Caring for patients with Ebola virus disease: Are U.S. biocontainment centers ready for the next outbreak?

The 2014 West African Ebola virus disease (EVD) outbreak is the largest and deadliest EVD epidemic to date, resulting in fivefold more cases than all other outbreaks combined. This outbreak was particularly devastating to healthcare workers in West Africa and resulted in several EVD patients being medically evacuated for treatment in the U.S. and Europe. Governmental agencies provide recommendations for triaging and testing patients with EVD, however best laboratory practices are still unknown and are very resource dependent.     

Analyses of the mitochondrial mutations in the Chinese patients with sporadic Creutzfeldt–Jakob disease

Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause a variety of chronic diseases in central nervous system (CNS). However, the role of mtDNA mutations in sporadic Creutzfeldt–Jakob disease (sCJD) has still been unknown. In this study, we comparatively analyzed complete mtDNA sequences of 31 Chinese sCJD patients and 32 controls. Using MITOMASTER and PhyloTree, we characterized 520 variants in sCJD patients and 507 variants in control by haplogroup and allele frequencies. We classified the mtDNAs into 40 sub-haplogroups of 5 haplogroups, most of them being Asian-specific haplogroups. Haplogroup U, an European-specific haplogroups mtDNA, was found only in sCJD. The analysis to control region (CR) revealed a 31% increase in the frequency of mtDNA CR mutations in sCJD versus controls. In functional elements of the mtDNA CR, six CR mutations were in conserved sequence blocks I (CSBI) in sCJD, while only one in control (P<0.05). More mutants in transfer ribonucleic acid-Leu (tRNA-Leu) were detected in sCJD. The frequencies of two synonymous amino-acid changes, m.11467A>G, p.(=) in NADH dehydrogenase subunit 4 (ND4) and m.12372G>A, p.(=) in NADH dehydrogenase subunit 5 (ND5), in sCJD patients were higher than that of controls. Our study, for the first time, screened the variations of mtDNA of Chinese sCJD patients and identified some potential disease-related mutations for further investigations.     

Characterisation of foot-and-mouth disease virus strains circulating in Turkey during 1996–2004

Summary. Two genotypes of foot-and-mouth disease virus serotype A were identified as the cause of disease outbreaks in Turkey during 1996–2004, while serotype O strains, identified during the same period, seem to represent an evolutionary continuum, and Asia1 strains were only rarely identified. The data presented are concordant with the conclusion that serotype A strains are repeatedly introduced to Turkey from the east and circulate only transiently in farming communities, while type O strains persist and re-emerge from endemic areas of Turkey. The co-circulation of strains belonging to two A genotypes for 6 years, as observed in the present study, is a remarkable difference compared to previous decades in which only one A genotype was transiently circulating, successively being replaced by others. This co-circulation was observed in spite of enforcement countrywide of biannual vaccination of more than 50% of the cattle during the same period. Mean r₁ values of 0.70 ± 0.19 and 0.39 ± 0.04 found for A96 and A99 isolates, respectively, compared to the A96 vaccine component reveal antigenic differences but also imply that the vaccine in use in Turkey should provide protection against both genotypes. It is suggested that further studies to reveal the nature of the difference in epidemiological dynamics of type A and type O strains might lead to an understanding of the measures required to control foot-and-mouth disease in islands of persistent circulation.     

Can immune-related genotypes illuminate the immunopathogenesis of cytomegalovirus disease in human immunodeficiency virus–infected patients?

Most human immunodeficiency virus (HIV) patients are seropositive for cytomegalovirus (CMV) but a smaller proportion experience end-organ disease. This observation may reflect variations in genes affecting inflammatory and natural killer cell responses. DNA samples were collected from 240 HIV-infected patients followed at the University Hospitals/Case Medical Center (Cleveland, OH) between 1993 and 2008. Seventy-eight patients (African Americans = 41, Caucasians = 37) experienced CMV disease. Genotypes were determined using allele-specific fluorescent probes or multiplex polymerase chain reaction sequence-specific primers. IL12B3'UTR*(1) and SLC11A1 D543N*(1,2) were associated with CMV disease in African American patients (p = 0.04 and p = 0.02, respectively). IL10-1082*(1,2) and LILRB1 I142T*(1) were associated with CMV disease in Caucasians (p = 0.02 and p = 0.07, respectively). DARC T-46C*(1) and CD14 C-159T*(2) were associated with low nadir CD4(+) T cell counts in African American patients (p = 0.002 and p = 0.01, respectively). Caucasian patients carrying TNFA-308*2, TNFA-1031*(2), IL2-330*(1), CCL2-2518*(2), or LILRB1 I142T*(1) had significantly lower nadir CD4(+) T cells in a bootstrapped multivariable model (p = 0.006-0.02). In general, polymorphisms associated with CMV disease and CD4(+) T cell counts were distinct in Caucasian and African American patients in the United States. The LILRB1 I142T polymorphism was associated with both CMV disease and low nadir CD4(+) T cell counts in Caucasians, but the clearest determinant of low nadir CD4(+) T cell count in African American patients was DARC T-46C.     

The outcome and timing of death of 17,767 nosocomial bloodstream infections in acute care hospitals in Finland during 1999–2014

Few studies covering all patient groups and specialties are available regarding the outcome of nosocomial bloodstream infections (BSI). We analyzed the role of patient characteristics and causative pathogens of nosocomial BSIs reported by the hospitals participating in national surveillance in Finland during 1999–2014, in terms of outcome, with particular interest in those leading to death within 2 days (i.e. early death). National nosocomial BSI surveillance was laboratory-based and hospital-wide. Data on nosocomial BSIs was collected by infection control nurses, and dates of death were obtained from the national population registry with linkage to national identity codes. A total of 17,767 nosocomial BSIs were identified; 557 BSIs (3%) were fatal within 2 days and 1150 (6%) within 1 week. The 1-month case fatality was 14% (2460 BSIs), and 23% of the deaths occurred within 2 days and 47% within 1 week. The patients who died early were older than those who survived >?28 days, and their BSIs were more often related to intensive care. Gram-positive bacteria caused over half of the BSIs of patients who survived, whereas gram-negative bacteria, especially Pseudomonas aeruginosa, caused more often BSIs of patients who died early, and fungi BSIs of patients who died within 1 week. A significant portion of patients with nosocomial BSIs died early, which underlines the importance of rapid recognition of BSI. Hospital-wide surveillance data of causative pathogens can be utilized when composing recommendations for empiric antimicrobial treatment in collaboration with clinicians, as well as when promoting infection prevention.     

Phylogeny and evolution of Newcastle disease virus genotypes isolated in Asia during 2008–2011

The full-length fusion (F) genes of 51 Newcastle disease (ND) strains isolated from chickens in Asia during the period 2008-2011 were genetically analyzed. Phylogenetic analysis showed that genotype VII of NDV still predominant in the domestic poultry of Asia. The sub-genotype VIIb circulated in the Iran and Indian sub-continent countries, whereas VIId sub-genotype existed in Far East countries. The non-synonymous to synonymous substitutions ratio was calculated 0.27 for VIId sub-genotype and 0.51 for VIIb sub-genotype indicates purifying/stabilizing selection which resulted in a low evolution rate in F gene of VIIb sub-genotype. There is evidence of localized positive selection when comparing these sub-genotypes protein sequences. Five codons in F gene of ND viruses had a posterior probability >90% using the Bayesian method, indicating these sites were under positive selection. To identify sites under positive selection; amino acid substitution classified depends on their radicalism and neutrality. The results indicate that although most positions were under purifying selection and can be eliminated, a few positions located in sub-genotype specific regions were subject to positive selection.     

Hyperferritinemia is a potential marker of chronic chikungunya: A retrospective study on the Island of Curaçao during the 2014–2015 outbreak

BackgroundRecently Chikungunya virus (CHIKV) outbreaks have been reported in the Carribean. There is no data regarding the outbreak in Curaçao. In addition, to date there is no biomarker that could be used to predict chronic infection.ObjectivesTo characterize the first CHIKV outbreak in Curaçao and to identify potential biomarkers for chronic infection.Study designA serological test and quantitative polymerase chain reaction (qPCR) were used on samples collected in Curaçao to confirm infection. Subsequently, six samples with high viral load were selected for phylogenetic analysis. Furthermore we investigated the association of macrophage-related biomarkers during CHIKV infection with chronic arthralgia/arthritis.Results116 patients in Curacao were diagnosed with CHIKV infection based on ELISA and 77% were tested positive for CHIKV by qPCR. Phylogenetic analysis showed that an Asian genotype was the cause of the outbreak. Elevated levels of ferritin and CRP were significantly associated with viraemia. In addition, elevated ferritin levels were significantly associated with chronic arthralgia.ConclusionsThe results showed that the presence of an Asian genotype of CHIKV in Curaçao for the first time. Moreover, we found an association between ferritin levels with chronic arthralgia.     

The patient–physician relationship in patients with chronic low back pain as a predictor of outcomes after rehabilitation

For patients with chronic diseases, especially those with chronic low back pain, the patient–physician relationship is significant for treatment adherence. In a sample of N = 688 low back pain patients, we examined the hypothesis that aspects of the patient–physician relationship (e.g. satisfaction with care, trust in the physician, patient participation) have a significant association with outcomes (pain, disability, quality of life, pain-related psychological impairment) after a multimodal treatment program (rehabilitation) after adjusting for a number of sociodemographic, medical, and psychological factors. Results show that the patient–physician relationship is significantly associated with the outcome. In the medium term (6 months after rehabilitation), the effect of the patient–physician relationship is clearer than in the short term (end of rehabilitation). In addition, risk factors for less improvement are female gender, higher age, low income, comorbidity, low treatment motivation, fear avoidance beliefs, and external locus of control. Future studies should examine the causal paths between the relationship variables and the outcome variables.     

The prevalence of human endogenous retroviruses in cerebrospinal fluids from patients with sporadic Creutzfeldt–Jakob disease

BackgroundAbout 8% of human genome is constituted by retroviral sequences. Some of these have been classified as human endogenous retroviruses (HERVs), which have been implicated in both health and disease. Recently, indirect evidence for a possible role of retroviral elements in neurological diseases has been provided by several studies.ObjectivesIn the present study, we aimed to evaluate the relationship between HERVs and sporadic Creutzfeldt–Jakob disease (CJD), one of the human forms of prion diseases.Study designWe investigated the prevalence of HERV families by RT-PCR in cell-free cerebrospinal fluids (CSFs) samples from normal controls, patients with sporadic CJD and other neurological diseases (OND).ResultsThe incidence rate of some HERV families were significantly different in CSF samples from the group of sporadic CJD compared to samples from normal individuals; HERV-W (P = 0.001), T (P = 0.039), FRD (P < 0.001), L (P = 0.003) and ERV-9 (P < 0.001) and the incidence rate of HERV-W (P = 0.021) and HERV-L (P = 0.049) were significantly increased in CSF samples from the group of sporadic CJD compared to samples from OND group. Moreover, our results from combining frequencies of two HERV families indicated that the prevalence of many combination groups was significantly different between sporadic CJD and normal CSF samples and between two patients’ CSF samples. In addition, a large number of HERV sequences were newly identified in CSFs from normal and diseased individuals.ConclusionsOur study about distinct prevalence patterns of HERVs reflects that some HERVs families may be associated with the development of prion diseases, and considered as a candidate marker for the diagnosis of sporadic CJD.     

The concept of structured treatment interruptions in the management of patients with human immunodeficiency virus (HIV) disease: where are we currently?

The failure to achieve viral eradication with currently available antiretroviral agents has spawned new approaches to limiting drug exposure. Highly active antiretroviral therapy (HAART) lowers morbidity and mortality of HIV disease but cannot eradicate the virus from the body. Structured treatment interruptions (STIs) have been proposed as a strategy to minimize the toxicities of HAART while providing a mechanism to enhance HIV-specific immunity. STIs have been investigated in three distinct clinical scenarios: during acute infection, during chronic infection, and during virologic failure. However, many questions still need to be answered in controlled trials before STIs can be adopted in clinical practice.     

Genetic characterization of feline calicivirus strains associated with varying disease manifestations during an outbreak season in Missouri (1995–1996)

Feline calicivirus (FCV) is a common cause of mild to severe upper respiratory tract disease (URTD) in cats. FCV strain 21223 was isolated from a kitten with severe pneumonia in a disease outbreak with unusually high mortality (35 %) that occurred in a Missouri feline colony in 1995–1996. Phylogenetic analysis of the genome sequence of strain 21223 indicated the emergence of a new FCV strain. Analysis of the full-length genome sequence of a closely related (99.5 % nucleotide identity) strain, 3786, obtained from an asymptomatic animal in the same colony four months later, showed the presence of seven amino acid substitutions, with six of them located in the VP1 capsid sequence encoded by ORF2. Comparative analysis of the E-region sequences (426–521 aa ORF2) presumably involved in virus-host cell receptor interactions did not identify amino acid substitutions unique to the virulent strain. We determined the complete genome sequences of four virus isolates that were collected in regional catteries in the months following the outbreak that were associated with different manifestations of the disease (URTD, chronic stomatitis, and gingivitis). We show that genetically distinct FCV strains were cocirculating in the area, and no apparent correlation could be made between overall sequence and observed disease.     

Clinical evaluation of the BioFire FilmArray® BioThreat-E test for the diagnosis of Ebola Virus Disease in Guinea

BackgroundThe recent West Africa Ebola outbreak highlighted the need to provide access to rapid, safe and reliable Ebola Virus Disease diagnostics.ObjectivesThe objective of this field study was to assess the clinical performance of the FilmArray^® BioThreat-E test for the detection of Ebola Zaïre virus in whole blood in symptomatic patients suspected of Ebola Virus Disease in Conakry (Guinea) from March to July 2015.Study designThe BioThreat-E test was compared to the two RT-PCRs, using serum, implemented at Donka Hospital in the emergency context: an in-house developed quantitative one-step RT-PCR adapted from the Weidmann technique, and the RealStar^® Filovirus RT-PCR Kit 1.0 (Altona-Diagnostics). We also assessed the performance of this assay in noninvasive specimens (urine and saliva) to detect infected patients.ResultsOf 135 patients enrolled and eligible for performance assessment on whole blood, the sensitivity was 95.7% [95% CI: 85.5–99.5] and specificity 100% [95% CI: 95.9–100]. Of the 37 symptomatic infected patients able to provide saliva and/or urine samples, 34 of the 35 saliva samples and all 3 of the urine samples were positive with the BioThreat-E test.ConclusionsThis study showed that the FilmArray BioThreat-E test performs comparably to conventional molecular tests under field conditions, providing results and interpretation in approximately 1 h. Due to its operational characteristics, it can be easily deployed in the field during an epidemic and could also be a useful tool for post-outbreak surveillance.     

Molecular epidemiology of respiratory syncytial virus during the 2009–2010 season in Latvia

For the first time, we studied molecular epidemiology of respiratory syncytial virus in hospitalized children in Latvia. During the study period, ten unique group A and three group B strains were identified and assigned to a single genotype within each group—GA2 for group A and BA-IV for group B.     

Effects of cyclodextrin in two patients with Niemann–Pick Type C disease

Niemann–Pick Type C disease (NPC) is an autosomal recessive lysosomal storage disorder characterized by progressive neurological deterioration. Currently, there are no effective treatments for NPC, although miglustat has shown some effectiveness in stabilizing neurological status in juvenile-onset NPC patients. Recent studies have demonstrated the efficacy of hydroxypropyl-β-cyclodextrin (HPB-CD) in NPC mice. Herein, we describe the effects of HPB-CD in two patients with NPC. The two patients received HPB-CD infusions twice (Patient 2) or thrice (Patient 1) weekly, starting with a dose of 80 mg/kg per dose that was increased gradually to 2 g/kg per dose (Patient 2) or 2.5 g/kg per dose (Patient 1). Although HPB-CD did not improve the neurological deficits in either patient, it was partially effective in improving hepatosplenomegaly and central nervous system dysfunction, especially during the first 6 months of treatment. No adverse effects were observed over the course of treatment, although Patient 1 exhibited transient cloudiness of the lungs with fever after 2 years. For more effective treatment of NPC patients with HPB-CD, it is necessary to improve drug delivery into the central nervous system.     

Field outbreak strains of serotype O foot-and-mouth disease virus from India with a deletion in the immunodominant βG-βH loop of the VP1 protein

Foot-and-mouth disease virus serotype O accounts for around 80?% of the outbreaks in India. Although Indian serotype O isolates belongs to the ME-SA topotype, circulation of different lineages has been noted. After its emergence in the year 2001, the 'Ind2001' lineage outcompeted the PanAsia lineage in causing serotype O outbreaks in the year 2009. Three isolates had an amino acid deletion at position 139 in the VP1 coding region and grouped with the 'Ind2001' lineage. The currently used Indian vaccine strain of serotype O covers all of the field isolates antigenically.