Artemether-Lumefantrine Treatment Failure despite adequate lumefantrine day 7 Concentration in a Traveller with Plasmodium Falciparum Malaria after Returning from Tanzania.

Artemether-lumefantrine is currently first-line therapy of Plasmodium falciparum malaria in many countries. This report describes a treatment failure despite adequate drug concentrations in a traveller returning from sub-Saharan Africa. Genotyping confirmed recrudescence and suggested reduced sensitivity. Potential sub-optimal effect of artemether-lumefantrine highlights the need to follow non-immune individuals the weeks after treatment

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

Peripheral Blood Mononuclear Cells' Proliferative Response to Human Parvovirus B19 Antigens in Patients with Rheumatoid Arthritis

Autore J.Pavlova Scopus datubāzē pie raksta nav norādīta, bet žurnāla "Proceedings of the Latvian Academy of Sciences, Section B: Natural, Exact, and Applied Sciences" PDF formāta publikācijā ir norādīta. Publisher Copyright: © 2016 by Svetlana Kozireva. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.This study aimed to determine peripheral blood mononuclear cells' (PBMC) proliferative response to parvovirus B19 (B19) antigens in rheumatoid arthritis (RA) patients and possible changes in proliferative response due to chemotherapy. Serum and blood samples of 52 RA patients and 25 sex and age matched healthy individuals were examined for the presence of anti-B19 IgG and IgM class antibodies and virus specific DNA sequence by the recomLine B19 test and nested polymerase chain reaction, respectively. The PBMC proliferative activity was estimated on the 3rd and 6th day of PBMC cultivation in the presence of virus and B19 VP1/VP2 peptide, using thymidine incorporation assay. On the 3rd day, PBMC response to B19 antigens was detected in 74.1% RA patients with active, in 44.8%-with remote and in 40%-with latent stage of persistent B19 infection, while in the control group the response was observed only in two individuals with active viral infection. On the 6th day, the response was found in 50% RA patients with active, 68.9%-with remote and in 80%-with latent stage of latent persistent infection as well as in 41.1% remotely infected control individuals. The highest PBMC mean stimulation indices were detected in the RA patients and control persons with active infection as well as in RA patients with latent stage of persistent viral infection. On the 3rd and 6th day, strong proliferative response was significantly more frequently observed in RA patients not receiving methotrexate treatment, compared to the patients receiving methotrexate treatment in different combinations with other drugs. RA patients had more frequent and faster response to B19 antigens than apparently healthy persons.publishersversionPeer reviewe

Model structure analysis to estimate basic immunological processes and maternal risk for parvovirus B19

After a steep monotone rise with age, the seroprevalence profiles for human parvovirus B19 (PVB19) display a decrease or plateau between the ages of 20 and 40, in each of 5 European countries. We investigate whether this phenomenon is induced by waning antibodies for PVB19 and, if this is the case, whether secondary infections are plausible, or whether boosting may occur. Several immunological scenarios are tested for PVB19 by fitting different compartmental dynamic transmission models to serological data using data on social contact patterns. The social contact approach has already been shown informative to estimate transmission rates and the basic reproduction number for infections transmitted predominantly through nonsexual social contacts. Our results show that for 4 countries, model selection criteria favor the scenarios allowing for waning immunity at an age-specific rate over the assumption of lifelong immunity, assuming that the transmission rates are directly proportional to the contact rates. Different views on the evolution of the immune response to PVB19 infection lead to altered estimates of the age-specific force of infection and the basic reproduction number. The scenarios which allow for multiple infections during one lifetime predict a higher frequency of PVB19 infection in pregnant women and of associated fetal deaths. When prevaccination serological data are available, the framework developed in this paper could prove worthwhile to investigate these different scenarios for other infections as well, such as cytomegalovirus

Parvovirus B19 infection and severe anaemia in Kenyan children: a retrospective case control study

Background: During acute Human parvovirus B19 (B19) infection a transient reduction in blood haemoglobin concentration is induced, due to a 5-7 day cessation of red cell production. This can precipitate severe anaemia in subjects with a range of pre-existing conditions. Of the disease markers that occur during B19 infection, high IgM levels occur closest in time to the maximum reduction in haemoglobin concentration. Previous studies of the contribution of B19 to severe anaemia among young children in Africa have yielded varied results. This retrospective case/control study seeks to ascertain the proportion of severe anaemia cases precipitated by B19 among young children admitted to a Kenyan district hospital.Methods: Archival blood samples from 264 children under 6 years with severe anaemia admitted to a Kenyan District Hospital, between 1999 and 2004, and 264 matched controls, were tested for B19 IgM by Enzyme Immunosorbent Assay and 198 of these pairs were tested for B19 DNA by PCR. 536 samples were also tested for the presence of B19 IgG.Results: 7 (2.7%) cases and 0 (0%) controls had high B19 IgM levels (Optical Density > 5 x cut-off value) (McNemar's exact test p = 0.01563), indicating a significant association with severe anaemia. The majority of strongly IgM positive cases occurred in 2003.10/264 (3.7%) cases compared to 5/264 (1.9%) controls tested positive for B19 IgM. This difference was not statistically significant, odds ratio (OR) = 2.00 (CI95 [0.62, 6.06], McNemar's exact test p = 0.3018. There was no significant difference between cases and controls in the B19 IgG (35 (14.8%) vs 32 (13.6%)), OR = 1.103 (CI95 [0.66, 1.89], McNemar's exact test, p = 0.7982), or the detection of the B19 DNA (6 (3.0%) vs 5 (2.5%)), OR = 1.2 (CI95 [0.33, 4.01], McNemar's exact test p = 1).Conclusions: High B19 IgM levels were significantly associated with severe anaemia, being found only among the cases. This suggests that 7/264 (2.7%) of cases of severe anaemia in the population of children admitted to KDH were precipitated by B19. While this is a relatively small proportion, this has to be evaluated in the light of the IgG data that shows that less than 15% of children in the study were exposed to B19, a figure much lower than reported in other tropical areas

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

High Frequency, Sustained T Cell Responses to PARV4 Suggest Viral Persistence In Vivo

Background. Parvovirus 4 (PARV4) is a recently identified human virus that has been found in livers of patients infected with hepatitis C virus (HCV) and in bone marrow of individuals infected with human immunodeficiency virus (HIV). T cells are important in controlling viruses but may also contribute to disease pathogenesis. The interaction of PARV4 with the cellular immune system has not been described. Consequently, we investigated whether T cell responses to PARV4 could be detected in individuals exposed to blood-borne viruses

Chloroquine and Its Derivatives Exacerbate B19V-Associated Anemia by Promoting Viral Replication

Human parvovirus B19 (B19V) is typically associated with a childhood febrile illness known as erythema infectiosum. The infection usually resolves without consequence in healthy individuals. However, in patients with immunologic and/or hematologic disorders, B19V can cause a significant pathology. The virus infects and kills red cell precursors but anemia rarely supervenes unless there is pre-existing anemia such as in children living in malaria-endemic regions. The link between B19V infection and severe anemia has, however, only been confirmed in certain malaria-endemic countries in parallel with chloroquine (CQ) usage. This raises the possibility that CQ may increase the risk of severe anemia by promoting B19V infection. To test this hypothesis, we examined the direct effect of CQ and other commonly used antimalarial drugs on B19V infection in cultured cell lines. Additionally, we examined the correlation between B19V infection, hemoglobin levels and use of CQ in children from Papua New Guinea hospitalized with severe anemia. The results suggest strongly that CQ and its derivatives aggravate B19V-associated anemia by promoting B19V replication. Hence, careful consideration should be given in choosing the drug partnering artemisinin compounds in combination antimalarial therapy in order to minimize contribution of B19V to severe anemia

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

Mannose-Binding Lectin 2 Polymorphisms Do Not Influence Frequency or Type of Infection in Adults with Chemotherapy Induced Neutropaenia

BACKGROUND: Mannose-binding Lectin protein (MBL) has been suggested to be relevant in the defence against infections in immunosuppressed individuals. In a Swedish adult cohort immunosuppressed from both the underlying disease and from iatrogenic treatments for their underlying disease we investigated the role of MBL in susceptibility to infection. METHODS: In this cross sectional, prospective study, blood samples obtained from 96 neutropaenic febrile episodes, representing 82 individuals were analysed for single nucleotide polymorphism (SNP) in the MBL2 gene. Concurrent measurement of plasma MBL protein concentrations was also performed for observation of acute response during febrile episodes. FINDINGS: No association was observed between MBL2 genotype or plasma MBL concentrations, and the type or frequency of infection. Adding to the literature, we found no evidence that viral infections or co-infections with virus and bacteria would be predisposed by MBL deficiency. We further saw no correlation between MBL2 genotype and the risk of fever. However, fever duration in febrile neutropaenic episodes was negatively associated with MBL2 SNP mutations (p<0.05). Patients with MBL2 SNP mutations presented a median febrile duration of 1.8 days compared with 3 days amongst patients with wildtype MBL2 genotype. INTERPRETATION: We found no clear association between infection, or infection type to MBL2 genotypes or plasma MBL concentration, and add to the reports casting doubts on the benefit of recombinant MBL replacement therapy use during iatrogenic neutropaenia