Viral disinfection is important for medical facilities, the food industry, and the veterinary field, especially in terms of controlling virus outbreaks. Therefore, standardized methods and activity ...levels are available for these areas. Usually, disinfectants used in these areas are characterized by their activity against test organisms (i.e., viruses, bacteria, and/or yeasts). This activity is usually determined using a suspension test in which the test organism is incubated with the respective disinfectant in solution to assess its bactericidal, yeasticidal, or virucidal activity. In addition, carrier methods that more closely reflect real-world applications have been developed, in which microorganisms are applied to the surface of a carrier (e.g., stainless steel frosted glass, or polyvinyl chloride (PVC)) and then dried. However, to date, no standardized methods have become available for addressing genetically modified vectors or disinfection-resistant oncolytic viruses such as the H1-parvovirus. Particularly, such non-enveloped viruses, which are highly resistant to disinfectants, are not taken into account in European standards. This article proposes a new activity claim known as "virucidal activity PLUS", summarizes the available methods for evaluating the virucidal activity of chemical disinfectants against genetically modified organisms (GMOs) using current European standards, including the activity against highly resistant parvoviridae such as the adeno-associated virus (AAV), and provides guidance on the selection of disinfectants for pharmaceutical manufacturers, laboratories, and clinical users.
Background: To minimize the risk of disease transmission in cornea transplantation, donor screening for blood-derived viral infections is mandatory. Ideally, pre-mortem blood samples are used, but ...based on availability, cadaveric blood samples of cornea donors may also be used. However, serological and nucleic acid amplification tests (NATs) need to be validated for the use of cadaveric specimens. Methods: Hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV) 1/2, and Treponema pallidum (syphilis)-specific serological and/or NAT assays were validated on different platforms (Abbott Alinity i, Alinity m, Roche Cobas 6800, and Roche Cobas AmpliPrep/Cobas TaqMan (CAP/CTM)) using (un)spiked paired pre- and post-mortem cornea donor blood samples from the same individual (up to 23.83 h after death) of 28 individuals in accordance with the specifications of the German Federal Institute for Vaccines and Biomedicines (Paul-Ehrlich-Institut PEI). In addition, routinely HBV-, HCV- and HIV-PCR-negative tested post-mortem blood samples of 24 individuals were used to assess NAT specificity. Results: For the majority of serological parameters on the Abbott Alinity i (HBsAg, anti-HBc, anti-HBs, anti-HCV, anti-HIV, anti-HTLV 1/2, and anti-Treponema pallidum), ratios of generated test results of (un)spiked paired pre- and post-mortem blood samples differed ≤25%, with an agreement of qualitative pre- and post-mortem test results ranging from 91.2 to 100%. For NAT parameters (HBV, HCV, and HIV) on the Cobas 6800, Alinity m, and CAP/CTM, no significant deviation in virus concentrations (factor >5) of spiked pre- and post-mortem blood samples could be observed. Ct-values of corresponding internal controls did also not differ significantly (>1.5 Ct-values). In addition, no false-positive test results were generated when specificity was assessed. Conclusion: Overall, fluctuations of test results for serological and NAT parameters in pre- and post-mortem blood samples examined in this study, were only limited and within the range of what is also observed when routinely testing fresh patient specimens. We conclude that all examined assays are eligible for the screening of blood samples taken up to about 24 h after the occurrence of death.
The antiviral drugs tecovirimat, brincidofovir, and cidofovir are considered for mpox (monkeypox) treatment despite a lack of clinical evidence. Moreover, their use is affected by toxic side‐effects ...(brincidofovir, cidofovir), limited availability (tecovirimat), and potentially by resistance formation. Hence, additional, readily available drugs are needed. Here, therapeutic concentrations of nitroxoline, a hydroxyquinoline antibiotic with a favourable safety profile in humans, inhibited the replication of 12 mpox virus isolates from the current outbreak in primary cultures of human keratinocytes and fibroblasts and a skin explant model by interference with host cell signalling. Tecovirimat, but not nitroxoline, treatment resulted in rapid resistance development. Nitroxoline remained effective against the tecovirimat‐resistant strain and increased the anti‐mpox virus activity of tecovirimat and brincidofovir. Moreover, nitroxoline inhibited bacterial and viral pathogens that are often co‐transmitted with mpox. In conclusion, nitroxoline is a repurposing candidate for the treatment of mpox due to both antiviral and antimicrobial activity.
Coxsackie A16 (CA16) and Enterovirus 71 (EV71) are members of the picornaviridae family and are associated with hand, foot and mouth disease (HFMD), in rare cases also to acute neurological diseases. ...HFMD outbreaks have been reported from many parts of the world, especially Southeast Asia. The objective of the study was to analyze CA16 and EV71 seroepidemiologically in the population of Frankfurt/M., Germany. A total of 696 individuals (349 males and 347 females, divided into seven different age groups, 1-4, 5-9, 10-14, 15-19, 20-39, 40-59 and >60 years) were tested for serum antibodies against CA16 and EV71 by the use of a microneutralization test. Sera were collected at the Frankfurt university hospital from patients suffering from other diseases between March and September 2006. CA16 and EV71 infections were observed to be widely present in the population. The age-adjusted seroprevalence for individuals ≥1 year was found to be 62.9% for CA16 and 42.8% for EV71 without a gender-specific significant difference. Only 12.0 and 27.0% of the children aged 1-4 had antibodies to EV71 and CA16, respectively - indicating that 88 and 73% of the children in this age group were susceptible to the infection. A total of 213 individuals (30.6%) was seropositive for both viruses, 303 (43.5%) showed neutralizing antibodies (NtAb) to at least one of the two viruses. A total of 180 individuals (25.9%) revealed no antibodies. High CA16 and EV71 antibody titers were found especially in the age group of the 10- to 14-year-olds, without gender-specific difference. The seroprevalence study demonstrates a common spread of CA16 and EV71 in Germany, but a relatively high susceptibility of the younger population to CA16 and EV71. Obviously, the manifestation rate, i.e., distinct disease of these infections is low.
Disinfection measures have become more important as a result of the COVID-19 pandemic in Germany. The increased need for disinfectants at the beginning of the pandemic required temporary legal ...regulations in order to provide a sufficient quantity of products for the necessary disinfection in the medical sector on the one hand and for the additional demand in the population on the other. For this purpose, the Federal Institute for Drugs and Medical Devices (BfArM) and the Federal Institute for Occupational Safety and Health (BAuA) issued a general ruling, which is explained in more detail in this article. The focus was on measures for hygienic hand disinfection. However, other applications such as surface disinfection in relation to pandemic respiratory diseases are also addressed. The experience gained in ensuring the supply of disinfectants that are effective and safe to use should be used to prepare for further pandemics.
Vaccinia virus strain Lister Elstree (VACV) is a test virus in the DVV/RKI guidelines as representative of the stable enveloped viruses. Since the potential risk of laboratory-acquired infections ...with VACV persists and since the adverse effects of vaccination with VACV are described, the replacement of VACV by the modified vaccinia Ankara strain (MVA) was studied by testing the activity of different chemical biocides in three German laboratories.
The inactivating properties of different chemical biocides (peracetic acid, aldehydes and alcohols) were tested in a quantitative suspension test according to the DVV/RKI guideline. All tests were performed with a protein load of 10% fetal calf serum with both viruses in parallel using different concentrations and contact times. Residual virus was determined by endpoint dilution method.
The chemical biocides exhibited similar virucidal activity against VACV and MVA. In three cases intra-laboratory differences were determined between VACV and MVA - 40% (v/v) ethanol and 30% (v/v) isopropanol are more active against MVA, whereas MVA seems more stable than VACV when testing with 0.05% glutardialdehyde. Test accuracy across the three participating laboratories was high. Remarkably inter-laboratory differences in the reduction factor were only observed in two cases.
Our data provide valuable information for the replacement of VACV by MVA for testing chemical biocides and disinfectants. Because MVA does not replicate in humans this would eliminate the potential risk of inadvertent inoculation with vaccinia virus and disease in non-vaccinated laboratory workers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Omeprazole was shown to improve the anti-cancer effects of the nucleoside analogue 5-fluorouracil. Here, we combined omeprazole with the antiviral nucleoside analogues ribavirin and acyclovir. ...Omeprazole did not affect the antiviral effects of ribavirin in non-toxic concentrations up to 80 μg/mL but increased the acyclovir-mediated effects on herpes simplex virus 1 and 2 (HSV-1 and -2) replication in a dose-dependent manner. Omeprazole alone reduced HSV-1 and -2 titers but not HSV-induced formation of cytopathogenic effects (CPE) at concentrations ≥40 μg/mL. However, it exerted substantially stronger effects on acyclovir activity and also increased acyclovir activity at lower concentrations that did not directly interfere with HSV replication. Omeprazole 80 μg/mL caused a 10.8-fold (Vero cells) and 47.7-fold (HaCaT cells) decrease of the acyclovir concentrations that reduced HSV-1-induced CPE formation by 50% (IC
). In HSV-2-infected cells, omeprazole 80 μg/mL reduced the acyclovir IC
by 7.3- (Vero cells) and 12.9-fold (HaCaT cells). In HaCaT cells, omeprazole 80 μg/mL reduced the HSV-1 titer in the presence of acyclovir 1 μg/mL by 1.6 × 10
-fold and the HSV-2 titer in the presence of acyclovir 2 μg/mL by 9.2 × 10
-fold. The proton pump inhibitors pantoprazole, rabeprazole, lansoprazole, and dexlansoprazole increased the antiviral effects of acyclovir in a similar fashion as omeprazole, indicating this to be a drug class effect. In conclusion, proton pump inhibitors increase the anti-HSV activity of acyclovir and are candidates for antiviral therapies in combination with acyclovir, in particular for topical preparations for the treatment of immunocompromised individuals who are more likely to suffer from severe complications.
Purpose
Exposures to bloodborne pathogens pose a serious risk to dental healthcare workers (DHCW). Despite improved methods of preventing exposures like needlestick injuries (NSI), occupational ...exposures still continue to occur. The purpose of this study was to evaluate the incidence of occupational exposures to patient body fluids among German DHCW, to assess the rate of reporting of such incidents, and to evaluate the association of various factors with these exposures.
Methods
Data was obtained through an anonymous questionnaire.
Results
Our study confirms that occupational skills are an important factor concerning NSI. It turned out that dental students (0.74 NSI p. a.) had nearly twice the number of NSI compared with dentists with more or less than 10 years working experience (0.42, 0.49 NSI p. a., respectively,
P
< 0.0001). Overall, 54.3% (
n
= 144/265) of respondents had sustained at least one NSI in their professional life. Only 28.5% of injured dental students and DHCW reported all of their NSI, the main reason (19.1%) for not reporting NSI was little or no perception of risk on behalf of the respondent. One-fourth of respondents were not wearing a mask and 55.6% were not wearing protective goggles during their last occupational exposures.
Conclusions
Occupational exposure to blood or body fluids is a common problem among DHCW and dental students. Measures must be adopted by official institutions, public health service, occupational health association and universities in order to reverse this situation.
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