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.

Prevalence and clinical features of HTLV neurologic disease in the HTLV Outcomes Study.

BACKGROUND: Almost 20 years after its discovery, the prevalence and clinical course of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM, also known as tropical spastic paraparesis [TSP]) remain poorly defined. Whereas the causative association of HTLV-I and HAM/TSP is generally recognized, controversy still surrounds the relationship between HTLV-II and HAM/TSP. METHODS: The HTLV Outcomes Study (HOST-formerly Retrovirus Epidemiology Donor Study [REDS]) is a prospective cohort study including 160 patients with HTLV-I, 405 patients with HTLV-II, and 799 uninfected controls who have been followed every 2 years since 1990-1992. Clinical outcomes are measured by health interviews and examinations, and blood samples are obtained. RESULTS: Six cases of HTLV-I-associated myelopathy (3.7%, 95% CI 1.4 to 8.0) and four cases of HTLV-II myelopathy (1.0%, 95% CI 0.3 to 2.5) have been diagnosed since the formation of the cohort. There have been no cases of HAM/TSP diagnosed among HTLV-negative subjects (0.0%, 95% CI 0.0 to 0.5). Clinical features of the cases include lower extremity hyperreflexia, variably associated with weakness, spasticity, and bladder dysfunction. CONCLUSIONS: Systematic screening of HTLV-infected blood donors reveals a high prevalence of HAM/TSP. The clinical course of HAM/TSP appears highly variable. HTLV-II-associated myelopathy generally presents with milder and more slowly progressive signs and symptoms.

Laboratory abnormalities in former blood donors seropositive for human T-lymphotropic virus types 1 and 2: a prospective analysis.

CONTEXT: The human T-lymphotropic viruses types 1 and 2 (HTLV-1 and HTLV-2) are highly prevalent among injection drug users in the United States. However, the clinical course of infection has not been well characterized. OBJECTIVE: To understand HTLV-1-and HTLV-2-associated laboratory abnormalities, which may provide insights into their underlying pathophysiology. DESIGN: Cohort study. SETTING: Five US blood centers. PARTICIPANTS: A total of 133 HTLV-1-and 332 HTLV-2-seropositive former blood donors and 717 HTLV-seronegative donors followed up prospectively since 1991. MAIN OUTCOME MEASURES: Selected serum chemistry tests and complete blood cell counts were analyzed at enrollment and approximately 2 years later in participants. Repeated-measures analyses were conducted to evaluate the effect of HTLV infection on laboratory measures. RESULTS: Compared with seronegative subjects, HTLV-1-seropositive subjects had 13% higher creatine kinase (P =.02) and slightly elevated lactate dehydrogenase (P =.03) levels at follow-up. The HTLV-2-seropositive participants had 11% higher absolute lymphocyte counts than seronegative subjects (P =.0001). Infection with HTLV-2 also appeared to be associated with slightly higher hemoglobin levels (P =.03) and hematocrit (P =.03) and with lower albumin levels (P =.01). CONCLUSIONS: These results further our understanding of the biological mechanisms underlying HTLV and suggest that HTLV-associated laboratory changes are unlikely to alter clinical evaluation or counseling of otherwise healthy HTLV-infected subjects.

Worldwide ethnic distribution of the G protein beta3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals.

Recently, it was demonstrated that one allele (825T) of the gene encoding the G protein beta3 subunit (GNB3) is associated with hypertension in Germans. This study investigates a possible association with obesity in young male Germans, Chinese, and black South Africans with low, intermediate, and high 825T allele frequencies, respectively. In each of these three distinct cohorts, the 825T allele frequency was increased significantly in overweight (body mass index [BMI] > or =25 kg/m2) and obese individuals (BMI >27 kg/m2) compared to those with normal weight. The 825T allele frequencies in these three BMI groups were, respectively, 29.5, 39.3, and 47.7% in Germans, 46.8, 53.9, and 58.6% in Chinese, and 83.1, 87.7, and 90.9% in South Africans. In each of these three distinct groups, the 825T allele was significantly associated with obesity with odds ratios between 2 and 3. More urban than rural black Africans were overweight despite similar 825T allele frequencies in both populations, which underscores the role of both genetic and environmental factors. BP values in young male whites increased significantly with increasing BMI values but were independent of the C825T polymorphism, suggesting that hypertension associated with the 825T allele could be a consequence of obesity. Genotyping of 5254 individuals from 55 native population samples from Africa, the Americas, Europe, Asia, Australia, and New Guinea demonstrated highest 825T allele frequencies in black Africans (82%) and intermediate values in east Asians (47%). It is anticipated that high frequencies of the 825T allele in Africans and Asians may contribute to an obesity and hypertension epidemic if Westernization of lifestyles continues.

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.

Laboratory test differences associated with HTLV-I and HTLV-II infection. Retrovirus Epidemiology Donor Study Investigators.

Reports of laboratory abnormalities associated with HTLV-I and HTLV-II infection are inconsistent. We assessed complete blood counts and selected serum chemistry measures at enrollment in a cohort of 153 HTLV-I-seropositive, 386 HTLV-II-seropositive, and 795 HTLV-seronegative blood donors. Linear and logistic regression were used to adjust for potential confounding variables including age, gender, race/ethnicity, education level, blood center, and injection drug use. Compared with seronegative donors, absolute lymphocyte counts were 6% and 10% higher, on average, in HTLV-I-infected (p = .03) and HTLV-II-infected (p = .0001) donors, respectively. HTLV-I- and HTLV-II-seropositive donors had, on average, 17,630 (p = .003) and 15,160 (p = .0005) more platelets, respectively. HTLV-I-infected donors also had an average of 30 fewer eosinophils/microl (p = .003) and a slightly higher level of lactic dehydrogenase (p = .05). HTLV-II-infected subjects had on average, an 11% decrease in creatine kinase (p = .006), a minor increase in mean corpuscular volume (p = .01), and a slightly lower serum calcium level (p = .0005). These results indicate that both HTLV-I and HTLV-II may raise levels of lymphocytes and platelets by unknown mechanisms. Lower eosinophil counts may be related to the increased susceptibility of HTLV-I-infected subjects to parasitic diseases.

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.

Practical aspects of out-of-hospital transfusion.

Out-of-hospital transfusion (OOHT) occurs in nontraditional settings, such as a patient's home, a physician's office, or a convalescent facility. Requests to issue components for OOHT present new challenges to some blood centers and transfusion services that are accustomed to issuing blood for use only in the hospital setting. Concerns about patient safety, a paucity of practical information on establishing programs, and a lack of specific practice guidelines may discourage some organizations from offering these services. Participation in OOHT programs, however, may present new patient care and customer service opportunities to blood centers and transfusion services. The purpose of this article is to familiarize readers with the essential elements for establishing a safe program. Relevant regulatory, legal, and financial issues are also addressed.

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.

Transfusion practice in medical patients.

OBJECTIVE: Blood transfusion raises serious issues of safety and economics. We therefore examined blood usage and its characteristics in medical inpatients, given the relative scarcity of existing data. DESIGN: During a 1-year period, transfusion episodes on two medical services were reviewed by five specialists for justifiability on the basis of generally agreed on guidelines. SETTING: The study was conducted at two institutions, a municipal teaching hospital where house staff deliver care and a community hospital where patients are under the direct care of private physicians. PATIENTS: Four hundred thirty-eight randomly selected transfusion episodes on the medical services of the two institutions were reviewed. MAIN OUTCOME MEASURES: The prevalence of unjustifiable transfusions based only on the information available to the managing physician at the time of transfusion. RESULTS: Eighteen percent of the 438 randomly selected transfusion episodes were viewed as not justifiable by at least four of five reviewers; another 17% were classified as equivocal because two or three reviewers judged them to be not justifiable. The most striking observation was the greater prevalence of nonjustifiable transfusion episodes at the community hospital (26% vs 16% at the teaching institution; P = .0121). Other observations included a tendency for physicians to prescribe transfusions by the numbers (at least 11% of nonjustifiable transfusions) and to overtransfuse. The routineness with which transfusion was viewed by managing physicians was also identifiable by the absence of written transfusion notes in 39% of all episodes reviewed, which incidentally raises questions about the adequacy of the medical chart's documentary functions today. CONCLUSIONS: The rate of nonjustifiable or equivocal transfusion on medical services may be as high as 35%. Reliance on numbers rather than clinical status seems to be a major problem. Education is obviously a critical issue and should also target private practitioners, who seemed to perform less well than physicians in training. Transfusion guidelines that use specific hematocrit values also need to be reexamined.

Fetal cystic hygroma and Turner's syndrome.

Large nuchal cystic hygromas were observed in five second-trimester aborted fetuses at autopsy. Two female fetuses with generalized edema were karyotyped as 45,X. One of these was the twin of a 46,XX normal female sibling. The association of generalized edema with large nuchal cystic hygromas was seen only in these two fetuses and represents strong phenotypic evidence of Turner's syndrome. However, the absence of hydrops was not a reliable indicator of normal karyotype. One fetus without generalized edema was karyotyped as 47,XY, +21, inv(9). The remaining cases had normal karyotypes. Placental histology was not useful in discriminating monosomy X from other conditions, but placental tissue culture was important in obtaining a cytogenetic diagnosis. Karyotyping is recommended in all cases of fetal cystic hygroma.