Simian foamy virus infection in a blood donor.

BACKGROUND: Infections with simian foamy virus (SFV) are widely prevalent in nonhuman primates. SFV infection was confirmed in a worker, occupationally exposed to nonhuman primates, who donated blood after the retrospectively documented date of infection. Human-to-human transmission of SFV through transfusion and its pathogenicity have not been studied. STUDY DESIGN AND METHODS: Recipients of blood from this donor were identified and blood samples from such recipients were tested for SFV infection by Western blot and PCR assay. RESULTS: One recipient of RBCs and another recipient of FFP had died; retroviral infections were not implicated. One platelet recipient could not be tested. Recipients of RBCs (two), a WBC-reduced RBC unit (one), and a platelet unit (one) tested SFV-negative 19 months to 7 years after transfusion. Tested recipients had transfusions 3 to 35 days after blood donation. Samples of one lot of albumin and three lots of plasma protein fraction (manufactured from recovered plasma from two donations) tested negative both for antibodies and for viral RNA. CONCLUSION: SFV transmission through transfusion was not identified among four recipients of cellular blood components from one SFV-infected donor. Derivatives containing plasma from that donor tested negative for SFV.

Lack of cross-species transmission of porcine endogenous retrovirus infection to nonhuman primate recipients of porcine cells, tissues, or organs.

BACKGROUND: Nonhuman primates (NHPs) have been widely used in different porcine xenograft procedures inevitably resulting in exposure to porcine endogenous retrovirus (PERV). Surveillance for PERV infection in these NHPs may provide information on the risks of cross-species transmission of PERV, particularly for recipients of vascularized organ xenografts for whom data from human clinical trials is unavailable. METHODS: We tested 21 Old World and 2 New World primates exposed to a variety of porcine xenografts for evidence of PERV infection. These NHPs included six baboon recipients of pig hearts, six bonnet macaque recipients of transgenic pig skin grafts, and nine rhesus macaque and two capuchin recipients of encapsulated pig islet cells. Serologic screening for PERV antibody was done by a validated Western blot assay, and molecular detection of PERV sequences in peripheral blood mononuclear cells (PBMCs) and plasma was performed using sensitive polymerase chain reaction and reverse transcriptase-polymerase chain reaction assays, respectively. Spleen and lymph node tissues available from six bonnet macaques and three rhesus macaques were also tested for PERV sequences. RESULTS: All plasma samples were negative for PERV RNA suggesting the absence of viremia in these xenografted animals. Similarly, PERV sequences were not detectable in any PBMC and tissue samples, arguing for the lack of latent infection of these compartments. In addition, all plasma samples were negative for PERV antibodies. CONCLUSION: These data suggest the absence of PERV infection in all 23 NHPs despite exposure to vascularized porcine organs or tissue xenografts and the use of immunosuppressive therapies in some animals. These findings suggest that PERV is not easily transmitted to these NHP species through these types of xenografts.

Evidence of infection with simian type D retrovirus in persons occupationally exposed to nonhuman primates.

Simian type D retrovirus (SRV) is enzootic in many populations of Asian monkeys of the genus Macaca and is associated with immunodeficiency diseases. However, the zoonotic potential of this agent has not been well defined. Screening for antibodies to SRV was performed as part of an ongoing study looking for evidence of infection with simian retroviruses among persons occupationally exposed to nonhuman primates (NHPs). Of 231 persons tested, 2 (0.9%) were found to be strongly seropositive, showing reactivity against multiple SRV antigens representing gag, pol, and env gene products by Western immunoblotting. Persistent long-standing seropositivity, as well as neutralizing antibody specific to SRV type 2, was documented in one individual (subject 1), while waning antibody with eventual seroreversion was observed in a second (subject 2). Repeated attempts to detect SRV by isolation in tissue culture and by using sensitive PCR assays for amplification of two SRV gene regions (gag and pol) were negative. Both individuals remain apparently healthy. We were also unable to transmit this seropositivity to an SRV-negative macaque by using inoculation of whole blood from subject 1. The results of this study provide evidence that occupational exposure to NHPs may increase the risk of infection with SRV and underscore the importance of both occupational safety practices and efforts to eliminate this virus from established macaque colonies.

Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group.

Pig organs may offer a solution to the shortage of human donor organs for transplantation, but concerns remain about possible cross-species transmission of porcine endogenous retrovirus (PERV). Samples were collected from 160 patients who had been treated with various living pig tissues up to 12 years earlier. Reverse transcription-polymerase chain reaction (RT-PCR) and protein immunoblot analyses were performed on serum from all 160 patients. No viremia was detected in any patient. Peripheral blood mononuclear cells from 159 of the patients were analyzed by PCR using PERV-specific primers. No PERV infection was detected in any of the patients from whom sufficient DNA was extracted to allow complete PCR analysis (97 percent of the patients). Persistent microchimerism (presence of donor cells in the recipient) was observed in 23 patients for up to 8.5 years.

Xenotransplantation and the risk of retroviral zoonosis.

It is hypothesized that xenotransplantation could facilitate the emergence of new human pathogens. Retroviruses might pose the greatest public health risk because of the possibility of undetected transmission within a population. Evidence from naturally occurring retroviral zoonoses and cross-species infections by animal retroviruses provides a basis for reasoned speculation on the risks posed by xenotransplantation.

No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts.

BACKGROUND: The study of whether porcine xenografts can lead to porcine endogenous retrovirus (PERV) infection of recipients is critical for evaluating the safety of pig-to-man xenotransplantation. PERV is carried in the pig germline, and all recipients of porcine tissues or organs will be exposed to the virus. METHODS: We studied 10 diabetic patients who had received porcine fetal islets between 1990 and 1993, looking for evidence of PERV infection by using PCR serology, PCR, and reverse transcriptase assays. Prolonged xenograft survival (up to a year) was confirmed in five patients by porcine C-peptide excretion and detection of pig mitochondrial DNA (mtDNA) in serum. FINDINGS: Despite the evidence for extended exposure to pig cells and despite concomitant immunosuppressive therapy, we were unable to detect markers of PERV infection in any patient. Screening for two PERV sequences in peripheral blood lymphocytes collected 4-7 years after the xenotransplantation was negative. Markers of PERV expression, including viral RNA and reverse transcriptase, were undetectable in sera from both early (day 3 to day 180) and late (4-7 years) time points. Western blot analysis for antibodies was consistently negative. INTERPRETATION: These results suggested the absence of PERV infection in these patients. Also this study establishes a minimum standard for post-transplant surveillance of patients given porcine xenografts.

Identification of a human population infected with simian foamy viruses.

Studying the transmission of simian retroviruses to humans can help define the importance of these infections to public health. We identified a substantial prevalence (4/231, 1.8%) of infection with simian foamy viruses (SFV) among humans occupationally exposed to nonhuman primates. Evidence of SFV infection included seropositivity, proviral DNA detection and isolation of foamy virus. The infecting SFV originated from an African green monkey (one person) and baboons (three people). These infections have not as yet resulted in either disease or sexual transmission, and may represent benign endpoint infections.

Rift Valley fever in rural northern Senegal: human risk factors and potential vectors.

To investigate past infection in and transmission of Rift Valley fever (RVF) virus to humans within an endemic focus, we undertook a retrospective cohort study of the seminomadic Peul people living in sub-Saharan northcentral Senegal. Residents of the rural settlement of Yonofere five years of age or older were studied during February-May 1989. Anti-RVF virus IgG was found in blood samples of 22.3% of 273 persons who responded to a standard questionnaire; none had IgM antibodies. Seropositivity was similar for males (25.4%) and females (21.1%), increased markedly with age for both sexes, and varied considerably among compounds (groups of huts) (0-37.5%). Risk factors for past RVF virus infection were nursing sick people, assisting animals during abortions/births, and treating sick animals. In all age groups, odds ratios (ORs) for RVF viral antibody among females who reported treating sick animals were three to six times greater than for those who did not. The ORs for males who reported assisting with animal births/abortions and nursing sick people were approximately five times those for males who did not. Serologic prevalence of RVF viral antibody among sheep averaged 30.1% overall (0.8% IgM), but varied among compounds (0-66.7%) in a manner different from that of humans. The seasonal abundance and relative density of potential mosquito vectors were estimated by monthly samples captured in Centers for Disease Control and Prevention-type traps. Mosquito abundance varied seasonally with rainfall (> 90% captures during four months). Species diversity was large (28 spp.), dominated by Aedes and Culex. Rift Valley fever virus was not isolated from 142 pools of 2,956 unengorged mosquitoes tested, although three other arboviruses were found. Results indicate that RVF is endemic in this region, people are at considerable risk of infection, and that a heretofore unrecognized mode of human infection under nonepizootic conditions may be transmission via contact with infected animals or humans.

Lack of evidence for infection with known human and animal retroviruses in patients with chronic fatigue syndrome.

We investigated 21 patients with chronic fatigue syndrome who were identified through the surveillance system of the Centers for Disease Control and Prevention (CDC) in Atlanta for the presence of several human and animal retroviruses. In addition, we evaluated 21 CDC employee controls matched with the patients for age (+/- 5 years), gender, and race. The viruses tested included human T-lymphotropic viruses types I and II; human spuma retrovirus; simian T-lymphotropic virus type I; simian retroviruses types 1, 2, and 3; bovine leukemia virus; feline leukemia virus; and gibbon ape leukemia virus. Samples of peripheral blood lymphocytes and leukocytes from patients and controls were analyzed in a blinded fashion for retroviral sequences; polymerase chain reaction (PCR) amplification assays and Southern blot hybridization to 32P-labeled internal oligoprobes were used. All PCR assays were optimized for maximal sensitivity on respective infected cell lines or plasmids, and sensitivity controls were included in each experiment. All samples from patients and controls were negative for the tested retroviral sequences. Our data indicate that none of these retroviruses plays an etiologic role or is a cofactor in the chronic fatigue syndrome illnesses of our study population.

Epidemic keratoconjunctivitis in a chronic care facility: risk factors and measures for control.

OBJECTIVE: To study patterns of transmission of epidemic keratoconjunctivitis (EKC) in a chronic care facility and to assess control measures and prevent future outbreaks in this setting. DESIGN: A retrospective cohort study. SETTING: A 120-bed, four-unit, skilled nursing facility. PATIENTS: Residents and employees of the above facility. INTERVENTIONS: Increased frequency of cleaning; use of bleach disinfectant; universal precautions in handling eye secretions from residents with conjunctivitis; cohorting residents by unit; suspension of new admissions; closure of common gathering areas. MEASUREMENTS: Resident demographics; possible risk factors for infection among residents (including mobility, underlying illness, medications, involvement in social activity, level of confusion) and among employees (including co-morbid illnesses and eye conditions, exposures to persons with conjunctivitis, visits to eye care specialists, use of contact lenses or glasses); testing of conjunctival specimens from symptomatic persons for viral and bacterial agents. RESULTS: Of 95 residents on three chronic care units, 47 (attack rate 49%) had onset of eye symptoms consistent with EKC between September 14 and December 7, 1990. Thirty-eight (81%) of these had onset following the onset of symptoms in a resident with dementia who, despite habitual eye-rubbing and wandering into other residents' rooms, was not isolated or restricted in any way. Attack rates were higher (though not statistically significant) among more mobile residents (60% for ambulatory residents) and among those considered by staff to be confused (56%). Rapid antigen detection and culture confirmed adenovirus type 37 as the etiologic agent. CONCLUSIONS: Transmission of infection with adenovirus type 37 was successfully interrupted following strict infection control, suspension of new admissions, cohorting of residents by unit, and change to a disinfectant that inactivates adenovirus. Recognition of conjunctivitis as an appropriate reason for restricting movement of an infected resident may have prevented extensive viral transmission in this outbreak.

Assessment of a retrovirus sequence and other possible risk factors for the chronic fatigue syndrome in adults.

OBJECTIVE: To assess whether the human T-lymphotropic virus type II (HTLV-II) gag gene sequence, a purportedly new laboratory marker of the chronic fatigue syndrome (CFS), and other possible risk factors for CFS, particularly those associated with retroviral transmission, are associated with well-characterized CFS. DESIGN: Two matched case-control studies. SETTING: The metropolitan Atlanta area. PATIENTS: Twenty-one patients with CFS who were identified by the Centers for Disease Control and Prevention CFS surveillance system; 21 CDC employee controls (laboratory study) and 42 neighborhood controls (risk-factor study) who were matched to patients by age, race, and gender. MEASUREMENTS: Peripheral blood lymphocytes and leukocytes were assayed for the HTLV-II gag gene sequence by polymerase chain reaction and specific Southern blot hybridization. Questionnaires elicited demographic and clinical information and a history of exposures associated with retrovirus transmission (for example, blood transfusions, sexual practices, intravenous drug use). RESULTS: All patients were white and 86% were female. The median age at illness onset was 34 years (range, 16 to 51 years). The HTLV-II gag gene sequence was not identified in the blood of any patient or control under conditions in which the appropriate assay controls were positive. No statistical differences were observed between patients and controls in frequency of blood transfusions (10% compared with 7%), median number of sex partners before illness (3 compared with 3), bisexual or homosexual behavior (14% compared with 7%), intravenous drug use (0% compared with 0%), and other factors associated with retroviral infection. CONCLUSIONS: The HTLV-II gag gene sequence was not a marker for CFS in this small study of well-defined patients, nor did other characteristics of the patients and controls support the hypothesis that a retrovirus, transmitted by usual modes, was a cause of CFS.

Risk factors for strongyloidiasis. A case-control study.

Although infection with Strongyloides stercoralis is usually only mildly symptomatic, it can persist for many years and occasionally progress to the hyperinfection syndrome, with a resultant high mortality rate. We studied factors associated with S stercoralis infection by comparing 28 domestic cases of S stercoralis infection with 76 controls with negative stool samples for ova and parasites. The relative risk (RR) of S stercoralis infection was increased for white patients (RR = 5.6), men (RR = 3.9), and patients who had recently used corticosteroids (RR = 3.3), had a hematologic malignancy (RR = 5.28) or had prior gastric surgery (RR = 11.5). These risk factors might be for initial infection, persistence of infection, or both. Although they are not necessarily causal, knowledge of them may lead to earlier recognition of this dangerous and treatable disease.