Epidemiology and Laboratory Diagnostics of Dengue, Yellow Fever, Zika, and Chikungunya Virus Infections in Africa

Arbovirus infections are widespread, and their disease burden has increased in the past decade. In Africa, arbovirus infections and fever with unknown etiology are common. Due to the lack of well-established epidemiologic surveillance systems and accurate differential diagnosis in most African countries, little is known about the prevalence of human arbovirus infections in Africa. The aim of this review is to summarize the available epidemiological data and diagnostic laboratory tools of infections with dengue, yellow fever, Zika, and chikungunya viruses, all transmitted by Aedes mosquitoes. Studies indicate that these arboviral infections are endemic in most of Africa. Surveillance of the incidence and prevalence of the infections would enable medical doctors to improve the diagnostic accuracy in patients with typical symptoms. If possible, arboviral diagnostic tests should be added to the routine healthcare systems. Healthcare providers should be informed about the prevalent arboviral diseases to identify possible cases

Kommunikationsstrukturen und Auswirkungen von Mode-Blogs

Blogs und Social Media Websites nehmen in unserer modernen Netzwerk-gesellschaft einen immer höheren Stellenwert ein. Interaktivität und Aktualität sind nur einige der Gründe warum Internetnutzer heute so gerne Informationen der unabhängigen Journalisten beziehen. Blogs weisen dabei ein besonders hohes Involvement der User auf. Durch die persönliche Berichterstattung und den privaten Einblick der Autoren, bauen regelmäßige Leser schnell ein starkes Vertrauen auf. Sie sehen den Blogger eher als Freund und setzten seine Vorschläge im alltäglichen Leben um. Die vorliegende Arbeit versucht, die vermuteten Auswirkungen auf die Nutzer wissenschaftlich zu erforschen. In der Studie wurden vorrangig die Kommunikationsstruktur der Mode-Blogs, das Modeverhalten der Nutzer, sowie deren Auswirkungen auf die Nutzer im Alltag untersucht. Im Rahmen einer inhaltsanalytischen Betrachtung der Blogs wurden zunächst Kernthemen und Interaktionsbereitschaft der User evaluiert. Anschließend fand eine Online-Befragung statt, die bestimmte Charakteristika der User, das regelmäßige Nutzungsverhalten sowie parasoziale Dispositionen untersucht. Auch die verschiedenen Modetypen konnten mittels subtiler Fragestellungen evaluiert werden, ebenso wie das zu überprüfende Nachahmungsverhalten der Nutzer. Die theoretische Basis der Studie bilden vor allem Theorien zur Struktur der Lebenswelt, die Theorie der Netzwerkgesellschaft als auch modesoziologische Aspekte. Dieses Konstrukt verschafft dem Leser einen fundierten Einblick in das Leben und die Prädispositionen der Blog-Nutzer, sowie die wesentlichen Aspekte der alltäglichen Lebenswelt, in der wir uns befinden. Es konnten im Rahmen der Studie Zusammenhänge zwischen dem Nachahmungsverhalten und der Intensität der Nutzung sowie der persönlichen Bindung zum Blogger nachgewiesen werden. Zudem konnten vermutete Zusammenhänge zwischen einzelnen kollektiven Identitäten und verschiedenen Typisierungen evaluiert werden und soziale Hintergründe und typische Charakteristika von typischen Blog-Nutzern festgestellt werden

Diagnostic Specificity of Two Dengue Virus IgG ELISAs after Yellow Fever and Japanese Encephalitis Virus Vaccination

Dengue virus (DENV) antibody assays frequently cross-react with sera from individuals who have been infected with or vaccinated against related flaviviruses. The goal of this study was to determine the specificity of two DENV ELISAs with sera from individuals vaccinated against yellow fever virus (YFV) and Japanese encephalitis virus (JEV). The Panbio and the Novatec Dengue IgG ELISAs were tested with sera obtained 3–4 weeks or 0.5–6 years after YFV or JEV vaccination and the diagnostic specificity of the assays was determined. As controls, the sera were tested using DENV, YFV, JEV, Zika and West Nile virus neutralization assays. The diagnostic specificity of the Panbio and the Novatec ELISA with sera from YFV-vaccinated subjects was 98.2% and 88.2%, respectively. Cross-reactions were rare in the first 4 weeks despite high YFV-neutralizing antibody titers and were mostly found later. The specificity of the Panbio and Novatec assays with sera from JEV-vaccinated individuals was 100% and 92.9%. Cross-reactions occurred in the early time period after vaccination. The measurement values of the two ELISAs correlated strongly. Thus, the Panbio ELISA showed higher diagnostic specificity and may be suitable for seroprevalence studies in areas with high disease prevalence

A Review of the Toxicity and Phytochemistry of Medicinal Plant Species Used by Herbalists in Treating People Living With HIV/AIDS in Uganda

Introduction: Despite concerns about toxicity, potentially harmful effects and herb-drug interactions, the use of herbal medicines remains widely practiced by people living with HIV/AIDS (PLHIV) in Uganda. Objective: The objective of the paper was to comprehensively review the literature on the toxicity and chemical composition of commonly used medicinal plant species in treating PLHIV in Uganda. Methods: We reviewed relevant articles and books published over the last sixty years on ethnobotany, antiviral/anti-HIV activity, toxicity, phytochemistry of Vachellia hockii, Albizia coriaria, Bridelia micrantha, Cryptolepis sanguinolenta, Erythrina abyssinica, Gardenia ternifolia, Gymnosporia senegalensis, Psorospermum febrifugium, Securidaca longipendunculata, Warburgia ugandensis and Zanthoxylum chalybeum and their synonyms. We searched PubMed, Web of Science, Scopus, Science Direct and Google Scholar. Discussion: Most of the plant species reviewed apart from P. febrifugium, S. longipedunculata and C. sanguinolenta lacked detailed phytochemical analyses as well as the quantification and characterization of their constituents. Crude plant extracts were the most commonly used. However, purified/single component extracts from different plant parts were also used in some studies. The U87 human glioblastoma was the most commonly used cell line. Water, ethanol, methanol and DMSO were the commonest solvents used. In some instances, isolated purified compounds/extracts such as Cryptolepine and Psorospermin were used. Conclusion: Cytotoxicity varied with cell type, solvent and extract type used making it difficult for direct comparison of the plant species. Five of the eleven plant species namely, A. coriaria, C. sanguinolenta, G. ternifolia, P. febrifugium and Z. chalybeum had no cytotoxicity studies in animal models. For the remaining six plant species, the crude aqueous and ethanol extracts were mainly used in acute oral toxicity studies in mice. Herbalists reported only A. coriaria and W. ugandensis to cause toxic side effects in humans. However, selective cytotoxic plant extracts can potentially be beneficial as anticancer or anti-tumour drugs

High inter-individual diversity of point mutations, insertions, and deletions in human influenza virus nucleoprotein-specific memory B cells

The diversity of virus-specific antibodies and of B cells among different individuals is unknown. Using single-cell cloning of antibody genes, we generated recombinant human monoclonal antibodies from influenza nucleoprotein-specific memory B cells in four adult humans with and without preceding influenza vaccination. We examined the diversity of the antibody repertoires and found that NP-specific B cells used numerous immunoglobulin genes. The heavy chains (HCs) originated from 26 and the kappa light chains (LCs) from 19 different germ line genes. Matching HC and LC chains gave rise to 43 genetically distinct antibodies that bound influenza NP. The median lengths of the CDR3 of the HC, kappa and lambda LC were 14, 9 and 11 amino acids, respectively. We identified changes at 13.6% of the amino acid positions in the V gene of the antibody heavy chain, at 8.4 % in the kappa and at 10.6 % in the lambda V gene. We identified somatic insertions or deletions in 8.1% of the variable genes. We also found several small groups of clonal relatives that were highly diversified. Our findings demonstrate broadly diverse memory B cell repertoires for the influenza nucleoprotein. We found extensive variation within individuals with a high number of point mutations, insertions, and deletions, and extensive clonal diversification. Thus, structurally conserved proteins can elicit broadly diverse and highly mutated B-cell responses

HIV-Specific Cd8+ T Cells Produce Antiviral Cytokines but Are Impaired in Cytolytic Function

The use of peptide–human histocompatibility leukocyte antigen (HLA) class I tetrameric complexes to identify antigen-specific CD8+ T cells has provided a major development in our understanding of their role in controlling viral infections. However, questions remain about the exact function of these cells, particularly in HIV infection. Virus-specific cytotoxic T lymphocytes exert much of their activity by secreting soluble factors such as cytokines and chemokines. We describe here a method that combines the use of tetramers and intracellular staining to examine the functional heterogeneity of antigen-specific CD8+ T cells ex vivo. After stimulation by specific peptide antigen, secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1β, and perforin is analyzed by FACS® within the tetramer-positive population in peripheral blood. Using this method, we have assessed the functional phenotype of HIV-specific CD8+ T cells compared with cytomegalovirus (CMV)-specific CD8+ T cells in HIV chronic infection. We show that the majority of circulating CD8+ T cells specific for CMV and HIV antigens are functionally active with regards to the secretion of antiviral cytokines in response to antigen, although a subset of tetramer-staining cells was identified that secretes IFN-γ and MIP-1β but not TNF-α. However, a striking finding is that HIV-specific CD8+ T cells express significantly lower levels of perforin than CMV-specific CD8+ T cells. This lack of perforin is linked with persistent CD27 expression on HIV-specific cells, suggesting impaired maturation, and specific lysis ex vivo is lower for HIV-specific compared with CMV-specific cells from the same donor. Thus, HIV-specific CD8+ T cells are impaired in cytolytic activity

Development and Potential Usefulness of the COVID-19 Ag Respi-Strip Diagnostic Assay in a Pandemic Context

Introduction: COVID-19 Ag Respi-Strip, an immunochromatographic (ICT) assay for the rapid detection of SARS-CoV-2 antigen on nasopharyngeal specimen, has been developed to identify positive COVID-19 patients allowing prompt clinical and quarantine decisions. In this original research article, we describe the conception, the analytical and clinical performances as well as the risk management of implementing the COVID-19 Ag Respi-Strip in a diagnostic decision algorithm. Materials and Methods: Development of the COVID-19 Ag Respi-Strip resulted in a ready-to-use ICT assay based on a membrane technology with colloidal gold nanoparticles using monoclonal antibodies directed against the SARS-CoV and SARS-CoV-2 highly conserved nucleoprotein antigen. Four hundred observations were recorded for the analytical performance study and thirty tests were analyzed for the crossreactivity study. The clinical performance study was performed in a retrospective multicentric evaluation on aliquots of 328 nasopharyngeal samples. COVID-19 Ag Respi-Strip results were compared with qRT-PCR as golden standard for COVID-19 diagnostics. Results: In the analytical performance study, the reproducibility showed a between-observer disagreement of 1.7%, a robustness of 98%, an overall satisfying user friendliness and no cross-reactivity with other virus-infected nasopharyngeal samples. In the clinical performance study performed in three different clinical laboratories during the ascendant phase of the epidemiological curve, we found an overall sensitivity and specificity of 57.6 and 99.5%, respectively with an accuracy of 82.6%. The cut-off of the ICT was found at CT < 22. User-friendliness analysis and risk management assessment through Ishikawa diagram demonstrate that COVID-19 Ag Respi-Strip may be implemented in clinical laboratories according to biosafety recommendations. Conclusion: The COVID-19 Ag Respi-Strip represents a promising rapid SARS-CoV-2 antigen assay for the first-line diagnosis of COVID-19 in 15min at the peak of the pandemic. Its role in the proposed diagnostic algorithm is complementary to the currently-used molecular techniques

Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia

<p>Abstract</p> <p>Background</p> <p>HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood.</p> <p>Methods</p> <p>To study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia. 46 brain regions from two rapidly progressing severely demented patients and 53 regions from 4 HIV+ non-dementia patients were analyzed. Macrophage and CD8+ T cell infiltration of the CNS in relation to HIV was assessed using immuno-histochemical analysis with anti-HIV (P24), anti-CD8 and anti-CD68, anti-S-100A8 and granzyme B antibodies (cellular activation). Statistical analysis was performed with SPSS 12.0 with Student's t test and ANOVA.</p> <p>Results</p> <p>Overall, the patterns of infiltration of macrophages and CD8+ T cells were indiscernible between patients with and without dementia, but the co-localization of macrophages and CD8+ T cells along with HIV P24 antigen in the deeper midline and mesial temporal structures of the brain segregated the two groups. This predilection of infected macrophages and CD8+ T cells to the middle part of the brain was unique to both HAD patients, along with unique nature of provirus gag gene sequences derived from macrophages in the midline and mesial temporal structures.</p> <p>Conclusion</p> <p>Strong predilection of infected macrophages and CD8+ T cells was typical of the deeper midline and mesial temporal structures uniquely in HAD patients, which has some influence on neurocognitive impairment during HIV infection.</p