Differential Resistance of Borrelia burgdorferi Clones to Human Serum-Mediated Killing Does Not Correspond to Their Predicted Invasiveness

Reservoir host associations have been observed among and within Borrelia genospecies, and host complement-mediated killing is a major determinant in these interactions. In North America, only a subset of Borrelia burgdorferi lineages cause the majority of disseminated infections in humans. We hypothesize that differential resistance to human complement-mediated killing may be a major phenotypic determinant of whether a lineage can establish systemic infection. As a corollary, we hypothesize that borreliacidal action may differ among human subjects. To test these hypotheses, we isolated primary B. burgdorferi clones from field-collected ticks and determined whether the killing effects of human serum differed among those clones in vitro and/or whether these effects were consistent among human sera. Clones associated with human invasiveness did not show higher survival in human serum compared to noninvasive clones. These results indicate that differential complement-mediated killing of B. burgdorferi lineages is not a determinant of invasiveness in humans. Only one significant difference in the survivorship of individual clones incubated in different human sera was detected, suggesting that complement-mediated killing of B. burgdorferi is usually similar among humans. Mechanisms other than differential human complement-mediated killing of B. burgdorferi lineages likely explain why only certain lineages cause the majority of disseminated human infections

What a Tick Can Tell a Doctor: Using the Human-Biting Tick in the Clinical Management of Tick-Borne Disease

With expanding concern about ticks, there is a general sense of uncertainty about the diagnosis and treatment of tick-borne diseases. The diagnosis process is often based on clinical judgment in conjunction with laboratory testing and can be pathogen specific. Treatments may require disease-dependent approaches, and co-infections complicate or increase the severity of the clinical picture. Measuring exposure indices in the tick has become popular among providers and their patients, though this practice is not universally understood, and certain public health agencies have voiced concerns regarding interpretation and rigor of testing. As many providers subscribe to or recommend these services to aid in pretest risk and exposure assessments, this work sought to clarify the role of pathogen testing human-biting ticks as a complement to the diagnostic pipeline and raises points that must be addressed through future research and interdisciplinary conversation. Future work is needed to develop quality control oversight for tick testing laboratories. Studies on the integration of tick testing with human cases to see how these services affect health outcomes are also needed. Alongside these, improvements in the quality and availability of diagnostics are of critical importance

Passive Surveillance of \u3cem\u3eIxodes scapularis\u3c/em\u3e (Say), Their Biting Activity, and Associated Pathogens in Massachusetts

A passive surveillance of tick-borne pathogens was conducted over a 7-year period (2006–2012), in which a total of 3551 ticks were submitted to the University of Massachusetts for PCR testing. The vast majority of these ticks were Ixodes scapularis from Massachusetts (N = 2088) and hence were the focus of further analysis. Two TaqMan duplex qPCR assays were developed to test I. scapularis ticks for the presence of three human pathogens: Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti. I. scapularis submissions were concentrated from Cape Cod, the eastern half of the state outside of the Boston metropolitan area, parts of Franklin and Hampshire counties along the Quabbin Reservoir watershed, and southwestern Berkshire county. Differences in seasonal activity pattern were observed for different developmental stages of I. scapularis. The largest proportion of tick bite victims were age 9 years and under. Nymphal ticks were found more often on lower extremities of their hosts, while more adult ticks were found on the head. Overall infection rate of B. burgdorferi, A. phagocytophilum, and B. microti in human-biting ticks was 29.6%, 4.6%, and 1.8%, respectively. B. burgdorferi-infected ticks were widely distributed, but A. phagocytophilum- and B. microti-infected I. scapularis were found mainly in the eastern half of the state. We found that 1.8%, 1.0%, and 0.4% of ticks were coinfected by B. burgdorferi and A. phagocytophilum, B. burgdorferi and B. microti, and A. phagocytophilum and B. microti, respectively, and 0.3% of ticks had triple coinfection

Cost model relationships between textile manufacturing processes and design details for transport fuselage elements

Textile manufacturing processes offer potential cost and weight advantages over traditional composite materials and processes for transport fuselage elements. In the current study, design cost modeling relationships between textile processes and element design details were developed. Such relationships are expected to help future aircraft designers to make timely decisions on the effect of design details and overall configurations on textile fabrication costs. The fundamental advantage of a design cost model is to insure that the element design is cost effective for the intended process. Trade studies on the effects of processing parameters also help to optimize the manufacturing steps for a particular structural element. Two methods of analyzing design detail/process cost relationships developed for the design cost model were pursued in the current study. The first makes use of existing databases and alternative cost modeling methods (e.g. detailed estimating). The second compares design cost model predictions with data collected during the fabrication of seven foot circumferential frames for ATCAS crown test panels. The process used in this case involves 2D dry braiding and resin transfer molding of curved 'J' cross section frame members having design details characteristic of the baseline ATCAS crown design

Use of whole plant Artemisia annua L. as an antimalarial therapy

Anti-malarial drugs are primary weapons for reducing Plasmodium transmission in human populations. Successful drugs have been highly efficacious and inexpensive to synthetically manufacture. Emergence of resistant parasites reduces the lifespan of each drug that is developed and deployed. Currently, the most effective anti-malarial is artemisinin (AN), which is extracted from the leaves of Artemisia annua. Because of its poor pharmacokinetic properties and prudent efforts to curtail emergence of resistance, AN is prescribed only in combination with other anti-malarials composing an Artemisinin Combination Therapy (ACT). Low yield in the plant and the added cost of secondary anti-malarials in the ACT, make AN in the developing world a costly treatment. Here we show that dried leaves of A. annua administered orally are more effective at killing malaria parasites than a comparable dose of purified drug in a rodent malaria model (P. chabaudi). A single dose of whole plant (WP) A. annua containing 24 mg/kg AN clears 99% of parasites, where a comparable dose of pure drug has half that effect. This is consistent with findings that blood levels of AN are 40 times greater in mice receiving WP versus those given pure drug. We hypothesize that in addition to increasing bioavailability of AN, administration of WP alone may constitute a combination therapy because it contains other anti-malarial compounds that have been shown to synergize with AN. Inexpensive, efficacious, and resilient treatment for malaria based upon WP A. annua that can be grown and processed locally would be an effective addition to the global effort to reduce malaria morbidity and mortality

X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor

The structure of a crystal complex of the chemically synthesized protease of human immunodeficiency virus 1 with a heptapeptide-derived inhibitor bound in the active site has been determined. The sequence of the inhibitor JG-365 is Ac-Ser-Leu-Asn-Phe-ψ[CH(OH)CH_2N]-Pro-Ile-Val-OMe; the K_i is 0.24 nM. The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate. The structure of the complex has been refined to an R factor of 0.146 at 2.4-Å resolution by using restrained least squares with rms deviations in bond lengths of 0.02 Å and bond angles of 4. The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is positioned between the active site aspartate carboxyl groups within hydrogen bonding distance. Comparison of this structure with a reduced peptide bond inhibitor-protease complex indicates that these contacts confer the exceptional binding strength of JG-365