Family outbreak of an infection with a recombinant Coxsackie A virus in eastern Switzerland

Purpose: We report on an unusual familial outbreak of a coxsackie virus infection in Switzerland in which five family members were affected. Most of the patients presented with signs of meningitis, and four were hospitalized. Methods: In three individuals, the virus was detected in the cerebrospinal fluid, pharynx, and stool, respectively. The genome was sequenced in specimens of two patients. Results: The nucleotide sequences of both virus strains were identical. Blast search revealed that the first half of the sequence was 88% homologous to Enterovirus 75 (EV-75), 87% with Echovirus 11 (E-11), and 84% homologous to Coxsackie virus A9 (CV-A9). The second half of the sequence was 77% homologous to EV-75, 75% to E-11, and 91% to CV-A9. Conclusion: We propose that the isolated virus strain is a recombinant strain with a 5′ untranslated region and with the start of the VP4 sequence originating from E-11/EV-75 and the rest of the genome originating from CV-A9. Interestingly, this novel virus strain showed an exceptional virulence and rapid spread. Twoweeks after the initial outbreak in this family, a similar outbreak was observed in a second geographic area roughly 100km distant to the primary identification site, and another 2months later this virus strain was found to circulate in the western part of Switzerland some 250km distant to the primary locus. These findings suggest that genetic recombination has resulted in a novel enterovirus with features of high virulence, contagiosity, and spreadin

Swiss recommendations for the management of varicella zoster virus infections.

Infections with varicella zoster virus (VZV) are common viral infections associated with significant morbidity. Diagnosis and management are complex, particularly in immunocompromised patients and during pregnancy. The present recommendations have been established by a multidisciplinary panel of specialists and endorsed by numerous Swiss medical societies involved in the medical care of such patients (Appendix). The aim was to improve the care of affected patients and to reduce complications

FLT3 mutations in canine acute lymphocytic leukemia

<p>Abstract</p> <p>Background</p> <p>FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, and a poorer prognosis. A better understanding of the molecular consequences of FLT3 activation would allow improved therapeutic strategies in these patients. Canine lymphoproliferative diseases, including lymphoma and acute leukemias, share evolutionarily conserved chromosomal aberrations and exhibit conserved mutations within key oncogenes when compared to their human counterparts. A small percentage of canine acute lymphocytic leukemias (ALL) also exhibit <it>FLT3 </it>ITD mutations.</p> <p>Methods</p> <p>We molecularly characterized <it>FLT3 </it>mutations in two dogs and one cell line, by DNA sequencing, gene expression analysis via quantitative real-time PCR, and sensitivity to the FLT3 inhibitor lestaurtinib via <it>in vitro </it>proliferation assays. FLT 3 and downstream mediators of FLT3 activation were assessed by Western blotting.</p> <p>Results</p> <p>The canine B-cell leukemia cell line, GL-1, and neoplastic cells from 2/7 dogs diagnosed cytologically with ALL were found to have <it>FLT3 </it>ITD mutations and <it>FLT3 </it>mRNA up-regulation. Lestaurtinib, a small molecule FLT3 inhibitor, significantly inhibited the growth of GL-1 cells, while not affecting the growth of two other canine lymphoid cell lines without the <it>FLT3 </it>mutation. Finally, western blots were used to confirm the conserved downstream mediators of <it>FLT3 </it>activating mutations.</p> <p>Conclusions</p> <p>These results show that ALL and FLT3 biology is conserved between canine and human patients, supporting the notion that canine ALL, in conjunction with the GL-1 cell line, will be useful in the development of a relevant large animal model to aid in the study of human FLT3 mutant leukemias.</p

Novel Vaccines to Human Rabies

Rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. Most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in Southeast Asia and Africa. Safe and efficacious vaccines are available to prevent rabies. However, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times for post-exposure prophylaxis (PEP). In cases of severe exposure, a regimen of vaccine combined with a rabies immunoglobulin (RIG) preparation is required. The high incidence of fatal rabies is linked to a lack of knowledge on the appropriate treatment of bite wounds, lack of access to costly PEP, and failure to follow up with repeat immunizations. New, more immunogenic but less costly rabies virus vaccines are needed to reduce the toll of rabies on human lives. A preventative vaccine used for the immunization of children, especially those in high incidence countries, would be expected to lower fatality rates. Such a vaccine would have to be inexpensive, safe, and provide sustained protection, preferably after a single dose. Novel regimens are also needed for PEP to reduce the need for the already scarce and costly RIG and to reduce the number of vaccine doses to one or two. In this review, the pipeline of new rabies vaccines that are in pre-clinical testing is provided and an opinion on those that might be best suited as potential replacements for the currently used vaccines is offered

Transfer of Lipophilic Markers from PLGA and Polystyrene Nanoparticles to Caco-2 Monolayers Mimics Particle Uptake

ISSN:0724-8741ISSN:1573-904