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Circulatory shock, caused by severe intravascular volume depletion resulting from gastrointestinal losses and profound capillary leak, is a common clinical feature of viral hemorrhagic fevers, including Ebola virus disease, Marburg hemorrhagic fever, and Lassa fever. These conditions are associated with high case fatality rates, and they carry a significant risk of infection for treating personnel. Optimized fluid therapy is the cornerstone of management of these diseases, but there are few data on the extent of fluid losses and the severity of the capillary leak in patients with VHFs, and no specific guidelines for fluid resuscitation and hemodynamic monitoring exist. We propose an innovative approach for monitoring VHF patients, in particular suited for low-resource settings, facilitating optimizing fluid therapy through remote-controlled and pulse pressure–guided fluid resuscitation. This strategy would increase the capacity for adequate supportive care, while decreasing the risk for virus transmission to health personnel.

The recent Ebola virus disease (EVD) epidemic in Guinea, Liberia and Sierra Leone demonstrated that the World Health Organization (WHO) is incapable to control outbreaks of infectious diseases in less developed regions of the world. This essay analyses the causes for the failure of the international response and proposes four measures to improve resilience, early detection and response to future outbreaks of infectious diseases.

Invasive aspergillosis (IA) is a serious hazard to high-risk haematological patients. There are increasing reports of azole-resistant Aspergillus spp. This study assessed the epidemiology of IA and azole-resistant Aspergillus spp. in patients with acute leukaemia in Germany. A prospective multicentre cohort study was performed in German haematology/oncology centres. The incidence of probable and proven aspergillosis according to the revised EORTC/MSG criteria was assessed for all patients with acute leukaemia [acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL)]. Cases were documented into a web-based case report form, and centres provided data on standards regarding prophylactic and diagnostic measures. Clinical isolates were screened centrally for azole resistance and, if applicable, underlying resistance mechanisms were analysed. Between September 2011 and December 2013, 179 cases of IA [6 proven (3.4%) and 173 probable (96.6%)] were diagnosed in 3067 patients with acute leukaemia. The incidence of IA was 6.4% among 2440 AML patients and 3.8% among 627 ALL patients. Mortality at Day 84 was 33.8% (49/145) and attributable mortality was 26.9% (39/145). At Day 84, 53 patients (29.6%) showed a complete response, 25 (14.0%) a partial response and 17 (9.5%) a deterioration or failure. A total of 77 clinical Aspergillus fumigatus isolates were collected during the study period. Two episodes of azole-resistant IA (1.1%) were caused by a TR/L98H mutation in the cyp51A gene. With only two cases of IA due to azole-resistant A. fumigatus, a change of antifungal treatment practices in Germany does not appear warranted currently.

Epstein-Barr virus (EBV) DNAemia and reactivation is a typical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The degree of immunosuppression is closely linked to the risk of developing EBV DNAemia. An association of cyclosporine levels with EBV DNAemia has not been interrogated. Here, we analyzed cyclosporine levels in 58 patients after allogeneic HSCT. We discovered a wide range of cyclosporine trough level variation in the individual patient (median coefficient of variation [CV] 0.29, range 0.19-0.78). To overcome this high intra-individual variation in serum trough levels of cyclosporine, we calculated respective areas under the curve (AUC) and performed correlations with EBV DNAemia in 28 stem cell recipients at increased risk for EBV DNAemia. This resulted in a significant association of high cyclosporine AUC (> 6000 ng/mL × days) with EBV DNAemia after day 30 (relative risk [RR] 6.067, 95% confidence interval [CI] 1.107-33.238, p = 0.038). Conversely, mean cyclosporine values (threshold 200 ng/mL) between days 0 and 30 were not found to correlate with EBV DNAemia after day 30. Furthermore, CD3 + CD8 + graft content was inversely correlated with EBV DNAemia after day 30. These findings might establish a clinical role for the AUC of cyclosporine.

An immunocompetent Nigerian developed a fulminant hemophagocytic lymphohistiocytosis due to Epstein-Barr virus reactivation. The patient initially presented with fever, hepatosplenomegaly and pancytopenia. The clinical status of our patient deteriorated quickly despite treatment with corticoids. Escalation of immunosuppressive treatment was not possible. He died of lung, liver and circulatory failure in our intensive care unit.Hemophagocytic lymphohistiocytosis is a rare disease characterized by inflammation due to prolonged and excessive activation of antigen-presenting cells. High plasma ferritin levels and phagocytosis of hematopoetic cells in bone marrow, spleen and liver lead to the diagnosis. Hemophagocytic lymphohistiocytosis should therefore be included in the differential diagnosis in patients with persistent fever, hepatosplenomegaly and cytopenia.

Objectives This study was a detailed investigation of Staphylococcus epidermidis clinical isolates exhibiting linezolid resistance. Methods Thirty-six linezolid-resistant S. epidermidis from eight German hospitals, including isolates from suspected hospital-associated outbreaks between January 2012 and April 2013, were analysed with respect to their antimicrobial susceptibility and the presence of cfr and/or mutations in the 23S rRNA, rplC, rplD and rplV genes. Relatedness of isolates was estimated by MLST and SmaI macrorestriction analysis. Characterization of cfr plasmids was carried out by means of Illumina sequencing. Results The MICs of linezolid varied substantially between the isolates. No apparent correlation was detected between the level of resistance, the presence of cfr and ribosomal target site mutations. S. epidermidis isolates from two hospitals were confirmed as clonally related, indicating the spread of the respective clone over a period of 1 year. Next-generation sequencing revealed two different categories of cfr-expressing plasmids, both of them varying in genetic arrangement and composition from previously published cfr plasmids: p12-00322-like plasmids showed incorporation of cfr into a pGO1-like backbone and displayed capabilities for intra- and inter-species conjugational transfer. Conclusions To date, linezolid-resistant S. epidermidis have rarely been isolated from human clinical sources in Germany. Here, we describe the emergence and outbreaks of these strains. We detected previously described and novel point mutations in the 23S ribosomal genes. The cfr gene was only present in six isolates. However, this is the first known description of cfr incorporation into conjugative vectors; under selective pressure, these vectors could give reasonable cause for concern.

GB virus B (GBV-B) is a virus of the family Flaviviridae that infects small primates ( Saguinus sp. [tamarins]) and shows similarities to hepatitis C virus (HCV) in genome organization, protein function, tissue tropism, and pathogenicity. This suggests the possibility of using tamarins infected by GBV-B or GBV-B/HCV chimeric viruses as a surrogate animal model of HCV infection. To achieve the construction of such chimeric viruses, it is essential to produce a complete and infectious GBV-B genomic RNA. We have identified a novel sequence at the 3′ end of the GBV-B genome and show that it can be arranged in a secondary structure resembling that of the 3′ end of the HCV genome, which is known to be essential for infectivity.

The Zika virus (ZIKV) has received considerable attention over the past two years. In view of its threat to the developing fetus and the absence of specific antiviral therapy, the public health response must focus on prevention. The two major preventive strategies are vaccine development and vector control, in addition to avoidance of pregnancy where transmission occurs. Logistical challenges of vaccine distribution and the epidemiology of Zika, which has so far been characterised by sporadic outbreaks, may pose challenges in the deployment of a potential ZIKV vaccine. Routine mass ZIKV vaccinations in the absence of an outbreak will have a disadvantageous cost/benefit ratio. Reactive targeted vaccinations require time to implement; by the time an outbreak has been detected and a reactive vaccination campaign is under way, the number of cases would likely have already peaked and susceptible people infected. Individuals should have the option to protect themselves through a safe and protective ZIKV vaccine, for which there will be considerable demand. From a public health perspective, targeting the mosquito vector Aedes aegypti to control and prevent ZIKV outbreaks is currently much more attractive than the vaccine approach. Besides, a potential ZIKV vaccine would only target that single virus. The recent ZIKV outbreak in many states of Brazil occurred between two other vector-borne disease outbreaks, dengue and chikungunya [1]. In contrast, vector control has the potential to prevent several mosquito-borne infections. In this issue of PLOS Medicine, Fernando Abad-Franch and colleagues describe a new method to curb the Ae. aegypti population in a city in Brazil [17].

Surfactant proteins (SP) have been studied intensively in the respiratory system. Surfactant protein A and surfactant protein D are proteins belonging to the family of collectins each playing a major role in the innate immune system. The ability of surfactant protein A and surfactant protein D to bind various pathogens and facilitate their elimination has been described in a vast number of studies. Surfactant proteins are very important in modulating the host's inflammatory response and participate in the clearance of apoptotic cells. Surfactant protein B and surfactant protein C are proteins responsible for lowering the surface tension in the lungs. The aim of this study was an investigation of expression of surfactant proteins in the central nervous system to assess their specific distribution patterns. The second aim was to quantify surfactant proteins in cerebrospinal fluid of healthy subjects compared to patients suffering from different neuropathologies. The expression of mRNA for the surfactant proteins was analyzed with RT-PCR done with samples from different parts of the human brain. The production of the surfactant proteins in the brain was verified using immunohistochemistry and Western blot. The concentrations of the surfactant proteins in cerebrospinal fluid from healthy subjects and patients suffering from neuropathologic conditions were quantified using ELISA. Our results revealed that surfactant proteins are present in the central nervous system and that the concentrations of one or more surfactant proteins in healthy subjects differed significantly from those of patients affected by central autoimmune processes, CNS infections or cerebral infarction. Based on the localization of the surfactant proteins in the brain, their different levels in normal versus pathologic samples of cerebrospinal fluid and their well-known functions in the lungs, it appears that the surfactant proteins may play roles in host defense of the brain, facilitation of cerebrospinal fluid secretion and maintenance of the latter's rheological properties.

Candida infections are a major cause of fungal septicemia in neonates and are associated with marked morbidity and mortality. Despite the spectrum of antifungal drugs being dramatically extended during the last decade, invasive fungal infections remain a serious challenge for neonatologists. Amphotericin B and its lipid formulations are the drugs of choice for the treatment of systemic candidiasis in neonates. The combination of antifungal drugs with different sites of action, like caspofungin and amphotericin B, may improve antifungal efficacy. Severe congenital ichthyosis often leads to death within the neonatal period. Main causes of death are dehydration, electrolyte disturbances, and respiratory or systemic infections. We report the case of a preterm infant with severe congenital ichthyosis and sepsis caused by Candida albicans. The infection did not improve despite proper liposomal amphotericin B treatment. After addition of caspofungin, the baby recovered. To our best knowledge, a case of a preterm infant suffering from severe congenital ichthyosis and Candida albicans sepsis, who survived, has not been previously described.

Chronic carriers of hepatitis B virus (HBV) who have to be immunosuppressed are at risk for HBV reactivation and hepatitis. Continuing immunosuppression in such patients and in immunosuppressed patients with active hepatitis B is strongly discouraged yet frequently inevitable. We here report on both the successful control of hepatitis and seroconversion after HBV reactivation following allogeneic hematopoietic stem cell transplantation (HSCT) with entecavir despite systemic immunosuppression.

Objectives: Although most susceptibility studies for linezolid have investigated aerobic bacteria, only a few have investigated anaerobe isolates. The aim of the present study was to determine the antibacterial activity of linezolid against a larger sample of clinical isolates of Fusobacterium spp. and to report on the detailed susceptibility, stratified by species. Methods: The in vitro susceptibility of 80 clinical isolates of Fusobacterium (Fusobacterium necrophorum, n = 34; Fusobacterium nucleatum, n = 20; Fusobacterium varium, n = 18; Fusobacterium mortiferum; n = 8) was tested and compared with the activity of the older compounds amoxicillin and amoxicillin/clavulanic acid. Results: The MIC of linezolid ranged from 0.016 to 1.0 mg/L, with the MIC90 being 0.5 mg/L. The highest MIC obtained for linezolid (1.0 mg/L) was measured for an F. varium isolate. The MIC90 for both, amoxicillin (range: 0.016–0.75 mg/L) and amoxicillin/clavulanic acid (range: 0.047–0.75 mg/L), was 0.5 mg/L. Overall, no resistant strains were found in the study. Conclusions: Compared with amoxicillin and amoxicillin/clavulanic acid, linezolid was less active against F. necrophorum (MIC90 0.25 mg/L) and F. nucleatum (MIC90 0.25 mg/L), equally active against F. varium (MIC90 0.75 mg/L) and slightly more active against F. mortiferum (MIC90 0.19 mg/L).

Sepsis in the early stage is a common disease in emergency medicine, and rapid diagnosis is essential. The aim of our monocentric observational study (characterization of patients with sepsis in the emergency department) was to compare pathogen diagnosis by blood cultures (BC) and PCR.