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The authors of a systematic review and meta-analysis conclude that the benefit of convalescent plasma (CP) in the treatment of COVID-19 is limited. Among other systematic reviews, only one found an indication of benefit of CP. However, a meta-analysis needs a focused and meaningful clinical question and should include studies which are designed to test a reasonable hypothesis. Clinical trials to support the licensing of medicines should aim to define as exactly as possible the investigational drug and target disease. In the case of COVID-19, trial details (e.g., duration, stage and severity of disease, and antibody content and dose of CP) are quite heterogeneous. The so far available evidence suggests that the hypothesis should be sharpened as to treat COVID -19 patients at risk for developing severe disease as early enough with a sufficiently high dose of specific antibodies. It has been demonstrated that such an approach is feasible, and the lack of an independent reproduction by further trials with a really comparable design can probably not be compensated by compiling all available, heterogenous trials, even with the best methodology of a systematic review and meta-analysis. Though the COVID-19 pandemic appears to be fading, we should not neglect the search for effective prevention and treatments, given the still high death toll of COVID-19. Monoclonal antibodies were found effective in the early phase of the pandemic; however, due to new variants of SARS-COV2 undermining their efficacy they are no longer recommended by the current NIH guidelines. CP can provide a spectrum of polyclonal antibodies in close timely and regional connection to the particular prevalent virus variant. It would be extremely valuable to obtain a solid scientific foundation for the principle of target specific and temporarily adapted passive immunization, which could be a fast and flexible instrument also in future outbreaks of novel pathogens.

Was unterscheidet den Menschen vom Schwein – immunologisch betrachtet? Und warum haben alle Säugetiere Transplantationsantigene, obwohl nur der Mensch Organe transplantiert? Durch die erste Transplantation eines genetisch veränderten Schweineherzens auf einen Menschen gewinnen solche scheinbar ungewöhnlichen Fragen an medizinischer Bedeutung.

Die transfusionsassoziierte akute Lungeninsuffizienz (TRALI) ist eine seltene, schwerwiegende Transfusionsreaktion, die durch plötzliche akute Atemnot während oder innerhalb von sechs Stunden nach einer Transfusion gekennzeichnet ist. TRALI gehörte viele Jahre zu den häufigsten Ursachen für transfusionsbedingte Todesfälle. Seit ihre Pathogenese besser erforscht ist, konnte durch spezifische Spenderselektion die Fallzahl und Todesrate deutlich gesenkt werden. Trotzdem ist Achtsamkeit geboten, denn vereinzelt gibt es immer noch tödliche Verläufe.

Infektionen mit Bakterien der Gattungen Chlamydia, Mycoplasma und Ureaplasma sind sowohl beim Tier als auch beim Menschen weit verbreitet. Sie werden wohl trotz der Möglichkeiten zur erfolgreichen Prävention und Therapie bei den sexuell übertragbaren Infektionen auch in Zukunft eine Rolle spielen. Eine Infektion kann asymptomatisch, aber auch tödlich verlaufen; besonders immungeschwächte Personen und Neugeborene sind gefährdet.

Since the end of 2019 a new coronavirus, SARS-CoV-2, first identified in Wuhan, China, is spreading around the world partially associated with a high death toll. Besides hygienic measurements to reduce the spread of the virus vaccines have been confected, partially based on the experiences with Ebola virus vaccine, based on recombinant human or chimpanzee adenovirus carrying the spike protein and its ACE2 receptor binding domain (RBD). Further vaccines are constructed by spike protein coding mRNA incorporated in lipid nano vesicles that after entry in human cells produce spike protein. Both vaccine types induce a strong immune response that lasts for months possibly for T-cell immunity a few years. Due to mutations in the coronavirus genome in several parts of the world variants selected, that were partially more pathogenic and partially easier transmissible - variants of concern (VOC). Until now vaccinees are protected against the VOC, even when protection might be reduced compared to the Wuhan wild virus.An open field is still how long the vaccine induced immunity will be sufficient to prevent infection and/or disease; and how long the time period will last until revaccination will be required for life saving protection, whether a third vaccination is needed, and whether revaccination with an adenovirus-based vaccine will be tolerated.

Die Forschung zu SARS-CoV-2, das im Dezember 2019 erstmals in China beschrieben wurde, läuft immer noch auf Hochtouren. Der große Wissenszuwachs zur Pathogenese des Virus hilft dabei, die (Begleit-)Diagnostik, Prävention und Therapie stetig zu verbessern.

The complex COVID-19-associated coagulopathy appears to impair prognosis. Recently, we presented the hypothesis that children are to some extent protected by higher α2-macroglobulin (α2-M) levels from severe COVID-19. In addition to endothelial cells, thrombin, and platelets, neutrophil granulocytes also appear to play an important role. Neutrophils extrude extracellular nets, which are histone- and protease-coated web-like DNA structures; activate coagulation and platelets; and release radicals and proteases such as elastase. The unique phylogenetically ancient and “versatile” inhibitor α2-M contributes particularly during childhood to the antithrombin activity of plasma, binds a broad spectrum of proteases, and interacts with other mediators of inflammation such as cytokines. It is suggested that the scope of basic research and clinical studies would include the potential role of α2-M in COVID-19.

Since the end of 2019 a new coronavirus, SARS-CoV-2, first identified in Wuhan, China, is spreading around the world partially associated with a high death toll. Besides hygienic measurements to reduce the spread of the virus vaccines have been confected, partially based on the experiences with Ebola virus vaccine, based on recombinant human or chimpanzee adenovirus carrying the spike protein and its ACE2 receptor binding domain (RBD). Further vaccines are constructed by spike protein coding mRNA incorporated in lipid nano vesicles that after entry in human cells produce spike protein. Both vaccine types induce a strong immune response that lasts for months possibly for T-cell immunity a few years. Due to mutations in the coronavirus genome in several parts of the world variants selected, that were partially more pathogenic and partially easier transmissible - variants of concern (VOC). Until now vaccinees are protected against the VOC, even when protection might be reduced compared to the Wuhan wild virus.An open field is still how long the vaccine induced immunity will be sufficient to prevent infection and/or disease; and how long the time period will last until revaccination will be required for life saving protection, whether a third vaccination is needed, and whether revaccination with an adenovirus-based vaccine will be tolerated.

We are overwhelmed by scientific publications on clinical observations, virology and epidemiology of SARS-CoV-2 infections. There is a growing body of evidence that hypercoagulability complicates COVID-19, probably contributing to poor prognosis.

The complex COVID‐19‐associated coagulopathy appears to impair prognosis. Recently, we presented the hypothesis that children are to some extent protected by higher α2‐macroglobulin (α2‐M) levels from severe COVID‐19. In addition to endothelial cells, thrombin, and platelets, neutrophil granulocytes also appear to play an important role. Neutrophils extrude extracellular nets, which are histone‐ and protease‐coated web‐like DNA structures; activate coagulation and platelets; and release radicals and proteases such as elastase. The unique phylogenetically ancient and “versatile” inhibitor α2‐M contributes particularly during childhood to the antithrombin activity of plasma, binds a broad spectrum of proteases, and interacts with other mediators of inflammation such as cytokines. It is suggested that the scope of basic research and clinical studies would include the potential role of α2‐M in COVID‐19.

We report a case of a probable HIV-1 transmission by human bite. The analyzed data from ten previously reported suspected or allegedly confirmed HIV transmissions revealed a deep bleeding bite wound as the primary risk factor. A high HIV plasma viral load and bleeding oral lesions are present most of the time during HIV transmission by bite. HIV post-exposure prophylaxis (PEP) should be recommended in case of a bleeding wound resulting from a bite of an HIV-infected person. PEP was missed in this presented case.

Background RNA viruses are associated with a high frequency of mutations because of the missing proofreading function of polymerases, such as reverse transcriptase. Between 2007 and 2010, six blood donations with false-negative nucleic acid technology (NAT) results were reported in Germany. Therefore, NAT screening in two viral genome regions was introduced by our blood donation service in 2010 on a voluntary basis and became mandatory in Germany since the beginning of 2015. Study design and methods Blood donor screening was done using, in parallel, the German Red Cross (GRC) HIV-1 CE long terminate repeats (LTR) PCR kit and the GRC HIV-1 gag CE PCR kit. In total, 7 million blood donations were screened during the study period from 2010 to 2014 with the GRC dual-target human immunodeficiency virus 1 (HIV-1) NAT system. Additionally, three suspicious specimens were analyzed by four monotargeted NAT assays and by five dual-target NAT assays. Results Three of 7 million donations tested negative using the 5'LTR-polymerase chain reaction, but they were positive if amplification was performed in the gag region. HIV antibodies were detected in all three donations. Nucleic acid sequence analysis identified a deletion of 22 bases within the 5'LTR probe binding region. Three different ltr-based monotargeted assays missed two donations, except for a low-reactive result obtained by one of the assays. In total, the detection rates for HIV-1-positive donations were 37.5% (3/8) for monotargeted assays and 100% (10/10) for dual-target assays. Conclusion The current data demonstrate that dual-target NAT systems reduce the risk of false-negative HIV-1 NAT screening results.

Als Reaktion auf eine SARS-CoV-2-Infektion werden vorwiegend Antikörper gegen die Rezeptor-bindende Domäne des S1-Teils des Spike-Proteins, das Nukleokapsid und die Chymotrypsin-ähnliche Protease gebildet. Die T-Zell-Reaktion richtet sich neben der S1-Domäne und M-, N- und ORF-Protein-Epitope in stärkerem Ausmaß auch gegen die S2-Domäne, was eine Erklärung für den milderen Verlauf bei Kindern sein könnte.

HIV-1 diversity poses major challenges to viral load assays because genetic polymorphisms can impede nucleic acid detection. In addition to the on-going viral diversification within the HIV-1 group M pandemic, HIV-1 genetic diversity is further increased by non-group M infections, such as HIV-1 groups O (HIV-1-O), N and P. We here conducted a systematic evaluation of commercially available PCR assays to detect HIV-1-O isolates. We collected 25 primary HIV-1-O isolates covering all genetic clusters within HIV-1-O. Subsequently, this panel of isolates was tested on eight commercially available quantitative and five qualitative HIV-1 PCR-based assays in serial dilutions. Sequence analyses were performed for severe cases of underquantification or lack of detection. We observed differences between the assays in quantification that depended on the HIV-1-O isolate's subgroup. All three tested HIV-1-O subgroup IV isolates were underquantified by the Roche CAP/CTM >800-fold compared to the Abbott RealTime assay. In contrast, the latter assay underquantified several subgroup I isolates >200-fold. Notably, the Xpert HIV-1 Viral Load test from Cepheid failed to detect two of the HIV-1-O isolates, whereas the Roche Cobas 8800 assay readily detected all isolates. Comparative sequence analyses identified polymorphisms in the HIV-1-O long-terminal repeat and integrase genes that likely underlie inadequate nucleic acid amplification. Potential viral load underquantification should be considered in therapeutic monitoring of HIV-1-O-infected patients. Pre-clinical assessments of HIV-1 diagnostic assays could be harmonized by establishing improved and internationally standardized panels of HIV-1 isolates that cover the dynamic diversity of circulating HIV-1 strains.

RNA viruses are associated with a high frequency of mutations because of the missing proofreading function of polymerases, such as reverse transcriptase. Between 2007 and 2010, six blood donations with false-negative nucleic acid technology (NAT) results were reported in Germany. Therefore, NAT screening in two viral genome regions was introduced by our blood donation service in 2010 on a voluntary basis and became mandatory in Germany since the beginning of 2015.Blood donor screening was done using, in parallel, the German Red Cross (GRC) HIV-1 CE long terminate repeats (LTR) PCR kit and the GRC HIV-1 gag CE PCR kit. In total, 7 million blood donations were screened during the study period from 2010 to 2014 with the GRC dual-target human immunodeficiency virus 1 (HIV-1) NAT system. Additionally, three suspicious specimens were analyzed by four monotargeted NAT assays and by five dual-target NAT assays.Three of 7 million donations tested negative using the 5'LTR-polymerase chain reaction, but they were positive if amplification was performed in the gag region. HIV antibodies were detected in all three donations. Nucleic acid sequence analysis identified a deletion of 22 bases within the 5'LTR probe binding region. Three different ltr-based monotargeted assays missed two donations, except for a low-reactive result obtained by one of the assays. In total, the detection rates for HIV-1-positive donations were 37.5% (3/8) for monotargeted assays and 100% (10/10) for dual-target assays.The current data demonstrate that dual-target NAT systems reduce the risk of false-negative HIV-1 NAT screening results.

The past decade has witnessed a dramatic increase of anti-retroviral treatment of human immunodeficiency virus (HIV) infected patients in many African countries. Due to costs and lack of currently available commercial viral load assays, insufficient attention has been paid to therapy monitoring through measurement of plasma viral load. This challenge of patient monitoring by tests as viral load, CD4 cell count, and finally HIV drug resistance could reverse achievements already made against HIV/AIDS infection. Loop-mediated isothermal amplification (LAMP) has been shown to be simple, rapid and cost-effective, characteristics which make this assay suitable for viral load monitoring in resource limited settings. This paper describes a revised LAMP assay using primers in the HIV-1 integrase region. The assay can be used for semi-quantitative measurement of HIV-1 group M viral load. The lower limit of detection (LLOD) was determined as 1200copies/mL and lower limit of quantitation (LLOQ) at 9800copies/mL. Sensitivities of 82 and 86% (in 135 and 99 plasma samples respectively from Kenya) and 93% (in 112 plasma samples from Germany) and specificities of 99 and 100% were realized. HIV-1 group O and HIV-2 virus samples were not detected. This LAMP assay has the potential for semi-quantitation of HIV-1 group M viral load in resource limited countries. There is still a need for further improvement by refinement of primers in respect to detection of HIV-1 group M non-B virus.

Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered.

Background: Scale-up of antiretroviral therapy (ART) and the growing number of longterm treated patients may favor multi-HIV drug resistance (HIVDR) in resource-limited settings. Understanding the burden of HIVDR with ART-exposure may provide new insights for an effective long-term management of infected patients. Methods: Sixty-six HIV-infected individuals (18 ART-naive, 24 failing first-line, 24 failing secondline ART) living in Yaounde-Cameroon were evaluated by sequencing protease-reverse transcriptase (PR-RT, n=62), envelope-V3 loop (V3, n=58) and integrase (IN, n=30) regions. Drug resistance mutations (DRMs) were interpreted using Stanford University HIV drug resistance database and geno2pheno, while viral tropism prediction was done using geno2pheno, position-specific scoring matrices (PSSM) and Net charge rule. Results: Participants, from naive, first- to second-line, had respectively 5.30, 4.85 and 4.66 log HIV RNA, and 532, 203 and 146 CD4 cells/mm 3 ), and infected with diverse HIV-1 non-B clades (58.1% CRF02_AG). Among ART-naive patients, 6.7% harbored K103N, 28.6% had IN accessory-mutations (L74I, E157Q) and 26.7% carried CXCR4-tropic viruses. At first-line failure, 79.2% harbored DRMs to nucleoside and non-nucleoside RT inhibitors, 33.3% had IN accessory-mutations (L68I, L74I, T97A, E157Q), and 47.4% carried CXCR4-tropic viruses. At second-line failure, 91.3% harbored multi-DRMs to PR-RT inhibitors (with 52.2% and 4.3% DRMs to second-generation NNRTIs and darunavir/ r, respectively), 27.3% had IN accessory-mutations (L74I, T97A, E157EQ), and 37.5% carried CXCR4-tropic viruses. Conclusion: Levels of PR-RT resistance increases with ART-exposure, with needs for new ART-options following second-line failure. IN inhibitors and darunavir/r are potentially suitable for a third-line regimen, while the use of maraviroc, etravirine or rilpivirine, requires individual genotypic testing.

Some alphaviruses and flaviviruses, such as the transfusion-relevant Chikungunya and West-Nile virus, are transmitted by mosquitoes. Such viruses are called arboviruses. Bacteria typically transmitted by ticks include Coxiella burnetii [1], Borrelia, Ehrlichia, and Anaplasma. These are referred to as arbobacteria [2]. Protozoae include plasmodia which are transmitted via mosquitoes, leishmania transmitted via sand flies (Phlebotomus), and for example trypanosoma transmitted via kissing bugs (Triatoma). The latter are grouped under the name arboprotozoa [3]. The following nematodes are transmitted by arthropods as vectors to humans: microfilaria of Wuchereria bancrofti via mosquitoes (Culex), Onchocera (Onchocera volvulus in Africa, O. caecutiens in South America) via black fly (Simulium) and Loa loa (African eye worm) via horse flies (Tabanidae) – therefore these agents are here grouped under the name arbonematodes.

Novel therapeutic options are urgently needed to improve global treatment of virus infections. Herbal products with confirmed clinical safety features are attractive starting material for the identification of new antiviral activities. Here we demonstrate that Cistus incanus (Ci) herbal products inhibit human immunodeficiency virus (HIV) infections in vitro. Ci extract inhibited clinical HIV-1 and HIV-2 isolates, and, importantly, a virus isolate with multiple drug resistances, confirming broad anti-HIV activity. Antiviral activity was highly selective for virus particles, preventing primary attachment of the virus to the cell surface and viral envelope proteins from binding to heparin. Bioassay-guided fractionation indicated that Ci extract contains numerous antiviral compounds and therefore has favorably low propensity to induce virus resistance. Indeed, no resistant viruses emerged during 24 weeks of continuous propagation of the virus in the presence of Ci extracts. Finally, Ci extracts also inhibited infection by virus particles pseudotyped with Ebola and Marburg virus envelope proteins, indicating that antiviral activity of Ci extract extends to emerging viral pathogens. These results demonstrate that Ci extracts show potent and broad in vitro antiviral activity against viruses that cause life-threatening diseases in humans and are promising sources of agents that target virus particles.

Antiretroviral drug resistance is mostly linked to a complex interaction of several amino acids with variable importance or a single amino acid. To facilitate the interpretation of observed mutation patterns, hospital university centers have developed several interpretation systems. All the currently available interpretation algorithms evolved, are being continuously updated and have been improved during the last decade. Some discrepancies are still evident that are partially smoothened by link of the individual programs with other systems. After the interpretation of HIV-1 group M subtype B mutations, a refined algorithm for the other group M subtypes was developed followed by the interpretation of HIV-1 group O and HIV-2 mutations. The process of improvement is ongoing, due to the better understanding and interpretation of single and cluster mutations and the availability of new antiretroviral substances. The knowledge gained from the experience of HIV drug resistance testing has been used to establish the interpretation of HBV polymerase mutations and will be extended for the treatment of HCV infected with protease inhibitors.

We report the second human immunodeficiency virus (HIV) belonging to the new HIV type 1 (HIV-1) group P lineage that is closely related to the simian immunodeficiency virus found in gorillas. This virus was identified in an HIV-seropositive male hospital patient in Cameroon, confirming that the group P virus is circulating in humans. Results from screening 1,736 HIV-seropositive specimens collected in Cameroon indicate that HIV-1 group P infections are rare, accounting for only 0.06% of HIV infections. Despite its rarity, group P shows evidence of adaptation to humans.

Zusammenfassung Pocken sind das dermatologische Erscheinungsbild einer milden bis teils todlich verlaufenden den gesamten Korper betreffenden Virusinfektion. Ursache ist das Variola-Virus, das in verschiedenen Varianten in der menschlichen Population bis 1979 vorgekommen ist. Pocken wurden durch konsequente, weltweite Impfung ausgerottet. Derzeit kommen gelegentlich beim Menschen Kuhpocken und Affenpocken vor. Beide verursachen einzelne Lasionen an der Haut und ausnahmsweise eine konsumptive Allgemeinerkrankung. Immunsupprimierte sind fur tierische Pockenviren sehr empfanglich, es sind Todesfalle durch das Katzenpockenvirus beschrieben. Zur Prophylaxe der Ubertragung des Pockenvirus sind Hygieneregeln einzuhalten mit zugiger Desinfektion kontaminierter Flachen und Gegenstande, 2 m Abstand zum Infizierten und Tragen von Mundschutz und Handschuhen. Das Vermeiden von Aerosolen ist bei allen Pockenvirusinfektionen essenziell. Quarantane von Patient und bei Variola-Virus zusatzlich von diagnostizierendem arztlichem Personal ist geboten. Des Weiteren steht eine Impfung mit dem Vaccinia-Virus oder, besser, mit dem nebenwirkungsarmen MVA-Virus zur Verfugung. Cidofovir hemmt effektiv die Replikation von Variola-Virus und anderen Pockenviren. Das Variola-Virus gilt als Waffe fur den Bioterrorismus. Derzeit sind Pocken nach Infektionsschutzgesetz nicht meldepflichtig.

The human immunodeficiency virus (HIV) had spread unrecognized in the human population as sexually transmitted disease and was finally identified by its disease AIDS in 1981. Even after the isolation of the causative agent in 1983, the burden and death rate of AIDS accelerated worldwide especially in young people despite the confection of new drugs capable to inhibit virus replication since 1997. However, at least in industrialised countries, this trend could be reversed by the introduction of combination therapy strategies. The design of new drugs is on going; besides the inhibition of the three enzymes of HIV for replication and maturation (reverse transcriptase, integrase and protease), further drugs inhibits fusion of viral and cellular membranes and virus maturation. On the other hand, viral diagnostics had been considerably improved since the emergence of HIV. There was a need to identify infected people correctly, to follow up the course of immune reconstitution of patients by measuring viral load and CD4 cells, and to analyse drug escape mutations leading to drug resistance. Both the development of drugs and the refined diagnostics have been transferred to the treatment of patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). This progress is not completed; there are beneficial aspects in the response of the scientific community to the HIV burden for the management of other viral diseases. These aspects are described in this contribution. Further aspects as handling a stigmatising disease, education of self-responsiveness within sexual relationships, and ways for confection of a protective vaccine are not covered.

BACKGROUND: In February 2007, a 63-year-old man underwent surgery. Retrospective testing with nucleic acid testing (NAT) showed that the patient was human immunodeficiency virus Type 1 (HIV-1) positive 10 days after transfusion. The transfusion-transmitted infection had been identified by a donor-related lookback started in April 2007 after anti-HIV seroconversion.METHODS: Sequence analysis was performed in the gag-pol region as well as in the V3 loop env region. Archived plasma from the transmitting donation was investigated for the individual-donation NAT with the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 test (Roche CAP/CTM HIV-1 test) and for HIV antigen/antibody combination testing (Abbott Architect). Additional testing was done on the donor's follow-up sample and on the recipient's sample. RESULTS: The Roche CAP/CTM HIV-1 test failed to detect viral RNA by minipool NAT in the index donation (April 2007) as well as in the donation that caused the infection (January 2007). Phylogenetic analysis showed a very high genetic similarity among viral sequences from both donor and recipient, proving the HIV-1 transmission by sequence data. CONCLUSION: This case represents the first documented HIV-1 transmission by transfusion of red blood cells after mandatory introduction of HIV-1 NAT for blood screening in Germany. Low viral load and mismatches in the primer/probe region might explain the detection failure of the NAT screening assay. A certain risk remains that new virus variants contain mutations at positions critical for amplification or detection of viral genomes. An option to reduce the risk of a detection failure by NAT is the simultaneous use of several conserved regions as amplification targets.

Recombinant forms of HIV-1 contribute significantly to the ongoing epidemic. In the present study, we characterized the near full-length genome of one candidate HIV-1 CRF25_cpx strain originating in Cameroon, 06CM-BA-040. Viral RNA was extracted from plasma, and the genome was obtained using RT-PCR amplification to generate 10 overlapping fragments. Bootscanning, recombination breakpoint analysis, and phylogenetic trees confirmed that 06CM-BA-040 had a genomic structure consistent with two available CRF25_cpx reference sequences. The CRF25_cpx mosaic composition consisted of nine segments derived from subtypes A and G as well as unclassified (U) regions. Subtype G and CRF25_cpx clusters diverged from each other with long branch lengths but were distinct from other known subtypes with high bootstrap support (94%). The epidemiological significance of CRF25_cpx strains is unknown; however, the availability of additional genomic sequences will improve our understanding of the overall genetic diversity within this recombinant form of HIV-1.

Sera obtained from 927 drug addicts in 1983 to 1985 were tested for antibodies against LAV/HTLV-III. There was a steadily rising proportion of positive results: 10.1% in 1983, 17.6% in 1984 and 23.9% in 1985. In each year the prevalence of anti-LAV/HTLV-III was higher among female than male addicts. No increased proportion of positive results was demonstrable in relation to age. Among 152 sera from 1983/84, hepatitis-B markers were found in 72 (43.7%), of whom 10 (14%) were also anti-LAV/HTLV-III positive. Among hepatitis-B marker-negative sera there were 8 (6%) which were also anti-LAV/HTLV-III positive. The prevalence of anti-LAV/HTLV-III in drug addicts in prisons, rehabilitation centres, hospitals and medical practices was similar. There is a danger that prostitution by addicts for obtaining drugs will cause a penetration of LAV/HTLV-III in the rest of the population.

Mit der Umsetzung der EU-Richtlinien 2004/23/EG und 2006/17/EG im Gewebegesetz sowie den begleitenden Verordnungen (Arzneimittel- und Wirkstoffherstellungsverordnung, Transplantationsgesetz-Gewebeverordnung) wurden die grundlegenden Anforderungen an die Virussicherheit der Gewebespenden allgemein definiert. Wahrend infektionsserologische Testungen (Anti-HIV 1/2, Anti-HCV, Hepatitis-B-Oberflachenantigen, Anti-Hepatitis-B-Core-Antigen, Treponema-pallidum-Hamagglutinationsassay) vorgeschrieben sind, wird der Nukleinsaure-Nachweis fur HIV, HBV und HCV nicht explizit gefordert. Anhand in der Literatur berichteter Virusubertragungen, gewebespezifischer Besonderheiten sowie Herstellungs- und gegebenenfalls Inaktivierungsverfahren wird eine Bewertung des Stellenwertes des HIV/HCV/HBV-Nachweises mittels Nukleinsaure-Amplifikationstechniken (NAT) bei Spendern unterschiedlicher Gewebe vorgenommen und mit den Erfahrungen des Blutspendewesens verglichen. Muskuloskelettale Gewebe besitzen infolge des zumeist hohen Blutgehalts der Gewebe, des umfangreichen Entnahmespektrums, der bisher beschriebenen Ubertragungen, der unterschiedlichen Herstellungsverfahren sowie der hohen Spender-Empfanger-Ratio ein signifikantes Risiko, HIV/HCV/HBV zu ubertragen. Daher sollte bei Spendern muskuloskelettaler Gewebe, die keinem effektiven Virusinaktivierungsverfahren unterzogen werden, eine HIV-, HBV- und HCV-NAT-Testung erfolgen. Kardiovaskulares Gewebe hat bei Durchfuhrung der serologischen Testung ein sehr geringes Restrisiko der HIV/HCV/HBV-Ubertragung. Aufgrund der fehlenden Moglichkeit einer effektiven Virusinaktivierung (Erhalt der Gewebemorphologie) und der Spender-Empfanger-Ratio von bis zu 1:10 sollte die HIV-, HCV- und HBV-NAT jedoch als zusatzliche Sicherheitsmasnahme erfolgen. Augenhornhaute besitzen aus physiologisch-morphologischer sowie epidemiologischer Sicht das geringste HIV/HCV/HBV-Ubertragungsrisiko, jedoch sollte die HCV-NAT durchgefuhrt werden. Eine Quarantanelagerung der Gewebe eines Spenders kann bei negativem Ergebnis der HIV/HCV/HBV-NAT grundsatzlich entfallen. Aufgrund der vielfaltigen Synergieeffekte mit der Transfusionsmedizin bietet es sich fur Gewebebanken an, die Testung der infektionsserologischen bzw. molekularbiologischen Laborparameter in Kooperation mit Blutspendediensten durchzufuhren.

Anaplasma phagocytophilum, marginatum; Bartonella henselae; Borrelia burgdorferi, afzelii, garinii; Coxiella burnetii; Ehrlichia chaffeensis; Francisella tularensis; Rickettsia prowazekii, akari, rickettsii andYersinia pestis are also known as arbobacteria. Diseases caused by these bacteria are basically zoonoses, i.e. diseases transmittable from animals to humans, and have been known as such for about 100 years (table ​(table1).1). A part of the individual pathogens have not been described until the past few decades. Based on molecular biology analyses, R. prowazekii, Ehrlichia and Anaplasma are categorised as Rickettsiales, while Bartonella is categorised as alpha-2-proteobacteria, Coxiella, Rickettsia grylli and F. tularensis as gamma proteobacteria, and Y. pestis as enterobacteria [1]. Table 1 Vectors for arbobacteria Most arbobacteria grow predominantly intracellularly. However, Borrelia bacteria grow intracellularly and extracellularly, and Yersinia mainly extracellularly. The above described arbobacteria, when transmitted by ticks, show seasonal occurrence and a partly changed antigen repertoire in vector and mammal. R. prowazekii is transmitted by lice world-wide throughout the year. The major clinical symptoms such infections have in common include fever, exanthema, headache, and lymph node swelling, partly a pronounced erythema at the site of the sting, and encephalitic disorders. Neutropenia and thrombocytopenia can occur later. Treatment: Doxycycline is the treatment of choice against most of these bacteria, followed by chloramphenicol and cephalosporins. Quinolones are ineffective against R. prowazekii. The treatment of choice against Y. pestis and F. tularensis is streptomycin or gentamycin, and in addition doxycycline or ciprofloxacine. C. burnetii has been dealt with separately [2]. Therefore, this pathogen is not included in the present review, neither are rare tropical and/or pure tropical diseases. The oriental flea (Xenopsylla cheopsis) is considered as the most effective transmitter for Y. pestis. More than 30 other flea species are known which can transmit Y. pestis as intermediary hosts, including Pulex irritans (human flea), which can play a role in human-to-human transmission. The human louse can also be a vector for transmission of Y. pestis [3]. The following section provides for each pathogen information on the general state of knowledge, characteristics of the pathogen, infectious disease, epidemiology, methods of detection and occurrence of the pathogen in the donor population. This is followed by information concerning all pathogens on epidemiology, defence situation, treatment and prevention in recipient populations as well as a summary evaluation.

It is assumed that HIV, the human immunodeficiency virus, started its spread after the Second World War. Molecular analysis of the genome of various HIV-1 types has shown that this virus can be divided into the groups M, N, and O and that these genome sequences fit perfectly to the genomes found in SIV of chimpanzees (SIVcpz) living in the area of West and Central Africa. SIVcpz is nonpathogenic for chimpanzees indicating that the virus and host have adapted for a long period. HIV-2 genome sequences converge with SIV sequences of sooty mangabey monkeys from West Africa (SIVsm), covering the subtypes A to G from HIV-2. SIVsm is nonpathogenic for mangabey monkeys. All available data indicate that HIV-1 and HIV-2 have been introduced into humans at least several times. Since SIVcpz and SIVs from other monkeys are recombinant viruses, it cannot be excluded that a new recombinant SIV might again enter the human population and initiate a new epidemic.

Clinical observations indicate that human immunodeficiency virus (HIV)‐positive women experience more postoperative problems than do HIV-negative women. To obtain a better estimate of the individual risk of postoperative morbidity among HIV-infected women, and to determine which procedures pose the greatest risk, we performed a retrospective case-control study in which we assessed the outcomes after 235 obstetric and gynecologic surgical procedures. For purposes of comparison, an HIV-negative control patient was matched for each of the 235 surgical procedures performed, on the basis of the type of procedure and patient age. We found a significantly greater number of postoperative complications among the HIV-positive women. Higher complication rates occurred after abdominal surgery (odds ratio [OR], 3.6; ) and curettage (OR, 7.7; P p .001 ). Among HIV-infected women, the risk of complications was associated with immune status. AntiP p .06 retroviral therapy and standard perioperative antibiotic prophylaxis did not decrease the risk of complications. Indications for performing abdominal surgery and curettage on HIV-infected women should be carefully weighed against the potential risk of postoperative complications.

Adenovirus (Ad) infection results in significant morbidity and mortality in both immunocompetent and immunosuppressed hosts. There is currently no licensed chemotherapy effective in dealing with this virus infection. In this study the anti-adenoviral activity of a group of modified nucleoside analogs was investigated. The most efficient 3-fluorosubstituted nucleoside triphosphate inhibitors of Ad DNA polymerase were 3'-fluorothymidine triphosphate (IC50 0.63 microM), 2',3'-dideoxy-3'-fluoroguanosine triphosphate (IC50 0.71 microM) and 2',3'-dideoxy-3'-fluorouridine triphosphate (IC50 2.96 microM). The most efficient 2',3'-dideoxynucleoside triphosphates were 2',3'-dideoxycytidine triphosphate (ddCTP; IC50 1.0 microM), 2',3'-dideoxyadenosine triphosphate (IC50 1.6 microM) and 2',3'-dideoxythymidine triphosphate (IC50 1.82 microM). Kinetic studies indicate competitive inhibition of adenovirus DNA polymerase by ddCTP. These data confirm results previously obtained at the cellular level using a focus reduction assay involving Ad2-infected FL cells. Whereas the D-enantiomers 3'-fluorothymidine and 2',3'-dideoxycytidine are potent inhibitors of adenoviral replication, the corresponding L-enantiomers exhibited no inhibitory activity.

Bei Raumtemperatur uberlebt HIV auserhalb des Korpers sechs bis zwolf Stunden unter sterilen Bedingungen, kurzer, wenn Blutgerinnung ablauft. HIV ist durch die Mehrzahl der Desinfektionsmittel einfach zu inaktivieren. Die human infektiose Dosis ist etwa 100 bis 1000 HIV-Partikel, abhangig vom Virus und der Eintrittspforte. Nach Inokulation kann nach 24 Stunden die HIV-Vermehrung gestartet sein, und das HIV verbreitet sich innerhalb von einer bis zwei Wochen im gesamten Korper. Uber Antikorpertests lasst sich die angehende HIV-Infektion innerhalb von vier bis zwolf Wochen nachweisen, unter Therapie ist die Antikorperantwort abgeschwacht; mit Nuleinsauretests gelingt der Nachweis etwa ab dem elften Tag.

The new large scale synthesis of the yellow colored vitamin B6 analogue 5′-O-phosphono-pyridoxylidenerhodanine (2) (B6PR) leads to oligohydrates of its monosodium salt (4). The light-red hemiheptadecahydrate (8 1 2 hydrate) (4a) was crystallized and its three-dimensional structure determined by X-ray crystallography. Special nucleotide and protein interaction properties together with scavenging antioxidative function are combined in this simple water-soluble vitamin B6 analogues B6PR. High (mM) concentrations were untoxic to ‘healthy’ not affected cells and primary tissues. Complexation of ions (e.g. Ca2+, Fe2+, and Zn2+), modulation of nitric oxide synthases (NOS I-III), nitric oxide (NO) metabolism, and reactive oxygen species (ROS) was found. Special cytoprotecting, immunomodulating, stimulating and inhibiting activities were observed in vitro, not in comparison with some natural and synthetic pyridoxines. Low B6PR suppressed proliferation, high induced selective cell death of some cancer cell lines. Low B6PR protected HIV-1-infected CD4+ HUT 78 cells against HIV-1-mediated destruction (complete inhibition of HIV-1-induced syncytia formation and cell death) and reduced p24 level. Autoreactive S100β-specific T cells of Lewis rat, a model of multiple sclerosis, could be influenced. Oxidative damage and age, acquired and inherited disease related pathophysiological disorders can be treated by this new cytopathology-selective versatile acting B6PR. ©

1IAME, UMR 1137, Univ Paris Diderot, Sorbonne Paris Cite, F-75018 Paris, France 2IAME, UMR 1137, INSERM, F-75018 Paris, France 3AP-HP, Hopital Bichat-Claude Bernard, Laboratoire de Virologie, F-75018 Paris, France 4Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium 5Universite catholique de Louvain, AIDS Reference Laboratory, Brussels, Belgium 6Max von Pettenkofer Institute, Ludwig Maximilian University Munich, Munich, Germany 7Max Planck Institute for Informatics, Saarbrucken, Germany 8Johann Wolfgang Goethe-University Hospital, Institute for Medical Virology, German National Reference Centre for Retroviruses, Frankfurt, Germany 9Institute of Virology, University of Cologne, Germany 10Medizinisches Labor Dr. Berg, Berlin, Germany

HIV-1 group O serological screening or confirmation strategies so far have not proved 100% sensitive and specific, indicating a lack of antibody reactivity or cross-reactivity with group O antigens. Therefore, genetic analysis currently represents the only method by which confirm presumed HIV-1 group O or group O/M infections. We have optimized the sensitivity (100%) and specificity (100%) of an HIV-1 group O/M-specific PCR of a pol gene fragment. In addition, we report on a highly sensitive (97.2%) and specific (100%) method for differentiation between HIV-1 group O and group M viruses, using PCR and PstI enzyme restriction fragment analysis of a pol fragment. Compared with sequencing, these methods are fast, inexpensive, and simple.

Objective. The effects of two antiretroviral triple combinations including the protease inhibitor indinavir on the surrogate markers, viral load and CD4 cells were evaluated. Methods. Fifteen patients with high viral load or disease progression under their prior antiretroviral therapy were switched to zidovudine/ lamivudine/indinavir (Group A, n = 10) or stavudine/lamivudine/indinavir (Group B, n = 5). Serial determinations of viral load and CD4 cells were performed. Results. The median reduction of the viral load was 0.6 log after 3 months and 0.8 log after 6 months in Group A and 2.5 and 2.4 log after 3 and 6 months in Group B, respectively. After 3 and 6 months 3 of 10 patients in Group A and 3 of 5 patients in Group B had viral load reductions below the detection limit of the assay. Patients with an additional switch of nucleoside analogues at start of indinavir therapy (regardless of the specific reverse transcriptase inhibitor used) had significantly better reductions of the viral load than patients without such a switch (median 2.3 log vs. 0.2 log after 6 months, P < 0.05). In Group A the median of the relative increase of CD4 cells was 37% after 3 months and 57% after 6 months (P = 0.002); in Group B the medians of the relative increase of CD4 cells were 145 and 163% (not significant), respectively. Two patients from Group A and 1 from Group B developed renal calculi, which resolved after adequate hydration. One patient was withdrawn because of intractable vomiting attributed to indinavir. Conclusion. In a small cohort of HIV-infected pediatric patients with extensive prior antiretroviral treatment, triple therapy including indinavir had a sustained effect on the decrease of the viral load and the increase of CD4 cells similar to results obtained in antiretrovirally experienced adults. This effect was significantly better in patients with an additional switch of a nucleoside analogue at start of triple therapy with indinavir than in patients without such a change.