Search

Abstract Toxoplasma (T.) gondii is an obligate intracellular parasite with a worldwide distribution. Congenital infection can lead to severe pathological alterations in the brain. To examine the effects of toxoplasmosis in the fetal brain, pregnant guinea pigs are infected with T. gondii oocysts on gestation day 23 and dissected 10, 17 and 25 days afterwards. We show the neocortex to represent a target region of T. gondii and the parasite to infect neural progenitor cells (NPCs), neurons and astrocytes in the fetal brain. Importantly, we observe a significant reduction in neuron number at end-neurogenesis and find a marked reduction in NPC count, indicating that impaired neurogenesis underlies the neuronal decrease in infected fetuses. Moreover, we observe focal microglioses to be associated with T. gondii in the fetal brain. Our findings expand the understanding of the pathophysiology of congenital toxoplasmosis, especially contributing to the development of cortical malformations.

Abstract Background Toxoplasma gondii is an obligate intracellular parasite with a worldwide distribution. Congenital infection in humans and animals may lead to severe symptoms in the offspring, especially in the brain. A suitable animal model for human congenital toxoplasmosis is currently lacking. The aim of this study is to establish and validate the guinea pig as a model for human congenital toxoplasmosis by investigating the impact of the T. gondii infection dose, the duration of infection and the gestational stage at infection on the seroconversion, survival rate of dams, fate of the offspring, T. gondii DNA loads in various offspring tissues and organs and the integrity of the offspring brain. Methods Pregnant guinea pigs were infected with three different doses (10, 100, 500 oocysts) of T. gondii strain ME49 at three different time points during gestation (15, 30, 48 days post-conception). Serum of dams was tested for the presence of T. gondii antibodies using immunoblotting. T. gondii DNA levels in the dam and offspring were determined by qPCR. Offspring brains were examined histologically. Results We found the survival rate of dams and fate of the offspring to be highly dependent on the T. gondii infection dose with an inoculation of 500 oocysts ending lethally for all respective offspring. Moreover, both parameters differ depending on the gestational stage at infection with infection in the first and third trimester of gestation resulting in a high offspring mortality rate. The duration of infection was found to substantially impact the seroconversion rate of dams with the probability of seroconversion exceeding 50% after day 20 post-infection. Furthermore, the infection duration of dams influenced the T. gondii DNA loads in the offspring and the integrity of offspring brain. Highest DNA levels were found in the offspring brain of dams infected for ≥ 34 days. Conclusion This study contributes to establishing the guinea pig as a suitable model for human congenital toxoplasmosis and thus lays the foundation for using the guinea pig as a suitable animal model to study scientific questions of high topicality and clinical significance, which address the pathogenesis, diagnosis, therapy and prognosis of congenital toxoplasmosis. Graphical abstract

Summary: The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a significant threat to global health. While respiratory aerosols or droplets are considered as the main route of human-to-human transmission, secretions expelled by infected individuals can also contaminate surfaces and objects, potentially creating the risk of fomite-based transmission. Consequently, frequently touched objects such as paper currency and coins have been suspected as potential transmission vehicle. To assess the risk of SARS-CoV-2 transmission by banknotes and coins, we examined the stability of SARS-CoV-2 and bovine coronavirus, as surrogate with lower biosafety restrictions, on these different means of payment and developed a touch transfer method to examine transfer efficiency from contaminated surfaces to fingertips. Although we observed prolonged virus stability, our results indicate that transmission of SARS-CoV-2 via contaminated coins and banknotes is unlikely and requires high viral loads and a timely order of specific events.

Abstract Background The use of disinfectant wipes in hospitals is increasing over the last years. These wipes should be able to inactivate microorganisms including viruses on environmental surfaces and to prevent their transfer to clean areas. The European norm (EN) 16615:2015 describes a wiping process over four fields starting on the contaminated field 1 followed by fields 2–4 and back to the starting point (4-field test). This test method exclusively describes killing and transfer of vegetative bacteria and fungi by disinfectant wipes without measuring virucidal activities. Therefore, it was the aim of this study to use the existing test methodology additionally to evaluate virus inactivation by wipes. Methods The 4-field test was performed with four commercially available disinfectant wipes including the examination of the active solutions of these wipes with a reference wipe. Murine norovirus (MNV) as surrogate of human noroviruses, adenovirus (AdV) type 5 and polyomavirus SV40 (SV40) were chosen as test viruses. Results The per acetic acid (PAA)-based wipe (wipe A) was able to inactivate all three test viruses resulting in a four log10 reduction on test field 1, whereas the quaternary ammonium compound (QAC)-based products (wipes B and C) failed to reach such reduction. Both QAC-based wipes were able to inactivate SV40 and only the active solution of wipe B was effective against MNV. Another wipe with 2-propanol as active ingredient (wipe D) was not able to show a sufficient efficacy against all three test viruses. There was a good agreement between the results of the wipes and the corresponding fluids showing no influence of the material of wipes. Tests with the 2-propanol-based wipe D showed a transfer of all test viruses to the non-contaminated test fields 2–4. SV40 was additionally transferred by the QAC-based wipe C with 0.78% active ingredients to these additional fields. In all other cases no virus transfer to test fields 2–4 was observed. Finally, no virus could be detected in the PAA-based wipe A after usage in the 4-field test in contrast to the other wipes examined. Conclusions The successful performance of a 4-field test with viruses demonstrated that the existing wiping method with bacteria and fungi can be used in addition for measuring virucidal efficacy. The virus-inactivating properties of surface disinfectants could be evaluated therefore with a test simulating practical conditions with mechanical action resulting in more reliable data than the existing quantitative suspension tests and/or a carrier test without any mechanical action.

The synchrony, spatial distribution and causes of the African Humid Period termination at 5.5 ka remain debated. Here, the authors show that rapid aridification in Cameroon and the central Sahel-Sahara took place between 5.8–4.8 ka and was likely triggered by high- and mid-latitude cooling.

Abstract Background Various peracetic-acid (PAA)-based products for processing flexible endoscopes on the market are often based on a two-component system including a cleaning step before the addition of PAA as disinfectant. The peracetic acid concentrations in these formulations from different manufacturers are ranging from 400 to 1500 ppm (part per million). These products are used at temperatures between 20 °C and 37 °C. Since information on the virus-inactivating properties of peracetic acid at different concentrations and temperature is missing, it was the aim of the study to evaluate peracetic acid solutions against test viruses using the quantitative suspension test, EN 14476. In addition, further studies were performed with the recently established European pre norm (prEN 17111:2017) describing a carrier assay for simulating practical conditions using frosted glass. Methods In the first step of examination, different PAA solutions between 400 and 1500 ppm were tested at 20 °C, 25 °C, and 35 °C with three test viruses (adenovirus, murine norovirus and poliovirus) necessary for creating a virucidal action according to the European Norm, EN 14476. A second step for simulating practical conditions based on prEN 17111:2017 followed by spreading a test virus together with soil load onto a glass carrier which was immerged into a peracetic acid solution. A fixed exposure time of five minutes was used in all experiments. Results In the quantitative suspension test 1500 ppm PAA solution was needed at 35 °C for five minutes for the inactivation of poliovirus, whereas only 400 ppm at 20 °C for adeno- and murine norovirus were necessary. In the carrier assay 400 ppm peracetic acid at 20 °C were sufficient for adenovirus inactivation, whereas 600 ppm PAA were needed at 25 °C and 35 °C and 1000 ppm at 20 °C for murine norovirus. A PAA solution with 1000 ppm at 35 °C was required for complete inactivation of poliovirus. However, a dramatically decrease of titer after the drying and immerging could be observed. In consequence, a four log reduction of poliovirus titer could not be achieved in the carrier test. Conclusion In summary, 1500 ppm PAA at 35 °C was necessary for a virucidal action in the quantitative suspension test. After passing the requirements of the suspension test, additional examinations with adeno- and murine norovirus on glass carriers based on prEN 17111:2017 will not additionally contribute to the final claim of an instrument disinfectant for virucidal efficacy. This is due to the great stability of poliovirus in the preceded quantitative suspension test and the fact that poliovirus could not serve as test virus in the following carrier assay.