A Note on the Risk of Infections Invading Unaffected Regions.

We present two probabilistic models to estimate the risk of introducing infectious diseases into previously unaffected countries/regions by infective travellers. We analyse two distinct situations, one dealing with a directly transmitted infection (measles in Italy in 2017) and one dealing with a vector-borne infection (Zika virus in Rio de Janeiro, which may happen in the future). To calculate the risk in the first scenario, we used a simple, nonhomogeneous birth process. The second model proposed in this paper provides a way to calculate the probability that local mosquitoes become infected by the arrival of a single infective traveller during his/her infectiousness period. The result of the risk of measles invasion of Italy was of 93% and the result of the risk of Zika virus invasion of Rio de Janeiro was of 22%

The effect of competition on the control of invading plant pathogens

1. New invading pathogen strains must compete with endemic pathogen strains to emerge and spread. As disease control measures are often non-specific, i.e. they do not distinguish between strains, applying control not only affects the invading pathogen strain but the endemic as well. We hypothesise that the control of the invasive strain could be compromised due to the non-specific nature of the control. 2. A spatially-explicit model, describing the East African cassava mosaic virus-Uganda strain (EACMV-UG) outbreak, is used to evaluate methods of controlling both disease incidence and spread of invading pathogen strains in pathosystems with and without an endemic pathogen strain present. 3. We find that while many newly introduced or intensified control measures (such as resistant cultivars or roguing) decrease the expected incidence, they have the unintended consequence of increasing, or at least not reducing, the speed with which the invasive pathogen spreads geographically. We identify which controls cause this effect and methods in which these controls may be applied to prevent it. 4. We found that the spatial spread of the invading strain is chiefly governed by the incidence at the wave front. Control can therefore be applied, or intensified, once the wave front has passed without increasing the pathogen’s rate of spread. 5. When trade of planting material occurs, it is possible that the planting material is already infected. The only forms of control in this study that reduces the speed of geographic spread, regardless of the presence of an endemic strain, are those that reduce the amount of trade and the distance over which trade takes place. 6. Synthesis and applications. Imposing trade restrictions before the epidemic has reached a given area and increasing other control methods only once the wave front has passed is the most effective way of both slowing down spread and controlling incidence when the presence of an endemic strain is unknow

Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo

Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX) interacts directly with the adenovirus type 5 (Ad5) hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX “coating” also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR) of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual functionality of FX in protecting Ad26.HVR5C against innate immune factors whilst determining liver targeting

Parasites, pathogens and commensals in the “low-impact” non-native amphipod host Gammarus roeselii

Background: Whilst vastly understudied, pathogens of non-native species (NNS) are increasingly recognised as important threats to native wildlife. This study builds upon recent recommendations for improved screening for pathogens in NNS by focusing on populations of Gammarus roeselii in Chojna, north-western Poland. At this location, and in other parts of continental Europe, G. roeselii is considered a well-established and relatively ‘low-impact’ invader, with little understanding about its underlying pathogen profile and even less on potential spill-over of these pathogens to native species. Results: Using a combination of histological, ultrastructural and phylogenetic approaches, we define a pathogen profile for non-native populations of G. roeselii in Poland. This profile comprised acanthocephalans (Polymorphus minutus Goese, 1782 and Pomphorhynchus sp.), digenean trematodes, commensal rotifers, commensal and parasitic ciliated protists, gregarines, microsporidia, a putative rickettsia-like organism, filamentous bacteria and two viral pathogens, the majority of which are previously unknown to science. To demonstrate potential for such pathogenic risks to be characterised from a taxonomic perspective, one of the pathogens, a novel microsporidian, is described based upon its pathology, developmental cycle and SSU rRNA gene phylogeny. The novel microsporidian Cucumispora roeselii n. sp. displayed closest morphological and phylogenetic similarity to two previously described taxa, Cucumispora dikerogammari Ovcharenko, 2010 and Cucumispora ornata Bojko, 2015. Conclusions: In addition to our discovery extending the host range for the genus Cucumispora Ovcharenko, 2010 outside of the amphipod host genus Dikerogammarus Stebbing, we reveal significant potential for the co-transfer of (previously unknown) pathogens alongside this host when invading novel locations. This study highlights the importance of pre-invasion screening of low-impact NNS and, provides a means to document and potentially mitigate the additional risks posed by previously unknown pathogens

Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

Background: Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods: Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS) alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR). These investigations were accomplished by MHC genotyping and a PCR screen for Marek’s disease virus (MDV). Results: Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelinbound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions: The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift

Impaired Autophagy of an Intracellular Pathogen Induced by a Crohn's Disease Associated ATG16L1 Variant

The genetic risk factors predisposing individuals to the development of inflammatory bowel disease are beginning to be deciphered by genome-wide association studies. Surprisingly, these new data point towards a critical role of autophagy in the pathogenesis of Crohn's disease. A single common coding variant in the autophagy protein ATG16L1 predisposes individuals to the development of Crohn's disease: while ATG16L1 encoding threonine at amino acid position 300 (ATG16L1*300T) confers protection, ATG16L1 encoding for alanine instead of threonine (ATG16L1*300A, also known as T300A) mediates risk towards the development of Crohn's disease. Here we report that, in human epithelial cells, the Crohn's disease-associated ATG16L1 coding variant shows impairment in the capture of internalized Salmonella within autophagosomes. Thus, we propose that the association of ATG16L1*300A with increased risk of Crohn's disease is due to impaired bacterial handling and lowered rates of bacterial capture by autophagy

Nakkuste poolt põhjustatud epidermise rakkude talitusliku aktiivsuse muutused kaladel

Previous results have suggested that epidermal club cells have a generic role in response to injury and that they display intense phagocytic activity, having an anti-parasitic function in the host. The presently reported doctoral theses focused on the alterations of epidermal club cell activity and on the integration with mucous cells in common carp epidermis by ichthyophthiriosis and mucus production in triploid Atlantic salmon by gyrodactylosis also elucidate processes involved in epidermal papillomatosis regeneration of koi carp which occurs during a steady temperature increase. The results of this thesis demonstrate the potential role of club cells in healing process during and after damages in carp, but not anti-parasite functions of these cells. For better understanding of club and mucous cells integrated functions further studies should conduct more extensive sampling from all parts of the freshwater fish.Mõnedel kalaliikidel asuvad epidermise ogakihis suured, ühe või kahetuumalised eosinofiilsed nuirakud, millede mõõtmed ulatuvad 40 μm. Viimased avaldatud uuringud näitavad, et nuirakkudel võib olla teatud roll epidermise struktuuri ennistumisel ja tervenemisel pärast vigastusi ning nad omavad teatud mõju sellesse tunginud välisparasiitidesse. Doktoritöö eesmärgiks oli, kasutades histoloogia ja histokeemia meetodeid, selgitada haigustekitajate poolt põhjustatud rakulise struktuuri ja aktiivsuse muutusi kalade epidermises. Doktoritöös avaldatud uuringute tulemused näitavad, et nuirakud täidavad olulist rolli epidermise tervenemisel ja seda, et need asendavad ogakihis prolifereerumise lõpetanud, välispinnale suundunud ja seal avanenud limarakke, kuid ei oma antiparasiitseid omadusi per se.The publication of this dissertation is granted by the Graduate School in Biomedicine and Biotechnology

Oral iron acutely elevates bacterial growth in human serum.

Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses