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In light of the recent Ebola virus outbreak, it has to be realized that besides medical treatment, precise algorithms for the management of complicating microbial infections are mandatory for Ebola virus disease (EVD) patients. While the necessity of such diagnostics is apparent, practical details are much less clear. Our approach, established during the treatment of an EVD patient at the University Hospital in Frankfurt am Main, Germany, provides a roadmap for reliable and safe on-site microbiological testing., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Patients suffering from highly contagious, life-threatening infections should be treated in specialized clinical facilities that follow the highest infection control standards. Consensus statements defining technical equipment and operational procedures have been published in recent years, but the level of adherence to these has not been evaluated., Methods: Data summarized here comparing German and European isolation facilities are the partial results of a cross-sectional analysis conducted by the "European Network for Highly Infectious Diseases" that included 48 clinical care facilities in 16 European nations. Data collection was conducted using questionnaires and on-site visits, focussing on aspects of infrastructure, technical equipment, and the availability of trained personnel., Results: Although all centres enrolled were listed as "isolation units", all aspects evaluated differed broadly. Eighteen facilities fulfilled the definition of a 'High Level Isolation Unit', as 6/8 enrolled German facilities did. In contrast, 24 facilities could not operate independently from their co-located hospital., Discussion: Within and between nations contributing data disparities regarding the fulfilment of guidelines published were seen. German isolation facilities mostly fulfilled all criteria evaluated and performed on a high technical level. However, data presented do not reflect the current situation in Germany due to the time that has elapsed since the study was conducted. Hence, longitudinal data collection and harmonisation of terminology at least on national level needs to be implemented.

Objectives: The renal elimination of tenofovir (TFV) may be subject to renal drug-drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug-drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells., Methods: A retrospective analysis of data for all patients from the Frankfurt HIV Cohort (FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out., Results: Among 89 patients with diclofenac use, 61 patients (68.5%) were treated with tenofovir disoproxil fumarate (TDF) and 28 patients (31.5%) were treated with TDF-sparing combination antiretroviral therapy (cART). Thirteen patients (14.6%) developed acute kidney injury (AKI) shortly after initiating diclofenac treatment. AKI occurred exclusively in TDF-treated patients, although all had previously stable renal function. All cases were accompanied by new onset of at least two parameters indicating proximal tubular damage, such as normoglycaemic-glucosuria and hypophosphataemia. TFV-associated nephrotoxicity was demonstrated by renal biopsy in four cases. Additionally, 11.5% of patients on TDF treatment developed new-onset proximal tubular damage, while having a preserved glomerular filtration rate. In contrast, diclofenac did not affect renal function in patients with TDF-sparing cART, as only one case of isolated hypophataemia was observed in these patients. In univariate analysis, risk factors for AKI were TDF-containing cART (P = 0.0076) and pre-existing hypophosphataemia (P = 0.0086)., Conclusions: Drug-drug interaction caused by diclofenac could exacerbate TFV-associated nephrotoxicity. Diclofenac should be used with caution in patients on TDF therapy, especially in those with hypophosphataemia. Our findings need to be confirmed in larger studies., (© 2013 British HIV Association.)

Background and Objective: Renal disease is a common complication in HIV-infected patients. The causes and spectrum of kidney disease among these patients is extensive, including HIV-related and HIV unrelated causes. Our objective was to assess the changes in distribution of renal disease under antiretroviral therapy (ART)., Patients and Methods: Retrospective analysis of all patients from the Frankfurt HIV Cohort (FHC) who underwent renal biopsy because of chronic, progressive renal disease between 1989 and 2012. Two time periods were defined: 1989-2001 (early period) and 2000-2012 (late period)., Results: 69 HIV-infected patients, mostly Caucasian and male, underwent renal biopsy (early period: 22 patients, late period: 47 patients). During the total observation time immuncomplex-mediated glomerulonephritis (26.1 %), hypertensive (20.3 %) and diabetic nephropathy (20.3 %) were the most frequent causes of chronic renal disease. HIV-associated renal diseases were predominant in the first period, whereas hypertensive and diabetic kidney disease accounted for almost 50 % of cases diagnosed in the late period. Other types of renal disease frequently encountered during the late period include renal AA-amyloidosis and tenofovir-related kidney disease., Conclusion: The underlying pathology of renal disease in HIV-infected patients is highly variable and evolving. Since the introduction of HAART, renal disease not directly related to HIV has become the predominant cause, reflecting the growing burden of co-morbidities in this aging population., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Renal disease is a common and serious complication in HIV-infected patients., Methods: A retrospective cohort analysis for the period 1989-2010 was carried out to determine the prevalence, incidence and risk factors for end-stage renal disease (ESRD). ESRD was defined as initiation of renal replacement therapy. Three time periods were defined: 1989-1996 [pre-highly active antiretroviral therapy (HAART)], 1997-2003 (early HAART) and 2004-2010 (late HAART)., Results: Data for 9198 patients [78.2% male; 88.9% Caucasian; cumulative observation time 68 084 patient-years (PY)] were analysed. ESRD was newly diagnosed in 35 patients (0.38%). Risk factors for ESRD were Black ethnicity [relative risk (RR) 5.1; 95% confidence interval (CI) 2.3-10.3; P < 0.0001], injecting drug use (IDU) (RR 2.3; 95% CI 1.1-4.6; P = 0.02) and hepatitis C virus (HCV) coinfection (RR 2.2; 95% CI 1.1-4.2; P = 0.03). The incidence of ESRD decreased in Black patients over the three time periods [from 788.8 to 130.5 and 164.1 per 100 000 PY of follow-up (PYFU), respectively], but increased in Caucasian patients (from 29.9 to 41.0 and 43.4 per 100 000 PYFU, respectively). The prevalence of ESRD increased over time and reached 1.9 per 1000 patients in 2010. Mortality for patients with ESRD decreased nonsignificantly from period 1 to 2 (RR 0.72; P = 0.52), but significantly from period 1 to 3 (RR 0.24; P = 0.006), whereas for patients without ESRD mortality decreased significantly for all comparisons. ESRD was associated with a high overall mortality (RR 9.9; 95% CI 6.3-14.5; P < 0.0001)., Conclusion: As a result of longer survival, the prevalence of ESRD is increasing but remains associated with a high mortality. The incidence of ESRD declined in Black but not in Caucasian patients. IDU and HCV were identified as additional risk factors for the development of ESRD., (© 2012 British HIV Association.)

In January 2012, a case of Human African Trypanosomiasis (HAT) has been identified in Germany in a traveller returning from the Masai Mara area in Kenya. The 62-year-old man had travelled to the Masai Mara game park from 18 to 19 January 2012 and developed fever on 28 January. The infection with Trypanosoma brucei rhodesiense was confirmed by laboratory testing three days hereafter.

Objective: To determine rates of seroconversion after single vaccination with a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HIV-1-infected patients (ClinicalTrials.gov Identifier: NCT01017172)., Design: Single center diagnostic study., Setting: Institutional HIV outpatient department of an urban university clinic., Participants: Adult HIV-1-infected individuals., Intervention: Serum samples were taken before and 21 days after vaccination., Main Outcome Measures: Antibody titers determined by hemagglutination inhibition assay. Seroconversion to vaccination was defined by either an antibody titer of 1: 10 or less before and of at least 1: 40 after or at least 1: 10 before and at least four-fold increase in antibody titer 21 days after single vaccination., Results: One hundred and sixty patients (125 men/35 women) were analyzed. Before vaccination, 23 patients (14.4%) had a hemagglutination inhibition assay titer of at least 1: 40. A median of 22 +/- 3 days after vaccination, 110 (69%) patients seroconverted. Seroconverters were younger (45.1 +/- 10.0 vs. 48.8 +/- 11.3 years; P = 0.04), had a higher CD4 cell count (532 +/- 227 vs. 475 +/- 281 cells/microl; P = 0.03) and were more likely to have received a previous H5N1 vaccination in 2009 (25 vs. 8%; P = 0.02) when compared to nonresponders. No other significant differences were found comparing the two groups (prevaccination hemagglutination inhibition assay titer of > or =1: 40, AIDS, HAART, HIV RNA PCR <50 copies/ml or CD4 nadir, CD4 and CD8 percentage, sex, BMI, chronic hepatitis B or C)., Conclusion: Seroconversion after one dose of a split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine of HIV-infected patients was 69%. Studies to investigate whether a second dose of the vaccine will increase seroconversion rate are needed.

Background and Objective: In February 2003, a newly emerged infectious disease was described, the etiology of which was initially unknown. It is referred to under the term SARS. In the beginning, it spread in some regions South-East Asia. Import infections appeared in many other parts of the world. Based on the first cases in Germany, this report illustrates the clinical appearance, the diagnostic results and the management of this new disease., Patients and Methods: We analysed the data of two patients with SARS and one suspected patient. The results of radiological, laboratory, microbiological and physical examinations were abstracted and compared with the data obtained in other regions., Results: Two of the three patients under our care developed SARS disease. This is characterised by fever of sudden onset lasting for more than 5 days, rapidly changing consolidations in chest x-ray not affected by antimicrobial therapy, leuko-, lympho- as well as thrombopenia with a compromised pulmonary function later in the course. Close contacts with SARS patients does not regularly result in full development of the disease. Secretion of a coronavirus could be detected in respiratory samples during the febrile phase and in feces for a longer time. It is still an open question whether bedrest and antibiotic prophylaxis by themselves or an additional administration of ribavirin and corticosteroids can improve the outcome., Conclusion: SARS is a new and highly contagious lung disease. It is crucial to be able to recognize the clinical appearance and the diagnostic features of this disease at an early stage, in order to prevent a further dissemination of the disease.

Postmortem neuropathologic reports for a consecutive series of 436 HIV-seropositive patients who died between 1985 and 1999 were matched with clinical data for 371 of them. Cases were divided into four groups depending on the date of death. The chosen time periods reflected the type of antiretroviral therapy available: before 1987 (before zidovudine); 1987-1992, the period of monotherapy (nucleoside analog reverse transcriptase inhibitors [NRTIs]); 1993-1995, the era of the use of dual NRTI combinations; and 1996-1999, the era of highly active antiretroviral therapy (HAART) containing protease inhibitors. Fifty-seven percent of our cases in this group had been prescribed HAART. In our study population, accessibility to the latest antiretroviral therapy was widespread. The total number of HIV autopsies declined after the advent of combination therapy. The prevalence of opportunistic infections-cytomegalovirus, toxoplasmosis, cryptococcosis, and central nervous system lymphoma-decreased over time. Cerebral tuberculosis, aspergillosis, herpes, and progressive multifocal leukoencephalopathy showed a downward trend, but the numbers were too low for statistical analyses. The incidence of HIV encephalopathy increased over time (p =.014). The rising prevalence of HIV encephalopathy at time of death may reflect a longer survival time after initial HIV infection in the HAART era. Although combination therapies decrease overall mortality and prevalence of CNS opportunistic infections, these therapies may be less active in preventing direct HIV-1 effects on the brain.

Background: Dengue fever is increasingly recognized in travelers returning from endemic areas with acute febrile illness; however, its true burden in nonendemic countries is unknown. Only few studies focus on clinical manifestations and serological findings in primarily nonimmune individuals., Patients and Methods: We analyzed the epidemiology, clinical manifestations and virological results in patients with imported acute dengue infection who presented at our travel clinic in Frankfurt am Main, Germany, between September 1998 and November 2000. An immunochromatographic test and an immunofluorescence assay were used for antibody testing., Results: Dengue fever was confirmed in 13 patients, thus being the second commonest tropical infection after malaria in patients with fever and a travel history to a tropical country (18 cases per 1,000 patient visits per year). Most patients had only spent a short time abroad, either in South Central or South East Asia or in the Caribbean., Conclusion: The clinical features considered typical for dengue were not always present. Antibody assays were typically negative early in the course of disease, with seroconversion occurring only after cessation of clinical symptoms. A high index of suspicion is needed in these patients who often present without typical features of dengue and whose early antibody tests may be negative.

Background and Objective: Because of the paucity of information on the epidemiology of acute poisoning requiring intensive medical care, all such patients treated on the medical intensive care unit of the university hospital in Frankfurt am Main, Germany, between January 1993 and December 1999, were retrospectively evaluated., Patients and Methods: Of the total of 6211 patients, 147 (80 women, 67 men, mean age 41 years, 2,3 %) were treated for acute intoxication in the intensive care unit., Results: Reasons for admission to the intensive care unit were the need for ventilator treatment or intensive monitoring of vital functions. 52 % of the patients (n = 76) had attempted suicide, most of them using anti-depressive drugs (n = 19), paracetamol (n = 16), or benzodiazepines (n = 9). Two patients (2,6 %) died. 48 % of the patients (n = 71) were admitted because of accidental poisoning. Leading toxic agents in this group were heroin (n = 19), alcohol (n = 18) and digitalis (n = 12). 11 patients had taken herbicides, animal poisons or chemicals used at work or for house cleaning. In this cohort, three i. v. drug abusers (4,2 %) had died. Depending on the agents used, a variety of treatments (charcoal, antidots, extracorporal therapy) were undertaken., Conclusion: Due to excellent care in the prehospital phase and in the emergency room the number of patients requiring treatment on the intensive care unit was rather low. The mortality was in the range of other reports.

Objective: To determine the influence of antimicrobial therapy and of predisposing illness on the septicemia mortality rate., Method: All blood-culture-positive episodes of septicemia in the Department of Medicine at the University Hospital in Frankfurt between 1989 and 1993 were entered on a database. Underlying illnesses were classified as immunocompromising diseases (hematological malignancies, AIDS and others), severe chronic and chronic illnesses and no predisposing illnesses. Therapy was judged on the basis of the in-vitro-susceptibility of the organism ('appropriate') and the interval (no. of days) between the onset of septicemia and start of appropriate treatment noted. For mortality all deaths within 28 days after the onset of septicemia were counted., Results: Overall mortality due to septicemia was 18.1%, ranging from 9.4% (organ transplantation) to 50% (liver cirrhosis) according to the underlying illness. Mortality in patients receiving appropriate treatment (83.1%) was 16% as opposed to 28%, if no appropriate treatment was given (p<0.001). Comparison of appropriate treatment started within and after 48 hours revealed a reduction in mortality from 30.9% to 15.4% for early appropriate therapy in patients with hematological malignancies (p<0.002). For septicemia in patients with AIDS and chronic illnesses mortality was significantly higher (p<0.05) if treatment remained inappropriate (AIDS 28.6%, chronic illness 33.3%), but was similar when early and delayed appropriate therapy were compared (AIDS: 13% vs. 12.8%, chronic illness 11.8% vs. 11.1%)., Conclusion: First-line treatment regimens for septicemia in patients with hematological malignancies should include the greatest possible part of the spectrum of causative organisms. In contrast to that it may be acceptable to rely to some extent on a change of treatment, when treating septicemia in patients with chronic illnesses or AIDS. These considerations are of value in the debate on rising health care costs. Several other facts, such as the stable mortality rate of 8 - 12% in previously healthy patients and the range of mortality from 9.4 - 50%, if predisposing illnesses are present, indicate the existence of adverse factors influencing the outcome of septicemia in spite of appropriate therapy. These pathophysiological factors will have to be studied in detail in order to improve the prognosis of septicemia further.

Objective: To determine the incidence of AIDS-defining opportunistic infections and malignancies over a 5-year period from 1992 to 1996., Study Population: Subcohort of 1003 homosexual men with HIV infection and CD4 count less than 200 x 10(6) cells/l from the Frankfurt AIDS Cohort Study., Methods: Data including the earliest date that a CD4 T-lymphocyte count < 200 x 10(6)/l was reached and the dates of AIDS-defining events were compiled from medical records. Incidence analyses for AIDS-defining events and death during the subsequent 5 years (1992-1996) were performed using rates per 100 person-years of exposure., Results: During the observation period, the number of patients per year with CD4 T-lymphocyte counts < 200 x 10(6)/l varied between 402 and 511. In 1992, 56.7% of patients experienced at least one AIDS-defining illness, and 20.7% in 1996. The annual number of AIDS-defining events per 100 patient-years of observation declined from 143.5 in 1992 to 38.3 in 1996, and the number of AIDS-related deaths fell from 25.7 to 12.9. Analysis of the number of events confirmed this trend for malignancies and single opportunistic infections, with the exception of mycobacterial diseases., Conclusions: The incidence of AIDS-defining events in patients with advanced HIV infection at Frankfurt University Hospital has declined by more than 70% from 1992 to 1996.

Frequency and risk of tuberculosis were studied among a large group of HIV-infected patients (n = 2556), 869 of whom had AIDS, over a period of ten years (February 1982 through February 1992) at the University Hospital Frankfurt. A total of 148 (5.8%) out of 2.556 patients had tuberculosis. With increasing immunodeficiency, the frequency of tuberculosis rose. The rate of tuberculosis in post-mortem was even higher, i.e. 17.3%. I.v. drug-addict AIDS patients were inflicted with 18.5% considerably more often than homo-/bisexual patients with 12.3%. The same holds true with 25% of tuberculosis infections for AIDS patients from endemic areas as compared with 13% for patients from countries with lower tuberculosis incidence. 18% of patients contracted tuberculosis already at > 200 CD4-positive cells/microliters before AIDS manifestation. Coming from endemic areas, drug addiction and lower number of T-cells signify a high risk for HIV-infected patients to acquire a post-primary or primary tuberculosis, respectively. HIV-infected patients represent a relevant danger of infection for partners and health-care personnel. In contrast to the United States, no increase in the tuberculosis incidence, except for some areas like Frankfurt, has been noted. Preventive measures, which include the IHN prophylaxis for patients with T-cell counts < 150/microliters, should be discussed.