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BENEFITS AND SAVINGS OF A MICROBIOLOGICAL MONITORING PROGRAM BASED ON EAD TESTING
The introduction of Exhaust Air Dust (EAD) testing by PCR in a health monitoring (HM) program of an animal facility equipped with individually ventilated cages can bring several benefits. These include the improved detection of rodent infectious agents, the reduction/replacement of the animals used as sentinels, labor, time, and cost savings. The authors manage a 600 m2 mouse facility housing around 6,000 ventilated cages, used both for breeding and experimental activities. The facility was opened in 2007 and its HM program was based on traditional soiled bedding sentinels (SBS). In 2016, the efficacy of PCR testing of EAD samples was evaluated in comparison to serology, bacteriology and parasitology carried out on SBS. The results of this test, together with the reports published by different groups, encouraged the authors to include EAD testing in the HM program of the facility. A hybrid program was developed and run for a few years, allowing comparative evaluations between EAD testing Vs SBS. The analysis of the results obtained showed that PCR testing of EAD samples confirmed or outperformed the results obtained by traditional methods on SBS, thus, supporting the authors in the decision to develop a new program, completely SBS-free. This new approach allowed the replacement of a significant number of animals used as sentinels (more than 700 every year) resulting both in ethical and economic benefits. Moreover, the new sentinel-free HM program allowed time and labor savings associated with the simplified samples preparation. Finally, this new solution contributed also to the reduction of the emotional fatigue of the staff of the facility.
Journal Article
Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study
We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015.
We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity.
We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6–50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7–3·8) hospital admissions, and 59 600 (48 000–74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2–1·7) hospital admissions, and 27 300 (UR 20 700–36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600–149 400). Incidence and mortality varied substantially from year to year in any given population.
Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group.
The Bill & Melinda Gates Foundation.
Journal Article
The SalmonellaTyphimurium effector protein SopE transiently localizes to the early SCV and contributes to intracellular replication
Summary Salmonella enterica serovar Typhimurium (S. Tm) is a facultative intracellular pathogen that induces entry into non-phagocytic cells by a Type III secretion system (TTSS) and cognate effector proteins. Upon host cell entry, S. Tm expresses a second TTSS and subverts intracellular trafficking to create a replicative niche - the Salmonella-containing vacuole (SCV). SopE, a guanidyl exchange factor (GEF) for Rac1 and Cdc42, is translocated by the TTSS-1 upon host cell contact and promotes entry through triggering of actin-dependent ruffles. After host cell entry, the bulk of SopE undergoes proteasomal degradation. Here we show that a subfraction is however detectable on the nascent SCV membrane up to 6h post infection. Membrane localization of SopE and the closely related SopE2 differentially depend on the Rho-GTPase-binding GEF domain, and to some extent involves also the unstructured N-terminus. SopE localizes transiently to the early SCV, dependent on continuous synthesis and secretion by the TTSS-1 during the intracellular state. Mutant strains lacking SopE or SopE2 are attenuated in early intracellular replication, while complementation restores this defect. Hence, the present study reveals an unanticipated role for SopE and SopE2 in establishing the Salmonella replicative niche, and further emphasizes the importance of entry effectors in later stages of host-cell manipulation.
Journal Article