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1.
Of the 267,650 blood donations from members of the US armed forces, 72 (0.027%) were serologically confirmed to be positive for human T-lymphotropic virus type I/II (HTLVpos) and 379 (0.14%) were Western blot (WB)-indeterminate with banding pattern restricted to the proteins encoded by the gag gene only (HTLVind). To determine whether these apparently healthy HTLVind blood donors are infected with HTLV-I or HTLV-II, coded specimens from randomly selected military blood donors (n = 73) were tested for antibodies to HTLV by WB and radioimmunoprecipitation assay (RIPA) using HTLV-I (MT-2) antigens, by enzyme immunoassay using synthetic peptides representing the immunodominant epitopes of HTLV, and for sequences of proviral HTLV DNA by the polymerase chain reaction (PCR). Of the 73 HTLVind donors, none showed presence of env reactivity by HTLV WB and RIPA. Minimal reactivity was observed with synthetic immunodominant motifs derived from the env protein of HTLV-I (Env-1(191-214) and Env-5(242-257)) or HTLV-II (Env-2(187-209) and Env-20(85-102)) and gag protein (Gag-1a(102-117) and Gag-10(364-385)). A peptide corresponding to the endogenous retroviral sequence with structural homologies to the gag protein of HTLVs (RTVLgag) reacted with antibodies not only in HTLVpos (88%) and HTLVind (42% to 66%) specimens, but also reacted with normal control subjects (60%). Furthermore, none of the 73 HTLVind specimens demonstrated presence of the HTLV genome when amplified with primers for the pol and tax/rex region. Six to 23 months from the initial test, 27 subjects still gave indeterminate WB patterns, and 13 of these repeat specimens were still negative for the presence of HTLV genome. We conclude that individuals at low risk for HTLV infection who have HTLVind WB reactivity are rarely, if ever, infected with HTLV-I or HTLV-II.  相似文献   

2.
The polymerase chain reaction (PCR) was used to confirm the presence of human T-cell lymphotropic viruses (HTLV) in intravenous drug users (IVDU) whose sera were reactive by immunofluorescence assay (IFA) for HTLV-1/-II antibody. Peripheral blood mononuclear cells from 41 IFA-positive and 19 IFA-negative individuals were analyzed. HTLV sequences were detected in 39/41 IFA-positive samples; 36 were HTLV-II positive and 3 were HTLV-I positive. Two IFA antibody-positives were negative by both PCR and by enzyme immunoassay (EIA). One IFA and EIA antibody-negative sample was positive for HTLV-II by PCR. This study indicates a high prevalence of HTLV-II among IVDUs and further demonstrates the feasibility of using PCR to differentiate between HTLV-I and -II.  相似文献   

3.
Testing problems in diagnosing human T-lymphotropic virus (HTLV) infection, mostly HTLV-II, have been documented in HIV/AIDS patients. Since December 1998, the Immunology Department of Instituto Adolfo Lutz (IAL) offers HTLV-I/II serology to Public Health Units that attend HTLV high-risk individuals. Two thousand, three hundred and twelve serum samples: 1,393 from AIDS Reference Centers (Group I), and 919 from HTLV out-patient clinics (Group II) were sent to IAL for HTLV-I/II antibodies detection. The majority of them were screened by two enzyme immunoassays (EIAs), and confirmed by Western Blot (WB 2.4, Genelabs). Seven different EIA kits were employed during the period, and according to WB results, the best performance was obtained by EIAs that contain HTLV-I and HTLV-II viral lysates and rgp21 as antigens. Neither 1st and 2nd, nor 3rd generation EIA kits were 100% sensitive in detecting truly HTLV-I/II reactive samples. HTLV-I and HTLV-II prevalence rates of 3.3% and 2.5% were detected in Group I, and of 9.6% and 3.6% in Group II, respectively. High percentages of HTLV-seroindeterminate WB sera were detected in both Groups. The algorithm testing to be employed in HTLV high-risk population from S?o Paulo, Brazil, needs the use of two EIA kits of different formats and compounds as screening, and because of high seroindeterminate WB, may be another confirmatory assay.  相似文献   

4.
This study sought to define the seroprevalence of human T cell leukemia virus (HTLV) types I and II in selected populations of homosexual men. Serum specimens were screened for antibodies to HTLV and to human immunodeficiency virus (HIV) by enzyme immunoassay; successive testing of specimens with positive results was done by Western blotting and radioimmunoprecipitation assay (RIPA) and then by polymerase chain reaction (PCR) assay on available peripheral blood mononuclear cells (PBMC). Of 1290 specimens, only 4 had antibodies against HTLV confirmed by RIPA. PCR analysis of DNA from PBMC from two subjects showed one to be HTLV-I and the other to be HTLV-II; both men also had HIV antibodies. These results demonstrate a lower seroprevalence rate for HTLV than some previous studies and emphasize the need for specific confirmatory tests.  相似文献   

5.
The transmissibility of human T lymphotropic virus (HTLV) type II from mother to child was investigated. Of 236 women enrolled during pregnancy in a study of mother-to-child transmission of human immunodeficiency virus in 1986-1988, 21 (8.9%) were seropositive for HTLV-I/II. All 21 mothers were infected with HTLV-II by synthetic peptide testing and polymerase chain reaction (PCR). HTLV-II-infected women were older (median age, 34 vs. 28 years), more likely to be black (70% vs. 38%), and more likely to report past or current intravenous drug use (85% vs. 56%) than HTLV-II-uninfected women. Of 20 non-breast-fed infants born to 19 of these HTLV-II-infected women, none had detectable HTLV-II by PCR done on peripheral blood mononuclear cells obtained at birth to 36 months of age. Serologic testing of these infants revealed gradual disappearance of HTLV-I/II antibody. While this study does not rule out the possibility of perinatal HTLV-II transmission, the data suggest that it occurs rarely in the absence of breast-feeding.  相似文献   

6.
BACKGROUND: Blood donors are routinely screened for antibodies to human T-cell lymphotropic viruses type I and II (HTLV-I and HTLV-II) in the United States, Canada, Japan, and some European countries. Previous reports from our group in relatively small numbers of donors have shown a zero prevalence of HTLV-I/II markers in our region. In this study, seven blood banks in the north and west of Greece participated in order to determine whether mandatory screening of blood donations for HTLV-I/II infection should be established. METHODS: Sera from 51,714 consecutive donors were investigated for anti-HTLV-I/II using two commercially available enzyme immunoassays (EIAs). Reactive samples in one or both EIAs were repeatedly evaluated further by Western blot, which is specific for both confirmation and differentiation of HTLV-I and HTLV-II seroreactivities. Investigation for HTLV DNA was also done in all EIA-reactive donors, irrespective of the WB result, using a combination assay based on the polymerase chain reaction (PCR) and a DNA EIA. RESULTS: A total of 115 donors (0.222%; 95% CI 0.018-0.26%) were initially considered reactive for anti-HTLV-I/II by EIAs. However, only 7 of the 115 were confirmed as positive by WB (five HTLV-I and two HTLV-I/II). Thus, the prevalence of anti-HTLV-I/II in donors from northern and western Greece was 0.013% (95% CI 0.003-0.023%). Interestingly, the majority of WB-confirmed anti-HTLV-positive individuals were detected in the blood bank of Corfu (5/7, all anti-HTLV-I). This prevalence (5/15383; 0.032%; 95% CI 0.004-0.061%) was six times the prevalence found at the other blood banks combined (2/36331; 0.0055%; 95% CI 0-0.013%), but it was not statistically significant. None of the EIA-reactive donors had detectable HTLV DNA. CONCLUSIONS: The very low prevalence of confirmed anti-HTLV-I/II infection markers in northern and western Greek blood donors, together with the negative PCR results in EIA-reactive subjects, indicates that anti-HTLV-I/I routine screening is not really justified in this area of our country. However, the increased prevalence of WB-confirmed anti-HTLV-I-positive donors in the Corfu blood bank calls for further prospective and careful investigation in order to address whether this finding represents a real cluster phenomenon of HTLV infection.  相似文献   

7.
The extent of human T-cell leukemia/lymphoma virus type II (HTLV-II) infection and its rate of spread have been difficult to determine owing to the serological cross-reactivity between HTLV-I and HTLV-II. The present study overcame this problem by directly detecting type-specific proviral sequences by means of the polymerase chain reaction (PCR) and liquid hybridization. Screening was performed on a cohort of primarily white intravenous drug abusers (IVDAs), and individuals of other behaviorally defined risk groups from the New York City area. Eleven percent (19 of 169) of the individuals in these high-risk groups were determined by PCR to have HTLV-II proviral infections. One of these patients displayed an exfoliative erythrodermatitis. Thirteen of the 19 subjects were positive in an HTLV-II enzyme-linked immunosorbent assay (ELISA). The remaining six individuals, although negative in the HTLV- II ELISA, were confirmed as HTLV-II positive by analyzing their DNA with a second HTLV-II-specific primer detector system. Four additional individuals were reactive in the HTLV-II ELISA but were PCR-negative for HTLV-II. PCR analysis for HTLV-I revealed that all four were positive for that virus. Thirty-seven percent (seven of 19) of the HTLV- II PCR-positive subjects were also PCR-positive for HTLV-I, and 84% (16 of 19) of the HTLV-II positive individuals were infected with human immunodeficiency virus (HIV-1). Six individuals were triply infected with HTLV-I, HTLV-II, and HIV-1.  相似文献   

8.
In order to assess the prevalence rate of HTLV-1-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, and patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4+ T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-1 positives had B-cell lymphomas, one HIV-1 positive had an HTLV-I-positive CD4+ T-cell lymphoma, and one infected with HIV-2 had a CD4+ T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials.  相似文献   

9.
The diagnosis and confirmation of human T cell lymphotropic virus (HTLV) type II infection has proven difficult, since most assays depend on antigenic cross-reactivity between HTLV-I antigens and HTLV-II antibodies. Type-specific HTLV infection rates were evaluated in a cohort of 233 injecting drug users screened with an HTLV EIA. Of the 52 EIA-reactive specimens, 48 were indeterminate or negative by standard Western blot. Type-specific HTLV results determined by polymerase chain reaction (PCR) were 0, HTLV-I; 92%, HTLV-II; 6%, type indeterminate; and 2%, negative. Among 42 EIA-reactive, HTLV-II-PCR-positive individuals tested by a p21 envr Western blot, all were positive and 74% had antibodies to the tax protein. This study found a high rate (22.3%) of HTLV reactivity, with HTLV-II usually the sole responsible agent; shortcomings in standard HTLV-I-based diagnostics but usefulness of PCR and p21 envr Western blots for typing and confirmation of HTLV reactivity; and a high prevalence (74%) of anti-tax antibody among HTLV-II-seropositive subjects, suggesting increased potential for infectivity.  相似文献   

10.
Serologic screening for human T-cell leukemia virus type I (HTLV-I) infection was begun in US blood banks with the licensure of enzyme- linked immunosorbent assays (ELISA) in December 1988. We examined the donation histories of the first 60 Western blot (WB)-confirmed HTLV- I/II positive donors to one blood center and found 8 had made 16 previous donations that scored negative on the screening ELISA. All 16 donations had ELISA absorbance below the cutoff for a positive assay, but still well above that of the average donation (17.6% +/- 5.7% of the cutoff). In a more extensive study, 17 donations from a total of 61,752 at six blood centers were both ELISA-positive and WB-positive for HTLV-I (4) or HTLV-II (13), and 218 samples had ELISA absorbance greater than 50% of the ELISA cutoff. One hundred seventy-eight of the 218 were tested further by WB and 11 were found positive. All 11 positives were confirmed by polymerase chain reaction; 10 had HTLV-II and 1 had HTLV-I. Thus, the HTLV-I-based screening ELISA missed at least 10 of 23, or 43% (95% confidence interval, 23% to 66%), of HTLV- II infections, compared with 1 of 5, or 20%, of HTLV-I infections.  相似文献   

11.
We studied results of a "lookback" program involving laboratory testing and interviews of 133 recipients of prior donations from blood donors seropositive for human T-lymphotropic virus types I and II (HTLV-I/II) identified at 28 American Red Cross blood centers. The study was designed to explore the natural course of posttransfusion HTLV-I/II infection among individuals who received blood components from donors subsequently identified as being HTLV-I/II seropositive. Seventeen recipients were seropositive, an apparent transmission rate of 12.8%. Red blood cells and platelets were the implicated components, and red blood cells that were less than 6 days old had a transmission efficiency of 80%. Virus typing enabled documentation of primary and secondary transfusion transmission of HTLV-I and HTLV-II, including the direct transmission of HTLV-II by a donor with a history of intravenous drug use. We conclude that transfusion transmission of HTLV-I/II to approximately 700 recipients per year occurred in the United States before routine donor testing began in 1988.  相似文献   

12.
The heterogeneity of immune responsiveness to the immunodominant epitopes of human T lymphotropic virus (HTLV) types I (MTA-1(162-209)) and II (K-55(162-205)) were determined in natural infections with HTLV-I and -II from diverse geographic areas (n = 285). Of the HTLV-I specimens confirmed by polymerase chain reaction (PCR), all North American (n = 37) and Peruvian (n = 19) specimens reacted with MTA-1. Of HTLV-II specimens confirmed by PCR, 44 (96%) of 46 from North American blood donors, 28 (97%) of 29 from native Americans, and all from intravenous drug users (n = 29) reacted with K-55. Specimens from other geographic areas (Peru, 30; Brazil, 4; Mexico, 10; Italy, 5; Somalia, 13; Ethiopia, 17; Japan, 32; and Jamaica, 15) all reacted either with MTA-1 or K-55. By synthetic peptide-based serologic typing, all of these specimens could be typed as HTLV-I or -II. In addition to the direct implications of these findings for diagnostic purposes, these data provide indirect evidence for the conservation of immunodominant HTLVenv epitopes in diverse geographic populations.  相似文献   

13.
Hjelle  B; Scalf  R; Swenson  S 《Blood》1990,76(3):450-454
The Albuquerque branch of the United Blood Services system was found to have an unusually high blood donor human T-cell leukemia/lymphoma virus (HTLV) seroprevalence (0.72 per 1,000). Many studies investigating HTLV seroprevalence and transmission have assumed that all seropositivity is due to HTLV type I (HTLV-I); recent data dispute this conclusion. We investigated the high prevalence of HTLV seropositivity in New Mexico by determining whether HTLV-I or HTLV-II is predominant in our donors. Using polymerase chain reaction (PCR) amplification of proviral DNA from peripheral blood, followed by sequence-specific hybridization with oligonucleotide probes to distinguish the two viruses, we demonstrate that 9 of 10 Western blot-confirmed HTLV-seropositive blood donors from New Mexico are infected with HTLV-II. Implications of this finding for donors and the safety of the blood supply are discussed.  相似文献   

14.
The seroprevalence and geographic distribution of HTLV-1/2 among blood donors are extremely important to transfusion services. We evaluated the seroprevalence of HTLV-1/2 infection among first-time blood donor candidates in Ribeir?o Preto city and region. From January 2000 to December 2010, 1,038,489 blood donations were obtained and 301,470 were first-time blood donations. All samples were screened with serological tests for HTLV-1/2 using enzyme immunoassay (EIA). In addition, the frequency of coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Chagas disease (CD) and syphilis was also determined. In-house PCR was used as confirmatory test for HTLV-1/2. A total of 296 (0.1%) first-time donors were serologically reactive for HTLV-1/2. Confirmatory PCR of 63 samples showed that 28 were HTLV-1 positive, 13 HTLV-2 positive, 19 negative and three indeterminate. Regarding HTLV coinfection rates, the most prevalent was with HBV (51.3%) and HCV (35.9%), but coinfection with HIV, CD and syphilis was also detected. The real number of HTLV-infected individual and coinfection rate in the population is underestimated and epidemiological studies like ours are very informative.  相似文献   

15.
Unlike human T cell leukemia-lymphoma virus type I (HTLV-I), HTLV-II has not been convincingly linked to a malignancy. In the first 10 months of serologic screening for HTLV-I/II among blood donors in New Mexico in 1988-1989, HTLV-I/II infection was found in 27 donors. HTLV-I/II infection was present in 1.0%-1.6% of American Indian and 0.16%-0.27% of Hispanic donors compared with 0.009%-0.06% of non-Hispanic white donors. HTLV-II was identified by DNA amplification in 12 of 13 samples from Indian and Hispanic seropositive donors. Despite apparent endemic HTLV-II infection in these populations, New Mexico Tumor Registry data showed that the incidences of hairy cell leukemia, mycosis fungoides, and chronic lymphocytic leukemia were comparable among the three ethnic groups. A population with endemic HTLV-II infection has been identified, and there is no evidence of increased risk for these three malignancies in the endemic groups.  相似文献   

16.
Sera from 5,244 blood donations collected between 1979 and 1987 were screened for antibody to HTLV-I with an enzyme immunoassay (EIA) whose result was confirmed with a two-step procedure including Western blot (WB) and radio immunoprecipitation. Of 20 repeatedly reactive samples, two were confirmed positive for HTLV-I infection. These blood units were transfused to patients undergoing cardiac surgery. Both recipients of the confirmed anti-HTLV-I positive units were infected with HTLV-I as evidenced by antibody seroconversion. In contrast, six recipients of EIA positive, WB indeterminate blood and nine recipients WB negative blood were not infected with HTLV-I. These results confirm a low prevalence of HTLV-I infection in US blood donors, the capacity of infected units to transmit the virus to recipients, and the importance of an appropriate confirmatory assay.  相似文献   

17.
OBJECTIVE: To evaluate the effectiveness of serologic testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types I and II (HTLV-I/II) infections and to estimate the risk for transmission of HIV-1 and HTLV-I/II by transfusion of seronegative blood from screened donors. DESIGN: A prospective multicenter cohort study of cardiac surgery patients who received multiple transfusions between 1985 and 1991. SETTING: Cardiac surgery services of three large tertiary care hospitals. PATIENTS: The study included 11,532 patients in three hospitals who had cardiovascular surgery. MEASUREMENTS: Incident HIV-1 and HTLV-I or HTLV-II infection. RESULTS: We detected two new HIV-1 infections among patients transfused with 120,312 units of blood components from seronegative donors. In each case a donor was detected on follow-up who had seroconverted since the donation. The HIV-1 infection rate was 0.0017% with an upper limit of the 95% CI of 0.0053%. Before donor screening for HTLV-I, transfusion of 51,026 units resulted in two HTLV-I infections (0.0039%) and four HTLV-II infections (0.0078%). After HTLV-I screening was instituted, one recipient was infected with HTLV-II among participants exposed to 69,272 units, a rate of 0.0014%. A corresponding HTLV-I/II-infected donor was found for this patient. CONCLUSION: Serologic screening of donors for antibodies to HIV-1 and HTLV-I coupled with exclusion of donors from groups having a relatively high risk for infection has led to a low incidence of transfusion-transmitted HIV-1 and HTLV-I/II infection in the United States. A small risk remains, however, despite these measures. We estimate the residual risk for HIV-1 and HTLV-II infection from transfusion of screened blood during the time of this study to be about 1 in 60,000 units.  相似文献   

18.
Abstract Human T-lymphotropic virus type 1/2 (HTLV-1/2) infection is endemic in Brazil but representative donor prevalence and incidence data are lacking. All blood donations (2007-2009) from three blood centers in Brazil were studied. Samples reactive on one HTLV screening test (EIA) were retested with a different EIA; dual EIA reactivity correlated strongly with a confirmatory Western blot. Prevalence, incidence, and residual transfusion risk were calculated. Among 281,760 first-time donors, 363 were positive for HTLV on both EIAs (135 per 10(5), 95% CI 122-150). Prevalence differed considerably by region, from 83 to 222 per 10(5). Overall incidence rate was 3.6/10(5) person-years and residual transfusion risk was 5.0/10(6) per blood unit transfused. The logistic regression model showed significant associations with: age [adjusted odds ratio (aOR)=5.23 for age 50+ vs. <20], female sex (aOR=1.97), black (aOR=2.70 vs. white), and mixed skin colors (aOR=1.78 vs. white), and inversely with education (aOR=0.49, college vs. less than high school). HTLV testing with a dual-EIA strategy is feasible and can be useful in areas with low resources. Incidence and residual risk of HTLV-1 transmission by transfusion were relatively high and could be reduced by improving donor recruitment and selection in high prevalence areas. Blood center data may contribute to surveillance for HTLV infection.  相似文献   

19.
Abrams A  Akahata Y  Jacobson S 《Viruses》2011,3(8):1320-1331
Human T-lymphotropic virus type I (HTLV-I) infects an estimated 15-20 million persons worldwide. A number of diseases have been associated with the virus including adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I uveitis, and HTLV-I-associated infective dermatitis. Once it was shown that there is an increased risk for developing HAM/TSP associated with blood transfusion, screening for HTLV-1 among blood banks was implemented in Japan, United States, France, and the Netherlands. This process includes detection by an enzyme immunoassay (EIA) followed by a confirmatory Western blot (WB) in which recombinant proteins specific for HTLV-I Env glycoproteins are incorporated into WB strips. HTLV-I seropositive results are defined by the presence of antibodies against either gp46 or gp62/68 (both Env protein bands) and either p19, p24, or p53 (one of the gag bands). HTLV-II seropositivity is confirmed by the presence of rgp46-II. However, numerous cases have been documented in which serum samples are reactive by EIA, but an incomplete banding pattern is displayed by subsequent confirmatory WB. Although the significance of these HTLV-I/II seroindeterminates is unclear, it may suggest a much higher incidence of exposure to HTLV-I/II than previously estimated.  相似文献   

20.
BACKGROUND: Cross-sectional studies support sexual transmission of human T lymphotropic virus (HTLV)-I/II; however, prospective incidence data, particularly for HTLV-II, are limited. METHODS: A cohort of 85 HTLV-positive (30 with HTLV-I and 55 with HTLV-II) blood donors and their stable (>or=6 months) heterosexual sex partners were followed biannually over the course of a 10-year period. RESULTS: Four of 85 initially seronegative sex partners of HTLV-I and -II carriers seroconverted, for an incidence rate (IR) of 0.6 transmissions/100 person-years (py) (95% confidence interval [CI], 0.2-1.6). This includes 2 HTLV-I transmissions/219 py (IR, 0.9 transmissions/100 py [95% CI, 0.1-3.3]) and 2 HTLV-II transmissions/411 py (IR, 0.5 transmissions/100 py [95% CI, 0.06-1.8]), with no significant difference by HTLV type. There were 2 male-to-female (IR, 1.2 transmissions/100 py [95% CI, 0.1-4.3]) and 2 female-to-male (IR, 0.4 transmissions/100 py [95% CI, 0.05-1.6) transmissions. HTLV-I or -II proviral load was 2 log10 lower in newly infected partners than in index positive partners who transmitted HTLV (P=.007). CONCLUSIONS: The incidence of sexual transmission of HTLV-II may be similar to that of HTLV-I, and female-to-male transmission may play a more important role than previously thought. HTLV-I and -II proviral load may be lower in sexually acquired infection, because of a small infectious dose.  相似文献   

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