Efficacy of Mesenchymal Stem Cells Therapy in Parasitic Infections: Are Anti-parasitic Drugs Combined with MSCs More Effective?

PURPOSE: Mesenchymal stem cells (MSCs) are mesodermal-origin postnatal stem cells that are able to self-renew and differentiate into several cell lineages. MSCs possess anti-inflammatory and anti-apoptotic activity, immunomodulatory action, as well as regenerative properties. Since MSCs also have antimicrobial properties, it has been suggested that they should be utilized for treating infectious diseases. In this study, the last pre-clinical advances in the efficacy of MSCs' therapy against parasitic diseases were reviewed. METHODS: Data about the effects of MSCs' therapy on experimental and pre-clinical parasitic infections were collected by searching relevant articles and reviewing them. RESULTS: In the present study, empirical findings on the impacts of MSCs' therapy against parasitic diseases were recapitulated. Studies have reported that the administration of MSCs reduces the burden of the parasite and modulates the levels of inflammatory and anti-inflammatory cytokines in parasitic diseases, including schistosomiasis, malaria, cystic echinococcosis, toxocariasis, leishmaniasis, and trypanosomiasis. Also, the administration of MSCs combined with anti-parasitic drugs enhanced anti-parasitic effects and immunomodulatory actions. CONCLUSION: Based on this review, empirical studies have revealed the beneficial effects of MSCs against some parasitic infections. This new therapeutic strategy showed both anti-parasitic and immunomodulatory effects. Also, the combination of anti-parasitic drugs with MSCs' therapy promoted anti-parasitic and immunomodulatory activities against parasitic infections.

Immunomodulatory Potential of Non-Classical HLA-G in Infections including COVID-19 and Parasitic Diseases.

Human Leukocyte Antigen-G (HLA-G), a polymorphic non-classical HLA (HLA-Ib) with immune-regulatory properties in cancers and infectious diseases, presents both membrane-bound and soluble (sHLA-G) isoforms. Polymorphism has implications in host responses to pathogen infections and in pathogenesis. Differential expression patterns of HLA-G/sHLA-G or its polymorphism seem to be related to different pathological conditions, potentially acting as a disease progression biomarker. Pathogen antigens might be involved in the regulation of both membrane-bound and sHLA-G levels and impact immune responses during co-infections. The upregulation of HLA-G in viral and bacterial infections induce tolerance to infection. Recently, sHLA-G was found useful to identify the prognosis of Coronavirus disease 2019 (COVID-19) among patients and it was observed that the high levels of sHLA-G are associated with worse prognosis. The use of pathogens, such as Plasmodium falciparum, as immune modulators for other infections could be extended for the modulation of membrane-bound HLA-G in COVID-19-infected tissues. Overall, such information might open new avenues concerning the effect of some pathogens such as parasites in decreasing the expression level of HLA-G to restrict pathogenesis in some infections or to influence the immune responses after vaccination among others.

Rhinosinusal myiasis by Oestrus ovis third stage larva / Miasis rinosinusal por larva de Oestrus ovis de tercer estadio

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The Roles of Type I Interferon in Co-infections With Parasites and Viruses, Bacteria, or Other Parasites.

Parasites, bacteria, and viruses pose serious threats to public health. Many parasite infections, including infections of protozoa and helminths, can inhibit inflammatory responses and impact disease outcomes caused by viral, bacterial, or other parasitic infections. Type I interferon (IFN-I) has been recognized as an essential immune effector in the host defense against various pathogens. In addition, IFN-I responses induced by co-infections with different pathogens may vary according to the host genetic background, immune status, and pathogen burden. However, there is only limited information on the roles of IFN-I in co-infections with parasites and viruses, bacteria, or other parasites. This review summarizes some recent findings on the roles of IFN-I in co-infections with parasites, including Leishmania spp., Plasmodium spp., Eimeria maxima, Heligmosomoides polygyrus, Brugia malayi, or Schistosoma mansoni, and viruses or bacteria and co-infections with different parasites (such as co-infection with Neospora caninum and Toxoplasma gondii, and co-infection with Plasmodium spp. and H. polygyrus). The potential mechanisms of host responses associated with co-infections, which may provide targets for immune intervention and therapies of the co-infections, are also discussed.

Viruses of protozoan parasites and viral therapy: Is the time now right?

Infections caused by protozoan parasites burden the world with huge costs in terms of human and animal health. Most parasitic diseases caused by protozoans are neglected, particularly those associated with poverty and tropical countries, but the paucity of drug treatments and vaccines combined with increasing problems of drug resistance are becoming major concerns for their control and eradication. In this climate, the discovery/repurposing of new drugs and increasing effort in vaccine development should be supplemented with an exploration of new alternative/synergic treatment strategies. Viruses, either native or engineered, have been employed successfully as highly effective and selective therapeutic approaches to treat cancer (oncolytic viruses) and antibiotic-resistant bacterial diseases (phage therapy). Increasing evidence is accumulating that many protozoan, but also helminth, parasites harbour a range of different classes of viruses that are mostly absent from humans. Although some of these viruses appear to have no effect on their parasite hosts, others either have a clear direct negative impact on the parasite or may, in fact, contribute to the virulence of parasites for humans. This review will focus mainly on the viruses identified in protozoan parasites that are of medical importance. Inspired and informed by the experience gained from the application of oncolytic virus- and phage-therapy, rationally-driven strategies to employ these viruses successfully against parasitic diseases will be presented and discussed in the light of the current knowledge of the virus biology and the complex interplay between the viruses, the parasite hosts and the human host. We also highlight knowledge gaps that should be addressed to advance the potential of virotherapy against parasitic diseases.

Two-day enema antibiotic therapy for parasite eradication and resolution of symptoms.

BACKGROUND: Blastocystis hominis (B. hominis) and Dientamoeba fragilis (D. fragilis) are two protozoan parasites of human bowel that are found throughout the world. There is still debate about the pathogenicity of these protozoans, despite them being commonly associated with gastrointestinal symptoms and can cause health issue in both children and adults. These parasites are usually transmitted through faecal-oral contact particularly under poor hygiene conditions or food/water contamination. Once a person is infected, the parasites live in the large intestine and are passed in the faeces. AIM: To investigate the effect of triple antibiotic therapy using enema infusion in the treatment of B. hominis and D. fragilis infections. METHODS: This retrospective longitudinal study was conducted in a single medical centre, which included fifty-four patients (≥ 18 years) who were positive for D. fragilis, B. hominis or both between 2017 and 2018. The treatment consisted of triple antibiotics that were infused over two consecutive days through rectal enema. Faecal samples were collected from participants pre- and post-treatment and were tested for parasites using microscopy and polymerase chain reaction. Patients' symptoms were recorded prior and after the treatment as well as patient demographic data. RESULTS: Patients (n = 54), were either positive for B. hominis (37%), D. fragilis (35%) or both (28%). All patients completed the two-day treatment and no serious adverse effect was reported. The most common side effect experienced by the patients during the treatment was urine discolouration which was cleared by six weeks of follow-up. Common symptoms reported prior to treatment were diarrhoea, abdominal pain, constipation and fatigue. Other symptoms included abdominal discomfort, dizziness and blood in the stool. Eighty-nine percent of patients completed a final stool test post-treatment. At six weeks post-treatment, 79% of patients cleared the parasites from their faeces. Symptoms such as abdominal discomfort, dizziness and blood in the stool decreased significantly at both seven days and six weeks post-treatment (P < 0.040). The enema retention time, bowel preparation, previous antibiotic treatment or previous gastrointestinal problems had no significant effect on parasite eradication. CONCLUSION: Overall, eradication of parasites and improvement of clinical outcomes were observed in treated patients, showing the efficacy of this combination to eradicate the parasites and provide positive clinical outcome.

The Role of MicroRNAs in Parasitology.

MicroRNAs (miRNAs), as epigenetic regulators, are small non-coding RNAs regulating gene expression in eukaryotes at the post-transcriptional level to control biological functions. MicroRNAs play a role in development, physiology, infection, immunity and the complex life cycles of parasites. Also, parasite infection can alter host miRNA expression that might result in either parasite clearance or infection. Over the past 20 years, thousands of miRNAs have been identified in the nematode Caenorhabditis elegans and other parasites. Thus, miRNA pathways are potential targets for the diagnostic and therapeutic control of parasitic diseases. Here, we review the current status and potential functions of miRNAs related to protozoans, helminths, and arthropods.

Aptamers as a novel diagnostic and therapeutic tool and their potential use in parasitology / [Los aptámeros como novedosa herramienta diagnóstica y terapéutica y su potencial uso en parasitología].

Aptamers are single-stranded DNA or RNA sequences that adopt unique three-dimensional structures that allow them to recognize a specific target with high affinity. They can potentially be used for the diagnosis of diseases, as new therapeutic agents, for the detection of food risks, as biosensors, for the detection of toxins, and as drug carriers and nanoparticle markers, among other applications. To date, an aptamer called pegaptanib is the only aptamer approved by the Food and Drug Administration (FDA) for commercial use. Other aptamers are in different clinical stages of development for the treatment of different diseases. In parasitology, investigations carried out with parasites such as Leishmania spp. allowed the acquisition of aptamers that recognize the polyA-binding protein LiPABP and may have potential applications in research and diagnosis and even as therapeutic agents. Regarding malaria, aptamers have been obtained that allow the identification of infected erythrocytes or inhibit the formation of rosettes, along with those that provide promising alternatives for diagnosis by specifically detecting the protein lactate dehydrogenase (PfLDH). In Cryptosporidium parvum allow the detection of oocysts in contaminated food or water. In Entamoeba histolytica, two aptamers called C4 and C5, which inhibit the proliferation of trophozoites in vitro and have potential use as therapeutic agents, have been isolated. Aptamers obtained against Trypanosoma cruzi inhibit the invasion of LLC-MK2 (from monkey kidney) cells by 50-70%, and in T. brucei, aptamers with the potential to transport toxic molecules to the parasitic lysosome were identified as a novel therapeutic strategy.

Los aptámeros son secuencias de ADN o ARN de cadena sencilla que adoptan la forma de estructuras tridimensionales únicas, lo cual les permite reconocer un blanco específico con gran afinidad. Sus usos potenciales abarcan, entre otros, el diagnóstico de enfermedades, el desarrollo de nuevos agentes terapéuticos, la detección de riesgos alimentarios, la producción de biosensores, la detección de toxinas, el transporte de fármacos en el organismo y la señalización de nanopartículas. El pegaptanib es el único aptámero aprobado para uso comercial por la Food and Drug Administration (FDA).  En parasitología, se destacan los estudios que se vienen realizando en Leishmania spp., con la obtención de aptámeros que reconocen la proteína de unión a poliA (LiPABP) y que pueden tener potencial utilidad en la investigación, el diagnóstico y el tratamiento de la leishmaniasis. En cuanto a la malaria, se han obtenido aptámeros que permiten identificar eritrocitos infectados e inhiben la formación de rosetas, y otros que prometen ser alternativas para el diagnóstico al detectar de forma específica la proteína lactato deshidrogenasa (PfLDH). Para Cryptosporidium parvuum se han seleccionado aptámeros que detectan ooquistes a partir de alimentos o aguas contaminadas. Para Entamoeba histolytica se han aislado dos aptámeros llamados C4 y C5, que inhiben la proliferación in vitro de los trofozoítos y tienen potencial terapéutico. Los aptámeros contra Trypanosoma cruzi inhiben la invasión de células LLC-MK2 (de riñón de mono) en un 50 a 70 % y aquellos contra T. brucei transportan moléculas tóxicas al lisosoma parasitario como una novedosa estrategia terapéutica.

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box.

The CCR5 molecule was reported in 1996 as the main HIV-1 co-receptor. In that same year, the CCR5Δ32 genetic variant was described as a strong protective factor against HIV-1 infection. These findings led to extensive research regarding the CCR5, culminating in critical scientific advances, such as the development of CCR5 inhibitors for the treatment of HIV infection. Recently, the research landscape surrounding CCR5 has begun to change. Different research groups have realized that, since CCR5 has such important effects in the chemokine system, it could also affect other different physiological systems. Therefore, the effect of reduced CCR5 expression due to the presence of the CCR5Δ32 variant began to be further studied. Several studies have investigated the role of CCR5 and the impacts of CCR5Δ32 on autoimmune and inflammatory diseases, various types of cancer, and viral diseases. However, the role of CCR5 in diseases caused by bacteria and parasites is still poorly understood. Therefore, the aim of this article is to review the role of CCR5 and the effects of CCR5Δ32 on bacterial (brucellosis, osteomyelitis, pneumonia, tuberculosis and infection by Chlamydia trachomatis) and parasitic infections (toxoplasmosis, leishmaniasis, Chagas disease and schistosomiasis). Basic information about each of these infections was also addressed. The neglected role of CCR5 in fungal disease and emerging studies regarding the action of CCR5 on regulatory T cells are briefly covered in this review. Considering the "renaissance of CCR5 research," this article is useful for updating researchers who develop studies involving CCR5 and CCR5Δ32 in different infectious diseases.

Machine learning in the clinical microbiology laboratory: has the time come for routine practice?

BACKGROUND: Machine learning (ML) allows the analysis of complex and large data sets and has the potential to improve health care. The clinical microbiology laboratory, at the interface of clinical practice and diagnostics, is of special interest for the development of ML systems. AIMS: This narrative review aims to explore the current use of ML In clinical microbiology. SOURCES: References for this review were identified through searches of MEDLINE/PubMed, EMBASE, Google Scholar, biorXiv, arXiV, ACM Digital Library and IEEE Xplore Digital Library up to November 2019. CONTENT: We found 97 ML systems aiming to assist clinical microbiologists. Overall, 82 ML systems (85%) targeted bacterial infections, 11 (11%) parasitic infections, nine (9%) viral infections and three (3%) fungal infections. Forty ML systems (41%) focused on microorganism detection, identification and quantification, 36 (37%) evaluated antimicrobial susceptibility, and 21 (22%) targeted the diagnosis, disease classification and prediction of clinical outcomes. The ML systems used very diverse data sources: 21 (22%) used genomic data of microorganisms, 19 (20%) microbiota data obtained by metagenomic sequencing, 19 (20%) analysed microscopic images, 17 (18%) spectroscopy data, eight (8%) targeted gene sequencing, six (6%) volatile organic compounds, four (4%) photographs of bacterial colonies, four (4%) transcriptome data, three (3%) protein structure, and three (3%) clinical data. Most systems used data from high-income countries (n = 71, 73%) but a significant number used data from low- and middle-income countries (n = 36, 37%). Performance measures were reported for the 97 ML systems, but no article described their use in clinical practice or reported impact on processes or clinical outcomes. IMPLICATIONS: In clinical microbiology, ML has been used with various data sources and diverse practical applications. The evaluation and implementation processes represent the main gap in existing ML systems, requiring a focus on their interpretability and potential integration into real-world settings.

Checkpoint Inhibition and Infectious Diseases: A Good Thing?

The mammalian immune system has evolved the capacity to detect and destroy tumor cells. Tumors utilize multiple strategies to evade host immune surveillance, including the induction of the checkpoint molecules cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) to suppress antitumor immunity. Pharmacologic blockade of these molecules with checkpoint inhibitors (CPIs) restores T cell function and prolongs survival in patients with various malignancies. Emerging evidence suggests that the same checkpoint pathways may play a crucial role during infections. Indeed, CPIs appear promising as immunotherapeutic agents in infectious diseases, although their efficacy varies depending on pathogen-, cell-, and organ-specific factors. More research will be necessary to clarify the effects and safety of CPIs on clinically relevant outcomes of human infection.

Chicken egg yolk antibody (IgY) as diagnostics and therapeutics in parasitic infections - A review.

Early diagnosis and treatment of parasitic diseases are indispensable to combat parasites mediated morbidity and mortality in humans and animals. Mammalian sourced antibodies are being successfully used in immunotherapy and immunoassays. However, their increased conservation amongst mammals, involves them in unnecessary interaction and immune mediated pathologies, obstructing their applications in certain approaches in immunoassays. Further, the high production cost and difficulty to achieve high and stable antibody titer hampers their utility for therapeutic purposes. In recent years, chicken egg yolk immunoglobulin, termed as immunoglobulin Y (IgY) has attracted noticeable consideration since it poses greater advantages than mammalian IgG including high yield, low cost and convenience. IgY has unique properties which are being exploited in different aspects for its applications in research, diagnosis and therapy. This review gives an overview of the research outcomes pertaining to chicken IgY as diagnostics and therapeutics in parasitology.

Parasitic infections of the spine: case series and review of the literature.

OBJECTIVEAlthough parasitic infections are endemic to parts of the developing world and are more common in areas with developing economies and poor sanitary conditions, rare cases may occur in developed regions of the world.METHODSArticles eligible for the authors' literature review were initially searched using PubMed with the phrases "parasitic infections" and "spine." After the authors developed a list of parasites associated with spinal cord infections from the initial search, they expanded it to include individual diagnoses, using search terms including "neurocysticercosis," "schistosomiasis," "echinococcosis," and "toxoplasmosis."RESULTSTwo recent cases of parasitic spinal infections from the authors' institution are included.CONCLUSIONSKey findings on imaging modalities, laboratory studies suggestive of parasitic infection, and most importantly a thorough patient history are required to correctly diagnose parasitic spinal infections.

Just Enough Cooks in the Kitchen: Key Ingredients for International Collaboration.

Research approaches that cross disciplinary silos, industry sectors, and political borders are now increasingly prioritized for tackling issues of global concern. Nevertheless, team science can be challenging. The goal of this article is to help researchers proactively consider factors influencing conflicts and successes with an emphasis on the health sciences.

Neurocysticercosis: mimics and chameleons.

Neurocysticercosis is the most common parasitic neurological disease worldwide, yet in Europe, it remains relatively uncommon, with many practitioners rarely seeing a case. However, immigration and international travel mean that it is becoming increasingly recognised and diagnosed in developed countries. Being a treatable condition, it is essential to be familiar with the diagnosis and to appreciate its mimics and breadth of its possible clinical presentations.

What's eating you? Ixodes tick and related diseases, part 1: life cycle, local reactions, and lyme disease.

The Ixodes tick is an important arthropod vector in the transmission of human disease. This 3-part review highlights the biology of the Ixodes tick and manifestations of related diseases. Part 1 addresses the Ixodes tick biology and life cycle; local reactions; and Lyme disease, the most prevalent of associated diseases. Part 2 will address human granulocytic anaplasmosis, babesiosis, Powassan virus infection, Borrelia miyamotoi disease, tick-borne encephalitis, and tick paralysis. Part 3 will address coinfection with multiple pathogens as well as methods of tick-bite prevention and tick removal.

Extracellular Vesicle-Mediated Communication Within Host-Parasite Interactions.

Extracellular vesicles (EVs) are small membrane-surrounded structures released by different kinds of cells (normal, diseased, and transformed cells) in vivo and in vitro that contain large amounts of important substances (such as lipids, proteins, metabolites, DNA, RNA, and non-coding RNA (ncRNA), including miRNA, lncRNA, tRNA, rRNA, snoRNA, and scaRNA) in an evolutionarily conserved manner. EVs, including exosomes, play a role in the transmission of information, and substances between cells that is increasingly being recognized as important. In some infectious diseases such as parasitic diseases, EVs have emerged as a ubiquitous mechanism for mediating communication during host-parasite interactions. EVs can enable multiple modes to transfer virulence factors and effector molecules from parasites to hosts, thereby regulating host gene expression, and immune responses and, consequently, mediating the pathogenic process, which has made us rethink our understanding of the host-parasite interface. Thus, here, we review the present findings regarding EVs (especially exosomes) and recognize the role of EVs in host-parasite interactions. We hope that a better understanding of the mechanisms of parasite-derived EVs may provide new insights for further diagnostic biomarker, vaccine, and therapeutic development.