as a measure to prevent and control viral transmission in the general population.

HTLV-1 and HTLV-2 Infection Among Warao Indigenous Refugees in the Brazilian Amazon: Challenges for Public Health in Times of Increasing Migration.

INTRODUCTION: Human T-lymphotropic virus (HTLV) infection is endemic in indigenous populations of the Americas. We describe herein the prevalence of HTLV-1 and HTLV-2 infection among Warao indigenous refugees from Venezuela living in Belém, Pará, Brazil. METHODS: In total, 101 individuals of both sexes (43 men and 58 women) between 18 and 77 years of age were investigated. Blood samples were collected and separated into plasma and leukocytes. Serological screening was performed using an enzyme-linked immunosorbent assay (ELISA; Murex HTLV-I+II, DiaSorin, Dartford, UK), and seropositive samples were submitted to proviral DNA extraction followed by real-time polymerase chain reaction (qPCR). A nested PCR of the env region (630 bp) followed by enzymatic digestion with XhoI was performed to identify the molecular subtype of HTLV-2, in addition to sequencing analysis of the 5'LTR-I and 5'-LTR-II regions. RESULTS: Of the 101 individuals analyzed, 3 (3.0%) were seropositive. Molecular analysis of the pol and tax genes confirmed the HTLV-1 infection in a 55-year-old woman and HTLV-2 infection in a man (68 years old) and a woman (23 years old). HTLV-2 strains were defined by enzymatic digestion as belonging to the HTLV-2b subtype. The sequencing of the 5'LTR regions confirmed the presence of subtype 2b and identified HTLV-1 as belonging to subtype 1A (Cosmopolitan) and the Transcontinental subgroup. Among the infected patients, it was possible to conduct medical interviews with two individuals after delivery of the result. One patient with HTLV-2 reported symptoms such as joint pain, foot swelling, frequent headache, dizziness and lower back pain. The HTLV-1-positive woman was diagnosed with a tumor, dementia, urinary incontinence, felt body pain, and had spots on her body. The presence of the HTLV-2b subtype highlights the prevalence of this molecular variant among indigenous South Americans, as well as the presence of HTLV-1 Transcontinental, which has a worldwide distribution. CONCLUSION: These results reveal a high prevalence of HTLV-1/2 infection among Warao immigrants, suggesting migratory flow as a virus spread mechanism among human populations and alert public authorities to the need to create epidemiological surveillance programs, public social and health policies aimed at welcoming immigrants in the Brazilian territory.

HTLV-1/2 in Indigenous Peoples of the Brazilian Amazon: Seroprevalence, Molecular Characterization and Sociobehavioral Factors Related to Risk of Infection.

HTLV-1/2 infection is endemic in Indigenous peoples of the Americas. Its origin is attributed to the migratory flow of Amerindian ancestral peoples. The present study aimed to investigate the seroprevalence of HTLV-1/2 infection in Indigenous peoples of the Brazilian Amazon. A total of 3350 Indigenous people belonging to 15 communities were investigated. The investigation was performed using serological (ELISA), molecular (qPCR) and confirmatory (Western blot and/or Inno-Lia) tests to detect and differentiate the infection. The seroprevalence was 8.3% for HTLV-1/2 infection, with 0.1% of individuals seropositive for HTLV-1 and 8.1% for HTLV-2. The prevalence of infection was statistically higher in women (10.1%) than in men (6.5%) (p = 0.0002). This female predominance was observed in all age groups; in females the prevalence was significant from 41 years old (p < 0.0001) and in males from 51 years old (p < 0.0001). Here, we present a prevalence of HTLV-1/2 among Indigenous peoples of the Brazilian Amazon. The endemic infection in these groups must reflect the different epidemiological profiles observed in these peoples, such as sexual transmission through rejection of condom use, breastfeeding, especially in cases of cross-breastfeeding, and the high rate of pregnancy in the villages.

TREX1 531C>T Polymorphism is Associated with High Proviral Load Levels in HTLV-1-Infected Persons.

Human T-lymphotropic virus type 1 (HTLV-1) deregulates the immune system and cell cycle, resulting in loss of immune tolerance and disease, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Three prime repair exonuclease 1 (TREX1) maintains innate immune tolerance of the host and host-cell permissiveness to retroviral infections. TREX1 polymorphisms may influence the course of infection and autoimmune manifestations. The influence of TREX1 531C/T polymorphism was investigated in HTLV-1 infection and development of symptoms among 151 persons infected with HTLV-1 (32 HAM/TSP, 19 rheumatologic manifestations, two dermatitis, five more than one diagnosis, two probable HAM/TSP, and 91 asymptomatic individuals) and 100 uninfected persons in the control group. Polymorphism genotyping and proviral load quantification were performed by real-time polymerase chain reaction (PCR) and antinuclear antibodies (ANAs) were screened by an indirect immunofluorescence assay. No statistically significant difference was found in polymorphism genotype and allele frequencies between the infected and control groups. HAM/TSP patients showed higher frequency of TT genotype than asymptomatic persons (p = 0.0339). Proviral load was significantly higher among individuals with CT/TT genotypes and CC genotype carriers had lower proviral load and higher levels of proinflammatory cytokines. ANAs were present only in the HAM/TSP group. TREX1 531C>T polymorphism seems to be associated with TREX-1 regulation and HTLV-1 infection.