[COVID-19: epidemiology and mutations : An update]. / COVID-19: Epidemiologie und Mutationen : Ein Update.

Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enhance the spread and the infectiousness and decrease the protective effect of antibodies present after infection, vaccination or antibody treatment. The alpha variant (B.1.1.7), first seen in Kent/United Kingdom, has increased the R­value and therefore the infectiousness by 75%; however, the effectiveness of the vaccines against SARS-CoV­2 available in Germany seems to be only slightly impaired by these mutations. In the case of the beta variant (B.1.351), first described in South Africa, the neutralization ability of antibodies towards SARS-CoV­2 is decreased. The monoclonal antibodies bamlanivimab and etesivimab, which are used therapeutically, are ineffective. The AstraZeneca vaccine offers almost no protection against mild or moderate disease caused by the beta variant. The gamma variant (P.1 or B.1.1.28.1), which was first found in Brazil, is probably 1.7-2.6 times more transmissible than previous virus strains circulating in Brazil. In addition to the infectiousness, the mortality risk of the gamma variant also seems to be increased between 1.2 and 1.9-fold in adults and between 5 and 8-fold in young persons. The delta variant (B.1.617), first described in India, is now dominant in most countries. It is 50% more infectious than the alpha variant, and the protective effect of vaccinations against symptomatic disease can be decreased (Biontech: delta variant 88%, alpha variant 93.7%; AstraZeneca: delta variant 67%, alpha variant 74.5%). Furthermore, the course of the disease with the delta variant is often more severe than with the wild type. Disease courses with the delta variant are less severe in vaccinated than in nonvaccinated persons, and fatal outcomes are substantially rarer. A high vaccination rate is essential in order to approach herd immunity and to bring the pandemic under control. Even where the protective effect towards mild or moderate disease is decreased, as a rule, vaccination still offers excellent protection against life-threatening and fatal disease courses.

[Multiple sclerosis and hepatitis B vaccination : What does the verdict of the European Court of Justice on liability after vaccination mean?] / Multiple Sklerose und Hepatitis-B-Impfung : Was bedeutet das Urteil des EuGH zur Haftung nach Impfung?

In June 2017 the European Court of Justice (ECJ) issued a verdict on the legal assessment of the association between hepatitis B immunization and the subsequent manifestation of multiple sclerosis (MS). This led to a high level of insecurity in the medical field as well as the normal population, especially in MS patients. The aim of this article is to briefly present the evidence-based medical facts and in particular to clearly highlight the legal aspects of the abovenamed ECJ verdict.

[Infection risks in multiple sclerosis therapy by infusion of disease modifying drugs]. / Infektiologische Risiken in der Multiple-Sklerose-Therapie durch infundierbare Immuntherapeutika.

The increased risk of developing infections when using disease-modifying drugs for treatment of multiple sclerosis (MS) is a major challenge in the daily clinical routine. In the growing field of treatment options specific knowledge of treatment-related risks of infections and appropriate preventive and countermeasures is mandatory. Current clinical experience shows that an individual risk stratification is necessary when choosing treatment options and while monitoring during and after treatment administration. The determination of the individual risk of infection in the context of serial use of disease-modifying drugs remains a challenging issue. In addition to the mechanisms of action, the warning notices and current recommendations on infection prophylaxis when using intravenous disease-modifying drugs, such as alemtuzumab, natalizumab and mitoxantron, are presented in detail.

[Immunotherapy and infectious issues in multiple sclerosis. Self-injectable and oral drugs for immunotherapy]. / Immuntherapien und infektiologische Probleme bei Multipler Sklerose. Selbst injizierbare und orale Immuntherapeutika.

Immunotherapy is generally associated with an increased risk for the development of infections. Due to the continuously expanding spectrum of new and potent immunotherapy treatment options for multiple sclerosis (MS), this article describes the currently known risks for treatment-related infections and the current recommendations for prevention of corresponding problems with drugs used in treatment strategies for MS and their mechanisms of action. The new treatment options in particular are linked to specific and severe infections; therefore, intensive and long-lasting monitoring is required before, during and after treatment and multidisciplinary surveillance of patients is needed. This article gives a detailed review of drug-specific red flags and current recommendations for the prophylaxis of infections associated with treatment of relapsing-remitting MS and when using self-injectable and oral disease-modifying immunotherapeutic drugs.

[Vaccinations in patients with immunodeficiency or immunosuppressive therapy]. / Impfen bei Immundefekten oder medikamentöser Immunsuppression.

Patients with immunodeficiency and patients under immunosuppressive therapy have an increased risk of infectious diseases. Vaccination strategies are needed to protect them from preventable diseases. The underlying disease and severity of the immune impairment may have influence on indications and contra-indications of vaccines. Inactivated vaccines can be administered safely according to the current recommendations of the Permanent Commission on Vaccinations of the Robert-Koch-Institut in Berlin, Germany (STIKO). Depending on the severity of the immune dysfunction, antibody response to vaccinations varies. Where possible, the antibody response following vaccinations should be tested. Previously, attenuated live vaccines were considered to be strictly contra-indicated in immunocompromised patients. Today, the administration of attenuated live vaccines is thought to be possible, depending on the degree and type of immunodeficiency or immunosuppression of the individual.

Ciprofloxacin reduces the risk of hemolytic uremic syndrome in patients with Escherichia coli O104:H4-associated diarrhea.

BACKGROUND: Whether antibiotic treatment in patients with enterohemorrhagic Escherichia coli (EHEC)-associated diarrhea influences the risk of hemolytic uremic syndrome (HUS) has still to be elucidated. PATIENTS AND METHODS: During the EHEC epidemic which occurred in northern Germany in spring 2011, 24 patients with E. coli O104:H4 infection were treated at our hospitals, 19 of whom developed HUS. The use of antibiotics before and after the onset of HUS was documented, and the outcome in patients with and without antibiotic treatment was evaluated. RESULTS: Of the 24 patients with EHEC-associated diarrhea, seven received antibiotics before any signs of HUS were present (ciprofloxacin, cefotaxime, amoxicillin and/or metronidazole). Four of these seven patients (57 %) and 15 of the 17 patients (88 %) who were treated without antibiotics developed HUS (p = 0.12). Microbiological testing showed all E. coli O104:H4 to be extended-spectrum beta lactamase producers and thus susceptible only to fluoroquinolones, aminoglycosides and carbapenems. Two of the five patients (40 %) treated with ciprofloxacin and 17 of the 19 patients (89 %) treated without ciprofloxacin developed HUS (p = 0.043). CONCLUSION: In our E. coli O104:H4-infected patients, treatment of diarrhea with antibiotics did not increase the risk of HUS. Significantly fewer patients treated with ciprofloxacin developed HUS than patients who did not receive ciprofloxacin.

[Emerging viral diseases in Europe]. / "Neue" Viren als bedrohliche Krankheitserreger in Europa.

Emergence of viral agents in Europe is influenced by various factors. Climatic changes influencing possible vectors, insufficient vaccination, and travel of man and goods are among the most important reasons to explain these changes. Fever and arthralgia are the leading symptoms in infection with Dengue, Sindbis, or Chikungunya virus. In contrast, tick-born encephalitis (TBE), Toscana, or West Nile virus infections mainly lead to meningo-encephalitis. In Europe, hemorrhagic fever is caused by Crimean Congo and Hanta virus. Protective vaccines are available for emerging viral agents like TBE, influenza and measles.

[Fingolimod treatment for multiple sclerosis patients. Infectiological aspects and recommendations for vaccinations]. / Therapie der Multiplen Sklerose mit Fingolimod. Infektiologische Aspekte und Hinweise zum Impfverhalten.

Since April 2011 fingolimod (FTY 720, Gilenya®), a new oral treatment, is available for relapsing-remitting multiple sclerosis (MS) in Germany. Adverse effects in pre-marketing clinical controlled multicenter studies have led to specific precautions that have to be followed before initiating treatment. According to the European Union prescribing information fingolimod is not to be used as a first-line treatment, but is licensed as a second-line option or escalating therapy of MS. During treatment physical and neurological examinations as well as regular blood counts should be performed. The immunosuppressive mode of action of fingolimod requires increased awareness of infectious complications. Due to two fatal herpetic infections during the TRANSFORMS trial all patients without a history of chicken pox or without vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV. Comparably to other immunosuppressive treatment strategies the immune response to vaccines may be hampered during treatment with fingolimod. Thus, on the one hand, vaccination gaps should be closed before initiation of fingolimod treatment and, on the other hand, success of vaccinations during fingolimod therapy may have to be checked by antibody titre assessment.

[Factitious recurrent septicemia and gastrointestinal corrosive burns]. / Rezidivierende Septikämien und gastrointestinale Verätzung.

HISTORY AND ADMISSION FINDINGS: A 39-year-old woman was admitted for the treatment of recurrent septicemia, corrosive esophageal and gastric mucosal injury, and bloody stools. INVESTIGATIONS: A search of her hospital room provided evidence of a self-inflicted disorder. Bacteremia with typical fecal flora had been caused by self-injected intravenous inoculation of stool and the esophageal ulcers by swallowed vinegar. TREATMENT AND COURSE: The patient was initially treated with meropenem. After initial clinical and psychological stabilization the patient refused further psychiatric or psychosomatic treatment. CONCLUSION: Fluctuating or bizarre symptoms and unusual diagnostic findings may indicate self-inflicted disorders, in which the symptoms of illness are caused by the afflicted person him/herself.

[Tick-borne encephalitis virus in humans and ticks in Northeastern Germany]. / Frühsommer-Meningoenzephalitis-Virus bei Menschen und Zecken in Mecklenburg-Vorpommern.

Tick-borne encephalitis (TBE) was known to have occurred in humans in the area of Mecklenburg-Western Pomerania in Germany, until 1985. Between 1992 and 2004 more than 16,000 ticks were tested and found to be negative for TBE virus in that area of Germany, wich was therefore thought to be free of TBE. But after 19 years three autochthonous cases of human TBE-infections were identified between 2004 and 2006. We subsequently collected ticks from the three areas where the infection had been acquired and tested them for the presence of TBE-virus RNA with a nested reverse transcription polymerase chain reaction (RT-PCR). Since there is evidence that a blood-meal leads to an increase of FSME-RNA in ticks, we tested both, unfed ticks and ticks after a blood-meal. Three unfed and one fed nymph from the area around Lake Woblitz and one unfed and one fed nymph from Thiessow were positive for TBE-virus RNA. A total of six of 250 (2.4%) ticks tested positive for TBE-virus. The emerging of human TBE infections in three regions in Mecklenburg-Western Pomerania shows that the activity of natural TBE virus foci does not cease even after decades, or that TBE-infected ticks could have recolonized these regions.

[Vaccination and multiple sclerosis]. / Impfen und Multiple Sklerose.

Vaccinations to prevent communicable diseases are, like in other chronic diseases, of special importance in patients with multiple sclerosis (MS). Various bacterial and viral infections have been shown to induce relapses of MS. Reports of possible adverse effects of vaccinations on the course of multiple sclerosis have led patients and treating physicians to exercise caution in the use of vaccines. A number of vaccines have been studied with respect to the risk in MS patients. Some vaccines, for example against yellow fever, are not indicated in MS due to the risk of MS exacerbation. In contrast, tetanus or hepatitis B vaccines do not represent a risk for manifestation or disease progression of MS. Before and during immunomodulatory therapy of MS special attention should be given to adequate protection against vaccine preventable diseases.This paper reviews the indications and specific side effects of vaccinations in MS patients. Additionally, issues of vaccination under immunomodulatory therapy of MS are discussed.

[Hit by lightning out of the blue]. / Aus heiterem Himmel vom Blitz getroffen.

HISTORY AND CLINICAL FINDINGS: A group of six hikers were hit by lightning out of the blue sky. The biggest harm was done to a 29-year-old man (size: 190 cm) while walking along a high spruce. He experienced a seizure with consecutive sinus tachycardia and hypertensive dysregulation. One year later he still complained about reduced physical strength. The other five hikers had less severe injuries. INVESTIGATIONS: Burns were detectable in five of six patients. Elevated creatine kinase and myoglobin were indicative for myolysis. Renal parameters were normal. DIAGNOSIS, THERAPY AND COURSE: All patients were treated with intravenous fluid and electrolyte substitution during transport to hospital. Two patients were additionally treated with metroprolol. CONCLUSION: Cardiac arrhythmias, usually tachycardia, myolysis, and seizures require early treatment with beta blockers, sufficient fluid supply, and antiepileptics. In patients with cardiac arrest after a lightning injury immediate cardiac resuscitation is crucial.

[A case of autochthonous early summer meningoencephalitis in Mecklenberg-Western Pomerania]. / Ein Fall einer autochthonen Frühsommermeningoenzephalitis (FSME) in Mecklenburg-Vorpommern.

HISTORY: A 61-year-old man was bitten by a tick at Lake Woblitz, near the town of Neustrelitz in former East Germany. Nine days later he saw his general practitioner because of fever and headache. Three weeks after the tick bite he was hospitalized with fever (39.2 degrees C) and mental confusion. Because he had taken a Nile cruise six months earlier, malaria was considered and he was transferred to the department of tropical medicine and infectious diseases of the University of Rostock. INVESTIGATIONS: The patient was somnolent, his speech was slurred, and he had amnesic aphasia, as well as impaired fine motor control, but no meningism, focal signs, pyramidal tract or sensory impairment. Cerebrospinal fluid (CSF) showed mild lymphocytosis (9,400 leukocytes per microL; 89% lymphocytes) and elevated protein concentration (1322 mg/L) with blood brain barrier impairment and intrathecal IgM synthesis. Anti-tick-bite encephalitis (TBE) antibodies (ELISA: IgG and IgM) were present in serum and CSF, and serum immunofluorescence showed an eight-fold titer increase within two weeks. These findings confirm the diagnosis of TBE. Other infections (including those with cross-reacting flaviviruses) were excluded by appropriate antibody testing. THERAPY AND CLINICAL COURSE: There is no specific antiviral treatment for TBE, but on symptomatic therapy the patient recovered fully within four weeks. CONCLUSION: The site of the patient's infection is located 10 km to the west of an old TBE focus, but no TBE virus had been detected there after 1975. The case demonstrates that TBE should be included in the differential diagnosis of meningoencephalitis, even if the patient has not been in an acknowledged TBE endemic area.