Auranofin is an FDA-approved disease-modifying anti-rheumatic drug that has been used for decades for treatment of rheumatoid arthritis. This gold(I) compound has anti-inflammatory properties because ...it reduces IL-6 expression
via
inhibition of the NF-κB-IL-6-STAT3 signaling pathway. Also, by inhibiting redox enzymes such as thioredoxin reductase, auranofin increases cellular oxidative stress and promotes apoptosis. Auranofin also possesses antiviral properties. Recently, it was reported that auranofin reduced by 95% SARS-CoV-2 RNA in infected human cells
in vitro
and decreased SARS-CoV-2-induced cytokine expression, including IL-6. During SARS-CoV-2 infection, a cytokine storm involving IL-6 increases severity of illness and worsens prognosis. Therefore, auranofin could, in our point of view, reduce pathology due to SARS-CoV-2-induced IL-6. COVID-19 is a rapidly-evolving respiratory disease now distributed worldwide. Strikingly high numbers of new COVID-19 cases are reported daily. We have begun a race to vaccinate people, but due to the complex logistics of this effort, the virus will continue to spread before all humans can be immunized, and new variants that may be less well contained by current vaccines are of concern. The COVID-19 pandemic has overwhelmed health care systems and new treatments to reduce mortality are urgently needed. We encourage to further evaluate the potential of auranofin in the treatment of COVID-19
in vitro
and in animal models of SARS-CoV-2 infection and, if preliminary data are promising, in clinical trials with COVID-19 patients. In our opinion, auranofin has the potential to become a valuable addition to available therapies in this pandemic.
Helminths contribute a larger global burden of disease than both malaria and tuberculosis. These eukaryotes have caused human infections since before our earliest recorded history (i.e.: earlier than ...1200 B.C. for
spp.). Despite the prevalence and importance of these infections, helminths are considered a neglected tropical disease for which there are no vaccines approved for human use. Similar to other parasites, helminths are complex organisms which employ a plethora of features such as: complex life cycles, chronic infections, and antigenic mimicry to name a few, making them difficult to target by conventional vaccine strategies. With novel vaccine strategies such as viral vectors and genetic elements, numerous constructs are being defined for a wide range of helminth parasites; however, it has yet to be discussed which of these approaches may be the most effective. With human trials being conducted, and a pipeline of potential anti-helminthic antigens, greater understanding of helminth vaccine-induced immunity is necessary for the development of potent vaccine platforms and their optimal design. This review outlines the conventional and the most promising approaches in clinical and preclinical helminth vaccinology.
The Polymerase Chain Reaction (PCR) test is a highly sensitive, specific, and rapid diagnostic tool for Chagas disease. Chagas disease is caused by the protozoan flagellate Trypanosoma cruzi and is ...endemic to the Americas. While conventional serological methods are still used in the diagnosis of Chagas disease, they are being gradually replaced by molecular methods like PCR. PCR can detect the parasite’s DNA in blood or tissue samples from humans and animals, including asymptomatic infections and animal reservoirs. In a study conducted on a colony of New World monkeys, PCR analysis was found to be superior to conventional screening tools for trypanosome infection, although false negatives can still occur. In clinical studies, PCR has been used to assess the effectiveness of Nifurtimox and Benznidazole in treating acute and chronic Chagas patients. However, the presence of low-grade and intermittent parasitemia in peripheral blood, even in the absence of treatment, renders PCR an unreliable test for evaluating successful treatment. Based on this limiting factor, among others, we do not believe that PCR is an appropriate gold standard test for Chagas in clinical and preclinical studies. Other diagnostic methods, such as serological and biomarker tests, should be used in conjunction with PCR techniques for more accurate diagnosis of Chagas.
Centuries of scientific breakthroughs have brought us closer to understanding and managing the spread of parasitic diseases. Despite ongoing technological advancements in the detection, treatment, ...and control of parasitic illnesses, their effects on animal and human health remain a major concern worldwide. Aptamers are single-stranded oligonucleotides whose unique three-dimensional structures enable them to interact with high specificity and affinity to a wide range of targets. In recent decades, aptamers have emerged as attractive alternatives to antibodies as therapeutic and diagnostic agents. Due to their superior stability, reusability, and modifiability, aptamers have proven to be effective bioreceptors for the detection of toxins, contaminants, biomarkers, whole cells, pathogens, and others. As such, they have been integrated into a variety of electrochemical, fluorescence, and optical biosensors to effectively detect whole parasites and their proteins. This review offers a summary of the various types of parasite-specific aptamer-based biosensors, their general mechanisms and their performance.
Cysteine proteases (CPs) play key roles in the pathogenesis of protozoan parasites, including cell/tissue penetration, hydrolysis of host or parasite proteins, autophagy, and evasion or modulation of ...the host immune response, making them attractive chemotherapeutic and vaccine targets. This review highlights current knowledge on clan CA cysteine proteases, the best-characterized group of cysteine proteases, from 7 protozoan organisms causing human diseases with significant impact: Entamoeba histolytica, Leishmania species (sp.), Trypanosoma brucei, T. cruzi, Cryptosporidium sp., Plasmodium sp., and Toxoplasma gondii. Clan CA proteases from three organisms (T. brucei, T. cruzi, and Plasmodium sp.) are well characterized as druggable targets based on in vitro and in vivo models. A number of candidate inhibitors are under development. CPs from these organisms and from other protozoan parasites should be further characterized to improve our understanding of their biological functions and identify novel targets for chemotherapy.
The implementation of real-time PCR for the diagnosis of malaria has been hampered by poor sensitivity for the detection of mixed infections. We have optimized a method that enhances the sensitivity ...of detection of minor species in mixed infections within a single multiplex reaction. Our assay uses species-specific forward primers in combination with a conserved reverse primer and largely overcomes primer competition for the minor species DNA. With a blind panel of clinical samples, we successfully identified the species in 13/16 mixed infections. This assay was further validated with 91 blood samples and demonstrated a specificity and sensitivity for single infections of 100% compared with nested PCR as the "gold standard." This test has been implemented for routine confirmation of malaria species in Alberta, Canada. In comparison with species identification by microscopy, the real-time PCR test demonstrated greater sensitivity for the identification of species causing low-level and mixed infections and for the discrimination of Plasmodium species other than Plasmodium falciparum. Our experience supports a role for real-time PCR in the identification of malarial species in conjunction with microscopy.
Prolonged eosinophilia is characteristic of trichinellosis. To determine the optimal eosinophil threshold for reflex Trichinella testing, we examined all 43 cases in Nunavik, Quebec, Canada, during ...2009-2019. Using receiver operating characteristic analysis, we determined that eosinophil counts >0.8 × 10
cells/L should prompt consideration of trichinellosis and testing to rapidly identify potential outbreaks.
Live attenuated Bacillus Calmette-Guérin (BCG) is the world's most widely used vaccine which is mainly administered for its protection against tuberculosis (TB), particularly in young children. ...However, since its initial use over 100years ago, it has also proven to offer a level of protection against various other pathogens, as a consequence of its non-specific immune enhancing effects. Thus, over the past few decades, recombinant BCG (rBCG) technology has been used as a vector to create rBCG vaccines expressing heterologous antigens that elicit immunity against a range of bacterial, viral, and parasitic diseases. Our goal with this mini-review is to provide an up-to-date survey of the various techniques, approaches, and applications of rBCG-based vaccines for targeting infectious diseases other than TB.
Trypanosoma cruzi is the causative agent of Chagas disease. Approximately 8 million people are thought to be affected worldwide. Several players in host lipid metabolism have been implicated in T. ...cruzi-host interactions in recent research, including macrophages, adipocytes, low density lipoprotein (LDL), low density lipoprotein receptor (LDLR), and high density lipoprotein (HDL). All of these factors are required to maintain host lipid homeostasis and are intricately connected via several metabolic pathways. We reviewed the interaction of T. cruzi with each of the relevant host components, in order to further understand the roles of host lipid metabolism in T. cruzi infection. This review sheds light on the potential impact of T. cruzi infection on the status of host lipid homeostasis.
Vaccines against parasites have lagged centuries behind those against viral and bacterial infections, despite the devastating morbidity and widespread effects of parasitic diseases across the globe. ...One of the greatest hurdles to parasite vaccine development has been the lack of vaccine strategies able to elicit the complex and multifaceted immune responses needed to abrogate parasitic persistence. Viral vectors, especially adenovirus (AdV) vectors, have emerged as a potential solution for complex disease targets, including HIV, tuberculosis, and parasitic diseases, to name a few. AdVs are highly immunogenic and are uniquely able to drive CD8+ T cell responses, which are known to be correlates of immunity in infections with most protozoan and some helminthic parasites. This review presents recent developments in AdV-vectored vaccines targeting five major human parasitic diseases: malaria, Chagas disease, schistosomiasis, leishmaniasis, and toxoplasmosis. Many AdV-vectored vaccines have been developed for these diseases, utilizing a wide variety of vectors, antigens, and modes of delivery. AdV-vectored vaccines are a promising approach for the historically challenging target of human parasitic diseases.
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