Platelet immune complex interaction in pathogenesis of Kawasaki disease and childhood polyarteritis.

The role of platelets in the pathogenesis of vasculitis and the formation of coronary artery aneurysms was studied in 19 children with Kawasaki disease and five with polyarteritis. All patients with Kawasaki disease developed thrombocytosis in the third week of illness. The peak platelet count was significantly correlated (p less than 0.005) with the subsequent development of coronary artery aneurysms. The rise in platelet count was associated with the appearance in the circulation of a factor that induced aggregation and serotonin release in normal platelets. This factor was shown to be of high molecular weight, and its activity was lost at low pH--features suggestive of an immune complex. Immune complexes, detected by precipitation with polyethylene glycol, also appeared in the circulation as the platelet count increased. These complexes induced platelet aggregation, and there was a significant correlation (p less than 0.001) between the concentrations of IgG and IgA in the polyethylene glycol precipitated material and the platelet aggregating activity. Similar platelet aggregating activity was also detected in patients with polyarteritis but followed a different time course, persisting in the circulation for several months in association with continued disease activity. These findings imply that different mechanisms have a role in distinct phases of Kawasaki disease. The initial feverish phase (probably infective) is probably followed by an immune complex vasculitis that occurs when antibodies to the initiating agent appear in the circulation. The immune complexes aggregate platelets and induce release of serotonin. Platelet derived vasoactive mediators may increase vascular permeability and facilitate further deposition of complexes in the tissues.     

On the determinants of population structure in antigenically diverse pathogens

Many pathogens exhibit antigenic diversity and elicit strain-specific immune responses. This potential for cross-immunity structure in the host resource motivates the development of mathematical models, stressing competition for susceptible hosts in driving pathogen population dynamics and genetics. Here we establish that certain model formulations exhibit characteristics of prototype pattern-forming systems, with pathogen population structure emerging as three possible patterns: (i) incidence is steady and homogeneous; (ii) incidence is steady but heterogeneous; and (iii) incidence shows oscillatory dynamics, with travelling waves in strain-space. Results are robust to strain number, but sensitive to the mechanism of cumulative immunity.     

A Cost Effectiveness and Capacity Analysis for the Introduction of Universal Rotavirus Vaccination in Kenya: Comparison between Rotarix and RotaTeq Vaccines

Background

Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination.

Methods

Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain.

Results

The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix.

Conclusion

Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability.     

Predicting vegetative inoculum performance to maximize phytase production in solid-state fermentation using response surface methodology

Microbial phytase is used to reduce the environmental loading of phosphorus from animal production facilities. The limiting factors in the use of this enzyme in animal feeds can be overcome by solid-state fermentation (SSF), which is a promising technology for commercial enzyme production with lower production costs. Inoculum quality and the influence of inoculum quality on phytase production are important factors which need in-depth investigation before scaling-up of high-yielding fermentation process. A full factorial experimental design for 240 h with sampling at every 24 h was used to determine the effects of the treatments, inoculum age (plate and liquid culture), media composition and the duration of SSF on the production of fungal biomass and phytase in SSF systems using Aspergillus niger. The optimal treatment combination for maximal phytase production was determined by statistically comparing all treatments at each sampling time. Both 7- and 14-day plate cultures and M1+ medium composition with 72-h-old liquid inoculum treatments resulted in optimal phytase production at 144 h of SSF, which was the shortest duration observed for maximal phytase production. This resulted in maximal phytase production with a mean of 884±121 U/g substrate, while the maximal phytase production observed at 216 h of SSF (mean phytase activity of 1008±121 U/g substrate), with the same treatment combinations, was not statistically significant from that at 144 h of SSF. Phytase production was strongly growth-associated with younger inocula. The significant treatment variables, age of liquid inoculum and the duration of SSF, were used to predict the system response for phytase production using response surface methodology. From the response surface model, the optimal response of the experiment was predicted and the reliability of the prediction was checked with the verification experiment. Journal of Industrial Microbiology & Biotechnology (2001) 26, 161–170. Received 06 June 2000/ Accepted in revised form 14 October 2000     

Mechanistic simulation of batch acetone–butanol–ethanol (ABE) fermentation with in situ gas stripping using Aspen Plus™

Bioprocess and Biosystems Engineering - Process simulations of batch fermentations with in situ product separation traditionally decouple these interdependent steps by simulating a separate...     

Analysis of composition and structure of <Emphasis Type="Italic">Clostridium thermocellum</Emphasis> membranes from wild-type and ethanol-adapted strains

Clostridium thermocellum is a candidate organism for consolidated bioprocessing of lignocellulosic biomass into ethanol. However, commercial use is limited due to growth inhibition at modest ethanol concentrations. Recently, an ethanol-adapted strain of C. thermocellum was produced. Since ethanol adaptation in microorganisms has been linked to modification of membrane lipids, we tested the hypothesis that ethanol adaptation in C. thermocellum involves lipid modification by comparing the fatty acid composition and membrane anisotropy of wild-type and ethanol-adapted strains. Derivatization to fatty acid methyl esters provided quantitative lipid analysis. Compared to wild-type, the ethanol-adapted strain had a larger percentage of fatty acids with chain lengths >16:0 and showed a significant increase in the percentage of 16:0 plasmalogens. Structural identification of fatty acids was confirmed through mass spectral fragmentation patterns of picolinyl esters. Ethanol adaptation did not involve modification at sites of methyl branching or the unsaturation index. Comparison of steady-state fluorescence anisotropy experiments, in the absence and presence of ethanol, provided evidence for the effects of ethanol on membrane fluidity. In the presence of ethanol, both strains displayed increased fluidity by approximately 12%. These data support the model that ethanol adaptation was the result of fatty acid changes that increased membrane rigidity that counter-acted the fluidizing effect of ethanol.     

Spatially resolved simulations of the spread of COVID-19 in three European countries

We explore the spatial and temporal spread of the novel SARS-CoV-2 virus under containment measures in three European countries based on fits to data of the early outbreak. Using data from Spain and Italy, we estimate an age dependent infection fatality ratio for SARS-CoV-2, as well as risks of hospitalization and intensive care admission. We use them in a model that simulates the dynamics of the virus using an age structured, spatially detailed agent based approach, that explicitly incorporates governmental interventions and changes in mobility and contact patterns occurred during the COVID-19 outbreak in each country. Our simulations reproduce several of the features of its spatio-temporal spread in the three countries studied. They show that containment measures combined with high density are responsible for the containment of cases within densely populated areas, and that spread to less densely populated areas occurred during the late stages of the first wave. The capability to reproduce observed features of the spatio-temporal dynamics of SARS-CoV-2 makes this model a potential candidate for forecasting the dynamics of SARS-CoV-2 in other settings, and we recommend its application in low and lower-middle income countries which remain understudied.     

Who mixes with whom? A method to determine the contact patterns of adults that may lead to the spread of airborne infections.

Although mixing patterns are thought to be important determinants of the spread of airborne infectious diseases, to our knowledge, there have been no attempts to directly quantify them for humans. We report on a preliminary study to identify such mixing patterns. A sample of 92 adults were asked to detail the individuals with whom they had conversed over the period of one, randomly assigned, day. Sixty-five (71%) completed the questionnaire, providing their age, the age of their contacts and the social context in which the contacts took place. The data were analysed using multilevel modelling. The study identified, and allowed the quantification of, contact patterns within this sample that may be of epidemiological significance. For example, the degree of assortativeness of mixing with respect to age was dependent not only on the age of participants but the number of contacts made. Estimates of the relative magnitude of contact rates between different social settings were made, with implications for outbreak potential. Simple questionnaire modifications are suggested which would yield information on the structure and dynamics of social networks and the intensity of contacts. Surveys of this nature may enable the quantification of who acquires infection from whom and from where.     

Screening of thermophilic anaerobic bacteria for solid substrate cultivation on lignocellulosic substrates

Interest in solid substrate cultivation (SSC) techniques is gaining for biochemical production from renewable resources; however, heat and mass transfer problems may limit application of this technique. The use of anaerobic thermophiles in SSC offers a unique solution to overcoming these challenges. The production potential of nine thermophilic anaerobic bacteria was examined on corn stover, sugar cane bagasse, paper pulp sludge, and wheat bran in submerged liquid cultivation (SmC) and SSC. Production of acetate, ethanol, and lactate was measured over a 10 day period, and total product concentrations were used to compare the performance of different organism-substrate combinations using the two cultivation methods. Overall microbial activity in SmC and SSC was dependent on the organism and growth substrate. Clostridium thermocellum strains JW20, LQRI, and 27405 performed significantly better in SSC when grown on sugar cane bagasse and paper pulp sludge, producing at least 70 and 170 mM of total products, respectively. Growth of C. thermocellum strains in SSC on paper pulp sludge proved to be most favorable, generating at least twice the concentration of total products produced in SmC (p-value < 0.05). Clostridium thermolacticum TC21 demonstrated growth on all substrates producing 30-80 and 60-116 mM of total product in SmC and SSC, respectively. Bacterial species with optimal growth temperatures of 70 degrees C grew best on wheat bran in SmC, producing total product concentrations of 45-75 mM. For some of the organism-substrate combinations total end product concentrations in SSC exceeded those in SmC, indicating that SSC may be a promising alternative for microbial activity and value-added biochemical production.