[Gastrointestinal symptoms may reflect complicated falciparum malaria]. / Gastrointestinale Symptome als Ausdruck einer komplizierten Malaria tropica.

HISTORY: A 42-year-old female presented with a two-day history of vomiting, diarrhea, fever and chills. Two weeks before she had returned to Germany from a Safari in Tanzania. She had disregarded the recommendation to take antimalarial chemoprophylaxis. CLINICAL FINDINGS AND DIAGNOSIS: The thin blood film showed Plasmodium falciparum-parasitized erythrocytes, and Plasmodium falciparum malaria was diagnosed. The full blood count showed thrombocytopenia and ultrasound imaging revealed splenomegaly. Initially the criteria for complicated malaria were not fulfilled. THERAPY AND COURSE: We started oral therapy with atovaquone/proguanil. The patient vomited the tablets twice. Therefore therapy was switched to intravenous artesunate. Subsequently, parasitemia dropped from 2.8 to 1.0 % within 22 hours. After 3 days of artesunate i. v., treatment could then be completed with oral atovaquone/proguanil, and the symptoms resolved. CONCLUSIONS: Patients with malaria and persistent vomiting should be treated intravenously and monitored closely, as severe gastrointestinal symptoms may reflect impending organ failure. We therefore propose including persistent vomiting in the list of criteria for complicated malaria.

Performance Analysis of Serodiagnostic Tests to Characterize the Incline and Decline of the Individual Humoral Immune Response in COVID-19 Patients: Impact on Diagnostic Management.

Serodiagnostic tests for antibody detection to estimate the immunoprotective status regarding SARS-CoV-2 support diagnostic management. This study aimed to investigate the performance of serological assays for COVID-19 and elaborate on test-specific characteristics. Sequential samples (n = 636) of four panels (acute COVID-19, convalescent COVID-19 (partly vaccinated post-infection), pre-pandemic, and cross-reactive) were tested for IgG by indirect immunofluorescence test (IIFT) and EUROIMMUN EUROLINE Anti-SARS-CoV-2 Profile (IgG). Neutralizing antibodies were determined by a virus neutralization test (VNT) and two surrogate neutralization tests (sVNT, GenScript cPass, and EUROIMMUN SARS-CoV-2 NeutraLISA). Analysis of the acute and convalescent panels revealed high positive (78.3% and 91.6%) and negative (91.6%) agreement between IIFT and Profile IgG. The sVNTs revealed differences in their positive (cPass: 89.4% and 97.0%, NeutraLISA: 71.5% and 72.1%) and negative agreement with VNT (cPass: 92.3% and 50.0%, NeutraLISA: 95.1% and 92.5%) at a diagnostic specificity of 100% for all tests. The cPass showed higher inhibition rates than NeutraLISA at VNT titers below 1:640. Cross-reactivities were only found by cPass (57.1%). Serodiagnostic tests, which showed substantial agreement and fast runtime, could provide alternatives for cell-based assays. The findings of this study suggest that careful interpretation of serodiagnostic results obtained at different times after SARS-CoV-2 antigen exposure is crucial to support decision-making in diagnostic management.

Serologic and Genomic Investigation of West Nile Virus in Kosovo.

The prevalence of West Nile virus (WNV) is increasing across Europe, with cases emerging in previously unaffected countries. Kosovo is situated in a WNV-endemic region where the seroepidemiological data on WNV in humans remains absent. To address this issue, we have conducted a seroepidemiological investigation of 453 randomly selected sera from a hospital in Kosovo, revealing a 1.55% anti-WNV IgG seroprevalence. Comparative and phylogeographic analyses of the WNV genomes obtained by sequencing archived samples from patients with West Nile fever indicate at least two recent and distinct introductions of WNV lineage 2 into Kosovo from neighboring countries. These findings confirm the eco-epidemiological status of WNV in southeast Europe, where long- and short-range dispersion of lineage 2 strains contributes to a wider circulation via central Europe. Our results suggest an increasing risk for WNV spreading in Kosovo, underscoring the need for an integrated national surveillance program targeting vectors and avian populations for early epidemic detection, as well as the screening of blood donors to gauge the impact of virus circulation on the human population.

Introduction of the Rapid Deployment Aortic Valve System Use in Elderly Patients With Endocarditis.

Introduction: The rapid-deployment valve system (RDVS) was introduced to facility minimally invasive aortic valve replacement. In this study we evaluate the potential benefits of RDVS in elderly high-risk patients with endocarditis of the aortic valve. Materials and Methods: Since the introduction of RDVS in our institution in December 2017 through October 2021, EDWARDS INTUITY rapid-deployment prosthesis (Model 8300A, Edwards Lifesciences, Irvine, CA, USA) has been implanted in a total of 115 patients for different indications by a single surgeon. Out of one-hundred and fifteen cases of RDVS implantation, seven patients with a median age of 77 yrs. (range 62-84yrs.), suffered from active infective endocarditis of the aortic valve. The median EuroSCORE II of these highly selected patient cohort was 77% (range 19-80%). Patient data were evaluated perioperatively including intra-operative data as well as in-hospital morbidity/mortality and follow-up after discharge from hospital. Results: Three patients underwent previous cardiac surgery. Concomitant procedures were performed in six patients including, ascending aorta replacement (n = 3), mitral valve repair (n = 1), pulmonary valve replacement (n = 1), bypass surgery (n = 1), left atrial appendix resection (n = 1) and anterior mitral valve repair (n = 1). Median aortic cross-clamp and cardiopulmonary bypass time was 56 min (range 29-122 min) and 81 min (range 45-162 min.), respectively. Post-operative complications in these elderly high-risk patients were atrial fibrillation (n = 3) and re-exploration for pericardial effusion (n = 1). One pacemaker implantation was required on postoperative day 6 due to sick sinus syndrome. There was one in-hospital death (14%) and one during follow-up (14%). Conclusion: Rapid-deployment aortic valve system seems to be a viable option with acceptable morbidity and mortality in elderly high-risk patients with active infective endocarditis of the aortic valve.

[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.

Longitudinal detection of SARS-CoV-2-specific antibody responses with different serological methods.

Serological testing for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is used to detect ongoing or past SARS-CoV-2 infections. To study the kinetics of anti-SARS-CoV-2 antibodies and to assess the diagnostic performances of eight serological assays, we used 129 serum samples collected on known days post symptom onset (dpso) from 42 patients with polymerase chain reaction-confirmed coronavirus disease 2019 (COVID-19) and 54 serum samples from healthy blood donors, and children infected with seasonal coronaviruses. The sera were analyzed for the presence of immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies using indirect immunofluorescence testing (IIFT) based on SARS-CoV-2-infected cells. They were further tested for antibodies against the S1 domain of the SARS-CoV-2 spike protein (IgG, IgA) and against the viral nucleocapsid protein (IgG, IgM) using enzyme-linked immunosorbent assays. The assay specificities were 94.4%-100%. The sensitivities varied largely between assays, reflecting their respective purposes. The sensitivities of IgA and IgM assays were the highest between 11 and 20 dpso, whereas the sensitivities of IgG assays peaked between 20 and 60 dpso. IIFT showed the highest sensitivities due to the use of the whole SARS-CoV-2 as substrate and provided information on whether or not the individual has been infected with SARS-CoV-2. Enzyme-linked immunosorbent assays provided further information about both the prevalence and concentration of specific antibodies against selected antigens of SARS-CoV-2.

Protection From COVID-19­The Efficacy of Face Masks.

BACKGROUND: Since the beginning of 2020 the SARS-CoV-2 virus has spread to nearly every country in the world. The mainly airborne pathogen has led to large numbers of deaths, principally in elderly and vulnerable segments of the population. Protective vaccines have recently become available, but it is not yet clear whether and when population-wide immunity will be achieved. The existence of evidence for the protective effect of masks covering the mouth and nose is a topic of public debate. METHODS: A selective literature search was carried out in PubMed. Data from the German Robert Koch Institute and the Centers for Disease Control and Prevention were also taken into account. RESULTS: When talking, as many as 20 000 droplets ranging in size from 20 to 500 µM are released every second. According to PCR tests, the amount of virus exhaled is highest immediately before the onset of symptoms. No randomized trials have been conducted on the effect of masks covering the mouth and nose. A metaanalysis of 29 studies on infection with SARS-CoV-2, SARS, or MERS revealed that type N-95 masks (corresponding approximately to FFP-2), surgical masks, or similar multilayer cotton masks can greatly reduce the infection risk for the wearers (RR 0.34 [0.26; 0.45], with moderate heterogeneity [I2 = 48%]). Model experiments and case reports suggest that masks covering the mouth and nose afford considerable protection against transmission of SARS-CoV-2 and other airborne diseases by reducing release of and exposure to potentially infectious droplets; in addition, infections that do occur take a milder course. A limitation of the studies analyzed is that in most cases, this effect cannot be viewed in isolation from the protective impact of other measures (distancing, hygiene precautions). CONCLUSION: It can plausibly be assumed that consistent use of masks covering the mouth and nose can play an important role in containing the spread of SARSCoV- 2.

Immunotherapy and vaccination against infectious diseases.

Due to the overuse of antibiotics, infections, in particular those caused by multidrug-resistant bacteria, are becoming more and more frequent. Despite the worldwide introduction of antibiotic therapy, vaccines and constant improvements in hygiene, the burden of multidrug-resistant bacterial infections is increasing and is expected to rise in the future. The development of monoclonal therapeutic antibodies and specific immunomodulatory drugs represent new treatment options in the fight against infectious diseases. This article provides a brief overview of recent advances in immunomodulatory therapy and other strategies in the treatment of infectious disease.

[COVID-19: epidemiology and clinical facts]. / COVID-19: Epidemiologische und klinische Fakten.

Until July 31, 2020, about 17.6 million SARS-CoV­2 infections and 680,000 deaths from COVID-19 were reported. SARS-CoV­2 is most likely transmitted by droplets and probably by aerosols. Patients become infectious 2-3 days before the onset of symptoms, and persons with asymptomatic infections are also infectious. COVID-19 affects the upper respiratory tract, lungs (pneumonia, acute respiratory distress syndrome [ARDS]), heart, liver, gastrointestinal tract, and other organs. SARS-CoV­2 uses ACE2 a receptor to enter host cells. Vasculitis, endothelial damage, thromboembolic events and organ failure are accompanied by a massive cytokine response. Elderly people and those with pre-existing diseases are particularly vulnerable. An efficient antiviral therapy is not yet available. Severely ill patients may benefit from dexamethasone and early treatment of complications. Candidate vaccines are currently being tested in clinical studies.

[Screening of Mothers in a COVID-19 Low-Prevalence Region: Determination of SARS-CoV-2 Antibodies in 401 Mothers from Rostock by ELISA and Confirmation by Immunofluorescence]. / Mütter-Screening in einem COVID-19-Niedrig-Pandemiegebiet: Bestimmung SARS-CoV-2-spezifischer Antikörper bei 401 Rostocker Müttern mittels ELISA und Immunfluoreszenz-Bestätigungstest.

BACKGROUND: In children, the infection with SARS-CoV-2, the cause of COVID-19, tends to be clinically inapparent more often or less severe than in adults. The spread of this infection from children poses a danger to vulnerable adults. Therefore, child care institutions and schools currently are widely closed. METHODS: Since the status of infection tends to be congruent in mothers and their children, we tested 401 mothers of children between 1 and 10 years in the city of Rostock (State of Mecklenburg-Westpomerania, northeast of Germany), for the presence of RNA of SARS-CoV-2 in throat swabs, and of antibodies against SARS-CoV-2 in serum. RESULTS: In none of the mothers tested, RNA of this virus was detected in the throat swab. In the ELISA test, IgG antibodies were positive in one serum sample, IgA antibodies were positive in 11, and borderline in 3 serum samples. All 401 sera were negative in the indirect immunofluorescence test (IIFT) with FITC-labeled IgG, IgA, und IgM antibodies. CONCLUSION: At the time of this study, neither SARS-CoV-2 RNA, nor specific antibodies against SARS-CoV-2 were detectable in the mothers tested in Rostock.

Crimean-Congo Hemorrhagic Fever, Kosovo, 2013-2016.

During 2013-2016, a total of 32 patients were treated for Crimean-Congo hemorrhagic fever in Prishtina, Kosovo; 11 died. In the 11 patients who died, findings included viral loads >1 × 108.5/mL, lactate dehydrogenase >2,700 U/mL, bleeding, and impaired consciousness. Ribavirin therapy had no noticeable effect in this small patient sample.

Bilateral deafness two days following influenza vaccination: a case report.

OBJECTIVE: We report a case of deafness occurring in a temporal context of an influenza vaccination in a 79-year-old woman. METHODS: Case report and review of the literature on influenza causing deafness. RESULTS: A 79-year-old woman with normal hearing developed acute bilateral sensorineural hearing loss two days after a seasonal influenza vaccination, other obvious reasons for acute hearing loss were excluded. CONCLUSION: This patient appears to be the first reported case of bilateral deafness following a trivalent seasonal influenza vaccination.

Tuberculosis-associated hemophagocytic lymphohistiocytosis with subsequent unmasking cryptococcal immune reconstitution inflammatory syndrome (IRIS) in an HIV-negative man.

A 22-year-old HIV-negative man from Ghana was diagnosed with severe hemophagocytic lymphohistiocytosis (HLH) induced by multiorgan tuberculosis with peritoneal, hepatic, pericardial, myocardial, pleural, pulmonary, and bone manifestation. His body mass index was 12.9 m2/kg. Bioptic material of a peritoneal biopsy grew M. tuberculosis, sensitive to all first-line antituberculous drugs. HLH resolved with antituberculous therapy, without additional anti-inflammatory therapy being given. The initial CT scan of his brain was normal. After 5 months of antituberculous treatment, he developed a paralysis of the left arm. A cerebral MRT showed ring-enhanced lesions. Blood cultures and lumbar puncture revealed Cryptococcus neoformans var. grubi. The HIV test was repeatedly negative. Antituberculous treatment was continued for a total of 9 months, and additional treatment with antifungal therapy was established. He recovered fully after 14 months of antifungal treatment.

[Mosquitoes and Ticks: The Influence of Global Warming in the Transmission of Infectious Diseases in Germany]. / Mücken und Zecken als Krankheitsvektoren: der Einfluss der Klimaerwärmung.

During the last 135 years, the average temperature in Germany has increased by 1.4 °C. By 2050, a further rise by 1.5 °C is expected. This is associated with an increase of precipitation during the winter months. This climate change probably will improve both the growth conditions for mosquitoes and ticks, as well as their ability to transmit infectious diseases. Today, vectors that have not yet been present are invading into Germany. Among them is Aedes albopictus, which transmits Chikungunya, Zika, and Dengue Fever. Also, spreading of autochthonous malaria and West Nile Fever appear possible in Germany. Because of the increased presence of Phlebotomus species, leishmaniasis should be considered as a potential differential diagnosis in unclear hematologic diseases. Among the tick-borne diseases, climate change has already led to increased case numbers of Borreliosis and Tick Borne Encephalitis (TBE), and Crimean Congo Virus is spreading from the Balkan region towards Central Europe. This requires physicians to consider additional differential diagnoses in febrile illnesses.

Effect of Tenofovor Diproxil Fumarate on Renal Function and Urinalysis Abnormalities in HIV-Infected Cameroonian Adults.

In Sub-Saharan Africa, the prevalence of HIV-associated kidney diseases is as high as 53.3%. Combined antiretroviral treatment (cART), especially tenofovir disoproxil fumarate (TDF), is known to be nephrotoxic. We undertook this cross-sectional study conducted in 2015 at the Regional Hospital Limbe in the Southwest Region of Cameroon to determine the prevalence of renal dysfunction and its correlates among treatment-experienced HIV-infected patients on TDF and treatment-naïve patients. In April 2016, a follow-up was performed on those who had been treatment-naïve and were started on cART after enrolment in the study. We compared 119 patients on TDF-containing regimens with 47 treatment-naïve patients. Proteinuria was significantly more prevalent, and creatinine was significantly higher among treatment-naïve patients than among those on treatment (52.2% versus 26.1%; P = 0.003 and P = 0.009, respectively). The proportion of patients with an estimated glomerular filtration rate (eGFR) < 60 mL/minute was significantly higher among treatment-naïve patients than among those on TDF treatment (40.4% versus 24.4%; P = 0.041). Treatment-naïve patients displayed an improvement in creatinine levels and eGFR after 6 months of treatment. To the best of our knowledge, this is the first study to investigate the impact of TDF on renal parameters in Cameroon. TDF appears to be safe and does not appear to be a significant cause of renal impairment. However, renal parameters should be monitored regularly, as recommended by the guidelines.

Activated protein C protects vascular endothelial cells from apoptosis in malaria and in sepsis.

OBJECTIVE: In malaria and sepsis, apoptotic endothelial damage is preventable in vitro by antioxidants and protease inhibitors. Activated protein C, which has anti-apoptotic effects, improves survival in sepsis. Therefore, we studied whether activated protein C prevents endothelial cell apoptosis, induced by serum from patients with malaria or sepsis. METHODS: Endothelial cells were incubated with patient sera (Plasmodium falciparum malaria, Escherichia coli sepsis, Staphylococcus aureus sepsis) or culture supernatants of the respective organisms, with or without neutrophils. Activated protein C was used to reduce endothelial cell apoptosis in vitro. The proportion of apoptotic endothelial cells was determined by TUNEL staining. RESULTS: The apoptosis-inducing effect of patient sera or culture supernatants (P. falciparum, E. coli, S. aureus) on endothelial cells was augmented by neutrophils and reduced by activated protein C in the presence of neutrophils. Pre-incubating either endothelial cells or neutrophils with activated protein C also reduced the endothelial cell apoptosis rate. The pro-apoptotic effect of P. falciparum supernatant was reduced by pan-caspase inhibitor and caspase 8 inhibitor, but not by caspase 9 inhibitor. The pro-apoptotic effect of E. coli and S. aureus supernatants was also reduced by caspase 9 inhibitor. CONCLUSIONS: Activated protein C protects vascular endothelial cells from apoptosis triggered by patient sera or culture supernatants in combination with neutrophils. It seems to act both on neutrophils and on endothelial cells. Activated protein C blocks caspase-8-dependent apoptosis, which accounts for endothelial damage in sepsis and malaria. Therefore, activated protein C might offer clinical benefit not only in sepsis but also in malaria.

Human cowpox virus infection acquired from a circus elephant in Germany.

A 40-year-old Asian circus elephant developed mouth and trunk ulcers. Three weeks later, her 19-year-old animal warden noticed a vesicle on his forearm, evolving into a scab. Identical cowpox strains were isolated from lesions of the elephant and the warden. Cowpox virus could no longer be isolated after the scab disappeared, but PCR still revealed orthopox DNA. Healing was complete seven weeks later, leaving a 1 cm scar.