Association between Epstein-Barr virus infection and gastric cancer: A systematic review and meta-analysis

Background: Numerous studies conducted over the past 30 years have pointed to the presence of Epstein-Barr virus (EBV) in gastric cancer samples. This study was aimed to provide a meta-analytic review of the prevalence of EBV in gastric cancer patients, and to clarify the relationship between EBV infection and gastric cancer. Methods: A literature search was performed electronically using online databases for English language publications until July 1, 2019. The pooled EBV prevalence and 95 confidence intervals (CIs) were estimated using a random-effects model. To determine the association between EBV and gastric cancer, pooled odds ratio (OR) and its 95 CI were computed for case-control studies. Two separate analyses were performed on data from case-control studies with matched and non-match pairs designs to calculate the pooled estimates of ORs. Results: The pooled prevalence of EBV in 20,361 gastric cancer patients was 8.77 (95 CI: 7.73-9.92; I2 = 83.2). There were 20 studies with matched pairs design, including tumor and tumor-adjacent normal tissue pairs from 4116 gastric cancer patients. The pooled ORs were 18.56 (95 CI: 15.68-21.97; I2 = 55.4) for studies with matched pairs design and 3.31 (95 CI: 0.95-11.54; I2 = 55.0) for studies with non-matched pairs design. The proportion of EBV-associated gastric cancer among male cases was significantly higher than among female cases (10.83, vs. 5.72) (P < 0.0001). However, the pooled OR estimate for EBV-associated gastric cancer was significantly higher among females (21.47; 95 CI: 15.55-29.63; I2 = 0) than in males (14.07; 95 CI: 10.46-18.93; I2 = 49.0) (P = 0.06). EBV was more prevalent in the cardia (12.47) and the body (11.68) compared to the antrum (6.29) (P = 0.0002). Conclusions: EBV infection is associated with more than 18 times increase the risk of gastric cancer. Although the prevalence of EBV was higher in male patients than in female patients with gastric cancer, women are more likely than men to develop EBV-associated gastric cancer. Our findings showed that using tumor-adjacent normal tissues as the control group provides more robust and accurate results regarding the relationship between EBV infection and gastric cancer. © 2020 The Author(s)

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

Towards the Establishment of a Porcine Model to Study Human Amebiasis

BACKGROUND: Entamoeba histolytica is an important parasite of the human intestine. Its life cycle is monoxenous with two stages: (i) the trophozoite, growing in the intestine and (ii) the cyst corresponding to the dissemination stage. The trophozoite in the intestine can live as a commensal leading to asymptomatic infection or as a tissue invasive form producing mucosal ulcers and liver abscesses. There is no animal model mimicking the whole disease cycle. Most of the biological information on E. histolytica has been obtained from trophozoite adapted to axenic culture. The reproduction of intestinal amebiasis in an animal model is difficult while for liver amebiasis there are well-described rodent models. During this study, we worked on the assessment of pigs as a new potential model to study amebiasis. METHODOLOGY/PRINCIPAL FINDINGS: We first co-cultured trophozoites of E. histolytica with porcine colonic fragments and observed a disruption of the mucosal architecture. Then, we showed that outbred pigs can be used to reproduce some lesions associated with human amebiasis. A detailed analysis was performed using a washed closed-jejunal loops model. In loops inoculated with virulent amebas a severe acute ulcerative jejunitis was observed with large hemorrhagic lesions 14 days post-inoculation associated with the presence of the trophozoites in the depth of the mucosa in two out four animals. Furthermore, typical large sized hepatic abscesses were observed in the liver of one animal 7 days post-injection in the portal vein and the liver parenchyma. CONCLUSIONS: The pig model could help with simultaneously studying intestinal and extraintestinal lesion development

Restricted genetic heterogeneity of the Plasmodium vivax transmission-blocking vaccine (TBV) candidate Pvs48/45 in a low transmission setting: Implications for the Plasmodium vivax malaria vaccine development

Plasmodium vivax is the most widespread malaria species parasitizing humans outside Africa, with approximately 100 million cases reported per year. Most human cases of P. vivax are asymptomatic with low parasitemia, making active case detection-based elimination programme challenging and less effective. Despite the widespread distribution of P. vivax, no effective vaccines are currently available. Transmission blocking vaccines have recently emerged as potential vaccine candidates to reduce transmission rates to below the essential levels required for the maintenance of the parasite life cycle. Here, we demonstrated that P. vivax was the predominant species found in a malaria-endemic area, although P. vivax/P. falciparum co-infections were also common. Through genomic sequence analysis and neighbor-joining algorithms, we demonstrated limited genetic heterogeneity in the P. vivax transmission-blocking vaccine candidate Pvs48/45 among clinical isolates of P. vivax. Restricted genetic polymorphism occurred at both nucleotide and amino acid levels. The most frequent mutation was A � G at nucleotide position 77 (46.7), whereas the least frequent was C � T at nucleotide position 1230 (3.3). The occurrence of single nucleotide polymorphisms (SNPs) distribution at 6/8 positions (75) led to changes in amino acid sequences in the Pvs48/45 loci, whereas 2/8 (25) of SNPs resulted in no amino acid sequence variations. Consistently, the nucleotide diversity in the Pvs48/45 locus among the P. vivax population studied was extremely low (� = 0.000525). Changes in amino acid sequences in the Pvs48/45 protein did not result in substantial conformational modifications in the tertiary structures of these proteins. Unveiling the population genetic structure and genetic heterogeneity of vaccine target antigens are necessary for rational design of transmission-blocking antibody vaccines and to monitor the vaccine efficacy in clinical trials in endemic areas for malaria. © 2021 Elsevier B.V

Restricted genetic heterogeneity of the Plasmodium vivax transmission-blocking vaccine (TBV) candidate Pvs48/45 in a low transmission setting: Implications for the Plasmodium vivax malaria vaccine development

Plasmodium vivax is the most widespread malaria species parasitizing humans outside Africa, with approximately 100 million cases reported per year. Most human cases of P. vivax are asymptomatic with low parasitemia, making active case detection-based elimination programme challenging and less effective. Despite the widespread distribution of P. vivax, no effective vaccines are currently available. Transmission blocking vaccines have recently emerged as potential vaccine candidates to reduce transmission rates to below the essential levels required for the maintenance of the parasite life cycle. Here, we demonstrated that P. vivax was the predominant species found in a malaria-endemic area, although P. vivax/P. falciparum co-infections were also common. Through genomic sequence analysis and neighbor-joining algorithms, we demonstrated limited genetic heterogeneity in the P. vivax transmission-blocking vaccine candidate Pvs48/45 among clinical isolates of P. vivax. Restricted genetic polymorphism occurred at both nucleotide and amino acid levels. The most frequent mutation was A � G at nucleotide position 77 (46.7), whereas the least frequent was C � T at nucleotide position 1230 (3.3). The occurrence of single nucleotide polymorphisms (SNPs) distribution at 6/8 positions (75) led to changes in amino acid sequences in the Pvs48/45 loci, whereas 2/8 (25) of SNPs resulted in no amino acid sequence variations. Consistently, the nucleotide diversity in the Pvs48/45 locus among the P. vivax population studied was extremely low (� = 0.000525). Changes in amino acid sequences in the Pvs48/45 protein did not result in substantial conformational modifications in the tertiary structures of these proteins. Unveiling the population genetic structure and genetic heterogeneity of vaccine target antigens are necessary for rational design of transmission-blocking antibody vaccines and to monitor the vaccine efficacy in clinical trials in endemic areas for malaria. © 2021 Elsevier B.V