[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.

A case of acute hepatitis A infection in an HIV-positive patient despite complete hepatitis A vaccination.

BACKGROUND: Vaccination against hepatitis A virus infection is recommended for men who have sex with men and other risk groups. The protection offered by the combined hepatitis A and B vaccine is comparable to that offered by the monovalent hepatitis A vaccine. CASE: A 38-year-old HIV-positive patient presented with right upper abdominal pain, fever and jaundice. Serological work-up and detection of hepatitis A RNA in stool sample revealed an acute hepatitis A infection despite a previous complete vaccination with the combined hepatitis A and B vaccine. CONCLUSION: Although the combined hepatitis A and B vaccine is associated with very good seroconversion rates, the effectiveness in HIV-positive patients is not ensured, even in cases with CD4 cell counts of > 500/µl. Therefore, regular post-vaccine testing should be encouraged to assess seroconversion in immunocompromised subjects.

[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.

Vacuum-assisted closure therapy of paradoxical reaction in tuberculous lymphadenopathy caused by Mycobacterium africanum.

A 26-year-old HIV-negative male from Ghana was treated for cervical, intrathoracic and abdominal lymph node tuberculosis (TB) and tuberculous hepatitis. Penetration of the thoracic trachea by a mediastinal lymph node had caused bronchomucosal TB. Sputum culture grew M. africanum, sensitive to all first-line antituberculous drugs. Four weeks after the beginning of directly observed treatment with isoniazid, rifampin, pyrazinamide and ethambutol, the right cervical lymph node increased in size, liquefied and caused a spontaneous fistula. A biopsy of the necrotized lymph node revealed rare acid-fast bacilli with a positive PCR for Mycobacterium tuberculosis complex. After debridement, vacuum-assisted closure therapy was performed for 6 weeks. Five months after the beginning of antituberculous therapy, a second paradoxical reaction occurred, with painful swelling of two contralateral supraclavicular lymph nodes. Extirpation of one node yielded a positive PCR for M. tuberculosis complex; the culture was negative. Antituberculous treatment was continued, and additional treatment with oral prednisolone 20 mg daily for 1 month tapering over 10 weeks was introduced, resulting in a decrease in lymphadenopathy. Antituberculous treatment was continued for a total of 9 months. The outcome was favorable, no further lymphadenopathy occurred over the following 6 months.

[Fever after travel to tropical regions: Malaria and other emergencies]. / Malaria und andere notfallmedizinische relevante Tropenerkrankungen mit dem Leitsymptom Fieber.

BACKGROUND: For people returning from the tropics, malaria is the most common cause of fever. Plasmodium falciparum causes the most common and most dangerous form of malaria, called malignant tertian malaria or falciparum malaria. METHOD: Search and evaluation of the current literature. RESULTS AND CONCLUSION: Over 90 % of all malaria cases and malaria deaths occur in Africa, while the remaining cases are divided between India, Southeast Asia, Oceania, and Latin America. In Germany, between 513 and 613 cases of malaria have been reportet annually over the last 10 years according to the Robert Koch Institute, including 389-541 cases of potentially fatal falciparum malaria (Plasmodium falciparum). All fever patients who have been in to the tropics during the last 4 months must be tested for malaria. However, immigrants from tropical regions might develop malaria even years after their last trip to their former home country. Rapid diagnostic tests are now available-particularly for falciparum malaria. However, the occasional negative or false-positive results are possible. The treatment of malaria depends on the Plasmodium species, the clinical severity, and the region in which the infection was acquired.

[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.

Pneumocystis jirovecii colonisation in HIV-positive and HIV-negative subjects in Cameroon.

OBJECTIVE: To determine the prevalence of Pneumocystis pneumonia (PCP), a major opportunistic infection in AIDS patients in Europe and the USA, in Cameroon. MATERIALS AND METHODS: Induced sputum samples from 237 patients without pulmonary symptoms (126 HIV-positive and 111 HIV-negative outpatients) treated at a regional hospital in Cameroon were examined for the prevalence of Pneumocystis jirovecii by specific nested polymerase chain reaction (nPCR) and staining methods. CD4 counts and the history of antiretroviral therapy of the subjects were obtained through the ESOPE database system. RESULTS AND CONCLUSION: Seventy-five of 237 study participants (31.6%) were colonised with Pneumocystis, but none showed active PCP. The Pneumocystis colonisation rate in HIV-positive subjects was more than double that of HIV-negative subjects (42.9% vs. 18.9%, P < 0.001). In the HIV-positive group, the colonisation rate corresponds to the reduction in the CD4 lymphocyte counts. Subjects with CD4 counts >500 cells/µl were colonised at a rate of 20.0%, subjects with CD4 counts between 200 and 500 cells/µl of 42.5%, and subjects with CD4 counts <200 cells/µl of 57.1%. Colonisation with Pneumocystis in Cameroon seems to be comparable to rates found in Western Europe. Prophylactic and therapeutic measures against Pneumocystis should be taken into account in HIV care in western Africa.

Ampicillin/sulbactam in elderly patients with community-acquired pneumonia.

PURPOSE: Age-related physiological changes affect body systems, altering pharmacokinetics, which may potentiate or alter the effects of drugs. The aim of this study was to assess the influence of age on the steady-state pharmacokinetics and pharmacokinetic/pharmacodynamic parameters of ampicillin/sulbactam in the population of elderly patients (age ≥65 years) with community-acquired pneumonia (CAP). PATIENTS AND METHODS: The pharmacokinetics and pharmacokinetic/pharmacodynamic parameters of ampicillin/sulbactam were determined at steady state in a total of 13 elderly patients with CAP following the administration of multiple intravenous doses of 2 g ampicillin + 1 g sulbactam (Unacid(®), Pfizer), each over 15 min thrice a day. RESULTS: A reduced C max, AUC0-8 h and total clearance, a prolonged half-life, and an increased steady-state volume of distribution were observed for ampicillin. The mean estimated free C min of 1.8 mg/L for ampicillin was higher than that predicted to be effective against Streptococcus pneumoniae. Based on an MIC90 of 1 mg/L for Streptococcus pneumoniae, the calculated T > MIC and T > 4 × MIC for ampicillin was 75-100 % (median 100 %) and 12.5-100 % (median 50 %), respectively. A T > 4 × MIC of at least 50 % was achieved in 7 of 13 elderly patients with CAP. CONCLUSIONS: Age and, probably, pneumonia did affect the pharmacokinetics of ampicillin and sulbactam. Despite the reduced C max, adequate free C min/MIC90 ratios due to impaired renal function were observed in elderly patients with CAP. In elderly patients without renal impairment and/or in severe infection with less susceptible pathogens, more frequent dosing of ampicillin 2 g/sulbactam 1 g can be necessary to avoid the risk of underdosing in CAP.

Multiple sclerosis treatment and infectious issues: update 2013.

Immunomodulation and immunosuppression are generally linked to an increased risk of infection. In the growing field of new and potent drugs for multiple sclerosis (MS), we review the current data concerning infections and prevention of infectious diseases. This is of importance for recently licensed and future MS treatment options, but also for long-term established therapies for MS. Some of the disease-modifying therapies (DMT) go along with threats of specific severe infections or complications, which require a more intensive long-term monitoring and multi-disciplinary surveillance. We update the existing warning notices and infectious issues which have to be considered using drugs for multiple sclerosis.

Hepatitis B and C: neglected diseases among health care workers in Cameroon.

BACKGROUND: Healthcare workers (HCW) are at risk of acquiring blood-borne viral infections, particularly hepatitis B (HBV), hepatitis C (HCV), and HIV, especially in high endemic regions such as sub-Saharan Africa. METHODS: Sera from 237 hospital workers in Southwest Cameroon were tested for anti-hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antigen (anti-HBs), anti-HCV and (on a voluntary basis) for anti-HIV. Information on pre-study testing for HBV, HCV and HIV and pre-study HBV vaccination status was collected from these individuals. RESULTS: The pre-study testing rate among participating hospital staff for HBV was 23.6% (56/237), for HCV 16% (38/237), and for HIV 91.6% (217/237). The pre-study HBV vaccination rate was 12.3% (29/237). Analysis of anti-HBc revealed that 73.4% (174/237) of the hospital staff had been infected by HBV. Active HBV infection (HBsAg positivity) was detected in 15 participants. Anti-HCV was found in four of 237 participants, HIV antibodies were detected in four of 200 participants tested. CONCLUSION: HBV and HCV are neglected diseases among HCW in sub-Saharan Africa. The vaccination rate against HBV was very low at 12.3%, and therefore anti-HBc testing should be mandatory to identify HCW requiring HBV vaccination. Testing for HBV and routine HBV vaccination for HBV-negative HCW should be strongly enforced in Cameroon.

[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.

Pneumocystis species in Brown Leghorn laying hens--a hint for an extra-mammalian reservoir.

The fungus Pneumocystis spp. causes Pneumocystis pneumonia in immunocompromised mammals including humans, whereas healthy individuals are often colonized and can transmit it to others. There is little evidence that Pneumocystis spp. is also present outside mammalian species. We describe the first detection of Pneumocystis DNA from the lungs and air sacs of laying hens from deep litter and floor husbandry systems. The DNA from chickens' lungs and air sacs was amplified with a Pneumocystis-specific mtLSU rRNA gene nested PCR and sequenced. Pneumocystis DNA was detected in 20 of 111 (18.0%) hens. The DNA sequences showed specific differences to all known Pneumocystis mtLSU sequences. In induced sputum samples of 2 of 7 farm workers at this poultry farm, human Pneumocystis jirovecii strains without these mutations were detected; therefore, a transmission between chickens and farm workers appears implausible.

[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.

[Value of fall-risk tests for patients with rheumatoid arthritis]. / Wertigkeit von Sturzrisikotests bei Patienten mit rheumatoider Arthritis.

The aim of the study was to quickly and efficiently determine the risk of falling in patients with rheumatoid arthritis over the age of 46 with established methods, to discover parameters which influence the risk of falling and fractures. The study group consisted of 67 patients (median age 69±7.4 years, duration of disease <10 years 71%).With the help of the present data on fractures the performance of the chair-rising (CR) test, the timed up-and-go (TUG) test and the tandem stand (TS) test plus determination of the average daily and cumulative glucocorticoid (GC) dosage, it was possible to detect parameters which influence the risk of falling and fractures.Higher age (>60 years), overweight, deficits in muscle strength in the lower extremities and very low GC dosage (≤5 mg) were found to be associated with an increased risk of falling, which is accompanied by an increased risk of fractures.

Schistosoma mansoni: schistosomicidal effect of mefloquine and primaquine in vitro.

We investigated the effects of the anti-malarials mefloquine and primaquine against the juvenile and adult life stages of Schistosoma mansoniin vitro. Cercariae were incubated with 0.5 µg/ml, 1 µg/ml and 2 µg/ml mefloquine or primaquine and with 1 µg/ml praziquantel for 12h. Schistosomula, pre-adults and adults were incubated with 0.5 µg/ml, 1 µg/ml and 2 µg/ml mefloquine or primaquine and with 1 µg/ml praziquantel for 7 days. The viability status was classified as viable, damaged or dead and was checked every 3h for cercariae and every 12h for schistosomula, pre-adults and adults. Both, mefloquine and primaquine show time and dose-dependent schistosomicidal effects on the four life stages of S. mansoni. The promising in vitro effects on all stages of the blood fluke S. mansoni warrants further evaluation of both anti-malarials and their derivatives for their prophylactic and therapeutic values in early and late schistosomiasis in field trials.

Safety and immunogenicity of a trivalent single dose seasonal influenza vaccine containing pandemic A(H1N1) antigen in younger and elderly subjects: a phase III open-label single-arm study.

BACKGROUND: During the pandemic of the 2009 A(H1N1) influenza virus strain, 20-40% of the population in some areas were infected. Infection with A(H1N1) may be mild, with an average case fatality rate below 0.25%, but severe disease is not limited to patients with underlying medical conditions. Since A(H1N1) is expected to continue to circulate it is included in the seasonal influenza vaccines for the 2010-2011 winter season. We investigated the immunogenicity and safety of a preservative-free non-adjuvanted seasonal trivalent influenza vaccine. METHODS: We conducted a single center single-arm study involving 142 subjects (77 adults of 18-60 years and 65 subjects 61 years and above) to test the immunogenicity, safety, and tolerability of a trivalent split influenza vaccine. The vaccine contained 15µg of hemagglutinin of each of the virus strains recommended for the 2010-2011 northern hemisphere winter season (A/California/7/2009 (H1N1)-like strain; A/Perth/16/2009 (H3N2)-like strain; B/Brisbane/60/2008-like strain) in a non-adjuvanted preservative-free formulation. Antibody response to each antigen was measured by hemagglutination inhibition (HI) 21 days after immunization. Subject diary cards and additional telephone interviews were used to assess the safety profile. RESULTS: By day 21 after the vaccination, seroconversion, or a 4-fold antibody increase in HI antibody titers, was detectable against A(H1N1) in 84% and 75% of younger and older adults, against A(H3N2) in 80% and 57%, and against the B influenza strain in 61% and 33%. HI antibody titers of 40 or more were observed against A(H1N1) in 99% and 90% of younger and older adults, against A(H3N2) in 100% and 90%, and against the B influenza strain in 91% and 78%. Pre-vaccination antibody titers were protective against A(H1N1), A(H3N2), and B in 26%, 44% and 33%, respectively of the adults below 61 years and in 27%, 54% and 44% of the subjects of 61 years and above. Local and systemic reactions were more common in younger than in older subjects and the most frequently reported reactions were pain at the injection site (36%), myalgia (24%), and fatigue (15%). Five percent elderly subjects and 1% of younger subjects had mild or moderate unsolicited adverse events such as prolonged ecchymosis or night sweats that resolved within 7 days after vaccination. CONCLUSIONS: This single dose trivalent seasonal influenza vaccine generated protective antibodies to all three viral strains and had an acceptable safety profile in both younger and older adults (ClinicalTrials.gov identifier: NCT01147081).