Efficacy of a Mouthwash Containing CHX and CPC in SARS-CoV-2-Positive Patients: A Randomized Controlled Clinical Trial.

Soon after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, preprocedural mouthwashes were recommended for temporarily reducing intraoral viral load and infectivity of individuals potentially infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to protect medical personnel. Particularly, the antiseptic cetylpyridinium chloride (CPC) has shown virucidal effects against SARS-CoV-2 in vitro. Therefore, the aim of this randomized controlled clinical trial was to investigate the efficacy of a commercially available mouthwash containing CPC and chlorhexidine digluconate (CHX) at 0.05% each in SARS-CoV-2-positive patients as compared to a placebo mouthwash. Sixty-one patients who tested positive for SARS-CoV-2 with onset of symptoms within the last 72 h were included in this study. Oropharyngeal specimens were taken at baseline, whereupon patients had to gargle mouth and throat with 20 mL test or placebo (0.9% NaCl) mouthwash for 60 s. After 30 min, further oropharyngeal specimens were collected. Viral load was analyzed by quantitative reverse transcriptase polymerase chain reaction, and infectivity of oropharyngeal specimens was analyzed by virus rescue in cell culture and quantified via determination of tissue culture infectious doses 50% (TCID50). Data were analyzed nonparametrically (α = 0.05). Viral load slightly but significantly decreased upon gargling in the test group (P = 0.0435) but not in the placebo group. Viral infectivity as measured by TCID50 also significantly decreased in the test group (P = 0.0313), whereas there was no significant effect but a trend in the placebo group. Furthermore, it was found that the specimens from patients with a vaccine booster exhibited significantly lower infectivity at baseline as compared to those without vaccine booster (P = 0.0231). This study indicates that a preprocedural mouthwash containing CPC and CHX could slightly but significantly reduce the viral load and infectivity in SARS-CoV-2-positive patients. Further studies are needed to corroborate these results and investigate whether the observed reductions in viral load and infectivity could translate into clinically useful effects in reducing COVID-19 transmission (German Clinical Trials Register DRKS00027812).

Are histopathological findings of diagnostic value in native valve endocarditis?

BACKGROUND: Optimal management of infective endocarditis (IE) depends on the early detection of IE-causing pathogens and on appropriate antimicrobial and surgical therapy. The current guidelines of the European Society of Cardiology (ESC) recommend histopathological examination as the gold standard for diagnosing IE Habib et al. (Eur Heart J 30:2369-2413, 2005). We hypothesize that histopathological findings do not provide additional information relevant to clinical decision-making. METHODS: We retrospectively reviewed a cohort of patients who had undergone surgery for native valve endocarditis (NVE) at the University Hospital Regensburg between September 1994 and February 2005. All episodes of intraoperatively confirmed endocarditis during this period were included in the study. Data were retrieved from surgical records, microbiological and histopathological reports, and medical files of the treating as well as admitting hospital. Pathogens were correlated with the site of manifestation of the affected heart valve and with clinical and histopathological findings. RESULTS: A total of 163 episodes of NVE were recorded and entered into our study for analysis. The valves affected were the aortic valve (45 %), the mitral valve (28 %), the aortic and mitral valve (22 %), and other valves (5 %). IE-causing pathogens were Staphylococcus aureus (22 %), viridans streptococci (18 %), enterococci (10 %), streptococci other than Streptococcus viridans (9 %), coagulase-negative staphylococci (5 %), miscellaneous pathogens (4 %), and culture-negative endocarditis (33 %). Infection with S. aureus was associated with high rates of sepsis, septic foci, and embolic events, while patients with enterococcal IE showed the highest rate of abscesses. Mortality rate in all subgroups was low without significant differences. However, histopathological findings correlated poorly with the pathogen involved and showed only few significant associations that were without clinical relevance. CONCLUSIONS: The clinical presentation of IE depends on the pathogen involved. Among the episodes of NVE examined, the histopathological examination of resected heart valves did not show any pathogen-specific morphological patterns and therefore did not provide any additional information of clinical value. Based on our findings, we recommend complementary cultures of the resected materials (valve tissue, thrombotic material, pacer wire) and implementation of molecular diagnostic methods (e.g., broad-range PCR amplification techniques) instead of histopathological analyses of resected valve tissue.

Redescription of Heligmosomoides neopolygyrus, Asakawa and Ohbayashi, 1986 (Nematoda: Heligmosomidae) from a Chinese rodent, Apodemus peninsulae (Rodentia: Muridae); with comments on Heligmosomoides polygyrus polygyrus (Dujardin, 1845) and related species in China and Japan.

Heligmosomoides neopolygyrus, Asakawa and Ohbayashi, 1986 (Nematoda, Heligmosomoidea) is redescribed from Apodemus peninsulae from Rangtang, Sichuan, China. A morphological review of the Heligmosomoides spp. belonging to the "polygyrus line" proposed by Asakawa (1988) is made using new characters. This enabled us to distinguish two subspecies in Mus musculus (Heligmosomoides polygyrus bakeri from Japan and H. p. polygyrus from China) and two valid species in Apodemus spp. (H. neopolygyrus from Japan (in A. peninsulae) and from China (in A. agrarius) and H. asakawae from China (in A. uralensis)). Three parasite species of A. agrarius and A. peninsulae, previously identified by Asakawa et al. (1993) as H. neopolygyrus, are considered to be Heligmosomoides incertae sedis. This is the first report of H. neopolygyrus in A. peninsulae from China.

[Suspected borreliosis - what's behind it?]. / Verdacht auf Borreliose - Was hat der Patient?

BACKGROUND AND OBJECTIVE: Borreliosis may be associated with unspecific symptoms and thus not only cause difficulties in diagnosis but also lead to overdiagnosis. PATIENTS AND METHODS: Data on 134 patients (mean age 47 [12 - 78] years, 51.5 % male) with suspected borreliosis presenting at the university hospital Regensburg were analyzed retrospectively. RESULTS: The majority of patients had been adequately treated for borreliosis previously. 34 patients (25.4 %) had proven or possible borreliosis, 20 patients (14.9 %) presented for consultation only. Regarding the remaining 80 patients (59.7 %), in 36 (45 %) a rheumatologic, orthopedic or neurologic disease was found as causal for the presenting symptoms, in 44 (55 %) no somatic disease could be diagnosed. CONCLUSION: A careful differential diagnosis seems mandatory in patients with suspected borreliosis and persistent complaints.

Description of a new species of Heligmosomoides (Nematoda: Heligmosomidae) parasitic in Microtus limnophius (Rodentia: Cricetidae) from Rangtang, Sichuan, China.

Heligmosomoides craigi n. sp. (Nematoda: Heligmosomoidea) is described from Microtus limnophilus Büchner, 1889 (Rodentia: Cricetidae) from Rangtang, Sichuan, China. It is related to H. protobullosus Asakawa, 1987 and H. longispiculum Tokobaev & Erkulov, 1966 both parasites of Microtus spp. from Japan and USSR, respectively by the following features: a ratio of spicule length/body length of more than 45% and rays 9 shorter than rays 10. The new species is differentiated by rays 8 being closed to rays 6 and 19-22 cuticular ridges versus 14 in H. protobullosus (synlophe not described in H. longispiculum). H. longicirratus (Schulz, 1954) also a parasite of Microtus sp. from the USSR is the most closely related species based on the number of cuticular ridges (20) and the ratio of spicule length/body length (48% versus 50%). There are no illustrations of this species and the female has not been described; for that reason, it is not possible to compare it accurately with our specimens.

Do lagomorphs play a relay role in the evolution of the Trichostrongyuna nematodes?

In order to confirm or refute the relay role of lagomorphs in the evolution of the Trichostrongylina (Nematoda), the following points were studied by summarizing previous works on the subject: the chronology of the life cycles (27 conducted in natural hosts, lagomorphs, ruminants or arvicolin rodents; 14 in experimental hosts); the parasitic phase in the experimental host and the adaptation involved; the migration of the parasites into the tissues of the host; the morphogenesis of larval stages and molecular phylogeny. These data confirm, in their entirety, that lagomorphs may be considered as "relay" hosts in the evolution of the Trichostrongylina.

[Clinical pathways--practical aid for the physician? Example: clarification of the suspicion of tuberculosis]. / Behandlungspfade--praktikable Hilfe für den behandelnden Arzt?: Beispiel: Abklärung bei Verdacht auf Tuberkulose.

Guidelines, clinical pathways and clinical algorithms are popular instruments nowadays to ensure quality as well as the economic efficiency of medical work. These terms themselves, however, are frequently defined only in a diffuse way. Thus, medical standard procedures often complicate clinical workflows more than to facilitate decision making in everyday life. In our department, feasible standardized approaches have been generated in the form of structured text documents, which on the one hand can aid clinical decision making at the bedside and on the other hand serve as medical sketches for the generation of operational treatment paths on an interdisciplinary level. Structure and content of such an instructional text are exemplified here using our standardized document for the diagnostic approach when tuberculosis is suspected.

Additional molecular evidence to support a sister taxon relationship between Heligmosomoidea and Molineoidea nematodes (Trichostrongylina).

Sequences of the first and second internal transcribed spacers of the ribosomal DNA were used to infer the evolutionary relationships of 19 species of parasitic nematode belonging to three superfamilies, Trichostrongyloidea, Molineoidea and Heligmosomoidea, within the sub-order Trichostrongylina. Analyses using maximum parsimony, maximum likelihood and neighbor-joining methods revealed strong statistical support for monophyly of each superfamily as defined on morphological criteria. Furthermore, in most analyses, there was also strong support for a sister taxon relationship between the Molineoidea and Heligmosomoidea, which supports the findings of a previous study based on partial LSU rDNA sequence data.

Development of Nematodirus spathiger (Nematoda, Molineoidea) in the rabbit and comparison with other Nematodirus spp parasites of ruminants.

The morphogenesis and chronology of the life cycle of Nematodirus spathiger (Railliet, 1896), a parasite of ruminants, were studied in detail in an experimental host. Twenty-four worm-free rabbits were each infected per os with N. spathiger larvae and were killed at 12 h after infection (12 HAI) and every day from 1 DAI to 23 DAI. By 12 HAI, all the larvae were exsheathed and present in the small intestine. The third moult occurred between 4 DAI and 5 DAI. The last moult occurred between 13 DAI and 16 DAI. The prepatent period lasted 21-24 days. The distribution of N. spathiger along the small intestine of the rabbit was assessed. The chronology of the life cycles was compared for various Nematodirus spp from ruminants in their natural hosts and in the rabbit (N. battus, N. spathiger).

["Tingling feet," forgetfulness, and progressive personality changes in a 63-year-old patient]. / "Fusskribbeln", Vergesslichkeit und progrediente Wesensveränderung bei einer 63-jährigen Patientin.

A 63-year-old female was admitted to the hospital with leg and forearm paresthesias. We found progressive ataxia, dementia, and psychosocial deterioration. The clinical symptoms, the neurologic and psychiatric abnormalities together with the inflammatory cerebrospinal fluid alteration and the cerebral magnetic resonance imaging changes suggested a paraneoplastic etiology. It was confirmed by paraneoplastic antineuronal antibodies in the patient's serum and the histological diagnosis of a small cell bronchial carcinoma. The prognosis of patients with paraneoplastic symptoms is the better the earlier a diagnosis is established and antitumor therapy is initiated.

Development of Trichostrongylus colubriformis and Trichostrongylus vitrinus, parasites of ruminants in the rabbit and comparison with Trichostrongylus retortaeformis.

The parasitic phase of development of both Trichostrongylus colubriformis and Trichostrongylus vitrinus, parasites of ruminants, was studied in detail in the rabbit. In T. colubriformis, the third moult appeared by 4 days after infection (DAI) and the last moult occurred between 10 and 11 DAI. In T. vitrinus, the third moult occurred between 8 and 11 DAI and the last one between 12 and 15 DAI. The prepatent period lasted 16-17 days for T. colubriformis and 20 days for T. vitrinus. The chronology of the life cycles and the distribution of the parasites along the small intestine for various Trichostrongylus spp. from lagomorphs and ruminants in the natural host or in the experimental host were compared. All of these biological parameters indicated a lower level of adaptation of T. vitrinus compared to the other species of Trichostrongylus. The results are fully compatible with the evolutionary scheme based on morphological analyses.

Intestinal migrations of Trichostrongylus retortaeformis (Trichostrongylina, Trichostrongylidae) in the rabbit.

Observations were made on histological sections of the stomach and small intestine of seven rabbits infected with Trichostrongylus retortaeformis and from one uninfected control rabbit. At 12h post-infection, larvae were found in the small intestine. At first, only a few larvae were observed entering the mucosa through capillaries of the stroma of villi; the majority of larvae remained in the intestinal lumen, within mucus of the crypts. We consider that the presence of the worms in the stroma is the result of a larval migration. From a phyletic point of view, this migration is interpreted as an ancestral memory of the pulmonary migration seen in the primitive Strongylida.

Life cycle of Trichostrongylus retortaeformis in its natural host, the rabbit (Oryctolagus cuniculus).

The chronology of the life cycle of Trichostrongylus retortaeformis (Zeder, 1800) (Nematoda, Trichostrongyloidea) is studied in its natural host Oryctolagus cuniculus. The free living period lasted 5 days at 24 degrees C. Worm-free rabbits were each infected per os with T. retortaeformis larvae. Rabbits were killed at 12 h post-infection (p.i.) and every day from one day to 13 days p.i. By 12 h p.i., all the larvae were exsheathed and in the small intestine. The third moult occurred between 3 and 5 days p.i. and the last moult between 4 and 7 days p.i. The prepatent period lasted 12 to 13 days. The patent period lasted five and a half months. The four known life cycles of species of Trichostrongylus in ruminants were compared with that of T. retortaeformis. No significant difference was found except in the duration of the prepatent period. These similarities in the life cycles confirm the previously formulated hypotheses on the relationship between the parasites of the two host groups (Durette-Desset, 1985).

The life cycle of Ohbayashinema erbaevae (Nematoda, Heligmosomoidea, Heligmosomidae) in Ochotona rufescens rufescens (Ochotonidae).

The morphogenesis and the chronology of the life cycle of Ohbayashinema erbaevoe Durette-Desset et al, 2000, a parasite of Ochotona daurica from Buriatia were studied in detail in an experimental host, Ochotona rufescens rufescens. Worm-free pikas were each infected per os with O. erbaevae larvae and were killed at one day post infection (DPI 1) and every 12 hours from 1.5 to 8 days post infection. By DPI 1, all the larvae were exsheathed and in the small intestine. The third moult occurred in 2.5-3.0 days. The last moult occurred in 4.0-4.5 days. The prepatent period was eight days and the patent period lasted between two and 12 weeks. The distribution of O. erbaevae along the small intestine of the pikas was assessed. For each experiment, a morphological description of the different stages of the life cycle was provided. The morphogenesis and the chronology of the life cycle of O. erbaevae appear to be identical with those of two other genera of the family of the Heligmosomidae, Heligmosomum Railliet & Henry, 1909 and Heligmosomoides Hall, 1916. They confirm that the three genera belong to the same family. The presence of an abortive posterior genital branch in the female of O. erbaevae, which represents the posterior part of the genital primordium of the didelphic females, supports the systematic position of the genus Ohbayashinema between the didelphic genus Citellinema Hall, 1916 and the monodelphic genera Heligmosomum and Heligmosomoides.

Morphogenesis and distribution of Trichostrongylus retortaeformis in the intestine of the rabbit.

The morphogenesis and the distribution along the digestive tract of Trichostrongylus retortaeformis(Zeder, 1800) (Nematoda) were studied in detail in one of its natural hosts, Oryctolagus cuniculus. Worm-free rabbits were each infected with T. retortaeformis larvae and were killed at 12 h post-infection (HPI) and on each day from 1 to 15 days post-infection (DPI). The distribution of worm populations along the small intestine was assessed. At the different dates of infection, more than 80% of the population was recovered from the first third of the intestine with more than 50% occurring in the first 30 cm. For each date, morphological descriptions of the different stages of the life cycle were also provided. In addition, adult worms collected from naturally infected rabbits from France were redescribed.

Internal transcribed spacer rDNA can be used to infer the phylogenetic relationships of species within the genus Nematodirus (Nematoda: molineoidea).

Sequences of the first internal transcribed spacer rDNA were characterised for four veterinary important species of gastrointestinal nematodes from the genus Nematodirus. The sequence data were combined with previously published data of the second internal transcribed spacer to determine whether these rDNA regions provided a suitable number of informative characters to determine the phylogenetic relationships of species within the genus. A total of 32 alignment positions of the first internal transcribed spacer data set and 33 characters from the second internal transcribed spacer data set were informative in phylogenetic analyses. Irrespective of whether the data from each spacer were analysed separately or combined, only one most parsimonious tree was produced, with the relationships of the four species fully resolved. In addition, several regions of conservatism in the first internal transcribed spacer sequence among the four Nematodirus species suggests that this rDNA region may also provide phylogenetic information for higher taxonomic levels within the Molineoidea.

Effect of antivenom on venom pharmacokinetics in experimentally envenomed rabbits: toward an optimization of antivenom therapy.

Antivenomous immunotherapy is still used empirically. To improve the efficacy and safety of immunotherapy, we studied the effects of administering antivenom antibodies (F(ab')2) on the pharmacokinetics of the Vipera aspis venom in rabbits. Free venom levels were measured by enzyme-linked immunosorbent assay and total concentrations were quantified by measuring the radioactivity of trichloroacetic acid-precipitable radioiodinated venom. The intravenous infusion of 125 mg of antivenom 7 h after intramuscular injection with 700 microg x kg(-1) of V. aspis venom produced a redistribution of the venom antigens from the extravascular to the vascular space. Moreover, anti-venom antibodies were able to neutralize the totality of venom antigens in the vascular space, because no free plasma venom was detectable by enzyme-linked immunosorbent assay within 15 min after antivenom injection. Similar effects were obtained after injection of 25 mg of antivenom; however, the venom was only partially neutralized with lower doses (5 and 2.5 mg). We further established that intravenous injection is the most efficient route for antivenom administration, and we examined the effects of early and late immunotherapy. Finally, the efficacy of Fab antibodies was compared with that of F(ab')2; the plasma redistribution and the immunoneutralization of the venom were lower than those induced after injection of the same dose of F(ab')2. The difference between the effects of F(ab')2 and Fab could be explained by the differential pharmacokinetics of the two fragments.