MicroRNAs in infectious diseases: potential diagnostic biomarkers and therapeutic targets.

MicroRNAs (miRNAs) are conserved, short, non-coding RNAs that play a crucial role in the post-transcriptional regulation of gene expression. They have been implicated in the pathogenesis of cancer and neurological, cardiovascular, and autoimmune diseases. Several recent studies have suggested that miRNAs are key players in regulating the differentiation, maturation, and activation of immune cells, thereby influencing the host immune response to infection. The resultant upregulation or downregulation of miRNAs from infection influences the protein expression of genes responsible for the immune response and can determine the risk of disease progression. Recently, miRNAs have been explored as diagnostic biomarkers and therapeutic targets in various infectious diseases. This review summarizes our current understanding of the role of miRNAs during viral, fungal, bacterial, and parasitic infections from a clinical perspective, including critical functional mechanisms and implications for their potential use as biomarkers and therapeutic targets.

Revisiting the antigen markers of vector-borne parasitic diseases identified by immunomics: identification and application to disease control.

INTRODUCTION: Protein microarray is a promising immunomic approach for identifying biomarkers. Based on our previous study that reviewed parasite antigens and recent parasitic omics research, this article expands to include information on vector-borne parasitic diseases (VBPDs), namely, malaria, schistosomiasis, leishmaniasis, babesiosis, trypanosomiasis, lymphatic filariasis, and onchocerciasis. AREAS COVERED: We revisit and systematically summarize antigen markers of vector-borne parasites identified by the immunomic approach and discuss the latest advances in identifying antigens for the rational development of diagnostics and vaccines. The applications and challenges of this approach for VBPD control are also discussed. EXPERT OPINION: The immunomic approach has enabled the identification and/or validation of antigen markers for vaccine development, diagnosis, disease surveillance, and treatment. However, this approach presents several challenges, including limited sample size, variability in antigen expression, false-positive results, complexity of omics data, validation and reproducibility, and heterogeneity of diseases. In addition, antigen involvement in host immune evasion and antigen sensitivity/specificity are major issues in its application. Despite these limitations, this approach remains promising for controlling VBPD. Advances in technology and data analysis methods should continue to improve candidate antigen identification, as well as the use of a multiantigen approach in diagnostic and vaccine development for VBPD control.

Modern Strategies for Diagnosis and Treatment of Parasitic Diseases.

Parasites are very widely distributed in the environment and form complex relationships with their hosts, forming host-parasite systems [...].

Nanotechnology: A promising strategy for the control of parasitic infections.

Annually 3.5 billion people are affected by the parasitic infections that results around 200,000 deaths per annum. Major diseases occur due to the neglected tropical parasites. Variety of methods have been used to treat the parasitic infections but now these methods have become ineffective due to the development of resistance in the parasites and some other side effects of traditional treatment methods. Previous methods include use of chemotherapeutic agents and ethnobotanicals for the treatment of parasites. Parasites have developed resistance against the chemotherapeutic agents. A major problem related to Ethnobotanicals is the unequal availability of drug at the target site which is responsible for the low efficacy of drug. Nanotechnology technology involves the manipulation of matter on a nanoscale level and has the potential to enhance the efficacy and safety of existing drugs, develop new treatments, and improve diagnostic methods for parasitic infections. Nanoparticles can be designed to selectively target parasites while minimizing toxicity to the host, and they can also be used to improve drug delivery and increase drug stability. Some important nanotechnology-based tools for parasitic control include nanoparticle-based drug delivery, nanoparticle diagnostics, nanoparticle vaccines, nanoparticle insecticides. Nanotechnology has the potential to revolutionize the field of parasitic control by providing new methods for detection, prevention and treatment of parasitic infections. This review discusses the current state of nanotechnology-based approaches for controlling parasitic infections and highlights their potential to revolutionize the field of parasitology.

Membrane Technology for Rapid Point-of-Care Diagnostics for Parasitic Neglected Tropical Diseases.

Parasitic neglected tropical diseases (NTDs) affect over one billion people worldwide, with individuals from communities in low-socioeconomic areas being most at risk and suffering the most. Disease management programs are hindered by the lack of infrastructure and resources for clinical sample collection, storage, and transport and a dearth of sensitive diagnostic methods that are inexpensive as well as accurate. Many diagnostic tests and tools have been developed for the parasitic NTDs, but the collection and storage of clinical samples for molecular and immunological diagnosis can be expensive due to storage, transport, and reagent costs, making these procedures untenable in most areas of endemicity. The application of membrane technology, which involves the use of specific membranes for either sample collection and storage or diagnostic procedures, can streamline this process, allowing for long-term sample storage at room temperature. Membrane technology can be used in serology-based diagnostic assays and for nucleic acid purification prior to molecular analysis. This facilitates the development of relatively simple and rapid procedures, although some of these methods, mainly due to costs, lack accessibility in low-socioeconomic regions of endemicity. New immunological procedures and nucleic acid storage, purification, and diagnostics protocols that are simple, rapid, accurate, and cost-effective must be developed as countries progress control efforts toward the elimination of the parasitic NTDs.

Where Have All the Diagnostic Morphological Parasitologists Gone?

Advances in laboratory techniques have revolutionized parasitology diagnostics over the past several decades. Widespread implementation of rapid antigen detection tests has greatly expanded access to tests for global parasitic threats such as malaria, while next-generation amplification and sequencing methods allow for sensitive and specific detection of human and animal parasites in complex specimen matrices. Recently, the introduction of multiplex panels for human gastrointestinal infections has enhanced the identification of common intestinal protozoa in feces along with bacterial and viral pathogens. Despite the benefits provided by novel diagnostics, increased reliance on nonmicroscopy-based methods has contributed to the progressive, widespread loss of morphology expertise for parasite identification. Loss of microscopy and morphology skills has the potential to negatively impact patient care, public health, and epidemiology. Molecular- and antigen-based diagnostics are not available for all parasites and may not be suitable for all specimen types and clinical settings. Furthermore, inadequate morphology experience may lead to missed and inaccurate diagnoses and erroneous descriptions of new human parasitic diseases. This commentary highlights the need to maintain expert microscopy and morphological parasitology diagnostic skills within the medical and scientific community. We proposed that light microscopy remains an important part of training and practice in the diagnosis of parasitic diseases and that efforts should be made to train the next generation of morphological parasitologists before the requisite knowledge, skills, and capacity for this complex and important mode of diagnosis are lost. In summary, the widespread, progressive loss of morphology expertise for parasite identification negatively impacts patient care, public health, and epidemiology.

Are humanized IgE reporter systems potential game changers in serological diagnosis of human parasitic infection?

Immunoglobulin E (IgE) is thought to have evolved to protect mammalian hosts against parasitic infections or toxins and plays a central role in the pathogenesis, diagnosis, and therapy of IgE-mediated allergy. Despite the prominence of IgE responses in most parasitic infections, and in stark contrast to its use in the diagnosis of allergy, this isotype is almost completely unexploited for parasite diagnosis. Here, we discuss the perceived or real limitations of IgE-based diagnosis in parasitology and suggest that the recent creation of a new generation of very sensitive cellular IgE-based reporters may represent a powerful new diagnostic platform, but needs to be based on a very careful choice of diagnostic allergens.

Multiplex Solid-Phase Real-Time Polymerase Chain Reaction without DNA Extraction: A Rapid Intraoperative Diagnosis Using Microvolumes.

PURPOSE: Current polymerase chain reaction (PCR) methods for the diagnosis of infections are time consuming and require large sample volume and skilled technicians. We developed a novel, easy-to-use, and rapid (processing time, 1 minute; total time, 33 minutes) multiplex real-time PCR test (Direct Strip PCR) that did not require DNA extraction to detect 9 pathogens that could cause uveitis in 20-µl samples. DESIGN: Multicenter prospective evaluation of a diagnostic PCR test. PARTICIPANTS: A total of 511 participants (patients with infectious uveitis and controls) were examined at 18 institutes worldwide. METHODS: After validation, intraocular fluid samples were subjected to etiologic or exclusive diagnosis, including intraoperative rapid diagnosis. MAIN OUTCOME MEASURES: The concordance and correlations between Direct Strip PCR and quantitative PCR (qPCR) results. RESULTS: Direct Strip PCR exhibited rapid detection, good repeatability and specificity, long storage stability, and detection ability equal to that of qPCR. It also showed low interinstitutional variability compared with qPCR, even when PCR beginners used various real-time PCR machines. The Direct Strip PCR for 9 pathogens exhibited high concordance against the qPCR (positive concordance rate, 98.8%-100%; negative concordance rate, 99.8%-100%; κ coefficient, 0.969-1.000; P < 0.001-0.031). Additionally, results obtained using Direct Strip PCR and qPCR were highly correlated (ρ = 0.748; P < 0.001). This assay was used for rapid intraoperative diagnosis. CONCLUSIONS: The Direct Strip PCR test may improve the prognosis of various infectious diseases because it facilitates rapid etiologic evaluation at the first hospital visit and can be used for intraoperative diagnosis.

Neglected Parasitic Infections: What Family Physicians Need to Know-A CDC Update.

Chagas disease, cysticercosis, and toxoplasmosis affect millions of people in the United States and are considered neglected parasitic diseases. Few resources are devoted to their surveillance, prevention, and treatment. Chagas disease, transmitted by kissing bugs, primarily affects people who have lived in Mexico, Central America, and South America, and it can cause heart disease and death if not treated. Chagas disease is diagnosed by detecting the parasite in blood or by serology, depending on the phase of disease. Antiparasitic treatment is indicated for most patients with acute disease. Treatment for chronic disease is recommended for people younger than 18 years and generally recommended for adults younger than 50 years. Treatment decisions should be individualized for all other patients. Cysticercosis can manifest in muscles, the eyes, and most critically in the brain (neurocysticercosis). Neurocysticercosis accounts for 2.1% of all emergency department visits for seizures in the United States. Diagnosing neurocysticercosis involves serology and neuroimaging. Treatment includes symptom control and antiparasitic therapy. Toxoplasmosis is estimated to affect 11% of people older than six years in the United States. It can be acquired by ingesting food or water that has been contaminated by cat feces; it can also be acquired by eating undercooked, contaminated meat. Toxoplasma infection is usually asymptomatic; however, people who are immunosuppressed can develop more severe neurologic symptoms. Congenital infection can result in miscarriage or adverse fetal effects. Diagnosis is made with serologic testing, polymerase chain reaction testing, or parasite detection in tissue or fluid specimens. Treatment is recommended for people who are immunosuppressed, pregnant patients with recently acquired infection, and people who are immunocompetent with visceral disease or severe symptoms.

A Mitocentric View of the Main Bacterial and Parasitic Infectious Diseases in the Pediatric Population.

Infectious diseases occur worldwide with great frequency in both adults and children. Both infections and their treatments trigger mitochondrial interactions at multiple levels: (i) incorporation of damaged or mutated proteins to the complexes of the electron transport chain, (ii) mitochondrial genome (depletion, deletions, and point mutations) and mitochondrial dynamics (fusion and fission), (iii) membrane potential, (iv) apoptotic regulation, (v) generation of reactive oxygen species, among others. Such alterations may result in serious adverse clinical events with great impact on children's quality of life, even resulting in death. As such, bacterial agents are frequently associated with loss of mitochondrial membrane potential and cytochrome c release, ultimately leading to mitochondrial apoptosis by activation of caspases-3 and -9. Using Rayyan QCRI software for systematic reviews, we explore the association between mitochondrial alterations and pediatric infections including (i) bacterial: M. tuberculosis, E. cloacae, P. mirabilis, E. coli, S. enterica, S. aureus, S. pneumoniae, N. meningitidis and (ii) parasitic: P. falciparum. We analyze how these pediatric infections and their treatments may lead to mitochondrial deterioration in this especially vulnerable population, with the intention of improving both the understanding of these diseases and their management in clinical practice.

Circulatory microRNAs: promising non-invasive prognostic and diagnostic biomarkers for parasitic infections.

MicroRNAs (miRNAs) are a non-coding subclass of endogenous small regulatory RNAs, with about 18-25 nucleotides length which play a critical role in the regulation of gene expression at the post-transcriptional level in eukaryotes. Aberrant expression of miRNAs has the potential to become powerful non-invasive biomarkers in pathological diagnosis and prognosis of different disorders including infectious diseases. Parasite's life cycle may require the ability to respond to environmental and developmental signals through miRNA-mediated gene expressions. Over the last years, thousands of miRNAs have been identified in the helminthic and protozoan parasites and many pieces of evidence have demonstrated the functional role of miRNAs in the parasites' life cycle. Detection of these miRNAs in biofluids of infected hosts as prognostic and diagnostic biomarkers in infectious diseases is growing rapidly. In this review, we have highlighted altered expressions of host miRNAs, detected parasitic miRNAs in the infected hosts, and suggested some perspectives for future studies.

Priorities in research on foodborne parasites indicated by short-term scientific missions as part of COST Action a European Network for Foodborne Parasites (Euro-FBP).

The European Cooperation in Science and Technology (COST) is a funding organization for the creation of research networks. These networks support collaboration and networking among scientists across Europe and thereby give impetus to research advancements and innovation. One of the most important mechanisms of COST actions are the short-term scientific missions (STSM), which are a funding mechanism that enables scientists, particularly those earlier in their careers, to visit an institution or laboratory in another COST Member state in order to learn techniques that will enhance their skills and improve the scientific knowledge of their institution. The European Network for Foodborne Parasites (Euro-FBP; FA1408) was a COST Action that ended in early 2019, which brought together different experts with knowledge and interest on a broad spectrum of different foodborne parasites of relevance in Europe. In the course of the Euro-FBP COST Action, 32 such STSM occurred. This article provides a short overview of the short-term scientific missions that were approved during this action, as well as the relation of these actions to several relevant socio-economic parameters. The subjects of these STSM, the majority of which were concerned with detection techniques, probably reflect the priorities for research skills on foodborne parasites in Europe.

Loop-Mediated Isothermal Amplification as Point-of-Care Diagnosis for Neglected Parasitic Infections.

The World Health Organisation (WHO) has placed twenty diseases into a group known as neglected tropical diseases (NTDs), twelve of them being parasitic diseases: Chagas' disease, cysticercosis/taeniasis, echinococcosis, food-borne trematodiasis, human African trypanosomiasis (sleeping sickness), leishmaniasis, lymphatic filariasis, onchocerciasis (river blindness), schistosomiasis, soil-transmitted helminthiasis (ascariasis, hookworm, trichuriasis), guinea-worm and scabies. Such diseases affect millions of people in developing countries where one of the main problems concerning the control of these diseases is diagnosis-based due to the most affected areas usually being far from laboratories having suitable infrastructure and/or being equipped with sophisticated equipment. Advances have been made during the last two decades regarding standardising and introducing techniques enabling diagnoses to be made in remote places, i.e., the loop-mediated isothermal amplification (LAMP) technique. This technique's advantages include being able to perform it using simple equipment, diagnosis made directly in the field, low cost of each test and the technique's high specificity. Using this technique could thus contribute toward neglected parasite infection (NPI) control and eradication programmes. This review describes the advances made to date regarding LAMP tests, as it has been found that even though several studies have been conducted concerning most NPI, information is scarce for others.

Elusive Diagnostic Markers for Russian Wheat Aphid Resistance in Bread Wheat: Deliberating and Reviewing the Status Quo.

Russian wheat aphid, Diuraphis noxia (Kurdjumov), is a severe pest of wheat, Triticum aestivum L., throughout the world. Resistant cultivars are viewed as the most economical and environmentally viable control available. Studies to identify molecular markers to facilitate resistance breeding started in the 1990s, and still continue. This paper reviews and discusses the literature pertaining to the D. noxia R-genes on chromosome 7D, and markers reported to be associated with them. Individual plants with known phenotypes from a panel of South African wheat accessions are used as examples. Despite significant inputs from various research groups over many years, diagnostic markers for resistance to D. noxia remain elusive. Factors that may have impeded critical investigation, thus blurring the accumulation of a coherent body of information applicable to Dn resistance, are discussed. This review calls for a more fastidious approach to the interpretation of results, especially considering the growing evidence pointing to the complex regulation of aphid resistance response pathways in plants. Appropriate reflection on prior studies, together with emerging knowledge regarding the complexity and specificity of the D. noxia-wheat resistance interaction, should enable scientists to address the challenges of protecting wheat against this pest in future.

Practical Guidance for Clinical Microbiology Laboratories: Laboratory Diagnosis of Parasites from the Gastrointestinal Tract

This Practical Guidance for Clinical Microbiology document on the laboratory diagnosis of parasites from the gastrointestinal tract provides practical information for the recovery and identification of relevant human parasites. The document is based on a comprehensive literature review and expert consensus on relevant diagnostic methods. However, it does not include didactic information on human parasite life cycles, organism morphology, clinical disease, pathogenesis, treatment, or epidemiology and prevention. As greater emphasis is placed on neglected tropical diseases, it becomes highly probable that patients with gastrointestinal parasitic infections will become more widely recognized in areas where parasites are endemic and not endemic. Generally, these methods are nonautomated and require extensive bench experience for accurate performance and interpretation.

Retrospective study of pleural parasitic infestations: a practical diagnostic approach.

BACKGROUND: Pleural parasitic infestation (PPI) is a disease prevalent in certain parts of the world. It is frequently misdiagnosed due to its lack of standardized diagnostic criteria. The purpose of this study was to evaluate the clinical characteristics of PPI patients and develop a practical diagnostic approach for PPI. METHODS: A retrospective study was conducted by reviewing the medical records of 11 patients with PPI. A practical diagnostic approach was proposed based on the unique laboratory findings. RESULTS: All patients demonstrated respiratory symptoms, including shortness of breath, cough, fever, chest pain, excessive sputum and hemoptysis. Leukocytosis (> 10,000/µL) and eosinophilia (> 500/µL) of peripheral blood were present in 45.5 and 36.4% patients, respectively. The mean concentrations of pleural effusion lactate dehydrogenase (LDH), adenosine deaminase (ADA), protein and carcinoembryonic antigen (CEA) were 338.2 U/L (range, 61-667 U/L), 11.6 U/L (range, 0.1-28.2 U/L), 43.7 g/dL (range, 21.9-88.1 g/dL), and 1.84 mg/mL (range, 0.28-4.8 mg/mL), respectively. The mean percentage of eosinophils in the pleural effusion was 19.5% (10.5-41%). Blood test was positive for parasite-specific IgG antibody in 9 patients, including 4 for Paragonimus westermani, 3 for Taenia solium, 1 for Clonorchis sinensis and 1 for Echinococcus granulosus. Eggs of Clonorchis sinensis were detected in the stool of two patients. Sparganum was found in the pleural effusion of one patient. Respiratory symptoms and abnormal appearances in pulmonary radiographic examination were disappeared in all patients who received anti-parasitic treatment. CONCLUSIONS: In patients with unexplained pleural effusion, parasite-specific IgG antibody tests should be performed when pleural fluid testing shows eosinophilic pleural effusion. It is preferable to consider the diagnosis of PPI in clinical practice when serum parasite-specific IgG antibody test is positive.

Glycans in the roles of parasitological diagnosis and host-parasite interplay.

The investigation of the glycan repertoire of several organisms has revealed a wide variation in terms of structures and abundance of glycan moieties. Among the parasites, it is possible to observe different sets of glycoconjugates across taxa and developmental stages within a species. The presence of distinct glycoconjugates throughout the life cycle of a parasite could relate to the ability of that organism to adapt and survive in different hosts and environments. Carbohydrates on the surface, and in excretory-secretory products of parasites, play essential roles in host-parasite interactions. Carbohydrate portions of complex molecules of parasites stimulate and modulate host immune responses, mainly through interactions with specific receptors on the surface of dendritic cells, leading to the generation of a pattern of response that may benefit parasite survival. Available data reviewed here also show the frequent aspect of parasite immunomodulation of mammalian responses through specific glycan interactions, which ultimately makes these molecules promising in the fields of diagnostics and vaccinology.

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.

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.