Prolonged Activation of Virus-Specific CD8(+)T Cells after Acute B19 Infection

BACKGROUND: Human parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8(+) T cells in acute B19 infection has not been studied previously. METHODS AND FINDINGS: The number and phenotype of B19-specific CD8(+) T cell responses during and after acute adult infection was studied using HLA–peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8(+) T cells. B19-specific T cells developed and maintained an activated CD38(+) phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%–0.5% of CD8(+) T cells, which were perforin, CD38, and CCR7 low. CONCLUSION: This is the first example to our knowledge of an “acute” human viral infection inducing a persistent activated CD8(+) T cell response. The likely explanation—analogous to that for cytomegalovirus infection—is that this persistent response is due to low-level antigen exposure. CD8(+) T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development

Flocked nasal swab versus nasopharyngeal aspirate for detection of respiratory tract viruses in immunocompromised adults: a matched comparative study

<p>Abstract</p> <p>Background</p> <p>Several studies have compared nasal swabs to the more invasive nasopharyngeal aspirate (NPA) for detection of respiratory viruses. Mostly, the comparisons have been performed on immunocompetent children with upper respiratory tract symptoms. The results range from a relatively poor sensitivity for the swabs to an even higher sensitivity than for the NPA. We aimed to investigate the sensitivity of a flocked nasal swab (fNS) on immunocompromised adults with febrile neutropenia.</p> <p>Methods</p> <p>During 16 months, adults with a hematological disorder presenting with febrile neutropenia were enrolled in the study. Paired samples of the fNS and NPA were collected in the outer part of the nasal cavity and the nasopharynx, respectively. The samples were analyzed regarding a panel of 15 respiratory viruses by means of quantitative polymerase chain reaction. Furthermore, as an indirect measure of cell yield by either method, the copy number of the human beta actin gene was also determined. Cohen's kappa was calculated as a measure of agreement of the results obtained from either method. Wilcoxon signed-rank test was used for comparison of cell yield.</p> <p>Results</p> <p>A total of 98 paired samples from a total of 89 patients were collected. Twenty of the pairs had virus detected in at least one of the specimens; 11 in both, 7 in NPA only, and 2 in fNS only. For the fNS, the overall sensitivity for any virus and for rhinovirus only was 65% and 78%, respectively. NPA was significantly superior to the fNS in collecting epithelial cells.</p> <p>Conclusion</p> <p>We found the overall sensitivity of 65% to be too low to replace NPA with this sampling technique in this patient category.</p

Viral Findings in Adult Hematological Patients with Neutropenia

BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT) recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA) as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159) were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22%) and NPA (18%) with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL) (p<0.01) and patients with fever (p<0.001) were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS) (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Clinical and immunological aspects of human parvovirus B19 infection

Human parvovirus B19 (B19) causes erythema infectiosum, a limited disease of childhood also known as the fifth disease or slapped cheek syndrome, referring to the characteristic facial rash. It normally infects through the respiratory route, even though transmission via blood products and transplanted organs occur. B 19 infection is common with a seroprevalence in the elderly of about 80%. In adults, the presentation is diffuse with arthropathy as a main feature. B 19 causes a lytic infection of predominantly erythroid precursors, resulting in a decrease in reticulocyte count and hemoglobin level. In patients with underlying hematological disease, transient aplastic crisis may ensue that is sometimes fatal. In immunocompromised individuals, B19 can cause persistent infection and chronic anemia. Mainly humoral responses are reported, although recent data has indicated an importance also of the cellular immune system, but little is known about the CD8+ T cell response in B19 infection and other resolving infections in man. Persistent infection despite the presence of neutralizing antibodies has been observed in individuals with long-lasting B19-related symptoms resembling those of the chronic fatigue syndrome. An association between B19 and this disease as well as some other clinical entities, such as rheumatoid arthritis, has been proposed but is not established. About one third of maternal infections are transmitted to the fetus, which may cause fetal hydrops and intrauterine fetal death (lUFD). Adverse outcome is reported to be confined to the second trimester, but indications of late cases warrant further study. We therefore examined all cases of IUFD in gestational week 22 or later that occurred in our geographical area between the years 1993 and 1999. By PCR, we found B19 DNA in 14% of the cases, suggesting B19 to be a common cause of IUFD also in late gestation. The lack of the classical clinical features of fetal hydrops and evident maternal infection, and a sometimes long time-span between maternal infection and IUFD, make early diagnosis and therapeutic intervention difficult in these cases. However, the inclusion of B19 PCR in the investigation of all cases of IUFD will contribute to increase the number where an etiology is established. In addition, this finding should be considered in a situation when vaccination of certain riskgroups is possible. We have previously reported an inhibitory effect on the erythropoiesis in vitro of empty capsids containing both structural proteins. Here we showed a similar effect on the hematopoiesis of only the major capsid protein that was retained also after fragmentation. Bone marrow cells from a patient with polycythemia vera were suppressed, and an effect of this protein in vivo was indicated in a pilot study in non-human primates. Together, these findings nourish the idea of a B19-derived medicament for hematopoietic suppression in various applications, such as for treatment of polycythemia vera. We assessed the CD8+ T cell responses, by means of interferon gamma detection in an enzyme-linked immunospot assay, to the entire B19 immunome in five IgM-positive symptomatic individuals. We detected sustained responses of high amplitudes for up to two years after primary infection. The responses were presumably antigen-driven and directed to a few epitopes that were unchanged over time. Our findings indicate a virus-host interaction not believed to be a feature of resolving infections. In contrast to the capsid-directed humoral response, we defined ten novel CD8+ T cell epitopes that all but one were directed to the non-structural protein. The epitopes open for further immunological study, and make a T cell directed vaccination approach possible. In symptomatic persistently infected individuals with an intact humoral response, we detected low CD8+ T cell responses that were skewed towards the capsid. This is the first finding of an aberration in the immunological response in these individuals, which may be the result of continuous antigenic stimulation or might represent a mechanism for the development of viral persistence

No evidence of presence of parvovirus 4 in a Swedish cohort of severely immunocompromised children and adults.

The recently discovered human parvovirus 4 (PARV4) has been associated with seropositivity for human immunodeficiency virus, hepatitis B virus and hepatitis C virus. High prevalence is seen especially in intravenous drug users. The virus has been detected in blood products and persons who have been repeatedly transfused have shown to be a risk-group. Furthermore, reports from different parts of the world suggesting a prevalence ranging from zero to one third of the healthy population and the virus is thought to cause a latent or persistent infection. We investigated the presence of PARV4 DNA and parvovirus B19 (B19) DNA in serum from 231 severely immunocompromised cancer patients that have been exposed for blood products. Compared to B19, which was found in 3.9% of the patients, we found no evidence of PARV4. Our results may indicate a very low prevalence of the virus in Sweden, and it would be useful to measure the real PARV4 exposure of the healthy population as well as individuals with known risk factors by serology

Characteristics of the parvovirus B19 positive and negative patients.

<p>NOTE. F, female; M, male; PARV4, parvovirus 4; Pos, positive; Neg, negative; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; B19, parvovirus B19; n, number.</p