Multi-locus sequence analysis reveals phylogenetically segregated Entamoeba histolytica population.

Amoebiasis, caused by the enteric parasite, Entamoeba histolytica, is one of the major food- and water-borne parasitic diseases in developing countries with improper sanitation and poor hygiene. Infection with E. histolytica has diverse disease outcomes, which are determined by the genetic diversity of the infecting strains. Comparative genetic analysis of infecting E. histolytica strains associated with differential disease outcomes from different geographical regions of the world is important to identify the specific genetic patterns of the pathogen that trigger certain disease outcomes of Amoebiasis. The strategy is able to elucidate the genealogical relation and population structure of infecting E. histolytica strains from different geographical regions. In the present study, we have performed a comparative genetic analysis of circulating E. histolytica strains identified from different parts of the world, including our study region, based on five tRNA-linked short tandem repeat (STR) loci (i.e., D-A, NK2, R-R, STGA-D and A-L) and evaluated their potential associations with differential disease outcomes of Amoebiasis. A number of regional-specific, emerging haplotypes of E. histolytica, significantly associated with specific disease outcomes have been identified. Haplotypes, which have a significant positive association with asymptomatic and amoebic liver abscess outcomes, showed a significant negative association with diarrheal outcome, or vice versa. Comparative multi-locus analysis revealed that E. histolytica isolates from our study region are phylogenetically segregated from the isolates of other geographical regions. This study provides a crucial overview of the population structure and emerging pattern of the enteric parasite, E. histolytica.

Amoebiasis: Advances in Diagnosis, Treatment, Immunology Features and the Interaction with the Intestinal Ecosystem.

This review of human amoebiasis is based on the most current knowledge of pathogenesis, diagnosis, treatment, and Entamoeba/microbiota interactions. The most relevant findings during this last decade about the Entamoeba parasite and the disease are related to the possibility of culturing trophozoites of different isolates from infected individuals that allowed the characterization of the multiple pathogenic mechanisms of the parasite and the understanding of the host-parasite relationship in the human. Second, the considerable advances in molecular biology and genetics help us to analyze the genome of Entamoeba, their genetic diversity, and the association of specific genotypes with the different amoebic forms of human amoebiasis. Based on this knowledge, culture and/or molecular diagnostic strategies are now available to determine the Entamoeba species and genotype responsible for invasive intestinal or extraintestinal amoebiasis cases. Likewise, the extensive knowledge of the immune response in amoebiasis with the appearance of new technologies made it possible to design diagnostic tools now available worldwide. Finally, the understanding of the interaction between the Entamoeba species and the intestinal microbiota aids the understanding of the ecology of this parasite in the human environment. These relevant findings will be discussed in this review.

The Gal/GalNac lectin as a possible acetylcholine receptor in Entamoeba histolytica.

Entamoeba histolytica (E. histolytica) is a protozoan responsible for intestinal amebiasis in at least 500 million people per year, although only 10% of those infected show severe symptoms. It is known that E. histolytica captures molecules released during the host immune response through membrane receptors that favor its pathogenetic mechanisms for the establishment of amebic invasion. It has been suggested that E. histolytica interacts with acetylcholine (ACh) through its membrane. This promotes the increase of virulence factors and diverse mechanisms carried out by the amoeba to produce damage. The aim of this study is to identify a membrane receptor in E. histolytica trophozoites for ACh. Methods included identification by colocalization for the ACh and Gal/GalNAc lectin binding site by immunofluorescence, western blot, bioinformatic analysis, and quantification of the relative expression of Ras 5 and Rab 7 GTPases by RT-qPCR. Results show that the Gal/GalNAc lectin acts as a possible binding site for ACh and this binding may occur through the 150 kDa intermediate subunit. At the same time, this interaction activates the GTPases, Ras, and Rab, which are involved in the proliferation, and reorganization of the amoebic cytoskeleton and vesicular trafficking. In conclusion, ACh is captured by the parasite, and the interaction promotes the activation of signaling pathways involved in pathogenicity mechanisms, contributing to disease and the establishment of invasive amebiasis.

Updates on the worldwide burden of amoebiasis: A case series and literature review.

BACKGROUND: Amoebiasis is an intestinal and tissue parasitic infection caused by the protozoan Entamoeba histolytica. Despite significant medical importance and worldwide dispersion, little is known about the epidemiology and distinct geographical distribution of various clinical forms of amoebiasis in the world. In this study, we present an amoebiasis case series referred to Avicenne Hospital (Bobigny, France) from 2010 to 2022 followed by an overview of the released literature to explore diverse clinico-pathology of amoebiasis and to update the actual epidemiological situation of this parasitosis worldwide. METHODS: The referred patients underwent a combination of clinical and parasitological examinations and imaging. The study was followed by an overview of released literature performed based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. RESULTS: A total of 15 patients with amoebiasis were diagnosed with an average age of 48.5 years old at the occurrence time of infection. Men (78%) were the most affected patients. Most of the cases were reported following a trip to endemic regions, such as Mali, India, Nepal, Algeria, Cameroon or Congo. All of the processed patients exhibited a hepatic amoebiasis. Amoebic abscess was observed in all cases with an average size of 6.3 cm. Of these patients, seven cases (46.7%) benefited from drainage following a risk of rupture or superinfection of the abscess. A compilation of findings extracted from 390 scientific publications via seven major medical databases, allowed us to update the main epidemiological and clinical events that has led to the current worldwide expansion of amoebiasis. We presented a clinical and epidemiological overview of the amoebiasis accompanied with a worldwide illustrative map displaying the current distribution of known amoebiasis foci in each geographical ecozone of Asia, Europe, Africa, Americas, and Australia. CONCLUSIONS: Although Metropolitan France is not known as an endemic region of amoebiasis, amoebic liver abscess was the most frequent clinical form observed among our 15 patients processed. Most of infected patients had a history of travel to or lived-in endemic areas before arriving in France.

An Unusual U2AF2 Inhibits Splicing and Attenuates the Virulence of the Human Protozoan Parasite Entamoeba histolytica.

E. histolytica is the etiological agent of intestinal amebiasis and liver abscesses, which still poses public health threat globally. Metronidazole is the drug of choice against amebiasis. However, metronidazole-resistant amoebic clinical isolates and strains have been reported recently, challenging the efforts for amebiasis eradication. In search of alternative treatments, E. histolytica transcriptomes have shown the association of genes involved in RNA metabolism with the virulence of the parasite. Among the upregulated genes in amoebic liver abscesses are the splicing factors EhU2AF2 and a paralog of EhSF3B1. For this reason and because EhU2AF2 contains unusual KH-QUA2 (84KQ) motifs in its lengthened C-terminus domain, here we investigated how the role of EhU2AF2 in pre-mRNA processing impacts the virulence of the parasite. We found that 84KQ is involved in splicing inhibition/intron retention of several virulence and non-virulence-related genes. The 84KQ domain interacts with the same domain of the constitutive splicing factor SF1 (SF1KQ), both in solution and when SF1KQ is bound to branchpoint signal RNA probes. The 84KQ-SF1KQ interaction prevents splicing complex E to A transition, thus inhibiting splicing. Surprisingly, the deletion of the 84KQ domain in EhU2AF2 amoeba transformants increased splicing and enhanced the in vitro and in vivo virulence phenotypes. We conclude that the interaction of the 84KQ and SF1KQ domains, probably involving additional factors, tunes down Entamoeba virulence by favoring intron retention.

Distribution of Intestinal Parasites Detected between September 2011-2018 at Dokuz Eylül University Medical Faculty Hospital.

OBJECTIVE: Intestinal parasitic diseases are important public health problems in our country as well as in the world. In this study, intestinal parasites were investigated in patients admitted to Dokuz Eylül University Hospital (DEUH) with various gastrointestinal system complaints. METHODS: Patients (n=18460) who were referred to the DEUH Central Parasitology Laboratory between January 2011 and December 2018, were included in the study. Fecal samples were examined with Nativ-lugol method and then formol ethyl-acetate precipitation method was applied. Trichrome and kinyoun acid-fast stainings were performed on the necessary samples. Demographic data of the patients were obtained from the hospital's and laboratory's information operating system. RESULTS: One or more parasites were detected in 6% (1128) of 18460 patients examined. The mean age of the patients with parasites was 39.7 (±23.1) years, of which 53.3% were male and 47.6% were female. The distribution of parasites detected were as follows; 4.8% (879) Blastocystis hominis, 0.7% (135) amoebas other than Entamoeba histolytica/dispar, 0.4% (70) Giardia intestinalis, 0.3% (49) Enterebius vermicularis, 0.1% (21) Entamoeba histolytica/dispar, and 0.01% (10) other rare parasites. CONCLUSION: Our study shows that intestinal parasitic infections are still an important public health problem in our region and that there is a decrease in their incidence.

Intestinal amoebiasis: 160 years of its first detection and still remains as a health problem in developing countries.

Amoebiasis is a parasitic disease caused by Entamoeba histolytica (E. histolytica), an extracellular enteric protozoan. This infection mainly affects people from developing countries with limited hygiene conditions, where it is endemic. Infective cysts are transmitted by the fecal-oral route, excysting in the terminal ileum and producing invasive trophozoites (amoebae). E. histolytica mainly lives in the large intestine without causing symptoms; however, possibly as a result of so far unknown signals, the amoebae invade the mucosa and epithelium causing intestinal amoebiasis. E. histolytica possesses different mechanisms of pathogenicity for the adherence to the intestinal epithelium and for degrading extracellular matrix proteins, producing tissue lesions that progress to abscesses and a host acute inflammatory response. Much information has been obtained regarding the virulence factors, metabolism, mechanisms of pathogenicity, and the host immune response against this parasite; in addition, alternative treatments to metronidazole are continually emerging. An accesible and low-cost diagnostic method that can distinguish E. histolytica from the most nonpathogenic amoebae and an effective vaccine are necessary for protecting against amoebiasis. However, research about the disease and its prevention has been a challenge due to the relationship between E. histolytica and the host during the distinct stages of the disease is multifaceted. In this review, we analyze the interaction between the parasite, the human host, and the colon microbiota or pathogenic microorganisms, which together give rise to intestinal amoebiasis.

Tinidazole efficacy for amebic colitis therapeutic prophylaxis in patients with de novo acute leukemia receiving intensive chemotherapy.

INTRODUCTION: In Mexico, seroprevalence of Entamoeba histolytica is 8.4%. The intestinal amebiasis in patients with acute leukemia of novo, after the start of chemotherapy (CT) in the Hematology Service of the CMN 20 de Noviembre is 12%, even if patients show a negative baseline coprological test. OBJECTIVE: To find out if the administration of tinidazole, in patients with acute leukemia and negative coprological test, at the beginning of the CT, decreases the incidence of amoebic colitis during the induction to remission. METHOD: Prospective and not comparative study. Patients with de novo diagnosis of acute leukemia who initiate induction and initial coprological CT. Tinidazole was indicated, 2 g/day for 5 days in the first week of CT started. They were monitored until the induction was concluded and hematopoietic recovery started. RESULTS: 38 patients, 15 women and 23 men with a mean age of 44 years (16-72), with acute lymphoblastic leukemia 19, myeloblastic 16 and promyelocytic 3. Cases without and with intestinal amebiasis were 35 and 3, respectively. Patients with amebiasis only received tinidazole for 3 days and it was given 2 days after the CT started. CONCLUSION: Tinidazole, in patients with acute de novo leukemia who initiate induction CT, is effective in the prevention of intestinal amebiasis, during the induction stage, if administered at 2 g/day, for five days, starting on day 1 of the CT.

Host-antibody inductivity of virulent Entamoeba histolytica and non-virulent Entamoeba moshkovskii in a mouse model.

BACKGROUND: Despite similarities in morphology, gene and protein profiles, Entamoeba histolytica and E. moshkovskii show profound differences in pathogenicity. Entamoeba histolytica infection might result in amoebic dysentery and liver abscess, while E. moshkovskii causes only mild diarrhea. Extensive studies focus on roles of host immune responses to the pathogenic E. histolytica; however, evidence for E. moshkovskii remains scarce. METHODS: To study differences in host-antibody response profiles between E. histolytica and E. moshkovskii, mice were immunized intraperitoneally with different sets of Entamoeba trophozoites as single species, mixed species and combinations. RESULTS: Mice prime-immunized with E. histolytica and E. moshkovskii combination, followed by individual species, exhibited higher IgG level than the single species immunization. Mice immunized with E. moshkovskii induced significantly higher levels and long-lasting antibody responses than those challenged with E. histolytica alone. Interestingly, E. histolytica-specific anti-sera promoted the cytopathic ability of E. histolytica toward Chinese hamster ovarian (CHO) cells, but showed no effect on cell adhesion. There was no significant effect of immunized sera on cytopathic activity and adhesion of E. moshkovskii toward both CHO and human epithelial human colonic (Caco-2) cell lines. Monoclonal-antibody (mAb) characterization demonstrated that 89% of E. histolytica-specific mAbs produced from mice targeted cytoplasmic and cytoskeletal proteins, whereas 73% of E. moshkovskii-specific mAbs targeted plasma membrane proteins. CONCLUSIONS: The present findings suggest that infection with mixed Entamoeba species or E. moshkovskii effectively induces an antibody response in mice. It also sheds light on roles of host antibody response in the pathogenic difference of E. histolytica and E. moshkovskii trophozoites, and cell surface protein modifications of the amoebic parasites to escape from host immune system.

Antiamoebic drugs for treating amoebic colitis.

BACKGROUND: Infection with the protozoan Entamoeba histolytica is common in low- and middle-income countries, and up to 100,000 people with severe disease die every year. Adequate therapy for amoebic colitis is necessary to reduce illness, prevent development of complicated disease and extraintestinal spread, and decrease transmission. OBJECTIVES: To evaluate antiamoebic drugs for treating amoebic colitis. SEARCH METHODS: We searched the available literature up to 22 March 2018. We searched the Cochrane Infectious Diseases Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, mRCT, and conference proceedings. We contacted individual researchers, organizations, and pharmaceutical companies, and we checked reference lists. SELECTION CRITERIA: Randomized controlled trials of antiamoebic drugs given alone or in combination, compared with placebo or another antiamoebic drug, for treating adults and children with a diagnosis of amoebic colitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and methodological quality of trials and extracted and analysed the data. We calculated clinical and parasitological failure rates and rates of relapse and adverse events as risk ratios (RRs) with 95% confidence intervals (CIs), using a random-effects model. We determined statistical heterogeneity and explored possible sources of heterogeneity using subgroup analyses. We carried out sensitivity analysis by using trial quality to assess the robustness of reported results. MAIN RESULTS: In total, 41 trials (4999 participants) met the inclusion criteria of this review. In this update, we added four trials to the 37 trials included in the first published review version. Thirty trials were published over 20 years ago. Only one trial used adequate methods of randomization and allocation concealment, was blinded, and analysed all randomized participants. Only one trial used an E histolytica stool antigen test, and two trials used amoebic culture.Tinidazole may be more effective than metronidazole for reducing clinical failure (RR 0.28, 95% CI 0.15 to 0.51; 477 participants, eight trials; low-certainty evidence) and is probably associated with fewer adverse events (RR 0.65, 95% CI 0.46 to 0.92; 477 participants, 8 trials; moderate-certainty evidence). Compared with metronidazole, combination therapy may result in fewer parasitological failures (RR 0.36, 95% CI 0.15 to 0.86; 720 participants, 3 trials; low-certainty evidence), but we are uncertain which combination is more effective than another. Evidence is insufficient to allow conclusions regarding the efficacy of other antiamoebic drugs. AUTHORS' CONCLUSIONS: Compared with metronidazole, tinidazole may be more effective in reducing clinical failure and may be associated with fewer adverse events. Combination drug therapy may be more effective for reducing parasitological failure compared with metronidazole alone. However, these results are based mostly on small trials conducted over 20 years ago with a variety of poorly defined outcomes. Tests that detect E histolytica more accurately are needed, particularly in countries where concomitant infection with other bacteria and parasites is common.

A case of amoebic colitis with amoeboma and simultaneous liver abscesses. A diagnosis by colonoscopy.

A 50-year-old patient was admitted to our department after developing severe abdominal cramps, watery diarrhea and fever, during four days whilst travelling abroad. Imaging identified a mass in the ascending colon with simultaneous liver lesions. Initially a diagnosis of metastatic colorectal cancer was suggested, however colonoscopy showed a large lesion with a central ulcer and surrounding inflammation in the ascending colon. Biopsies confirmed our clinical suspicion of amoebic colitis, complicated by development of an amoeboma and simultaneous liver abscesses. Amoeboma formation is a rare complication of amoebiasis, however a simultaneous presentation with liver abscesses, amoebic colitis and an amoeboma might even be less frequent. Despite its rarity physicians should maintain a high index of suspicion of patients presenting with synchronous liver and colon lesions, especially as travel to endemic areas has increased.

Update on laboratory diagnosis of amoebiasis.

Amoebiasis, an enteric protozoan disease caused by Entamoeba histolytica, is a public health problem in many developing countries, causing up to 100,000 fatal cases annually. Detection of the pathogenic E. histolytica and its differentiation from the non-pathogenic Entamoeba spp. play a crucial role in the clinical management of patients. Laboratory diagnosis of intestinal amoebiasis in developing countries still relies on labour-intensive and insensitive methods involving staining of stool sample and microscopy. Newer and more sensitive methods include a variety of antigen detection ELISAs and rapid tests; however, their diagnostic sensitivity and specificity seem to vary between studies, and some tests do not distinguish among the Entamoeba species. Molecular detection techniques are highly sensitive and specific and isothermal amplification approaches may be developed into field-applicable tests; however, cost is still a barrier for their use as a routine laboratory test method in most endemic areas. Laboratory diagnosis of extraintestinal amoebiasis faces challenges of lack of definitive detection of current infection and commercially available point-of-care tests. For both types of amoebiasis, there is still a need for highly sensitive and specific tests that are rapid and cost-effective for use in developing countries where the disease is prevalent. In recent years, new molecules of diagnostic value are being discovered and new tests developed. The advances in 'omics' technologies are enabling discoveries of new biomarkers that may help distinguish between different infection stages.

Entamoeba Histolytica: Updates in Clinical Manifestation, Pathogenesis, and Vaccine Development.

Entamoeba histolytica is the responsible parasite of amoebiasis and remains one of the top three parasitic causes of mortality worldwide. With increased travel and emigration to developed countries, infection is becoming more common in nonendemic areas. Although the majority of individuals infected with E. histolytica remain asymptomatic, some present with amoebic colitis and disseminated disease. As more is learned about its pathogenesis and the host's immune response, the potential for developing a vaccine holds promise. This narrative review outlines the current knowledge regarding E. histolytica and E. dispar and insight in the development of a vaccine.

Amebiasis intestinal y hepática / Intestinal and hepatic amebiasis

Amebiasis is the infection by Entamoeba histolytica, a protozoan capable of invading the colonic mucosa causing a diarrheic syndrome, although most of the time is mild, it can lead to a fulminating colitis. Sometimes it can spread to other organs; among extra-intestinal manifestations of this parasite, the most frequent is the amebic liver abscess. In the next pages, general aspects of this protozoan, its epidemiology, clinical findings, diagnosis and treatment are reviewed, emphasizing the possibilities of diagnosis and treatment available in Chile.

La amebiasis corresponde a la infección por Entamoeba histolytica, protozoo capaz de invadir la mucosa del colon provocando un cuadro diarréico que, si bien la mayoría de las veces es leve, puede llegar a una colitis fulminante. En algunas oportunidades puede diseminarse a otros órganos; dentro de las manifestaciones extra-intestinales de este parásito, la más frecuente es el absceso hepático amebiano. A continuación se revisan aspectos generales de este protozoo, su epidemiología, cuadro clínico, diagnóstico y tratamiento, destacando las posibilidades de diagnóstico y tratamiento disponibles en Chile.

IL-17A contributes to reducing IFN-γ/IL-4 ratio and persistence of Entamoeba histolytica during intestinal amebiasis.

Amebiasis is an infectious disease caused by Entamoeba histolytica, an anaerobic protozoan parasite, and is a major public health problem worldwide, particularly in areas with inadequate sanitation and poor hygiene. Th1 responses, represented by interferon gamma (IFN-γ), play a protective role by clearing the amebae from the gut, whereas Th2 responses are responsible for chronic infection. Th17 responses preconditioned by vaccination or by modulating the intestinal microbiome protect mice from the settlement of E. histolytica. However, the role of interleukin-17A (IL-17A), which is upregulated during the natural course of intestinal amebiasis, has not been clarified. The aim of this study was to investigate the role of IL-17A during intestinal amebiasis in a mouse model. IL-17A knockout and wild-type CBA/J mice were challenged intracecally with 2×106E. histolytica trophozoites, and their infection, pathology, and immune responses were monitored. Neither the initial settlement of E. histolytica nor the inflammation of the cecum was affected by the absence of IL-17A for week 1, but the infection rate and parasite burden declined in a late stage of infection, accompanied by an increased IFN-γ/IL-4 ratio. Therefore, IL-17A contributes to the persistence of E. histolytica and modulates the immune response, including the IFN-γ/IL-4 ratio, which may be responsible for the reduction of the parasite burden in the IL-17A knockout mice during the chronic phase of intestinal amebiasis.