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The protozoan parasite Entamoeba histolytica is the microbial agent of amoebiasis – an infection that is endemic worldwide and is associated with high morbidity and mortality rates. As the disease develops, virulent E. histolytica deplete the mucus layer, interact with the intestinal epithelium, and then degrade the colonic mucosa and disrupt the extracellular matrix (ECM). Our research demonstrated that virulent parasites with an invasive phenotype display rapid, highly specific changes in their transcriptome (notably for essential factors involved in carbohydrate metabolism and the processing of glycosylated residues). Moreover, combined activation of parasite and host lytic enzymes leads to the destruction of the intestinal parenchyma. Together, these enzymes degrade the mucus layer and the ECM, and trigger the inflammatory response essential to the development of amoebiasis.

The free-living amoeba Acanthamoeba castellanii is a unicellular eukaryote distributed in a wide range of soil or aquatic environments, either natural or human-made, such as rivers, lakes, drinking water, or swimming pools. Besides its capacity to transport potential pathogens, such as bacteria or viruses, Acanthamoeba spp. can have intrinsic pathogenic properties by causing severe infections at the ocular and cerebral level, named granulomatous amoebic encephalitis and amoebic keratitis, respectively. During its life cycle, A. castellanii alternates between a vegetative and mobile form, named the trophozoite, and a resistant, latent, and non-mobile form, named the cyst. The cyst wall of Acanthamoeba is double-layered, with an inner endocyst and an outer ectocyst, and is mainly composed of cellulose and proteins. The resistance of cysts to many environmental stresses and disinfection treatments has been assigned to the presence of cellulose. The current review aims to present the importance of this glycopolymer in Acanthamoeba cysts and to further report the pathways involved in encystment and excystment.

Amebiasis remains a public health challenge in Mexico, especially in areas with poor sanitation. Despite declining prevalence (2014-2023), hotspots persist because of socioeconomic factors such as poverty. Addressing regional disparities through targeted interventions, improved infrastructure, and education is crucial to further reduce the disease burden and prevent future outbreaks.

Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and evolutionary processes makes it an attractive model organism. There is a significant emphasis on Acanthamoeba as a Trojan horse of other microbes including viral, bacterial, protists and yeast pathogens.

Naegleria fowleri is a climate-sensitive, thermophilic ameba found in warm, freshwater lakes and rivers. Primary amebic meningoencephalitis (PAM), which is almost universally fatal, occurs when N. fowleri-containing water enters the nose, typically during swimming, and migrates to the brain via the olfactory nerve. In August 2013, a 4-year-old boy died of meningoencephalitis of unknown etiology in a Louisiana hospital. Clinical and environmental testing and a case investigation were initiated to determine the cause of death and to identify potential exposures. Based on testing of cerebrospinal fluid and brain specimens, the child was diagnosed with PAM. His only reported water exposure was tap water; in particular, tap water that was used to supply water to a lawn water slide on which the child had played extensively prior to becoming ill. Water samples were collected from both the home and the water distribution system that supplied the home and tested; N. fowleri was identified in water samples from both the home and the water distribution system. This case is the first reported PAM death associated with culturable N. fowleri in tap water from a US treated drinking water system. This case occurred in the context of an expanding geographic range for PAM beyond southern states, with recent case reports from Minnesota, Kansas, and Indiana. This case also highlights the role of adequate disinfection throughout drinking water distribution systems and the importance of maintaining vigilance when operating drinking water systems using source waters with elevated temperatures.

[b]Abstract Introduction[/b]. Among free-living amoebae that are widely distributed in nature only four genera/species are known as agents of human infections:[i] Acanthamoeba spp., Naegleriafowleri, Balamuthia mandrillaris[/i] and[i] Sappiniapedata[/i]. These amoebae are not well adapted to parasitism, and could exist in the human environment without the need for a host. Infections due to these amoebae, despite low morbidity, are characterized by relatively high mortality rate and pose serious clinical problems. [b]Objectve[/b]. This review study presents and summarizes current knowledge about infections due to pathogenic and opportunistic free-living amoebae focused on epidemiology, clinical manifestations, diagnosis and treatment based on global literature. [b]State of knowledge[/b]. All four genera have been recognized as etiologic factors of fatal central nervous system infections and other serious diseases in humans. [i]N. fowleri[/i] causes an acute fulminating meningoencephalitis in children and young adults. [i]Acanthamoeba spp[/i]. and [i]B.mandrillaris[/i] are opportunistic pathogens causing granulomatous amoebic encephalitis and disseminated or localized infections which could affect the skin, sinuses, lungs, adrenals and/or bones. [i]Acanthamoeba spp[/i]. is also the main agent of acute eye infection -[i] Acanthamoeba keratitis, [/i]mostly in contact lens wearers. However, there is only one recognized case of encephalitis caused by [i]S. pedata. [/i] [b]Conclusions[/b]. Amoebic diseases are difficult to diagnose which leads to delayed treatment, and result in a high mortality rate. Considering those issues, there is an urgent need to draw more attention to this type of diseases.

About the Authors: Debbie-Ann T. Shirley Affiliation: Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America ORCID logo http://orcid.org/0000-0003-1718-0901 Koji Watanabe Affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan Shannon Moonah * E-mail: sm5fe@virginia.edu Affiliation: Department of Medicine, University of Virginia School of Medicine Charlottesville, Virginia, United States of America Introduction Nearly 150 years since the first detailed description of the invasive, tissue-destroying intestinal parasite, Entamoeba histolytica, amebiasis remains an infection of consequential global importance. In a large, multinational, prospective case-based study of children with moderate-to-severe diarrhea using molecular methods to identify etiology, however, amebiasis ranked among the top 15 causes of diarrhea in the first two years of life in children living in developing countries, where diarrhea remains the fifth leading cause of death in children under the age of five years [1, 3–5]. Amebiasis was the third most frequently isolated pathogen among returning travelers presenting to one of 42 GeoSentinel Surveillance Network sites globally and seeking medical attention for gastrointestinal infection [14]. Several properties of the E. histolytica cyst, such as low infectious dose and relative resistance to chlorine, facilitate the ease with which it can be disseminated through contamination of food and water supplies, even in low incidence areas. [...]E. histolytica is classified as a category B priority biodefense pathogen by the National Institute of Allergy and Infectious Diseases.

This study examines the potential implications of biofouling management on the development of an infectious disease in Norwegian farmed salmon. The hydroid Ectopleura larynx frequently colonises cage nets at high densities (thousands of colonies per m2) and is released into the water during regular in-situ net cleaning. Contact with the hydroids’ nematocysts has the potential to cause irritation and pathological damage to salmon gills. Amoebic gill disease (AGD), caused by the amoeba Paramoeba perurans, is an increasingly international health challenge in Atlantic salmon farming. AGD often occurs concomitantly with other agents of gill disease. This study used laboratory challenge trials to: (1) characterise the gill pathology resulting from the exposure of salmon to hydroids, and (2) investigate if such exposure can predispose the fish to secondary infections–using P. perurans as an example. Salmon in tanks were exposed either to freshly ‘shredded’ hydroids resembling waste material from net cleaning, or to authentic concentrations of free-living P. perurans, or first to ‘shredded’ hydroids and then to P. perurans. Gill health (AGD gill scores, non-specific gill scores, lamellar thrombi, epithelial hyperplasia) was monitored over 5 weeks and compared to an untreated control group. Nematocysts of E. larynx contained in cleaning waste remained active following high-pressure cleaning, resulting in higher non-specific gill scores in salmon up to 1 day after exposure to hydroids. Higher average numbers of gill lamellar thrombi occurred in fish up to 7 days after exposure to hydroids. However, gill lesions caused by hydroids did not affect the infection rates of P. perurans or the disease progression of AGD. This study discusses the negative impacts hydroids and current net cleaning practices can have on gill health and welfare of farmed salmon, highlights existing knowledge gaps and reiterates the need for alternative approaches to net cleaning.

Background Amebiasis represents a significant global health concern. This is especially evident in developing countries, where infections are more common. The primary diagnostic method in laboratories involves the microscopy of stool samples. However, this approach can sometimes result in the misinterpretation of amebiasis as other gastroenteritis (GE) conditions. The goal of the work is to produce a machine learning (ML) model that uses laboratory findings and demographic information to automatically predict amebiasis. Method Data extracted from Jordanian electronic medical records (EMR) between 2020 and 2022 comprised 763 amebic cases and 314 nonamebic cases. Patient demographics, clinical signs, microscopic diagnoses, and leukocyte counts were used to train eight decision tree algorithms and compare their accuracy of predictions. Feature ranking and correlation methods were implemented to enhance the accuracy of classifying amebiasis from other conditions. Results The primary dependent variables distinguishing amebiasis include the percentage of neutrophils, mucus presence, and the counts of red blood cells (RBCs) and white blood cells (WBCs) in stool samples. Prediction accuracy and precision ranged from 92% to 94.6% when employing decision tree classifiers including decision tree (DT), random forest (RF), XGBoost, AdaBoost, and gradient boosting (GB). However, the optimized RF model demonstrated an area under the curve (AUC) of 98% for detecting amebiasis from laboratory data, utilizing only 300 estimators with a max depth of 20. This study highlights that amebiasis is a significant health concern in Jordan, responsible for 17.22% of all gastroenteritis episodes in this study. Male sex and age were associated with higher incidence of amebiasis ( P = 0.014), with over 25% of cases occurring in infants and toddlers. Conclusions The application of ML to EMR can accurately predict amebiasis. This finding significantly contributes to the emerging use of ML as a decision support system in parasitic disease diagnosis. Graphical Abstract

Entamoeba histolytica is a protozoan parasite belonging to the phylum Amoebozoa that causes amebiasis, a global public health problem. E . histolytica alternates its form between a proliferative trophozoite and a dormant cyst. Trophozoite proliferation is closely associated with amebiasis symptoms and pathogenesis whereas cysts transmit the disease. Drugs are available for clinical use; however, they have issues of adverse effects and dual targeting of disease symptoms and transmission remains to be improved. Development of new drugs is therefore urgently needed. An untargeted lipidomics analysis recently revealed structural uniqueness of the Entamoeba lipidome at different stages of the parasite’s life cycle involving very long (26–30 carbons) and/or medium (8–12 carbons) acyl chains linked to glycerophospholipids and sphingolipids. Here, we investigated the physiology of this unique acyl chain diversity in Entamoeba , a non-photosynthetic protist. We characterized E . histolytica fatty acid elongases (EhFAEs), which are typically components of the fatty acid elongation cycle of photosynthetic protists and plants. An approach combining genetics and lipidomics revealed that EhFAEs are involved in the production of medium and very long acyl chains in E . histolytica . This approach also showed that the K3 group herbicides, flufenacet, cafenstrole, and fenoxasulfone, inhibited the production of very long acyl chains, thereby impairing Entamoeba trophozoite proliferation and cyst formation. Importantly, none of these three compounds showed toxicity to a human cell line; therefore, EhFAEs are reasonable targets for developing new anti-amebiasis drugs and these compounds are promising leads for such drugs. Interestingly, in the Amoebazoan lineage, gain and loss of the genes encoding two different types of fatty acid elongase have occurred during evolution, which may be relevant to parasite adaptation. Acyl chain diversity in lipids is therefore a unique and indispensable feature for parasitic adaptation of Entamoeba .