Prevalence of Protozoan Pathogens Among Diarrheic Children Under 5 Years in Public Hospital of Ethiopia During the Global COVID 19 Pandemic.

Acute childhood diarrhea is one of the leading causes of childhood morbidity and mortality in sub-Saharan African countries. Entamoeba histolytica and Giardia lamblia are the common cause of childhood diarrhea in the region. However, there are only few studies on protozoa causing diarrhea in sub-Saharan African countries. This study was conducted to investigate the relative prevalence and explore risk factors of E. histolytica and G. lamblia among diarrheic children of under 5 years in a public hospital of Ethiopia. A retrospective study was conducted among diarrheic children at Hiwot Fana hospital, Ethiopia. Records of all diarrheic children less than 5 years who had sought medical treatment in the hospital from September 1, 2020 to December 31, 2022 were included. Data were collected from 1257 medical records of the children using a structured data-collection format. Data were entered into an Excel sheet and exported into SPSS version 22 for data processing and analysis. Descriptive statistical tests, Chi-square, and logistic region analysis were applied to determine predictors of protozoa infections. Of the 1257 cases, 962 (76.5%) had watery diarrhea and the remaining 239 (19.0%) had dysentery. The combined prevalence of E. histolytica and G. lamblia among diarrheic children was 11.8% (95% CI: 9.6-13.4). As the age of children increased, the frequency of these two protozoan infections was significantly increased compared to children with other causes. There were more diarrhea cases during the summer season including those associated with E. histolytica and G. lamblia. This study revealed that 1 in 10 causes of diarhhea among young children in the study area was likely caused by E. histolytica and G. lamblia. These findings call for community-based safe water and food safety interventions in order to reduce childhood diarrhea caused by protozoan infections in resource-poor settings.

Melatonin: A look at protozoal and helminths.

Melatonin is a pleiotropic neurohormone found in different animal, plant, and microorganism species. It is a product resulting from tryptophan metabolism in the pineal gland and is widely known for its ability to synchronize the circadian rhythm to antitumor functions in different types of cancers. The molecular mechanisms responsible for its immunomodulatory, antioxidant and cytoprotective effects involve binding to high-affinity G protein-coupled receptors and interactions with intracellular targets that modulate signal transduction pathways. In vitro and in vivo studies have reported the therapeutic potential of melatonin in different infectious and parasitic diseases. In this review, the protective and pathophysiological roles of melatonin in fighting protozoan and helminth infections and the possible mechanisms involved against these stressors will be discussed.

State-of-the-art Review on the Antiparasitic Activity of Benzimidazolebased Derivatives: Facing Malaria, Leishmaniasis, and Trypanosomiasis.

Protozoan parasites represent a significant risk for public health worldwide, afflicting particularly people in more vulnerable categories and cause large morbidity and heavy economic impact. Traditional drugs are limited by their toxicity, low efficacy, route of administration, and cost, reflecting their low priority in global health management. Moreover, the drug resistance phenomenon threatens the positive therapy outcome. This scenario claims the need of addressing more adequate therapies. Among the diverse strategies implemented, the medicinal chemistry efforts have also focused their attention on the benzimidazole nucleus as a promising pharmacophore for the generation of new drug candidates. Hence, the present review provides a global insight into recent progress in benzimidazole-based derivatives drug discovery against important protozoan diseases, such as malaria, leishmaniasis and trypanosomiasis. The more relevant chemical features and structure-activity relationship studies of these molecules are discussed for the purpose of paving the way towards the development of more viable drugs for the treatment of these parasitic infections.

Outcomes of patients in Chagas disease of the central nervous system: a systematic review.

Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi. One of the complications of the disease is the infection of the central nervous system (CNS), as it can result from either the acute phase or by reactivation during the chronic phase, exhibiting high mortality in immunocompromised patients. This systematic review aimed to determine clinical and paraclinical characteristics of patients with Chagas disease in the CNS. Articles were searched from PubMed, Scopus and LILACS until January 2023. From 2325 articles, 59 case reports and 13 case series of patients with Chagas in the CNS were retrieved from which 138 patients were identified. In this population, 77% of the patients were male, with a median age of 35 years old, from which most of them came from Argentina and Brazil. Most of the individuals were immunocompromised from which 89% were HIV-positive, and 54 patients had an average of 48 cells per mm3 CD4+ T cells. Motor deficits and seizures were the most common manifestation of CNS compromise. Furthermore, 90 patients had a documented CNS lesion by imaging from which 89% were supratentorial and 86% were in the anterior/middle cranial fossa. The overall mortality was of 74%. Among patients who were empirically treated with anti-toxoplasma drugs, 70% died. This review shows how Chagas disease in the CNS is a devastating complication requiring prompt diagnosis and treatment to improve patients' outcomes.

Emerging and Re-Emerging Parasitic Infections of the Central Nervous System (CNS) in Europe.

In a rapidly evolving global landscape characterized by increased international travel, migration, and ecological shifts, this study sheds light on the emergence of protozoal and helminthic infections targeting the central nervous system (CNS) within Europe. Despite being traditionally associated with tropical regions, these infections are progressively becoming more prevalent in non-endemic areas. By scrutinizing the inherent risks, potential outcomes, and attendant challenges, this study underscores the intricate interplay between diagnostic limitations, susceptibility of specific population subsets, and the profound influence of climate fluctuations. The contemporary interconnectedness of societies serves as a conduit for introducing and establishing these infections, warranting comprehensive assessment. This study emphasizes the pivotal role of heightened clinician vigilance, judicious public health interventions, and synergistic research collaborations to mitigate the potential consequences of these infections. Though rare, their profound impact on morbidity and mortality underscores the collective urgency required to safeguard the neurological well-being of the European populace. Through this multifaceted approach, Europe can effectively navigate the complex terrain posed with these emergent infections.

Host-Derived Extracellular Vesicles in Blood and Tissue Human Protozoan Infections.

Blood and tissue protozoan infections are responsible for an enormous burden in tropical and subtropical regions, even though they can also affect people living in high-income countries, mainly as a consequence of migration and travel. These pathologies are responsible for heavy socio-economic issues in endemic countries, where the lack of proper therapeutic interventions and effective vaccine strategies is still hampering their control. Moreover, the pathophysiological mechanisms associated with the establishment, progression and outcome of these infectious diseases are yet to be fully described. Among all the players, extracellular vesicles (EVs) have raised significant interest during the last decades due to their capacity to modulate inter-parasite and host-parasite interactions. In the present manuscript, we will review the state of the art of circulating host-derived EVs in clinical samples or in experimental models of human blood and tissue protozoan diseases (i.e., malaria, leishmaniasis, Chagas disease, human African trypanosomiasis and toxoplasmosis) to gain novel insights into the mechanisms of pathology underlying these conditions and to identify novel potential diagnostic markers.

Unlocking the potential of snake venom-based molecules against the malaria, Chagas disease, and leishmaniasis triad.

Malaria, leishmaniasis and Chagas disease are vector-borne protozoal infections with a disproportionately high impact on the most fragile societies in the world, and despite malaria-focused research gained momentum in the past two decades, both trypanosomiases and leishmaniases remain neglected tropical diseases. Affordable effective drugs remain the mainstay of tackling this burden, but toxicicty, inneficiency against later stage disease, and drug resistance issues are serious shortcomings. One strategy to overcome these hurdles is to get new therapeutics or inspiration in nature. Indeed, snake venoms have been recognized as valuable sources of biomacromolecules, like peptides and proteins, with antiprotozoal activity. This review highlights major snake venom components active against at least one of the three aforementioned diseases, which include phospholipases A2, metalloproteases, L-amino acid oxidases, lectins, and oligopeptides. The relevance of this repertoire of biomacromolecules and the bottlenecks in their clinical translation are discussed considering approaches that should increase the success rate in this arduous task. Overall, this review underlines how venom-derived biomacromolecules could lead to pioneering antiprotozoal treatments and how the drug landscape for neglected diseases may be revolutionized by a closer look at venoms. Further investigations on poorly studied venoms is needed and could add new therapeutics to the pipeline.

Two cases of Lophomonas blattarum infection combined with paragonimiasis and literature review / 中国基层医药

Objective:To investigate the clinical manifestations, diagnosis, and treatment methods of Lophomonas blattarum infection combined with paragonimiasis in children, and improve pediatricians' understanding of the disease. Methods:The clinical data of two children with Lophomonas blattarum infection combined with paragonimiasis who received treatment in the Department of Pediatrics of The First People's Hospital of Yunnan Province were retrospectively analyzed. Children's clinical manifestation and diagnosis and treatment were analyzed. Relative literature was reviewed. Results:Case 1 had the onset of gastrointestinal symptoms. Case 2 had the onset of headache and liver dysfunction. Routine blood tests showed elevated eosinophils two cases and sputum examination results revealed the presence of live eggs of Lophomonas blattarum and paragonimiasis in two cases. Fecal roundworm eggs were also detected in case 1. Follow-up results showed that both cases were cured after treatment with metronidazole injection and praziquantel tablets. Conclusion:Lophomonas blattarum infection is a relatively rare opportunistic infection. Paragonimiasis is a natural parasitic disease that affects both humans and animals. Mixed infection of the two pathogens is rare. We hope that the findings from this paper will broaden clinical physicians' thoughts and guide clinical practice.

Concurrent infections of cells by two pathogens can enable a reactivation of the first pathogen and the second pathogen's accelerated T-cell exhaustion.

When multiple intracellular pathogens, such as viruses, bacteria, fungi and protozoan parasites, infect the same host cell, they can help each other. A pathogen can substantially help another pathogen by disabling cellular immune defenses, using non-coding ribonucleic acids and/or pathogen proteins that target interferon-stimulated genes and other genes that express immune defense proteins. This can enable reactivation of a latent first pathogen and accelerate T-cell exhaustion and/or T-cell suppression regarding a second pathogen. In a worst-case scenario, accelerated T-cell exhaustion and/or T-cell suppression regarding the second pathogen can impair T-cell functionality and allow a first-time, immunologically novel second pathogen infection to escape all adaptive immune system defenses, including antibodies. The interactions of herpesviruses with concurrent intracellular pathogens in epithelial cells and B-cells, the interactions of the human immunodeficiency virus with Mycobacterium tuberculosis in macrophages and the interactions of Toxoplasma gondii with other pathogens in almost any type of animal cell are considered. The reactivation of latent pathogens and the acceleration of T-cell exhaustion for the second pathogen can explain several puzzling aspects of viral epidemics, such as COVID-19 and their unusual comorbidity mortality rates and post-infection symptoms.

Análisis retrospectivo de un protozoo emergente en México: Blastocystis spp

Blastocystis spp. es el protista intracelular que en los últimos años ha infectado a más de mil millones de personas a nivel mundial. Sin embargo, el aumento en la prevalencia en México y su potencial patógeno son inciertos, por lo que este microorganismo aún se encuentra bajo investigación. Principalmente a nivel pediátrico, la blastocistosis es estudiada con mayor atención, debido a que destaca sobre otros agentes en diversos estudios realizados mundialmente y en México. El objetivo de este trabajo fue mediante revisión bibliográfica, evidenciar la frecuencia y su transición parasitaria como el agente más prevalente en la actualidad, pese a que no se asocia a sintomatología clínica.

Blastocystis spp. is the intracellular protist that in recent years has infected more than a billion people worldwide. However, the increase in prevalence in Mexico and its pathogenic potential are uncertain, so this microorganism is still under investigation. Mainly at the pediatric level, blastocystosis is studied with greater attention, due to the fact that it stands out over other agents in various studies carried out worldwide and in Mexico. The objective of this work was to show the frequency and its parasitic transition as the most prevalent agent today through a bibliographic review, despite the fact that it is not associated with clinical symptoms.

The Potential Role of the Serotonin Transporter as a Drug Target against Parasitic Infections: A Scoping Review of the Literature.

BACKGROUND: Several in vitro and in vivo biological activities of serotonin, 5- hydroxytryptamine (5-HT), as a bioactive molecule, and its transporter (5-HT-Tr) were evaluated in parasitic infections. OBJECTIVE: Herein, the roles of 5-HT and 5-HTR in helminths and protozoan infections with medical and veterinary importance are reviewed. METHODS: We searched information in 4 main databases and reviewed published literature about the serotonin transporter's role as a promising therapeutic target against pathogenic parasitic infections between 2000 and 2021. RESULTS: Based on recent investigations, 5-HT and 5-HT-Tr play various roles in parasite infections, including biological function, metabolic activity, organism motility, parasite survival, and immune response modulation. Moreover, some of the 5-HT-TR in Schistosoma mansoni showed an excess of favorite substrates for biogenic amine 5-HT compared to their mammalian hosts. Furthermore, the main neuronal protein related to the G protein-coupled receptor (GPCR) was identified in S. mansoni and Echinococcus granulosus, playing main roles in these parasites. In addition, 5-HT increased in toxoplasmosis, giardiasis, and Chagas disease. On the other hand, in Plasmodium spp., different forms of targeted 5-HTR stimulate Ca2+ release, intracellular inositol triphosphate (ITP), cAMP, and protein kinase A (PKA) activity. CONCLUSION: This review summarized the several functional roles of the 5-HT and the importance of the 5-HT-TR as a drug target with minimal harm to the host to fight against helminths and protozoan infections. Hopefully, this review will shed light on research regarding serotonin transporter-based therapies as a potential drug target soon.

Use of laboratory methodologies to confirm an outbreak of acute diarrheal disease caused by multiple pathogens / Uso de metodologias laboratoriais para confirmação de surto de doença diarreica aguda causada por múltiplos patógenos

The aim of this study was to investigate an outbreak caused by protozoa, which occurred in a municipality in the Brazil southern region. The investigations were carried out analyzing 47 fresh stool samples and 26 water samples by parasitological and molecular methods, as well as, direct immunofluorescence. After the filtrations of water samples and purification of stool samples, the concentrates were evaluated microscopically for presence of parasites. Molecular analyses were performed by polymerase chain reaction (PCR) for DNA detection of Giardia spp., Cryptosporidium parvum, C. hominis and Cyclospora cayetanensis. Out of 26 water samples, 30.8% (8/26) had waterborne protozoa and C. cayetanensis was the most prevalent (15.5%). Out of the 47 stool samples, 23.4% (11/47) were infected with C. cayetanensis and Giardia spp. The results showed that backwash water samples from filters of the Water Treatment Station were contaminated with C. cayetanensis, C. hominis and Giardia spp., suggesting the contamination of water sources with human waste brought by sewage. These results show the importance of protozoa investigation in water and stool samples by laboratory methodologies principally in outbreaks causing acute diarrheal disease (AU).

O objetivo do presente estudo foi investigar um surto causado por protozoários, ocorrido em um município da região sul do Brasil. As investigações foram realizadas analisando 47 amostras de fezes frescas e 26 amostras de água por métodos parasitológicos, moleculares e de imunofluorscência direta. Após as filtrações das amostras de água e purificação das amostras de fezes, os concentrados foram avaliados microscopicamente a procura de parasitas. A seguir, foram analisadas, pela reação em cadeia da polimerase (PCR), a detecção de DNA de Giardia spp., Cryptosporidium parvum, C. hominis e Cyclospora cayetanensis. Das 26 amostras de água, 30,8% (8/26) apresentaram protozoários de veiculação hídrica, sendo que, C. cayetanensis foi o mais prevalente (15,5%). Das 47 amostras de fezes, 23,4% (11/47) estavam infectadas por C. cayetanensis e Giardia spp. Os resultados mostraram que as águas de retrolavagem dos filtros da Estação de Tratamento de Água estavam contaminadas com C. cayetanensis, C. hominis e Giardia spp. sugerindo a contaminação dos mananciais com dejetos humanos trazidos pelo esgoto. Estes resultados mostram a importância da investigação de protozoários em água e fezes por metodologias laboratoriais, principalmente em surtos que causam doença diarreica aguda (AU).

Frequency of intestinal protozoan infections diagnosed in patients from a clinical analysis laboratory

This study aimed to determine the frequency of infection by intestinal protozoa diagnosed in patients from a clinical analysis laboratory in Maceió, Alagoas, Brazil. This was a retrospective descriptive study, using a database of stool examination results from July to December 2015. The study population consisted of males and females of all ages, from the greater area of Alagoas. Data on epidemiological variables such as age and gender were obtained using a collection instrument. Protozoan species were identified from stool examinations. Results on the prevalence of intestinal parasites are described as simple and relative frequencies. We examined a total of 1277 stool samples, of which 12.69% were positive for one or more protozoa. 43.83% were from men and 56.17% were from women. Endolimax nana was the most prevalent (59.22%) protozoan species followed by Entamoeba coli (23.45%). Although non-pathogenic, they indicate fecal contamination of drinking water. The highest number (23.46%) of infected individuals was observed among children in the 0 to 11 years age group. A high prevalence (93.83%) of monoparasitism was noted. We concluded that there was a high frequency of infection and a high prevalence of E. nana. Infections were more common in women than in men. Our results emphasize the need for preventive measures to control intestinal parasitic infections.

The link between Toxoplasma gondii infections and higher mortality in COVID-19 patients having schizophrenia.

A strong link between schizophrenia and a higher mortality rate from SARS-CoV-2 infections has been reported for schizophrenia patients, with a mortality odds ratio (OR) of 2.67 compared to normal patients, after adjustment of the OR for age, sex, race and extra risk factors. In addition, an extensive number of papers have reported a very strong link between schizophrenia and Toxoplasma gondii infections. A meta-analysis of 38 studies of links between schizophrenia and T. gondii antibody seroprevalence resulting from previous infections indicated that the likelihood of T. gondii infection in schizophrenia patients was 2.7 times higher than the general population. In other words, the meta-analysis indicated that schizophrenia patients had an odds ratio of 2.7 of T. gondii infection compared to the general population. This indicates that compared to the general population, schizophrenia patients have virtually the same odds ratio for having a T. gondii infection and for mortality from a COVID-19 infection. This suggests that T. gondii infections, directly or indirectly, have a relationship with higher mortality in COVID-19 patients having schizophrenia. This conclusion would also apply to the general population.

Specificity of SARS-CoV-2 Antibody Detection Assays against S and N Proteins among Pre-COVID-19 Sera from Patients with Protozoan and Helminth Parasitic Infections.

We aimed to assess the specificity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody detection assays among people with tissue-borne parasitic infections. We tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 neutralization antibody detection kit [cPass], Abbott SARS-CoV-2 IgG assay [Abbott Architect], and Standard Q COVID-19 IgM/IgG combo rapid diagnostic test [SD RDT IgM/SD RDT IgG]) among 559 pre-COVID-19 seropositive sera for several parasitic infections. The specificity of assays was 95 to 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 to 95]) and visceral leishmaniasis (SD RDT IgG; 80% [95% CI, 30 to 99]), and from patients with recent malaria in areas of Senegal where malaria is holoendemic (ranging from 91% for Abbott Architect and SD RDT IgM to 98 to 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 to 100%. The majority (>85%) of false-positive results were positive by only one assay. 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.

The role of polyspecific T-cell exhaustion in severe outcomes for COVID-19 patients having latent pathogen infections such as Toxoplasmagondii.

Various categories of coronavirus disease 19 (COVID-19) patients have exhibited major mortality rate differences and symptoms. Some papers have recently explained these differences in mortality rates and symptoms as a consequence of this virus infection acting in synergy with one or more latent pathogen infections in some patients. A latent pathogen infection likely to be involved in millions of these patients is the protozoan parasite Toxoplasma gondii, which infects approximately one third of the global human population. However, other papers have concluded that latent protozoan parasite infections can reduce the severity of viral infections. The aims and purposes of this paper include providing explanations for the contradictions between these studies and introducing a significant new category of T-cell exhaustion. Latent pathogens can have different genetic strains with great differences in their effects on a second pathogen infection. Furthermore, depending on the timing and effectiveness of drug treatments, pathogen infections that become latent may or may not later induce immune cell dysfunctions, including T-cell exhaustion. Concurrent multiple pathogen T-cell exhaustion is herein called "polyspecific T-cell exhaustion."

In vitro and in vivo effectiveness of disinfectants against Trypanosoma vivax.

Trypanosoma vivax causes bovine trypanosomosis in cattle and resulting in economic losses to farmers. In Brazil, shared contaminated materials is the main transmission pathway. To evaluate the effectiveness of different disinfectants for T. vivax, in vitro and in vivo analyses were performed. At the laboratory, 21 disinfectants were tested. The disinfectants were placed in microtubes containing blood with approximately 1.0 × 106 trypomastigotes of T. vivax. The viability and motile of trypomastigotes after 30 s, one, 10, 15 and 30 min was evaluated by the thick drop method and the efficacy calculated. Disinfectants that showed 100% effectiveness were used in in vivo tests. Thirty calves negative for T. vivax were divided into six groups and were inoculated with disinfectant solutions (46% alcohol, 70% alcohol, or 0.5% iodine) + 1 × 106 trypomastigotes of the protozoa. Blood from each animal was collected at seven, 14 and 21 days after inoculation to verify the viability and presence of the protozoan by Woo, Brener, PCR, and LAMP methods. In the in vitro step, 13 of the 21 disinfected solutions exhibited 100% effectiveness against T. vivax at all evaluation times. In contrast, 70% alcohol and 0.5% iodine solutions exhibited 100% effectiveness in the in vivo tests and can be used to disinfect needles and syringes. The use of disinfectants is a rapid and efficient procedure to disinfect materials utilized in the field and concomitantly could help to reduce the dissemination of T. vivax in the cattle herd in cases of iatrogenic transmission.

A role for T-cell exhaustion in Long COVID-19 and severe outcomes for several categories of COVID-19 patients.

Unusual mortality rate differences and symptoms have been experienced by COVID-19 patients, and the postinfection symptoms called Long COVID-19 have also been widely experienced. A substantial percentage of COVID-19-infected individuals in specific health categories have been virtually asymptomatic, several other individuals in the same health categories have exhibited several unusual symptoms, and yet other individuals in the same health categories have fatal outcomes. It is now hypothesized that these differences in mortality rates and symptoms could be caused by a SARS-CoV-2 virus infection acting together with one or more latent pathogen infections in certain patients, through mutually beneficial induced immune cell dysfunctions, including T-cell exhaustion. A latent pathogen infection likely to be involved is the protozoan parasite Toxoplasma gondii, which infects approximately one third of the global human population. Furthermore, certain infections and cancers that cause T-cell exhaustion can also explain the more severe outcomes of other COVID-19 patients having several disease and cancer comorbidities.

Mammalian Neuropeptides as Modulators of Microbial Infections: Their Dual Role in Defense versus Virulence and Pathogenesis.

The regulation of infection and inflammation by a variety of host peptides may represent an evolutionary failsafe in terms of functional degeneracy and it emphasizes the significance of host defense in survival. Neuropeptides have been demonstrated to have similar antimicrobial activities to conventional antimicrobial peptides with broad-spectrum action against a variety of microorganisms. Neuropeptides display indirect anti-infective capacity via enhancement of the host's innate and adaptive immune defense mechanisms. However, more recently concerns have been raised that some neuropeptides may have the potential to augment microbial virulence. In this review we discuss the dual role of neuropeptides, perceived as a double-edged sword, with antimicrobial activity against bacteria, fungi, and protozoa but also capable of enhancing virulence and pathogenicity. We review the different ways by which neuropeptides modulate crucial stages of microbial pathogenesis such as adhesion, biofilm formation, invasion, intracellular lifestyle, dissemination, etc., including their anti-infective properties but also detrimental effects. Finally, we provide an overview of the efficacy and therapeutic potential of neuropeptides in murine models of infectious diseases and outline the intrinsic host factors as well as factors related to pathogen adaptation that may influence efficacy.