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One Health (Amsterdam, Netherlands) Jun 2024Vector-borne diseases (VBDs) are considered as (re-)emerging, but information on the transmission cycles and wildlife reservoirs is often incomplete, particularly with...
Vector-borne diseases (VBDs) are considered as (re-)emerging, but information on the transmission cycles and wildlife reservoirs is often incomplete, particularly with regard to urban areas. The present study investigated blood samples from European hedgehogs () presented at wildlife rehabilitation centres in the region of Hanover. Past exposure to sensu lato (s.l.) and tick-borne encephalitis virus (TBEV) was assessed by serological detection of antibodies, while current infections with spp., , spp., , spp., spp. and were investigated by (q)PCR. Of 539 hedgehogs tested for anti- antibodies, 84.8% (457/539) were seropositive, with a higher seropositivity rate in adult than subadult animals, while anti-TBEV antibodies were detected in one animal only (0.2%; 1/526). By qPCR, 31.2% (168/539) of hedgehog blood samples were positive for spp., 49.7% (261/525) for , 13.0% (68/525) for spp., 8.2% for (43/525), 8.0% (42/525) for spp. and 1.3% (7/525) for spp., while was not detected. While further differentiation of spp. infections was not successful, 63.2% of the infections were assigned to the zoonotic ecotype I and among spp. infections, 50.0% to by ecotype- or species-specific qPCR, respectively. Sequencing revealed the presence of a sp. closely related to in addition to a sp. previously described from hedgehogs, as well as and . These findings show that hedgehogs from rehabilitation centres are valuable sources to identify One Health pathogens in urban areas. The hedgehogs are not only exposed to pathogens from fleas and ticks in urban areas, but they also act as potent amplifiers for these vectors and their pathogens, relevant for citizens and their pets.
PubMed: 38855195
DOI: 10.1016/j.onehlt.2024.100764 -
Ticks and Tick-borne Diseases Sep 2024A promising alternative approach to conventional vector and rodent control practices is the use of a bait containing a rodenticide and acaricide in controlling vectors...
A rodent and tick bait for controlling white-footed mice (Peromyscus leucopus) and blacklegged ticks (Ixodes scapularis), the respective pathogen host and vector of the Lyme disease spirochetes.
A promising alternative approach to conventional vector and rodent control practices is the use of a bait containing a rodenticide and acaricide in controlling vectors and pathogen reservoirs concurrently. In the United States, Lyme disease continues to be the most prevalent vector-borne disease with approximately 500,000 Lyme disease cases estimated each year. Previous research has demonstrated the usefulness of a low dose fipronil bait in controlling Ixodes scapularis larvae feeding on white-footed mice. However, considering white-footed mice can be an unwanted species because of their association with tick-borne disease and hantaviruses, a combination rodent and tick bait (RTB) might provide a useful alternative to encourage additional community participation in integrated tick management (ITM) efforts. The purpose of this research was to evaluate the use of RTB (0.025 % warfarin, 0.005 % fipronil) in controlling white-footed mice and I. scapularis larvae. Studies were designed in part based on Environmental Protection Agency (EPA) guidelines. A laboratory choice test was conducted to evaluate the use of RTB in controlling white-footed mice over 15-day exposure when they were exposed to an alternative diet. Mice were observed every day for mortality and signs of warfarin toxicity. A simulated field test was conducted to evaluate the use of RTB, presented in the presence of an alternative diet, in controlling I. scapularis parasitizing white-footed mice over 4-day exposure. Mice were fitted with capsules and manually infested with I. scapularis larvae. The inside of each capsule was observed to evaluate tick attachment. Replete larvae detaching from each mouse were collected. Blood was collected from all treatment group mice via cardiac puncture to determine the fipronil sulfone concentration in plasma for each animal. Results indicated that RTB would be adequately consumed in the presence of an alternative diet under laboratory and simulated field conditions. Treatment with RTB resulted in 100 % mortality of white-footed mice during 15-day exposure and prevented 100 % larvae from feeding to repletion during 4-day exposure. All mice succumbing to RTB showed signs of warfarin toxicity. All mice parasitized with ticks that were exposed to RTB had fipronil sulfone detectable in plasma, with even the lowest concentration detected (8.1 parts per billion) controlling 100 % parasitizing I. scapularis larvae. The results suggest that RTB could be a useful means of rodent and tick control for use in ITM programs.
Topics: Animals; Ixodes; Peromyscus; Lyme Disease; Tick Control; Tick Infestations; Larva; Rodenticides; Acaricides; Pyrazoles; Female; Arachnid Vectors
PubMed: 38852539
DOI: 10.1016/j.ttbdis.2024.102362 -
BMC Microbiology Jun 2024People living with HIV (PLWH) are at increased risk of acquisition of multidrug resistant organisms due to higher rates of predisposing factors. The gut microbiome is...
BACKGROUND
People living with HIV (PLWH) are at increased risk of acquisition of multidrug resistant organisms due to higher rates of predisposing factors. The gut microbiome is the main reservoir of the collection of antimicrobial resistance determinants known as the gut resistome. In PLWH, changes in gut microbiome have been linked to immune activation and HIV-1 associated complications. Specifically, gut dysbiosis defined by low microbial gene richness has been linked to low Nadir CD4 + T-cell counts. Additionally, sexual preference has been shown to strongly influence gut microbiome composition in PLWH resulting in different Prevotella or Bacteroides enriched enterotypes, in MSM (men-who-have-sex-with-men) or no-MSM, respectively. To date, little is known about gut resistome composition in PLWH due to the scarcity of studies using shotgun metagenomics. The present study aimed to detect associations between different microbiome features linked to HIV-1 infection and gut resistome composition.
RESULTS
Using shotgun metagenomics we characterized the gut resistome composition of 129 HIV-1 infected subjects showing different HIV clinical profiles and 27 HIV-1 negative controls from a cross-sectional observational study conducted in Barcelona, Spain. Most no-MSM showed a Bacteroides-enriched enterotype and low microbial gene richness microbiomes. We did not identify differences in resistome diversity and composition according to HIV-1 infection or immune status. However, gut resistome was more diverse in MSM group, Prevotella-enriched enterotype and gut micorbiomes with high microbial gene richness compared to no-MSM group, Bacteroides-enriched enterotype and gut microbiomes with low microbial gene richness. Additionally, gut resistome beta-diversity was different according to the defined groups and we identified a set of differentially abundant antimicrobial resistance determinants based on the established categories.
CONCLUSIONS
Our findings reveal a significant correlation between gut resistome composition and various host variables commonly associated with gut microbiome, including microbiome enterotype, microbial gene richness, and sexual preference. These host variables have been previously linked to immune activation and lower Nadir CD4 + T-Cell counts, which are prognostic factors of HIV-related comorbidities. This study provides new insights into the relationship between antibiotic resistance and clinical characteristics of PLWH.
Topics: Adult; Female; Humans; Male; Middle Aged; Bacteria; Dysbiosis; Feces; Gastrointestinal Microbiome; HIV Infections; HIV-1; Homosexuality, Male; Metagenomics; Prevotella; Sexual Behavior; Spain
PubMed: 38851693
DOI: 10.1186/s12866-024-03335-z -
Italian Journal of Food Safety May 2024Hepatitis E is a disease sustained by RNA viruses, which have four different genotypes, all of which are responsible for acute forms of hepatitis. Genotypes 1 and 2...
Hepatitis E is a disease sustained by RNA viruses, which have four different genotypes, all of which are responsible for acute forms of hepatitis. Genotypes 1 and 2 infect only humans, causing epidemics mainly transmitted by contaminated water, while geno-types 3 and 4 are zoonotic, and the infection is linked to the consumption of raw or undercooked meat or meat products. Hepatitis E virus (HEV) genotypes 3 and 4 have been detected in domestic , considered the asymptomatic reservoir of HEV, and in wild animals such as wild boar and deer. Despite scientific studies that have highlighted the presence of HEV in cured meat products, such as pork liver sausages, the viral persistence in the different production steps of curing has not been evaluated. Therefore, this study aimed to evaluate the persistence of HEV genotype 3 during the different curing and storage times of experimentally contaminated pork liver sausages using biomolecular methods. The sausages tested positive at all curing and storage times. This study confirms the potential risk attributed to pork liver sausages in HEV transmission. However, to guarantee an efficient risk assessment, future studies will be performed to correlate the presence of HEV RNA with infectious viral particles.
PubMed: 38846049
DOI: 10.4081/ijfs.2024.12286 -
Current Research in Parasitology &... 2024Rats, being synanthropic, are hosts to agents of zoonotic diseases that pose a threat to human and domestic animal health. The nematode parasite , commonly known as the...
Rats, being synanthropic, are hosts to agents of zoonotic diseases that pose a threat to human and domestic animal health. The nematode parasite , commonly known as the rat lungworm, is no exception; it can cause potentially fatal neural disease in humans, dogs and other species. The distribution of (haplotypes SYD.1 and Ac13) and its close relative, is not well understood in Australia. We investigated the prevalence of in rats in Sydney, Australia, primarily faecal qPCR, and identified the species and haplotypes using partial 1 sequencing. We found a moderate prevalence of infection (29%; 95% CI: 16.1-46.6%) in black () and brown () rats around public parks and residential areas. This study demonstrates that Sydney's urban rat population is a reservoir for . Modelling infection status as a function of rat species, sex, tibia length (as a proxy for age), and health index (a measure of weight by size) revealed that older rats are statistically more likely to be infected ( = 5.331, = 0.021). We observed a dominant presence of the SYD.1 haplotype, for which the implications are not yet known. No was detected, leading us to suspect it may have a more restricted host- and geographical range. Overall, this study illustrates the presence and potential risk of infection in Sydney. Public education regarding transmission routes and preventative measures is crucial to safeguard human and animal health.
PubMed: 38845789
DOI: 10.1016/j.crpvbd.2024.100179 -
Antimicrobial Stewardship & Healthcare... 2024This study aimed to investigate the contamination status of hospital sinks with carbapenemase-producing Enterobacterales (CPE), the efficacy of daily cleaning with...
Carbapenemase-producing Enterobacterales isolated from hospital sinks: molecular relationships with isolates from patients and the change in contamination status after daily disinfection with sodium hypochlorite.
OBJECTIVE
This study aimed to investigate the contamination status of hospital sinks with carbapenemase-producing Enterobacterales (CPE), the efficacy of daily cleaning with sodium hypochlorite, and the relationships between CPEs isolated from contaminated sinks and patients.
DESIGN
Pre/postintervention surveys of the CPE-contaminated sinks.
SETTING
Hospital wards including pediatric intensive care unit in a children's hospital.
PARTICIPANTS
Consenting CPE-colonized patients admitted between November 2018 and June 2021 in our hospital.
METHODS
Environmental culture of 180 sinks from nine wards in our hospital was performed three times with an interval of 2 years (2019, 2021, 2023). Molecular typing of the isolated strains from the sinks and patients was performed. After the first surveillance culture, we initiated daily disinfection of the sinks using sodium hypochlorite.
RESULTS
Before the intervention, we detected 30 CPE-positive sinks in 2019. After the intervention with sodium hypochlorite, we observed a substantial decline in the number of sinks contaminated with CPE; 13 in 2021 and 6 in 2023. However, the intervention did not significantly reduce the number of CPE-contaminated sinks used for the disposal of nutrition-rich substances. The CPE isolates from the patients and those from the sinks of the wards or floors where they were admitted tended to have similar pulse-field gel electrophoresis patterns.
CONCLUSION
Contaminated sinks could be reservoirs of disseminating CPE to the patients. Daily disinfection of sinks with sodium hypochlorite may be effective in eliminating CPE, although the effect could be weaker in sinks with a greater risk of contact with nutrition-rich substances.
PubMed: 38836042
DOI: 10.1017/ash.2024.94 -
A helping HAND: therapeutic potential of MAGL inhibition against HIV-1-associated neuroinflammation.Frontiers in Immunology 2024Human immunodeficiency virus (HIV) affects nearly 40 million people globally, with roughly 80% of all people living with HIV receiving antiretroviral therapy....
BACKGROUND
Human immunodeficiency virus (HIV) affects nearly 40 million people globally, with roughly 80% of all people living with HIV receiving antiretroviral therapy. Antiretroviral treatment suppresses viral load in peripheral tissues but does not effectively penetrate the blood-brain barrier. Thus, viral reservoirs persist in the central nervous system and continue to produce low levels of inflammatory factors and early viral proteins, including the transactivator of transcription (Tat). HIV Tat is known to contribute to chronic neuroinflammation and synaptodendritic damage, which is associated with the development of cognitive, motor, and/or mood problems, collectively known as HIV-associated neurocognitive disorders (HAND). Cannabinoid anti-inflammatory effects are well documented, but therapeutic utility of cannabis remains limited due to its psychotropic effects, including alterations within brain regions encoding reward processing and motivation, such as the nucleus accumbens. Alternatively, inhibiting monoacylglycerol lipase (MAGL) has demonstrated therapeutic potential through interactions with the endocannabinoid system.
METHODS
The present study utilized a reward-related operant behavioral task to quantify motivated behavior in female Tat transgenic mice treated with vehicle or MAGL inhibitor MJN110 (1 mg/kg). Brain tissue was collected to assess dendritic injury and neuroinflammatory profiles, including dendritic microtubule-associated protein (MAP2ab) intensity, microglia density, microglia morphology, astrocyte density, astrocytic interleukin-1ß (IL-1ß) colocalization, and various lipid mediators.
RESULTS
No significant behavioral differences were observed; however, MJN110 protected against Tat-induced dendritic injury by significantly upregulating MAP2ab intensity in the nucleus accumbens and in the infralimbic cortex of Tat(+) mice. No or only minor effects were noted for Iba-1 microglia density and/or microglia morphology. Further, Tat increased GFAP astrocyte density in the infralimbic cortex and GFAP astrocytic IL-1ß colocalization in the nucleus accumbens, with MJN110 significantly reducing these measures in Tat(+) subjects. Lastly, selected HETE-related inflammatory lipid mediators in the striatum were downregulated by chronic MJN110 treatment.
CONCLUSIONS
These findings demonstrate anti-inflammatory and neuroprotective properties of MJN110 without cannabimimetic behavioral effects and suggest a promising alternative to cannabis for managing neuroinflammation.
Topics: Animals; Mice; HIV-1; Neuroinflammatory Diseases; Mice, Transgenic; Female; Monoacylglycerol Lipases; tat Gene Products, Human Immunodeficiency Virus; HIV Infections; Humans; Brain; Disease Models, Animal; Microglia; AIDS Dementia Complex
PubMed: 38835765
DOI: 10.3389/fimmu.2024.1374301 -
Proceedings of the National Academy of... Jun 2024Angiotensin-convertingenzyme 2 (ACE2) has dual functions, regulating cardiovascular physiology and serving as the receptor for coronaviruses. Bats, the only true flying...
Angiotensin-convertingenzyme 2 (ACE2) has dual functions, regulating cardiovascular physiology and serving as the receptor for coronaviruses. Bats, the only true flying mammals and natural viral reservoirs, have evolved positive alterations in traits related to both functions of ACE2. This suggests significant evolutionary changes in ACE2 during bat evolution. To test this hypothesis, we examine the selection pressure in ACE2 along the ancestral branch of all bats (AncBat-ACE2), where powered flight and bat-coronavirus coevolution occurred, and detect a positive selection signature. To assess the functional effects of positive selection, we resurrect AncBat-ACE2 and its mutant (AncBat-ACE2-mut) created by replacing the positively selected sites. Compared to AncBat-ACE2-mut, AncBat-ACE2 exhibits stronger enzymatic activity, enhances mice's performance in exercise fatigue, and shows lower affinity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our findings indicate the functional pleiotropy of positive selection in the ancient ACE2 of bats, providing an alternative hypothesis for the evolutionary origin of bats' defense against coronaviruses.
Topics: Chiroptera; Animals; Angiotensin-Converting Enzyme 2; Mice; Selection, Genetic; Genetic Pleiotropy; Evolution, Molecular; SARS-CoV-2; COVID-19; Coronavirus; Humans; Phylogeny
PubMed: 38833475
DOI: 10.1073/pnas.2321619121 -
The Journal of Clinical Investigation Jun 2024Despite effective antiretroviral therapy (ART), persons living with HIV (PWH) harbor reservoirs of persistently infected CD4+ cells, which constitute a barrier to cure....
Despite effective antiretroviral therapy (ART), persons living with HIV (PWH) harbor reservoirs of persistently infected CD4+ cells, which constitute a barrier to cure. Initiation of ART during acute infection reduces the size of the HIV reservoir, and we hypothesized that in addition, it would favor integration of proviruses in HIV-specific CD4+ T cells, while initiation of ART during chronic HIV infection would favor relatively more proviruses in herpesvirus-specific cells. We further hypothesized that proviruses in acute-ART-initiators would be integrated into antiviral genes, whereas integration sites in chronic-ART-initiators would favor genes associated with cell proliferation and exhaustion. We found the HIV DNA distribution across HIV-specific vs. herpesvirus-specific CD4+ T cells was as hypothesized. HIV integration sites (IS) in acute-ART-initiators were significantly enriched in gene sets controlling lipid metabolism and HIF-1α-mediated hypoxia, both metabolic pathways active in early HIV infection. Persistence of these infected cells during prolonged ART suggests a survival advantage. IS in chronic-ART-initiators were enriched in a gene set controlling EZH2 histone methylation; and methylation has been associated with diminished LTR transcription. These differences we found in antigen specificities and IS distributions within HIV-infected cells might be leveraged in designing cure strategies tailored to the timing of ART initiation.
PubMed: 38833307
DOI: 10.1172/JCI159569 -
Journal of Virology Jun 2024Porcine hemagglutinating encephalomyelitis virus (PHEV), a neurotropic betacoronavirus, is prevalent in natural reservoir pigs and infects mice. This raises concerns...
Porcine hemagglutinating encephalomyelitis virus (PHEV), a neurotropic betacoronavirus, is prevalent in natural reservoir pigs and infects mice. This raises concerns about host jumping or spillover, but little is known about the cause of occurrence. Here, we revealed that dipeptidyl peptidase 4 (DPP4) is a candidate binding target of PHEV spikes and works as a broad barrier to overcome. Investigations of the host breadth of PHEV confirmed that cells derived from pigs and mice are permissive to virus propagation. Both porcine DPP4 and murine DPP4 have high affinity for the viral spike receptor-binding domain (RBD), independent of their catalytic activity. Loss of DPP4 expression results in limited PHEV infection. Structurally, PHEV spike protein binds to the outer surface of blades IV and V of the DPP4 β-propeller domain, and the DPP4 residues N229 and N321 (relative to human DPP4 numbering) participate in RBD binding via its linked carbohydrate entities. Removal of these -glycosylations profoundly enhanced the RBD-DPP4 interaction and viral invasion, suggesting they act as shielding in PHEV infection. Furthermore, we found that glycosylation, rather than structural differences or surface charges, is more responsible for DPP4 recognition and species barrier formation. Overall, our findings shed light on virus-receptor interactions and highlight that PHEV tolerance to DPP4 orthologs is a putative determinant of its cross-species transmission or host range expansion.IMPORTANCEPHEV is a neurotropic betacoronavirus that is circulating worldwide and has raised veterinary and economic concerns. In addition to being a reservoir species of pigs, PHEV can also infect wild-type mice, suggesting a "host jump" event. Understanding cross-species transmission is crucial for disease prevention and control but remains to be addressed. Herein, we show that the multifunctional receptor DPP4 plays a pivotal role in the host tropism of PHEV and identifies the conserved glycosylation sites in DPP4 responsible for this restriction. These findings highlight that the ability of PHEV to utilize DPP4 orthologs potentially affects its natural host expansion.
PubMed: 38829136
DOI: 10.1128/jvi.00753-24