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.

Extracellular vesicles in parasitic diseases - from pathogenesis to future diagnostic tools.

Parasitic diseases are still a major public health problem especially among individuals of low socioeconomic status in underdeveloped countries. In recent years it has been demonstrated that parasites can release extracellular vesicles that participate in the host-parasite communication, immune evasion, and in governing processes associated with host infection. Extracellular vesicles are membrane-bound structures released into the extracellular space that can carry several types of biomolecules, including proteins, lipids, nucleic acids, and metabolites, which directly impact the target cells. Extracellular vesicles have attracted wide attention due to their relevance in host-parasite communication and for their potential value in applications such as in the diagnostic biomarker discovery. This review of the literature aimed to join the current knowledge on the role of extracellular vesicles in host-parasite interaction and summarize its molecular content, providing information for the acquisition of new tools that can be used in the diagnosis of parasitic diseases. These findings shed light to the potential of extracellular vesicle cargo derived from protozoan parasites as novel diagnostic tools.

The postmortem diagnosis of an Armillifer infection case in a cynomolgus macaque (Macaca fascicularis).

Armillifer moniliformis belongs to the order Porocephalida and family Porocephalidae, and it can cause zoonotic pentastomiasis. A suspected parasitic infection was incidentally discovered in the abdominal cavity of a cynomolgus macaque that died of persistent diarrhea. 18S rDNA amplification and sequencing revealed a high similarity (99.83%) to the Armillifer moniliformis Guangxi isolate. The isolated parasite was named the Armillifer moniliformis Yunnan isolate (GenBank accession no. HM048870). Our report presents a case of Armillifer moniliformis infection in macaques. The results indicated that early quarantine and diagnosis should be employed for animal health.

Galectins in Protozoan Parasitic Diseases: Potential Applications in Diagnostics and Therapeutics.

Neglected tropical diseases (NTDs) constitute a group of diseases that generally develop in tropical or subtropical climatic conditions and are related to poverty. Within the spectrum of NTDs, diseases caused by protozoa such as malaria, Chagas disease, and leishmaniasis exhibit elevated mortality rates, thereby constituting a substantial public health concern. Beyond their protozoan etiology, these NTDs share other similarities, such as the challenge of control and the lack of affordable, safe, and effective drugs. In view of the above, the need to explore novel diagnostic predictors and therapeutic targets for the treatment of these parasitic diseases is evident. In this context, galectins are attractive because they are a set of lectins bound to ß-galactosides that play key roles in a variety of cellular processes, including host-parasite interaction such as adhesion and entry of parasites into the host cells, and participate in antiparasitic immunity in either a stimulatory or inhibitory manner, especially the galectins-1, -2, -3, and -9. These functions bestow upon galectins significant therapeutic prospects in the context of managing and diagnosing NTDs. Thus, the present review aims to elucidate the potential role of galectins in the diagnosis and treatment of malaria, leishmaniasis, and Chagas disease.

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.

Abdominal Calcifications in a Patient From the Congo Basin with History of Snake Meat Consumption: Radiographic Evidence of Prior Armillifer Infection.

We report a case of a 60-year-old asymptomatic male with history of consumption of uncooked snake meat while living in the Congo basin and prior imaging showing multiple abdominal calcifications. Patient had multiple subepithelial colonic lesions identified during screening colonoscopy and microscopic examination of the lesions demonstrated a calcified nodule in the submucosa with overlying normal mucosa. However, no parasite was identified within the calcified nodule. Given the history of consumption of uncooked snake meat and the typical radiographic feature of multiple abdominal calcifications, it is very likely that the patient's radiographic abnormalities are due to prior Armillifer armillatus infection, a parasitic infection acquired from consumption of uncooked snake meat. Patient was asymptomatic at the time of evaluation and was not given anti-parasitic treatment.

Neuropsychiatric Aspects of Parasitic Infections-A Review.

Neuropsychiatric disorders, ranging from mild cognitive impairment to frank psychosis, have been associated with certain parasitic infections. The parasite may cause damage to the central nervous system in several ways: as a space-occupying lesion (neuro-cysticercosis), alteration of neurotransmitters (toxoplasmosis), generation of the inflammatory response (trypanosomiasis, schistosomiasis), hypovolemic neuronal injury (cerebral malaria), or a combination of these. Certain drugs like quinacrine (mepacrine), mefloquine, quinolone, and interferon alpha which are used to treat these parasitic infections can further cause neuropsychiatric adverse effects. This review summarizes the major parasitic infections that are associated with neuropsychiatric disorders and the pathogenesis involved in their processes. A high index of suspicion for parasitic diseases, especially in endemic areas, should be kept in patients presenting with neuropsychiatric symptoms. A multidimensional approach to identification of the offending parasite using serological, radiological, and molecular tests is required not only to ensure proper and prompt treatment of the primary parasitic infection but also to improve the prognosis of patients by complete resolution of neuropsychiatric symptoms.

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.

Modular nanotheranostic agents for protistan parasitic diseases: Magic bullets with tracers.

Protistan parasitic infections contribute significantly to morbidity and mortality, causing more than 2 billion human infections annually. However, current treatments are often limited; due to ineffective drugs and drug resistance, thus better options are urgently required. In the present context, theranostics agents are those that offer simultaneous detection, diagnosis and even treatment of protistan parasitic diseases. "Nanotheranostics" is the term used to describe such agents, that are around 100 nm or less in size. Anti-parasitic activity of nanoparticles (NPs) has been reported, and many have useful intrinsic imaging properties, but it is perhaps their multifunctional nature that offers the greatest potential. NPs may be used as adapters onto which various subunits with different functions may be attached. These subunits may facilitate targeting parasites, coupled with toxins to eradicate parasites, and probe subunits for detection of particles and/or parasites. The modular nature of nano-platforms promises a "mix and match" approach for the construction of tailored agents by using combinations of these subunits against different protistan parasites. Even though many of the subunits have shown promise alone, these have not yet been put together convincingly enough to form working theranostics against protistan parasites. Although the clinical application of nanotheranostics to protistan parasitic infections in humans requires more research, we conclude that they offer not just a realisation of Paul Ehrlich's long imagined "magic bullet" concept, but potentially are magic bullets combined with tracer bullets.

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.

Non invasive tests for diagnosis of parasitic infections of CNS.

Central nervous system (CNS) infections are among the most devastating diseases with high mortality and morbidity. In the pre-human immunodeficiency virus (HIV) era, the occurrence of CNS infections was very infrequent. However, in the past four decades or so, with a global increase in the immunocompromised population, the incidence of opportunistic infections of the CNS has changed. This includes a global increase in the incidence of parasitic infections such as Toxoplasma gondii. Infections such as neurocysticercosis and cerebral malaria are quite prevalent in developing countries. Early diagnosis of these infections is crucial for instituting accurate therapy and preventing mortality and morbidity. Despite advances in neuroimaging techniques, laboratory diagnosis remains the mainstay for confirmation of diagnosis. We present an update on the noninvasive tests available for laboratory diagnosis of parasitic infections of the CNS.

[Parasites - important endemic and imported pathogens]. / Parasiten ­ wichtige endemische und importierte Erreger.

Parasites are a diverse group of pathogens; they range from unicellular protozoa (e. g. Giardia lamblia) to tapeworms that can grow several meters long. Parasites have adapted to humans over millions of years and cause a wide, colorful variety of diseases. Due to increasing travel and climate change, previously rare pathogens occur more frequently in patients in Germany.Often the history, clinical findings and imaging are suggestive of the causative parasite and the suspected diagnosis only needs to be confirmed with pathogen detection in order to initiate targeted therapy. Nonetheless, the diagnosis is often delayed due to lack of experience of attending clinicians with parasitic infections.In this review article we give an overview of the epidemiology, transmission, diagnosis and treatment of some of the most common parasitic infections that are endemic, or regularly imported to Germany. We also discuss current and future challenges in the diagnosis, treatment and control of these pathogens.

A review on point of care tests in parasitology.

BACKGROUND: Infectious diseases can be of serious public concerns because of its transmissibility. The parasitic infectious diseases in particular are often seen as neglected diseases of poverty. The diagnostic tests for parasitic diseases barring malaria are not easily available specially in low resources settings where they are needed most. The conventional mode of diagnosis based on centralized laboratory is time consuming and resource intensive. The modern-day medicine has shifted the focus to patient care. The use of point of care tests (POCT) has increased worldwide because they provide rapid diagnosis within the consultation time that too near patient care areas. This is very useful for starting initial treatment. These POCT provide excellent solution for rural and hard to reach areas where parasitic diseases are most prevalent. Despite the high demand, a relatively limited number of validated rapid diagnostics are commercially available for parasitic infections. OBJECTIVES AND CONTENT: This review aims to discuss various POCT available for these neglected parasitic diseases. Accurate detection of parasitic infection underpins a holistic approach to its control and management. The POCT can also be used to screen mass population to detect asymptomatic reservoirs and monitor interventions planned for elimination programs for many parasitic diseases. Recently focus is on integrated platforms and analysis of multiple analytes from single sample. Researchers are striving to produce POCT based on innovative technology such as lab-on-chip that can be made more affordable and suitable for low resource settings.

Liquid Biopsy for Promising Non-invasive Diagnostic Biomarkers in Parasitic Infections.

BACKGROUND: Liquid biopsy refers to the sampling and molecular analysis of body fluids such as blood, saliva, and urine in contrast to conventional tissue biopsies. Liquid biopsy approach can offer powerful non-invasive biomarkers (circulating markers) for diagnosis and monitoring treatment response of a variety of diseases, including parasitic infections. METHODS: In this review, we concentrate on cell-free DNA (cfDNA), microRNA (miRNA), and exosomes in the published literature. RESULTS: Considering the high prevalence and severity of parasitic infections worldwide, circulating biomarkers can provide a new insight into the diagnosis and prognosis of parasites in the near future. Moreover, identifying and characterizing parasite- or host-derived circulating markers are important for a better understanding of the pathogenesis of parasite infection and host-parasite relationship at the molecular level. Profiling of biomarkers for parasitic diseases is a promising potential field, though further studies and optimization strategies are required, both in vitro and in vivo. CONCLUSION: In this review, we discuss three approaches in the liquid biopsy including circulating cfDNA, miRNAs, and exosomes for diagnosis and evaluation of parasites and summarize circulating biomarkers in non-invasive samples during parasitic infections.

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.

Pediatric Care for Immigrant, Refugee, and Internationally Adopted Children.

Immigrant children are a diverse group and include refugees, asylees, and internationally adopted children. They have various infectious disease risk factors, depending on conditions within their country of origin, journey, and current living conditions. Infectious disease screening should take place within the framework of a comprehensive medical evaluation in the medical home. Some screening is recommended for all immigrant children including hepatitis B, syphilis, HIV, tuberculosis, and intestinal parasites; other diseases can be tested for based on individual risks. Although guidelines and resources are available, there is limited evidence supporting much of the care of immigrant children and youth.

Endoparasite diversity and liver alterations in Hoplerythrinus unitaeniatus and Cichlasoma bimaculatum in a quilombola area in Maranhão, Brazil / Diversidade endoparasitária e alterações hepáticas em Hoplerythrinus unitaeniatus e Cichlasoma bimaculatum de área quilombola maranhense, Brasil

Our aim was to assess endoparasite diversity and liver alterations in Hoplerythrinus unitaeniatus (jeju) and Cichlasoma bimaculatum (acará preto) in a quilombola area in Maranhão, Brazil. For this, 21 H. unitaeniatus and 21 C. bimaculatum were caught in a natural environment and transported to a laboratory. After these had been euthanized, endoparasites were collected and identified. Liver alterations were evaluated histological analysis based on the severity of each lesion: stage I, organ functioning not compromised; stage II, more severe lesions that impair normal functioning of the organs; and stage III, very severe and irreversible lesions. Among the fish evaluated, 71.43% H. unitaeniatus and 61.90% C. bimaculatum were parasitized. Contracaecum sp. was found in both species; while acanthocephalans, only in H. unitaeniatus. The alterations were vacuolization, nucleus in the cell periphery, deformation of the cell outline, melanomacrophage center, hyperemia, cytoplasmic degeneration and nuclear vacuolization. Through calculating a histological alteration index, it was found that 26.19% of the specimens presented lesions in stage I; 38.09% lesions in stage II and 9.52% lesions in stage III. It was concluded that there is high prevalence of Contracaecum sp. and that the liver lesions may be adaptive responses by the fish to endoparasitic infection.(AU)

Objetivou-se avaliar a diversidade de endoparasitos e alterações hepáticas em Hoplerythrinus unitaeniatus (jeju) e Cichlasoma bimaculatum (acará preto) de área quilombola maranhense, Brasil. Assim, 21 H. unitaeniatus e 21 C. bimaculatum foram capturados de ambiente alagável e transportados vivos ao laboratório. Após a eutanásia, procedeu-se à coleta, identificação de endoparasitos e avaliação de alterações hepáticas por meio de análise histológica, baseada na severidade das lesões: (i) alterações de estágio I, não comprometem o funcionamento dos órgãos; (ii) estágio II, lesões mais severas que prejudicam o funcionamento normal dos órgãos; (iii) estágio III, lesões muito severas e irreversíveis. Dos peixes avaliados, 71,43% H. unitaeniatus e 61,90% C. bimaculatum estavam parasitados. Contracaecum sp. foi encontrado nas duas espécies e acantocéfalos apenas em H. unitaeniatus. As alterações hepáticas foram vacuolização, núcleo na periferia das células, deformação do contorno celular, centro de melanomacrófagos, hiperemia, degeneração citoplasmática e vacuolização nuclear. Com o cálculo do índice das alterações, constatou-se que 26,19% dos exemplares apresentaram alterações de estágio I; 38,09% de estágio II e 9,52% de estágio III com a constatação de larvas de Contracaecum sp. encistadas no fígado. Conclui-se que existe alta prevalência de Contracaecum sp., e lesões hepáticas podem ser respostas adaptativas dos peixes à infecção endoparasitária.(AU)