Weltweiter SARS-Alarm : eine neue Seuche auf dem Vormarsch?

Mitte März 2003 löste die WHO einen weltweiten Alarm aus, nachdem sich eine neuartige, schwere und unter bestimmten Umständen hochansteckende Atemwegserkrankung scheinbar unaufhaltsam über weite Teile der Welt auszubreiten schien. Am 15. März desselben Jahres landeten die ersten Patienten mit Verdacht auf Schweres Akutes Respiratorisches Syndrom (SARS) in Frankfurt und wurden auf die Isolierstation des Universitätsklinikums aufgenommen. Auslöser war ein zuvor nicht bekanntes Coronavirus, das heute als SARS-CoV bezeichnet wird. Derzeit laufen Untersuchungen zur Biologie und Epidemiologie des neuen Erregers, zu antiviralen Hemmstoffen sowie zu Desinfektions- und Inaktivierungsmöglichkeiten und neuen Therapieoptionen. Daneben wird analysiert, wie sich das öffentliche Gesundheitswesen auf eine mögliche Wiederkehr vorbereiten muss. SARS ist ein Beispiel dafür, wie schnell sich eine Infektionskrankheit in der modernen Welt international ausbreiten kann und wie wichtig in einem solchen Falle eine gut koordinierte internationale Kooperation ist. Frankfurter Forscher berichten

S2k guidelines for the diagnosis and treatment of herpes zoster and postherpetic neuralgia

The present guidelines are aimed at residents and board-certified specialists in the fields of dermatology, ophthalmology, ENT, pediatrics, neurology, virology, infectious diseases, anesthesiology, general medicine and any other medical specialties involved in the management of patients with herpes zoster. They are also intended as a guide for policymakers and health insurance funds. The guidelines were developed by dermatologists, virologists, ophthalmologists, ENT physicians, neurologists, pediatricians and anesthesiologists/pain specialists using a formal consensus process (S2k). Readers are provided with an overview of the clinical and molecular diagnostic workup, including antigen detection, antibody tests and viral culture. Special diagnostic situations and complicated disease courses are discussed. The authors address general and special aspects of antiviral therapy for herpes zoster and postherpetic neuralgia. Furthermore, the guidelines provide detailed information on pain management including a schematic overview, and they conclude with a discussion of topical treatment options

Inhibition of apoptosis prevents West Nile virus induced cell death

We found that WNV infection induces cell death in the brain-derived tumour cell line T98G by apoptosis under involvement of constituents of the extrinsic as well as the intrinsic apoptotic pathways. Our results illuminate the molecular mechanism of WNV-induced neural cell death

Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants

BACKGROUND: Experimental animal data show that protection against severe acute respiratory syndrome coronavirus (SARS-CoV) infection with human monoclonal antibodies (mAbs) is feasible. For an effective immune prophylaxis in humans, broad coverage of different strains of SARS-CoV and control of potential neutralization escape variants will be required. Combinations of virus-neutralizing, noncompeting mAbs may have these properties. METHODS AND FINDINGS: Human mAb CR3014 has been shown to completely prevent lung pathology and abolish pharyngeal shedding of SARS-CoV in infected ferrets. We generated in vitro SARS-CoV variants escaping neutralization by CR3014, which all had a single P462L mutation in the glycoprotein spike (S) of the escape virus. In vitro experiments confirmed that binding of CR3014 to a recombinant S fragment (amino acid residues 318–510) harboring this mutation was abolished. We therefore screened an antibody-phage library derived from blood of a convalescent SARS patient for antibodies complementary to CR3014. A novel mAb, CR3022, was identified that neutralized CR3014 escape viruses, did not compete with CR3014 for binding to recombinant S1 fragments, and bound to S1 fragments derived from the civet cat SARS-CoV-like strain SZ3. No escape variants could be generated with CR3022. The mixture of both mAbs showed neutralization of SARS-CoV in a synergistic fashion by recognizing different epitopes on the receptor-binding domain. Dose reduction indices of 4.5 and 20.5 were observed for CR3014 and CR3022, respectively, at 100% neutralization. Because enhancement of SARS-CoV infection by subneutralizing antibody concentrations is of concern, we show here that anti-SARS-CoV antibodies do not convert the abortive infection of primary human macrophages by SARS-CoV into a productive one. CONCLUSIONS: The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection

Human immunodeficiency virus: 25 years of diagnostic and therapeutic strategies and their impact on hepatitis B and C virus

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

Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression

Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease

Novel swine-origin influenza A virus in humans: another pandemic knocking at the door.

Influenza A viruses represent a continuous pandemic threat. In April 2009, a novel influenza A virus, the so-called swine-origin influenza A (H1N1) virus (S-OIV), was identified in Mexico. Although S-OIV originates from triple-reassortant swine influenza A (H1) that has been circulating in North American pig herds since the end of the 1990s, S-OIV is readily transmitted between humans but is not epidemic in pigs. After its discovery, S-OIV rapidly spread throughout the world within few weeks. In this review, we sum up the current situation and put it into the context of the current state of knowledge of influenza and influenza pandemics. Some indications suggest that a pandemic may be mild but even "mild" pandemics can result in millions of deaths. However, no reasonable forecasts how this pandemic may develop can be made at this time. Despite stockpiling by many countries and WHO, antiviral drugs will be limited in case of pandemic and resistances may emerge. Effective vaccines are regarded to be crucial for the control of influenza pandemics. However, production capacities are restricted and development/production of a S-OIV vaccine will interfere with manufacturing of seasonal influenza vaccines. The authors are convinced that S-OIV should be taken seriously as pandemic threat and underestimation of the menace by S-OIV to be by far more dangerous than its overestimation