Gerrit Kann

Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care

BACKGROUND In the current epidemic of Ebola virus disease in western Africa, many aid workers have become infected. Some of these aid workers have been transferred to specialised hospitals in Europe and the USA for intensified treatment, providing the potential for unique insight into the clinical course of Ebola virus disease under optimised supportive measures in isolation units. METHODS A 38-year-old male doctor who had contracted an Ebola virus infection in Sierra Leone was airlifted to University Hospital Frankfurt, Germany, on day 5 after disease onset. Within 72 h of admission to the hospitals high-level isolation unit, the patient developed signs of severe multiorgan failure, including lungs, kidneys, and gastrointestinal tract. In addition to clinical parameters, the diagnostic work-up included radiography, ultrasound, pulse contour cardiac output technology, and microbiological and clinical chemistry analyses. Respiratory failure with pulmonary oedema and biophysical evidence of vascular leak syndrome needed mechanical ventilation. The patient received a 3 day treatment course with FX06 (MChE-F4Pharma, Vienna, Austria), a fibrin-derived peptide under clinical development for vascular leak syndrome. After FX06 administration and concurrent detection of Ebola-virus-specific antibodies and a fall in viral load, vascular leak syndrome and respiratory parameters substantially improved. We gave broad-spectrum empiric antimicrobial therapy and the patient needed intermittent renal replacement therapy. The patient fully recovered. FINDINGS This case report shows the feasibility of delivery of successful intensive care therapy to patients with Ebola virus disease under biosafety level 4 conditions. INTERPRETATION The effective treatment of vascular leakage and multiorgan failure by combination of ventilatory support, antibiotic treatment, and renal replacement therapy can sustain a patient with severe Ebola virus disease until virological remission. FX06 could potentially be a valuable agent in contribution to supportive therapy. FUNDING University Hospital of Frankfurt.

Impact of Stereotactic Biopsy in HIV Patients

OBJECTIVE During their disease a significant number of human immunodeficiency virus (HIV)-infected patients develop neurologic symptoms due to intracerebral pathologies. Entities commonly found are toxoplasmosis, lymphomas, or progressive multifocal leukoencephalopathy. In some patients, diagnosis is not feasible with imaging alone, requiring biopsy. The objective of this study was to evaluate the impact of stereotactic biopsy in HIV patients on adjustment of therapy. METHODS Between January 2004 and May 2015 at our clinic, 26 HIV-infected patients underwent stereotactic biopsy. Thin-layer magnetic resonance images were obtained and fused with computed tomography scans, taken with the stereotactic frame (Leksell) mounted. Biopsy material was evaluated pathologically and microbiologically. RESULTS Histologic analysis revealed B-cell lymphoma in 6 patients (23.1%) and progressive multifocal leukoencephalopathy in 2 patients (7.7%). Abscess and toxoplasmosis were found in 3 patients each (11.5% and 11.5%), and encephalitis occurred in 4 patients (15.4%). In 2 patients each (7.7%), vasculitis, metastasis, and glioblastoma were diagnosed. Further findings comprised non-Hodgkin lymphoma and Burkitt lymphoma in 1 patient each. After biopsy, treatment was significantly changed in 18 (69.2%) patients (P < 0.01). Antibiotic therapy was adjusted in 6 patients (23.1%), and chemotherapy in 3 patients (16.7%). Other changes included antibiotic/antiviral therapy to chemotherapy in 3 patients (16.7%), chemotherapy to radiation, cortisone to chemotherapy, and aciclovir to cortisone in 1 patient each. One patient with glioblastoma underwent resection, and another patient received radiation. One patient underwent palliative care. CONCLUSION Stereotactic biopsy in HIV-infected patients results in significant changes of therapy in more than two thirds of the patients.

Pathogen‐reduced Ebola virus convalescent plasma: first steps towards standardization of manufacturing and quality control including assessment of Ebola‐specific neutralizing antibodies

Ebola virus disease is a public health emergency of international concern, and enormous efforts are being made in the development of vaccines and therapies. Ebola virus convalescent plasma is a promising anti‐infective treatment of Ebola virus disease. Therefore, we developed and implemented a pathogen‐reduced Ebola virus convalescent plasma concept in accordance with national, European and global regulatory framework.

Genome Sequence of Lassa Virus Isolated from the First Domestically Acquired Case in Germany

ABSTRACT Lassa virus (LASV) is a zoonotic, hemorrhagic fever-causing virus endemic in West Africa, for which no approved vaccines or specific treatment options exist. Here, we report the genome sequence of LASV isolated from the first case of acquired Lassa fever disease outside of Africa.

Successful treatment of AIDS-associated, primary CNS lymphoma with rituximab- and methotrexate-based chemotherapy and autologous stem cell transplantation

Primary central nervous system lymphoma (PCNSL) is an Epstein–Barr virus (EBV)-associated, acquired immunodeficiency syndrome (AIDS)-defining malignancy. Even in the HAART (highly active antiretroviral therapy) era, in which the survival of patients with PCNSL has improved and the incidence has sharply reduced [1, 2], the median survival time is\6 months [1]. PCNSL has become a rare disease and, consequently, there is no consensus and only anecdotal evidence on the best treatment. Options include high-dose methotrexate (MTX) and radiotherapy. In the non-human immunodeficiency virus (HIV) setting, sequential high-dose MTX/cytarabin regimens followed by autologous stem cell transplantation (SCT) have been shown to improve 5-year overall survival from 69 to 87 % [3]. The addition of radiation therapy to such regimens, however, was found to be associated with increased neurotoxicity [4]. There is currently no data on the feasibility and efficacy of such protocols in the clinical setting of HIV. We report here on a young patient who was administered high-dose MTX/cytarabin chemotherapy combined with rituximab, followed by autologous peripheral SCT (PSCT) without radiotherapy, and achieved a durable complete remission. A 36-year-old male was transferred to our infectious diseases ward from a neurology department where he had been admitted with a series of generalized seizures, an acute paresis of the left upper limb and aphasia as well as disorientation. Imaging showed two brain lesions, one frontal and one parietal. As the patient had cutaneous kaposi sarcoma (KS) lesions, he was tested for HIV and found to be positive. The initial CD4 count was 96/ll. Serological testing was negative for toxoplasmosis and cryptococcal antigen. Cerebral biopsy showed a highly proliferative diffuse large cell lymphoma positive for EBV and the B cell marker CD20. The cerebral spinal fluid showed a high HIV load of 12,600 copies/ml (peripheral blood 817,000/ml) and was negative for Polyomavirus JC (John Cunningham) based on PCR assay. Antiretroviral therapy with tenofovir/ emtricitabine, raltegravir and ritonavir-boosted darunavir was initiated. This therapy was chosen in order to achieve a faster decay of HIV with integrase inhibitors, as well as to provide a potential independent effect of protease inhibitors on the KS. The HIV load decreased to \20 copies/ml after 4 months. Combination antiretroviral therapy (cART) was administered throughout the complete chemotherapy and PBSCT treatment and continues to be administered to date. Staging revealed no further manifestation, and PCNSL was diagnosed. Chemotherapy containing two doses of rituximab (2 9 375 mg/m), high-dose MTX (3,500 mg/m) and cytarabin (2,000 mg/m) was initiated. This was used analogously to a large phase 2 trial (EUDRA-CT no. 2009-012432-32, IELSG 32). No further seizures occurred, and the neurological deficits and the disorientation resolved within 2 weeks. The patient received two cycles of treatment, which were tolerated with moderate hematotoxicity (lowest neutrophile count 0.01/nl, lowest platelet count 4/nl). This case was presented at the 14th EACS Conference, October 16–19th, 2013, Brussels, Belgium.

Management of Microbiological Samples in a Confirmed Case of Ebola Virus Disease: Constraints and Limitations.

ABSTRACT 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.

New Lineage of Lassa Virus, Togo, 2016

We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo.

Complete Genome Sequence of an Ebola Virus Isolate Imported from Sierra Leone to Germany Determined by Circle Sequencing.

ABSTRACT We report here a complete genome sequence of Ebola virus Makona from a nonfatal patient sample that originated in Sierra Leone during the last Ebola virus outbreak in West Africa (species Zaire ebolavirus) using a highly accurate circle sequencing (Cir-seq) method.

Autologous stem cell transplantation in HIV-related lymphoma in the rituximab era - a feasibility study in a monocentric cohort.

Since the introduction of highly active antiretroviral therapy (HAART) [ 1 ] and later on the availability of anti‐CD20 monoclonal antibody treatment [ 2 ], the therapeutic options as well as the prognosis of AIDS related lymphoma (ARL) have been improved. There is however no uniform agreement on how to treat patients who do not achieve a partial remission, who experience a relapse or who have very aggressive subtypes. Autologous hematopoietic stem cell transplantation (ASCT) has become an option for those patients. We retrospectively examined ARL patients to elucidate the feasibility of high‐dose chemotherapy and autologous stem cell transplantation.