Showing papers on "Viremia published in 1993"
TL;DR: Data from retrovirus-infected animal models treated with antiviral agents suggests that therapy at the time of viral dissemination may be an effective strategy that may modify disease progression, and clinical trials to evaluate this approach are in progress.
Abstract: Primary human immunodeficiency virus type 1 (HIV-1) infection can present clinically as the abrupt onset of a febrile illness resembling acute mononucleosis. The symptoms coincide with high titers of culturable plasma viremia, cell-associated virus, and antigenemia, which rapidly decrease coincident with the emergence of detectable HIV-specific antibody and HIV-specific cytotoxic T lymphocytes. This article reviews the human and animal model data on the virologic and immunologic events that occur during primary HIV-1 and animal retrovirus infections, evaluates the prophylactic treatment experience of retrovirus infections in the animal model, and provides a plausible rationale for treatment intervention of primary HIV-1 infection in humans. Recent work delineating the pathogenesis of primary HIV-1 infection provides insight into the major mechanisms of viral dissemination and host immune response. The results from retrovirus-infected animal models treated with antiviral agents suggests that therapy at the time of viral dissemination may be an effective strategy that may modify disease progression. Clinical trials to evaluate this approach are in progress.
145 citations
TL;DR: Ribavirin treatment reduced CCHF virus growth in liver and significantly decreased, but did not prevent, viremia, and a hepatotropic virus subpopulation with less neurovirulence than the parent was isolated from liver of ribavirin-treated mice.
131 citations
TL;DR: The results indicate that the down-regulation in the levels of virus replication associated with the clinical transition from acute to chronic infection does not necessarily reflect a reduction in viral burden, thus suggesting the involvement of additional factors.
Abstract: HIV-1 replication and viral burden in peripheral blood mononuclear cells (PBMC) have been reported to be high in primary infection but generally very low during the prolonged period of clinical latency. It is uncertain precisely when this transition occurs during the HIV-1 infection and what the relationship is between the changes in HIV-1 replication versus the clearance of infected cells in the overall control of viral replication. In the present study, the kinetics of viral burden (i.e., frequency of HIV-1-infected cells) and replication during primary and early-chronic infection were analyzed in PBMC of four acutely infected individuals. High frequencies of HIV-1-infected cells and high levels of virus replication were observed in PBMC after primary HIV-1 infection. Down-regulation of virus replication in PBMC was observed in all four patients coincident with the emergence of HIV-1-specific immune responses. Other parameters of virus replication, such as circulating plasma p24 antigen and plasma viremia showed similar kinetics. In contrast, a significant decline in viral burden in PBMC was observed in only one of four patients. These results indicate that the down-regulation in the levels of virus replication associated with the clinical transition from acute to chronic infection does not necessarily reflect a reduction in viral burden, thus suggesting the involvement of additional factors. Identification of these factors will be important in elucidating the host mechanisms involved in the early control of HIV-1 infection and disease.
131 citations
TL;DR: A need for liver biopsy and antiviral treatment before kidney transplantation is suggested and the isolation of anti-HCV positive subjects in the dialysis setting should be evaluated to reduce patient-to-patient transmission of HCV.
126 citations
TL;DR: It is concluded that there is an age-related restriction of A7(74) replication in mouse neurons and that this restriction is not associated with the maturity of virus-specific immune responses but probably reflects age- related changes in neurons.
121 citations
TL;DR: Immunophenotyping of the patients after BMT in addition to a highly sensitive virus detection assay might help to identify patients at high risk to develop CMV disease and indicate the need for additional adoptive immunotherapy.
106 citations
TL;DR: A review of available information on vaccines for infectious pancreatic necrosis virus, viral hemorrhagic septicemia virus, infectious hematopoietic necrot virus, spring viremia of carp virus, and channel catfish virus is presented.
105 citations
TL;DR: Results indicate that differences in more than one region of the viral genome are responsible for the lack of virulence of SIVmac1A11.
Abstract: To identify viral determinants of simian immunodeficiency virus (SIV) virulence, two pairs of reciprocal recombinants constructed from a pathogenic (SIVmac239) and a nonpathogenic (SIVmac1A11) molecular clone of SIV were tested in rhesus macaques. A large 6.2-kb fragment containing gag, pol, env, and the regulatory genes from each of the cloned (parental) viruses was exchanged to produce one pair of recombinant viruses (designated SIVmac1A11/239gag-env/1A11 and SIVmac239/1A11gag-env/239 to indicate the genetic origins of the 5'/internal/3' regions, respectively, of the virus). A smaller 1.4-kb fragment containing the external env domain of each of the parental viruses was exchanged to create the second pair (SIVmac1A11/239env/1A11 and SIVmac239/1A11env/239) of recombinant viruses. Each of the two parental and four recombinant viruses was inoculated intravenously into four rhesus macaques, and all 24 animals were viremic by 4 weeks postinoculation (p.i.). Virus could not be isolated from peripheral blood mononuclear cells (PBMC) of any animals infected with SIVmac1A11 after 6 weeks p.i. but was consistently isolated from all macaques inoculated with SIVmac239 for 92 weeks p.i. Virus isolation was variable from animals infected with recombinant viruses; SIVmac1A11/239gag-env/1A11 and SIVmac239/1A11env/239 were isolated most frequently. Animals inoculated with SIVmac239 had 10 to 100 times more virus-infected PBMC than those infected with recombinant viruses. Three animals infected with SIVmac239 died with simian AIDS (SAIDS) during the 2-year observation period after inoculation, and the fourth SIVmac239-infected animal had clinical signs of SAIDS. Two animals infected with recombinant viruses died with SAIDS; one was infected with SIVmac239/1A11gag-env/239, and the other was infected with SIVmac1A11/239gag-env/1A11. The remaining 18 macaques remained healthy by 2 years p.i., and 13 were aviremic. One year after inoculation, peripheral lymph nodes of some of these healthy, aviremic animals harbored infected cells. All animals seroconverted within the first few weeks of infection, and the magnitude of antibody response to SIV was proportional to the levels and duration of viremia. Virus-suppressive PBMC were detected within 2 to 4 weeks p.i. in all animals but tended to decline as viremia disappeared. There was no association of levels of cell-mediated virus-suppressive activity and either virus load or disease progression. Taken together, these results indicate that differences in more than one region of the viral genome are responsible for the lack of virulence of SIVmac1A11.
94 citations
TL;DR: Five cynomolgus monkeys (Macaca fascicularis) developed hepatitis after inoculation with a prototype strain of hepatitis E virus (HEV) from Pakistan, and one of these monkeys had a more severe hepatitis, with peak ALT values more than twice the peak levels of the other monkeys.
Abstract: Five cynomolgus monkeys (Macaca fascicularis) developed hepatitis after inoculation with a prototype strain of hepatitis E virus (HEV) from Pakistan. Although all 5 monkeys displayed liver enzyme elevations, viremia, virus secretion in feces, and seroconversion, two different patterns of these parameters were observed. For 4 monkeys, increased alanine aminotransferase (ALT) activity was first observed on days 21-26, viremia occurred before and during enzyme elevation, and the animals seroconverted coincidentally with the end of viremia or shortly thereafter. One of these monkeys had a more severe hepatitis, with peak ALT values more than twice the peak levels of the other monkeys. The fifth monkey developed biphasic hepatitis with peaks of ALT activity on days 26 and 54. In this case, viremia and seroconversion were correlated only with the second peak of enzyme elevation and liver histopathology only with the first peak. Viral shedding in this fifth animal lasted two times longer than in other animals.
91 citations
TL;DR: In patients who were clinically stable while on AZT, HIV-1 titers in plasma and mononuclear cells were generally low but resistant viruses already predominated, and the resistance phenotype was nearly universal, to emphasize the magnitude of the AZT-resistance problem in patients on drug treatment.
Abstract: A nonselective ex vivo assay was used to directly detect and quantify zidovudine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) in the blood of treated and untreated patients. In contrast to previous reports, drug-resistant virus was detected in peripheral blood mononuclear cells of a few of the patients who had never received AZT. The AZT resistance of HIV-1 isolates from one untreated individual was confirmed by further susceptibility studies in vitro and by the finding of a characteristic mutation (Lys-->Arg at codon 70) in the reverse transcriptase. In patients who were clinically stable while on AZT, HIV-1 titers in plasma and mononuclear cells were generally low but resistant viruses already predominated. In those individuals who were deteriorating despite AZT administration, high levels of viremia were observed, and the resistance phenotype was nearly universal. These findings serve to emphasize the magnitude of the AZT-resistance problem in patients on drug treatment.
91 citations
TL;DR: Thirty-three infants born to human immunodeficiency virus type 1 (HIV-1)-seropositive women were evaluated from birth using plasma and peripheral blood mononuclear cell (PBMC) cultures, polymerase chain reaction, and serum p24 antigen assays, suggesting in utero infection.
Abstract: Thirty-three infants born to human immunodeficiency virus type 1 (HIV-1)-seropositive women were evaluated from birth using plasma and peripheral blood mononuclear cell (PBMC) cultures, polymerase chain reaction, and serum p24 antigen assays. Five children were identified as infected. Evidence of infection was found in cord blood and subsequent samples from 2 infected children, suggesting in utero infection. Virologic studies on cord blood and early neonatal specimens from the 3 other infected children were negative but became positive by 8 weeks of age, suggesting either intrapartum transmission or sequestration of virus with subsequent detection. An increase in blood (plasma and PBMC) virus titers consistent with primary viremia was observed in 4 infants between 3 and 16 weeks of age. Blood virus titers subsequently declined in the absence of antiretroviral therapy and in the absence of activated HIV-1-specific cytotoxic T lymphocyte responses or broadly neutralizing antibodies. Confirmation of these results in larger studies may be helpful in the design of clinical trials to interrupt vertical transmission or to modify the course of infection.
TL;DR: A model of disease development is described in which HIV infection is both active and progressive in the lymphoid organs during the clinically latent period of HIV infection when there are few, if any, signs of disease activity in peripheral blood.
TL;DR: The study shows that, in the presence of specific B19 IgM, circulating virus may still be present but can be detected only by PCR, the only method for virus detection.
Abstract: Persistent B19 parvovirus infection has been recognized in immunocompromised patients, often occurring with a low-titer viremia. In this study, nested polymerase chain reaction (PCR) for the detection of B19 parvovirus DNA was carried out on the sera of 49 human immunodeficiency virus (HIV)-1-seropositive patients, negative for the detection of B19 DNA at dot blot hybridization assay and with different values of serum anti- B19 IgM (27 patients proved positive and 22 negative). Of the 49 HIV-seropositive samples tested by nested PCR, seven were positive for the detection of B19 DNA. All seven belonged to the group of subjects seropositive for specific anti-B19 IgM. The study shows that, in the presence of specific B19 IgM, circulating virus may still be present but can be detected only by PCR. In that B19 infection can occur with low-titer viremia in immunocompromised patients, PCR may be the only method for virus detection. © 1993 Wiley-Liss, Inc.
TL;DR: It is suggested that B19 infection should be considered in anemic patients with AIDS who were being treated with dideoxyinosine and who developed severe anemia while receiving zidovudine.
Abstract: To determine the incidence of B19 infection in patients with AIDS who were being treated with dideoxyinosine, serial sera (n = 28) taken over a 2-year period from 14 individuals were analyzed with respect to anti-B19 serology and the presence of B19 DNA. All 14 individuals were anti-B19 IgM negative. Nine of 14 had B19 viremia by Southern analysis of polymerase chain reaction product. Five of 9 with B19 viremia had > or = 1 anti-B19 IgG-positive sample; none of 5 without viremia had anti-B19 IgG. Four of 9 viremic individuals had serially positive samples. All 4 had severe anemia (hemoglobin < 8.5 g/dL) while taking zidovudine. A fifth individual whose severe anemia resolved after zidovudine was discontinued did not have B19 viremia. Therefore, a significant proportion of this group of patients with AIDS who developed severe anemia while receiving zidovudine had persistent B19 infection. These results suggest that B19 infection should be considered in anemic patients with AIDS.
TL;DR: Intranasal infection of Balb/c mice with 106 plaque forming units of wild-type cowpox virus and rabbitpox virus induced strikingly different pulmonary pathology despite nearly identical clinical signs of illness and LD50.
TL;DR: The results show that viremia in HAV infection lasts longer than has been previously thought, and give a warning of possible secondary blood‐borne infection.
Abstract: Viremia in hepatitis A viral (HAV) infection is said to be limited to pre-symptomatic period. However, it is not clear how long viremia lasts in human infection due to the lack of a simple and sensitive detection system. In an attempt to find HAV genome in patients' sera, we used the RT-PCR method by setting a pair of primers in the 5' non-coding region. While in most cases HAV-RNA was detected only before alanine aminotransferase (ALT) reached peak levels with this sensitive system, the viral genome was observed in some patients' sera even after ALT reached peak levels. Some patients also had HAV viremia after seroconversion to HAV antibody. These results show that viremia in HAV infection lasts longer than has been previously thought, and give a warning of possible secondary blood-borne infection.
TL;DR: The phenotype of recovery from viremia in Fv4-11 mice was unexpected and suggests that low levels of expression of the Fv-4 gene enhance the effectiveness of the immune response.
Abstract: Fv-4 is a mouse gene that confers resistance to infection with ecotropic retroviruses. A candidate Fv-4 gene was cloned previously and found to resemble the 3' half of a murine leukemia virus (MuLV). To study the effect of this gene in vivo, we generated two transgenic mouse strains carrying the Fv-4 env gene under control of its presumed natural promoter, a cellular sequence unrelated to retroviruses. Transgenic progeny expressed a 3-kb Fv-4 env RNA in all of the organs and tissues examined, as well as an Fv-4 envelope antigen on the surface of thymocytes and spleen cells, similar to mice carrying the natural Fv-4 gene. One of the two transgenic strains (designated Fv4-2) expressed three to nine times as much transgene RNA and protein as the other strain (Fv4-11). When challenged with a Friend virus complex containing up to 10(4) XC PFU of Friend MuLV, Fv4-2 mice were completely resistant to development of splenomegaly and had no detectable ecotropic virus in the spleen or blood, confirming that the cloned Fv-4 gene is responsible for resistance to ecotropic MuLV in vivo. In contrast, Fv4-11 mice were only partially resistant, developing viremia and splenomegaly at the highest inoculum dose but recovering from viremia several weeks after inoculation with 10-fold less virus. The phenotype of recovery from viremia in Fv4-11 mice was unexpected and suggests that low levels of expression of the Fv-4 gene enhance the effectiveness of the immune response.
TL;DR: It is concluded that although L-697,661 has potent antiretroviral activity in vivo, its utility may be compromised by rapid emergence of L-699,661-resistant virus.
Abstract: L-697,661 is a non-nucleoside analogue with potent, selective inhibitory activity against the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1). The present study evaluated the potential role of this compound in the treatment of HIV-1-infected patients in a double-blinded, placebo- and zidovudine-controlled trial using plasma viremia as a marker of antiviral activity and real-time phenotypic evaluation of viral isolates for the emergence of resistance. Participants received 12 weeks of either placebo, 25 mg twice a day, 100 mg three times a day, or 500 mg twice a day of L-697,661, or zidovudine, 100 mg five times a day. Mean logarithmic reciprocal titers of plasma virus in patients taking either L-697,661 or zidovudine decreased by week 4 of therapy; for L-697,661 recipients these changes were dose-dependent and, at the highest dose tested, were comparable in magnitude to those seen with zidovudine. Viral suppression induced by L-697,661 persisted through 8 weeks of treatment but decreased by week 12. This rebound paralleled emergence of viral isolates showing resistance to L-697,661. We conclude that although L-697,661 has potent antiretroviral activity in vivo, its utility may be compromised by rapid emergence of L-697,661-resistant virus. Plasma viremia is a highly sensitive technique affording considerable utility in the early testing of such agents.
TL;DR: The results suggest that measurement of HIV present in plasma under optimal conditions could be an efficient way of monitoring the clinical state of an individual and the effects of antiviral therapy.
Abstract: Free virus (virus not present within cells) was detected in the plasma of all human immunodeficiency virus (HIV)-infected individuals studied. Plasma samples from asymptomatic individuals and individuals with HIV disease were tested. The levels of virus varied, but high virus titers correlated directly with HIV-related symptoms and low CD4+ lymphocyte counts. Effective detection of infectious virus depended on the use of an enzyme-linked immunosorbent assay for p24 core antigen and culture conditions in which plasma was added to mitogen-stimulated lymphocytes within 3 h of venipuncture. When there were delays in the time to culturing of plasma, neutralizing antibodies and perhaps other factors present in the plasma were found to reduce the efficiency of virus recovery. Plasma stored at -70 degrees C for several months maintained a stable level of free virus. These results suggest that measurement of HIV present in plasma under optimal conditions could be an efficient way of monitoring the clinical state of an individual and the effects of antiviral therapy.
TL;DR: This study extends previous work demonstrating that the acute clinical syndrome produced by SIVsmmPBj14 in pig-tailed macaques represents a unique model of lentiviral pathogenesis.
Abstract: We have studied the early pathogenesis of infection by molecular clone 1.9 of SIVsmmPBj14 in pig-tailed and cynomolgus macaques. Like the uncloned PBj14 parent, SIVsmmPBj14-1.9 consistently induced an acute clinical syndrome characterized by behavioral depression, fever, profuse diarrhea, dehydration, lymphadenopathy, splenomegaly, and mucocutaneous exanthema that began at 7 days postinfection (DPI). The acute clinical disease coincided with a marked cell-associated and cell-free viremia, during which SIV p27 was demonstrated in 4 to 68% of circulating mononuclear leukocytes between 4 and 17 DPI. Also characteristic were monocytosis and reductions in CD4+ and CD8+ T lymphocytes, as well as CD20+ B lymphocytes. The most profound depletion occurred in the CD44hi subset of CD4+ T cells. Unlike animals infected previously with uncloned or biologically cloned PBj14, however, all SIVsmmPBj14-1.9-infected macaques survived the acute-phase disease to progress to a chronic, largely asymptomatic phase of infection. Recovery from the acute-phase disease correlated with down modulation of virus replication and the appearance of antibodies to SIV Env and Gag proteins. Similar to the PBj14 parent, PBj14-1.9 targeted to intestine, spleen, bone marrow, lymph node, and cerebellum. Saliva contained substantial quantities of infectious virus and no viral antibodies during the early phase of infection. By contrast, saliva from chronically infected animals usually contained antibodies but no virus. This study extends previous work demonstrating that the acute clinical syndrome produced by SIVsmmPBj14 in pig-tailed macaques represents a unique model of lentiviral pathogenesis.
TL;DR: It is suggested that viremia may be transient or fluctuating among some individuals who are nonreactive for hepatitis C virus antibodies by the recombinant immunoblot assay.
TL;DR: Early intervention with anti-retroviral and immune modulatory agents has the potential to alter the natural history of patients with this syndrome.
TL;DR: Results indicate that HCV-RNA testing by polymerase chain reaction is required to correctly identify HCV infection in patients with leukemia while on chemotherapy.
TL;DR: The relationship between infectious virus titre and proviral copy number in peripheral blood mononuclear cells (PBMC) of infected subjects and to ascertain which, if either, is most closely related to CD4+ cell loss and disease progression was determined.
Abstract: The authors sought to determine the relationship between infectious virus titer and proviral copy number in peripheral blood mononuclear cells (PBMC) of infected subjects and to ascertain which if either is most closely related to CD4+ cell loss and disease progression. Cellular HIV-1 viremia was quantified in 45 infected subjects who had not received antiretroviral therapy using limiting dilution tissue culture infective dose (PBMC TCID) and quantitative polymerase chain reaction (PCR) techniques. Proviral DNA was detected in 44 (98%) and infectious virus in 38 (82%) of the 45 subjects. Viremia as measured by both culture and PCR was inversely correlated with patient CD4+ cell count and associated with disease status. Measurement using both techniques correlated with each other (Spearmans rank correlation rho = 0.52; p = 0.0006). The ratio of proviral copies to PBMC TCID ranged from 1:1 to > 1000:1. the ratio of provirus:PBMC TCID was highest when the PBMC TCID was low and approached unity when PBMC TCID was high. This ratio could be influenced by a variety of factors but did not correlate significantly with patient disease status or CD4+ cell count. (authors)
TL;DR: Reassortants between virulent and avirulent virus clones have been used to map virulence determinants in mice as well as determinants of infectivity in mosquitoes, suggesting that cell-specific differences in the function of the viral polymerase can also determine virulence and host range.
Abstract: California bunyaviruses cause encephalitis in mammalian hosts after peripheral infection. The virulence of these viruses is determined by their ability to replicate sequentially in striated muscle, cause viremia, and invade and replicate in the central nervous system. These viruses are also able to infect vector mosquitoes following ingestion of a blood meal containing virus. Bunyaviruses are negative stranded RNA viruses with a trisegmented genome, and the large, medium, and small RNA segments encode the polymerase, the glycoproteins, and the nucleoprotein, respectively. Reassortants between virulent and avirulent virus clones have been used to map virulence determinants in mice as well as determinants of infectivity in mosquitoes. Attenuation in mice and infectivity in mosquitoes of some virus clones maps to the medium RNA segment, implying that the virus glycoproteins, which are involved in virus entry, play a role in virulence. Attenuation in mice and mosquito infectivity of other clones maps to the l...
TL;DR: Although 20% of the patients in this study whose sera reacted to all of the antigens were HCV RNA negative, the positive predictive value of a RIBA considered positive by the manufacturer, was rather high and may allow suspicion of viremia in EIA2 enzyme-linked immunosorbent assay-positive patients.
Abstract: Hepatitis C virus (HCV) infection is currently assessed by detection of antibodies to HCV with immunoassays. However, in the absence of an in vitro system to isolate the virus, or an immunoassay to identify HCV antigen in blood, an ongoing acute or chronic HCV infection can be diagnosed only by detection of HCV RNA by polymerase chain reaction. We used a reverse transcription-nested polymerase chain reaction to detect an HCV 59 noncoding viral RNA sequence in serum specimens collected from anti-HCV-positive individuals belonging to different risk groups and compared the results with those obtained with a prototype recombinant immunoblot assay (Chiron HCV SIA prototype recombinant immunoblot assay [RIBA]) containing four different viral peptides (c22, c33c, c100, and NS5). The prevalence of HCV viremia ranged from 25.9% in HCV antibody-positive blood donors to 92% in HCV antibody-positive hemophiliacs. Elevated alanine aminotransferase values in HCV antibody-positive patients were clearly associated with viremia. Ninety-six percent of HCV RNA-positive patients reacted to two viral antigens or more, compared with only 64% of HCV RNA-negative patients. Contrary to previous reports, HCV viremia was not associated with either the presence or the absence of a particular antibody specificity. The newly introduced NS5 peptide did not improve the sensitivity or specificity of the RIBA. Although 20% of the patients in our study whose sera reacted to all of the antigens were HCV RNA negative, the positive predictive value of a RIBA considered positive by the manufacturer (two or more bands), was rather high (78%) and may allow suspicion of viremia in EIA2 enzyme-linked immunosorbent assay-positive patients. Images
TL;DR: Reported data suggest that viral replication may occur not only in MNL, but also in PMNL, and interaction between HCMV-infected circulating leukocytes and CGC may represent one of the major pathogenetic pathways for the development and dissemination of H CMV infection in immunocompromised patients.
TL;DR: Results indicate that anti‐HCV‐positive blood donors with normal ALT levels constitute a heterogeneous group, as HCV viremia is detectable in only a small proportion of cases.
TL;DR: Eight rhesus macaques inoculated with molecularly cloned SIVmac239 developed viremia and virus-binding antibodies, but only one (macaque 2D) developed neutralizing antibodies to the virus, which failed to neutralize the plasma viruses isolated after the appearance ofneutralizing antibodies.
TL;DR: Bird species of all three orders tested could function as incidental hosts of the virus and passeriforms of the genera Turdus and Fringilla could serve as amplification hosts for Ockelbo virus based on the presently demonstrated viremia of high titer and long duration.
Abstract: One-hundred six birds of 14 species were inoculated with approximately 1027 plaqueforming units of Ockelbo virus and bled daily for 5 days to determine viremia levels. Virus was detected in birds of all 14 species tested (four Anseriformes, one Galliformes and nine Passeriformes). The onset of viremia occurred earlier and viral titers were higher in very young anseriforms and galliforms than in older birds. Adult passeriforms had Ockelbo viremias of higher titer and longer duration than did adult anseriforms. Viremia titers in adult birds of all three orders tested were sufficient to induce high transmission rates in enzootic mosquito vectors, and viremias in passeriforms could induce high transmission rates in bridging vectors as well. Passeriforms of the genera Turdus and Fringilla could serve as amplification hosts for Ockelbo virus based on the presently demonstrated viremia of high titer and long duration in these birds, and the previously demonstrated high prevalence of Ockelbo virus neutralizing an...