Absence of evidence for bornavirus infection in schizophrenia, bipolar disorder and major depressive disorder.

In 1983, reports of antibodies in subjects with major depressive disorder (MDD) to an as-yet uncharacterized infectious agent associated with meningoencephalitis in horses and sheep led to molecular cloning of the genome of a novel, negative-stranded neurotropic virus, Borna disease virus (BDV). This advance has enabled the development of new diagnostic assays, including in situ hybridization, PCR and serology based on recombinant proteins. Since these assays were first implemented in 1990, more than 80 studies have reported an association between BDV and a wide range of human illnesses that include MDD, bipolar disorder (BD), schizophrenia (SZ), anxiety disorder, chronic fatigue syndrome, multiple sclerosis, amyotrophic lateral sclerosis, dementia and glioblastoma multiforme. However, to date there has been no blinded case-control study of the epidemiology of BDV infection. Here, in a United States-based, multi-center, yoked case-control study with standardized methods for clinical assessment and blinded serological and molecular analysis, we report the absence of association of psychiatric illness with antibodies to BDV or with BDV nucleic acids in serially collected serum and white blood cell samples from 396 subjects, a study population comprised of 198 matched pairs of patients and healthy controls (52 SZ/control pairs, 66 BD/control pairs and 80 MDD/control pairs). Our results argue strongly against a role for BDV in the pathogenesis of these psychiatric disorders.

Indeterminate HTLV serologic results in U.S. blood donors: are they due to HTLV-I or HTLV-II?

Current screening tests to detect human T-lymphotropic virus type I (HTLV-I) in volunteer blood donors commonly yield indeterminate HTLV serologic results (mostly isolated gag reactors). To assess the significance of indeterminate HTLV serologic results in U.S. blood donors, we compared 56 persons who had such serologic patterns with 30 HTLV seropositive blood donors and with HTLV seronegative controls. Polymerase chain reaction assays showed that none of the 56 individuals with indeterminate HTLV serologic results were infected with HTLV-I or HTLV-II, while all 30 HTLV seropositive blood donors were infected with either HTLV-I (in 15) or HTLV-II (in the other 15). The seroindeterminate blood donors were also different from the HTLV seropositive blood donors and more like HTLV seronegative controls in their demographic characteristics and the presence of HTLV risk factors. These results are evidence that volunteer blood donors with isolated and persistent gag seroreactivity in the United States are unlikely to be infected with HTLV-I or HTLV-II.

The risk of development of HTLV-I-associated myelopathy/tropical spastic paraparesis among persons infected with HTLV-I.

Using data obtained in national surveys of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) conducted in Japan in 1987 and 1988, we estimated the yearly and lifetime risk that HAM/TSP will develop in an HTLV-I-infected person. "Definite" HAM/TSP was defined as slowly progressive myelopathy with antibodies to HTLV-I in both serum and cerebrospinal fluid. Estimates of HTLV-I infection rates in eight endemic prefectures, by age group and sex, were obtained from serologic studies of blood donors; population figures, by age group, sex, and prefecture, were obtained from the census. Of 589 definite cases of HAM/TSP reported nationally, 397 occurred in residents of the eight endemic prefectures; of these, 170 reported onset of illness during the years 1982-1988 (average incidence, 24.3 cases/year). Using the estimated HTLV-I infection rates and the 1985 census figures, we estimated the number of HTLV-I-infected persons in the eight prefectures in 1985 at 794,800. We therefore estimated the incidence of HAM/TSP among HTLV-I-infected persons at 3.1 x 10(-5) cases/year; assuming a lifetime of 75 years, the lifetime incidence is approximately one quarter of 1%. This estimate is important in counseling persons such as blood donors found to be infected with HTLV-I.

The search for human infection with simian type D retroviruses.

Evidence has recently been presented for an infection with a simian type D retrovirus in a patient with AIDS and lymphoma. We tested for simian type D infection in three groups of subjects: 375 patients with lymphoproliferative diseases (255 non-Hodgkin's, 88 Hodgkin's, and 32 chronic lymphoproliferative disease), of whom 75 were human immunodeficiency virus (HIV)-1 infected; seven persons with unexplained low CD4 lymphocyte counts with clinical conditions; and 45 blood donors, of whom 37 were human T-lymphocyte virus (HTLV)-I/II seroindeterminate and eight were HTLV-I/II and HIV-1 seronegative. Serum samples were screened for antibodies against simian type D retroviruses by an enzyme immunoassay, and reactive samples were analyzed by Western blotting. None of the samples were seropositive, but eight (five from non-Hodgkin's and three from Hodgkin's lymphoma patients) were seroindeterminate. Polymerase chain reaction analysis of genomic DNA from peripheral blood lymphocytes of all eight of these patients was carried out using simian type D gag generic primers with generic internal oligoprobing. All samples were negative. We conclude that simian type D infection is rare among HIV-infected and noninfected lymphoma patients, persons with unexplained low CD4 counts, and persons with HTLV-seroindeterminate test results.

HTLV-I-associated myelopathy/tropical spastic paraparesis in the United States.

HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is endemic in the Caribbean basin and Japan. Because of the close proximity of the United States to the Caribbean and the presence of HTLV-I-seropositive persons in the United States, we sought reports of patients who were HTLV-I seropositive and had a slowly progressive myelopathy. Over a 2-year period, there were 25 patients reported, 19 of whom were black and 12 of whom had been born in the United States. All patients except two had become symptomatic while living in the United States. Six patients had no apparent risk factor for acquiring HTLV-I. These data demonstrate that HAM/TSP is occurring in the United States and that the diagnosis of HAM/TSP should be considered in patients with a slowly progressive myelopathy regardless of risk factors for acquiring HTLV-I.

Pseudomonas aeruginosa serotype 0:9. New cause of whirlpool-associated dermatitis.

In a five-day period, dermatitis developed in nearly one fourth of the guests staying at a large Georgia hotel. Dermatitis was associated with use of the hotel's whirlpool (p less than 0.001) and indoor swimming pool (p less than 0.001). Attack rates were highest among persons more frequently exposed to the whirlpool, in persons under 10 years of age, and during periods of heaviest bather load. Pseudomonas aeruginosa was isolated from skin lesions of 13 of 20 patients from whom culture specimens were taken. Ten isolates were serotype 0:9. The whirlpool's water grew P. aeruginosa serotype 0:9; however, the whirlpool's automatic chlorinator was functioning properly, the pH of the water was 7.2, and the free chlorine level was 0.6 mg/liter. This is the first report of a whirlpool-associated outbreak caused by P. aeruginosa serotype 0:9. Our findings suggest that this strain may not be readily sensitive to recommended chlorine concentrations.

Pseudomonas fluorescens bacteremia from blood transfusion.

In October 1980, two units of blood contaminated with Pseudomonas fluorescens caused septic transfusion reactions in two recipients at a Chicago hospital; one patient died. Both units had been purchased from the same blood center. Investigation at the blood center and at other hospitals it supplied revealed another fatal case of P. fluorescens sepsis that had occurred one year earlier. Despite extensive environmental culturing at the blood center, the source of P. fluorescens was not identified. However, comparison of the interval between collection and administration of contaminated and non-contaminated units indicated that prolonged storage was a risk factor that may have caused clustering of cases in one hospital. Laboratory studies showed that small inocula of P. fluorescens proliferated in refrigerated fresh whole blood and reached 10(6) to 10(7) colony-forming units per milliliter seven days after incubation. These data suggest that prolonged storage of blood may be an important risk factor for the development of transfusion-related sepsis.

Hantavirus pulmonary syndrome in Florida: association with the newly identified Black Creek Canal virus.

Hantavirus pulmonary syndrome (HPS) is a recently recognized viral zoonosis. The first recognized cases were caused by a newly described hantavirus. Sin Nombre virus (previously known as Muerto Canyon virus), isolated from Peromyscus maniculatus (deer mouse). We describe a 33-year-old Floridian man who resided outside the ecologic range of P maniculatus but was found to have serologic evidence of a hantavirus infection during evaluation of azotemia associated with adult respiratory distress syndrome. Small mammal trapping conducted around this patient's residence demonstrated the presence of antihantaviral antibodies in 13% of Sigmodon hispidus [cotton rat). Serologic testing using antigen derived from the Black Creek Canal hantavirus subsequently isolated from this rodent established that this patient was acutely infected with this new pathogenic American hantavirus. HPS is not confined to the geographical distribution of P maniculatus and should be suspected in individuals with febrile respiratory syndromes, perhaps associated with azotemia, throughout the continental United States.

Investigation of proviral load in individuals infected with human T-lymphotropic virus type II.

Human T-lymphotrophic virus type II (HTLV-II) has not yet been associated with any disease. Little is known about the proviral loads of HTLV-II in vivo and its relationship, if any, to lack of pathogenicity. We determined the HTLV-II proviral copy number in peripheral blood lymphocyte (PBL) samples from 49 HTLV-II-infected individuals, of whom 25 were coinfected with human immunodeficiency virus type 1 (HIV-1). The HTLV-II copy numbers were determined by polymerase chain reaction (PCR) amplification of end-point dilutions of PBL lysates, followed by hybridization to a 32P-labeled HTLV-II-specific probe. The proviral copy number for the 49 samples ranged from < 0.02 to 200 per 1000 PBLs; 6% had < 0.02, 16% had 0.02, 20% had 0.2, 18% had 2, 31% had 20, and 8% had 200 copies per 1000 PBLs. The distributions of HTLV-II copy numbers in the coinfected and singly infected subgroups were not significantly different (Wilcoxon rank sum, p = 0.24). In the coinfected subgroup, there was no significant correlation between the HTLV-II proviral load and the counts of CD4-positive lymphocytes or CD8-positive lymphocytes (Spearman Coefficient = 0.26, p = 0.20; = 0.091, p = 0.67, respectively). Our data demonstrate the presence of a wide range of viral loads in HTLV-II-infected individuals. The high viral loads (> or = 20 copies/1000 lymphocytes) detected in 39% of our samples suggest that the low pathogenicity of HTLV-II is not related to the presence of low viral loads in the infected subjects. Our data from the HIV-1 coinfected individuals show no apparent effect of HIV-1 on HTLV-II proviral loads.

Infection control in Maryland nursing homes.

We surveyed 53 randomly chosen Maryland nursing homes for infection control policies and practices. The majority had written infection control policies, an infection control committee, and a designated practitioner for infection control; in most facilities, however, the infection control practitioner had other major duties, spent little time on infection control, and had no specific training in the field. Thirty-four percent of homes in the survey performed routine environmental cultures, and more than half had insufficient or no isolation policies for infected decubiti and acute diarrhea. In general, the intensity of infection surveillance and the extent of infection control measures increased with the level of care provided, from domiciliary homes to homes providing chronic care. Employee health care fared generally well: 60% of homes offered influenza vaccine to employees and 66% had restriction policies for employees with upper respiratory infections. While the majority of homes offered the influenza vaccine to residents, acceptance of other vaccines recommended for the elderly was less widespread. We conclude that infection control efforts are made in most Maryland nursing homes; however, appropriate guidelines and more effort to educate nursing home personnel in proper infection control practices are badly needed.

Emerging issues in blood safety.

Improvements in donor selection, testing of donors for markers of infection, and viral inactivation of plasma-derived products have helped reduce the risk of transfusion-associated infections, including hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency viruses (HIV). The potential for transmission of emerging infections is illustrated by current concerns about group O strains of HIV, nonenveloped viruses, newly discovered microbial agents, prions, Chagas' disease, tick-borne infections, and the need to assess the frequency of transfusion reactions associated with bacterial contamination.

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.

Seroprevalence of human T lymphotropic virus type I in Puerto Rico.

Serum specimens from Puerto Rican residents were tested for antibodies to human T lymphotropic virus type I (HTLV-I) using an enzyme immunoassay, Western immunoblot, and radioimmunoprecipitation assays. Of 1,279 specimens obtained during a dengue virus surveillance program in 1986 and 1987, 3 (0.2%) tested positive; an additional 11 were indeterminate. Of 602 specimens obtained from blood donors in Ponce in 1987, 1 (0.2%) was positive; an additional specimen was indeterminate. Of 21 persons hospitalized for problems related to intravenous drug use in 1986 and 1987, 1 (5%) tested positive for HTLV-I antibodies.

Detection of human T-lymphotropic virus type-I/II env antibodies by immunoassays using recombinant fusion proteins.

Two recombinant fusion proteins representing the C-terminus of the envelope glycoprotein of HTLV-I (rEnv-93(201-440)) and the C-terminus of the external glycoprotein (RE-3(165-306)) were tested in a Western blot (WB) assay for their ability to detect the presence of env antibodies in serum specimens from HTLV-I (n = 27) and HTLV-II (n = 22) infected individuals. The rEnv-93 reacted with 27 (100%) of 27 HTLV-I-infected specimens and 19 (86%) of 22 of HTLV-II-infected specimens. In contrast, RE-3 reacted with 25 (93%) of 27 HTLV-I-infected specimens, and only six (27%) of 22 HTLV-II-infected specimens, thus demonstrating predominant reactivity with HTLV-I compared with HTLV-II. Because of the high sensitivity of rEnv-93 reactivity in both HTLV-I and HTLV-II, the specificity of this env protein was evaluated in specimens with isolated gag reactivity (HTLVind). Of the 44 HTLVind specimens, four (9%) demonstrated reactivity to rEnv-93 in WB assay. We, therefore, conclude that although rEnv-93 is highly sensitive for detection of env protein, it has the potential to yield some false-positive reactions presumably due to the conserved nature of retroviral transmembrane epitopes.

Assessment of occupational risk for hantavirus infection in Arizona and New Mexico.

Differentiating occupational exposure from other potential domestic or recreational exposure(s) for Sin Nombre virus (SNV) infection is an epidemiologic challenge. Interviews on work-related activities were conducted, and serum specimens were obtained from 494 workers in Arizona and New Mexico. These workers may have been exposed to rodents and rodent excreta at work, but their primary occupation did not require rodent contact (National Park Service [n = 193]; Navajo Agricultural Product Industry [n = 65], utility companies [n = 169] and plumbing and heating contractors [n = 67]. Within each occupational group (farm workers [n = 57], laborers [n = 20], professionals [n = 70], repairers [n = 211], service industry workers [n = 83], and technicians [n = 53], the majority of workers reported working in areas that had rodent droppings (range, 75 to 95%); 70% of laborers and 64% of service industry workers reported handling rodents. More than 60% of workers in each group, except technicians, reported reopening and cleaning or working in closed spaces. Approximately 90% of laborers, repairers, and farm workers reported hand-plowing. Although the risk for occupationally related SNV infection appears to be low, workers frequently performed risk activities associated with hantavirus pulmonary syndrome (HPS). All workers were seronegative for SNV by enzyme-linked immunoassay or Western blot testing. These findings, the known occupational exposure of some HPS cases, and the high HPS case-fatality rate (52%) support the need for recommendations to reduce human contact with rodents in the workplace. Increased understanding of hantavirus transmission to humans will help focus future recommendations to minimize human exposures effectively.

Retrospective diagnosis of hantavirus pulmonary syndrome, 1978-1993: implications for emerging infectious diseases.

OBJECTIVE: To investigate the occurrence of unrecognized cases of hantavirus pulmonary syndrome preceding the detection of the 1993 outbreak in the southwestern United States and the initial description of the syndrome. DESIGN: Retrospective clinicopathologic and immunohistologic study. PATIENTS: Eighty-two patients who died prior to April 1993 with histologically unexplained noncardiogenic pulmonary edema. METHODS: Clinicopathologic review and immunohistochemical evaluation of autopsy tissues for evidence of hantaviral infection. RESULTS: Twelve retrospective fatal cases of hantavirus pulmonary syndrome were identified through clinicopathologic review and immunohistochemical testing of tissues. Patients' ages ranged from 16 to 49 years. The earliest identified case occurred in 1978, 15 years prior to the outbreak of hantavirus pulmonary syndrome in the southwestern United States. Immunohistochemical testing showed widespread deposition of hantaviral antigens, primarily within endothelial cells, similar to the pattern observed with current hantavirus pulmonary syndrome cases. CONCLUSIONS: Although hantavirus pulmonary syndrome was first recognized in 1993, the findings from this study document the earlier existence of this disease. These findings underscore the need for systematic archiving and analysis of clinical information and specimens from patients with diseases of unknown etiology to facilitate the study of new clinical entities and their associated etiologic agents.