A new approach to the treatment of acute infection diseases with antibiotic-pectin formulae.

INTRODUCTION: Intestinal infections are a significant health issue; antibiotics are essential in treating acute intestinal infections. However, evidence in the literature shows that the excessive use of antibiotics has created many threats to human health. This work aimed to study the impact of apple pectin in combination with antibiotics on treating patients with amebiasis and dysentery. METHODOLOGY: Patients suffering from acute intestinal diseases (amebiasis and dysentery) were treated with traditional antibiotic therapy and a new formula containing antibiotics with low and high methoxylated apple pectin in a randomized block design. Four clinical trials were performed at the Infection Disease Hospital from 1998 until 2013. RESULTS: The study demonstrated that the antibiotic-pectin formulae (APF) significantly reduced the severity of acute intestinal infection diseases and allowed patients to recover faster than conventional treatment. APF reduced the patient's stay in the hospital by 3.0 ± 1.0 days. The clinical trial findings demonstrated that applying APF in intestinal infection diseases helped maintain a constant concentration of the antibiotic in the blood and accelerated the clinical recovery of the patients. CONCLUSIONS: It was concluded that using pectin with antibiotics could improve clinical outcomes in patients with acute infectious diseases. Research on elucidating the mechanisms of pectin digestion in the colon, polyphenol content, and its role in dysbiosis recovery, etc., is also considered.

A case report of refractory amebic colitis and literature review.

RATIONALE: Amebic colitis has been less prevalent in recent times in China, and the similarity of its symptoms to those of inflammatory bowel disease (IBD) results in the difficulty of early identification and diagnosis. PATIENT CONCERNS: A 31-year-old male who exhibited intermittent diarrhea and hematochezia was highly suspected as IBD initially. Despite the partial relief of symptoms following the administration of mesalamine, the endoscopic ulcers remained largely unchanged. DIAGNOSES: Two years after the onset of mesalamine therapy, amebic cysts were detected in stool microscopy and trophozoites were found on the surface of cecal ulcers. The patient was then diagnosed with amebic colitis. INTERVENTIONS: After 2 rounds of standardized metronidazole treatment, amebic colitis remained refractory until diloxanide was administered. OUTCOMES: The patient remained asymptomatic, and the mucosa of colon was normal during the annual follow-up. LESSONS: Individuals newly diagnosed with IBD should undergo essential screening for amebiasis. And the use of steroids should be taken with caution, especially in cases where the effect of mesalamine is limited. For symptomatic intestinal amebiasis, even after the administration of tissue amebicides, the continued use of luminal amebicides is necessary to prevent recurrence.

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.

Amoebic colitis and liver abscess: A rare case of autochthonous invasive infection due to Entamoeba histolytica.

We report an unusual and confirmed case of invasive amebiasis in a non-endemic area where the source of infection remains unknown. During her admission, the patient developed amebic colitis and extraintestinal liver abscess with a favorable outcome following the antiparasitic therapy.

Effects of Serum Antibody Test Reagent Discontinuation on Diagnosis of Amebiasis in Japan: Interrupted Time-Series Analysis.

Amebiasis is a notifiable infectious disease in Japan, and the number of reported cases had been on the rise, but since the discontinuation of insurance-covered serum antibody testing reagent in 2017, concerns have arisen regarding the decrease in reported cases. This study aimed to investigate changes occurring after discontinuation of the serum antibody test reagent production. We retrospectively analyzed amebiasis cases from January 2014 to December 2019 using the National Center for Epidemiology of Infectious Diseases system. Interrupted time-series regression analysis was used to evaluate trends in weekly amebiasis cases before and after the discontinuation period. The study period was divided into prediscontinuation (2014-2017) and discontinuation (2018-2019) periods. A total of 6,179 amebiasis cases were reported. The average numbers of weekly cases were 21.5 during 2014-2017 and 16.3 during 2018-2019. The frequency of diagnoses decreased in the discontinuation period (prevalence rate ratio = 0.78; 95% CI, 0.67-0.89; P < 0.01). Subgroup analysis showed lower diagnostic rates, particularly for extraintestinal amebiasis (prevalence rate ratio = 0.37; 95% CI, 0.22-0.55; P < 0.01). We observed a significant decrease in the number of reported amebiasis cases per week after discontinuation of the serum antibody test reagent in Japan. Our findings hold significance for both public health policy and practice in Japan, underscoring the requirement for enhanced amebiasis diagnostic tools and strategies. To ensure accurate diagnosis, availability of antibody reagents for serum testing, covered by insurance, should be encouraged.

Fulminant amoebic colitis co-infection in a patient with COVID-19.

A woman in her 80s who presented with sudden abdominal pain and bloody stool associated with fever, dry cough and malaise, was found to be COVID-19 RT-PCR positive with fulminating necrotising amoebic colitis. She underwent right extended hemicolectomy with ileostomy and survived despite an unpredictable post-operative course, the need for aggressive intensive care and other major risk factors, and was discharged home after the twentieth day of her presentation.This case summarises the survival of a geriatric patient diagnosed with two lethal complications - amoebic colitis and COVID-19 respiratory infection with the aid of prompt surgical intervention and appropriate critical care.

A case of fulminant amoebic colitis during systemic chemotherapy for gastric cancer.

Amoebiasis is a parasitic infection caused by the protozoan, Entamoeba histolytica. At times, amoebiasis is activated under immunosuppressive conditions such as chemotherapy. We report a case of fulminant amoebic colitis resulting from an asymptomatic Entamoeba histolytica infection, which was activated by chemotherapy for gastric cancer. The patient developed diarrhea and fever after three courses of chemotherapy for gastric cancer and was diagnosed with acute enteritis. A colonoscopy and biopsy were performed because of the bloody stool. Histopathological findings revealed amoebic invasion of the rectum. Therefore, the patient was diagnosed with amoebic colitis and was treated with metronidazole. Emergency surgery was performed because intestinal perforation was suspected after which his general condition improved and was discharged. Subsequently, gastric cancer surgery was performed and the patient was discharged without postoperative complications. Hence, amoebic colitis should be listed as a differential diagnosis, and a colonoscopic biopsy should be performed when colitis occurs during chemotherapy for cancer.

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.

High-throughput phenotypic screen identifies a new family of potent anti-amoebic compounds.

Entamoeba histolytica is a disease-causing parasitic amoeba which affects an estimated 50 million people worldwide, particularly in socioeconomically vulnerable populations experiencing water sanitation issues. Infection with E. histolytica is referred to as amoebiasis, and can cause symptoms such as colitis, dysentery, and even death in extreme cases. Drugs exist that are capable of killing this parasite, but they are hampered by downsides such as significant adverse effects at therapeutic concentrations, issues with patient compliance, the need for additional drugs to kill the transmissible cyst stage, and potential development of resistance. Past screens of small and medium sized chemical libraries have yielded anti-amoebic candidates, thus rendering high-throughput screening a promising direction for new drug discovery in this area. In this study, we screened a curated 81,664 compound library from Janssen pharmaceuticals against E. histolytica trophozoites in vitro, and from it identified a highly potent new inhibitor compound. The best compound in this series, JNJ001, showed excellent inhibition activity against E. histolytica trophozoites with EC50 values at 0.29 µM, which is better than the current approved treatment, metronidazole. Further experimentation confirmed the activity of this compound, as well as that of several structurally related compounds, originating from both the Janssen Jump-stARter library, and from chemical vendors, thus highlighting a new structure-activity relationship (SAR). In addition, we confirmed that the compound inhibited E. histolytica survival as rapidly as the current standard of care and inhibited transmissible cysts of the related model organism Entamoeba invadens. Together these results constitute the discovery of a novel class of chemicals with favorable in vitro pharmacological properties. The discovery may lead to an improved therapy against this parasite and in all of its life stages.

Prevalence of amoebiasis and associated risk factors among population in Duhok city, Kurdistan Region, Iraq.

INTRODUCTION: Entamoeba histolytica, a protozoan parasite, is the third major contributor to human mortality and morbidity outside of malaria and schistosomiasis. The purpose of this cross-sectional study was to estimate the prevalence of Entamoeba spp. among outpatients of two teaching hospitals in Duhok city who agreed to participate in the study from April 2021 to March 2022 to assess the impact of associated risk variables on the infection rate. METHODOLOGY: Stool specimens were collected from outpatients suffering from diarrhea and other gastrointestinal symptoms in two teaching hospitals: Azadi and Heevi Pediatric in Duhok city, Kurdistan Region- Iraq. The collected stool specimens were examined macroscopically, followed by microscopic examination using the direct wet mount and zinc sulfate flotation methods, respectively. RESULT: Infection with Entamoeba species was recorded in 21.68% (562/2592) of the analyzed specimens. Males had a significantly higher infection rate than females (67.43% vs. 32.56%). This difference was statistically significant (p < 0.000). The highest rate was seen in the age group 1-10 years (p < 0.001). Lower levels of education, low incomes, eating unwashed fruits and vegetables, drinking well water, eating frequently outside of homes, not using antidiarrheal medications and living in overcrowded families were risk factors that showed high levels of infection (p < 0.0001). CONCLUSIONS: The present study concluded that improving living conditions, providing clean water, and promoting health education programs are essential to reduce the rate of this disease among the population.

Amoebic colitis masquerading as inflammatory bowel disease for a decade.

Nil.

Fulminant Amebic Enteritis in the Perinatal Period.

Pregnancy is a known risk factor for amebic enteritis, which develops into potentially fatal fulminant amebic enteritis in some cases. We describe a case of a 27-year-old non-immunosuppressed pregnant woman with fulminant amebic enteritis complicated with cytomegalovirus enteritis. She improved with intensive care and intravenous metronidazole and ganciclovir but eventually required subtotal colectomy for intestinal stenosis. It is difficult to diagnose amebic enteritis, especially in a non-endemic area. Amebic enteritis must be considered as a differential diagnosis for refractory diarrhea with bloody stools in women in the perinatal period, even those without immunosuppression.

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.

Gene expression of axenically-isolated clinical Entamoeba histolytica strains and its impact on disease severity of amebiasis.

The severity of Entamoeba histolytica infection is determined by host immunology, pathogen virulence, and the intestinal environment. Conventional research for assessing pathogen virulence has been mainly performed using laboratory strains, such as a virulent HM-1: IMSS (HM-1) and an avirulent Rahman, under various artificial environmental conditions because of the difficulties of axenic isolation of the clinical strains. However, it is still unclear whether scientific knowledge based on laboratory strains are universally applicable to the true pathogenesis. Hereby, we performed transcriptomic analysis of clinical strains from patients with different degrees of disease severity, as well as HM-1 under different conditions. Even after several months of axenization, Clinical strains show the distinct profile in gene expression during in vitro passage, moreover, difference between any 2 of these strains was much greater than the changes on the liver challenge. Interestingly, 26 DEGs, which were closely related to the biological functions, were oppositely up- or down regulated between virulent Ax 19 (liver abscess) and avirulent Ax 11 (asymptomatic carrier). Additionally, RNAseq using laboratory strain (HM1) showed more than half of genes were differently expressed between continuously in vitro passaged HM1 (in vitro HM1) and periodically liver passaged HM1 (virulent HM1), which was much greater than the changes on the liver passage of virulent HM1. Also, transcriptomic analysis of a laboratory strain revealed that continuous environmental stress enhances its virulence via a shift in its gene expression profile. Changes in gene expression patterns on liver abscess formation were not consistent between clinical and laboratory strains.

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.

[Early endoscopic diagnosis can save lives and reduce the extent of colon resection for acute fulminant amebic colitis: a case report with review].

A man in his 50s was referred to the hospital with fever, right lower abdominal pain, and bloody diarrhea. Based on computed tomography images and characteristic varioliform erosions observed during the colonoscopic examination, the patient was diagnosed with fulminant amebic colitis. Intravenous metronidazole was administered immediately. After symptom improvement, a second colonoscopic examination revealed inflammation localized to the right hemicolon. A right colectomy was performed on the 75th hospital day, and the patient was discharged without further problems. Prompt antiamebic therapy based on early endoscopic diagnosis was effective in quelling colonic inflammation in a life-threatening case of acute fulminant amebic colitis. Moreover, colonoscopic reexamination was useful in determining the extent of inflammation and minimizing colon resection.

Fulminant necrotizing amoebic colitis presenting as acute appendicitis: a case report and comprehensive literature review.

Intestinal amoebiasis is a parasitic infection caused by Entamoeba histolytica. It is commonly found in developing countries with poor hygiene. A rare, life-threatening complication of amoebiasis is fulminant necrotizing amoebic colitis (FulNAC). We report a 59-year-old male with acute lower right abdominal pain. Before coming to our institution, he was diagnosed with acute appendicitis. Extensive necrosis near the caecum involving the appendix and colon was observed intraoperatively. The patient underwent a right hemicolectomy, followed by an ileostomy and colostomy. Histopathologic examination confirmed the diagnosis of FulNAC. After the surgery, the patient was transferred to the high care unit and treated with metronidazole after histopathologic findings confirmed the etiology. The patient showed excellent response to the antibiotic prescribed, and the symptoms subsided. He was discharged from the hospital on day nine. Additionally, we reviewed fifty-one existing case reports on invasive intestinal amoebiasis worldwide, confirmed by histopathological examination following their preoperative diagnosis, surgery, pharmacology treatment, and outcomes. The learning point of this case is that intestinal amoebiasis should be considered a differential diagnosis for patients around fifty years old with bowel symptoms and travel history or living in tight quarters. Blood tests, radiological examinations, and serological evaluations are valuable diagnostic modalities. Metronidazole should be given as early as possible, and health promotion is recommended to prevent this disease in the population.

A rare case of an intestinal ulcer: AIDS and amebic colitis in a homosexual man with ulcerative colitis.

A 56-year-old man with half of year history of UC was admitted to our hospital due to abdominal pain, diarrhea, and hematochezia (more than ten times per day) for two weeks. He had had homosexual intercourse with many men. Subsequent laboratory findings revealed that there was a significant increase in elevated white blood cells (WBC, 11.77x109/L), C-Reactive Protein (CRP, 83.7 mg/L), tumor necrosis factor-alpha (TNF-ɑ, 6.83 pg/ml), interleukin-2 (IL-2, 75.78 pg/ml), IL-6 (124.68 pg/ml), IL-10 (58.24 pg/ml) and IL-17 (128.76 pg/ml), and fecal calprotectin (FC >1800 µg/g). Albumin (ALB, 22.5 g/L) and Hemoglobin (Hb, 98 g/L) were significantly decreased. Amoeba was identified in the stool. The abdominal contrast-enhanced Computed Tomography (CT) showed that there was thickened intestinal wall in the sigmoid colon and rectum. Colonoscopy and intestinal histopathology suggested active severe UC (E2) and Entamoeba Histolytica (trophozoites) in the necrotic tissue (Figure 1). The result of enzyme immunoassay (EIA) screening for HIV was positive. The HIV viral load was 7.85x109 copies/mL, and the CD4+ cell count was 43/µL.