We herein describe the case of a 33-year-old male patient who presented at our emergency department with concomitant flu symptoms and a maculopapular rash. The evening prior to consultation he had first noticed erythematous macules on the trunk and arms, which had then rapidly progressed overnight. The rash was markedly pronounced at injection sites of interferon-beta (IFN-β) administered for relapsing remitting multiple sclerosis (RRMS) (see Fig. 1a). Pruritus was moderate (3/10 numeric rating scale). Fever up to 38°C, fatigue, hoarseness and muscle and joint pain had begun four days prior to consultation. Another four days earlier, the patient and his family had visited a private party. Some of the guests as well as the patient\u0027s wife and children experienced equivalent flu symptoms albeit no skin eruptions.

Objectives: In Germany, previous reports have demonstrated transmitted human immunodeficiency virus type 1 (HIV-1) drug-resistance mutations (DRM) in 11% of newly diagnosed individuals, highlighting the importance of drug-resistance screening before the initiation of antiretroviral therapy (ART). Here, we sought to understand the molecular epidemiology of HIV DRM transmission in the Cologne-Bonn region of Germany, given one of the highest rates of new HIV diagnoses in western Europe (13.7 per 100 000 habitants). Methods: We analysed 714 HIV-1 ART-naive infected individuals diagnosed at the University Hospitals Cologne and Bonn between 2001 and 2016. Screening for DRM was performed according to the Stanford University Genotypic Resistance Interpretation. Shared DRM were defined as any DRM present in genetically linked individuals (<1.5% genetic distance). Phylogenetic and network analyses were performed to infer putative relationships and shared DRM. Results: The prevalence of any DRM at time of diagnosis was 17.2% (123/714 participants). Genetic transmission network analyses showed comparable frequencies of DRM in clustering versus non-clustering individuals (17.1% (85/497) versus 17.5% (38/217)). The observed rate of DRM in the region was higher than previous reports 10.8% (87/809) (p < 0.001), revealing the need to reduce onward transmission in this area. Genetically linked individuals harbouring shared DRM were more likely to live in suburban areas (24/38) than in central Cologne (1/38) (p < 0.001). Conclusion: The rate of DRM was exceptionally high. Network analysis elucidated frequent cases of shared DRM among genetically linked individuals, revealing the potential spread of DRM and the need to prevent onward transmission of DRM in the Cologne-Bonn area. (C) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The increasing incidence of acyclovir (ACV) and multidrug-resistant strains in patients with Herpetic Stromal Keratitis (HSK) is a major health problem and often results in blindness. In the study we examined the effectivity of mAb 2c in preventing experimental HSK in BALB/c mice. Mice were infected with HSV-1 (KOS) and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis) or 24, 40, and 56 hours after infection (post-exposure immunotherapy). For topical treatment antibody-containing eye drops or PBS as control was administered (5 times per day). Systemic antibody treatment markedly reduced viral loads and completely protected mice from developing HSK. The administration of antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be effective for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c) was equally potent in protecting mice from HSV-induced HSK when compared to the parental mouse antibody.

Severe neurologic complications have been rarely reported during novel pandemic influenza A(H1N1) virus infections. We describe the case of an 10-year-old boy with new onset seizures and proven influenza A(H1N1) 2009 infection showing a reversible hyperintense lesion in the splenium of the corpus callosum on T2-weighted and FLAIR magnetic resonance images without contrast enhancement. Transient splenial lesions have been described in the context of virus encephalopathy and do not require specific treatment.

The clinical presentation of the viral enteric pathogens in newborn infants has not been adequately examined. The aim of this study was to evaluate the clinical characteristics of viral intestinal infections in newborn infants. Clinical data of all term and preterm infants admitted to our tertiary neonatal intensive care unit from 1998 to 2007 with clinical signs of gastroenteritis (GE) or necrotizing enterocolitis (NEC) were retrospectively reviewed and compared between infants with different viral enteric pathogens in stool specimens. In 34 infants with signs of GE or NEC, enteropathogenic viruses were found in stool specimens. Rotavirus was detected in 12 cases, of which two infants had NEC. Compared with infants with rotavirus or norovirus, infants with astrovirus more frequently suffered from NEC (p<0.05). In addition, an acute systemic inflammatory response was significantly more common in patients with astrovirus infection (astrovirus vs. rotavirus and astrovirus vs. norovirus, p < 0.01 and p < 0.05, respectively). Of eight children infected with norovirus, one infant had a systemic acute inflammatory response and NEC. This study demonstrates that in newborn infants, intestinal rotavirus, norovirus, and astrovirus infections may be associated with severe illness such as hemorrhagic enteritis resulting in bloody diarrhea or even NEC.

Einführung: Parvovirus B19 Infektionen während der Schwangerschaft können v.a. während des ersten Trimenons zu fetaler Anämie, Hydrops fetalis oder intrauterinem Fruchttod führen1. Wir beschreiben eine schwere thromboembolische Komplikation bei einem Neugeborenen assoziiert mit einer pränatalen Parvovirus B19 Infektion im letzten Trimenon.

Hintergrund: Hauptursache der weltweiten Morbidität und Mortalität schwerer gastrointestinaler Infektionen bei Kindern sind virale Erreger. Bei Säuglingen und Kleinkindern stellen Noroviren (NV) nach den Rotaviren (RV) sowie Astro- (HAstV) und Adenoviren (AV) die häufigsten Erreger akuter Gastroenteritiden dar. Während bei immunkompetenten Säuglingen die gastrointestinalen Viren zumeist nur eine milde, selbstlimitierende Symptomatik verursachen, werden bei immuninkompetenten Kindern schwere protrahierte Verläufe beschrieben, die bei Frühgeborenen zur Entwicklung einer nekrotisierenden Enterokolitis (NEC) beitragen können. Die klinische Bedeutung der gastrointestinalen Viren bei Früh- und Neugeborenen ist bislang nur unzureichend untersucht. Ziel dieser retrospektiven Analyse ist es, die klinische Symptomatik und den Verlauf der viralen intestinalen Infektionen in dieser Patientengruppe zu analysieren. Patienten und Methoden: Es wurden alle Früh- und Neugeborenen mit Verdacht auf eine nosokomiale gastrointestinale Infektion identifiziert, bei denen zwischen 1998 und 2007 Stuhl-Proben (Stuhl-Kultur, EIA, PCR) auf pathogene Bakterien und auf Viren (RV, NV, HAstV, AV) untersucht wurden. Die klinischen Daten wurden retrospektiv analysiert und Unterschiede in Symptomatik und Verlauf zwischen den viralen Erregern verglichen. Ergebnisse: Viren konnten in Stuhl-Proben von 37 Patienten mit einem medianen Gestationsalter (GA) von 32 Wochen (Range, 25–40) und einem medianen Geburtsgewicht von 1620g (Range 618–3790g) identifiziert werden, bei 34 Patienten (92%) bestanden klinische Zeichen einer Gastroenteritis (n=22) oder NEC (n=12). Drei Patienten (2xRV, 1xHAstV) waren asymptomatisch. RV wurde bei 14 Patienten während eines nosokomialen Gastroenteritis Ausbruchs zwischen Januar und Juni 1998 isoliert. Obwohl die Patienten mit RV zumeist milde und selbstlimitierende Verläufe zeigten, trat bei 2 Frühgeborenen eine NEC auf. NV wurde bei 8 Patienten (22%) isoliert. Die häufigsten Symptome bei diesen Patienten waren abdominelle Distention (100%), Durchfall (100%), und Apnoen (57%). Vier Patienten (50%) setzten blutigen Stuhl ab, davon hatten 3 Patienten GE und 1 Patient NEC Stadium 1b. Im Vergleich zu den Patienten mit RV oder NV, trat eine NEC bei den Patienten mit HAstV signifikant häufiger auf (p<0.05). Weiterhin zeigten die Patienten mit HAstV-Gastroenteritis eine signifikante Akut-Phase-Reaktion (HAstV vs. RV und HAstV vs. NV, p<0.01 und p<0.05). Diskussion: Die Ergebnisse der hier vorgestellten Studie zeigen erstmals, dass NV und HAstV insbesondere bei Frühgeborenen mit der Entwicklung komplizierter Verläufe mit blutigen Diarrhoen oder NEC assoziiert sind und weisen auf die Bedeutung von intestinalen Virusinfektionen in der Ätiologie und Pathogenese der NEC hin. Neben den bakteriologischen Untersuchungen sollten bei Kindern mit gastrointestinalen Symptomen oder NEC auch virologische Untersuchungen unter Einschluss von HAstV, RV, NV und AV durchgeführt werden.

Unter den Todesursachen von Säuglingen und Kleinkindern nehmen Infektionen einen nennenswerten Anteil ein; hierbei variiert das Erregerspektrum je nach Kindesalter, Grunderkrankung oder vorbestehenden Risikofaktoren. Unter den bakteriellen Infektionen stehen Septitiden im Vordergrund, die zur Hälfte nosokomialen Ursprungs sind. Die viralbedingten Todesfälle gehen vornehmlich auf tiefe Atmwegs- und Zentralnervensysteminfektionen sowie Myokarditiden zurück. Erhebung und Interpretation mikrobiologischer Untersuchungsergebnisse stellen aufgrund der postmortalen Prozesse eine Herausforderung dar. In Zusammenschau mit histopathologischen und anderen post- oder antemortalen Befunden kann die mikrobiologische Diagnostik aber neben dem möglichen Nachweis des todesursächlichen Agens Informationen zur Effektivität einer vorausgegangenen antiinfektiven Therapie liefern und damit zur forensischen Beweisführung beitragen.

Cytomegalovirus (CMV) infection is the most important congenital viral infection. Intravenous (i.v.) Ganciclovir (GCV) improved outcome in term infants with symptomatic congenital CMV infection. We present data on oral valganciclovir (VGCV) in an extremely low birth weight infant. A male preterm infant was delivered at 28 weeks of gestation because of abnormal fetal perfusion with severe intrauterine growth retardation. The infant developed hepatitis and a severe thrombocytopenia. Serology revealed a positive CMV IgM in maternal serum 3 days after delivery and CMV DNA was detected in plasma and urine samples of the infants. Treatment with i.v. GCV was started at day 4 of life for 35 days and continued with oral VGCV for further 6 weeks. Plasma GCV levels were 1.68 ng ml−1 (peak) and 0.92 ng ml−1 (trough) on day 10 of oral treatment. Clinical signs resolved and virus load decreased slowly during therapy. At discharge brain stem-evoked audiometry was normal. Oral treatment with VGCV in an extremely low birth weight preterm infant with congenital CMV infection resulted in adequate GCV plasma levels, reduced effectively the CMV viral load and was well tolerated without apparent adverse effects.

Hintergrund: Nekrotisierende Enterokolitis (NEC) ist der wichtigste gastrointestinale Notfall, der mit einer hohen Morbität und Mortalität bei Frühgeborenen mit sehr niedrigem Geburtsgewicht (<1500g Geburtsgewicht) verbunden ist. Bekannte Risikofaktoren sind die Unreife des Darmes, enterale Ernährung, intestinale Minderperfusion und Immundefizienz. Weiterhin kann durch intestinale Besiedlung mit Bakterien eine Entzündungsreaktion getriggert werden, die die Mucosabarriere schädigt. Die genaue Pathophysiologie ist jedoch weiterhin nicht vollständig verstanden. Regelmäßig werden Cluster von NEC's auf den neonatologischen Intensivstationen beobachtet, so dass auch pathogene Erreger eine Schlüsselrolle spielen könnten. So wurden auch gastrointestinale Viren wie z.B. Rotaviren in Zusammenhang mit der Entwicklung einer NEC beschrieben. Das Ziel dieser Analyse war es, die Rolle von Astrovirus (HAstV) bei Frühgeborenen mit NEC zu untersuchen.

Human parvovirus genotype 1 (B19-like) DNA was frequently present in coagulation factor VIII concentrates used until the beginning of the eighties (contamination rate 81%). In concentrates presently used for replacement therapy, overall genotype 1 DNA contamination was about 42.5%. The level of viral load was similar in formerly used and presently used concentrates. Genotype 2 DNA was detected much less frequently in coagulation factor concentrates than genotype 1 DNA. Overall, 2.5% of the lots proved to be contaminated. In the present study, all genotype 2 DNA-contaminated lots were also genotype 1-contaminated.

Giant cell hepatitis (GCH) is frequently found in neonates, but rarely in adults. Diagnosis is made on the basis of the presence of hepatocellular multinucleate giant cells. The disease often takes a fulminant course with the development of cirrhosis within months, requiring transplantation or leading to death in a high percentage of cases. The aetiology and pathogenesis are unclear. Association with autoimmune disorders, viral infections and drug reactions, but also with congenital metabolic diseases such as alpha 1-antitrypsin deficiency or haemosiderosis has been described. In some cases, no causative event has been found. Therefore, therapeutic options are controversially discussed. We present a patient with GCH with autoimmune features after a human herpesvirus 6 (HHV6)induced adverse drug reaction, a combination that has not been reported before. High-dose immunosuppression led to dramatic improvements over the past year.

Due to viral replication in erythroid precursor cells, severe anemia represents a major complication of B19 infection. However, cytomegalovirus (CMV) is the leading cause of virus-induced complications with a significant impact on graft outcome of renal transplant patients. Herein, we present a long-term B19 infection in a 45-year-old female renal transplant patient, which aggravated the renal anemia associated with a concomitant CMV infection. Since no data were available on the seroprevalence of this virus in pretransplant patients, we determined the B19 serostatus of 90 dialyzed pretransplant adult subjects.

ABSTRACT An infectious parvovirus B19 (B19V) genotype 2 variant was identified as a high-titer contaminant in a human plasma donation. Genome analysis revealed a 138-bp insertion within the p6 promoter. The inserted sequence was represented by an additional 30 bp from the end of the inverted terminal repeat adjacent to a 108-bp element found also, in inverted orientation, at the extreme right end of the unique sequence of the genome. However, despite the profound variations in the promoter region, the pattern of gene expression and DNA replication did not differ between genotype 1 and genotype 2 in permissive erythroid KU812Ep6 cells. Capsid proteins of both genotypes differ in their amino acid sequences. However, equivalent kinetics of virus inactivation at 56°C or pH 4 indicated a comparable physicochemical stability of virus capsids. Sera from six individuals infected by B19V genotype 1 were investigated on cross-neutralization of B19V genotype 2 in vitro. Similar neutralization of both B19V genotypes was observed in sera from three individuals, while the sera from three other individuals showed weaker cross-neutralization for genotype 2. In conclusion, the in vitro replication characteristics and physical stability of B19V capsids are very similar between human parvovirus B19 genotypes 1 and 2, and cross-neutralization indicates a close antigenic relation of genotypes 1 and 2.

TT virus (TTV) is a newly discovered human virus of high genotypic diversity. TTV is widely distributed among humans, but the possible genotype-related differences in TTV biology are not well known. The prevalence and amount of TTV-DNA, especially of genotype 6, was determined by nested-PCR in various human tissues, and human parvovirus B19, another ssDNA virus, was used as a reference. TTV DNA was detected simultaneously in bile, peripheral blood mononuclear cells (PBMC) and plasma of 77% subjects, in 38% skin samples, in 38% synovial samples and in all (100%) adenoids, tonsils and liver samples. The relative concentrations of TTV-DNA did not vary significantly among the different samples. Genotype 6 TTV-DNA was detected in bile and plasma of one subject (3%), in skin and serum of one subject (8%) and in one liver (5%). The overall prevalence of TTV genotype 6 was 4% in subjects and 4% in sera. TTV genotype 6 was shown to occur in human tissues with no obvious tissue-type or symptom specificity. Parvovirus B19 DNA was detected overall in 38% subjects, and bile was the only sample type tested that did not persistently harbour B19 DNA.