Summary During mammalian pregnancy the maternal thymus undergoes significant involution, and then recovers in size after birth. The mechanism behind this involution is not known, but it has been suggested that elevated levels of hormones during pregnancy induce the involution. We have recently shown that injection of 17β‐oestradiol into mice causes loss of early thymocyte precursors and inhibits proliferation of developing thymocytes. This suggests that elevated oestrogen in pregnancy may contribute to thymic involution. We have investigated this idea by examining the fate of thymocytes during mouse pregnancy in much greater detail than has been previously reported. Looking over a broad time–course, we find that pregnancy does not affect thymocyte precursor populations in the bone marrow, but induces a profound loss of early thymic progenitors in the thymus as early as day 12·5 of pregnancy. This loss is accompanied by decreased thymocyte proliferation, which returns to normal 2–4 days postpartum. No enhancement of apoptosis is detectable at any stage of pregnancy. We also find that there is a reduction in recent thymic emigrants after oestrogen treatment and at day 17·5 of pregnancy, suggesting that thymic involution during pregnancy influences the peripheral T‐cell repertoire. The similarities between oestrogen‐mediated involution and pregnancy‐mediated involution suggest that oestrogen is a significant contributor to loss of thymocyte cellularity during pregnancy, and probably functions primarily by reducing thymocyte proliferation.
Abstract Background Q fever, brucellosis, and leptospirosis are zoonoses typically associated with terrestrial animal reservoirs. These bacterial agents are now known to infect marine mammal species, though little is known about potential human health risks from marine mammal reservoir species. We investigated potential risks of these bacteria in humans associated with marine mammal exposure. Methods The Marine Mammal Center (TMMC) in Sausalito, California, requested a Health Hazard Evaluation by the National Institute for Occupational Safety and Health. In June 2011, an investigation occurred, which included a written questionnaire and serosurvey among workers for Coxiella burnetii , Brucella spp., and Leptospira spp., and an environmental assessment for C. burnetii . Results Serologic evidence of past exposure was detected in 4% ( C. burnetii ), 0% ( Brucella ), and 1% ( Leptospira ) of 213 participants, respectively. One of 130 environmental samples tested positive for C. burnetii . No significant marine mammal‐specific risk factors were identified, but some safety deficiencies were noted that could lead to a higher risk of exposure to zoonotic diseases. Conclusion Although this study did not identify disease exposure risks associated with marine mammals, additional studies in different settings of other groups with frequent exposure to marine mammals are warranted. Some deficiencies in safety were noted, and based on these, TMMC modified protocols to improve safety.
The brown dog tick, Rhipicephalus sanguineus sensu lato (s.l.), is an important vector for Rickettsia rickettsii, causative agent of Rocky Mountain spotted fever. Current public health prevention and control efforts to protect people involve preventing tick infestations on domestic animals and in and around houses. Primary prevention tools rely on acaricides, often synthetic pyrethroids (SPs); resistance to this chemical class is widespread in ticks and other arthropods. Rhipicephalus sanguineus s.l. is a complex that likely contains multiple unique species and although the distribution of this complex is global, there are differences in morphology, ecology, and perhaps vector competence among these major lineages. Two major lineages within Rh. sanguineus s.l., commonly referred to as temperate and tropical, have been documented from multiple locations in North America, but are thought to occupy different ecological niches. To evaluate potential acaricide resistance and better define the distributions of the tropical and temperate lineages throughout the US and in northern Mexico, we employed a highly multiplexed amplicon sequencing approach to characterize sequence diversity at: 1) three loci within the voltage-gated sodium channel (VGSC) gene, which contains numerous genetic mutations associated with resistance to SPs; 2) a region of the gamma-aminobutyric acid-gated chloride channel gene (GABA-Cl) containing several mutations associated with dieldrin/fipronil resistance in other species; and 3) three mitochondrial genes (COI, 12S, and 16S). We utilized a geographically diverse set of Rh sanguineus s.l. collected from domestic pets in the US in 2013 and a smaller set of ticks collected from canines in Baja California, Mexico in 2021. We determined that a single nucleotide polymorphism (T2134C) in domain III segment 6 of the VGSC, which has previously been associated with SP resistance in Rh. sanguineus s.l., was widespread and abundant in tropical lineage ticks (>50 %) but absent from the temperate lineage, suggesting that resistance to SPs may be common in the tropical lineage. We found evidence of multiple copies of GABA-Cl in ticks from both lineages, with some copies containing mutations associated with fipronil resistance in other species, but the effects of these patterns on fipronil resistance in Rh. sanguineus s.l. are currently unknown. The tropical lineage was abundant and geographically widespread, accounting for 79 % of analyzed ticks and present at 13/14 collection sites. The temperate and tropical lineages co-occurred in four US states, and as far north as New York. None of the ticks we examined were positive for Rickettsia rickettsii or Rickettsia massiliae.
Purpose: A one year longitudinal study of Q fever among dairy farms and farmers was conducted in June 2015 in the areas of Chiang-Mai where Q fever was reported. This study was conducted by the collaboration between public health and animal health sectors. We reported a preliminary analysis of baseline information to describe the magnitude and factors associated with C.burnetii infection in this high risk population. Methods & Materials: Two-stage random sampling of the farms and farmers was performed to identify cohort of dairy farms farmers. We conducted face to face interview with farmers, and collected blood for baseline assessment. Bulk tank milk samples from each farm were screened and specimens were collected from cows, other animals, and farm environment in the farms with milk positive. Farmer sera were tested using Indirect Immunofluorescense Assay (IFA). Milk and cow sera were tested using Enzyme-Linked Immunosorbent Assay. Vaginal swabs and environmental samples were tested using Polymerase Chain Reaction. Descriptive statistics and multivariate logistic regression were performed to describe baseline seroprevalence and factors associated with milk positive. This cohort of farms was followed up at 6 and 12 month after the baseline assessment. Results: Totally, 282/306 (92.2%) randomly selected farms, and 532/637 (83.5%) randomly selected farmers participated. The overall seroprevalence of antibodies to C.burnetii was 40.8% (115/282) in milk, and 16.9% (90/532) in farmers (IFA cut-off value 1:64). We visited 99 from115 positive farms and collected samples from 790 cows. In the milk positive farms, seroprevalence to C.burnetii infection was 28.4% (224/790) at the individual cow and 91.9% (91/99) at the herd level. Multivariate logistic regression model showed that every 10 increase in number of cows age ≥ 2 years (OR 1.32, 95%CI 1.15-1.52), farms located in 1 kilometer from milk positive farm (OR 2.8, 95%CI 1.15 – 6.84), ever clean birthing area after calving (OR 0.31, 95%CI 0.91 – 0.99), and quarantine newly purchased animals (OR 0.54, 95%CI 0.35 – 0.97) were associated with milk positive. Conclusion: Farm practices were associated with the presence of C.burnetii infection. Further assessment is needed to determine the incidence of seroconversion and other risk behavior among dairy farmers.
We have produced transgenic mice that express rearranged T cell Ag receptor gamma and delta transgenes in the alpha beta lineage of thymocytes. Thymi in these mice contain normal numbers of CD4+CD8+ cells that express low levels of the TCR-gamma delta. Analysis of the delta locus in these thymi indicates that these cells are in the alpha beta lineage even though they express the TCR-gamma delta. This shows that expression of the TCR-gamma delta in early thymocytes can lead to all of the consequences that are normally mediated by the beta-chain. These consequences include maturation to the CD4+CD8+ stage, entry into the cell cycle, and cessation of beta rearrangement. Therefore, the data support a model in which formation of a functional CD3 complex on immature CD4-CD8- thymocytes leads to further development in the absence of extracellular ligand recognition. The data also show that the gamma delta vs alpha beta lineage decision is made in a manner that is independent of gamma and beta gene expression.
Alpha-gal syndrome (AGS) is an emerging, tick bite-associated immunoglobulin E-mediated allergic condition characterized by a reaction to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), which is found in mammalian meat and products derived from mammals, including milk, other dairy products, and some pharmaceutical products. Symptoms range from mild (e.g., a rash or gastrointestinal upset) to severe (anaphylaxis); onset typically occurs ≥2 hours after exposure to alpha-gal. No treatment or cure is currently available. Despite the potential life-threating reactions associated with AGS, most patients perceive that health care providers (HCPs) have little or no knowledge of AGS. A U.S. web-based survey of 1,500 HCPs revealed limited knowledge of AGS, identified areas for continuing medical education, and described self-reported diagnostic and management practices. Overall, 42% of surveyed HCPs had never heard of AGS, and among those who had, fewer than one third knew how to diagnose the condition. Two thirds of respondents indicated that guidelines for the diagnosis and management of AGS would be useful clinical resources. Limited awareness and knowledge of AGS among HCPs likely contributes to underdiagnosis of this condition and inadequate patient management, and underestimates of the number of AGS patients in the United States, which currently relies on laboratory testing data alone.
Methods for the extraction of PCR-quality DNA from environmental soil samples by using pairs of commercially available kits were evaluated. Coxiella burnetii DNA was detected in spiked soil samples at <1,000 genome equivalents per gram of soil and in 12 (16.4%) of 73 environmental soil samples.
