Canine Parvovirus remains a leading cause of enteritis in dogs in South Africa and many other countries despite the wide availability of effective vaccines. The virus does not affect all dogs equally and the course of the disease depends on the age, immune status and breed of the puppies as well as the viral dose, route of exposure and the virulence of the strain. Although aggressive supportive treatment can be successful, the treatment and convalescent periods may be prolonged and consequently expensive and the mortality rate relatively high, causing many clients to forego treatment and elect for euthanasia of their pet. Acute phase proteins (APP) are proteins that change in concentration by at least 25% in animals subjected to external or internal inflammatory challenges, such as infection, inflammation or surgical trauma. Increased concentrations are associated with poor outcome in certain diseases. C-reactive protein (CRP) is the most sensitive APP in dogs. Its normal physiological concentration is low but increases rapidly with inflammation or tissue destruction. Due to the fact that CRP has a relatively short half life in serum (6-8 hours) and a high response in diseased animals, it can be used as a valid measure of a systemic response to an initiating stimulus at the time of blood sampling. By taking serial measurements, objective information about the extent of the ongoing lesions in the patient can be obtained and therefore may be used as a prognostic indicator. The objective of this prospective observational study was to evaluate the association of serum CRP concentrations in puppies suffering from canine parvoviral enteritis with morbidity and mortality, and to determine the usefulness of CRP to predict duration of hospitalisation time. Seventy-nine client owned puppies naturally infected with canine parvovirus were included. Parvovirus infection was diagnosed on electron microscopic examination of faeces from the puppies. CRP was measured using an automated human C-Reactive Protein Turbidimetric Immunoassay (TIA), which has been validated for use in dogs. Serum CRP measurements were performed at admission, twice daily for the first 48 hours, then once daily until death or discharge. There was a positive association between odds of mortality and CRP concentration on admission, as well as 12 and 24 hours after admission (P=0.04,P=0.005 and P=0.003, respectively). Survival time was negatively associated with CRP concentration at 12 and 24 hours after admission (P=0.002and P=0.001, respectively). Among the survivors, length of hospitalisation was positively associated with CRP concentration at 12, 24 and 36 hours after admission (P=0.012, P=0.001 and P=0.002, respectively). Utility for CRP concentration to correctly differentiate between survivors and non-survivors at 24 hours after admission had a sensitivity and specificity of 78.7% and 86.7% respectively. Although serum CRP concentration is associated with outcome in puppies infected with canine parvovirus, when used alone it did not prove to be a good predictor of survival. / Dissertation (MMedVet)--University of Pretoria, 2012. / Companion Animal Clinical Studies / unrestricted

Purpose: The objective of this thesis is to evaluate clinical studies that have used oncolytic viruses as treatment and to compare their treatment-outcomes on patients with malignant glioma. Method: This thesis is a systematic literature review where PubMed has been used as the database for data collection. Two searches were done using the search phrases oncolytic virus AND Glioma and oncolytic virus AND brain tumor. Several of the articles showed up multiple times in different searches. After having applied the inclusion criteria, ten of the seventeen articles were removed. Remaining were seven articles used for the thesis. Results: The study conducted by Forsythe et al., using reovirus showed the median overall survival (OS) to be 21 weeks and the median time to progression (TTP) was 4.3 weeks. The study conducted by Kicielinski et al., using REOLYSIN showed the median OS to be 140 days. Median TTP was 61 days. The study conducted by Geletneky et al., 2017 was the first dose-escalating clinical trial for the use of H-1 parvovirus. The median TTP was 111 days and the median OS was 464 days. The study conducted by Lang et al., DNX-2401 was used and in group A the median OS time was 9.5 months. In group B the median OS in the group was 13 months. In another example of an oncolytic adenovirus is ONYX-015, the median TTP after treatment for all patients was 46 days. The median OS for patients diagnosed with glioblastoma multiforme was 4.9 months and for patients with anaplastic astrocytoma and anaplastic oligodendroglioma was 11.3 months across. In a study conducted by Freeman et al. using newcastle disease virus, the OS ranged from 3-66 weeks from the start of treatment and TTP ranged from 2-53 weeks. The study conducted by Markert et al., the median OS from treatment with G207 was 7.5 months. The median TTP was around 2.5 months. Conclusion: Oncolytic viruses are promising agents for treatment against malignant gliomas. No definite outcomes of the treatment could be concluded, however, the median survival was extended in certain cases. The patients tolerated the oncolytic viruses well with no adverse effects correlated with the treatments. There are currently more virus vectors being tested as new developments are needed in this field.

Excerpt: Tell patients that parvovirus infections before 20 weeks' gestation confer a risk of fetal morbidity and mortality as high as 16%, but don't significantly increase long-term developmental sequelae.

Background: Persistent anemia has been described in kidney transplant (KTx) recipients with parvovirus B19 virus infection. However, the epidemiology of parvovirus B19 and parvovirus B19-related anemia after KTx remains unclear. We conducted this systematic review (1) to investigate the incidence of parvovirus B19 infection after KTx and (2) to assess the incidence of parvovirus B19 among KTx patients with anemia. Materials and Methods: A systematic review was conducted in EMBASE, MEDLINE, and Cochrane databases from inception to March 2019 to identify studies that reported the incidence rate of parvovirus B19 infection and/or seroprevalence of parvovirus B19 in KTx recipients. Effect estimates from the individual studies were extracted and combined using random-effects, generic inverse variance method of DerSimonian and Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42019125716). Results: Nineteen observational studies with a total of 2108 KTx patients were enrolled. Overall, the pooled estimated seroprevalence of parvovirus B19 immunoglobulin G was 62.2% (95% confidence interval [CI]: 45.8%-76.1%). The pooled estimated incidence rate of positive parvovirus B19 DNA in the 1st year after KTx was 10.3% (95% CI: 5.5%-18.4%). After sensitivity analysis excluded a study that solely included KTx patients with anemia, the pooled estimated incidence rate of positive parvovirus B19 DNA after KTx was 7.6% (95% CI: 3.7%-15.0%). Among KTx with anemia, the pooled estimated incidence rate of positive parvovirus B19 DNA was 27.4% (95% CI: 16.6%-41.7%). Meta-regression analysis demonstrated no significant correlations between the year of study and the incidence rate of positive parvovirus B19 DNA (P = 0.33). Egger's regression asymmetry test was performed and demonstrated no publication bias in all analyses. Conclusion: The overall estimated incidence of positive parvovirus B19 DNA after KTX is 10.3%. Among KTx with anemia, the incidence rate of positive parvovirus B19 DNA is 27.4%. The incidence of positive parvovirus B19 DNA does not seem to decrease overtime.

Made available in DSpace on 2015-03-26T13:46:45Z (GMT). No. of bitstreams: 1 texto completo.pdf: 191521 bytes, checksum: 8cc1697b6f7161f0189c3b17dfab9fa4 (MD5) Previous issue date: 2005-03-11 / Observations of clinical cases suspected of canine parvovirus attended at the Veterinary Hospital at the Federal University of Viçosa indicate that the dogs vaccinated in stores which commercialize agropecuary products showed a greater frequency of the disease compared to the ones vaccinated at veterinary clinics. The objective of this study is the evaluation of the answer to the vaccines commercialized in different stores and following or not the vaccination protocol indicated by the literature, the antibody titers against the canine parvovirus in dogs serum in the urban area of the city of Viçosa-MG was determined. Blood serum sample was obtained from each of the 150 selected dogs. These animals were healthy and were from six months to six years old. The animals belong to several breeds and both sex. The dogs were selected following pre-established characteristics to form five groups of 30 animals each: A) dogs vaccinated in veterinary clinics following the literature patterns; B) dogs vaccinated in veterinary clinics not following the indicated protocol; C) dogs vaccinated in agropecuary product stores following the indicated protocol; D) dogs vaccinated in agropecuary product stores not following the indicated protocol; E) dogs not vaccinated. The antibody titers were measured in each animal serum through the hemagglutination inhibition test. According to the results of this study, it was concluded that the vaccination against canine parvovirus is important, considering the difference between the titers of vaccinated and non-vaccinated dogs. Furthermore dogs vaccinated in veterinary clinics are more protected than that vaccinated in agropecuary product stores, mainly if this vaccination followed the literature patterns. / Observações de casos clínicos suspeitos de parvovirose, atendidos no Hospital Veterinário da Universidade Federal de Viçosa, indicam que os cães vacinados em lojas que comercializam produtos agropecuários apresentam maior freqüência da doença, quando comparados aos cães vacinados em clínicas veterinárias. Com o objetivo de avaliar a resposta às vacinas comercializadas em diferentes estabelecimentos e seguindo ou não o protocolo de vacinação indicado pela literatura, foi determinado o título de anticorpos contra a parvovirose no soro de cães da área urbana do município de Viçosa-MG. Para tanto, uma amostra de soro sanguíneo foi obtida de cada um dos 150 cães selecionados. Estes animais estavam sadios e tinham entre seis meses e seis anos de idade. Os animais pertenciam a diversas raças e eram de ambos os sexos. Os cães foram selecionados segundo características pré-estabelecidas para compor cinco grupos de 30 animais: A) cães vacinados em clínicas veterinárias, seguindo o protocolo indicado na literatura; B) cães vacinados em clínicas veterinárias, não seguindo o protocolo indicado; C) cães vacinados em lojas de produtos agropecuários, seguindo o protocolo indicado; D) cães vacinados em lojas de produtos agropecuários, não seguindo o protocolo indicado; E) cães não vacinados. O título de anticorpos foi mensurado no soro de cada animal, por meio do teste de inibição da hemaglutinação. De acordo com os resultados deste estudo, pôde-se concluir que a vacinação contra parvovirose é importante, considerando a diferença encontrada entre o título de anticorpos dos cães vacinados e não vacinados. Além disso, os cães vacinados contra parvovirose em clínicas veterinárias ficaram mais bem protegidos do que aqueles que foram vacinados em lojas de produtos agropecuários, principalmente quando essa vacinação foi realizada de acordo com o protocolo indicado pela literatura.

Das porzine Parvovirus (PPV), 2013 vom International Committee on taxonomy of Viruses (ICTV) in ungulate Protoparvovirus 1 umbenannt, ist ein unbehülltes, einzelsträngiges DNA Virus und gehört innerhalb der Familie Parvoviridae zur Subfamilie Parvovirinae. Es ist weltweit in allen Bereichen der Schweinehaltung endemisch und verursacht große wirtschaftliche Verluste in den Betrieben (TRUYEN und STRECK 2012). Anders als die verwandten caninen und felinen Parvoviren (seit 2013 arnivore Protoparvovirus 1) ist es nicht durch zum Teil tödlich verlaufende Durchfallerkrankungen, sondern durch Fruchtbarkeitsstörungen wie Abort, Mumifikation und Unfruchtbarkeit, auch bekannt als SMEDI – Syndrom (Stillbirth = Totgeburt, Mummification =Mumifikation, Embryonic Death = embryonaler Tod und Infertility = Unfruchtbarkeit), gekennzeichnet. Die Schwere des Verlaufs hängt dabei wesentlich vom Zeitpunkt sowie von dem, für die Infektion verantwortlichen Isolats ab. Als besonders gefährdet gelten ungeimpfte Jungsauen, die innerhalb der ersten 70 Tage der Trächtigkeit in Kontakt mit dem Virus treten. Das Virus verfügt über eine ausgesprochen hohe Tenazität gegenüber äußeren Einflüssen. Es ist hitzestabil, unempfindlich gegenüber pH-Werten zwischen 3-9 sowie äther- und chloroformresistent (CARTWRIGHT und HUCK 1967, MAYR et al. 1968, JOHNSON und COLLINGS 1969, BACHMANN 1970, MORIMOTO 1972). Einmal im Bestand bleibt es somit über Monate infektiös. Es stehen für die Bekämpfung nur wenige Mittel zur Verfügung. Eine entscheidende Möglichkeit ist die Einhaltung eines strikten Impfregimes, wobei Impfstoffe zum Einsatz kommen, die seit etwa 3 Jahrzehnten auf den gleichen inaktivierten Virus-Isolaten beruhen. In den letzten zehn Jahren wurden zunehmend neue Isolate entdeckt, die sich, wie das hochvirulente Isolat Kresse und das wenig virulente Isolat NADL2, nur in wenigen Aminosäuren unterscheiden. Zum Teil weisen sie aber gravierende Unterschiede in ihrer Pathogenität auf. Daraus ergeben sich neben dem dringenden Rat zur Beobachtung der aktuellen Entwicklung mehrere Fragen hinsichtlich der zukünftigen Handhabung des Virus (SOARES et al. 2003, ZIMMERMANN et al. 2006). So sollte geklärt werden: • wie verbreitet sind diese neuen Isolate • was könnte ihre Entwicklung begünstigt haben • wie effizient ist der Schutz, den herkömmliche Impfstoffe gegen die neuen Isolate bieten • kann eines der Isolate eine Grundlage für einen neuen, effizienteren Impfstoff liefernDiese Dissertation umfasst insgesamt drei Veröffentlichungen, welche versuchen, die gestellten Fragen zu beantworten. Im ersten Artikel wird die Wirksamkeit eines neuen Impfstoffes auf Grundlage des hochvirulenten, vorherrschenden Isolat 27a untersucht. Im zweiten Manuskript wird mit Hilfe von in vitro- und in silico- Modellen die Populationsdynamik demonstriert. Die dritte Veröffentlichung widmet sich der Beschreibung der neuen Parvotypen (PPV2, PPV3 und PPV4), welche aus Herzen und Tonsillen von deutschen, klinisch gesunden Schlachtschweinen isoliert werden konnten.

Auf dem Gebiet der Veterinärmedizin wird in Deutschland die Desinfektionsmittelprüfung nach den Richtlinien der Deutschen Veterinärmedizinischen Gesellschaft e.V. (DVG) durchgeführt. Diese Richtlinien realisieren derzeit eine Viruzidieprüfung nur für den Bereich Tierhaltung. Daher wurde in dieser Arbeit eine praxisnahe Methodik zur Prüfung der viruziden Wirksamkeit von Desinfektionsmitteln für den Bereich der Lebensmittelproduktion und der tierärztlichen Praxis entwickelt. Neben dem Einsatz von zwei relevanten Prüfviren, erfolgte die Prüfung der viruziden Wirksamkeit anhand fünf verschiedener chemischer Grundsubstanzen. Um praxisähnliche Bedingungen zu simulieren, wurden unterschiedliche Belastungssubstanzen und Prüftemperaturen zur Testung herangezogen. Die gewonnenen Erkenntnisse können somit auf dem Gebiet der Viruzidieprüfung in zukünftige Neufassungen der DVG-Richtlinie berücksichtigt werden.

Background: Although infectious diseases are less common in high-income countries compared to low-income countries, they should still be seriously considered as a relevant public health issue. Some professions, such as healthcare workers, laboratory workers, and care providers may be at a particularly high risk of acquiring infections. In Germany, work-related infectious diseases are after skin diseases, the most common cause of occupational diseases reported to the Institution for Statutory Social Accident Insurance and Prevention in the Health Care and Welfare Services (BGW). An occupational disease, as defined by the WHO, is “any disease contracted primarily as a result of an exposure to risk factors arising from work activity”, although this definition varies between countries. In order for infections to be recognized as an occupational disease, either the identification of an index case is needed or it must be shown that the likelihood in which a particular case of illness was attributable to the occupation: the probability of causation must be greater than 50% (the “more-likely-than-not” rule). A general “rule-of-thumb” is to equate the probability of causation of 50% with a relative risk of disease equal to two (the “doubling of the risk”). This principle is used by many countries for the recognition of an occupational disease. Few studies have concentrated on the risk of infectious disease in daycare workers, who may be at higher risk than the general population due to their frequent and close contact to young children. Research questions: The primary aim of this review was to summarize the evidence on the relationship between being a daycare worker working with children and the possible increased risk for infections not preventable by vaccines. Furthermore, research gaps were to be identified. Finally, the implications for practice and health policy based on the evidence were to be described. Methods: For the systematic reviews with meta-analysis, the Medline and Embase databases were searched using search strings defined according to the Population, Exposure, Comparison, and Outcomes (PECO) applicable to the research questions in order to find studies on vaccine non-preventable infections in daycare workers published since 2000. The search hits were evaluated using predefined inclusion and exclusion criteria by two independent reviewers. A separate manual search was performed by reviewing the reference lists of key articles and systematic reviews. The “citation tracking factor” by Google scholar was used to find additional relevant studies. The resulting studies were extracted and were assessed in eight risk of bias domains for the judgement of study quality. With a meta-analysis, the pooled risk of infections for daycare workers compared to the general or a reference population was calculated. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: After evaluating the 6879 records, ten methodologically adequate studies were identified regarding parvovirus B19 infection (four studies) and cytomegalovirus (CMV) infection (six studies). No adequate studies on other infections were found. For parvovirus B19 infection, three cross-sectional studies and one retrospective cohort study were identified. The pooled parvovirus B19 seroprevalence in daycare workers was 70.3% (95% CI 59.5-80.4). Of three studies investigating the relative risk (RR) of parvovirus B19 infection on daycare workers, only one study evaluated seroconversion rates. There was an indication for an increased risk of parvovirus B19 infection for daycare workers compared to the unexposed population (RR = 1.12, 95% CI 0.98–1.27) using prevalence estimators. Furthermore, daycare workers had a higher parvovirus B19 seroconversion rate compared to the unexposed population (RR = 2.63, 95% CI 1.27–5.45) in the low risk of bias study. For CMV infection, five cross-sectional studies and one cohort study were included. The pooled CMV seroprevalence of daycare workers was 59.3% (95% CI 47.6-70.9). The four studies investigating risk of infection indicated an increased seroprevalence for daycare workers compared to a reference population (prevalence ratio, RR=1.54, 95% CI 1.33-1.77). No study evaluated CMV seroconversions for daycare workers. Conclusions: The findings suggest higher parvovirus B19 and cytomegalovirus seroprevalence for daycare workers compared to the general population. There is a need for longitudinal and higher-quality studies regarding infections not preventable by vaccines in daycare workers, as well as a need to study other infections for which daycare workers may be at higher risk. Nonetheless, when the actual occupational seroconversion risk is considered by taking into account the pre-occupational seroprevalences, the pooled relative risks for both parvovirus B19 and CMV infection are compatible with a doubled seroconversion risk corresponding to a probability of causation due to the occupation of at least 50%. Preventative efforts in the workplace are needed based on the legally required risk assessment at the workplace. Moreover, it is important to raise awareness of the potential risk of infection in women trying to conceive or during pregnancy. Recommendations to prevent infections in the day care center include using gloves and frequent handwashing after exposure to young children’s bodily fluids, cleaning surfaces, and avoiding intimate contact with young children if pregnant, although these measures alone may not completely protect the daycare worker from infection. Currently, in Germany, an employment ban for pregnant daycare workers depends on the federal state. To avoid occupational risks for pregnant daycare workers, scientific-based guidelines should be developed and applied consistently.

Auf dem Gebiet der Veterinärmedizin wird in Deutschland die Desinfektionsmittelprüfung nach den Richtlinien der Deutschen Veterinärmedizinischen Gesellschaft e.V. (DVG) durchgeführt. Diese Richtlinien realisieren derzeit eine Viruzidieprüfung nur für den Bereich Tierhaltung. Daher wurde in dieser Arbeit eine praxisnahe Methodik zur Prüfung der viruziden Wirksamkeit von Desinfektionsmitteln für den Bereich der Lebensmittelproduktion und der tierärztlichen Praxis entwickelt. Neben dem Einsatz von zwei relevanten Prüfviren, erfolgte die Prüfung der viruziden Wirksamkeit anhand fünf verschiedener chemischer Grundsubstanzen. Um praxisähnliche Bedingungen zu simulieren, wurden unterschiedliche Belastungssubstanzen und Prüftemperaturen zur Testung herangezogen. Die gewonnenen Erkenntnisse können somit auf dem Gebiet der Viruzidieprüfung in zukünftige Neufassungen der DVG-Richtlinie berücksichtigt werden.

Die entzündliche Kardiomyopathie ist eine heterogene Erkrankung. Die häufigste Ursache ist eine Virusinfektion, wobei Parvovirus B19 (B19V) der bedeutendste Erreger ist. In dieser Arbeit wurden potenzielle Therapie für die speziellen klinischen Verläufe und deren Phänotypen untersucht. In vitro konnte gezeigt werden, dass Telbivudin in B19V-infizierten/B19V-non-structural protein-1-stimulierten humanen mikrovaskulären Endothelzellen (HMEC-1) endothelial-protektiv wirkt. In einem klinischen Versuch wurden dann 4 Patienten, bei denen eine aktive Transkription des B19V nachgewiesen wurde, für 6 Monate mit Telbivudin behandelt. Alle Patienten verbesserten sich. Ein anderes klinisches Szenario stellt die schwere Entzündung des Myokards dar, welche gewöhnlich mit einer inaktiven/persistierenden Infektion des B19V verbunden ist. Eine Behandlung mit Immunsuppressiva ist hier umstritten, da eine Reaktivierung des Virus befürchtet wird. Um diesen Aspekt weiter zu untersuchen, würde eine Therapie mit Prednisolon in Kombination mit Azathioprin bei 51 B19V-positiven und 17 B19V-negativen Patienten angewandt. Beide Gruppen profitierten in ähnlichem Maße von der Kombinationstherapie, wobei sich die Virusmenge nicht signifikant veränderte. Bei B19V-negativen Patienten konnte über die Persistenz von CD20+ B-Lymphozyten in den EMBs die Untergruppe der „Steroide non-responder“ klassifiziert werden. Im weiteren Verlauf wurden 6 Patienten mit Rituximab, einem monoklonalen Antikörper, der spezifisch gegen CD20+ B-Lymphozyten gerichtet ist, behandelt. Hiervon zeigten 5 Patienten eine ausgezeichnete klinische Verbesserung. Ein Patient mit Myokarditis-induzierten kardiogenen Schock zeigt, dass die Entlastung des linken Ventrikels mittels eines Mikroaxialpumpensystems zu einer rapiden Abnahme der Entzündungszellen führt. Zusammenfassend liefert diese Arbeit Belege für die Wirksamkeit und die Notwendigkeit einer phänotypbasierten Behandlung bei der entzündlichen Kardiomyopathie. / Inflammatory cardiomyopathy is a heterogenous disease. Viral etiologies are the most common, with parvovirus B19 (B19V) being the most prominent culprit. Currently, no specific treatment for inflammatory cardiomyopathy exists. In this study, tailored treatment strategies were investigated as potential therapies for specific clinical scenarios. The antiviral drug telbivudine was investigated in the setting of EMB-proven B19V-associated inflammatory cardiomyopathy. In cell culture, telbivudine exhibited endothelial-protective effects on B19V-infected/B19V-non-structural protein-1-stimulated human microvascular endothelial cells (HMEC-1). Clinically, four B19V-positive patients improved following six-month telbivudine regimen in a single-patient use approach. The results were translated to the “PreTOPIC” clinical study, for further evaluation in a randomized placebo-controlled setting. In a different clinical scenario, severe myocardial inflammation is usually associated with inactive/persistent B19V. Here, the use of immunosuppression is controversial, fearing viral flare-up. We investigated combined prednisolone/azathioprine therapy in 51 B19V-positive and 17 B19V negative patients in a single-center observational study. Both groups gained similar benefit, while viral loads did not significantly vary. Among virus-negative phenotypes, EMB-proven CD20+ B lymphocyte persistence characterized a subgroup of steroid non-responders. In this cohort, six patients were treated with rituximab, a monoclonal antibody selectively targeting CD20+ B lymphocytes. Five patients showed outstanding clinical improvement parallel to CD20+ B lymphocyte depletion. Lastly, in a single case of myocarditis-induced cardiogenic shock, mechanical left ventricular unloading via axial flow pump proved to exert disease-modifying effects. In conclusion, this thesis provides evidence for the efficacy and need for phenotype-based inflammatory cardiomyopathy treatment.