Phylogeography and Genetic Diversity of Francisella tularensis subsp. holarctica in France (1947-2018)

In France, tularemia is caused by Francisella tularensis subsp. holarctica and is a sporadic disease affecting mainly wildlife animals and humans. F. tularensis species presents low genetic diversity that remains poorly described in France, as only a few genomes of isolates from the country are available so far. The objective of this study was to characterize the genetic diversity of F. tularensis in France and describe the phylogenetic distribution of isolates through whole-genome sequencing and molecular typing. Whole genomes of 350 strains of human or animal origin, collected from 1947 to 2018 in France and neighboring countries, were sequenced. A preliminary classification using the established canonical single nucleotide polymorphism (canSNP) nomenclature was performed. All isolates from France (except four) belonged to clade B.44, previously described in Western Europe. To increase the resolution power, a whole-genome SNP analysis was carried out. We were able to accurately reconstruct the population structure according to the global phylogenetic framework, and highlight numerous novel subclades. Whole-genome SNP analysis identified 87 new canSNPs specific to these subclades, among which 82 belonged to clade B.44. Identifying genomic features that are specific to sublineages is highly relevant in epidemiology and public health. We highlighted a large number of clusters among a single clade (B.44), which shows for the first time some genetic diversity among F. tularensis isolates from France, and the star phylogeny observed in clade B.44-subclades revealed that F. tularensis biodiversity in the country is relatively recent and resulted from clonal expansion of a single population. No association between clades and hosts or clinical forms of the disease was detected, but spatiotemporal clusters were identified for the first time in France. This is consistent with the hypothesis of persistence of F. tularensis strains found in Western Europe in the environment, associated with slow replication rates. Moreover, the presence of identical genotypes across long periods of time, and across long distances, supports this hypothesis but also suggests long-distance dispersal of the bacterium.This work was supported by the French National Research Agency (ANR) and the Direction Générale de l’Armement (DGA) (No. ANR-15-ASTR-0021-01). MK is a Ph.D. student co-supported by Université Paris-Est and DGA grants

Diseases and causes of death among alpacas in Sweden: a retrospective study

Background: Due to increasing popularity in Sweden during the last decade, alpacas are frequently encountered by practising veterinarians and pathologists. Knowledge regarding their health and diseases under Swedish conditions is, however, limited. Objectives: To improve knowledge about the health of alpacas in Sweden by collecting information on diseases and health status. Design: A retrospective study was made of 93 necropsies conducted on alpacas in Sweden during the period 2001–2013. Setting Data were obtained from the two major veterinary pathology centres in Sweden. The alpacas were hobby or farm animals and they were submitted by veterinarians in local practices or at a national animal healthcare organisation. Results: The digestive system was most frequently affected (29 per cent), with parasitic gastroenteritis (17 per cent) and hepatic disease being especially prevalent (15 per cent fascioliasis and 7 per cent hepatitis). Cardiovascular conditions (9 per cent), systemic diseases (7 per cent) and perinatal deaths were also common, including abortions (10 per cent) and fatal septicaemia (4 per cent). Wasting/emaciation was a frequent finding (26 per cent). Other diagnoses included dermatitis (8 per cent), diseases of the central nervous system (8 per cent), traumatic injuries (7 per cent), neoplasia (5 per cent), pneumonia (5 per cent) and nephritis (3 per cent). Conclusions: This study identified areas of concern regarding diagnostic and pathological procedures, for which specific measures have been recommended. One particular cause for concern was the number of deaths from emaciation in weanling alpacas during late winter or early spring. For adult alpacas, infectious and noninfectious causes of death were approximately equally frequent. Many of the diseases were considered clinically acute but pathology often showed them to be chronic conditions that had eventually deteriorated and presented as acute cases in the late stages. This study revealed similarities in the health/disease status reported in other European countries and in North America. The results can be used by alpaca keepers and veterinary practitioners to improve management, diagnosis and treatment of alpacas

Heterogeneity of pathological prion protein accumulation in the brain of moose (<i>Alces alces</i>) from Norway, Sweden and Finland with chronic wasting disease

Prion diseases are a group of neurodegenerative, transmissible, and fatal disorders that affect several animal species. They are characterized by the conformational conversion of the cellular prion protein (PrPC) into the pathological prion protein (PrPSc). In 2016, chronic wasting disease (CWD) gained great importance at European level due to the first disease detection in a wild reindeer (Rangifer tarandus) in Norway. The subsequent intensive CWD surveillance launched in cervids resulted in the detection of CWD in moose (Alces alces), with 11 cases in Norway, 3 in Finland and 4 in Sweden. These moose cases differ considerably from CWD cases in North American and reindeer in Norway, as PrPSc was detectable in the brain but not in lymphoid tissues. These facts suggest the occurrence of a new type of CWD. Here, we show some immunohistochemical features that are clearly different from CWD cases in North American and Norwegian reindeer. Further, the different types of PrPSc deposits found among moose demonstrate strong variations between the cases, supporting the postulation that these cases could carry multiple strains of CWD

A new HaCV-EBHSV recombinant lagovirus circulating in European brown hares (Lepus europaeus) from Catalonia, Spain

In 2020/2021, several European brown hare syndrome virus (EBHSV) outbreaks were recorded in European hares (Lepus europaeus) from Catalonia, Spain. Recombination analysis combined with phylogenetic reconstruction and estimation of genetic distances of the complete coding sequences revealed that 5 strains were recombinants. The recombination breakpoint is located within the non-structural protein 2C-like RNA helicase (nucleotide position similar to 1889). For the genomic fragment upstream of the breakpoint, a non-pathogenic EBHSV-related strain (hare calicivirus, HaCV; GII.2) was the most closely related sequence; for the rest of the genome, the most similar strains were the European brown hare syndrome virus (EBHSV) strains recovered from the same 2020/2021 outbreaks, suggesting a recent origin. While the functional impact of the atypical recombination breakpoint remains undetermined, the novel recombinant strain was detected in different European brown hare populations from Catalonia, located 20-100 km apart, and seems to have caused a fatal disease both in juvenile and adult animals, confirming its viability and ability to spread and establish infection. This is the first report of a recombination event involving HaCV and EBHSV and, despite the recombination with a non-pathogenic strain, it appears to be associated with mortality in European brown hares, which warrants close monitoring

Detection of gastric Helicobacter species in free-ranging lynx (Lynx lynx) and red foxes (Vulpes vulpes) in Sweden

Specimens of gastric mucosa and liver of 25 free-ranging Eurasian lynx (Lynx lynx), and four red foxes (Vulpes vulpes) shot in Sweden during 1999-2000, were investigated for the presence of Helicobacter species. Histopathology, bacteriologic culture and urease test, Helicobacter genus-specific 16S rDNA PCR analysis, and DNA sequence analysis were applied. Numerous Helicobacter-like organisms were observed histologically in the gastric mucosa of one fox. Helicobacter spp. were detected in the stomach by PCR analysis in 17 (68%) of the lynx and in three (755) of the foxes. Seven of the positive lynx were also positive in the urease test. PCR fragments, amplified from lynx and foxes, were sequenced and compared with those of known Helicobacter species. PCR products from lynx were closely related (>= 98% homology) to H. heilmannii, and PCR fragments from foxes demonstrated close homology to H. heilmannii and H. salomonis. No Helicobacter spp. or Helicobacter-like organisms could be cultured. The PCR analysis of the liver was negative for all animals, The pathologic significance of the presence of Helicobacter spp. in the stomach of free-ranging lynx and foxes remains uncertain

The ecology of wildlife disease surveillance: demographic and prevalence fluctuations undermine surveillance

1. Wildlife disease surveillance is the first line of defence against infectious disease. Fluctuations in host populations and disease prevalence are a known feature of wildlife disease systems. However, the impact of such heterogeneities on the performance of surveillance is currently poorly understood. 2. We present the first systematic exploration of the effects of fluctuations prevalence and host population size on the efficacy of wildlife disease surveillance systems. In this study efficacy is measured in terms of ability to estimate long term prevalence and detect disease risk. 3. Our results suggest that for many wildlife disease systems fluctuations in population size and disease lead to bias in surveillance-based estimates of prevalence and over-confidence in assessments of both the precision of prevalence estimates and the power to detect disease. 4. Neglecting such ecological effects may lead to poorly designed surveillance and ultimately to incorrect assessments of the risks posed by disease in wildlife. This will be most problematic in systems where prevalence fluctuations are large and disease fade-outs occur. Such fluctuations are determined by the interaction of demography and disease dynamics and although particularly likely in highly fluctuating populations typical of fecund short lived hosts, can’t be ruled out in more stable populations of longer lived hosts. 5. Synthesis and Applications: Fluctuations in population size and disease prevalence should be considered in the design and implementation of wildlife disease surveillance and the framework presented here provides a template for conducting suitable power calculations. Ultimately understanding the impact of fluctuations in demographic and epidemiological processes will enable improvements to wildlife disease surveillance systems leading to better characterisation of, and protection against endemic, emerging and re-emerging disease threats

STAT3 expression by myeloid cells is detrimental for the T- cell-mediated control of infection with <i>Mycobacterium tuberculosis</i>

<div><p>STAT3 is a master regulator of the immune responses. Here we show that <i>M</i>. <i>tuberculosis</i>-infected <i>stat3</i>^<i>fl/fl</i> <i>lysm cre</i> mice, defective for STAT3 in myeloid cells, contained lower bacterial load in lungs and spleens, reduced granuloma extension but higher levels of pulmonary neutrophils. STAT3-deficient macrophages showed no improved control of intracellular mycobacterial growth. Instead, protection associated to elevated ability of <i>stat3</i>^<i>fl/fl</i> <i>lysm cre</i> antigen-presenting cells (APCs) to release IL-6 and IL-23 and to stimulate IL-17 secretion by mycobacteria-specific T cells. The increased IL-17 secretion accounted for the improved control of infection since neutralization of IL-17 receptor A in <i>stat3</i>^<i>fl/fl</i> <i>lysm cre</i> mice hampered bacterial control. APCs lacking SOCS3, which inhibits STAT3 activation via several cytokine receptors, were poor inducers of priming and of the IL-17 production by mycobacteria-specific T cells. In agreement, <i>socs3</i>^<i>fl/fl</i> <i>cd11c cre</i> mice deficient of SOCS3 in DCs showed increased susceptibility to <i>M</i>. <i>tuberculosis</i> infection. While STAT3 in APCs hampered IL-17 responses, STAT3 in mycobacteria-specific T cells was critical for IL-17 secretion, while SOCS3 in T cells impeded IL-17 secretion. Altogether, STAT3 signalling in myeloid cells is deleterious in the control of infection with <i>M</i>. <i>tuberculosis</i>.</p></div

Data from: The ecology of wildlife disease surveillance: demographic and prevalence fluctuations undermine surveillance

Wildlife disease surveillance is the first line of defence against infectious disease. Fluctuations in host populations and disease prevalence are a known feature of wildlife disease systems. However, the impact of such heterogeneities on the performance of surveillance is currently poorly understood. We present the first systematic exploration of the effects of fluctuations' prevalence and host population size on the efficacy of wildlife disease surveillance systems. In this study, efficacy is measured in terms of ability to estimate long-term prevalence and detect disease risk. Our results suggest that for many wildlife disease systems, fluctuations in population size and disease lead to bias in surveillance-based estimates of prevalence and overconfidence in assessments of both the precision of prevalence estimates and the power to detect disease. Neglecting such ecological effects may lead to poorly designed surveillance and ultimately to incorrect assessments of the risks posed by disease in wildlife. This will be most problematic in systems where prevalence fluctuations are large and disease fade-outs occur. Such fluctuations are determined by the interaction of demography and disease dynamics. Although particularly likely in highly fluctuating populations typical of fecund short-lived hosts, such fluctuations cannot be ruled out in more stable populations of longer-lived hosts. Synthesis and applications. Fluctuations in population size and disease prevalence should be considered in the design and implementation of wildlife disease surveillance, and the framework presented here provides a template for conducting suitable power calculations. Ultimately, understanding the impact of fluctuations in demographic and epidemiological processes will enable improvements to wildlife disease surveillance systems leading to better characterization of, and protection against endemic, emerging and re-emerging disease threats