Work-Related Human T-lymphotropic Virus 1 and 2 (HTLV-1/2) Infection: A Systematic Review.

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.

The Link between Cannabis Use, Immune System, and Viral Infections.

Cannabis continues to be the most used drug in the world today. Research shows that cannabis use is associated with a wide range of adverse health consequences that may involve almost every physiological and biochemical system including respiratory/pulmonary complications such as chronic cough and emphysema, impairment of immune function, and increased risk of acquiring or transmitting viral infections such as HIV, HCV, and others. The review of published research shows that cannabis use may impair immune function in many instances and thereby exerts an impact on viral infections including human immune deficiency virus (HIV), hepatitis C infection (HCV), and human T-cell lymphotropic type I and II virus (HTLV-I/II). The need for more research is also highlighted in the areas of long-term effects of cannabis use on pulmonary/respiratory diseases, immune dysfunction and the risk of infection transmission, and the molecular/genetic basis of immune dysfunction in chronic cannabis users.

Sexually Transmitted Diseases: from HPV to HTLV--clinical profile and associated factors.

The Brazilian Ministry of Health recommends the performance of serological tests in patients with clinical signs of Sexually Transmitted Diseases. However, data are lacking to affirm the necessity of testing these patients for human T-lymphotropic virus type 1 or type 2. This is a cross-sectional study with 120 patients seen at the Sexually Transmitted Diseases unit of the Sanitary Dermatology Outpatient Clinic of Rio Grande do Sul. The serum from none of the patients was positive for human T-lymphotropic virus type 1 or type 2. Viral warts were the most frequent diagnosis. Drug use was confirmed as a risk factor and high educational levels were found to be a protective factor against Sexually Transmitted Diseases.

Infecções pelo vírus linfotrópico humano (HTLV) / Infections by human lymphotropic virus (HTLV)

No presente artigo são revistos os aspectos clínicos das infecções pelo HTLV-I e HTLV-II.

In the present paper the clinical aspects of HTLV-I and HTLV-II infections are reviewed.

Tropical pyomyositis in a patient with systemic lupus erythematosus and HTLV 1/2 infection.

Tropical pyomyositis (TP) is an unusual infectious disease of skeletal muscles, caused by bacteria, and often associated with immunodeficiency conditions. The involvement of deep pelvic muscles, such as the iliac muscle, is even rarer. The association of systemic lupus erythematosus (SLE) and PT is seldom reported in the literature. Because SLE involves a state of immunosuppression resulting from both the disease itself and its medicamentous treatment, SLE patients are at higher risk for developing infections, such as PT. Infection by HTLV 1/2 is increasingly identified and associated with autoimmune diseases, such as SLE. This is a case report of PT in the pelvic muscles of a female patient with SLE, chronic kidney failure, on hemodialysis, and HTLV1/2 infection, admitted to the Hospital Heliópolis, in the city of São Paulo, Brazil.

Piomiosite tropical em paciente com lúpus eritematoso sistêmico e infecção por HTLV 1/2 / Tropical pyomyositis in a patient with systemic lupus erythematosus and HTLV 1/2 infection

A piomiosite tropical (PT) é uma doença infecciosa da musculatura esquelética, de etiologia bacteriana, incomum, e muitas vezes associada a situações de imunodeficiência. O envolvimento de musculatura pélvica profunda, como o músculo ilíaco, é uma condição ainda mais incomum. A associação de lúpus eritematoso sistêmico (LES) e PT é pouco relatada na literatura. Como o LES é uma situação de imunodepressão tanto pela doença em si como pelas medicações utilizadas no seu tratamento, esses pacientes tornam-se grupo de risco para o desenvolvimento de infecções, como PT. A infecção pelo HTLV está cada vez sendo mais identificada e associada a patologias nas quais autoimunidade está implicada, como é o caso do LES. Os autores descrevem um caso de PT de localização no músculo ilíaco em paciente portadora de LES, insuficiência renal crônica, em hemodiálise, além de portadora do vírus HTLV 1/2, internada no Hospital Heliópolis, em São Paulo, Brasil.

Tropical pyomyositis (TP) is an unusual infectious disease of skeletal muscles, caused by bacteria, and often associated with immunodeficiency conditions. The involvement of deep pelvic muscles, such as the iliac muscle, is even rarer. The association of systemic lupus erythematosus (SLE) and PT is seldom reported in the literature. Because SLE involves a state of immunosuppression resulting from both the disease itself and its medicamentous treatment, SLE patients are at higher risk for developing infections, such as PT. Infection by HTLV 1/2 is increasingly identified and associated with autoimmune diseases, such as SLE. This is a case report of PT in the pelvic muscles of a female patient with SLE, chronic kidney failure, on hemodialysis, and HTLV1/2 infection, admitted to the Hospital Heliópolis, in the city of São Paulo, Brazil.

HTLV-2 infection in injection drug users in King County, Washington.

Human T-cell lymphotropic virus type 2 (HTLV-2) is endemic in injection drug users (IDU), and native American populations in the Americas. Transmission is associated with high-risk injection and sexual practices. A cohort of 2561 IDU in King County, Washington completed 2 study visits over 1 y. HTLV-2 infection was detected in 190 (7.4%) of 2561 IDU, and 13 (7.8 cases per 1000 person-y) incident infections occurred during the study. Prevalent infection was associated with female gender, non-white race, longer duration as IDU, having a tattoo, combined injection of heroin and cocaine, and with serologic evidence of hepatitis B and C infection. Seroconversion was more common in women, and was associated with African American race, heterosexual identity and longer duration as IDU. In conclusion, increased risk of HTLV-2 infection was associated with non-white race, and injection drug of choice, suggesting injection networks may play an important role in transmission of HTLV-2. The high correlation of HTLV-2 infection with HCV infection suggests the major route of transmission in IDU is via injection practices. Additional studies are needed to examine the clinical manifestations of HTLV-2 infection, as well as the clinical and virological manifestations of HTLV-2/HCV coinfection.

Risk factors for HTLV-II infection in Peruvian men who have sex with men.

Human T-cell lymphotropic virus type-II (HTLV-II) infection is endemic in indigenous groups in the Americas and injection drug users (IDUs) worldwide. In Peru, HTLV-II infection was previously identified in two indigenous Amazonians. We examined risk factors for HTLV-II infection in 2,703 Peruvian men who have sex with men (MSM): 35 (1.3%) were HTLV-II positive. HTLV-II infection was associated with syphilis, HSV-2 infection, unprotected receptive anal intercourse, and older age. This is the first report of HTLV-II in a non-indigenous non-IDU population in Peru. Additional studies are needed to determine if HTLV-II is a sexually transmitted infection in this and other sexually active populations.

Human T lymphotropic virus type I/II infection: prevalence and risk factors in individuals testing for HIV in counseling centers from Southern Brazil.

OBJECTIVE: The objective of this study was to ascertain the prevalence and to investigate risk factors for human T lymphotropic virus type I/II (HTLV I/II) infection among subjects who tested for HIV at three counseling centers in Porto Alegre, Brazil. METHODS: The authors conducted a cross-sectional study in which subjects screened for HIV were tested for HTLV. Socioeconomic and demographic data, social and sexual behavior, history of having been breastfed, and past blood transfusion or drug use were gathered with a standardized questionnaire. RESULTS: Among 2985 participants, 2.4% had HTLV infection confirmed (1.4% HTLV I). The risk increased with age, but there was no difference among genders. The multivariate model shows that injecting cocaine users were 5.2 (95% confidence interval, 2.5-10.7) times more likely to be HTLV I/II-positive than non-injecting cocaine users and HIV infection persisted as an independent risk factor. CONCLUSION: Among persons presenting at HIV testing centers in Porto Alegre, Brazil, HTLV I was three times more common than HTLV II; injection drug use was the predominant mode of transmission.

Seroprevalence and risk factors for human T cell lymphotropic virus type 1 and 2 infection in human immunodeficiency virus-infected patients attending AIDS referral center health units in Londrina and other communities in Paraná, Brazil.

The municipality of Londrina ranks second in the number of AIDS cases in the state of Paraná, Brazil, with the Ministry of Health notified of 1070 cases from 1984 to 2002. The aim of this study was to determine the seroprevalence and risk factors for HTLV-1/2 infection in HIV-infected patients attending the AIDS Reference Center serving Londrina (and surrounding region), Paraná, Brazil. Data concerning sociodemographic conditions and risk factors were collected from 784 HIV-infected patients, using a questionnaire. Blood samples were obtained from 758 of the patients and subjected to serologic screening tests for the determination of HTLV-1/2, as well as hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis. Most patients were white (mean age, 35.9 years); 55.9% were males and 44.1% were females. The most frequent sexually transmitted disease was gonorrhea (28.5%), followed by syphilis (14.3%) and condyloma (12.2%). The major risk factors associated with the acquisition of retroviruses were sexual contact (84.8%) and intravenous drug use (IDU, 11.9%). The overall infection seroprevalence was 6.4% for HTLV-1/2, 37.2% for HBV, 21.0% for HCV, and 24.4% for syphilis. HTLV-1 and HTLV-2 infections were confirmed in 0.8 and 4.9% of patients, respectively. HIV/HTLV-1/2 coinfection was more frequent in IDUs (59.2% of cases) and was strongly associated with HCV (22.60 [95% CI, 10.35-49.35]). A weak association with HBV (2.09 [95% CI, 1.13-3.90]) and no association with syphilis were observed. The results showed that human retroviruses are circulating in southern Brazil, mainly among white people of both genders of low socioeconomic conditions and educational level. Although the sexual route was considered to be the major risk factor for HIV infection, HTLV-1/2 infection was strongly associated with IDU.

Epidemiologic features of HTLV-II: serologic and molecular evidence.

PURPOSE: A literature review was performed of the three principal subpopulations most commonly associated with human T-cell lymphotropic virus type II (HTLV-II) with the view of identifying the prevalence and transmission routes of HTLV-II. These included blood donors (BDs), intravenous drug users (IVDUs), and Amerindians (Indian populations from the Americas). We used the major criterion of serological and molecular distinction between human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II). Three questions were formulated in addressing the possibility that HTLV-II might be responsible for the reported prevalence and transmission of this virus in these groups. Question One: Which population groups have the highest HTLV-II seroprevalence rates? Question Two: Are worldwide HTLV infection rates among the three sub-populations associated predominantly with the HTLV-II retrovirus type? Question three: What are the principal modes of transmission of HTLV-II? METHODS: Since earlier epidemiologic studies did not routinely use assays capable of distinguishing between HTLV-I and HTLV-II antibodies, their findings are necessarily inaccurate. However, with the more recent development of enhanced serologic assays, using recombinant antigens that are capable of accurately making this differentiation, it is now possible to more precisely define the epidemiology of HTLV-II. We reviewed only those studies where serological and molecular methods of accurately distinguishing between the two retroviruses were utilized. Initially, we located 36 studies, which met this particular review criterion. Of the five different assays we identified, the most prevalent were the polymerase chain reaction (PCR) (n = 14) and the synthetic peptide-based enzyme-linked immunoassay (Synth EIA) (n = 13). Our BD, IVDU, and Amerindian groups were also evaluated according to this differentiation schema. We were able to locate over 100 prevalence studies where focus was on some aspect of analysis of at least one or more of these three groups. By using many search terms - such as HTLV-II endemic population, seroepidemiological, as well as case control and cohort studies - we were able to create a comprehensive bibliographic database. RESULTS: The two groups identified with high HTLV-II prevalence rates are the IVDUs and Amerindian population. The importance of breast-feeding, IVDU, and contaminated blood products in the HTLV-II transmission process is confirmed. Sexual intercourse, however, as a mode of HTLV-II transmission remains problematic. CONCLUSIONS: By confining our evaluation to only those studies that used serological and/or molecular methods capable of distinguishing between the two retroviruses, we have been able to establish with confidence that there are consistent emerging patterns of HTLV-II infection in these populations.

Restricción étnica y geográfica de la infección causada por el virus HTLV-II y su asociación con el polimorfismo del complejo mayor de histocompatibilidad en tres subpoblaciones del Caribe colombiano

Las infecciones causadas por los virus HTLV-I y II parecen tener una distribución geográfica y étnica entre amerindios y otras poblaciones nativas en el mundo. En Colombia existe un foco endémico entre afrocolombianos del litoral Pacífico, no así en la costa del Caribe. Objetivos: Establecer una asociación entre la diversidad genética del MHC y la infección causada por el virus HTLV-II en tres grupos étnicos representativos del Caribe colombiano. Encontrar la prevalencia de la infección causada por los virus HTLV-II en una muestra representativa de estos respectivos grupos étnicos. Métodos: Se colectó suero de 157 indios wayuu, 840 mestizos y 580 afro-colombianos, buscando la presencia de anticuerpos anti HTLV-I/II usando dos técnicas diferentes: Una pueba de aglutinación pasiva (PA, Serodia, Fujirobio, Tokio) y una prueba de micro Elisa (Murex). La oligotipificación de los antígenos HLA clase-II fue realizada mediante PCR-SSOP, siguiendo el protocolo de la 12 IHWSC y se realizó en un total de 41 muestras indigenas wayuu, 61 mestizos y 100 afrocolombianos. Resultados: las muestras pertenecientes a los mestizos y a los afrocolombianos resultaron negativas; once sueros de la población wayuu fueron repetidamente reactivas con PA y micro Elisa, reconfirmadas usando una prueba de Western Blot (HTLV-Blot, 2.4 Gene Laboratory), obteniéndose una seroprevalencia al HTLV-II de 7 por ciento entre los wayuu. Los alelos con mayor frecuencia en los wayuu fueron DRb1*0411 (46 por ciento), y DQb1*0302 (83 por ciento). Analizando los haplotipos en los 11 wayuu seropositivos encontramos en todos ellos la expresión del haplotipo HLA DRb1*0411-DQB1*0302, (p<005). Ninguno de los 75 mestizos y los 100 afro-colombianos lo expresaron. Conclusiones: Los resultados obtenidos sugiren una restricción genética de la suceptibilidad a ser infectado por este virus y podrían explicar la distribución geográfica y étnica de la infección causada por HTLV-II en estos grupos estudiados.

Increased incidence of infectious diseases during prospective follow-up of human T-lymphotropic virus type II- and I-infected blood donors. Retrovirus Epidemiology Donor Study.

BACKGROUND: To determine whether human T-lymphotropic virus type II (HTLV-II) infection is associated with an increased incidence of bacterial infections, we prospectively observed cohorts of HTLV-I- and HTLV-II-infected and seronegative subjects in 5 US cities. METHODS: Of 1340 present and former blood donors examined at enrollment, 1213 (90.5%) were re-examined after approximately 2 years, including 136 HTLV-I- and 337 HTLV-II-seropositive subjects and 740 demographically stratified HTLV-seronegative subjects. All subjects were seronegative for human immunodeficiency virus. Odds ratios (ORs) for incident disease outcomes were adjusted for covariates, including age, sex, race or ethnicity, education, and, if significantly associated with the outcome, blood center, donation type, income, smoking, alcohol intake, and injected drug use. RESULTS: Compared with seronegative status, HTLV-II infection was associated with an increased incidence of bronchitis (OR, 1.81; 95% confidence interval [CI], 1.20-2.75), bladder and/or kidney infection (OR, 1.94; 95% CI, 1.26-2.98), oral herpes infection (OR, 9.54; 95% CI, 3.33-27.32), and a borderline increased incidence of pneumonia (OR, 2.09; 95% CI, 0.92-4.76); HTLV-I infection was associated with an increased incidence of bladder and/or kidney infection (OR, 2.79; 95% CI, 1.63-4.79). One incident case of HTLV-I-positive adult T-cell leukemia was observed (incidence, 348 per 100,000 HTLV-I person-years), and 1 case of HTLV-II-positive tropical spastic paraparesis-HTLV-associated myelopathy was diagnosed (incidence, 140 per 100,000 HTLV-II person-years). CONCLUSIONS: These data support an increased incidence of infectious diseases among otherwise healthy HTLV-II- and HTLV-I-infected subjects. They are also consistent with the lymphoproliferative effects of HTLV-I, and with neuropathic effects of HTLV-I and HTLV-II.

Mecanismos de oncogénesis viral / Mechanisms of viral oncogenesis

Actualmente se sabe que el 20 por ciento de los cánceres humanos están asociados con virus oncogénicos. El virus papiloma humano con cáncer anogenital, los virus de la hepatitis B y C con carcinoma hepatocelular, el virus Epstein Barr con carcinomas nasofaríngeos y linfomas, el virus de la leucemia-linfoma T con leucemias en el adulto. Un rasgo común en todos los tumores asociados con infección viral es el largo período de latencia entre la infección y la aparición de la neoplasia y la baja proporción de individuos infectados que desarrollan un tumor maligno. Estas observaciones indican que los virus oncogénicos son necesarios pero no suficientes para inducir cáncer, otros factores podrían estar involucrados. Esta actualización resume informaciones recientes acerca de los mecanismos de carcinogénesis viral, en particular, la interacción de oncoproteínas virales y proteínas supresoras tumorales. La inactivación de estas proteínas supresoras podría representar una estrategia común a través de la cual los virus tumorales pueden contribuir a la transformación maligna de la célula

Epidemiology of human T-lymphotropic virus type II (HTLV-II) infection in Spain. HTLV Spanish Study Group.

The human T-lymphotropic virus type II (HTLV-II) has recently been associated with the genesis of some subacute neurological syndromes and, rarely, with atypical T-lymphoid malignancies. The virus is endemic in some Amerindian and African tribes, and among intravenous drug users (IDUs) in North America and Europe. Given that HTLV-II is transmitted by the same routes as other human retroviruses, the screening of antibodies to HTLV-II in blood donors has became a matter of controversy in some countries. Herein, we describe the clinical, epidemiological and virological features of 113 individuals with HTLV-II infection identified in Spain up to September 1995. Most of them (94/113; 83%) were male, and all but seven were natives. Four were African immigrants living in Madrid and 3 had been born in other European countries. All but six subjects were IDUs, and sexual transmission of HTLV-II and transfusion were involved in five and one individual, respectively. Eighty-four percent of the IDUs infected with HTLV-II were co-infected by HIV-I (93/107). Clinical manifestations potentially linked to HTLV-II were absent, although an IDU male co-infected by HIV-1 and HTLV-II developed a severe non-inflammatory proximal myopathy. In conclusion, HTLV-II infection is present in Spain, mainly among IDUs, with a growing incidence and a current overall prevalence of 2.0 percent.

HIV and infections of similar transmission patterns in a drug injectors community of Santos, Brazil.

To study the prevalence of HIV and infections with related transmission patterns, we interviewed and obtained blood samples from 220 injecting drug users (IDUs), sampled by snowballing, from the city of Santos in the state of São Paulo, Brazil, where the estimated number of IDUs (10,000) comprises approximately 2% of the entire population. Seroprevalence of HIV, hepatitis B and C, syphilis, and HTLV (1 and 2) was assessed and compared with that in 197 blood donors from the same city, matched for age and gender. Risk behavior related to HIV was assessed by a standard questionnaire applied to the IDU sample. Univariate and multivariate analyses of the risk factors were performed. Seroprevalences found were 62% for HIV, 75% for HCV, 75% for HBV, 34% for syphilis, and 25% for HTLV (1 and 2) among IDUs, which compare with 0.0%, 2%, 23%, 12%, and 1% for blood donors, respectively. The risk for parenterally transmitted infections in this IDU community was higher than that for sexually transmitted infections (odds ratio for syphilis, 3.57; hepatitis B, 10.0; and hepatitis C, 100). The results of the mutivariate risk analysis showed that daily rate of ID use >5 times/day (OR = 6.73), not changing behavior to avoid AIDS (OR= 3.28), ID use >15 days/month (OR = 2.72), and ID use in the last 2 months (OR = 2.23) were the risk behaviors significantly associated with HIV infection.

Identification of IIa and IIb molecular subtypes of human T-cell lymphotropic virus type II among Italian injecting drug users.

The molecular characterization of two human T-cell lymphotropic virus type II (HTLV-II) isolates, Gu and Va, obtained from Italian injecting drug users (IDUs) has indicated that these isolates belong to the HTLV-IIb subtype. To establish whether Italian IDUs are also infected by the HTLV-IIa variant, sequencing of the gp21 env gene of proviral DNA from further patients was carried out. Two new isolates, Bo and Md, were found, which presented a divergence of 0.4-0.7% from the IIa prototype HTLV-II-Mo, thus indicating that they belong to the HTLV-IIa subtype. The results strongly support the existence of two distinct molecular subtypes of HTLV-II infecting Italian IDUs and demonstrate that, although the IIb subtype appears to be prevalent, there is the same variability for this virus in Europe as found in the United States. The Italian IIb isolates were also seen to encode an additional 25 amino acids at the C-terminal end of tax protein, as already shown for other IIb isolates. The identification of two HTLV-II molecular subtypes among Italian drug addicts will be useful in tracing the worldwide distribution of this virus and in further understanding its molecular structure and biology.

Endemic human T cell leukemia virus type II infection in southwestern US Indians involves two prototype variants of virus.

Human T cell leukemia virus (HTLV) type II is endemic in certain American Indians, and high rates of infection occur in intravenous drug users (IVDUs). North American IVDUs are infected with two distinct variants, HTLV-IIa and -IIb. If IVDUs became infected as a result of interaction with members of an American Indian population, both viral forms should be demonstrable in such populations. Nucleotide sequence analysis of 630 bases of the env gene encoding the gp21 protein was done on DNA from 12 New Mexico Indians (8 Pueblo, 4 Navajo). All samples were typical subtype a or b viruses. Seven of the 8 Pueblo and 2 of 4 Navajo had subtype b; the rest had subtype a. The results are compatible with an indigenous New World origin for both subtypes of HTLV-II.