Human T Cell Lymphotropic Virus Type II Infection Research Articles

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-cell lymphotropic virus type II in Guaraní Indians, Southern Brazil

Human T-cell lymphotropic virus type II (HTLV-II) is found in many New World Indian groups on the American continent. In Brazil, HTLV-II has been found among urban residents and Indians in the Amazon region, in the North. Guaraní Indians in the South of Brazil were studied for HTLV-I/II infection. Among 52 individuals, three (5.76%) showed positive anti-HTLV-II antibodies (enzyme-linked immunosorbent assay and Western blot). This preliminary report is the first seroepidemiological study showing HTLV-II infection among Indians in the South of Brazil.

ASSOCIATION AND EPIDEMIOLOGIC FEATURES OF TRYPANOSOMA CRUZI AND HUMAN T CELL LYMPHOTROPIC A VIRUS TYPE II IN INHABITANTS OF THE PARAGUAYAN GRAN CHACO

Serologic evidence of Trypanosoma cruzi infection was demonstrated in 43.5% of 519 Paleoamerindians and in only 2.5% of 161 non-Indians (Mennonites of German descent and Paraguayans of Spanish descent) inhabiting an area of western Paraguay that belongs to the Gran Chaco territory. These people ranged in age between two and 80 years. All were also tested for infection with the human T cell lymphotropic virus type II (HTLV-II). The prevalence of HTLV-II infection was 22.1% in Indians and 3.7% in non-Indians. As determined by a multivariate logistic regression analysis that controlled for relevant confounders, an HTLV-II-infected individual was 2.28 times more likely to be seropositive for T. cruzi than an HTLV-II negative. Possible explanations for this finding are discussed. The difference in T. cruzi prevalence between Indians and non-Indians was associated with differences between these groups in exposure to known risk factors for infection with the parasite. There were significant differences in the seroprevalence of T. cruzi among the two predominant Indian groups, even when they inhabited communities that were close to each other. These differences were associated with differences in the prevalence of HTLV-II infection but not with differences in exposure to known risk factors for T. cruzi infection. Infection with T. cruzi increased with age, was greater in males than in females, and clustered in families.

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.

Risk factors for human T cell lymphotropic virus type II infection among the Guaymi Indians of Panama.

To examine risk factors for human T cell lymphotropic virus type II (HTLV-II) infection, a case-control study was conducted among the Guaymi Indians of Panama. In females, HTLV-II seropositivity was associated with early sexual intercourse (</=13 vs. >15 years; odds ratio [OR], 2.50; 95% confidence interval [CI], 1.11-6.14) and number of lifetime sex partners. One partner increased risk of seropositivity by 30% (OR, 1.30; CI, 1.05-1.64), and risk increased with number of partners. Similar risk was associated with number of long-term sexual relationships. Among males, intercourse with prostitutes was associated with HTLV-II seropositivity (OR, 1.68; CI, 1.04-2.72). These data support a role for sexual transmission in HTLV-II infection. Association of seropositivity with primary residence in a traditional village (OR, 3.75; CI, 1.02-15.38) and lack of formal education (0 vs. >6 years [OR, 3.89; CI, 1.67-9.82]) observed in males may reflect differences in sexual practices associated with acculturation.

Evolutionary rate and genetic heterogeneity of human T-cell lymphotropic virus type II (HTLV-II) using isolates from European injecting drug users.

Seven new Italian and two new British HTLV-II isolates were obtained from injecting drug users and the entire long terminal repeat (LTR) region was sequenced. Restriction analysis showed that all the Italian isolates are of the IIb subtype, whereas the British isolates are of the IIa subtype. To understand whether the further differentiation of each two principal HTLV-II subtypes in several subgroups could be statistically supported by phylogenetic analysis, the neighbor-joining, parsimony, and maximum likelihood methods were used. The separation between IIa and IIb is very well supported by all three methods. At least two phylogenetic subgroups exist within the HTLV-IIa and at least three within the HTLV-IIb subtype. In the present analysis, no statistical support was obtained for additional phylogroups. Two particular subgroups seem interesting because they include all European and North American injecting drug user strains within the IIa and IIb subtypes, respectively. These data confirm that European HTLV-II infection among drug users is probably derived from North America. They also suggest that though a certain differentiation by restriction analysis in different subgroups is possible, carefully interpreted phylogenetic analyses remain necessary. Using the likelihood ratio test, a molecular clock for the drug user strains was calibrated. A fixation rate between 1.08 x 10(-4) and 2.7 x 10(-5) nucleotide substitutions per site per year was calculated for the IIa and IIb injecting drug user strains. This is the lowest fixation rate so far reported for RNA viruses, including for HIV, which typically range between 10(-2) and 10(-4).

Neurologic consequences of HTLV-II infection in injection-drug users

Several case reports have suggested an association between human T-cell lymphotropic virus type II (HTLV-II) infection and chronic neurologic disease. We performed serial neurologic examinations in injection-drug users (IDU), a group known to be at increased risk for HTLV-II infection. At baseline, those infected with HTLV-II alone, human immunodeficiency virus (HIV) alone, or both were significantly more likely to have neurologic disability than uninfected subjects. Longitudinally, HTLV-II infection was independently associated with the development of global neurologic disability and neuropathy, suggesting that HTLV-II causes neurologic disease.

What is the situation of human T cell lymphotropic virus type II (HTLV-II) in Africa? Origin and dissemination of genomic subtypes.

Human T cell lymphotropic virus type II (HTLV-II) and its two genomic subtypes, A and B, which differ by 3 to 6% at the nucleotide level (depending on the gene studied), were until recently considered to be endemic only in certain Indian tribes in the Americas and were therefore considered mainly as a "New World virus." First, the evidence of HTLV-II antibodies and later characterization of isolates from sex workers or individuals living in large West and Central African cities suggested that HTLV-II subtype A could have been imported recently in Africa. However, the findings of HTLV-II infection in two Pygmy populations living in remote areas of Zaire and Cameroon suggest that HTLV-II might have been in Africa for a very long time. Furthermore, the discovery of HTLV-II subtype B virus in some of these Pygmies, but also in other individuals from Zaire and within a family in Gabon for three generations, confirms the hypothesis of a very ancient presence of this HTLV-II subtype B on the African continent Recent data indicate also that there exist in Central Africa specific HTLV-II divergent strains including an HTLV-II B variant strain in Gabon. In the context of recent evidence for interspecies transmission in Central and West Africa of HTLV-I/simian T cell lymphotropic virus type I (STLV-I) strains, leading to the two major HTLV-I African subtypes, we would like to suggest that some STLV-II (closely related to HTLV-II subtype B) still exist or might have existed in Central/East Africa. The recent finding of quite divergent primate T cell lymphotropic viruses (PTLVs) in several Pygmy chimpanzees of Zairian origin (PTLV-PP1664 and STLV-PP) and in wild-caught baboons in Eritrea, Ethiopia (PTLV-L), also supports the complementary hypothesis of a yet to be discovered new HTLV-II-related virus in humans. Careful study of the indeterminate Western blot patterns present in some populations in Central Africa strongly suggests that such an exciting possibility exists, thus opening new avenues of research on both the history of primate retroviruses and that of early human groups.

Identification of Human T Cell Lymphotropic Virus Type IIa Infection in the Kayapo, an Indigenous Population of Brazil

Human T cell lymphotropic virus type II (HTLV-II) infection is endemic in a number of indigenous populations in North, Central, and South America. In the present study we have employed serological and molecular methods to identify HTLV-II infection in Indian communities in the Amazon region of Brazil. Sera (1324) from 25 different Indian communities were analyzed by ELISA and Western blot. One hundred and four samples (7.8%) from a number of culturally distinct and geographically unrelated populations were found to have reactivities consistent with HTLV-II infection. Of these, 67 were from the Kayapo Indian communities, which had an overall seroprevalence rate of greater than 30%. In addition, high seroprevalence rates were observed in three other communities, the Munduruku, Arara do Laranjal and the Tyrio, suggesting that there are additional foci of endemic infection in the Amazon region. In the Kayapo, seroprevalence rates tended to increase with age, supporting the importance of sexual transmission of the virus, and family studies demonstrated that vertical transmission is also an important route of infection. Restriction fragment length polymorphism (RFLP) and nucleotide sequence analysis of a region of the env gene demonstrated that the Kayapo are infected with the HTLV-IIa subtype. Moreover, nucleotide sequence analysis of the LTR demonstrated that this belonged to a distinct HTLV-IIa phylogenetic group. The identification of HTLV-IIa in the Kayapo is, as far as we are aware, the first identified endemic focus of infection by this subtype of HTLV-II in the Americas.

Evidence for Sexual and Mother-to-Child Transmission of Human T Lymphotropic Virus Type II among Guaymi Indians, Panama

Guaymi Indians, a non-intravenous drug-using population in which human T cell lymphotropic virus type II (HTLV-II) is endemic, were studied in Changuinola, Panama, to identify the prevalence and modes of transmission of HTLV-II. A population-based survey showed that 352 (9.5%) of the 3686 participants were seropositive for HTLV-II. Infection rates were the same for male and female subjects and increased significantly with age, beginning in young adulthood. HTLV-II infection status was highly concordant among spouses (P < .001) and between mother and child; of children aged 1-10 years, 36 of 219 born to seropositive mothers were seropositive compared with 3 of 997 born to seronegative mothers (P < .001). The strong associations of HTLV-II infection with age and with an infected spouse in adults and of infection in children with infection in their mothers strongly suggest sexual and mother-to-child transmission of HTLV-II in this population.

Prevalence of human T cell lymphotropic virus type II in American Indian populations of the southwestern United States.

We investigated the seroprevalence of human T cell lymphotropic virus type II (HTLV-II) using a screening enzyme-linked immunosorbent assay (ELISA) and immunoblot confirmation among the predominant tribes (Pueblo and Athapaskan) served by two large Indian Health Service facilities in New Mexico. Among persons being treated for sexually transmitted diseases, eight (3.2%) of 250 were seropositive for HTLV II, compared with eight (2.1%) of 385 women attending prenatal clinics. In a survey of unselected patients at one of the facilities, 15 (3.4%) of 446 were seropositive. Of 31 seropositive subjects, 25 were infected with HTLV-II and six infections could not be typed. Sera from nine (29%) of the 31 infected subjects had absorbance values less than the manufacturer's cutoff in the ELISA. Both Pueblo and Athapaskan groups had similar overall seroprevalences, but women tended to have a slightly higher seroprevalence than men, and seroprevalence tended to increase with age. These data show that HTLV-II infection is present among diverse groups of American Indians in the southwestern United States. Present ELISA screening tests, such as those used in this study, lack sensitivity to HTLV-II infection unless a reduced absorbance cutoff is used.

Infectious transmission of human T-cell lymphotropic virus type II in rabbits

To determine the susceptibility of rabbits to experimental infection with human T-cell lymphotropic virus type-II (HTLV-II), four separate groups of four weanling rabbits each were inoculated intravenously with lethally irradiated HTLV-II-infected human cell lines Mo-T (HTLV-IIMo- infected T cells), WIL-NRA (an Epstein-Barr virus [EBV]-transformed B- lymphoblastoid cell line infected with HTLV-IINRA), 729pH6neo (an EBV- transformed lymphoblastoid cell line transfected with a molecular clone of HTLV-IIMo), or G12.1 (HTLV-II-infected T cells from a Panamanian Guaymi Indian). Two additional groups of four rabbits each were similarly inoculated with control uninfected 729 or HuT 78 cells. Early and persistent seroconversion to HTLV-II core antigen p24, as determined by Western immunoblot, occurred in all HTLV-II-inoculated rabbits and was most intense in rabbits inoculated with G12.1 cells; seroreactivity to other HTLV-II gag or env antigens occurred later, with less intensity, or not in all inoculated rabbits. Peripheral blood mononuclear cells (PBMC) and other lymphoid cells from HTLV-II- inoculated rabbits produced minimal p24 in vitro, as determined by enzyme immunosorbent capture assay. Virus was more readily detected by polymerase chain reaction amplification of HTLV-II pol sequences; this occurred most frequently in rabbits inoculated with Mo-T cells, and most frequently in PBMC as compared with other tissues tested (bone marrow, brain, and liver). No evidence of disease occurred in HTLV-II- inoculated rabbits observed for as long as 24 weeks. All control rabbits remained negative for evidence of HTLV-II infection, as determined by the same procedures. These results provide the first evidence of HTLV-II infection in a species other than humans, and demonstrate the usefulness of the rabbit as an animal model to study the biologic response to different isolates of this human retrovirus.

Infectious Transmission of Human T-Cell Lymphotropic Virus Type II in Rabbits

To determine the susceptibility of rabbits to experimental infection with human T-cell lymphotropic virus type-II (HTLV-II), four separate groups of four weanling rabbits each were inoculated intravenously with lethally irradiated HTLV-II-infected human cell lines Mo-T (HTLV-IIMo-infected T cells), WIL-NRA (an Epstein-Barr virus [EBV]-transformed B-lymphoblastoid cell line infected with HTLV-IINRA), 729pH6neo (an EBV-transformed lymphoblastoid cell line transfected with a molecular clone of HTLV-IIMo), or G12.1 (HTLV-II-infected T cells from a Panamanian Guaymi Indian). Two additional groups of four rabbits each were similarly inoculated with control uninfected 729 or HuT 78 cells. Early and persistent seroconversion to HTLV-II core antigen p24, as determined by Western immunoblot, occurred in all HTLV-II-inoculated rabbits and was most intense in rabbits inoculated with G12.1 cells; seroreactivity to other HTLV-II gag or env antigens occurred later, with less intensity, or not in all inoculated rabbits. Peripheral blood mononuclear cells (PBMC) and other lymphoid cells from HTLV-II-inoculated rabbits produced minimal p24 in vitro, as determined by enzyme immunosorbent capture assay. Virus was more readily detected by polymerase chain reaction amplification of HTLV-II pol sequences; this occurred most frequently in rabbits inoculated with Mo-T cells, and most frequently in PBMC as compared with other tissues tested (bone marrow, brain, and liver). No evidence of disease occurred in HTLV-II-inoculated rabbits observed for as long as 24 weeks. All control rabbits remained negative for evidence of HTLV-II infection, as determined by the same procedures. These results provide the first evidence of HTLV-II infection in a species other than humans, and demonstrate the usefulness of the rabbit as an animal model to study the biologic response to different isolates of this human retrovirus.

Relative prevalence and risk factors of HTLV-I and HTLV-II infection in US blood donors

The clinical significance of human T-cell lymphotropic virus type II (HTLV-II) infection, unlike that of HTLV-I, is unknown, and the major known association of HTLV-II seropositivity is with intravenous drug abuse. Screening of blood donors for HTLV-I, now routine in North America, does not distinguish this retrovirus from HTLV-II. To find out more about the seroepidemiology of and risk factors for HTLV I and II, blood from 480,000 volunteer donors in five geographically separate US urban centres was tested for antibodies to HTLV-I/II and HIV-1. Confirmed HTLV-I/II seropositive donors were then followed up by DNA amplification to distinguish type I from type II and by interviews focusing on possible risk factors. HTLV seroprevalence was 3.3 times greater than that for HIV-1 (0.043% vs 0.013%). DNA amplification on 65 of the 207 HTLV-I/II seropositive donors revealed that 34 (52%) had HTLV-II infection and 28 (43% had HTLV-I; 3 samples were uninformative. Interviews of 49 donors showed that whereas HTLV-I was principally associated with donor origin from endemic regions, the major risk factor for HTLV-II infection was intravenous drug use. The surprisingly high rate of HTLV-II infection in US blood donors raises important public health and donor counselling issues since HTLV-I infection is associated with adult T-cell leukaemia and a neurological disorder while the pathogenicity of HTLV-II is as yet unclear.