Ebola viral load at diagnosis associates with patient outcome and outbreak evolution

BACKGROUND. Ebola virus (EBOV) causes periodic outbreaks of life-threatening EBOV disease in Africa. Historically, these outbreaks have been relatively small and geographically contained; however, the magnitude of the EBOV outbreak that began in 2014 in West Africa has been unprecedented. The aim of this study was to describe the viral kinetics of EBOV during this outbreak and identify factors that contribute to outbreak progression.METHODS. From July to December 2014, one laboratory in Sierra Leone processed over 2,700 patient samples for EBOV detection by quantitative PCR (qPCR). Viremia was measured following patient admission. Age, sex, and approximate time of symptom onset were also recorded for each patient. The data was analyzed using various mathematical models to find trends of potential interest.RESULTS. The analysis revealed a significant difference (P = 2.7 × 10^–77) between the initial viremia of survivors (4.02 log₁₀ genome equivalents [GEQ]/ml) and nonsurvivors (6.18 log₁₀ GEQ/ml). At the population level, patient viral loads were higher on average in July than in November, even when accounting for outcome and time since onset of symptoms. This decrease in viral loads temporally correlated with an increase in circulating EBOV-specific IgG antibodies among individuals who were suspected of being infected but shown to be negative for the virus by PCR.CONCLUSIONS. Our results indicate that initial viremia is associated with outcome of the individual and outbreak duration; therefore, care must be taken in planning clinical trials and interventions. Additional research in virus adaptation and the impacts of host factors on EBOV transmission and pathogenesis is needed.     

Comparison of difloxacin, enoxacin, and cefoperazone for treatment of experimental Enterobacter aerogenes endocarditis.

This study compared difloxacin administered orally, enoxacin administered orally, and cefoperazone administered intramuscularly for the treatment of experimental Enterobacter aerogenes endocarditis. Difloxacin significantly reduced bacterial counts of vegetations, as compared with enoxacin and cefoperazone. Enoxacin and cefoperazone did not differ significantly. This study demonstrated that difloxacin was significantly more effective than enoxacin and cefoperazone for the treatment of E. aerogenes endocarditis in rabbits.     

Therapy vs no therapy for bacteriuria in elderly ambulatory nonhospitalized women

This prospective randomized study was undertaken to determine the efficacy of antimicrobial therapy compared with no therapy for bacteriuria in elderly ambulatory nonhospitalized women. Sixty-one women (mean age, 85.8 years) with bacteriuria were in the no therapy control group and 63 women (mean age, 85.8 years) with bacteriuria were in the therapy group; none had symptoms of urinary tract infection. One short course of antimicrobial therapy achieved a cure rate of 68.3% (43 of 63 women cured) two weeks after treatment. During the six-month follow-up period, ten (16.4%) of 61 women in the no therapy group and five (7.9%) of 63 women in the therapy group developed symptomatic urinary tract infection. At the time of six-month follow-up, 19 (34.5%) of 55 women in the no therapy group and 35 (63.6%) of 55 women in the therapy group did not have bacteriuria. We conclude that for asymptomatic bacteriuria in elderly ambulatory nonhospitalized women, short-course antimicrobial therapy is effective at two-week follow-up and that antimicrobial therapy can eliminate bacteriuria in most of these women for at least a six-month period.     

Inhibition of multiple subtypes of influenza A virus in cell cultures with morpholino oligomers

Peptide-conjugated phosphorodiamidate morpholino oligomers (P-PMO) are single-stranded nucleic acid-like antisense agents that can reduce gene expression by sterically blocking complementary RNA sequence. P-PMO are water soluble and nuclease resistant, and they readily achieve uptake into cells in culture under standard conditions. Eight P-PMO, each 20 to 22 bases in length, were evaluated for their ability to inhibit influenza A virus (FLUAV) A/PR/8/34 (H1N1) replication in cell culture. The P-PMO were designed to base pair with FLUAV RNA sequences that are highly conserved across viral subtypes and considered critical to the FLUAV biological-cycle, such as gene segment termini and mRNA translation start site regions. Several P-PMO were highly efficacious, each reducing viral titer in a dose-responsive and sequence-specific manner in A/PR/8/34-infected cells. Two P-PMO, one designed to target the AUG translation start site region of PB1 mRNA and the other the 3'-terminal region of nucleoprotein viral genome RNA, also proved to be potent against several other FLUAV strains, including A/WSN/33 (H1N1), A/Memphis/8/88 (H3N2), A/Eq/Miami/63 (H3N8), A/Eq/Prague/56 (H7N7), and the highly pathogenic A/Thailand/1(KAN-1)/04 (H5N1). The P-PMO exhibited minimal cytotoxicity in cell viability assays. High efficacy by two of the P-PMO against multiple FLUAV subtypes suggests that these oligomers represent a broad-spectrum therapeutic approach against a high percentage of known FLUAV strains.     

Characterization of a trypsin-dependent avian influenza H5N1-pseudotyped HIV vector system for high throughput screening of inhibitory molecules

In this study, we have generated and characterized an avian influenza H5N1 hemagglutinin (HA), neuraminidase (NA) and M2 ion channel pseudotyped HIV-based vector system (HaNaM-pseudotyped HIV vector). The cleavage site of the HA protein was modified to necessitate trypsin-dependent maturation of the glycoprotein. HA, NA and M2 were efficiently incorporated in HIV vector particles which could transduce different cell lines in a trypsin-dependent manner. Results also showed that the presence of avian influenza M2 and NA proteins maximized both vector production and transduction and that transduction was highly sensitive to the specific NA inhibitor oseltamivir (Tamiflu). H5N1 HaNaM-pseudotyped HIV vector system was also adapted for cell-based high throughput screening of drug candidates against influenza virus infection, and its high sensitivity to the specific oseltamivir validates its potential utility in the identification of new influenza inhibitors. Overall, the trypsin-dependent H5N1-pseudotyped HIV vector can mimic avian influenza virus infection processes with sufficient precision to allow for the identification of new antivirals and to study avian influenza virus biology in a lower biosafety level laboratory environment.     

State Anxiety Following Resistance Exercise: The Role of Gender and Exercise Intensity

Two experiments were conducted to investigate the effect of resistance exercise on state anxiety. In experiment 1, participants engaged in three 20-min bouts of resistance exercise, with intensity set as a function of perceived exertion. Results indicated that the relationship between resistance exercise and anxiety was moderated by both exercise intensityand gender. Although females reported no change in anxiety, males reported an increase in anxietyfollowing moderateand high-intensity exercise, and a decrease in anxiety following low intensity exercise. Experiment 2 was designed to replicate these findings utilizing a more precise manipulation of exercise intensity. Results indicated that the change in anxiety was again moderated by exercise intensity but was unaffected by gender. Both males and females reported increases in anxiety following 20 min of high-intensity exercise (75-85% of 1 RM), as well as significant decreases in anxiety following low-intensity exercise (40-50% of 1 RM).     

Hantavirus Cardiopulmonary Syndrome in Canada

Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory disease caused by Sin Nombre virus in North America (SNV). As of January 1, 2020, SNV has caused 143 laboratory-confirmed cases of HCPS in Canada. We review critical aspects of SNV virus epidemiology and the ecology, biology, and genetics of HCPS in Canada.     

An Autochthonous Case of Severe Plasmodium knowlesi Malaria in Thailand

A 58-year-old Thai man was infected with Plasmodium knowlesi in Chantaburi Province, eastern Thailand. In addition to pyrexia, the patient developed hypotension, renal failure, jaundice, and severe thrombocytopenia. The parasitemia at the time of admission was 16.67% or ∼503,400 parasites/μL. With artesunate treatment and supportive care, the patient recovered uneventfully. The occurrence of complicated knowlesi malaria in a low-endemic area underscores the risk of high morbidity from this simian malaria.     

Immunogenicity of novel consensus-based DNA vaccines against avian influenza

The frequency of H5N1 avian influenza outbreaks in China and Eastern Europe has raised concern in the world health community regarding the potential for an influenza pandemic. Efforts to monitor the disease will only provide minimal warning in a global society, and steps must be taken to prevent the morbidity and mortality associated with past pandemics. The current stockpiling of antibody-inducing "bird flu" vaccines assumes the strain that emerges will be the same as strains currently circulating. We propose a novel consensus-based approach to vaccine development, employing a DNA vaccine strategy that can provide more highly cross-reactive cellular immunity against lethal influenza infection. We show such constructs can induce strong cellular immunity against H5 influenza antigens.     

Type A and hardiness

The study examined the relationship between the Type A behavior pattern and personality hardiness and predicted an interaction between the two that would be influential for illness onset. Type A and hardiness were found to be conceptually different and empirically independent factors. Under high stressful life events, male executives who were high in Type A and low in hardiness tended toward higher general illness scores than any other executives. Type A and hardiness emerge from this study as bases for extrinsic and intrinsic motivation, respectively.