Neurologic abnormalities in HTLV-I- and HTLV-II-infected individuals without overt myelopathy.

BACKGROUND: Human T-lymphotropic virus (HTLV) type I is the causative agent of HTLV-associated myelopathy (HAM)/tropical spastic paraparesis, and a number of HAM cases with HTLV-II infection have also been reported. However, despite some reports, it is unclear whether HTLV-I or -II infection is associated with other neurologic manifestations. METHODS: An analysis of medical histories and screening neurologic examinations from a prospective cohort of 153 HTLV-I, 388 HTLV-II, and 810 HTLV-seronegative individuals followed up for means of 11.5, 12.0, and 12.2 years was performed. Participants diagnosed with HAM were excluded. We calculated odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, sex, race or ethnicity, income, educational attainment, body mass index, alcohol and cigarette consumption, injection drug use, diabetes, and hepatitis C virus status, using generalized estimating equations for repeated measures. RESULTS: HTLV-I and -II participants were more likely than seronegative participants to have leg weakness (ORs 1.67 [95% CI 1.28-2.18] and 1.44 [1.16-1.78]), impaired tandem gait (ORs 1.25 [95% CI 1.07-1.47] and 1.45 [1.27-1.64]), Babinski sign (ORs 1.54 [95% CI 1.13-2.08] and 1.51 [1.18-1.93]), impaired vibration sense (ORs 1.16 [95% CI 1.01-1.33] and 1.27 [1.14-1.42]), and urinary incontinence (ORs 1.45 [95% CI 1.23-1.72] and 1.70 [1.50-1.93]). For both HTLV-I and -II participants, higher odds of sensory neuropathy by monofilament examination were no longer significant after adjustment for confounding. CONCLUSIONS: These results provide strong evidence that human T-lymphotropic virus (HTLV)-I and -II are associated with a spectrum of predominantly motor abnormalities in patients without overt HTLV-associated myelopathy. Further investigation of the clinical course and etiology of these abnormalities is warranted.

Analysis of hepatitis G virus (HGV) RNA, antibody to HGV envelope protein, and risk factors for blood donors coinfected with HGV and hepatitis C virus.

Serologic, biochemical, and molecular analyses were used to study hepatitis G virus (HGV), antibody to the HGV envelope protein (anti-E2), risk factors, clinical significance, and the impact of HGV on coexistent hepatitis C virus (HCV). Among 329 donors with confirmed HCV infection, 12% were HGV RNA-positive and 44% were anti-E2-positive (total exposure, 56%). HGV RNA and anti-E2 were mutually exclusive except in 9 donors (1.5%); 8 of 9 subsequently lost HGV RNA but anti-E2 persisted. HGV had little impact on alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transpeptidase in donors with HGV infection alone or those coinfected with HCV. A multivariate analysis showed that intravenous drug abuse was the leading risk factor for HGV transmission, followed by blood transfusion, snorting cocaine, imprisonment, and a history of sexually transmitted diseases. In summary, HGV and HCV infections were frequently associated and shared common parenteral risk factors; HGV did not appear to cause hepatitis or to worsen the course of coexistent hepatitis C.

Increased prevalence of infectious diseases and other adverse outcomes in human T lymphotropic virus types I- and II-infected blood donors. Retrovirus Epidemiology Donor Study (REDS) Study Group.

Disease associations of human T lymphotropic virus types I and II (HTLV-I and -II) infection were studied in 154 HTLV-I-infected, 387 HTLV-II-infected, and 799 uninfected blood donors. Adjusted odds ratios (ORs) and 99% confidence intervals (CIs) were derived from logistic regression models controlling for demographics and relevant confounders. All subjects were human immunodeficiency virus type 1-seronegative. HTLV-II was significantly associated with a history of pneumonia (OR, 2.6; 99% CI, 1.2-5.3), minor fungal infection (OR, 2.9; 99% CI, 1.2-7.1), and bladder or kidney infection (OR, 1.6; 99% CI, 1.0-2.5) within the past 5 years and with a lifetime history of tuberculosis (OR, 3.9; 99% CI, 1.3-11.6) and arthritis (OR, 1.8; 99% CI, 1.2-2.9). Lymphadenopathy (> or =1 cm) was associated with both HTLV-I (OR, 6.6; 99% CI, 2.2-19.2) and HTLV-II (OR, 2.8; 99% CI, 1.1-7.1) infection, although no case of adult T cell leukemia/lymphoma was diagnosed. Urinary urgency and gait disturbance were associated with both viruses. This new finding of increased prevalence of a variety of infections in HTLV-II-positive donors suggests immunologic impairment.

HTLV-associated myelopathy in a cohort of HTLV-I and HTLV-II-infected blood donors. The REDS investigators.

OBJECTIVE: HTLV-I-associated myelopathy (HAM) is a slowly progressive spastic paraparesis caused by infection with human T-lymphotropic virus type I (HTLV-I). The prevalence of HAM among those infected with HTLV-I is poorly defined, and the association of a similar myelopathy with HTLV-II infection has not been confirmed. DESIGN: Cross-sectional examination of HTLV-I, HTLV-II, and control subjects from the baseline visit of a cohort study. SETTING/ SUBJECTS: Persons testing HTLV seropositive at the time of blood donation at five U.S. blood centers, their seropositive sex partners, and a matched control group of HTLV seronegative blood donors. MEASUREMENTS: HTLV-I and HTLV-II were differentiated by serology and/or polymerase chain reaction. All subjects received systematic neurologic screening examinations. RESULTS: A diagnosis of myelopathy was confirmed in four of 166 HTLV-I subjects (2.4%, 95% confidence interval 0.7%, 6.1%) and in one of 404 HTLV-II subjects (0.25%, 95% confidence interval 0.0%, 0.6%). None of the 798 controls had a similar myelopathy, although one had longstanding typical multiple sclerosis. CONCLUSIONS: Our data also suggest that HAM occurs more frequently among HTLV-I-infected subjects than reported by previous studies. The HTLV-II infected myelopathy patient identified in this cohort, together with three other case reports in the literature, implies a pathogenic role for this human retrovirus. The diagnosis of HTLV-associated myelopathy should be considered in cases of spastic paraparesis or neurogenic bladder when risk factors for HTLV-I or HTLV-II infection are present.

Regulations prohibiting blood donation by individuals with seizures or epilepsy are not necessary.

Throughout the world people who have epilepsy and seizures are prohibited from donating blood. These restrictions are based on the assumption that they are prone to adverse donor reactions, specifically, syncope and convulsions. We describe a study evaluating whether that concern is warranted. During a two year period beginning in 1987, blood donors with a history of seizures were actively recruited by the American Red Cross in the state of Maryland, USA. According to accepted standards, adverse reactions were classified as "slight", for dizziness and nausea without loss of consciousness; "moderate", denoting syncope; and "severe", indicating convulsive syncope. We reviewed a total of 329,143 satisfactory blood donations, and 613 individuals reporting a history of seizures donated blood 723 times. Among donors with seizures, 186 (25.7%) were taking antiepileptic medication, and 61 (8.4%) had one or more seizures in the preceding year. Individuals with seizures had a low incidence of adverse reactions (3.34%). Although slightly higher than the entire population (2.24%), this difference was not statistically significant. In particular, the risk of syncope with or without convulsive activity was low for people with seizures (.21%) and not significantly increased as compared to other donors (.28%). Our study supports the view that individuals with seizures or epilepsy are not at greater risk for adverse reactions after blood donation. Major restrictions on individuals with epilepsy and seizures as blood donors are not warranted.

Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection.

BACKGROUND: For many people infected with the hepatitis C virus (HCV), the route of exposure, risk of transmission, and severity of associated liver disease are unknown. We studied these variables in people who donated blood voluntarily. METHODS: Blood donors who tested positive for HCV antibodies on enzyme immunoassay were classified according to whether the results of a confirmatory second-generation recombinant immunoblot assay (RIBA) for HCV were positive, negative, or indeterminate. The evaluations also included an assessment of risk factors, a physical examination, serial determinations of alanine aminotransferase levels and HCV serologic assays, a polymerase-chain-reaction assay for HCV RNA, testing of sexual contacts and family members, and liver biopsies in some participants who were HCV-positive by RIBA. RESULTS: A total of 481 donors were studied, among whom 248 were positive for HCV by RIBA, 102 had indeterminate results, and 131 were HCV-negative. In a logistic-regression analysis, significant risk factors for HCV infection among the HCV-positive participants were a history of blood transfusion in 66 (27 percent; P < 0.001 for the comparison with RIBA-negative donors), intranasal cocaine use in 169 (68 percent, P < 0.001), intravenous drug use in 103 (42 percent, P = 0.001), sexual promiscuity in 132 (53 percent, P = 0.002), and ear piercing among men (P < 0.05). Nine of 85 sexual partners of HCV-positive donors were anti-HCV-positive; 8 had used intravenous drugs or received transfusions. HCV RNA was found in 213 HCV-positive donors (86 percent), 3 who had indeterminate results by RIBA (2 of these 3 tested positive with a more specific, third-generation RIBA), and none who were HCV-negative. Of the HCV-positive donors, 69 percent had biochemical evidence of chronic liver disease; among 77 donors positive for HCV by RIBA who underwent liver biopsy, 5 had severe chronic hepatitis or cirrhosis, 66 had mild-to-moderate chronic hepatitis, and 6 had no evidence of hepatitis. CONCLUSIONS: Among volunteer blood donors, prior blood transfusion, intranasal cocaine use, intravenous drug use, sexual promiscuity, and ear piercing in men are risk factors for HCV infection. The high frequency of intravenous drug use was unexpected, because these donors had denied such use when questioned directly at the time of their blood donations.

Adverse reactions in blood donors with a history of seizures or epilepsy.

BACKGROUND: Individuals with epilepsy or seizure disorders are restricted from donating blood because of concern that they are prone to adverse donor reactions such as syncope and convulsions. A study evaluating whether that concern is warranted is reported. STUDY DESIGN AND METHODS: During a 2-year period beginning in 1987, blood donors in Maryland with a history of seizures were actively recruited by the American Red Cross. Adverse donor reactions were classified as "slight", indicating dizziness and nausea without loss of consciousness; "moderate," denoting syncope; and "severe," indicating convulsive syncope. RESULTS: There were 329,143 satisfactory blood donations; 613 individuals reporting a history of seizures donated blood a total of 723 times. Among donors with seizures, 186 (35.7%) were taking antiepileptic medication, and 61 (8.4%) had had one or more seizures in the preceding year. Individuals with seizures had a low incidence of adverse reactions (3.34%). Although this incidence was slightly higher than that in the entire population (2.24%), the difference was not significant. In particular, the risk of syncope with or without convulsive activity was low for people with seizures (0.21%) and not significantly greater than that in other donors (0.28%). CONCLUSION: Individuals with seizures or epilepsy are not at greater risk for adverse reactions after blood donation, and major restrictions on their participation as blood donors are not warranted.

Maternal immunity to red cell antigens and fetal transfusion.

This article has presented an overview of developments in the treatment of HDN. The number of cases requiring treatment that have occurred in the last decade has dropped because of the development and implementation of Rh immunoprophylaxis, although this treatment still appears to be underutilized in the United States. Failure to recognize the need for immunoprophylaxis in certain situations (including unrecognized abortion) has led to a small residual population of alloimmunized mothers who will require comprehensive treatment during subsequent pregnancies. Alloimmunization to other red cell antigens remains a small but significant problem in other women. Although great advances have been made in the monitoring of these pregnancies, amniotic fluid analysis remains a mainstay for the third-trimester evaluation of alloimmunized pregnancies. Noninvasive methods such as ultrasound evaluation and the monocyte assays may supplement, but cannot entirely replace, the need for direct assessment. The most striking advancement in the evaluation and treatment of these infants has been the ability to access the fetal circulation directly through intravenous umbilical cord sampling. This method allows for an immediate assessment of fetal anemia as well as a route for direct fetal transfusion. The method has also permitted a more complete assessment of fetal physiology. However, the method may be overutilized at the present time and has some degree of risk to the fetus, even in experienced hands. Additional methods of treatment for the alloimmunized pregnancy include plasma exchange, intravenous immunoglobulin infusion, and promethazine hydrochloride. The popularity of plasma exchange has probably decreased with the advent of more direct fetal sampling and treatment techniques, but it may be useful in the treatment of first-trimester pregnancy losses. Intravenous immunoglobulin and promethazine hydrochloride appear to be promising alternatives that require more investigation. It is apparent that efforts need to be channeled towards prevention of HDN in a health system that is highly aware of increasing costs and the benefits of preventive medicine.

The Du phenotype, serology, and clinical relevance.

In this article, the authors examine the nature of the Du phenomenon through a comprehensive historical review beginning with the initial description of the Du factor in the 1940s. Pertinent developments in serologic testing methods and genetic concepts are described. Evidence of the importance of the Du factor in transfusion and hemolytic disease of the newborn is also presented. Selected articles on the frequency of Du in Caucasian and Negro populations are cited. Finally, the authors review current theoretical concepts concerning the nature of the Du factor, its importance in current transfusion practice and maternal Rh immune globulin administration, and the use of microscopic Du testing as a screening procedure for fetomaternal hemorrhage.

Red cell sensitization due to anti-D in anti-lymphocyte globulin.

Four Rh-positive patients with severe aplastic anemia received equine anti-lymphocyte globulin. Each developed a positive direct antiglobulin test. Anti-D was identified in eluates prepared from the patients' sensitized red cells. The administered lot of anti-lymphocyte globulin was found to contain anti-D. Red cell sensitization due to passively acquired Rh antibodies can result from the administration of anti-lymphocyte globulin.

Comparison of antibody elution techniques by enzyme-linked antiglobulin test.

The enzyme-linked antiglobulin test was used to determine the percentage of antibody removed from sensitized red cells by five elution methods: Rubin ether, xylene, digitonin-acid, glycine, and heat. Antibodies examined in the study included anti-D, -c, -E, and -K. With two examples of anti-D, more antibody was eluted by the Rubin ether method (45.5% average) than the xylene (38%) or the digitonin acid method (35%) (p less than 0.05); the glycine (8%) and heat method (15%) were less efficient. With one example of anti-E and one example of anti-c, more antibody was eluted by the ether method. The percentage of anti-K recovery, however, was greater with the digitonin acid method (45%) than with the ether (30%). We found the enzyme-linked antiglobulin test method useful in the quantitative evaluation of elution procedures.