Temperature and Risk of Infectious Diarrhea: A Systematic Review and Meta-analysis

There are many studies that have explored the relationship between temperature and the spread of infectious diarrhea (ID), but the results obtained are inconsistent. It is necessary to systematically evaluate the impact of temperature on the incidence of ID. ID is an intestinal infectious disease including cholera, typhoid and paratyphoid fever, bacterial and amebic dysentery, and other infectious diarrhea. This study is based on the PRISMA statement to report this systematic review. We conduct literature searches from CNKI, VIP databases, CBM, PubMed, Web of Science, Cochrane Library and other databases. The number registered in PROSPERO is CRD42021225472. Finally, after searching a total of 4,915 articles in the database and references, a total of 27 studies were included. The number of people involved exceeded 7.07 million. The overall result demonstrated when the temperature rises, there is a significant increase in infectious diarrhea (RRcumulative=1.42, 95%CI:1.07–1.88, RRsingle−day=1.08, 95%CI:1.03–1.14). Subgroup analysis found that the cumulative effect of temperature on the bacillary dysentery group and other diarrhea groups. The result of the single-day effect subgroup analysis was similar to the result of the cumulative effect. And the sensitivity analysis proves that the above results were robust. This systematic review and meta-analysis support that temperature will increase the risk of ID, which is helpful for ID prediction and early warning in the future.

Queuine Is a Nutritional Regulator of Entamoeba histolytica Response to Oxidative Stress and a Virulence Attenuator

ABSTRACT Queuosine is a naturally occurring modified ribonucleoside found in the first position of the anticodon of the transfer RNAs for Asp, Asn, His, and Tyr. Eukaryotes lack pathways to synthesize queuine, the nucleobase precursor to queuosine, and must obtain it from diet or gut microbiota. Here, we describe the effects of queuine on the physiology of the eukaryotic parasite Entamoeba histolytica, the causative agent of amebic dysentery. Queuine is efficiently incorporated into E. histolytica tRNAs by a tRNA-guanine transglycosylase (EhTGT) and this incorporation stimulates the methylation of C38 in tRNAGUCAsp. Queuine protects the parasite against oxidative stress (OS) and antagonizes the negative effect that oxidation has on translation by inducing the expression of genes involved in the OS response, such as heat shock protein 70 (Hsp70), antioxidant enzymes, and enzymes involved in DNA repair. On the other hand, queuine impairs E. histolytica virulence by downregulating the expression of genes previously associated with virulence, including cysteine proteases, cytoskeletal proteins, and small GTPases. Silencing of EhTGT prevents incorporation of queuine into tRNAs and strongly impairs methylation of C38 in tRNAGUCAsp, parasite growth, resistance to OS, and cytopathic activity. Overall, our data reveal that queuine plays a dual role in promoting OS resistance and reducing parasite virulence. IMPORTANCE Entamoeba histolytica is a unicellular parasite that causes amebiasis. The parasite resides in the colon and feeds on the colonic microbiota. The gut flora is implicated in the onset of symptomatic amebiasis due to alterations in the composition of bacteria. These bacteria modulate the physiology of the parasite and affect the virulence of the parasite through unknown mechanisms. Queuine, a modified nucleobase of queuosine, is exclusively produced by the gut bacteria and leads to tRNA modification at the anticodon loops of specific tRNAs. We found that queuine induces mild oxidative stress resistance in the parasite and attenuates its virulence. Our study highlights the importance of bacterially derived products in shaping the physiology of the parasite. The fact that queuine inhibits the virulence of E. histolytica may lead to new strategies for preventing and/or treating amebiasis by providing to the host queuine directly or via probiotics.

Queuine is a nutritional regulator of Entamoeba histolytica response to oxidative stress and a virulence attenuator

Queuosine is a naturally occurring modified ribonucleoside found in the first position of the anticodon of the transfer RNAs for Asp, Asn, His and Tyr. Eukaryotes lack pathways to synthesize queuine, the nucleobase precursor to queuosine, and must obtain it from diet or gut microbiota. Here we describe the effects of queuine on the physiology of the eukaryotic parasite, Entamoeba histolytica, the causative agent of amebic dysentery. Queuine is efficiently incorporated into E. histolytica tRNAs by a tRNA-guanine transglycosylase (EhTGT) and this incorporation stimulates the methylation of C38 in tRNAAspGUC. Queuine protects the parasite against oxidative stress (OS) and antagonizes the negative effect that oxidation has on translation by inducing the expression of genes involved in OS response, such as heat shock protein 70 (Hsp 70), antioxidant enzymes, and enzymes involved in DNA repair. On the other hand, queuine impairs E. histolytica virulence by downregulating the expression of genes previously associated with virulence, including cysteine proteases, cytoskeletal proteins, and small GTPases. Silencing of EhTGT prevents incorporation of queuine into tRNAs and strongly impairs methylation of C38 in tRNAAspGUC, parasite growth, resistance to OS, and cytopathic activity. Overall, our data reveal that queuine plays a dual role in promoting OS resistance and reducing parasite virulence.

PHYTOCHEMICAL SCREENING AND ANTIAMEBIC STUDIES OF TAMARINDUS INDICA OF LEAVES EXTRACT

Objective: The present study deals with preliminary phytochemical screening of Tamarindus indica extracts and investigates its antiamebic effect against Entamoeba histolytica in vitro. Methods: E. histolytica was isolated from stools of patients with amebic dysentery and cultivated in lock-egg medium. The leaves extract was added to check its antiamebic activity. Results: The phytochemical screening shows that T. indica contains alkaloids, flavonoids, phenol, and tannins. T. indica extracts (aqueous and ethanolic) were added to culture media E. histolytica. It was observed that E. histolytica count reduced to zero after 72 h and 96 h when 15 mg/ml of aqueous and ethanolic extracts were added, respectively. It is also revealed that there is no cytotoxicity against erythrocytes even when high concentration of plant leaves extract is used. Conclusion: The in vitro sensitivity of T. indica leaves extract against the E. histolytica is established.

Genome-Wide Association Study Reveals Genetic Link between Diarrhea-Associated Entamoeba histolytica Infection and Inflammatory Bowel Disease

ABSTRACT Entamoeba histolytica is the etiologic agent of amebic dysentery, though clinical manifestation of infection is highly variable ranging from subclinical colonization to invasive disease. We hypothesize that host genetics contribute to the variable outcomes of E. histolytica infection; thus, we conducted a genome-wide association study (GWAS) in two independent birth cohorts of Bangladeshi infants monitored for susceptibility to E. histolytica disease in the first year of life. Children with at least one diarrheal episode positive for E. histolytica (cases) were compared to children with no detectable E. histolytica infection in the same time frame (controls). Meta-analyses under a fixed-effect inverse variance weighting model identified multiple variants in a region of chromosome 10 containing loci associated with symptomatic E. histolytica infection. An intergenic insertion between CREM and CCNY (rs58000832) achieved genome-wide significance (P value from meta-analysis [Pmeta] = 6.05 × 10−9), and each additional risk allele of rs58000832 conferred 2.42 increased odds of a diarrhea-associated E. histolytica infection. The most strongly associated single nucleotide polymorphism (SNP) within a gene was in an intron of CREM (rs58468612; Pmeta = 8.94 × 10−8), which has been implicated as a susceptibility locus for inflammatory bowel disease (IBD). Gene expression resources suggest associated loci are related to the lower expression of CREM. Increased CREM expression is also observed in early E. histolytica infection. Further, CREM−/− mice were more susceptible to E. histolytica amebic colitis. These genetic associations reinforce the pathological similarities observed in gut inflammation between E. histolytica infection and IBD. IMPORTANCE Diarrhea is the second leading cause of death for children globally, causing 760,000 deaths each year in children less than 5 years old. Amebic dysentery contributes significantly to this burden, especially in developing countries. The identification of host factors that control or enable enteric pathogens has the potential to transform our understanding of disease predisposition, outcomes, and treatments. Our discovery of the transcriptional regulator cAMP-responsive element modulator (CREM) as a genetic modifier of susceptibility to amebic disease has implications for understanding the pathogenesis of other diarrheal infections. Further, emerging evidence for CREM in IBD susceptibility suggests that CREM is a critical regulator of enteric inflammation and may have broad therapeutic potential as a drug target across intestinal inflammatory diseases.

Primary Pulmonary Amebiasis Complicated with Multicystic Empyema

Amebiasis is a parasitic infection caused by the protozoanEntamoeba histolytica. While most infections are asymptomatic, the disease could manifest clinically as amebic dysentery and/or extraintestinal invasion in the form of amebic liver abscess or other more rare manifestations such as pulmonary, cardiac, or brain involvement. Herein we are reporting a case of a 24-year-old male with history of Down syndrome who presented with severe right side pneumonia complicated with multicystic empyema resistant to regular medical therapy. Further investigation revealed a positive pleural fluid forE. histolyticacysts and trophozoites. The patient was diagnosed with primary pleuropulmonary amebiasis and he responded promptly to surgical drainage and metronidazole therapy. In patients from endemic areas all physicians should keep a high index of suspicion of amebiasis as a cause of pulmonary disease.