Biomedical subjects
Publications and source records attributed to W Blattner.
Trends in the vertical transmission rate of HIV and evolving antiretroviral usage between 1990 and 1998 within the Women and Infants Transmission Study were evaluated. A decline in mother-infant transmission was temporally associated with advances in therapy, especially when regimens including a protease inhibitor were included in the analysis.
We describe 195 cases of adult T-cell leukemia/lymphoma (ATLL) reported to the national registry of T-cell malignancies in Brazil between 1994 and 1998. We compared the effect of demographic differences and clinical features of 150 consecutive ATLL cases in different regions of this diverse country. At diagnosis, the predominant clinical sub-type was the acute type (60%), followed by lymphoma (22%), chronic (10%) and smoldering (8%) types. Although we expected that different sub-types would be present in different regions, on the basis of immunogenetic factors determined by ethnicity, we did not demonstrate these differences. There were no significant differences among ATLL subtypes by age or gender. No ethnic group predominated in the total population of patients, but significant differences were noted when examining ethnic distribution by region. Reflecting the general population distribution, white patients were seen more often in São Paulo and black patients in Bahia, than in other regions. In most regions, cases were equally distributed between blacks and mulattos, except in Pernambuco, where blacks were less frequent. The main clinical features were lymphadenopathy, skin lesions, hypercalcemia and hepatomegaly. Fourteen patients (9%) suffered from HTLV-I-associated myelopathy (HAM/TSP), either at diagnosis or during follow-up of ATLL. All cases but one had antibodies to HTLV-I, with concordant results with ELISA, WB and PCR analyses. For the antibody-negative case, pol and tax gene sequences were present in tumor cells when subjected to PCR analyses. The prognosis was generally poor, suggesting that the disease in Brazil behaves in similar fashion regardless of ethnic or geographical differences.
Mother-to-child transmission of human T-cell lymphotropic virus type I (HTLV-I) is primarily due to prolonged breast-feeding (>6 months) in the postnatal period. Most infant infections are not identifiable until 12 to 18 months of age by available whole virus Western blot serologic tests because of their inability to distinguish passively transferred maternal antibody from infant antibody. We investigated two methods to assess more accurately the time of infant infection. In prospectively collected serial biospecimens, HTLV-I-specific immunoglobulin (Ig) isotypes of IgM and IgA were determined by Western blot and HTLV-I proviral DNA was detected by polymerase chain reaction (PCR). IgA and IgG reactivity was assessed in periodic serum samples from 16 HTLV-I-seropositive children while IgM reactivity was assessed in 9 of the 16 children. Approximately three to five samples were tested for each child. IgG reactivity was observed in 100% of children at 24 months of age and 73% of children at 6-12 months of age; however, this could represent maternal and not infant antibody. Both IgA and IgM reactivity were insensitive indicators of infection, with only 50% of children showing reactivity at 24 months of age. PCR testing was performed in biospecimens obtained from 11 of these children. An estimated median time of infection of 11.9 months was determined by PCR, which was similar to the median time to infection determined by whole virus Western blot (12.4 months; P = 0.72). PCR tests support a median time to infection that is similar to that estimated by whole virus Western blot.
BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM; also known as tropical spastic paraparesis [TSP]), a chronic neurodegenerative disorder. Worldwide, several million HTLV-I carriers are at risk for disease, with an estimated lifetime cumulative risk of 1%-5%. However, the determinants of disease progression are relatively unknown. We studied human leukocyte antigens (HLA class II) that have been implicated in the pathogenesis of HTLV-I-related diseases. METHODS: We analyzed HLA class II alleles among asymptomatic HTLV-I carriers (n = 45), patients with ATL (n = 49) or HAM/TSP (n = 54), and HTLV-I seronegative control subjects (n = 51). All participants were of African descent and were enrolled in epidemiologic studies conducted at the University of the West Indies, Kingston, Jamaica. We used standard microlymphocytotoxicity assays for HLA antigen serotyping and polymerase chain reaction-based methods to examine HLA class II DRB1 and DQB1 alleles. RESULTS: Two antigens determined by serotyping, DR15 and DQ1, occurred at significantly increased frequency among HTLV-I carriers compared with seronegative control subjects (42% versus 22% for DR15 [odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.0-7.2] and 78% versus 53% for DQ1 [OR = 3.1; 95% CI = 1.2-8.5]). Asymptomatic carriers were shown to have an HLA class II allele distribution similar to that of patients with ATL, and the frequencies of the alleles DRB1*1501, DRB1*1101, and DQB1*0602 were significantly greater in patients with ATL and asymptomatic carriers than in patients with HAM/TSP. In addition, haplotypes DRB1*1101-DQB1*0301 and DRB1*1501-DQB1*0602 were significantly increased among patients with ATL compared with patients with HAM/TSP. CONCLUSIONS: These data suggest that host genetic background is an important factor in determining whether HTLV-I carriers develop either ATL or HAM/TSP.
Of 970 sexually transmitted disease (STD) patients enrolled at the Comprehensive Health Centre, Kingston, Jamaica, between November 1990 and January 1991, 710 (73%, 333 men and 377 women) were reexamined between January 1992 and July 1993 to estimate the incidence of HIV and HTLV-I infection and to identify risk factors for infection. Of those reexamined, 20% were recruited passively when they returned to the clinic of their own accord, and 80% were recruited actively through field visits to their homes. Passively recruited persons were significantly more likely than active recruits to have had a sexually transmitted disease since enrollment or at their follow-up visit. Seven men and one woman became HIV positive during the period of follow-up. The overall HIV incidence rate was 0.7 per 100 person years (95% confidence interval [CI] = 0.3 to 1.4), 1.4 (CI = 0.6 to 2.8) for men and 0.2 (CI = 0.004 to 0.9) for women. Four of 270 men and 4 of 318 women were HTLV-I positive, an overall incidence of 0.9 per 100 person years (CI = 0.4 to 1.7), 1.0 for men and 0.8 for women. HTLV-I infection was associated with an age of 30 years or older (p < 0.01). The presumed lower transmission probability for HTLV-I may combine with a higher prevalence of HTLV-I in sexual partners to produce similar overall incidence rates for the two infections. The HIV and HTLV-I incidence rates may have been underestimated, because the study subjects who did not return to the clinic may have had a somewhat higher risk. On univariate analysis, there were significant associations between HIV infection in men and drinking alcohol before sex, cocaine use, total number of sex partners, sex with a prostitute since enrollment, ever accepting money for sex, the average number of sex partners per month, bruising during sex, and genital ulcers found on follow-up examination. This analysis needs to be interpreted with caution in view of the small number of seroconverters, which did not allow testing for independent effects in a logistic regression model.
To assess the association of the human T-cell lymphotropic virus type I (HTLV-I) and idiopathic facial nerve palsy of the lower motor neuron type, we studied 78 patients consecutively admitted to the Port of Spain General Hospital in Trinidad, the West Indies, with a confirmed diagnosis of idiopathic facial nerve palsy. Patients were compared with two control groups: a population-based group of persons 20 years and older and a hospital-based group of patients 15 to 84 years old admitted to the medical wards. Sixty-two patients were Trinidadians of African origin and 16 were Trinidadians of East Indian origin. None of the East Indian patients was HTLV-I antibody positive. Three Afro-Trinidadians were infected with human immunodeficiency virus type 1 and 1 was coinfected with this virus and HTLV-I. Of the remaining 58 Afro-Trinidadians, 12 (20.7%) were HTLV-I positive only. This rate was statistically higher than the HTLV-I seroprevalence in the Afro-Trinidadian general population (3.5%) and the hospital control group (5.6%). After age standardization, the HTLV-I prevalence for patients with facial nerve palsy remained significantly elevated. HTLV-I antibody assays should be performed on all patients with idiopathic facial nerve palsy of the lower motor neuron type who live in HTLV-I endemic areas or are migrants from these areas.
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Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV-1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV-1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections.
In a study to determine the reliability, sensitivity, and specificity of the Chiron RIBA HIV-1/HIV-2 Strip Immunoblot Assay (RIBA HIV-1/2 SIA) for confirmation of human immunodeficiency virus type 1 (HIV-1) and HIV-2 antibodies, 1,263 serum samples from various populations in the United States, Caribbean, Africa, India, and Thailand were evaluated by RIBA HIV-1/2 SIA, and the results were compared with those obtained by an HIV-1 Western blot (immunoblot) assay. All sera were tested by HIV enzyme immunoassay, RIBA HIV-1/2 SIA, and Western blotting. Samples with discrepant results were further tested by an HIV-1 and/or HIV-2 immunofluorescent-antibody assay and HIV-1 p24 antigen assay. The RIBA HIV-1/2 SIA detected all 17 HIV-1 and HIV-2 dually reactive serum samples, all 215 HIV-2-positive serum samples, and 480 of 481 HIV-1-positive serum samples for a sensitivity of 99.8%. Of 548 negative samples, 523 were RIBA HIV-1/2 SIA negative, for a specificity of 95.4%, with 22 (4%) samples interpreted as indeterminate and 3 (0.6%) interpreted as falsely positive. Western blotting detected 391 of 548 negative samples (specificity, 71.4%), with 152 (27.7%) samples interpreted as indeterminate and 5 (0.9%) interpreted as falsely positive. In conclusion, the RIBA HIV-1/2 SIA had a sensitivity comparable to that of Western blotting and could discriminate HIV-1 from HIV-2 in one blot, providing a cost advantage. Because of its high degree of specificity, the RIBA HIV-1/2 SIA further reduced the number of indeterminate results found by Western blotting, providing a more accurate means of assessing seronegative individuals.
Human T-cell lymphotropic virus type I (HTLV-I) is endemic in the Caribbean basin and in Japan. HTLV-II, a closely related virus, is endemic in several groups of native Americans, including Panamanian Guaymi. In Panama, a nationwide HTLV-I/II seroprevalence of 1-2% has been reported. We evaluated the frequency of HTLV-I/II infection in patients with neurologic diseases admitted to state tertiary hospitals in Panama City between 1985 and 1990. Nineteen of 322 patients with eligible diagnoses had antibodies to HTLV-I/II, 17 with HTLV-I and 2 with HTLV-II. HTLV-I was associated with spastic paraparesis (13 of 23, 56.5% versus 4 of 299, 1.3%, p < 0.001) and with cerebellar syndrome (2 of 13, 15.4%) and multiple sclerosis (2 of 54, 3.7%) (p < 0.05 for both diseases compared with subject with none of these diagnoses). The two HTLV-I infected patients with cerebellar syndrome later developed spastic paraparesis. HTLV-II infection was noted in one patient with cerebellar syndrome and one with amyotrophic lateral sclerosis. All patients with other diagnoses were seronegative. Among patients with spastic paraparesis, HTLV-I-infected patients were clinically indistinguishable from seronegative subjects. There is apparently an overlapping clinical spectrum of neurologic diseases associated with HTLV-I and HTLV-II infection.
Human T-cell lymphotropic virus type 1 (HTLV-I) status was assessed in 994 patients attending a sexually transmitted disease (STD) clinic in Kingston, Jamaica, between November 1990 and January 1991 for a new STD complaint. Of 515 heterosexual men, 36 (7.0%) were HTLV-I seropositive, as were 38 (7.9%) of 479 women. HTLV-I seroprevalence increased with age in women. A history of blood transfusion was associated with HTLV-I in both sexes, significantly so in men [odds ratio (OR) 4.7, confidence interval (CI) 1.1-17 for men; OR 1.9, CI 0.6-5.0 for women]. Further analysis excluded all persons reporting a transfusion. On multiple logistic regression analysis, independent associations with HTLV-I infection in men were shown for marital status (OR 3.5, CI 1.2-10 for married/common law vs. single/visiting unions), agricultural occupation (OR 9.0, CI 2.0-41), bruising during sex (OR 2.9, CI 1.0-8.1), > or = 15 years at first sexual intercourse (OR 2.9, CI 1.0-8.2), and a positive test for hepatitis B surface antigen (OR 7.3, CI 1.2-52). In women, associations were shown for two or more sex partners in the 4 weeks prior to complaint (OR 4.9, CI 1.8-13), 11 or more lifetime sexual partners (OR 5.9, CI 1.3-27), aged < 15 years at first sexual intercourse (OR 2.3, 1.0-5.4), bruising during sex (OR 2.7, CI 1.1-6.6), microhaemagglutination-Treponema pallidum positivity (OR 3.6, CI 1.6-8.4), and human immunodeficiency virus infection (OR 14, CI 2.1-92).(ABSTRACT TRUNCATED AT 250 WORDS)
Cultured peripheral blood lymphocytes (PBL) from HTLV-I-infected individuals proliferate in the absence of added mitogens and/or cytokines. In an attempt to answer questions regarding the activating signals for cells and virus, antibodies that react with cell surface components that are known to regulate cell activation and antibodies reacting with viral proteins were added to cultures of PBL from HTLV-I-infected, disease-free individuals. Spontaneous proliferation and virus production increased in the presence of antibodies reacting with CD3 and alpha/beta T cell receptors (TCR) while antibodies to HLA class II and viral proteins had no effect. Addition of HLA class I antibodies shut down virus production and cell proliferation. These observations indicate that both virus and cell activation may occur through the alpha/beta TCR on the infected cell. Cyclosporin A, however, markedly decreased cell proliferation but had only a modest suppressive effect on virus production. Thus, the uncoupling of cell proliferation from virus production by cyclosporin A suggests the possibility that the signal transduction pathways for these two events are different.
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Between November 1990 and January 1991, status of human immunodeficiency virus (HIV) infection was assessed for 522 men and 484 women attending the Comprehensive Health Centre in Kingston, Jamaica, for a new sexually transmitted disease (STD) complaint. Prevalence of HIV type 1 (HIV-1) infection was 3.1% (31 of 1,006), a tenfold rise in seroprevalence in 4.5 years. Nineteen of 517 (3.7%) heterosexual men, 3 of 5 (60%) homosexual/bisexual men, and 9 of 484 (1.9%) women were infected with HIV. In heterosexual men, factors associated with HIV infection after age adjustment included present complaint of genital ulcer [odds ratio (OR) 7.3; 95% confidence interval (CI) 1.4-72], past history of genital ulcer (OR, 4.3; CI, 1.4-12), positive MHATP syphilis serology (OR, 3.4; CI, 1.1-10), sex with a prostitute in the past month (OR, 3.8; CI, 1.1-11). Three or more sex partners in the month prior to complaint (OR, 3.6; CI, 1.0-12), and bruising during sex (OR, 4.0; CI, 1.4-13). On multiple logistic regression analysis, independent associations with HIV infection were shown for bruising during sex (OR, 3.0; CI, 1.1-8.3), positive MHATP syphilis serology (OR, 3.2; CI, 1.1-9.5), and history of genital ulcer (OR, 2.9; CI, 1.0-8.0).(ABSTRACT TRUNCATED AT 250 WORDS)
We evaluated the reliability, sensitivity, and specificity of two rapid assays, TestPack HIV-1/HIV-2 and Genie HIV-1/HIV-2, in Lagos, Nigeria. An alternative algorithm to EIA and Western blot was then examined with the TestPack HIV-1/HIV-2 used as the screening test and the Genie HIV-1/HIV-2 used as the supplemental test to differentiate HIV-1 and HIV-2 infection. In all, 845 prostitutes were evaluated for HIV-1 and HIV-2 infection using one of the two rapid tests and compared to EIA and Western blot results. Of these 845 cases, 437 samples were analyzed by both assays. Overall, 109 (12.7%) prostitutes were antibody positive for HIV-1, 13 (1.5%) for HIV-2, and six (0.7%) were dually reactive for both HIV-1 and HIV-2. Compared to Western blot, the Genie HIV-1/HIV-2 had a slightly higher sensitivity and specificity (98.4% and 99.7%) than the TestPack HIV-1/HIV-2 (97.6% and 99.3%). The alternative algorithm using both rapid assays had a sensitivity of 96.9% and a specificity of 99.9%. The Genie HIV-1/HIV-2 correctly identified 104 of 108 HIV-1 positive sera, 12 of 13 HIV-2 positive sera, and all six dually positive sera. Both assays performed well in the field. They required < 10 min to complete, no equipment, and little training. An algorithm incorporating two rapid assays can be used as a less expensive alternative to traditional testing strategies comparable in reliability to ELISA and Western blot; it provides the additional advantage of differentiating between HIV-1 and HIV-2.
Three hundred and forty-six sera collected over a 2-year period from 154 San Francisco IV drug users were subjected to HTLV-I/II RIPA, Western blot (WB), Du Pont ELISA, and p24 radioimmunoassay (RIA). Tests were performed at separate sites and code not broken until study end. RIPA-positive and -negative controls consisted of Japanese adult T cell leukemia patients, healthy blood donors, and non-IV drug-using HIV-positive men. RIPA identified HTLV-I/II-positive sera not identified by the other tests. Positive RIPAs were noted in 43% of negative ELISAs (n = 279), 34% of negative WBs (n = 243), and 40% of negative RIAs (n = 270). Seventy-two sera were negative by all 3 assays, but were RIPA positive. All sera positive by RIA (n = 76) and WB (n = 67), and 66 of 67 by ELISA, were positive by RIPA. Thirty-five of 36 indeterminate WBs were RIPA positive. Seven samples indeterminate by RIPA were negative by WB and RIA; one of seven was positive by ELISA. In all instances, samples negative by RIPA (n = 154) were ELISA, p24 RIA, and WB negative or indeterminate. We conclude that when studying HTLV-I/II-endemic cohorts, screening ELISA or RIA followed by confirmatory WB or RIPA only of seropositive samples may result in a substantial number of undetected cases. Additional studies focusing on performance characteristics of serodiagnostic tests are needed to ensure accurate inferences are made in assessing HTLV-I/II prevalence rates among high-risk groups. The RIPA may be a uniquely sensitive assay to detect HTLV-I/II gene-encoded products.
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