Tissue Invasion by Entamoeba histolytica: Evidence of Genetic Selection and/or DNA Reorganization Events in Organ Tropism

Entamoeba histolytica infection may have various clinical manifestations. Nine out of ten E. histolytica infections remain asymptomatic, while the remainder become invasive and cause disease. The most common form of invasive infection is amebic diarrhea and colitis, whereas the most common extra-intestinal disease is amebic liver abscess. The underlying reasons for the different outcomes are unclear, but a recent study has shown that the parasite genotype is a contributor. To investigate this link further we have examined the genotypes of E. histolytica in stool- and liver abscess-derived samples from the same patients. Analysis of all 18 paired samples (16 from Bangladesh, one from the United States of America, and one from Italy) revealed that the intestinal and liver abscess amebae are genetically distinct. The results suggest either that E. histolytica subpopulations in the same infection show varying organ tropism, or that a DNA reorganization event takes place prior to or during metastasis from intestine to liver

Interleukin 21 collaborates with interferon-γ for the optimal expression of interferon-stimulated genes and enhances protection against enteric microbial infection.

The mucosal surface of the intestinal tract represents a major entry route for many microbes. Despite recent progress in the understanding of the IL-21/IL-21R signaling axis in the generation of germinal center B cells, the roles played by this signaling pathway in the context of enteric microbial infections is not well-understood. Here, we demonstrate that Il21r-/- mice are more susceptible to colonic microbial infection, and in the process discovered that the IL-21/IL-21R signaling axis surprisingly collaborates with the IFN-γ/IFN-γR signaling pathway to enhance the expression of interferon-stimulated genes (ISGs) required for protection, via amplifying activation of STAT1 in mucosal CD4+ T cells in a murine model of Citrobacter rodentium colitis. As expected, conditional deletion of STAT3 in CD4+ T cells indicated that STAT3 also contributed importantly to host defense against C. rodentium infection in the colon. However, the collaboration between IL-21 and IFN-γ to enhance the phosphorylation of STAT1 and upregulate ISGs was independent of STAT3. Unveiling this previously unreported crosstalk between these two cytokine networks and their downstream genes induced will provide insight into the development of novel therapeutic targets for colonic infections, inflammatory bowel disease, and promotion of mucosal vaccine efficacy

A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis.

BackgroundMetronidazole is the most commonly used drug for the treatment of giardiasis in humans. In spite of its therapeutic efficacy for giardiasis, low patient compliance, especially in children, side effects, and the emergence of metronidazole-resistant strains may restrict its use. Albendazole has been used to treat Giardia duodenalis infections in recent years. However, efficacy studies in vivo and in vitro have produced diverse results as to its effectiveness. A moderately benign side effect profile, combined with established efficacy against many helminths, renders it promising for treatment of giardiasis in humans.Methodology and principal findingsWe performed a search in the PubMed, Scopus, EMBASE, the ISI Web of Science, LILIACS, and Cochrane Controlled Trials Register for trials published before February 2010 as well as in references of relevant research and review articles. Eight randomized clinical trials (including 900 patients) comparing the effectiveness of albendazole with that of metronidazole were included in meta-analysis. After extracting and validating the data, the pooled risk ratio (RR) was calculated using an inverse-variance random-effects model. Albendazole was found to be equally as effective as metronidazole in the treatment of giardiasis in humans (RR 0.97; 95% CI, 0.93, 1.01). In addition, safety analysis suggested that patients treated with albendazole had a lower risk of adverse effects compared with those who received metronidazole (RR 0.36; 95% CI, 0.10, 1.34), but limitations of the sample size precluded a definite conclusion.Conclusions/significanceThe effectiveness of albendazole, when given as a single dose of 400 mg/day for 5 days, was comparable to that of metronidazole. Patients treated with albendazole tended to have fewer side effects compared with those who took metronidazole. Given the safety, effectiveness, and low costs of albendazole, this drug could be potentially used as an alternative and/or a replacement for the existing metronidazole therapy protocols in the treatment of giardiasis in humans

Internal validity (methodological and parasitological) of included trials.

<p>§Range 0–5 (5 exemplifies articles with the highest quality).</p><p>¥Range 0–15, (15 indicates most optimal diagnostic procedure employed).</p><p>€Represents generation of allocation sequence.</p><p>®Represents allocation concealment.</p

Sensitivity-analysis of the effect of the quality of methods implemented for the measurement of parasitological cure.

<p>A, all eight studies included <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000682#pntd.0000682-Misra1" target="_blank">[29]</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000682#pntd.0000682-Alizadeh1" target="_blank">[39]</a>–<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000682#pntd.0000682-Dutta1" target="_blank">[45]</a>.</p><p>B, one study with unclear outcome measure excluded <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000682#pntd.0000682-Dutta1" target="_blank">[45]</a>.</p><p>C, studies using a single diagnostic method excluded <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000682#pntd.0000682-Alizadeh1" target="_blank">[39]</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000682#pntd.0000682-Karabay1" target="_blank">[40]</a>.</p><p>D, one study which used the most sensitive methods excluded <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000682#pntd.0000682-Yereli1" target="_blank">[41]</a>.</p

Flow diagram deciphering the article selection process for this meta-analysis study.

<p>Individual searches do not add up to 56 as some of the same articles were retrieved by multiple search engines.</p

Forest plot showing the effects of albendazole and metronidazole on human giardiasis.

<p>Relative risk was calculated for each study separately. n/N = number described as cured over number of participants completing study.</p