Meningitis and spondylodiscitis due to Nocardia nova in an immunocompetent patient.

BACKGROUND: Disseminated nocardiosis is a very rare disease. By now only few cases of meningitis and spondylodiscitis have been reported. To our knowledge, this is the first case of meningitis caused by Nocardia nova. CASE PRESENTATION: We report on a case of bacteraemia, meningitis and spondylodiscitis caused by N. nova in an immunocompetent patient. We describe the long, difficult path to diagnosis, which took two months, including all diagnostic pitfalls. After nocardiosis was diagnosed, intravenous antibiotic therapy with ceftriaxone, later switched to imipenem/cilastatin and amikacin, led to rapid clinical improvement. Intravenous therapy was followed by oral consolidation with co-trimoxazole for 9 months without any relapse within 4 years. CONCLUSIONS: Establishing a diagnosis of nocardiosis is a precondition for successful antibiotic therapy. This requires close communication between clinicians and laboratory staff about the suspicion of nocardiosis, than leading to prolonged cultures and specific laboratory methods, e.g. identification by 16S rDNA PCR.

[Puzzling B symptoms in a 61-year-old patient under treatment for rheumatoid arthritis]. / Rätselhafte B-Symptomatik bei einem 61-Jährigen unter Therapie einer rheumatoiden Arthritis.

A patient with rheumatoid arthritis and immunosuppression developed symptoms of wasting, neuropathy and lung cavitations eventually leading to central nervous system symptoms and fatal multi-organ failure. Disseminated infection with Histoplasma capsulatum proved to be the underlying cause. The primary infection had apparently been acquired 4 years earlier on a holiday to the Caribbean. Rare infectious diseases should be considered in patients under immunosuppression and travel activities to specific endemic areas.

[Intensive care back up for infectious disease disasters]. / Intensivmedizinisches Back-up bei infektiologischen Katastrophen.

BACKGROUND: Outbreaks of infectious diseases pose particular challenges for hospitals and intensive care units. OBJECTIVES: Typical infectiological scenarios and their significance for modern intensive care medicine are presented. MATERIALS AND METHODS: Selected pathogens/infectious diseases that have significantly strained the resources of intensive care units are described. RESULTS: Intensive medical care is necessary in severe cases of many infectious diseases. In the context of epidemics/pandemics, many critically ill patients have to be admitted within a short time. Examples are the 2009 H1N1 influenza pandemic, the 2011 enterohemorrhagic Escherichia coli (EHEC) outbreak in northern Germany, the 2014/2015 Ebola fever outbreak and the 2020 coronavirus disease 19 (COVID-19) pandemic. Multidisciplinary teams, protocol development, adequate staffing, and training are required to achieve optimal treatment outcomes, including prevention of healthcare worker infections. CONCLUSIONS: Pandemics and epidemics are unique challenges for intensive care unit preparedness planning.

[A chronic wound from Vietnam]. / Eine chronische Wunde aus Vietnam.

Chronic skin lesions that occur in patients who have previously stayed in tropical countries pose a diagnostic challenge for physicians. In particular, if there is a granulomatous inflammatory reaction histologically, infectious diseases should also be included in the differential diagnosis. Particularly in persons returning from high-risk regions such as Vietnam, this includes cutaneous tuberculosis, which entails a thorough examination of the patient and comprehensive therapy. This case study shows which steps should be considered if cutaneous tuberculosis is suspected.

[Acute renal failure and rare severe complication of systemic steroid treatment in a 73-year-old woman]. / Akutes Nierenversagen und seltene schwere Komplikation einer systemischen Steroidtherapie bei einer 73­Jährigen.

This article reports about a 73-year-old woman of Bosnian descent who presented with acute renal failure. A renal biopsy was diagnostic for a postinfect necrotizing and extracapillary proliferative glomerulonephritis. The patient reported a febrile infection fever 2 weeks previously. The diagnostics did not reveal any indications of an ongoing infection. The glomerulonephritis responded to treatment with systemic steroids. The patient was readmitted to hospital 6 weeeks later in a severely ill condition. A gastric biopsy revealed a Strongyloides stercoralis infestation. Due to the systemic steroid therapy the patient had developed a so-called hyperinfection syndrome and died despite treatment on the intensive care unit. This case illustrates the need for awareness of this rare parasitosis, particularly in patients from endemic areas. A likely causal relationship with the glomerulonephritis is discussed and an overview of the diagnostics, course of the disease and treatment of this parasitosis is given.

[Pancytopenia of unknown origin in a 52-year-old patient]. / Unklare Panzytopenie bei einem 52-jährigen Patienten.

A 52-year-old patient developed pancytopenia of unknown origin 1.5 years after allogeneic stem cell transplantation. The bone marrow aspirate showed visceral leishmaniasis (VL). Although VL is distributed world-wide, the incidence in patients after allogeneic stem cell transplantation is rare.

Dynamic changes of circulating miRNAs induced by the Ebola virus vaccine VSV-EBOV.

VSV-EBOV is a replication-competent Ebola virus (EBOV) vaccine, which was tested in clinical trials as response to the Ebola virus disease (EVD) outbreak 2013-2016. It is the most advanced EBOV candidate currently in the licensure process. The experimental vaccine was again administered as response to outbreaks in the Democratic Republic of Congo. However, underlying molecular mechanisms that convey protection remain incompletely understood. MicroRNAs (miRNAs) are known key regulators that influence gene expression on a post-transcriptional level. The miRNA-mediated control has emerged as a critical regulatory principle in the immune system, which strongly influences the balance of innate and adaptive immune responses by modulation of signaling pathways critical for differentiation of immune cells. We investigated expression levels of circulating miRNAs (c-miRNAs) in plasma from healthy vaccinees, as they may reflect cellular dynamics following VSV-EBOV immunization and additionally may serve as potential biomarkers for vaccine efficacy. As part of the WHO-led VEBCON consortium, we investigated safety and immunogenicity of VSV-EBOV in a phase I trial. A comprehensive analysis of expression levels on c-miRNAs from plasma samples following VSV-EBOV immunization (day 0, 1, 3 post vaccination) was conducted using RT-qPCR assays. Potential biological relevance was assessed using in silico analyses. Additionally, we correlated dynamics of miRNA expressions with our previously reported data on vaccine-induced antibody and cytokine responses and finally evaluated the prognostic power by generating ROC curves. We identified four promising miRNAs (hsa-miR-146a, hsa-miR-126, hsa-miR-199a, hsa-miR-484), showing a strong association with adaptive immune responses, exhibited favourable prognostic performance and are implicated in immunology-related functions. Our results provide evidence that miRNAs may serve as useful biomarkers for prediction of vaccine-induced immunogenicity. Furthermore, our unique data set provides insight into molecular mechanisms that underlie VSV-EBOV-mediated protective immune responses, which may help to decipher VSV-EBOV immune signature and accelerate strategic vaccine design or personalized approaches.

[Eosinophilia in pulmonary infections]. / Eosinophilie bei pulmonalen Infektionen.

Eosinophilia can be caused by a variety of diseases including allergies, autoimmune diseases, vasculitides, dermatoses, malignancies and drug-induced side effects as well as parasitic and non-parasitic infections. In patients returning from the tropics parasitic infections are the most frequent cause of eosinophilia. The extent of eosinophilia can provide information about the type of pathogen. The diagnostic approach to eosinophilia in travelers returning from the tropics primarily includes three stool examinations for worm eggs and, if necessary, serological tests for helminths. Additionally, a chest x­ray, an ultrasound of the abdomen and an electrocardiogram (ECG) provide information about organ involvement. Recently, specialized laboratories use molecular techniques (multiplex PCR) to detect worm eggs and intestinal parasites in the stool, which provide a significantly higher sensitivity than traditional stool examination techniques. Cryptococcosis, endemic systemic mycoses (coccidioidomycosis, very rarely histoplasmosis) and invasive mould infections (Aspergillus fumigatus, Mucor spp.) are non-parasitic causes of eosinophilia in blood and bronchoalveolar lavage (BAL).

[Intensive care treatment of a patient with Ebola virus disease in Germany]. / Intensivmedizinische Behandlung eines Patienten mit Ebola-Virusinfektion in Deutschland.

In this case report, we describe the clinical course of a patient with Ebola virus disease who was transferred to the Highly Contagious Pathogens Treatment Unit at the Hamburg University Medical Center. High volume turnover, electrolyte imbalances, paralytic ileus, sepsis with multiresistant gram-negative pathogen, and respiratory failure due to blood aspiration were major clinical challenges.

[A Somali refugee with fever and abnormal blood smear]. / Somalischer Flüchtling mit Fieber und auffälligem Blutausstrich.

The increasing migration into Europe may confront clinicians with diseases barely known any more in this part of the world. We present a case of louse-borne relapsing fever in a Somali refugee. Blood smears led to the diagnosis of relapsing fever and DNA sequencing was positive for Borrelia recurrentis. This disease should be considered in all patients with unclear fever and a compatible travel or migration history. Blood smears are employed as the primary diagnostic method. Therapy harbors the danger of a Jarisch-Herxheimer reaction, a complication that may require intensive medical care.

[Multiple abscesses after a cruise along the Latin American coast]. / Multiple Abszesse nach Südamerikakreuzfahrt.

We report a case of an extracutaneous involvement of pyoderma gangrenosum. The patient initially presented with multiple sterile abscesses of the skin, heart, prostate, and kidney. Extracutaneous involvement in pyoderma gangrenosum is very rare. Confirmation of the diagnosis was only possible after exclusion of other relevant differential diagnoses. Continuous search for microbes proved negative and after an empiric therapeutic attempt with prednisolone, the patient improved quickly. However, each time we reduced the steroids even in combination with methotrexate or with azathioprine the patient relapsed. Only after therapy with the tumor necrosis factor-α-inhibitor infliximab was permanent remission achieved.

[Knowledge and attitude of medical students in Germany towards palliative care : Does the final year of medical school make a difference?]. / Wissen und Selbsteinschätzung in Bezug auf palliativmedizinische Fragestellungen bei Medizinstudierenden : Macht das praktische Jahr einen Unterschied?

BACKGROUND: The practical year (PY) during the final year of medical education is intended to deepen and broaden knowledge, skills, and abilities that were acquired during previous years of their studies. Against this background, this study pursues the question of how the knowledge of future physicians and their confidence in terms of cancer pain therapy and other palliative care issues develops during the PY. MATERIALS AND METHODS: At the end of the PY, students from two university hospitals completed a 3-part online questionnaire (self-assessment of the confidence, questions about palliative care knowledge, and assessment of palliative care training during the PY). These results are compared with previously published data from the same collective that had been collected at the beginning of the PY. RESULTS: Overall, 92 of 318 students participated (28.9 %). Less than 10 % of students said that they were more confident regarding palliative care topics at the end of their medical studies. Improvements in the self-assessment could only be observed in the recognition of and screening for cancer pain (increase from 36 % to 65%). With regard to the palliative care knowledge, only the knowledge of how to treat symptoms other than pain improved significantly; however, knowledge in this regard prior to the PY was particularly low (an increase from 25 % to 35 %, p < 0.05). In the only multiple-choice question about ethics, the correct answer rose slightly from 51 % (before) to 55 % (after the PY). Of participating students, 21% (prior to the PY 27 %) stated that not providing fluids to dying patients is a form of euthanasia. In terms of palliative care training, between 36 and 83 % of participants stated having insufficient opportunities to gain knowledge and experience on various topics in the treatment of patients with advanced and incurable diseases during their PY. CONCLUSION: In the present study, considerable deficits in confidence and knowledge regarding palliative care issues were also observed at the end of PY. Integration of palliative care into the medical school curriculums should be given special attention in terms of a longitudinal training of the PY.

Virological failure after 1 year of first-line ART is not associated with HIV minority drug resistance in rural Cameroon .

OBJECTIVES: The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon. METHODS: In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (≥1000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls. RESULTS: At Month 12, 38/238 (16%) patients experienced virological failure (≥1000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n = 18) and K103N (n = 10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P = 0.77). Lower CD4 count at baseline (OR per 100 cells/mm(3) lower 1.41, 95% CI 1.02-1.96, P = 0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P < 0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence. CONCLUSIONS: Virological failure after 1 year of ART was not associated with minority drug resistance at baseline but with incomplete adherence. Strategies to assure adherence and uninterrupted drug supplies are pivotal factors for therapy success.

Immune activation despite suppressive highly active antiretroviral therapy is associated with higher risk of viral blips in HIV-1-infected individuals.

OBJECTIVES: Viral blips are thought to represent random biological variations around a steady state of residual HIV viraemia and to lack clinical significance. We aimed to assess the association of immune activation and the occurrence of blips. METHODS: HIV-infected patients from our out-patient cohort who developed a blip after having been on fully suppressive highly active antiretroviral therapy (HAART) for at least 180 days were matched with patients without blips according to duration of complete viral suppression (CVS), age, sex and Centers for Disease Control and Prevention (CDC) stage. Frequencies of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(+) HLA-DR(+), CD4(+) CD45RA(+), CD16(+) CD56(+) CD3(-) and CD19(+) cells, as well as C-reactive protein (CRP) levels and clinical parameters, were included in conditional logistic regression models. Adherence to HAART was assessed by measuring prescribed nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) plasma levels in a sample of 57 patients. RESULTS: Eighty-two patients with viral blip were matched with 82 controls from the same cohort. The mean age was 47.2 years [standard deviation (SD) 12.1 years], 80.5% of patients were male and 42.7% had CDC stage C disease. Viral blips occurred after a median of 14 months [interquartile range (IQR) 8-34 months] of CVS. In the logistic regression, activated CD3(+) HLA-DR(+) lymphocytes [odds ratio (OR) 1.25 per 100 cells/µL; 95% confidence interval (CI) 1.02-1.54; P = 0.03] were significantly associated with blips and there was a trend for an association of longer time on HAART with blips (OR 1.31 per year; 95% CI 0.96-1.78; P = 0.09). No between-group difference regarding subtherapeutic drug levels was found (P = 0.46). CONCLUSIONS: The occurrence of viral blips after suppressive HAART was associated with elevated markers of T-cell activation. Blips may identify a subset of patients with higher immune activation and increased risk for HIV disease progression.

High HIV prevalence among children presenting for general consultation in rural Cameroon.

Data on the HIV-prevalence children presenting to health care facilities in sub-Saharan Africa are scant in general, and the debate about opportunities for paediatric HIV screening is ongoing. Nine hundred and eighty-one children with unknown HIV-status presenting to a large general paediatric outpatient department in rural Cameroon were tested using the Determine HIV-1/2 rapid test (Abbott), and positive results were confirmed with the Hexagon HIV rapid test (Human Diagnostics). In children younger than 18 months, HIV infection was confirmed by PCR testing. Median age was 1.3 years and 52.8% were of male gender. In 514 children below 18 months of age, 16 (3.1%) tested positive. Of those, HIV-1 PCR was available for 11 children, of whom 6 had a positive PCR result. HIV prevalence was highest in the age group 5-9 years, being 8.8%. Malnutrition (33.3 vs 5.2%, p < 0.001) was associated with HIV infection. Our study results indicate that HIV testing should be offered to all children at possible entry points to medical care, irrespective of symptoms, in order to reduce HIV-associated mortality through timely initiation of antiretroviral therapy.

Parity as a cofactor for high-grade cervical disease among women with persistent human papillomavirus infection: a 13-year follow-up.

BACKGROUND: Several environmental factors have been associated with increased risks for cervical cancer. We examined whether reproductive history, contraceptive use, or sexual behaviour increase the risk for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among women with persistent human papillomavirus (HPV) infection. METHODS: A population-based cohort of women participated in a personal interview and underwent a gynaecological examination at which cervical specimens were obtained for HPV DNA testing. Follow-up information (~13 years) on cervical lesions was obtained from the Danish Pathology Data Bank. Women who had a high-risk HPV infection comprised the overall study population (n=1353). A subgroup of women with persistent high-risk HPV infection (n=312) was identified. Hazard ratios (HRs) for a diagnosis of CIN3+ and the corresponding 95% confidence intervals (CIs) were calculated. RESULTS: Women with persistent HPV infection who had given birth had a significantly increased risk for CIN3+ (HR=1.78; 95% CI: 1.07-2.94). No association was found with pregnancy, use of intrauterine devices, or sexual behaviour. Based on small numbers, women with persistent HPV infection had a decreased risk for CIN3+ with any use of oral contraceptives (HR=0.54; 95% CI: 0.29-1.00). CONCLUSION: Childbirth increases the risk for subsequent CIN3+ among women with persistent HPV infection.

[Prevention of nosocomial transmission of human immunodeficiency virus (HIV) from HIV-positive healthcare workers. Recommendations of the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V]. / Prävention der nosokomialen Übertragung von humanem Immunschwächevirus (HIV) durch HIV-positive Mitarbeiterinnen und Mitarbeiter im Gesundheitswesen. Empfehlungen der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) e.V. und der Gesellschaft für Virologie (GfV) e.V.

To the best of our knowledge, the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V. are the first in Europe to provide precise recommendations for the management of health care workers (HCWs) who are infected with human immunodeficiency virus (HIV). Requirements for HIV-infected HCWs need to be clearly defined. With a permanent viral burden of less than or equal to 50 copies/mL, HIV-positive HCWs are allowed to perform any surgery and any invasive procedure, as long as the infected HCW uses double-gloving, undergoes follow-up routinely by occupational medicine professionals, undergoes a quarterly examination of viral burden, and has a regular medical examination by a physician who has expertise in the management of HIV. Unrestricted professional activity is only possible with a strict compliance to take antiretroviral therapy and if the HIV-infected HCW strictly adheres to the recommended infection control procedures. Complete compliance with the recommendation almost certainly leads to no HIV transmission risk in patient care.