Gene expression profiling of p53 and c-myc in HTLV-1 positive blood donors in Congo.

OBJECTIVES: The HTLV-1 infection persists for life, remaining as asymptomatic viral reservoirs in most patients, ensuring the chain of transmission, but around 4% develop adult T-cell leukemia/lymphoma (ATLL). HTLV-1 is an oncogenic retrovirus that transforms CD4+ T lymphocytes and deregulates the lymphoproliferative pathways that contribute to the development of ATLL. To achieve cell transformation, most oncogenic retroviruses use proto-oncogene capture transduction, with proviral integration disrupting the expression of tumor suppressors or proto-oncogenes. THE AIM: We conducted this study on the prevalence of HTLV-1 infection in blood donors to expand the HTLV-1 database, assess the risk of transmission via blood products, as well as evaluate the risk of persistent infection or development of neoplastic diseases in HTLV-1 carriers. MATERIALS AND METHODS: This is a cross-sectional study of blood donors of all categories. For this study, 265 blood donors were recruited at the Centre National de Transfusion Sanguine in Brazzaville. After testing for HTLV-1 antibodies by ELISA, proviral DNA was extracted from all ELISA-positive samples for detection by nested PCR, followed by RT qPCR using specific primers p53 and c-myc for gene expression. RESULTS: 20/265 were positive for anti-HTLV-1 antibody, 5 donors were positive for proviral DNA. The prevalence of HTLV-1 was 1.8%. All HTLV-1-positive donors were male (1.8%), with a positive correlation (p = 0.05); the 1.1% of positive donors were regular, with the majority aged between 31 and 45 years (1.5%), and concubine donors were the most frequent (1.1%). All samples showed normal expression of the p53 and c-myc genes. CONCLUSION: The prevalence, though low, remains a serious problem. No abnormal p53 or c-myc gene expression was detected in HTLV-1-positive donors, which could mean that none of the T lymphocytes in these donors had been transformed by HTLV-1.

Period prevalence of uveitis in human T-lymphotropic virus 1 carriers versus noncarriers in a highly endemic area: The Nagasaki Islands Study.

The magnitude of the effect of human T-lymphotropic virus 1 (HTLV-1) infection on uveitis remains unclear. We conducted a cross-sectional study in a highly endemic area of HTLV-1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle-aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV-1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age- and sex-adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV-1 infection status. Thirty-two (0.8%) participants had uveitis. For HTLV-1 carriers, the age- and sex-adjusted OR (95% CI) of uveitis was 3.27 (1.57-6.72) compared with noncarriers. In conclusion, HTLV-1 infection was associated with a higher risk of uveitis among mostly middle-aged and older Japanese residents in a highly endemic HTLV-1 area. Our findings suggest that physicians who treat HTLV-1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV-1 infection.

Impact and economic analysis of human T-cell lymphotropic virus type 1 (HTLV-1)-targeted antenatal screening, England and Wales, 2021.

BackgroundHuman T-cell lymphotropic virus type 1 (HTLV-1) is a neglected virus that can cause severe disease and be transmitted from mother to child through breastfeeding. Avoidance of breastfeeding prevents 80% of vertical transmission. The United Kingdom (UK) is currently assessing whether HTLV-1-targeted antenatal screening should be implemented.AimWe aimed to assess the impact and cost-effectiveness of a targeted programme to prevent HTLV-1 vertical transmission in England and Wales.MethodsWe estimated the number of pregnant women who have high risk of HTLV-1 infection based on their or their partner's country of birth. With data from 2021, we used a mathematical model to assess cost-effectiveness of HTLV-1 antenatal screening. We also estimated the annual number of infant infections and the number that could be prevented with screening and intervention.ResultsWe estimate that ca 99,000 pregnant women in England and Wales have high risk of HTLV-1 infection. In the absence of screening, 74 (range: 25-211) HTLV-1 infections in infants would be expected to occur every year in England and Wales. Implementation of targeted screening would prevent 58 (range: 19-164) infant infections annually. The intervention is effective (incremental 0.00333 quality-adjusted life years (QALY)) and cost-saving (GBP -57.56 (EUR -66.85)).ConclusionOur findings support implementation of HTLV-1 targeted antenatal screening to reduce vertical transmission from mothers to infants in the UK.

Human T-lymphotropic virus 1/2 infection among prisoners of a major penitentiary complex of Goiás State, Central-West Brazil.

Introduction: Studies on human T-lymphotropic virus 1/2 (HTLV-1/2) infection are scarce in incarcerated population. Therefore, this study estimated the prevalence of HTLV-1/2 infection among prisoners of the major penitentiary complex of Goiás State, Central-West Brazil, comparing it with available data from other Brazilian regions. Methods: A cross-sectional study was conducted with 910 prisoners of the major penitentiary complex in the State of Goiás, Central-West Brazil. All participants were interviewed, and their serum samples were tested for anti-HTLV-1/2 using an enzyme-linked immunosorbent assay (ELISA; Murex HTLV-I + II, DiaSorin, Dartford, UK). Seropositive samples were submitted for confirmation by a line immunoassay (INNO-LIA HTLV I/II, Fujirebio, Europe N.V., Belgium). Results: The majority of participants were males (83.1%), between 25 and 39 years old (56.1%; mean age: 31.98 years), self-reported brown ethnicity (56.2%) and reported 9 years or less of formal education (41.4%). Most reported using non-injectable illicit drugs and various sexual behaviors that present risk for sexually transmitted infections (STIs). The prevalence of anti-HTLV-1/2 was 0.33% (95% CI: 0.07-0.96), HTLV-1 (0.22%) and HTLV-2 (0.11%). The two HTLV-1 seropositive prisoners reported high-risk sexual behaviors, and the HTLV-2 seropositive individual was breastfed during childhood (> 6 months) by her mother and three other women. Conclusion: These data revealed a relatively low seroprevalence of HTLV-1/2 in prisoners in Central-West Brazil, and evidence of HTLV-1 and HTLV-2 circulation in the major penitentiary complex of Goiás State. Given the prevalence of high-risk sexual behaviors, there is a crucial need to intensify education and health programs in prisons to effectively control and prevent HTLV-1/2 and other STIs.

A systematic review of immunosuppressive risk factors and comorbidities associated with the development of crusted scabies.

OBJECTIVES: Crusted scabies (CS, Norwegian scabies) is a severe form of scabies, characterized by hyper-infestation of Sarcoptes scabiei mites. CS is commonly associated with immunosuppression but is also reported in overtly immunocompetent individuals. We reviewed immunosuppressive risk factors and comorbidities associated with CS. METHODS: The National Library of Medicine (PubMed) database was reviewed for patient case reports of CS from January 1998 to July 2023. Two authors screened records for eligibility, extracted data, and one critically appraised the quality of the studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023466126. RESULTS: A total of 436 records were identified, of which 204 were included for systematic review. From these, 683 CS patients were included. CS impacted both genders equally. Adults (21-59 years) were more commonly affected (45.5%) compared to children (0-20 years, 21%). Corticosteroid use was the most prevalent immunosuppressive risk factor identified (27.7% of all cases). About 10.2% of reports were associated with HIV/AIDS, and 8.5% with HTLV-1 infection. 10.5% of patients were overtly immunocompetent with no known risk factors. Overall, 41 (6.0%) died, many subsequent to secondary bacteremia. CONCLUSION: This study represents the first systematic review undertaken on immunosuppressive risk factors associated with CS. This provides insights into trends of immunosuppression and mechanisms of CS development.

HTLV in Sweden.

Sweden is a country with a low prevalence of human lymphotropic T-cell virus (HTLV) infection, estimated at < 0.005%, but the infection rate is notably higher in specific risk groups such as HTLV-2 among intravenous drug users (IVDU) and people originating from HTLV-1 highly endemic areas. Thus, in the most recent study from 2012, the prevalence of HTLV-2 among IVDU in Stockholm was 3.2%. However, much of the epidemiological data on HTLV in Sweden stems from studies conducted primarily between the 1990s and 2007, and the impact of migration to Sweden during the past 15 years has not been evaluated. Despite Sweden's status as a country with generally low prevalence of HTLV, it is prudent to anticipate and prepare for several potential challenges associated with HTLV infection in the future. Proactive measures to enhance awareness, alongside strategies to curtail transmission and mitigate complications, are crucial for addressing this relatively rare, but significant health issue. In this work, we review the current epidemiological knowledge about HTLV in Sweden and discuss future Swedish perspectives.

Prevalence of HTLV-1/2 infection in pregnant women in Central and South America and the Caribbean: a systematic review and meta-analysis.

BACKGROUND: Human T-lymphotropic viruses (HTLV)-1 infection is endemic in many countries of Central and South America and Caribbean (CSA&C). Neither screening nor surveillance programs exist for HTLV-1/2 infection among pregnant women in this region. Neither in Western nations with large migrant flows from HTLV-1/2 endemic regions. METHODS: Systematic review and meta-analysis of the prevalence of HTLV-1/2 infection among CSA&C pregnant women. We included studies searching EMBASE, PubMed/MEDLINE, Scopus, and Web of Science from inception to February 15, 2023. This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. RESULTS: We identified a total of 620 studies. Only 41 were finally included in the meta-analysis. Most studies (61.0%) were from Brazil and Peru (14.6%). The total number of participants was 343,707. The pooled prevalence of HTLV-1/2 infection among CSA&C pregnant women was 1.30% (95% CI: 0.96-1.69) using anti-HTLV-1/2 antibody screening tests. There was a high heterogeneity (I2 = 98.6%). Confirmatory tests gave an HTLV-1 infection rate of 1.02% (95% CI: 0.75-1.33). CONCLUSIONS: The prevalence of HTLV-1/2 infection among CSA&C pregnant women is 1.3%, most cases being HTLV-1. This rate is greater than for other microbial agents regularly checked as part of antenatal screening (such as HIV, hepatitis B, or syphilis). Thus, HTLV-1/2 antenatal testing should be mandatory among CSA&C pregnant women everywhere.

Non-cancerous complications in HTLV-1 carriers.

INTRODUCTION: Human T-cell leukemia virus type 1 (HTLV-1) carriers may develop adult T-cell leukemia (ATL), or HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The evidence is limited regarding other diseases potentially associated with HTLV-1, such as HTLV-1-associated autoimmune diseases. AREA COVERED: We summarized the available information on complications associated with HTLV-1 infection. EXPERT OPINION: Previous studies showed that HTLV-1 carriers have an increased incidence of collagen diseases including Sjögren's syndrome, as well as dysthyroidism, diabetes mellitus, and atherosclerosis. Furthermore, cognitive deficits are observed in asymptomatic carriers and in symptomatic carriers who develop HAM/TSP. It is hypothesized that altered immunoregulation occurs as a result of persistent HTLV-1 infection. A systematic review and meta-analysis demonstrated that HTLV-1 infection itself has an adverse impact on overall survival. ATL alone cannot entirely explain the adverse impact of HTLV-1 infection on overall mortality, because the incidence is low, and therefore HTLV-1-associated diseases as a whole may contribute to the inferior clinical outcome. However, there are insufficient data to determine the causal relationship between HTLV-1 infection and each complication. While non-cancerous events linked to HTLV-1 infection are not fatal, they are likely to reduce quality of life. Large prospective studies should be conducted by international collaborators.

How do socioeconomic determinants of health affect the likelihood of living with HTLV-1 globally? A systematic review with meta-analysis.

Introduction: Human T Lymphotropic Virus type 1 (HTLV-1) is a neglected retrovirus associated with many clinical disorders, most notably Adult T-cell Leukemia/Lymphoma and HTLV-1-Associated Myelopathy (HAM). Found in endemic clusters across the world, high prevalence has been reported in minoritized groups who suffer from health inequities. This study investigates the association between HTLV-1 prevalence and the following socioeconomic determinants of health: education, income, and employment, which are markers of health inequity. Methods: A systematic review was conducted by searching the following databases: Ovid/Medline, Embase, Global Health Database, Web of Science, LILACS and SciELO. Primary studies in English, Spanish and Portuguese mentioning HTLV-1 and one of education, income and/or employment were included. A random-effects meta-analysis was performed, and odds ratios (OR) were calculated to determine the association between these socioeconomic determinants of health and HTLV-1 prevalence. Results: 42 studies were included. The likelihood of having HTLV-1 was higher in individuals with less than completed primary education compared to those who completed primary education (OR 1.86 [95% CI 1.34-2.57]; p < 0.01). This may be because individuals with low education have reduced access to and understanding of health information, thus increasing the prevalence of risk factors associated with HTLV-1 infection. No other determinants were found to be statistically significant. Conclusion: Fewer years of schooling are associated with increased likelihood of contracting HTLV-1. Therefore, health promotion materials and public health policies regarding HTLV-1 must consider those with lower educational levels to effectively reduce disease transmission. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335004, identifier (CRD42022335004).

Geographic characteristics of HTLV-1 molecular subgroups and genetic substitutions in East Asia: Insights from complete genome sequencing of HTLV-1 strains isolated in Taiwan and Japan.

BACKGROUND: Although Japan is a major endemic area for human T-lymphotropic virus type 1 (HTLV-1) and the virus has been well-studied in this region, there is limited research on HTLV-1 in surrounding regions. In this study, we determined the complete genome sequences of HTLV-1 strains isolated from Taiwan and Japan and investigated the geographic characteristics of molecular subgroups and substitution mutations to understand the spread of HTLV-1 and its correlation with human migration. METHODOLOGY/PRINCIPAL FINDINGS: The complete genome sequences of 26 HTLV-1 isolates from Taiwan were determined using next-generation sequencing and were compared with those of 211 isolates from Japan in terms of subgroup and genetic mutations. In total, 15/26 (58%) isolates from Taiwan belonged to the transcontinental subgroup and 11/26 (42%) isolates belonged to the Japanese subgroup. The transcontinental subgroup was significantly more prevalent among Taiwanese isolates than Japanese isolates (58% vs 18%, P < 0.0001). The mutation rate for the complete HTLV-1 sequence was as low as 0.2%. On examining individual base substitutions, the G-to-A mutation was predominant. Bayesian phylogenetic tree analysis estimated the time to the most recent common ancestor for the transcontinental and Japanese subgroups to be 28447 years. The transcontinental subgroups from Taiwan and Japan appeared to form clusters according to their respective regions. CONCLUSIONS/SIGNIFICANCE: The transcontinental subgroup of HTLV-1 is predominant in Taiwan, while the Japanese subgroup is common in Japan. The difference in subgroup distribution may be attributed to the initial spread of the transcontinental subgroup in East Asia, followed by the influx of the Japanese subgroup.

Screening for HTLV-1 infection should be expanded in Europe.

Human T-cell lymphotropic virus type 1 (HTLV-1) infection is spreading globally at an uncertain speed. Sexual, mother-to-child, and parenteral exposure are the major transmission routes. Neither vaccines nor antivirals have been developed to confront HTLV-1, despite infecting over 10 million people globally and causing life-threatening illnesses in 10% of carriers. It is time to place this long-neglected disease firmly into the 2030 elimination agenda. Current evidence supports once-in-life testing for HTLV-1, as recommended for HIV, hepatitis B and C, along with targeted screening of pregnant women, blood donors, and people who attended clinics for sexually transmitted infections (STIs). Similar targeted screening strategies are already being performed for Chagas disease in some Western countries in persons from Latin America. Given the high risk of rapid-onset HTLV-1-associated myelopathy, universal screening of solid organ donors is warranted. To minimize organ wastage, however, the specificity of HTLV screening tests must be improved. HTLV screening of organ donors in Europe has become mandatory in Spain and the United Kingdom. The advent of HTLV point-of-care kits would facilitate testing. Finally, increasing awareness of HTLV-1 will help those living with HTLV-1 to be tested, clinically monitored, and informed about transmission-preventive measures.

Performance evaluation of Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test for different diagnostic situations.

IMPORTANCE: The World Health Organization estimated that 5-10 million people are infected with human T-cell leukemia virus type 1 (HTLV-1). This number is likely to be underestimated because reliable endemic data are available for only approximately 1.5 billion people worldwide. The point-of-care test is a powerful tool for the easy and quick detection of infections without the requirement for expensive instruments and laboratory equipment. Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test that was evaluated in this study, might significantly advance our understanding of the global epidemiology of HTLV-1 infection.

Advances in the treatment of human T-cell lymphotropic virus type-I associated myelopathy.

INTRODUCTION: Nearly 2-3% of those 10 to 20 million individuals infected with the Human T-cell lymphotropic virus type-1 (HTLV-1); are predisposed to developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is a neuro-inflammatory disease; differentiated from multiple sclerosis based on the presence of typical neurologic symptoms, confirmation of HTLV-1 infection, and other molecular biomarkers. AREAS COVERED: A brief review of the epidemiology, host immune responses, and molecular pathogenesis of HAM/TSP is followed by detailed discussions about the host-related risk factors for developing HAM/TSP and success/failure stories of the attempted management strategies. EXPERT OPINION: Currently, there is no effective treatment for HAM/TSP. Anti-retroviral therapy, peculiar cytokines (IFN-α), some anti-oxidants, and allograft bone marrow transplantation have been used for treating these patients with limited success. Under current conditions, asymptomatic carriers should be examined periodically by a neurologist for early signs of spinal cord injury. Then it is crucial to determine the progress rate to adapt the best management plan for each patient. Corticosteroid therapy is most beneficial in those with acute myelitis. However, slow-progressing patients are best managed using a combination of symptomatic and physical therapy. Additionally, preventive measures should be taken to decrease further spread of HTLV-1 infection.

HTLV-1-associated myelopathy in Spain.

BACKGROUND: HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1 carriers develop HTLV-1-associated myelopathy (HAM), a progressive subacute neurological disabling disease. METHODS: We report the main features of patients diagnosed with HAM up to date in Spain, a non-endemic country with a relatively high migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic. RESULTS: A total of 451 cases of HTLV-1 had been recorded in Spain until the end of year 2022. HAM had been diagnosed in 58 (12.9%). The current incidence is of 2-3 new cases per year. Women represent 76%. Mean age at diagnosis is 49 years-old. Nearly 60% are Latin Americans. Although sexual transmission is the most likely route of HTLV-1 acquisition, up to 6 individuals had been infected following solid organ transplantation. Rapid onset myelopathy developed in all but one of these transplant recipients from three HTLV-1-positive donors. HTLV-1 subtype 1a transcontinental was the only variant recognized in HAM patients. HTLV-1 proviral load was significantly greater in HAM patients than in asymptomatic HTLV-1 carriers (677 vs 104 HTLV-1 DNA copies/104 PBMC; p = 0.012). Symptom relief medications and physiotherapy have been the only treatment providing some benefit to HAM patients. Neither significant clinical nor virological efficacy was noticed using antiretrovirals in at least 9 HAM patients. Two thirds of HAM patients ended up in a wheelchair and with urinary/fecal sphincter incontinence. CONCLUSION: HAM is the most frequent clinical manifestation of HTLV-1 infection in Spain, a non-endemic country. Middle aged women migrants from Latin America are the most frequently affected. Two thirds end up in a wheelchair despite using antiretroviral therapy.

Human T-lymphotropic virus 1/2 infection among immigrants and refugees in Central Brazil, an emerging vulnerable population.

Introduction: Migratory flows play a significant role in the spread of human T-lymphotropic virus 1/2 (HTLV-1/2). In the last decade, a substantial migration of individuals occurred from Haiti and Venezuela to Brazil. However, data on the prevalence of HTLV-1/2 infection among these international migrants in Brazil are scarce. This study describes the prevalence of this infection among immigrants and refugees in Central Brazil. Methods: A cross-sectional study was conducted with 537 international migrants in the State of Goiás, Central Brazil. Participants were interviewed, and blood samples were collected. Serological screening for anti-HTLV-1/2 was performed using an enzyme-linked immunosorbent assay (ELISA; Murex HTLV-I + II, DiaSorin, Dartford, UK), and seropositive samples were submitted for confirmation by a line immunoassay (INNO-LIA HTLV I/II, Fujirebio, Europe N.V., Belgium). Results: The majority of participants were males (54.4%), between 18 and 50 years old (78%; mean age: 29.1 years), self-declared black (55.1%), reported 1 to 12 years of formal education (70.9%), and were either Venezuelans (47.9%) or Haitians (39.7%). Additionally, 50.1% were immigrants, 49% were refugees, and five were Brazilian children (0.9%) born to Haitian immigrant parents. The overall prevalence of anti-HTLV-1/2 was 0.95% (95% CI: 0.31-2.28), with HTLV-1 at 0.19% and HTLV-2 at 0.76%. All seropositive individuals (n = 5) were refugees from Venezuela, resulting in a rate of 2.26% for anti-HTLV-1/2, HTLV-1 (0.45%) and HTLV-2 (1.81%) among Venezuelan refugees. Of the demographic and behavioral characteristics evaluated, unprotected sexual intercourse and having more than one sexual partner (≥2) in the previous 12 months were associated with HTLV-1/2 seropositivity among Venezuelans. Conclusion: This study revealed, despite the low seroprevalence of HTLV-1/2 among international migrants in Central Brazil, evidence of HTLV-1 and HTLV-2 infections in Venezuelan refugees. In addition, their characteristics highlight that specific social and health programs should be implemented for these emergent and socially vulnerable migrant groups.

Seroprevalence of Human T-Cell Lymphotropic Virus-1 in a Jamaican Antenatal Population and Assessment of Pooled Testing as a Cost Reduction Strategy for Implementation of Routine Antenatal Screening.

Mother to child transmission (MTCT) of human T-cell lymphotropic virus (HTLV)-1 is associated with increased risk of adult T-cell leukemia and can be unrecognized without routine antenatal screening. We assessed the seroprevalence of HTLV-1/2 among pregnant women attending The University Hospital of the West Indies Antenatal Clinic, 2019, and validated a cost-effective strategy to screen antenatal clinic attendees for HTLV-1/2. Residual antenatal samples from 370 women were tested for HTLV-1/2 by chemiluminescence microparticle immunoassay (CMIA). Six samples were confirmed HTLV-1 positive by Western blot (none for HTLV-2) for a prevalence of 1.62%. Four mother-child pairs were able to be recruited for HTLV testing of children, with two children testing HTLV-1/2 positive. Medical records of HTLV-1-infected women revealed that all women breastfed, indicating an unrecognized risk for HTLV MTCT. To assess whether pooling of samples as a cost-reduction strategy could be introduced, we pooled all antenatal samples received between November and December 2021 into 12 pools of eight samples/pool. Two pools were CMIA positive, and de-pooling of samples identified two CMIA-positive samples (one per pool), both confirmed as HTLV-1 by Western blot. These results indicate that HTLV-1 remains prevalent in pregnant Jamaican women and that sample pooling can be a cost-effective strategy to limit MTCT in Jamaica.

Epidemiological and molecular evidence of intrafamilial transmission through sexual and vertical routes in Bahia, the state with the highest prevalence of HTLV-1 in Brazil.

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.