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Parasitology Research Jun 2024Cutaneous leishmaniasis (CL), a neglected tropical disease, is a major public health concern in Yemen, with Leishmania tropica identified as the main causative agent....
First report of Leishmania tropica in domestic and wild animal hosts in hyperendemic areas of human cutaneous leishmaniasis in western Yemen: a neglected tropical disease needing One Health approach.
Cutaneous leishmaniasis (CL), a neglected tropical disease, is a major public health concern in Yemen, with Leishmania tropica identified as the main causative agent. This study aims to investigate the occurrence and distribution of Leishmania parasites in domestic and wild animals in CL endemic areas in the western highlands of Yemen. A cross-sectional study was conducted in the Utmah District of western Yemen. Blood and skin scraping specimens were collected from 122 domestic and wild animals and tested for the Leishmania DNA using internal transcribed spacer 1 (ITS1) nested polymerase chain reaction. Phylogenetic analyses were performed on 20 L. tropica sequences obtained from animals in this study and 34 sequences from human isolates (collected concurrently from the same study area) retrieved from the GenBank. Overall, L. tropica was detected in 16.4% (20/122) of the examined animals, including 11 goats, two dogs, two bulls, one cow, one donkey, one rabbit, one rat and one bat. None of the examined cats and sheep was positive. The animal sequences were segregated into four different L. tropica haplotypes, with the majority of the animal (15/20) and human (32/34) sequences composed of one dominant haplotype/genotype. These findings represent the first confirmed evidence of natural L. tropica infections in different kinds of domestic and wild animals in western Yemen, suggesting these animals potentially have a role in the transmission of CL in Yemen. Therefore, a One Health approach is required for the effective prevention and control of this devastating disease among endemic populations.
Topics: Animals; Leishmania tropica; Leishmaniasis, Cutaneous; Yemen; Humans; Cross-Sectional Studies; Animals, Wild; Animals, Domestic; Phylogeny; One Health; DNA, Protozoan; Neglected Diseases; Endemic Diseases; DNA, Ribosomal Spacer; Polymerase Chain Reaction; Sequence Analysis, DNA; Male
PubMed: 38935203
DOI: 10.1007/s00436-024-08273-3 -
Frontiers in Public Health 2024Leptospirosis is a bacterial disease that affects both humans and animals worldwide. Currently, a positional war is ongoing in Ukraine, and the military is encountering...
Leptospirosis is a bacterial disease that affects both humans and animals worldwide. Currently, a positional war is ongoing in Ukraine, and the military is encountering a significant number of rodents in trenches and dugouts, which are known reservoirs for , the causative agent of leptospirosis-a potentially dangerous infectious disease with a high mortality rate. The civilian population is also at potential risk of leptospirosis. The destruction of the Kakhovka Dam on June 6, 2023, has led to widespread devastation and human suffering. In the short term, there is a significant risk of rodent-borne diseases such as leptospirosis. We utilized data from the Ukrainian Centre for Disease Prevention Control and observed a substantial increase in prevalence in 2023. The notification rate in Ukraine in 2023 was 1.06 per 100,000 persons, which is higher than that of other countries in the European Union. Particular attention is being given to Zakarpattia Oblast, located on the western border of Ukraine, which shares boundaries with Romania, Hungary, Poland, and Slovakia, with an extremely high incidence rate of 12.08 per 100,000 persons. Based on these findings, we recommend education and awareness campaigns, vaccination, personal protective measures, and improved surveillance to address the increasing incidence of leptospirosis in Ukraine.
Topics: Ukraine; Humans; Leptospirosis; Adult; Male; Female; Middle Aged; Prevalence; Incidence; Adolescent; Young Adult; Child; Aged; Leptospira; Child, Preschool; Population Surveillance; Animals
PubMed: 38932783
DOI: 10.3389/fpubh.2024.1394781 -
Vaccines May 2024Noroviruses constitute a significant aetiology of sporadic and epidemic gastroenteritis in human hosts worldwide, especially among young children, the elderly, and... (Review)
Review
Noroviruses constitute a significant aetiology of sporadic and epidemic gastroenteritis in human hosts worldwide, especially among young children, the elderly, and immunocompromised patients. The low infectious dose of the virus, protracted shedding in faeces, and the ability to persist in the environment promote viral transmission in different socioeconomic settings. Considering the substantial disease burden across healthcare and community settings and the difficulty in controlling the disease, we review aspects related to current knowledge about norovirus biology, mechanisms driving the evolutionary trends, epidemiology and molecular diversity, pathogenic mechanism, and immunity to viral infection. Additionally, we discuss the reservoir hosts, intra-inter host dynamics, and potential eco-evolutionary significance. Finally, we review norovirus vaccines in the development pipeline and further discuss the various host and pathogen factors that may complicate vaccine development.
PubMed: 38932319
DOI: 10.3390/vaccines12060590 -
Viruses Jun 2024Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is... (Review)
Review
Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection.
Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus's direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection.
Topics: Simian Immunodeficiency Virus; Animals; HIV Infections; Simian Acquired Immunodeficiency Syndrome; Humans; HIV; Disease Models, Animal; Haplorhini; Lymphocyte Depletion
PubMed: 38932264
DOI: 10.3390/v16060972 -
Pharmaceuticals (Basel, Switzerland) Jun 2024In the New World, dogs are considered the main reservoir of visceral leishmaniasis (VL). Due to inefficacies in existing treatments and the lack of an efficient vaccine,...
Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis.
In the New World, dogs are considered the main reservoir of visceral leishmaniasis (VL). Due to inefficacies in existing treatments and the lack of an efficient vaccine, dog culling is one of the main strategies used to control disease, making the development of new therapeutic interventions mandatory. We previously showed that Tanespimycin (17-AAG), a Hsp90 inhibitor, demonstrated potential for use in leishmaniasis treatment. The present study aimed to test the safety of 17-AAG in dogs by evaluating plasma pharmacokinetics, dose-proportionality, and the tolerability of 17-AAG in response to a dose-escalation protocol and multiple administrations at a single dose in healthy dogs. Two protocols were used: Study A: four dogs received variable intravenous (IV) doses (50, 100, 150, 200, or 250 mg/m) of 17-AAG or a placebo ( = 4/dose level), using a cross-over design with a 7-day "wash-out" period; Study B: nine dogs received three IV doses of 150 mg/m of 17-AAG administered at 48 h intervals. 17-AAG concentrations were determined by a validated high-performance liquid chromatographic (HPLC) method: linearity (R = 0.9964), intra-day precision with a coefficient of variation (CV) ≤ 8%, inter-day precision (CV ≤ 20%), and detection and quantification limits of 12.5 and 25 ng/mL, respectively. In Study A, 17-AAG was generally well tolerated. However, increased levels of liver enzymes-alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)-and bloody diarrhea were observed in all four dogs receiving the highest dosage of 250 mg/m. After single doses of 17-AAG (50-250 mg/m), maximum plasma concentrations (Cmax) ranged between 1405 ± 686 and 9439 ± 991 ng/mL, and the area under the curve (AUC) plotting plasma concentration against time ranged between 1483 ± 694 and 11,902 ± 1962 AUC 0-8 h μg/mL × h, respectively. Cmax and AUC parameters were dose-proportionate between the 50 and 200 mg/m doses. Regarding Study B, 17-AAG was found to be well tolerated at multiple doses of 150 mg/m. Increased levels of liver enzymes-ALT (28.57 ± 4.29 to 173.33 ± 49.56 U/L), AST (27.85 ± 3.80 to 248.20 ± 85.80 U/L), and GGT (1.60 ± 0.06 to 12.70 ± 0.50 U/L)-and bloody diarrhea were observed in only 3/9 of these dogs. After the administration of multiple doses, Cmax and AUC 0-48 h were 5254 ± 2784 μg/mL and 6850 ± 469 μg/mL × h in plasma and 736 ± 294 μg/mL and 7382 ± 1357 μg/mL × h in tissue transudate, respectively. In conclusion, our results demonstrate the potential of 17-AAG in the treatment of CVL, using a regimen of three doses at 150 mg/m, since it presents the maintenance of high concentrations in subcutaneous interstitial fluid, low toxicity, and reversible hepatotoxicity.
PubMed: 38931434
DOI: 10.3390/ph17060767 -
Pharmaceuticals (Basel, Switzerland) Jun 2024With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in...
With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4 T cells. Although most patients are asymptomatic, HTLV-1-associated pathologies are often debilitating and include adult T-cell leukaemia/lymphoma (ATLL), which presents in mature adulthood and is associated with poor prognosis with short overall survival despite treatment. Curiously, the strongest indicator for the development of ATLL is the acquisition of HTLV-1 through breastfeeding. There are no therapeutic or preventative regimens for HTLV-1. However, antiretrovirals (ARVs), which target the essential retrovirus enzymes, have been developed for and transformed HIV therapy. As the architectures of retroviral enzyme active sites are highly conserved, some HIV-specific compounds are active against HTLV-1. Here, we expand on our work, which showed that integrase strand transfer inhibitors (INSTIs) and some nucleoside reverse transcriptase inhibitors (NRTIs) block HTLV-1 transmission in cell culture. Specifically, we find that dolutegravir, the INSTI currently recommended as the basis of all new combination antiretroviral therapy prescriptions, and the latest prodrug formula of the NRTI tenofovir, tenofovir alafenamide, also potently inhibit HTLV-1 infection. Our results, if replicated in a clinical setting, could see transmission rates of HTLV-1 and future caseloads of HTLV-1-associated pathologies like ATLL dramatically cut via the simple repurposing of already widely available HIV pills in HTLV-1 endemic areas. Considering our findings with the old medical saying "it is better to prevent than cure", we highly recommend the inclusion of INSTIs and tenofovir prodrugs in upcoming HTLV-1 clinical trials as potential prophylactics.
PubMed: 38931397
DOI: 10.3390/ph17060730 -
Microorganisms Jun 2024is responsible for causing bacillary necrosis (BNP) in striped catfish () in Vietnam. This study offers a comprehensive genomic characterization of to enhance...
is responsible for causing bacillary necrosis (BNP) in striped catfish () in Vietnam. This study offers a comprehensive genomic characterization of to enhance understanding of the molecular epidemiology, virulence, and antimicrobial resistance. isolates were collected from diseased striped catfish in the Mekong Delta. The species was confirmed through PCR. Antimicrobial susceptibility testing was conducted using minimum inhibitory concentrations for commonly used antimicrobials. Thirty representative isolates were selected for whole genome sequencing to delineate their genomic profiles and phylogeny. All strains belonged to ST-26 and exhibited genetic relatedness, differing by a maximum of 90 single nucleotide polymorphisms. Most isolates carried multiple antimicrobial resistance genes, with the () gene present in 63% and in 77% of the genomes. The ESBL gene, , was identified in 30% of the genomes. Three plasmid replicon types were identified: IncA, p0111, and IncQ1. The genomes clustered into two clades based on their virulence gene profile, one group with the T3SS genes and one without. The genetic similarity among Vietnamese isolates suggests that disease spread occurs within the Mekong region, underscoring the importance of source tracking, reservoir identification, and implementation of necessary biosecurity measures to mitigate spread of BNP.
PubMed: 38930563
DOI: 10.3390/microorganisms12061182 -
Antioxidants (Basel, Switzerland) May 2024Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an...
BACKGROUND
Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an immune response in basal keratinocytes, which may transform into a reservoir of antigens able to initiate an autoimmune reaction. However, other pathogenic pathways complement these mechanisms. Recent studies highlight the involvement of nitrosative stress in the pathogenesis of chronic inflammatory skin diseases. Current data on its role in the pathogenesis of LP are scarce.
METHODS
In this article, we investigated nitrosative stress in 40 cutaneous LP (CLP) patients compared to 40 healthy subjects using serum markers including nitrosative stress markers-direct nitrite, total nitrite, nitrate and symmetric dimethylarginine (SDMA), total antioxidant status (TAS), and hsCRP, a marker of inflammation, and analyzed the relationship between nitrosative stress, antioxidant defense, and inflammation to offer new insights into the role of the NO pathway in LP pathogenesis.
RESULTS
We identified significantly higher serum levels of direct nitrite, total nitrite, nitrate, SDMA and hsCRP, and significantly lower levels of TAS in CLP patients versus controls. There were significant negative correlations between the serum levels of TAS and significantl positive correlations between the serum levels of hsCRP and the analyzed nitrosative stress markers in patients with CLP.
CONCLUSION
Our results indicate an increased level of nitrosative stress in LP patients that correlates with a pro-inflammatory status and altered antioxidant defense.
PubMed: 38929109
DOI: 10.3390/antiox13060670 -
Biology Jun 2024is a protozoan tick-borne parasite infecting domestic and wild canids, including foxes, wolves, and jackals. It is mainly found in dogs but has also been detected in...
is a protozoan tick-borne parasite infecting domestic and wild canids, including foxes, wolves, and jackals. It is mainly found in dogs but has also been detected in several wild carnivores, including foxes, wolves, and jackals. Host transmission primarily occurs through the ingestion of infected ticks, typically , with documented instances of transplacental transmission from infected females to cubs. In Serbia, the golden jackal is common throughout the country, and its population has increased in recent years. Previous research has documented the presence of several vector-borne pathogens in the jackal population in Serbia, so we conducted this study to determine the presence, prevalence, and genetic variability of . Over eleven years (2010-2020), 114 animal samples were collected from 23 localities in Serbia. A total of 90/114 (78.95%) jackals were positive for , and they came from 22 localities. Among 15 juveniles, almost half (6/15 (40%)) tested positive for . In addition to the high prevalence, high genetic variability of the pathogen was also found. According to the mutated positions, four sequence types (S4-S7) of were determined. Based on our earlier research on the grey wolf and on this study, it can be observed that various sequence types of circulate within wild canid populations in Serbia. The prevalence of infection in wild carnivores raises significant concerns for wildlife conservation and animal health. Infected animals may act as reservoirs for the disease, posing a potential risk to domestic animals by acting as a source of infection.
PubMed: 38927291
DOI: 10.3390/biology13060411 -
Antibiotics (Basel, Switzerland) Jun 2024Carbapenemases, a class of enzymes specialized in the hydrolysis of carbapenems, represent a significant threat to global public health. These enzymes are classified... (Review)
Review
Carbapenemases, a class of enzymes specialized in the hydrolysis of carbapenems, represent a significant threat to global public health. These enzymes are classified into different Ambler's classes based on their active sites, categorized into classes A, D, and B. Among the most prevalent types are IMI/NMC-A, KPC, VIM, IMP, and OXA-48, commonly associated with pathogenic species such as , , and . The emergence and dissemination of carbapenemase-producing bacteria have raised substantial concerns due to their ability to infect humans and animals (both companion and food-producing) and their presence in environmental reservoirs. Adopting a holistic One Health approach, concerted efforts have been directed toward devising comprehensive strategies to mitigate the impact of antimicrobial resistance dissemination. This entails collaborative interventions, highlighting proactive measures by global organizations like the World Health Organization, the Center for Disease Control and Prevention, and the Food and Agriculture Organization. By synthesizing the evolving landscape of carbapenemase epidemiology in Portugal and tracing the trajectory from initial isolated cases to contemporary reports, this review highlights key factors driving antibiotic resistance, such as antimicrobial use and healthcare practices, and underscores the imperative for sustained vigilance, interdisciplinary collaboration, and innovative interventions to curb the escalating threat posed by antibiotic-resistant pathogens. Finally, it discusses potential alternatives and innovations aimed at tackling carbapenemase-mediated antibiotic resistance, including new therapies, enhanced surveillance, and public awareness campaigns.
PubMed: 38927223
DOI: 10.3390/antibiotics13060557