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BMC Veterinary Research Oct 2023Sarcoptic mange is a common, pruritic parasitic skin disease of dogs. Due to its highly contagious character, it represents a potential veterinary and public health... (Review)
Review
BACKGROUND
Sarcoptic mange is a common, pruritic parasitic skin disease of dogs. Due to its highly contagious character, it represents a potential veterinary and public health risk. Because of clinical similarity with other diseases, cross-antigenicity, and low sensitivity of available diagnostic methods, therapeutical trial is frequently used to confirm the disease. Considering the variety of available acaricidal molecules as well as the need to use the most effective treatment, the present paper reviews evidence comparing different types of systemic treatment of canine scabies.
RESULTS
Analysis of the results showed that afoxolaner, fluralaner and sarolaner as well as several macrocyclic lactones such as selamectin, moxidectin and milbemycin oxime can lead to parasitological and clinical cure.
CONCLUSION
The similarity in the clinical and parasitological efficacy of these substances enhances the need for comparative studies, which could allow the identification of the most efficacious product.
Topics: Animals; Dogs; Scabies; Dog Diseases; Acaricides; Administration, Cutaneous; Treatment Outcome; Sarcoptes scabiei
PubMed: 37798627
DOI: 10.1186/s12917-023-03759-1 -
PloS One 2023Toxoplasma gondii, a ubiquitous parasitic protozoan, may be an important cause of neurological and psychiatric diseases. The present systematic review and meta-analysis,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Toxoplasma gondii, a ubiquitous parasitic protozoan, may be an important cause of neurological and psychiatric diseases. The present systematic review and meta-analysis, therefore, was conducted to investigate the scientific evidence regarding the potential association between T. gondii infection and psychiatric disorders in Iran.
METHODS
We systematically reviewed articles from world-wide databases, including PubMed, Scopus, Science Direct, Web of Science, Google Scholar, and Iranian national databases up to July 30th, 2021. The Newcastle Ottawa Scale (NOS) was used to assess the quality of included studies. The common odds ratio (OR) was estimated using inverse variance and a random-effects model. Heterogeneity was assessed using the χ2-based Cochrane test (Q) and the I2 index. Also, sensitivity analyses and publication bias were calculated. Moreover, subgroup analysis was performed based on the type of disorder and quality score of different eligible studies.
RESULTS
16 studies were included in this meta-analysis. Our meta-analyses found that the OR of the risk of anti- T. gondii IgG and IgM in psychiatric patients compared to the control group was 1.56 (95% CI; 1.23-1.99) and 1.76 (95% CI: 1.19-2.61), respectively. Subgroup analysis based on the type of disorder showed that the OR of the risk of anti- T. gondii IgG in Iranian schizophrenia patients and other psychiatric disorders compared to the control group were 1.50 (95% CI; 1.09-2.07) and 2.03 (95% CI: 1.14-3.60), respectively, which are statistically significant. Also, the OR of the risk of anti- T. gondii IgM in Iranian schizophrenia and depression patients compared to the control group was 1.54 (95% CI; 0.9-2.64) and 1.03 (95% CI: 0.2-5.24), respectively, which are not statistically significant. Additionally, subgroup analysis based on quality scores showed no significant influence on the results according to the moderate quality studies. However, this association was significant according to the high quality studies. The obtained results of Egger's test were 1.5 (95% CI; -0.62-3.73, P = 0.15) and 0.47 (95% CI; -0.82-1.76, P = 0.45), respectively, indicating publication bias. The significant results of the heterogeneity analysis confirmed a high level of heterogeneity in the IgG test (P = 0.000, I2 = 66.6%). However, no significant results from the test of heterogeneity were detected in the IgM test (P = 0.15, I2 = 27.5%). The results of the sensitivity analysis showed that the impact of each study on the meta-analysis was not significant on overall estimates.
CONCLUSIONS
Despite the limited number of studies, these outcomes supported a possible link between T. gondii infection and psychiatric disorders in Iran. However, more high-quality investigations are needed in the future.
Topics: Humans; Iran; Toxoplasmosis; Toxoplasma; Schizophrenia; Immunoglobulin G; Immunoglobulin M; Seroepidemiologic Studies
PubMed: 37552680
DOI: 10.1371/journal.pone.0284954 -
Journal of Medicinal Chemistry Aug 2023There is an urgent need for new treatments for Chagas disease, a parasitic infection which mostly impacts South and Central America. We previously reported on the...
There is an urgent need for new treatments for Chagas disease, a parasitic infection which mostly impacts South and Central America. We previously reported on the discovery of GSK3494245/DDD01305143, a preclinical candidate for visceral leishmaniasis which acted through inhibition of the proteasome. A related analogue, active against , showed suboptimal efficacy in an animal model of Chagas disease, so alternative proteasome inhibitors were investigated. Screening a library of phenotypically active analogues against the proteasome identified an active, selective pyridazinone, the development of which is described herein. We obtained a cryo-EM co-structure of proteasome and a key inhibitor and used this to drive optimization of the compounds. Alongside this, optimization of the absorption, distribution, metabolism, and excretion (ADME) properties afforded a suitable compound for mouse efficacy studies. The outcome of these studies is discussed, alongside future plans to further understand the series and its potential to deliver a new treatment for Chagas disease.
Topics: Mice; Animals; Trypanosoma cruzi; Proteasome Inhibitors; Proteasome Endopeptidase Complex; Chagas Disease; Leishmaniasis, Visceral; Trypanocidal Agents
PubMed: 37506194
DOI: 10.1021/acs.jmedchem.3c00582 -
Cell Reports Aug 2023Infections cause catabolism of fat and muscle stores. Traditionally, studies have focused on understanding how the innate immune system contributes to energy stores...
Infections cause catabolism of fat and muscle stores. Traditionally, studies have focused on understanding how the innate immune system contributes to energy stores wasting, while the role of the adaptive immune system remains elusive. In the present study, we examine the role of the adaptive immune response in adipose tissue wasting and cachexia using a murine model of the chronic parasitic infection Trypanosoma brucei, the causative agent of sleeping sickness. We find that the wasting response occurs in two phases, with the first stage involving fat wasting caused by CD4+ T cell-induced anorexia and a second anorexia-independent cachectic stage that is dependent on CD8+ T cells. Fat wasting has no impact on host antibody-mediated resistance defenses or survival, while later-stage muscle wasting contributes to disease-tolerance defenses. Our work reveals a decoupling of adaptive immune-mediated resistance from the catabolic response during infection.
Topics: Animals; Mice; Cachexia; Anorexia; CD4-Positive T-Lymphocytes; Neoplasms; Adipose Tissue; Parasitic Diseases
PubMed: 37490905
DOI: 10.1016/j.celrep.2023.112814 -
Mucosal Immunology Dec 2023Cluster of differentiation (CD4) T cells consist of multiple subtypes, defined by expression of lineage-specific transcription factors, that contribute to the control of...
Cluster of differentiation (CD4) T cells consist of multiple subtypes, defined by expression of lineage-specific transcription factors, that contribute to the control of infectious diseases by providing help to immune and nonimmune target cells. In the current study, we examined the role of B cell lymphoma (Bcl)-6, a transcriptional repressor and master regulator of T follicular helper cell differentiation, in T cell-mediated host defense against intestinal and systemic parasitic infections. We demonstrate that while Bcl-6 expression by CD4 T cells is critical for antibody-mediated protective immunity against secondary infection with the nematode Heligmosoides polygyrus bakeri, it paradoxically compromises worm expulsion during primary infection by limiting the generation of interleukin-10 (IL-10)-producing Gata3 T helper 2 cells. Enhanced worm expulsion in the absence of Bcl-6 expressing T cells was associated with amplified intestinal goblet cell differentiation and increased generation of alternatively activated macrophages, effects that were reversed by neutralization of IL-10 signals. An increase in IL-10 production by Bcl-6-deficient CD4 T cells was also evident in the context of systemic Leishmania donovani infection, but in contrast to Heligmosoides polygyrus bakeri infection, compromised T helper 1-mediated liver macrophage activation and increased susceptibility to this distinct parasitic challenge. Collectively, our studies suggest that host defense pathways that protect against parasite superinfection and lethal systemic protozoal infections can be engaged at the cost of compromised primary resistance to well-tolerated helminths.
Topics: Animals; Interleukin-10; Parasitic Diseases; Th2 Cells; Nematoda
PubMed: 37659724
DOI: 10.1016/j.mucimm.2023.08.004 -
Nature Communications Jul 2023The reduced prevalence of insulin resistance and type 2 diabetes in countries with endemic parasitic worm infections suggests a protective role for worms against... (Randomized Controlled Trial)
Randomized Controlled Trial
The reduced prevalence of insulin resistance and type 2 diabetes in countries with endemic parasitic worm infections suggests a protective role for worms against metabolic disorders, however clinical evidence has been non-existent. This 2-year randomised, double-blinded clinical trial in Australia of hookworm infection in 40 male and female adults at risk of type 2 diabetes assessed the safety and potential metabolic benefits of treatment with either 20 (n = 14) or 40 (n = 13) Necator americanus larvae (L3) or Placebo (n = 13) (Registration ACTRN12617000818336). Primary outcome was safety defined by adverse events and completion rate. Homoeostatic model assessment of insulin resistance, fasting blood glucose and body mass were key secondary outcomes. Adverse events were more frequent in hookworm-treated participants, where 44% experienced expected gastrointestinal symptoms, but completion rates were comparable to Placebo. Fasting glucose and insulin resistance were lowered in both hookworm-treated groups at 1 year, and body mass was reduced after L3-20 treatment at 2 years. This study suggests hookworm infection is safe in people at risk of type 2 diabetes and associated with improved insulin resistance, warranting further exploration of the benefits of hookworms on metabolic health.
Topics: Animals; Male; Female; Diabetes Mellitus, Type 2; Insulin Resistance; Hookworm Infections; Necator americanus; Fasting
PubMed: 37495576
DOI: 10.1038/s41467-023-40263-4 -
Emerging Infectious Diseases Dec 2023Neurocysticercosis is almost exclusively caused by Taenia solium tapeworms. We describe a case of neurocysticercosis in Switzerland caused by infection with Taenia... (Review)
Review
Neurocysticercosis is almost exclusively caused by Taenia solium tapeworms. We describe a case of neurocysticercosis in Switzerland caused by infection with Taenia martis, the marten tapeworm, and review all 5 published cases of human infection with the marten tapeworm. In epidemiologically nonplausible cases of neurocysticercosis, zoonotic spillover infections should be suspected.
Topics: Animals; Humans; Mustelidae; Neurocysticercosis; Switzerland; Taenia; Taenia solium
PubMed: 37987597
DOI: 10.3201/eid2912.230697 -
European Journal of Medicinal Chemistry Dec 2023Parasitic diseases still pose a serious threat to human and animal health, particularly for millions of people and their livelihoods in low-income countries. Therefore,... (Review)
Review
Parasitic diseases still pose a serious threat to human and animal health, particularly for millions of people and their livelihoods in low-income countries. Therefore, research into the development of effective antiparasitic drugs remains a priority. Ivermectin, a sixteen-membered macrocyclic lactone, exhibits a broad spectrum of antiparasitic activities, which, combined with its low toxicity, has allowed the drug to be widely used in the treatment of parasitic diseases affecting humans and animals. In addition to its licensed use against river blindness and strongyloidiasis in humans, and against roundworm and arthropod infestations in animals, ivermectin is also used "off-label" to treat many other worm-related parasitic diseases, particularly in domestic animals. In addition, several experimental studies indicate that ivermectin displays also potent activity against viruses, bacteria, protozoans, trematodes, and insects. This review article summarizes the last 40 years of research on the antiparasitic effects of ivermectin, and the use of the drug in the treatment of parasitic diseases in humans and animals.
Topics: Animals; Humans; Antiparasitic Agents; Ivermectin; Parasitic Diseases
PubMed: 37793327
DOI: 10.1016/j.ejmech.2023.115838 -
EBioMedicine Aug 2023Schistosomiasis is a disease that significantly impacts human health in the developing world. Effective diagnostics are urgently needed for improved control of this...
BACKGROUND
Schistosomiasis is a disease that significantly impacts human health in the developing world. Effective diagnostics are urgently needed for improved control of this disease. CRISPR-based technology has rapidly accelerated the development of a revolutionary and powerful diagnostics platform, resulting in the advancement of a class of ultrasensitive, specific, cost-effective and portable diagnostics, typified by applications in COVID-19/cancer diagnosis.
METHODS
We developed CRISPR-based diagnostic platform SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the detection of Schistosoma japonicum and S. mansoni by combining recombinase polymerase amplification (RPA) with CRISPR-Cas13a detection, measured via fluorescent or colorimetric readouts. We evaluated SHERLOCK assays by using 150 faecal/serum samples collected from Schistosoma-infected ARC Swiss mice (female), and 189 human faecal/serum samples obtained from a S. japonicum-endemic area in the Philippines and a S. mansoni-endemic area in Uganda.
FINDINGS
The S. japonicum SHERLOCK assay achieved 93-100% concordance with gold-standard qPCR detection across all the samples. The S. mansoni SHERLOCK assay demonstrated higher sensitivity than qPCR and was able to detect infection in mouse serum as early as 3 weeks post-infection. In human samples, S. mansoni SHERLOCK had 100% sensitivity when compared to qPCR of faecal and serum samples.
INTERPRETATION
These schistosomiasis diagnostic assays demonstrate the potential of SHERLOCK/CRISPR-based diagnostics to provide highly accurate and field-friendly point-of-care tests that could provide the next generation of diagnostic and surveillance tools for parasitic neglected tropical diseases.
FUNDING
Australian Infectious Diseases Research Centre seed grant (2022) and National Health and Medical Research Council (NHMRC) of Australia (APP1194462, APP2008433).
Topics: Humans; Female; Animals; Mice; Sensitivity and Specificity; Australia; COVID-19; Schistosomiasis; Schistosoma japonicum; COVID-19 Testing
PubMed: 37487416
DOI: 10.1016/j.ebiom.2023.104730 -
PeerJ 2024Cancer is one of the leading causes of death, with an estimated 19.3 million new cases and 10 million deaths worldwide in 2020 alone. Approximately 2.2 million cancer... (Review)
Review
Cancer is one of the leading causes of death, with an estimated 19.3 million new cases and 10 million deaths worldwide in 2020 alone. Approximately 2.2 million cancer cases are attributed to infectious diseases, according to the World Health Organization (WHO). Despite the apparent involvement of some parasitic helminths (especially trematodes) in cancer induction, there are also records of the potential suppressive effects of helminth infections on cancer. Tapeworms such as , , and more seem to have the potential to suppress malignant cell development, although in a few cases the evidence might be contradictory. Our review aims to summarize known epidemiological data on the cancer-helminth co-occurrence in the human population and the interactions of tapeworms with cancers, ., proven or hypothetical effects of tapeworms and their products on cancer cells (., in experimental animals) or . The prospect of bioactive tapeworm molecules helping reduce the growth and metastasis of cancer is within the realm of future possibility, although extensive research is yet required due to certain concerns.
Topics: Animals; Humans; Cestoda; Taenia; Cestode Infections; Helminthiasis; Helminths; Neoplasms
PubMed: 38563013
DOI: 10.7717/peerj.17196