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A silent spread of human T cell lymphotropic virus type 1 (HTLV-1) has been occurring for thousands of years, with a high prevalence in some regions due to the sexual and vertical transmission and formation of family clusters. The time from HTLV-1 infection until the onset of virus-associated diseases is extremely long, approximately one to three decades. In this study, we evaluated intrafamilial HTLV-1 transmission and associated diseases in 1,204 individuals enrolled and followed up by the GIPH cohort between 1997 and 2017. The family groups ( n  = 43) were composed of 279 individuals who were tested for HTLV-1/human T cell lymphotropic virus type 2 (HTLV-2) and were classified as two groups according to the index case: blood donor (blood donors referred to the GIPH cohort) and nondonor (individuals referred to the GIPH cohort by other health services). The observed rates of HTLV-1 transmission and associated diseases among the relatives were high. Of 236 family members and sexual partners tested for HTLV, 104 (44.1%) were confirmed as having HTLV infection, with 36.7% of relatives whose index case was blood donors and 56.9% of relatives with nondonor index cases. At least one case of HTLV-1-associated myelopathy was observed in 42.9% of the families with intrafamilial transmission of HTLV-1. Brazil is an endemic area for HTLV-1/2 and has implemented mandatory universal screening of blood donors for HTLV-1/2 since 1993. However, the lack of public health services offer diagnosis for HTLV to the general population and pregnant women in the country makes it difficult to identify infected people, and contributes to the silent spread of the virus.

Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed., Competing Interests: The authors have declared that no competing interests exist.

Human T-lymphotropic virus 1 and 2 (HTLV-1/2) belong to the delta group of retroviruses which may cause a life-long infection in humans, HTLV-1 leading to adult T-cell leukemia/lymphoma and other diseases. Different transmission modes have been described, such as breastfeeding, and, as for other blood-borne pathogens, unsafe sexual activity, intravenous drug usage, and blood transfusion and transplantation. The present systematic review was conducted to identify all peer-reviewed studies concerning the work-related infection by HTLV-1/2. A literature search was conducted from January to May 2021, according to the PRISMA methodology, selecting 29 studies: seven related to health care workers (HCWs), five to non-HCWs, and 17 to sex workers (SWs). The findings showed no clear evidence as to the possibility of HTLV-1/2 occupational transmission in HCWs, according to the limited number and quality of the papers. Moreover, non-HCWs showed a higher prevalence in jobs consistent with a lower socioeconomic status or that could represent a familial cluster, and an increased risk of zoonotic transmission from STLV-1-infected non-human primates has been observed in African hunters. Finally, a general increase of HTLV-1 infection was observed in SWs, whereas only one paper described an increased prevalence for HTLV-2, supporting the urgent need for prevention and control measures, including screening, diagnosis, and treatment of HTLV-1/2, to be offered routinely as part of a comprehensive approach to decrease the impact of sexually transmitted diseases in SWs.

Independent epidemiology for respective human T-cell lymphotropic virus (HTLV) types 1 and 2 is little known in blood donors in Brazil, where screening for HTLV-1/2 is mandatory at blood banks, but no testing to confirm/differentiate these viruses. Therefore, this study aims to assess the prevalence of HTLV-1 and -2 in a first-time blood donor population in Northeastern Brazil and to carry out molecular characterization of respective isolates. A cross-sectional study was conducted at the State Blood Bank in Piauí. Samples were screened for anti-HTLV-1/2 by enzyme immunoassay, and reactive samples were confirmed using a line immunoassay and polymerase chain reaction (PCR). Of 37 306 blood donors, 47 were anti-HTLV-1/2 reactive by enzyme immunoassay. After confirmed by line immunoassay, 22 were positive for HTLV-1 (0.59 per 1000; 95% CI: 0.38-0.87), 14 were positive for HTLV-2 (0.37 per 1000; 95% CI: 0.21-0.61), 1 was indeterminate, and the remaining donors were negative. The HTLV-1 infection was also confirmed by PCR in all anti-HTLV-1-positive samples, and sequencing classified these isolates as belonging to the Transcontinental (A) subgroup of the Cosmopolitan (1a) subtype. Of 14 anti-HTLV-2-positive samples, 11 were also PCR positive, which belonged to subtype a (HTLV-2a/c). In addition, 38 family members of 5 HTLV-1- and 3 HTLV-2-infected donors were analyzed. Familial transmission of HTLV-1 and -2 was evidenced in 3 families. In conclusion, in Northeastern Brazil, where HTLV-1 and -2 are endemic, counseling blood donor candidates and their families might play a key role in limiting the spread of these viruses., (© 2018 Wiley Periodicals, Inc.)

Many countries currently perform antibody screening for HTLV-1 infection in blood donors, and this intervention is likely cost-effective in preventing HTLV-1 related diseases in high prevalence countries. However, a number of high-income countries with low prevalence of HTLV-1 infection also perform universal HTLV-1 screening and debate has arisen regarding the cost-effectiveness of these strategies. Filter-based leukoreduction is likely to substantially reduce HTLV-1 transmission by removing infected lymphocytes, but actual laboratory data on its efficacy is currently lacking. Similarly, cost-effectiveness research on HTLV-1 prevention strategies is limited by poor data on prevalence, transmission efficacy and the cost of treating HTLV1 diseases., Competing Interests: of interest The author declares that he has no competing interest., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: In the United States, blood products are tested for infectious diseases including human T-lymphotropic virus (HTLV)-I/II. Positive results of maternal blood samples at the time of cord blood (CB) donation must be reported to mother and physician. Tests for HTLV have a high false-positive rate. This is problematic because there is no prenatal testing of the mother., Study Design and Methods: This study involves 119,769 maternal blood samples at time of CB donation and evaluates positive results for HTLV in screening tests, supplemental immunoassays, and nucleic acid tests (NATs). Infectious disease markers (IDMs) and maternal health histories of HTLV-positive and -negative mothers were compared., Results: Of 119,769 mothers donating CB, 545 tested positive with the screening test, 33 were positive with the supplemental tests, and two were positive with NAT. When indeterminate results were excluded from the supplemental test only six were positive. Eight of 34 mothers with positive or indeterminate supplemental test results had received intravenous immunoglobulin. There were no significant differences between HTLV-positive and -negative mothers with regard to the incidence of other IDMs., Conclusions: Testing maternal blood for HTLV is problematic for CB banks, obstetricians, and mothers because of the high false-positive rate. CB banks need rapid turnaround time and supplemental testing. If results on the latter are positive the obstetrician should be notified, educated, do follow-up testing, and counseling. Indeterminate results on supplemental tests are most likely false positives. We recommend that mothers with positive or indeterminate supplemental test results have follow-up NAT., (© 2012 American Association of Blood Banks.)

Background: Human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) causes serious diseases and is endemic in many parts of the world. It is transmitted from mother to child in 15-25% of the cases, primarily through breastfeeding. Proviral load and duration of breastfeeding are thought to play a role in transmission. This study aimed to detect HTLV-seropositive mothers through testing of neonates, to evaluate maternal HTLV proviral load and to measure the rates of transmission blocking when interruption of breastfeeding was implemented., Methods: Neonates were screened for HTLV-1/2 IgG by enzyme immunoassay using the neonatal screening program of Minas Gerais State, Brazil. Breastfeeding interruption was recommended to those whose mothers were confirmed HTLV-positive. Children were tested by polymerase chain reaction at birth and at 12 months of age., Results: Of 55,293 neonates tested, 42 (0.076%) were positive for HTLV-1 or HTLV-2 IgG. All 42 were polymerase chain reaction-negative at birth and 1 of 37 (2.7%) became antibody-positive after 12 months. His mother had delivered him vaginally and was informed of the positive HTLV-1 polymerase chain reaction after 7 days of breastfeeding. The mother's proviral load was 271 copies/10,000 cells, whereas the average is 109.2 copies/10,000 cells (95% confidence interval: 70.56-147.83)., Conclusions: Maternal HTLV-1 proviral load and the route of delivery may have played a role in the transmission observed. Avoidance of breastfeeding was an effective measure to reduce HTLV transmission. In endemic countries, routine prenatal or neonatal screening combined with formula feeding for mothers confirmed HTLV-positive may be an important strategy to prevent future development of illnesses related to HTLV.

Background: The human T-lymphotropic virus I (HTLV-I) causes spastic para-paresis and adult T-cell leukemia/lymphoma. It can be sexually transmitted and is highly prevalent in Central and South America., Aim: To study HTLV-I/IIprevalence in serum samples obtained from two Sexually Transmitted Diseases (STD) clinics., Material and Methods: Two hundred serum samples were randomly chosen from two reference STD centers of Santiago. The presence of specific HTLV I/II antibodies was detected by indirect immunofluorescence., Results: The analyzed samples came from participants aged 14 to 70 years. Forty nine percent were women and 76% were heterosexual. Only one of the 200 samples was positive (0.5%) and it came from a 70 year-old woman, housewife, with a stable single partner, a history of recurrent genital ulcers, VDRL (-) and positive serology for herpes simplex virus., Conclusions: The prevalence of HTLV-I found in this group is similar to that demonstrated in other populations in Chile, except for aboriginal populations, and similar to international STD studies. Our data is consistent with the low transmissibility by sexual contact.

In France, the screening for human T-cell leukemia/ lymphoma virus type 1 and 2 (HTLV-1 and HTLV-2) during the donation of human milk has been carried out from 1992 with the application of the circular DGS 24 November 1992. The screening for antibodies against these viruses is regulated and done systematically during every donation of milk. Breast feeding being the main mode of transmission of the HTLV-1, the last ministerial decree of 25 August 2010 has made the screening test compulsory for the anonymous donation and for the personalized donation (of a mother for her own child) from all women including those affected by the infection. The milk delivered by milk banks is pasteurized (62.5 °C for 30 minutes) before freezing at -18 °C, which inactivates the pathogens. This double means of prevention of the transmission of the HTLV-1 paradoxically seems disproportionate in the absence of any precautionary measure in the case of direct breast-feeding and the use of mother's raw milk. Indeed, in most neonatal intensive care units in maternity hospitals, unpasteurized milk is administered to the neonates without any systematic preliminary testing of the serological HTLV-1 status of the mother. An increased sensitization of the community of the obstetricians, midwives and neonatologists by the Association of the Milk Banks of France (ADLF) and the Société de pathologie exotique could address the issue of screening for HTLV-1 in "donated" milk and breast-feeding.

Objective: To evaluate the geographic distribution of human T-lymphotropic virus types 1 and 2 (HTLV-1/2) in the State of Minas Gerais, Brazil, in puerperal women whose newborns were tested for HTLV-1/2 during neonatal screening, and to overlap seropositivity with social and economic status determinants., Methods: During September-November 2007, the dry-blood samples taken from newborns on filter paper for routine screening were also tested for maternal IgG anti-HTLV-1/2 antibodies. For reactive samples, the mothers of the newborns had blood drawn to test for these viruses., Results: The study analyzed 55,293 specimens taken from newborns. Of these, 52 (9.4 per 10,000) were reactive and 42 mothers (7.6 per 10,000) were confirmed with HTLV-1/2 infection. HTLV-1/2 geographic distribution was heterogeneous, with a tendency to be higher in the North and North-East parts of Minas Gerais. The highest rates of seropositivity were observed in Vale do Mucuri (55.9 per 10,000) and in Jequitinhonha (16.0 per 10,000), overlapping with the State's worst social and economic indicators., Conclusions: To our knowledge this was the first time that neonatal screening for HTLV-1/2 was performed in Brazil. This model could be used in other areas with high HTLV-1/2 prevalence rates. The detection of carrier mothers can enable intervention measures, such as providing infant formula to newborns, to be implemented expeditiously to reduce vertical transmission.

The objective of this study was to perform lookback study in recipients of blood components from human T-lymphotropic virus (HTLV) seropositive donors. HTLV-1/2 may be transmitted by blood transfusion. Brazil is an endemic area for the virus and its screening in blood donors is mandatory since 1993. Hemominas Foundation (HF) is the public transfusion centre in Minas Gerais, Brazil. Data on HTLV-1/2 seropositive donors and recipients from 1993 to 2004 were obtained at HF and 24 contracting hospitals. From 1993 to 2004, HTLV-1/2 enzyme immunoassay (EIA) was performed in 918 678 donations of approximately 422 600 blood donor candidates. Of these, 456 donors (0.1%) were reactive and confirmed by Western blot (WB): 449 HTLV-1 and 7 HTLV-2. Sixty-six (14.5%) were repeat donors and had 194 blood cellular components produced from their previous donations. Of the distributed components, 119/146 (81.5%) had the recipient traced, with a total of 114 individuals. Of these, only 13 recipients were tested: six (46%) were HTLV-1 positive (four recipients of red cell units, two of platelets) and seven (54%) were negative (six of red cell units and one of platelets). Eleven did not respond and 62/114 (54.0%) were deceased. Another 28/114 (25.0%) could not be located. All six seropositive HTLV-1 recipients identified had no symptoms suggestive of HTLV-1-associated diseases. Acellular components, when used alone, were not associated with HTLV seropositivity. HTLV-1 transmission by cellular blood components occurred before screening for the virus was introduced. Haemovigilance was difficult to perform due to unavailability of computer systems before 1999 and to inadequate medical records at hospitals.

Human T-cell lymphotropic virus type 1 (HTLV-1) is transmitted through a viral synapse and enters target cells via interaction with the glucose transporter GLUT1. Here, we show that Neuropilin-1 (NRP1), the receptor for semaphorin-3A and VEGF-A165 and a member of the immune synapse, is also a physical and functional partner of HTLV-1 envelope (Env) proteins. HTLV-1 Env and NRP1 complexes are formed in cotransfected cells, and endogenous NRP1 contributes to the binding of HTLV-1 Env to target cells. NRP1 overexpression increases HTLV-1 Env-dependent syncytium formation. Moreover, overexpression of NRP1 increases both HTLV-1 and HTLV-2 Env-dependent infection, whereas down-regulation of endogenous NRP1 has the opposite effect. Finally, overexpressed GLUT1, NRP1, and Env form ternary complexes in transfected cells, and endogenous NRP1 and GLUT1 colocalize in membrane junctions formed between uninfected and HTLV-1-infected T cells. These data show that NRP1 is involved in HTLV-1 and HTLV-2 entry, suggesting that the HTLV receptor has a multicomponent nature.

Background: This study reports on the efficacy of an investigational human T-lymphotropic virus (HTLV)-I and -II lookback program in the context of differing confirmatory testing algorithms., Study Design and Methods: The results of testing approximately 35 million donations for anti-HTLV-I and -II were evaluated for two recent periods reflecting the use of two different confirmatory algorithms. The number of seroconverting donors was established for the entire period, and the results of lookback on their prior donations were investigated., Results: The dual enzyme immunoassay (EIA) strategy was used throughout both study periods and resulted in a 57 to 76 percent reduction in the number of samples requiring confirmatory testing. From May 2000 to February 2002, a total of 9138 samples were repeatedly reactive by the primary screening test; of the concordant EIA-reactive samples, 461 (12%) were confirmed by Western blot, whereas 3083 (79%) were indeterminate. From March 2002 to December 2004, a total of 21,291 samples were repeatedly reactive; of the concordant EIA-reactive samples, 1099 (22%) were confirmed by the State of California's reference laboratory and only 273 (5%) were equivocal. Overall, 38 or 1 in 921,000 donations were from a seroconverting donor with 32 prior donations within the lookback period. Of those 32, components from only 11 were transfused to recipients who survived; of these, 4 were tested and all were nonreactive for HTLV-I and -II antibodies., Conclusion: Use of creative algorithms can increase the efficacy of anti-HTLV-I and -II confirmatory testing and reduce the number of indeterminate results. Currently, lookback for HTLV-I and -II has a very low yield, and its public health benefit is questionable.

Human T cell lymphotropic virus (HTLV) I/II is a retrovirus that is usually transmitted through transfusion of cellular blood products, sexual contact, and vertically from mother to child through breastfeeding. Policies to screen donated blood for this virus have varied from country to country, based on seroepidemiological data. Before 1991, no such data existed on HTLV-I/II among the Saudi population. Since then, several reports have documented a low seroprevalence rate among Saudi blood donors (0-0.026%). We did a retrospective review of all blood donated at King Fahad National Guard Hospital over the preceding 3 years to assess the seroprevalence of HTLV-I/II. After retesting positive and borderline samples, we were able to detect 1 positive and 38 borderline samples. As well, we reviewed the Saudi literature to identify the national seroprevalence of the disease and propose a cost-effective approach for screening donated blood in Saudi Arabia for HTLV-I/II.

Human T-cell lymphotropic virus (HTLV) type I (HTLV-I) is the etiological agent of adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-II is a closely related virus, and this infection is not clearly associated with clinical disease, although neurologic disorders are observed resembling HAM/TSP. Prevalence rates for HTLV-I infection in the general population are greater than 1% in the Caribbean Basin, Central Africa, and South Japan. In most other areas in the world, as far as we know, HTLV-I/II infections are mainly found in high-risk groups (ie, immigrants from endemic areas, their offspring, their sexual contacts and in patients and intravenous injection users attending sexually transmitted disease clinics). Also, a high rate of infection for both HTLV-I and HTLV-II infection was observed in the native Amerindian population in North America as well as South America. Blood donors are routinely screened for HTLV-I/II in North America, several countries in Europe, Japan, and Taiwan.

Using both env and long terminal repeat (LTR) sequences, with maximal representation of genetic diversity within primate strains, we revise and expand the unique evolutionary history of human and simian T-cell leukemia/lymphotropic viruses (HTLV/STLV). Based on the robust application of three different phylogenetic algorithms of minimum evolution-neighbor joining, maximum parsimony, and maximum likelihood, we address overall levels of genetic diversity, specific rates of mutation within and between different regions of the viral genome, relatedness among viral strains from geographically diverse regions, and estimation of the pattern of divergence of the virus into extant lineages. Despite broad genomic similarities, type I and type II viruses do not share concordant evolutionary histories. HTLV-I/STLV-I are united through distinct phylogeographic patterns, infection of 20 primate species, multiple episodes of interspecies transmission, and exhibition of a range in levels of genetic divergence. In contrast, type II viruses are isolated from only two species (Homo sapiens and Pan paniscus) and are paradoxically endemic to both Amerindian tribes of the New World and human Pygmy villagers in Africa. Furthermore, HTLV-II is spreading rapidly through new host populations of intravenous drug users. Despite such clearly disparate host populations, the resultant HTLV-II/STLV-II phylogeny exhibits little phylogeographic concordance and indicates low levels of transcontinental genetic differentiation. Together, these patterns generate a model of HTLV/STLV emergence marked by an ancient ancestry, differential rates of divergence, and continued global expansion.

Studies on human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II) are briefly reviewed from the viewpoint of molecular evolution, with special reference to the evolutionary rate and evolutionary relationships among these viruses. In particular, it appears that, in contrast to the low level of variability of HTLV-I among different isolates, individual isolates form quasispecies structures. Elucidating the mechanisms connecting these two phenomena will be one of the future problems in the study of the molecular evolution of HTLV-I and HTLV-II.

The human T-cell lymphotropic viruses type I and type II are closely related human retroviruses that have similar biological properties, genetic organization and tropism for T lymphocytes. Along with the simian T-cell lymphoma virus type I, they define the group of retroviruses known as the primate T-cell leukemia/lymphoma viruses. Initially identified in 1980, the human T-cell lymphotropic virus type I has been implicated as the etiologic agent of adult T-cell leukemia/lymphoma and of a degenerative neurologic disorder known as tropical spastic paraparesis or human T-cell lymphotropic virus type I-associated myelopathy. The intriguing link between human T-cell lymphotropic virus type, T-cell malignancy, and a totally unrelated and non-overlapping neurological disorder suggests divergent and unique pathogenetic mechanisms. This review will address the epidemiology, molecular biology, and pathogenesis of human T-cell leukemia viruses.

The past five years have seen significant advances in understanding the origin and evolution of human T-cell leukemia/lymphotropic virus types I and II. The highlights include the identification of human T-cell leukemia/lymphotropic virus types I and II genotypic variants in remote human populations and the discovery of widely divergent simian T-cell leukemia virus in African and Asian non-human primates.

Blood donors have been screened for antibodies to human T cell lymphotropic virus (HTLV) type I since December 1988. Screening for HTLV-II has been simultaneously done because of cross-reactivity between antibodies to the two viruses. Currently, < 1 in 10,000 US blood donors is positive for HTLV-I or -II. Lookback studies led to the identification of 6 HTLV-II-infected patients. Three received transfusions before introduction of HTLV-I screening tests, while the other 3 received blood components that tested negative for HTLV-I. The HTLV-II subtypes of each of 4 donor/recipient pairs, as determined by DNA amplification using polymerase chain reaction, were identical, supporting the view that transfusions were the source of infection. In conclusion, currently licensed blood donor screening tests for HTLV-I lack sensitivity for HTLV-II, and transfusion of blood from HTLV-II-infected donors that test negative on HTLV-I screening tests may result in infection.

To determine the transmissibility of human T-lymphotropic virus types I and II (HTLV-I and HTLV-II) via transfusion, persons who, from 1983 to 1989, received blood components donated by persons who subsequently tested anti-HTLV-I-positive were evaluated. It was found that 16 (30%) of 54 evaluable recipients of transfused cellular components became infected with one of the HTLVs: 8 had HTLV-I and 8 had HTLV-II. Forty percent of platelet recipients and 28 percent of red cell recipients acquired infection. The rate of transmission of HTLV-I and HTLV-II was significantly correlated with storage age of red cell units prior to transfusion: 47 percent for red cells stored < or = 14 days and 0 for red cells stored > 14 days (p < 0.01). Multiple confirmatory serologic tests performed in 46 anti-HTLV-I enzyme immunoassay-negative recipients revealed that HTLV infection could not be excluded in 3 recipients of blood components from HTLV-II-infected donors. Polymerase chain reaction established HTLV-II infection in one recipient, and the other two recipients could not be classified with respect to HTLV infection status. It appears that some HTLV-II-infected transfusion recipients will not be detected by existing HTLV-I antigen-based reagents. If it is deemed necessary to initiate or continue look-back programs to detect transfusion transmission of HTLV-II infection, it is suggested that the current testing algorithm be modified in selected cases.

Background: Previous studies have demonstrated that HTLV-I is present in Italy both in endemic form in Southern Apulia and in epidemic form among the population of intravenous drug addicts. In the present paper we intend to evaluate the risk for transfusional HTLV-I transmission in our country, as well as the already known risk for HIV1., Methods: A population of 41 polytransfused Italian beta-thalassemic patients was examined by serological methods and PCR (polymerase chain reaction) for human retrovirus infection. Genomic DNA from PBMCs was analyzed by PCR with primer pairs specific for the HTLV-I gag, pol and env regions, and the HTLV-II env region., Results: Two patients were found to be weakly seroreactive to p19 and p24 HTLV-I/HTLV-II proteins by Western blot. The analysis of genomic DNA from PBMCs by PCR revealed sequence homology to HTLV-I only in these two patients. On the contrary, PCR with primer pairs specific for HTLV-II showed no beta-thalassemic patient was infected by this retrovirus. Surprisingly, Western blot analysis for detecting anti-HIV1 antibodies in these polytransfused subjects showed a seropositivity in two patients (not the same found to be infected with HTLV-I) in spite of a screening for HIV1 antibodies in the blood bank., Conclusions: These findings suggest that in Italy polytransfused people should still be considered at risk for HIV1 as well as HTLV-I infection, even if the incidence cannot be evaluated from such a small sample. The authors stress the importance of a through medical history of potential blood donors to eliminate possibly infected subjects.