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The parasite Entamoeba histolytica , the causal agent of amebiasis, is considered a worldwide emergent disease and still represents an important cause of death in Mexico. Here, we describe a clinical case, involving an inflammatory response to both Coronavirus Infectious Disease 2019 (COVID-19) and intestinal amebiasis 54-year-old, COVID-positive Mexican gentleman was admitted to surgery following 6 days of hematochezia. An exploratory laparotomy and colonoscopy revealed multiple fibrous and amebic ulcerations (5–10 cm in diameter), with necrotic tissue predominantly localized in the sigmoid, descending and ascending colon. We discuss the pathophysiological interplay of both COVID-19 and intestinal amebiasis with the aim of highlighting a potentially novel aggravating mechanism in surgical patients suffering from colonic perforation in the setting of abdominal sepsis. [ABSTRACT FROM AUTHOR]

We report the case of a 62-year-old male with cough and abdominal pain for two weeks, associated with pulmonary tomographic findings compatible with probable infection by SARS-CoV-2, and who received high doses of early corticotherapy as an outpatient. The patient showed clinical deterioration, was hospitalized and died in the immediate postoperative period due to acute surgical abdomen. The anatomopathological study showed parasitic structures with characteristics compatible with amebae, which was pointed to as the cause of a complicated acute fulminant colitis, with multiple perforations and acute peritonitis. Acute fulminant colitis due to intestinal amebiasis in the context of a patient with probable COVID-19 had not been previously reported in Peru. It is important to highlight the fulminant presentation with fatal outcome of this prevalent parasitic infection, in the context of corticosteroids use in a probable SARS-CoV-2 pulmonary infection. [ABSTRACT FROM AUTHOR]

Reliable detection the etiological agent of amoebic dysentery and extra-intestinal amoebiasis have Public health importance specially in asymptomatic individual .The objective of the study includes two aspects, the first to give correct perception of infection rate in asymptomatic individuals and the second aspect about detection and diagnosis of the pathogenic species of Entamoeba histolytica from another morphologically similar and commensal one using the molecular technique in stool samples of asymptomatic individuals. During the study period from the beginning of April to the end of Jun /2018, a total of 95 stool sample was collected from asymptomatic 71 male and 24 female ages between 25-55 years old. Microscopic and molecular diagnosis for E. histolytica was done using wet mount method and Real Time polymerase chain reaction employing 18S rRNA gene Respectively. The result highlighted the microscopic diagnosis of cyst stage in 33 asymptomatic patient out of 95 (34.73%) with significant differences P<0.05 between males 22/71 (66.66%) and females 11/24 (33.33%). On the other hand the molecular diagnosis results showed presence of Entamoeba histolytica in 19 sample out of 33 (63.33%) with significant differences P<0.05 between males 15/22 (68.18%) and females 4/11 (36.36%). Conclusion, The microscopic examination of stool sample show a possibility of error to differentiate pathogenic E. histolytica from those of morphologically similar non-pathogenic species lead to inaccurate results therefore, the molecular methods must be adopted for diagnosis. There is also a sign that the pollution problem is still not controlled and is a risk factor for infection transmitted [ABSTRACT FROM AUTHOR]

Background: Cap polyposis (CP) is extremely rare in Japan, and there is no established cure. We report a case in which CP was improved by surgical treatment. Case presentation: A 48-year-old man was investigated at a local hospital because of diarrhea and bloody stools in 2018. The patient was treated with metronidazole for suspected amoebic dysentery, but his symptoms did not improve. Subsequent close examination revealed possible CP, but treatment with 5-aminosalicylic acid and a steroid enema had no effect. The patient was then referred to our hospital. The bloody stools, diarrhea, and abdominal pain worsened despite medical treatment, so laparoscopic-assisted total proctocolectomy and ileal J-pouch anal anastomosis with ileostomy were performed. CP has no known cause or established treatment, but Helicobacter pylori (HP) infection has been reported in many CP cases in Japan, and HP eradication is often successful. This patient was HP-negative and did not improve with antimicrobial treatment, but the symptoms improved after surgery. Conclusions: Even after surgery, CP recurrence reportedly occurs within a short period in many cases. However, our patient has had no signs of CP recurrence during 1 year of follow-up. [ABSTRACT FROM AUTHOR]

Amebiasis is a neglected tropical disease caused by Entamoeba histolytic a. Although the disease burden varies geographically, amebiasis is estimated to account for some 55,000 deaths and millions of infections globally per year. Children and travelers are among the groups with the greatest risk of infection. There are currently no licensed vaccines for prevention of amebiasis, although key immune correlates for protection have been proposed from observational studies in humans. We previously described the development of a liposomal adjuvant formulation containing two synthetic TLR ligands (GLA and 3M-052) that enhanced antigen-specific fecal IgA, serum IgG2a, a mixed IFNγ and IL-17A cytokine profile from splenocytes, and protective efficacy following intranasal administration with the LecA antigen. By applying a statistical design of experiments (DOE) and desirability function approach, we now describe the optimization of the dose of each vaccine formulation component (LecA, GLA, 3M-052, and liposome) as well as the excipient composition (acyl chain length and saturation; PEGylated lipid:phospholipid ratio; and presence of antioxidant, tonicity, or viscosity agents) to maximize desired immunogenicity characteristics while maintaining physicochemical stability. This DOE/desirability index approach led to the identification of a lead candidate composition that demonstrated immune response durability and protective efficacy in the mouse model, as well as an assessment of the impact of each active vaccine formulation component on protection. Thus, we demonstrate that both GLA and 3M-052 are required for statistically significant protective efficacy. We also show that immunogenicity and efficacy results differ in female vs male mice, and the differences appear to be at least partly associated with adjuvant formulation composition. [ABSTRACT FROM AUTHOR]

Entamoeba histolytica is distributed throughout the world. Invasive amebiasis affects millions of people globally, and the associated complications cause 40,000–100,000 deaths per year. In countries where fecal–oral transmission is unusual, amebic colitis is not common, and the infection may be seen in travelers to and emigrants from endemic areas. Without adequate treatment, amebic colitis may develop into fulminant and become rapidly fatal. With the current increase in global mobility, amebic colitis should be suspected even in patients not in the endemic areas. CT plays an important role in the diagnosis of amebic colitis by demonstrating the presence of colitis with the typical involvement of the cecum and rectum. Pathological features of atypical involvement are also demonstrated. Since preoperative diagnosis can reduce the mortality associated with necrotizing colitis, radiologists need to recognize the typical as well as atypical CT findings of amebic colitis. Considering this requirement, this paper aims to describe the histopathologic features of amebic colitis and to illustrate the spectrum of corresponding CT findings. [ABSTRACT FROM AUTHOR]

The protozoan parasite Entamoeba histolytica causes amoebiasis, a global public health problem. Amoebiasis is solely transmitted by cysts that are produced from proliferative trophozoites by encystation in the large intestine of humans. During encystation, various metabolites, pathways, and cascades sequentially orchestrate the morphological and physiological changes required to produce cysts. Cholesteryl sulfate (CS) has recently been revealed to be among the key molecules that control the morphological and physiological changes of encystation by exerting pleiotropic effects. CS promotes the rounding of encysting Entamoeba cells and maintains this spherical morphology as encysting cells are surrounded by the cyst wall, a prerequisite for resistance against environmental stresses. CS is also involved in the development of membrane impermeability, another prerequisite for resistance. The initiation of cyst wall formation is, however, CS-independent. Here, we overview CS-dependent and -independent processes during encystation and discuss their functional linkage. We also discuss a potential transcriptional cascade that controls the processes necessary to produce dormant Entamoeba cysts. [ABSTRACT FROM AUTHOR]

Liver abscesses are a common complication in patients with amebiasis. Rarely, these will rupture across the diaphragm causing life-threatening empyemas. Evidence justifies performing surgical debridement or decortication for their treatment, given the better overall performance in comparison to open surgeries. However, no current guideline specifies which is the best approach. This report presents the case of a 39-year-old male with clinical, radiographical and microbiological evidence of an amebic empyema secondary to an amebic liver abscess, who received treatment by video-assisted thoracoscopy. The case description highlights the surgical technique, findings and operative outcomes that could be taken into consideration by other physicians to timely manage similar cases. The latter is especially relevant in underdeveloped and developing countries, where the burden of amebiasis appears to be greater. To the best of the authors' knowledge, this is the first description of a transdiaphragmatic amebic infection treated in a minimally invasive fashion. [ABSTRACT FROM AUTHOR]

The objective of this work is investigating the effect of Entamoeba histolytica on adiponectin and histamine levels in children. The current work was preformed among children aged 8 years to 12 years. The blood and feces samples obtained from children who attended Children's Hospital between June to September 2021. 50 children used in current, who diagnosed with diarrhea and abdominal pain, on the other hand, 25 healthy children, were used in this study as control group. The findings of current study were exhibit significant (P<0.05) reduce in adiponectin levels of infected children compared with healthy children. While the findings of this study exhibit significant elevate in histamine concentration of infected children. So, E. histolytica may stimulate the secretion of adiponectin and reduce the release of histamine in children. [ABSTRACT FROM AUTHOR]

Background: Entamoeba histolytica (Eh) causes amebiasis in humans and is in charge of 100,000 deaths yearly, making it the third driving reason for death because of a protozoan parasite. Giardiasis is a main diarrheal disease with international allocation caused by Giardia lamblia. Aim of the Study: To show the current prevalence of Eh and G. lamblia infection among people living in Al-Shomally region in Babil, Middle of Iraq, as a cause of diarrhea in the community and for thorough recognition of this social problem and its important drawbacks on the general health. Methods: A total of 3176 patients with different ages attending the Al-Shomally General Hospital in Babil Province, middle of Iraq, in 2015 were involved. After collection, samples examined via macroscopic and microscopic examination for the presence of Eh and G. lamblia utilizing normal saline and lugholes iodine by direct method examination. Results: From 3176 patients with diarrheal episodes, 699 (22%) were infected by either of Eh (17.91%) or by G. lamblia (4.09%). The highest rate of infections of Eh and G. lamblia was in the age group of 15–44 years and more than 45 years, respectively. Most infection of Eh occurs in February. No significant differences between male and female (50.65% and 49.35% respectively) were observed. Conclusions: This study demonstrated high prevalence of intestinal parasitic infection (Eh and G. lamblia) in the investigation region. Eh is prominent etiology of dysentery in Al-Shomally region. There is an urgent need to improve the living conditions, providing proper sewage disposal system and health education, and treat the infected persons by applying survey programs for parasites.

Background and Objectives: Amebiasis remains an important public health problem worldwide, and immigration and increased international travel have affected incident disease cases. This study assesses the prevalence of Entamoeba histolytica in Taiwan between 2011 and 2020 by analyzing data from surveillance programs conducted by the Centers for Disease Control of Taiwan (TCDC) on laboratory-confirmed cases. Materials and Methods: The E. histolytica infection-related data reported to the National Infectious Diseases Statistics System at the TCDC from 1 January 2011 to 31 December 2020 were collected, including age, gender, place of residence, and the geographic season of exposure for each case. Results: In total, 3066 cases with E. histolytica infections were included in our analysis. Among them, 1735 (57%) cases were imported, and 1331 (43%) were locally acquired. The average annual incidence rate of E. histolytica infections in Taiwan between 2011 and 2020 was 10.6 and 16.1 per 1,000,000 patients. There were statistical differences in gender, age group, and place of residence (p < 0.001) by the source distribution of cases. Also, these differences were found every year (p < 0.05). There were statistical differences in gender and age group (p < 0.001) by place of residence (p < 0.001). The only difference between the distribution of cases and age group was in gender (p < 0.001). Eight patients with amebiasis died, and the fatality rate was 0.3% (8/3066), of whom 75% (6/8) were male, and 75% (6/8) were over 45 years old. This study demonstrates that multiple linear regression analysis shows positive associations between NO2 concentration and amebiasis cases (B value = 2.569, p = 0.019), O3 concentration and amebiasis cases (B value = 0.294, p = 0.008), and temperature and amebiasis cases (B value = 1.096, p = 0.046). Conclusions: This study is the first report of confirmed E. histolytica cases from TCDC surveillance data between 2011 and 2020. This study showed the importance of long periods, air pollutants, and geographically comprehensive analysis for estimating the effect of amebiasis transmission in Taiwan’s populations.

Entamoeba histolytica infections are increasingly diagnosed as sexually transmitted infections in Japan. However, the stool ova–parasite examination (O&P) test has been the only approved diagnostic method used in Japan since production of the indirect immunofluorescence assay (IFA) serum antibody test was discontinued at the end of 2017. Herein, we assessed whether an enzyme-linked immunosorbent assay (ELISA)-based serological test could substitute for IFA. This cross-sectional study used stored frozen serum samples from the Biobank of the National Center for Global Health and Medicine. A serological ELISA-based test was performed on these samples and their titers were compared with those previously measured by IFA based on the medical record data. Sixty seven stored frozen serum samples with differing recorded IFA antibody titers (16 samples with titers < ×100, 13 samples × 100, 16 samples × 200, 11 samples × 400, and 11 samples ≥ × 800) were analyzed. The sensitivity and specificity values for ELISA vs. IFA were 92.2% [95% confidential interval: 81.5–96.9] and 87.5% [64.0–97.8], respectively. A strong correlation between the antibody titers was confirmed by a one-way ANOVA (R square 0.83, p value < 0.0001) for the two diagnostic methods. The ELISA and IFA antibody titers for E. histolytica were well correlated, and results from these methods were highly concordant. Introduction of an ELISA-based serological test for E. histolytica should be considered to improve E. histolytica infection diagnosis in Japan. [ABSTRACT FROM AUTHOR]

The management practices of liver abscess (LA) have evolved over time. The precise diagnosis of etiology and complications is pivotal for appropriate management. Descriptive analyses of consecutive patients treated for LA using electronic medical records at a liver unit between years 2010 and 2020 and investigate relationships between clinical, imaging, laboratory and microbiological findings, treatment strategies and mortality. Of 1630 LA patients, the most common aetiologies were amoebic liver abscess (ALA; 81%) and pyogenic liver abscess (PLA; 10.3%, mainly related to biliary disease and/or obstruction). Abdominal pain (86%) and fever (85.3%) were the commonest presenting symptoms (median duration—10 days). Almost 10% had jaundice at presentation, 31.1% were diabetic, 35.5% had chronic alcohol use and 3.3% had liver cirrhosis. Nearly 54% LA were solitary, 77.7% localized to the right liver lobe (most commonly segment VII/VIII). Patients with large LA (>10 cm, 11.9%) had more frequent jaundice and abscess rupture (p-0.01). Compared with ALA, patients with PLA were older, more often had multiple and bilobar abscesses with local complications. Over four-fifth of the patients received percutaneous interventions (catheter drainage [PCD; 36.1%] alone and needle aspiration [PNA] plus PCD [34.1%] as most common). Fifty-eight patients underwent endoscopic retrograde cholangiography for intrabiliary abscess rupture (n = 36) or cholangitic abscess (n = 22). The median duration of hospital stay and PCD were 7 (4–10) days and 5 (4–8 days), respectively. The overall in-hospital mortality was 1.1%. Presence of septic encephalopathy (HR: 20.8; 95% CI: 1.9–220.7; p-0.012), liver cirrhosis (HR: 20.1; 95% CI: 2.7–146.9; p-0.003) and jaundice (HR: 7.6; 95% CI:1.7–33.1; p-0.006) were independent predictors of mortality. The commonest presentation was middle age male with right lobe solitary ALA. Patients with large, bilobar and/or pyogenic abscess had more complications. Nearly 70% patients require percutaneous interventions, which if given early improve treatment outcomes. Presence of jaundice, liver cirrhosis and septic encephalopathy were independent predictors of mortality. [ABSTRACT FROM AUTHOR]

• Prevalence of asymptomatic IPI is much higher than that of symptomatic cases. • Prevalence of some symptomatic IPIs was reduced after OH intervention. • Knowledge, attitude, and practice significantly improved after OH intervention. • Holistic surveillance of humans, animals, and environment is vital for zoonotic IPIs. • OH or multisectorial collaboration is the key to form specific intervention for IPIs. [Display omitted] Tha Song Yang District, located on the Thai-Myanmar border, contributes to the second highest cases of amoebic dysentery due to intestinal parasitic infections (IPI). However, there were limited disease prevalence data, specific surveillance systems, and interventions available. This study aimed to explore the epidemiological features of the IPIs and apply the One Health (OH) approach to solve IPI-related problems. Prevalence of asymptomatic infections in human and animals, yearly symptomatic cases, and associated risk factors were investigated. The OH intervention included improving the knowledge, attitude, and practice (KAP) of the community, microscopic diagnosis training, and stakeholder engagement for IPI prevention designs. The prevalence of asymptomatic cases was much higher than that of the symptomatic cases. Infective stages of the intestinal parasites were discovered in animal stool and water samples, indicating possible transmission routes. One year after the intervention, there were significant declines in asymptomatic IPIs and symptomatic cases of amoebic dysentery. Significant improvements in KAP and awareness regarding water and manure-waste management of the community were observed. We reported the successful application of the OH intervention in reducing the IPI prevalence and mitigating disease-related risks. The intervention might be applied to address other infectious diseases in the future. [ABSTRACT FROM AUTHOR]

Free-living amoebas (FLA) are protozoan parasites that occasionally cause disease in humans after contact with contaminated water or soil. We describe a series of three cases of encephalitis in a family group with a fatal outcome that occurred in the Tumbes region between December 2019 and February 2020. Acanthamoeba sp. was identified in the cerebrospinal fluid sample from case 1. All three cases had a history of entering a swimming pool months before the disease. In the Tumbes region there is no previous record of encephalitis due to FLA and its occurrence in a family cluster has never been reported before. [ABSTRACT FROM AUTHOR]

Entamoeba histolytica is an intestinal parasite that causes dysentery and amebic liver abscess. E. histolytica has the capability to invade host tissue by union of virulence factor Gal/GalNAc lectin; this molecule induces an adherence-inhibitory antibody response as well as to protect against amebic liver abscess (ALA). The present work showed the effect of the immunization with PEΔIII-LC3-KDEL3 recombinant protein. In vitro, this candidate vaccine inhibited adherence of E. histolytica trophozoites to HepG2 cell monolayer, avoiding the cytolysis, and in a hamster model, we observed a vaccine-induced protection against the damage to tissue liver and the inhibition of uncontrolled inflammation. PEΔIII-LC3-KDEL3 reduced the expression of TNF-α, IL-1β, and NF-κB in all immunized groups at 4- and 7-day postinfection. The levels of IL-10, FOXP3, and IFN-γ were elevated at 7 days. The immunohistochemistry assay confirmed this result, revealing an elevated quantity of +IFN-γ cells in the liver tissue. ALA formation in hamsters immunized was minimal, and few trophozoites were identified. Hence, immunization with PEΔIII-LC3-KDEL3 herein prevented invasive amebiasis, avoided an acute proinflammatory response, and activated a protective response within a short time. Finally, this recombinant protein induced an increase of serum IgG. [ABSTRACT FROM AUTHOR]

Entamoeba histolytica is an intestinal parasite that causes dysentery and amebic liver abscess. E. histolytica has the capability to invade host tissue by union of virulence factor Gal/GalNAc lectin; this molecule induces an adherence-inhibitory antibody response as well as to protect against amebic liver abscess (ALA). The present work showed the effect of the immunization with PEΔIII-LC3-KDEL3 recombinant protein. In vitro, this candidate vaccine inhibited adherence of E. histolytica trophozoites to HepG2 cell monolayer, avoiding the cytolysis, and in a hamster model, we observed a vaccine-induced protection against the damage to tissue liver and the inhibition of uncontrolled inflammation. PEΔIII-LC3-KDEL3 reduced the expression of TNF-α, IL-1β, and NF-κB in all immunized groups at 4- and 7-day postinfection. The levels of IL-10, FOXP3, and IFN-γ were elevated at 7 days. The immunohistochemistry assay confirmed this result, revealing an elevated quantity of +IFN-γ cells in the liver tissue. ALA formation in hamsters immunized was minimal, and few trophozoites were identified. Hence, immunization with PEΔIII-LC3-KDEL3 herein prevented invasive amebiasis, avoided an acute proinflammatory response, and activated a protective response within a short time. Finally, this recombinant protein induced an increase of serum IgG. [ABSTRACT FROM AUTHOR]

Amebiasis is a neglected tropical disease which is caused by the protozoan parasite Entamoeba histolytica. This disease is one of the leading causes of diarrhea globally, affecting largely impoverished residents in developing countries. Amebiasis also remains one of the top causes of gastrointestinal diseases in returning international travellers. Despite having many side effects, metronidazole remains the drug of choice as an amebicidal tissue-active agent. However, emergence of metronidazole resistance in pathogens having similar anaerobic metabolism and also in laboratory strains of E. histolytica has necessitated the identification and development of new drug targets and therapeutic strategies against the parasite. Recent research in the field of amebiasis has led to a better understanding of the parasite’s metabolic and cellular pathways and hence has been useful in identifying new drug targets. On the other hand, new molecules effective against amebiasis have been mined by modifying available compounds, thereby increasing their potency and efficacy and also by repurposing existing approved drugs. This review aims at compiling and examining up to date information on promising drug targets and drug molecules for the treatment of amebiasis.

Entamoeba histolytica is an invasive enteric protozoan, whose infections are associated to high morbidity and mortality rates. However, only less than 10% of infected patients develop invasive amebiasis. The ability of E. histolytica to adapt to the intestinal microenvironment could be determinant in triggering pathogenic behavior. Indeed, during chronic inflammation, the vagus nerve limits the immune response through the anti-inflammatory reflex, which includes acetylcholine (ACh) as one of the predominant neurotransmitters at the infection site. Consequently, the response of E. histolytica trophozoites to ACh could be implicated in the establishment of invasive disease. The aim of this study was to evaluate the effect of ACh on E. histolytica virulence. Methods include binding detection of ACh to plasma membrane, quantification of the relative expression of virulence factors by RT-PCR and western blot, evaluation of the effect of ACh in different cellular processes related to E. histolytica pathogenesis, and assessment of the capability of E. histolytica to migrate and form hepatic abscesses in hamsters. Results demonstrated that E. histolytica trophozoites bind ACh on their membrane and show a clear increase of the expression of virulence factors, that were upregulated upon stimulation with the neurotransmitter. ACh treatment increased the expression of L220, Gal/GalNAc lectin heavy subunit (170 kDa), amebapore C, cysteine proteinase 2 (ehcp-a2), and cysteine proteinase 5 (ehcp-a5). Moreover, erythrophagocytosis, cytotoxicity, and actin cytoskeleton remodeling were augmented after ACh treatment. Likewise, by assessing the formation of amebic liver abscess, we found that stimulated trophozoites to develop greater hamster hepatic lesions with multiple granulomas. In conclusion, ACh enhanced parasite pathogenicity by upregulating diverse virulence factors, thereby contributing to disease severity, and could be linked to the establishment of invasive amebiasis.

Naegleria fowleri is a unicellular eukaryote causing primary amoebic meningoencephalitis, a neuropathic disease killing 99% of those infected, usually within 7-14 days. Naegleria fowleri is found globally in regions including the US and Australia. The genome of the related nonpathogenic species Naegleria gruberi has been sequenced, but the genetic basis for N. fowleri pathogenicity is unclear. To generate such insight, we sequenced and assembled the mitochondrial genome and a 60-kb segment of nuclear genome from N. fowleri. The mitochondrial genome is highly similar to its counterpart in N. gruberi in gene complement and organization, while distinct lack of synteny is observed for the nuclear segments. Even in this short (60-kb) segment, we identified examples of potential factors for pathogenesis, including ten novel N. fowleri-specific genes. We also identified a homolog of cathepsin B; proteases proposed to be involved in the pathogenesis of diverse eukaryotic pathogens, including N. fowleri. Finally, we demonstrate a likely case of horizontal gene transfer between N. fowleri and two unrelated amoebae, one of which causes granulomatous amoebic encephalitis. This initial look into the N. fowleri nuclear genome has revealed several examples of potential pathogenesis factors, improving our understanding of a neglected pathogen of increasing global importance.

Amebiasis is a neglected tropical disease which is caused by the protozoan parasite Entamoeba histolytica. This disease is one of the leading causes of diarrhea globally, affecting largely impoverished residents in developing countries. Amebiasis also remains one of the top causes of gastrointestinal diseases in returning international travellers. Despite having many side effects, metronidazole remains the drug of choice as an amebicidal tissue-active agent. However, emergence of metronidazole resistance in pathogens having similar anaerobic metabolism and also in laboratory strains of E. histolytica has necessitated the identification and development of new drug targets and therapeutic strategies against the parasite. Recent research in the field of amebiasis has led to a better understanding of the parasite's metabolic and cellular pathways and hence has been useful in identifying new drug targets. On the other hand, new molecules effective against amebiasis have been mined by modifying available compounds, thereby increasing their potency and efficacy and also by repurposing existing approved drugs. This review aims at compiling and examining up to date information on promising drug targets and drug molecules for the treatment of amebiasis. [ABSTRACT FROM AUTHOR]

The eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein and is essential in all eukaryotes. However, the specific roles of eIF5A in translation and in other biological processes remain elusive. In the present study, we described the role of eIF5A, its posttranslational modifications (PTM), and the biosynthetic pathway needed for the PTM in Entamoeba histolytica, the protozoan parasite responsible for amoebic dysentery and liver abscess in humans. E. histolytica encodes two isotypes of eIF5A and two isotypes of enzymes, deoxyhypusine synthase (DHS), responsible for their PTM. Both of the two eIF5A isotypes are functional, whereas only one DHS (EhDHS1, but not EhDHS2), is catalytically active. The DHS activity increased ~2000-fold when EhDHS1 was co-expressed with EhDHS2 in Escherichia coli, suggesting that the formation of a heteromeric complex is needed for full enzymatic activity. Both EhDHS1 and 2 genes were required for in vitro growth of E. histolytica trophozoites, indicated by small antisense RNA-mediated gene silencing. In trophozoites, only eIF5A2, but not eIF5A1, gene was actively transcribed. Gene silencing of eIF5A2 caused compensatory induction of expression of eIF5A1 gene, suggesting interchangeable role of the two eIF5A isotypes and also reinforcing the importance of eIF5As for parasite proliferation and survival. Furthermore, using a sibling species, Entamoeba invadens, we found that eIF5A1 gene was upregulated during excystation, while eIF5A2 was downregulated, suggesting that eIF5A1 gene plays an important role during differentiation. Taken together, these results have underscored the essentiality of eIF5A and DHS, for proliferation and potentially in the differentiation of this parasite, and suggest that the hypusination associated pathway represents a novel rational target for drug development against amebiasis. Author summary: Eukaryotic initiation factor 5A is a ubiquitous protein that is essential for cell proliferation. We examined the maturation, regulation, and function of eIF5A in E. histolytica. We found by small antisense RNA-mediated gene silencing that EhDHS1/2 and EheIF5A2 are essential for growth of E. histolytica trophozoites. We further found that only one of two isotypes of eIF5A, EheIF5A2, was constitutively expressed in the trophozoite stage and silencing of EheIF5A2 gene caused overexpression of the other eIF5A isotype (EheIF5A1) to partially rescue the growth defect in this parasite. Furthermore, we found that transcription of eIF5A1 gene was stage-specifically upregulated during excystation in E. invadens. Taken together, we have demonstrated for the first time that the two eIF5As play important and distinct roles in Entamoeba biology. This study has also provided an answer to a long-standing conundrum on the biological importance of polyamines: spermidine is needed for eIF5A hypusination, which is essential for protein translation in Entamoeba. Our work will provide an insight into the physiological significance of eIF5A and its post-translational modifications in other pathogenic eukaryotes and potentially lead to the formulation of control measures against parasitic diseases. [ABSTRACT FROM AUTHOR]

The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis, an infection that manifests as colitis and, in some cases, liver abscess. A better understanding of host protective factors is key to developing an effective remedy. Recently, significant advances have been made in understanding the mechanisms of MUC2 production by goblet cells upon amebic infection, regulation of antimicrobial peptide production by Paneth cells, the interaction of commensal microbiota with immune stimulation, and host genetics in conferring protection from amebiasis. In addition to host pathways that may serve as potential therapeutic targets, significant progress has also been made with respect to development of a vaccine against amebiasis. Here, we aim to highlight the current understanding and knowledge gaps critically. Vesicle-mediated exocytosis of MUC2 is critical in providing protection against tissue damage, and MUC2 regulates antimicrobial peptide production by Paneth cells during Entamoeba histolytica infection. While certain pathobionts can defend the ameba from oxidative stress in the colon, other commensal microbiota can protect the host by controlling the recruitment of neutrophils. Amebic infection downregulates interleukin (IL)-25 production in mice and humans. Exogenous treatment with IL-25 induces eosinophilia to confer protection. Children with a polymorphism in transcription factor cAMP response element modulator (CREM), and CREM knockout mice, are more susceptible to amebiasis. Vaccination with amebic surface protein LecA combined with Toll-like receptor (TLR)4 and TLR7/8 agonists induces a robust mucosal IgA, interferon (IFN)-γ, and IL-17a response to provide protection from amebiasis. [ABSTRACT FROM AUTHOR]

Entamoeba histolytica is an invasive enteric protozoan, whose infections are associated to high morbidity and mortality rates. However, only less than 10% of infected patients develop invasive amebiasis. The ability of E. histolytica to adapt to the intestinal microenvironment could be determinant in triggering pathogenic behavior. Indeed, during chronic inflammation, the vagus nerve limits the immune response through the anti-inflammatory reflex, which includes acetylcholine (ACh) as one of the predominant neurotransmitters at the infection site. Consequently, the response of E. histolytica trophozoites to ACh could be implicated in the establishment of invasive disease. The aim of this study was to evaluate the effect of ACh on E. histolytica virulence. Methods include binding detection of ACh to plasma membrane, quantification of the relative expression of virulence factors by RT-PCR and western blot, evaluation of the effect of ACh in different cellular processes related to E. histolytica pathogenesis, and assessment of the capability of E. histolytica to migrate and form hepatic abscesses in hamsters. Results demonstrated that E. histolytica trophozoites bind ACh on their membrane and show a clear increase of the expression of virulence factors, that were upregulated upon stimulation with the neurotransmitter. ACh treatment increased the expression of L220, Gal/GalNAc lectin heavy subunit (170 kDa), amebapore C , cysteine proteinase 2 (ehcp-a2), and cysteine proteinase 5 (ehcp-a5). Moreover, erythrophagocytosis, cytotoxicity, and actin cytoskeleton remodeling were augmented after ACh treatment. Likewise, by assessing the formation of amebic liver abscess, we found that stimulated trophozoites to develop greater hamster hepatic lesions with multiple granulomas. In conclusion, ACh enhanced parasite pathogenicity by upregulating diverse virulence factors, thereby contributing to disease severity, and could be linked to the establishment of invasive amebiasis. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to evaluate the present status of amoebiasis in Thi-Qar Province in southern Iraq, and to determine the presence of Entamoeba histolytica and Entamoeba dispar with nested and real-time polymerase chain reaction (PCR).Methods: Epidemiological data were obtained from the public health department of the Thi-Qar Health Office (2015-2020). Eighty stool samples were also randomly collected from patients ≤12 year of age with diarrhea at 2 hospitals between the beginning of February 2020 and the end of October 2020. These samples were selected after microscopy to identify the 18S rRNA gene in Entamoeba DNA.Results: Of the 341,554 cases of intestinal parasitic infections, 38,004 (11.1%) individuals were recorded as having amoebiasis, which accounted for the highest proportion of infections in 2015 (26.1%) and the lowest in 2020 (8.1%). Amoebiasis was distributed among all age groups, with the age group of 5-14 years accounting for the highest proportion (27.3%). In molecular testing, 42 (52.5%) out of 80 samples were positive for the 18S rRNA gene (888 bp). Using nested PCR, E. histolytica (439 bp) was detected in 25 (31.3%) samples and E. dispar (174 bp) in 14 (17.5%), while using real-time PCR, E. histolytica and E. dispar were detected in 28 (35.0%) and 15 (18.8%) samples, respectively.Conclusions: Epidemiological data confirmed that amoebiasis is endemic in this province, and is not limited to certain months. Our study confirms the applicability of molecular identification to detect pathogenic and non-pathogenic Entamoeba to prescribe the appropriate drug. [ABSTRACT FROM AUTHOR]

Bacground: Amoebiasis is a protazon infection of the human intestine spread through the world the most prevelant form of the disease is amebic dysenterywhich characterizes acute diarrhoea with observable blood and mucus in stools. Aims: This article aimed to detects the role of IL-25 and IL-35 in the immune response against amebic dysentery. Methods: This study was conducted in Thi-Qar province-Al-Nasiriyah city in Muhammad Al-Mousawi Hospital for Children, the study included collection of (60)blood samples from amebiasis patients and (30) apparently healthy children at a period from September 2019 to March 2020 with the age less than one year to 15 years that divides to four age groups, the levels of IL-25 and IL-35 were determined by ELISA technique. Results:The results indicate that the IL-25 and IL-35 concentrations in serum samples from amoebiasis patients were significantly higher when compared with that from healthy controls. The highest level of IL-25 was recordsin the third age group of patients with level 1677.2 ± 867.2ng /ml,compare with the high level in the third age group of control with level 450.40 ± 97.31ng /ml.Also, the findings indicates the highest level of IL-35 records35 in the second age group of patients with level 291.0 ± 62.3ng /ml, while the high level recorded in the first age group of control with level 8.246± 0.60 ng /ml. [ABSTRACT FROM AUTHOR]

Amebiasis is an important cause of diarrheal disease worldwide and has been associated with childhood malnutrition. E.histolytica diagnosed usually by microscope, which consider as traditional diagnosis and are neither sensitive nor specific detection of Entamoeba histolytica(1). Real-time PCR assay developed for sensitive and specific detection of the intestinal Protozoan parasites Entamoeba histolytica directly from human feces(2). The RT-PCR assay was able to detect as little as 0.1 parasite per g of feces(3). The current study based on Phosphoglycerate kinase gene (PGK) is a major enzyme used in glycolysis, in the first ATPgenerating step of the glycolytic pathway so the PGK is an enzyme that catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate (1,3-BPG) to ADP producing 3-phosphoglycerate (3-PG) and ATP(4). In our study, depend on PGK as target for Real time PCR assay for detection the trophozoite stage of E.histolytica in stool samples of infected persons. In the current study, a total of 300 human fecal samples were collected from children (less than one year-15 year) that suspected to infection with amoebiasis which admitted to hospitals and primary care centers in the city center, Al-Hindiya district and Nahiat Al-Hurr (100 samples from each region) during the period from February 2019 to January 2020. Fecal samples processed by direct wet smear and formalin ethyl acetate concentration method followed by iodine staining and was microscopically examined for E.histolytica. Microscopically positive samples were then subject to Real-time PCR. This is the first study in Iraq using the Phosphoglyceratekinase gene as target for molecular techniques to determine the presence of E. histolytica trophozoites in stool samples. [ABSTRACT FROM AUTHOR]

Amebic liver abscess (ALA) is still a common problem in the tropical world, where it affects over three-quarters of patients with liver abscess. It is caused by an anaerobic protozoan Entamoeba hystolytica , which primarily colonises the cecum. It is a non-suppurative infection of the liver consisting primarily of dead hepatocytes and cellular debris. People of the male gender, during their reproductive years, are most prone to ALA, and this appears to be due to a poorly mounted immune response linked to serum testosterone levels. ALA is more common in the right lobe of the liver, is strongly associated with alcohol consumption, and can heal without the need for drainage. While majority of ALA patients have an uncomplicated course, a number of complications have been described, including rupture into abdomino-thoracic structures, biliary fistula, vascular thrombosis, bilio-vascular compression, and secondary bacterial infection. Based on clinico-radiological findings, a classification system for ALA has emerged recently, which can assist clinicians in making treatment decisions. Recent research has revealed the role of venous thrombosis-related ischemia in the severity of ALA. Recent years have seen the development and refinement of newer molecular diagnostic techniques that can greatly aid in overcoming the diagnostic challenge in endemic area where serology-based tests have limited accuracy. Metronidazole has been the drug of choice for ALA patients for many years. However, concerns over the resistance and adverse effects necessitate the creation of new, safe, and potent antiamebic medications. Although the indication of the drainage of uncomplicated ALA has become more clear, high-quality randomised trials are still necessary for robust conclusions. Percutaneous drainage appears to be a viable option for patients with ruptured ALA and diffuse peritonitis, for whom surgery represents a significant risk of mortality. With regard to all of the aforementioned issues, this article intends to present an updated review of ALA., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: The aim of the study was to evaluate the efficiency of mimivirus as a potential therapeutic and prophylactic tool against Acanthamoeba castellanii, the etiological agent of Acanthamoeba keratitis, a progressive corneal infection, that is commonly associated with the use of contact lenses and can lead to blindness if not properly treated., Methods and Results: Mimivirus particles were tested in different multiplicity of infection, along with commercial multipurpose contact lenses' solutions, aiming to assess their ability to prevent encystment and excystment of A. castellanii. Solutions were evaluated for their amoebicidal potential and cytotoxicity in MDCK cells, as well as their effectiveness in preventing A. castellanii damage in Madin-Darby canine kidney (MDCK) cells. Results indicated that mimivirus was able to inhibit the formation of A. castellanii cysts, even in the presence of Neff encystment solution. Mimivirus also showed greater effectiveness in controlling A. castellanii excystment compared to commercial solutions. Additionally, mimivirus solution was more effective in preventing damage caused by A. castellanii, presented greater amoebicidal activity, and were less cytotoxic to MDCK cells than commercial MPS., Conclusions: Mimivirus demonstrates a greater ability to inhibit A. castellanii encystment and excystment compared to commercial multipurpose contact lens solutions. Additionally, mimivirus is less toxic to MDCK cells than those commercial solutions. New studies utilizing in vivo models will be crucial for confirming safety and efficacy parameters., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary Amebiasis is rarely encountered in the United States, and when it is, it is usually seen in individuals who have migrated from endemic areas. Travelers who spend less than a month in an endemic area rarely acquire intestinal amebiasis. Although amebic dysentery can occur, presenting with diarrhea and bloody stools, most (approximately 90%!) Entamoeba infections are asymptomatic. The current case occurred in a patient from an endemic area, but with an important list of comorbid conditions, including renal failure managed with hemodialysis, as well as diabetes. Notably in this case, the patient did not have any GI symptoms, and it was an abnormal positron emission tomography scan that led to the diagnosis of amebic colitis with multiple masslike lesions. It is known that kidney failure as well as diabetes can negatively affect general immunity, increasing susceptibility to infection. It is likely that this patient’s comorbidities contributed to the unusual clinical presentation of this parasitic infection of the colon. David Diehl, MD, GIE Senior Associate Editor Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

The aim of this study is to provide an overview of the geographical distribution of Ascariasis, Amebiasis and Giardiasis, and to identify specific geographical, socioeconomic and environmental factors that are associated with the incidence of these infections in Mexican children. We made use of publicly available data that was reported by federal organizations in Mexico for the year 2010. The contribution of geographical, socioeconomic and environmental factors to the incidence of infections was assessed by a multivariable regression model using a backwards selection procedure. A. lumbricoides incidence was associated with mean minimum temperature of the state, the state-wide rate of households without access to piped water and toilet, explaining 77% of the incidence of A. lumbricoides infections. Mean minimum precipitation in the state, the rate of households without access to a toilet, piped water and sewage system best explained (73%) the incidence of E. histolytica infections. G. lamblia infections were only explained by the latitude of the state (11%). In addition to the well-known socioeconomic factors contributing to the incidence of A. lumbricoides and E. histolytica we found that temperature and precipitation were associated with higher risk of infection. [ABSTRACT FROM AUTHOR]

Entamoeba histolytica infects 50 million people worldwide and causes 55 thousand fatalities every year. Current anti-amebic drugs (e.g. paromomycin) work either at the level of the intestinal lumen (where trophozoites proliferate via cell divisions) or on the invasive trophozoites that have penetrated the gut or colonized internal organs (e.g. metronidazole). Some of these drugs are highly toxic to patients, have generated trophozoite resistance, or caused mutations and cancer in laboratory animals. Thus, alternative anti-amebic compounds need to be identified to minimize the side effects (on patients) or resistance (by amebas) to current treatments. The literature suggests that anthraquinones (chemicals found in medicinal plants) have antibacterial, antiparasitic, anti-inflammatory and antioxidant properties. Here we provide experimental evidence that Chinese rhubarb (Rheum palmatum) leaves' extract (rich in the anthraquinone rhein) inhibits E. histolytica trophozoite growth in vitro. In addition, from a set of ten isolated/synthetic anthraquinones (which we suspected to have anti-amebic properties), four analogs (rhein; AHHDAC = 1-amino-4-hydroxy-9, 10-dioxo-9, 10-dihydro-anthracene-2-carboxylic acid; unisol blue AS; and sennoside B) efficiently inhibited amebic growth at EIC50 concentrations comparable to metronidazole. The mechanism of action of these compounds still needs to be determined, although anthraquinones might enhance the production of toxic oxygen metabolites as it has been suggested for various protists (e.g. Leishmania, Plasmodium, Trypanosoma). Our research is the first to explore anti-amebic effects of Chinese rhubarb leaves' extract and isolated/synthetic anthraquinones on pathogenic Entamoeba.

Abstract Background Primary pulmonary amoeba is very rare and here we report a case of a 68-year-old man presenting with primary pulmonary amoeba after undergoing chemotherapy for lung adenocarcinoma. Case presentation In October 2016, the man aged 68 was admitted to our hospital because of repeated cough for 8 months and hemoptysis for 1 month. He was diagnosed lung adenocarcinoma and underwent surgery in 2012 without receiving chemotherapy. In March 2016, the patients suffered recurrence of cancer and was treated with chemotherapy. After 2 months of chemotherapy, the patient had consistent cough with white sputum, and chest CT showed a local lung nodule. The physicians suspected that the patient had pulmonary infectious diseases, and he was treated with empirical antibacterial treatment. However, his symptom wasn’t relieved and later the percutaneous lung biopsy found trophozites of Entamoeba histolytica. After administration of metronidazole, the symptoms of the patient were markedly relieved and the lesions were absorbed. Conclusions In such cases where patients with pulmonary nodules were in immunodeficiency state and had adequate but ineffective anti-bacterial treatment, Entamoeba histolytica infection could be one of the rare causes. Percutaneous lung biopsy should be recommended and specific dying for parasites should be done when necessary.

In an effort to develop novel antiamoebic scaffolds having better efficacy than the standard drug metronidazole (IC50 = 1.80 μM) used against Entamoeba histolytica, quinazolin-4(3H)-one Schiff base conjugates were synthesized and evaluated against HM1: IMSS strain of E. histolytica. Out of the thirteen compounds (S2-S14), six compounds (S2, S3, S4, S5, S6 and S11) were found to be better inhibitors than metronidazole and showed low cytotoxicity on HeLa cells, a cervical cancer cell line. The structure of intermediate compound S1 was confirmed by crystal structure studies.

Amebiasis is a common protozoan disease with a worldwide distribution. It is endemic in tropical developing countries, and cases are being detected in subtropical countries as well. It usually presents with intestinal manifestations. An extraintestinal manifestation of this disease, amebic vaginitis and amebic cervicitis, is rare and often misinterpreted clinically as vaginal and cervical carcinoma because of its overall ulcerated and necrotic appearance. Awareness of this rare manifestation is important for preventing unnecessary interventions and for effectively managing the patients with antiamebic treatment. Herewith, we report three cases of amebic vulvovaginitis and cervicitis in elderly women clinically masquerading as carcinomas.