Bacterial growth rate and host factors as determinants of intracellular bacterial distributions in systemic Salmonella enterica infections.

Bacteria of the species Salmonella enterica cause a range of life-threatening diseases in humans and animals worldwide. The within-host quantitative, spatial, and temporal dynamics of S. enterica interactions are key to understanding how immunity acts on these infections and how bacteria evade immune surveillance. In this study, we test hypotheses generated from mathematical models of in vivo dynamics of Salmonella infections with experimental observation of bacteria at the single-cell level in infected mouse organs to improve our understanding of the dynamic interactions between host and bacterial mechanisms that determine net growth rates of S. enterica within the host. We show that both bacterial and host factors determine the numerical distributions of bacteria within host cells and thus the level of dispersiveness of the infection.

Earthquakes, influenza and cycles of Indian kala-azar.

It is suggested that previous data indicate 3 major epidemics of kala-azar in Assam between 1875 and 1950, with inter-epidemic periods of 30-45 and 20 years. This deviates from the popular view of regular cycles with a 10-20 year period. A deterministic mathematical model of kala-azar is used to find the simplest explanation for the timing of the 3 epidemics, paying particular attention to the role of extrinsic (drugs, natural disasters, other infectious diseases) versus intrinsic (host and vector dynamics, birth and death rates, immunity) processes in provoking the second. We conclude that, whilst widespread influenza in 1918-1919 may have magnified the second epidemic, intrinsic population processes provide the simplest explanation for its timing and synchrony throughout Assam. The model also shows that the second inter-epidemic period is expected to be shorter than the first, even in the absence of extrinsic agents, and highlights the importance of a small fraction of patients becoming chronically infectious (with post kala-azar dermal leishmaniasis) after treatment during an epidemic.

An error free passive UHF RFID system using a new form of wireless signal distribution

A wide area and error free ultra high frequency (UHF) radio frequency identification (RFID) interrogation system based on the use of multiple antennas used in cooperation to provide high quality ubiquitous coverage, is presented. The system uses an intelligent distributed antenna system (DAS) whereby two or more spatially separated transmit and receive antenna pairs are used to allow greatly improved multiple tag identification performance over wide areas. The system is shown to increase the read accuracy of 115 passive UHF RFID tags to 100% from <60% over a 10m × 8m open plan office area. The returned signal strength of the tag backscatter signals is also increased by an average of 10dB and 17dB over an area of 10m 8m and 10m × 4m respectively. Furthermore, it is shown that the DAS RFID system has improved immunity to tag orientation. Finally, the new system is also shown to increase the tag read speed/rate of a population of tags compared with a conventional RFID system. © 2012 IEEE.

Live Attenuated S. Typhimurium Vaccine with Improved Safety in Immuno-Compromised Mice

Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV). Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb-/-nos2-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb-/-nos2-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093), was >1000-fold attenuated in cybb-/-nos2-/- mice and ≈100 fold attenuated in tnfr1-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA) response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety. © 2012 Periaswamy et al.

An Error Free Passive UHF RFID System using a New Form of Wireless Signal Distribution

A wide area and error free ultra high frequency (UHF) radio frequency identification (RFID) interrogation system based on the use of multiple antennas used in cooperation to provide high quality ubiquitous coverage, is presented. The system uses an intelligent distributed antenna system (DAS) whereby two or more spatially separated transmit and receive antenna pairs are used to allow greatly improved multiple tag identification performance over wide areas. The system is shown to increase the read accuracy of 115 passive UHF RFID tags to 100% from <60% over a 10m x 8m open plan office area. The returned signal strength of the tag backscatter signals is also increased by an average of 10dB and 17dB over an area of 10m x 8m and 10m x 4m respectively. Furthermore, it is shown that the DAS RFID system has improved immunity to tag orientation. Finally, the new system is also shown to increase the tag read speed/rate of a population of tags compared with a conventional RFID system.

Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment.

In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics.