Facing Diseases Caused by Trypanosomatid Parasites: Rational Design of Pd and Pt Complexes With Bioactive Ligands

Human African Trypanosomiasis (HAT), Chagas disease or American Trypanosomiasis (CD), and leishmaniases are protozoan infections produced by trypanosomatid parasites belonging to the kinetoplastid order and they constitute an urgent global health problem. In fact, there is an urgent need of more efficient and less toxic chemotherapy for these diseases. Medicinal inorganic chemistry currently offers an attractive option for the rational design of new drugs and, in particular, antiparasitic ones. In this sense, one of the main strategies for the design of metal-based antiparasitic compounds has been the coordination of an organic ligand with known or potential biological activity, to a metal centre or an organometallic core. Classical metal coordination complexes or organometallic compounds could be designed as multifunctional agents joining, in a single molecule, different chemical species that could affect different parasitic targets. This review is focused on the rational design of palladium(II) and platinum(II) compounds with bioactive ligands as prospective drugs against trypanosomatid parasites that has been conducted by our group during the last 20 years.

Toxoplasma gondii GRA15 DNA Vaccine with a Liposomal Nanocarrier Composed of an SS-Cleavable and pH-Activated Lipid-like Material Induces Protective Immunity against Toxoplasmosis in Mice

Toxoplasma gondii affects the health of humans and livestock and causes severe illness in the fetus and immunocompromised individuals. Because of the high incidence and severe consequences of T. gondii infection, a safe and suitable vaccine is needed. We found that lipid nanoparticles (LNPs) consisting of a series of functional materials prepared with vitamin E, such as SS-cleavable and pH-activated lipid-like materials (ssPalmE), were a safe and efficient way to develop next-generation DNA vaccines. In this study, we prepared ssPalmE-LNP to encapsulate pCpG-free-T. gondii dense granule protein 15 DNA (ssPalmE-LNPTgGRA15). Following a challenge infection with avirulent PLK strain of T. gondii, the mice immunized with ssPalmE-LNPTgGRA15 had a significantly higher survival rate and lower clinical scores compared with unimmunized and ssPalmE-LNPnon-coding-immunized mice. Immunization of mice with the ssPalmE-LNPTgGRA15 led to a significantly higher production of specific IgG1 and IG2c antibodies compared with unimmunized and ssPalmE-LNPnon-coding-immunized mice, while there was no statistically significant difference in the concentration of serum interferon-gamma at the acute stage of the infection. These findings indicate that ssPalmE-LNP is an effective cargo for the transportation of DNA vaccines for protozoan infections. To explore the mechanism of protective immunity induced by ssPalmE-LNPTgGRA15, further immunological study is needed in the future.

Syndromic Approach to Neuroinfectious Diseases

A general approach to clinical syndromes associated with infection of the nervous system can be useful when an infectious agent is suspected. This chapter provides a general overview of clinical syndromes of neurologic infectious disease. Subsequent chapters review bacterial, viral, fungal, and protozoan infections and prion disorders. Meningitis refers to inflammation of the leptomeninges caused by either infectious or noninfectious processes. It is associated with an increased white blood cell count in the cerebrospinal fluid. Infectious agents may be bacteria, viruses, or fungi. Noninfectious causes include autoimmune conditions, malignancies, and medications.

Monoclonal Antibodies for Protozoan Infections: A Future Reality or a Utopic Idea?

Following the SARS-CoV-2 pandemic, several clinical trials have been approved for the investigation of the possible use of mAbs, supporting the potential of this technology as a therapeutic approach for infectious diseases. The first monoclonal antibody (mAb), Muromonab CD3, was introduced for the prevention of kidney transplant rejection more than 30 years ago; since then more than 100 mAbs have been approved for therapeutic purposes. Nonetheless, only four mAbs are currently employed for infectious diseases: Palivizumab, for the prevention of respiratory syncytial virus (RSV) infections, Raxibacumab and Obiltoxaximab, for the prophylaxis and treatment against anthrax toxin and Bezlotoxumab, for the prevention of Clostridium difficile recurrence. Protozoan infections are often neglected diseases for which effective and safe chemotherapies are generally missing. In this context, drug resistance and drug toxicity are two crucial problems. The recent advances in bioinformatics, parasite genomics, and biochemistry methodologies are contributing to better understand parasite biology, which is essential to guide the development of new therapies. In this review, we present the efforts that are being made in the evaluation of mAbs for the prevention or treatment of leishmaniasis, Chagas disease, malaria, and toxoplasmosis. Particular emphasis will be placed on the potential strengths and weaknesses of biological treatments in the control of these protozoan diseases that are still affecting hundreds of thousands of people worldwide.

Prevalence of Gastrointestinal Parasites on Beef Cattle in Jombang District

The disease that is quite detrimental to cattle is gastrointestinal parasitic infection. Gastrointestinal parasites infect the cattle by taking host nutrients that would caused emaciation, lethargy, and decreased productivity. This study aims to determine the prevalence of gastrointestinal parasites in cattle in Jombang District. This research was conducted in July to August 2019 with 100 samples of cattle feces. Sample examinations were carried out in the laboratory of the Division of Veterinary Parasitology, Universitas Airlangga using the sedimentation and floating methods. Detection of parasites in all samples using microscope with magnification of 100x and 400x. On examination, several types of parasites were found included Strongyloides papillosus, Toxocara vitulorum, Oesophagostomum spp., Moniezia expansa, Blastocystis spp. and Eimeria spp. The results of this study were found the prevalence of gastrointestinal parasites on beef cattle in Jombang district was 35% with a worm infection prevalence of 15% and protozoan infections of 20%.

A SYSTEMATIC REVIEW AND META-ANALYSIS TO ASSESS THE SIGNIFICANCE OF MICROBIAL INFECTIONS IN ZEBRA

Wild equids can harvest multiple-host infectious agents that are able to affect other wildlife species, but also domestic animals and humans. The contact between wild and domestic equids is constantly increasing due to the depletion of natural areas, climate and land-usage changes, which could result in burdensome epidemics. Nevertheless, currently there is a lack of adequate epidemiological data from zebra. Three electronic databases were searched from 10 to 20 March 2021 for publications reporting bacterial, viral and protozoan infections in zebra. Data for a total of 12 nominal variables were extracted from reviewed papers to undergo a qualitative analysis on microbial infections in zebra. Prevalence-reporting studies were subjected to meta-analysis for estimating the pooled prevalence and seroprevalence of infectious agents in wild zebra populations. We identified 29 pathogen species and the most represented were Equine Herpesvirus 1 and 9, Bacillus anthracis, African Horse Sickness virus and Theileria equi. They were reported from all the three zebra species, both in captivity and wilderness. Pooled seroprevalences were estimated for the equine Orbiviruses AHSV (70%; 95%CI: 35-96%) and EEV (21%; 95%CI: 8-38%) and for the equine α -Herpesviruses EHV-1 (72%; 95%CI: 43-93%), EHV-4 (40%; 95%CI: 0-100%) and EHV-9 (58%; 95%CI: 9-98%), and pooled prevalences for the equine piroplasms T. equi (100%; 95%CI: 94-100%) and B. caballi (8%; 95%CI: 0-28%). Zebra is most probably a reservoir from which AHSV, EHV-1 and T. equi can be transmitted to horse populations, potentially causing disastrous epidemics. Zebra can also harvest zoonotic pathogens like B. anthracis, A. phagocytophylum, CCHFV and T. brucei. Other agents like EHV-9, BPV-1 and BPV-2 have the potential to spread from zebra to other wild endangered animal species. We conclude that zebra is an important host for multiple and dangerous pathogens. Alert and epidemiological research should be increased on infectious agents of zebra.

Metronidazole Induced Cerebellar Toxicity: A Case Report

Metronidazole is a widely used antibiotic against bacterial and protozoan infections. Even though the therapeutic use of the drug is high, it is associated with some severe side effects like neurotoxicity such as optic neuropathy, peripheral neuropathy, encephalopathy and cerebellar toxicity. We present a case of a 55-years male presented with dysarthria, who had positive cerebellar sign and magnetic resonance imaging findings suggestive of metronidazole induced cerebellar toxicity following metronidazole therapy for two months in a case of liver abscess. And, the symptoms resolved after cessation of metronidazole.

Can Eucalyptol Replace Antibiotics?

One of the primary reasons for the search for new antimicrobial agents is the increasing and spreading resistance of microorganisms to previously used drugs. This is particularly important in the case of rapidly progressing infections that require the rapid administration of an appropriately selected antibiotic. However, along with the administration of antibiotics, complications in the disease-weakened body may arise in the form of systemic mycoses, viral infections, and protozoan infections. Therefore, there is an increasing interest among researchers focusing on the use of naturally occurring terpenic compounds in stand-alone or combined therapies with antibiotics. In this publication, the aim of our work is to present the results of a literature review on the antimicrobial activity of eucalyptol.

Specificity of SARS-CoV-2 antibody-detection assays against S and N protein among pre-COVID-19 sera from patients with protozoan and helminth parasitic infections

Background: We aimed to assess the specificity of SARS-CoV-2 antibody detection assays among people with known tissue-borne parasitic infections. Methods: We tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 Neutralization Antibody Detection Kit, Abbott SARS-CoV-2 IgG assay, and STANDARD Q COVID-19 IgM/IgG Combo Rapid Test) among 559 pre-COVID-19 sera. Results: The specificity of assays was 95-98% overall. However, lower specificity was observed among sera from patients with protozoan infections of the reticuloendothelial system, such as human African trypanosomiasis (Abbott Architect; 88% [95%CI 75-95]), visceral leishmaniasis (SD RDT IgG; 80% [95%CI 30-99]), and from patients with recent malaria from a holoendemic area of Senegal (ranging from 91% for Abbott Architect and SD RDT IgM to 98-99% for cPass and SD RDT IgG). For specimens from patients with evidence of past or present helminth infection overall, test specificity estimates were all ≥ 96%. Sera collected from patients clinically suspected of parasitic infections that tested negative for these infections yielded a specificity of 98-100%. The majority (>85%) of false-positive results were positive by only one assay. Conclusions: The specificity of SARS-CoV-2 serological assays among sera from patients with tissue-borne parasitic infections was below the threshold required for decisions about individual patient care. Specificity is markedly increased by the use of confirmatory testing with a second assay. Finally, the SD RDT IgG proved similarly specific to laboratory-based assays and provides an option in low-resource settings when detection of anti-SARS-CoV-2 IgG is indicated.