Incidence of Low Seroimmunity to Hepatitis B Virus in Children with Inflammatory Bowel Disease: A Single Center Experience.

Purpose: Immunosuppressive therapy is frequently administered to patients with inflammatory bowel disease (IBD), which may make them more susceptible to infections like hepatitis B. Methods: A cross-sectional study was conducted on patients aged 5-18 years diagnosed with IBD who visited a gastroenterology clinic along with controls who were the same age as the patients with IBD and were healthy overall. A logistic regression analysis using the independent variables of age, sex, race, disease phenotype, surgery, and medications and the dependent variable of adequate hepatitis B surface antibody (HBsAb) titers (>10 mIU/mL) was performed on quantitative serum HBsAb titers. Results: The study enrolled 62 patients, including 37 males and 25 females. Crohn's disease, ulcerative colitis, and indeterminate colitis were diagnosed in 16, 22, and 24 patients, respectively. Thirty-nine patients were taking corticosteroids at the time of the study, 42 were taking immunomodulators, and four were taking biologics. Compared to 44.7% of the control group, 9.3% of the patients had protective titers. Only 12 out of 62 patients had HBsAb titers greater than 10 million IU/mL. None of the patients who received biologics or corticosteroids and 3.2% of those who received immunomodulators were found to be seroimmuned. Conclusion: The younger patients had the highest titers. Patient-specific factors that may impact these low titers include the length of the patient's illness and the use of immunosuppressants.

Characterization of GEXP15 as a Potential Regulator of Protein Phosphatase 1 in Plasmodium falciparum.

The Protein Phosphatase type 1 catalytic subunit (PP1c) (PF3D7_1414400) operates in combination with various regulatory proteins to specifically direct and control its phosphatase activity. However, there is little information about this phosphatase and its regulators in the human malaria parasite, Plasmodium falciparum. To address this knowledge gap, we conducted a comprehensive investigation into the structural and functional characteristics of a conserved Plasmodium-specific regulator called Gametocyte EXported Protein 15, GEXP15 (PF3D7_1031600). Through in silico analysis, we identified three significant regions of interest in GEXP15: an N-terminal region housing a PP1-interacting RVxF motif, a conserved domain whose function is unknown, and a GYF-like domain that potentially facilitates specific protein-protein interactions. To further elucidate the role of GEXP15, we conducted in vitro interaction studies that demonstrated a direct interaction between GEXP15 and PP1 via the RVxF-binding motif. This interaction was found to enhance the phosphatase activity of PP1. Additionally, utilizing a transgenic GEXP15-tagged line and live microscopy, we observed high expression of GEXP15 in late asexual stages of the parasite, with localization predominantly in the nucleus. Immunoprecipitation assays followed by mass spectrometry analyses revealed the interaction of GEXP15 with ribosomal- and RNA-binding proteins. Furthermore, through pull-down analyses of recombinant functional domains of His-tagged GEXP15, we confirmed its binding to the ribosomal complex via the GYF domain. Collectively, our study sheds light on the PfGEXP15-PP1-ribosome interaction, which plays a crucial role in protein translation. These findings suggest that PfGEXP15 could serve as a potential target for the development of malaria drugs.

Very-early-onset inflammatory bowel disease versus late-onset inflammatory bowel disease in relation to clinical phenotype: A cross-sectional study.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic condition and children are affected by the disease's burden and therapeutic interventions for much longer than adults. Children of various ages can be diagnosed with IBD. METHODS: The research was carried out at the Pediatric Gastroenterology Clinic at Cairo University's Faculty of Medicine's Children's Hospital. From January 2013 to December 2017, this single-center observational cross-sectional study included 197 children aged 14 years and compared the clinical phenotypes of very-early-onset IBD (VEO-IBD) in patients aged six years and late-onset IBD (LO-IBD) in patients aged six to 14 years. RESULTS: Children with IBD at less than six years of age have a more colonic phenotype than children diagnosed later in life, who are more likely to have ileocolonic diseases (p = 0.002). In VEO-disease Crohn's (VEO-CD), growth failure/poor weight gain was 14%, while in LO-CD, it was 31%. Children with VEO-IBD do not always present with more severe disease than older children. Most clinical features in children with VEO-ulcerative colitis (VEO-UC) and LO-UC were similar at the first presentation, with the exception of abdominal pain, which was significantly less common in the VEO-UC group (p = 0.001) and hematochezia, which was significantly more common in the LO-UC group (p = 0.048). Children with VEO-disease Crohn's (VEO-CD) had a higher risk of bloody stools, diarrhea and fever (p = 0.013, p = 0.001 and p = 0.008, respectively), but a lower risk of abdominal pain (p = 0.000). CONCLUSIONS: Growth failure/poor weight gain occurred in 14% of VEO-CD patients and 31% of LO-CD patients. In LO-UC, abdominal pain and hematochezia were significantly more common. In LO-CD, hematochezia, diarrhea and fever were significantly more common. In LO-IBD-U, abdominal pain and diarrhea were significantly more common.

Serologic, endoscopic and pathologic findings in pediatric celiac disease: A single center experience in a low/middle income country.

BACKGROUND: Studies in Africa, Asia, and Latin America are needed to provide a comprehensive picture of the global incidence of celiac disease (CD). AIM: To describe the serology, endoscopic and histological findings in typical and atypical presentations of pediatric CD at a tertiary referral hospital in an African low/middle income country (LMIC). METHODS: This observational study was conducted on 199 patients with CD from 2010 to 2019. The patients were divided into typical and atypical groups according to the presenting symptoms including 120 and 79 patients respectively. Serology, upper gastrointestinal endoscopy with duodenal biopsy were performed for patients who had symptoms suggestive of CD. The severity of the intestinal damage was graded according to the histo-pathologic Marsh-Oberhuber classification. RESULTS: Chronic diarrhea was the main intestinal presentation in the typical group. Anemia was the most common extraintestinal symptom in both the typical and atypical group. Marsh-Oberhuber type 3b and 3c was significantly higher in the seropositive patients with a P value of 0.007. A significant correlation was observed between the histological grade of the biopsied duodenal mucosa and the clinical presentation (P < 0.001). Age was significantly higher in the atypical group (P value < 0.001). CONCLUSION: Although typical CD was observed in 120 patients in this study, the clinical variability of the condition was frequently observed. Age only was a significant predictor for the appearance of atypical CD. Therefore, CD presentations in LMIC are not different from industrialized countries.

Sleep patterns, problems, and habits in a sample of Egyptian preschoolers.

Objective: Sleep problems are common among preschoolers. We conducted this study to investigate sleep problems in a sample of Egyptian preschoolers attending pediatric outpatient clinics and examine the relationship between their sleep problems, patterns, and hygiene. Methods: The parents of 319 preschoolers, aged 2-5 years, completed the BEARS(which represent the fve major sleep domains, i.e., bedtime problems, excessive daytime sleepiness, awakenings during the night, regularity and duration of sleep, and snoring) questionnaire in Arabic and a short survey on their educational status, significant medical problems and/or their child's medications , and sleeping habits. Results: The frequency of bedtime problems, excessive daytime sleepiness, awakenings during the night, regularity of sleep, and snoring were 58.9%, 17.9%, 31%, 60.5%, and 20.4%, respectively. More than a third of the samples had poor sleep hygiene practices, ranging from 41.7% to 70.5%. Multivariate analyses revealed that age and body mass index (BMI) are predictors of bedtime problems. Conclusions: Our fndings indicate that sleep problems and poor sleep hygiene are common among this sample of preschoolers. This study also suggests an association between age and BMI and sleep disturbances.

Stool antigen detection versus 13C-urea breath test for non-invasive diagnosis of pediatric Helicobacter pylori infection in a limited resource setting.

INTRODUCTION: The prevalence of childhood infection with Helicobacter pylori is high, especially in developing countries. Non-invasive methods for detection of infection in children should be inexpensive, easy to perform, well tolerated and have a high diagnostic accuracy. We aimed to compare the reliability, specificity and sensitivity of the H. pylori stool antigen (HpSA) test with the 13C-urea breath test (13C-UBT) for the diagnosis of H. pylori infection in a limited resource setting. MATERIAL AND METHODS: The stool samples of 60 symptomatic and dyspeptic children with a mean age of 7.2 ±3.7 years (2-15 years) were evaluated using the rapid One step HpSA test by lateral flow immunoassay. The 13C-UBT was used as the gold standard method for the diagnosis of H. pylori infection. RESULTS: The HpSA test detected H. pylori antigen in 34 out of 38 positive patients with 4 false-negatives (sensitivity 89.5%, 95% confidence interval (CI): 75.2-97.1%), while 21 patients had true-negative results and one false-positive (specificity 95.5%, 95% CI: 77.2-99.9%), with a strong measure of agreement between the HpSA test and the 13C-UBT (κ = 0.83, 95% CI: 68-97%, p < 0.001). It had a positive predictive value of 97.1% (95% CI: 85.1-99.9%), a negative predictive value of 84% (95% CI: 63.9-95.5%) and an accuracy of 91.7%. CONCLUSIONS: The rapid lateral flow HpSA test is a reliable method for the primary diagnosis of H. pylori infections in children, though not as accurate as the 13C-UBT. It is more affordable, simpler to perform and more tolerable, representing a viable alternative, especially in developing countries.

Evidence for an antagonist form of the chemokine CXCL10 in patients chronically infected with HCV.

Chronic infection with hepatitis C virus (HCV) is a major public health problem, with nearly 170 million infected individuals worldwide. Current treatment for chronic infection is a combination of pegylated IFN-α2 and ribavirin (RBV); however, this treatment is effective in fewer than 50% of patients infected with HCV genotype 1 or 4. Recent studies identified the chemokine CXCL10 (also known as IP-10) as an important negative prognostic biomarker. Given that CXCL10 mediates chemoattraction of activated lymphocytes, it is counterintuitive that this chemokine correlates with therapeutic nonresponsiveness. Herein, we offer new insight into this paradox and provide evidence that CXCL10 in the plasma of patients chronically infected with HCV exists in an antagonist form, due to in situ amino-terminal truncation of the protein. We further demonstrated that dipeptidyl peptidase IV (DPP4; also known as CD26), possibly in combination with other proteases, mediates the generation of the antagonist form(s) of CXCL10. These data offer what we believe to be the first evidence for CXCL10 antagonism in human disease and identify a possible factor contributing to the inability of patients to clear HCV.

Circulating plasmacytoid dendritic cells in acutely infected patients with hepatitis C virus genotype 4 are normal in number and phenotype.

The incidence of hepatitis C virus (HCV) genotype 4 infection in Egypt provides a unique opportunity to study the innate immune response to symptomatic acute HCV infection. We investigated whether plasmacytoid dendritic cells (pDCs) are activated as a result of HCV infection. We demonstrate that, even during symptomatic acute infection, circulating pDCs maintained a similar precursor frequency and resting phenotype, compared with pDCs in healthy individuals. Moreover, stimulation with a Toll-like receptor 9 agonist resulted in an intact inflammatory response. These data support the growing consensus that pDCs are not directly activated by HCV and therefore are viable targets for immunotherapy throughout HCV infection.

Symptomatic acute hepatitis C in Egypt: diagnosis, spontaneous viral clearance, and delayed treatment with 12 weeks of pegylated interferon alfa-2a.

BACKGROUND AND OBJECTIVES: The aim of this study was to estimate the proportion of spontaneous viral clearance (SVC) after symptomatic acute hepatitis C and to evaluate the efficacy of 12 weeks of pegylated interferon alfa-2a in patients who did not clear the virus spontaneously. METHODS: Patients with symptomatic acute hepatitis C were recruited from two "fever hospitals" in Cairo, Egypt. Patients still viremic three months after the onset of symptoms were considered for treatment with 12 weeks of pegylated interferon alfa-2a (180 microg/week). RESULTS: Between May 2002 and February 2006, 2243 adult patients with acute hepatitis were enrolled in the study. The SVC rate among 117 patients with acute hepatitis C was 33.8% (95%CI [25.9%-43.2%]) at three months and 41.5% (95%CI [33.0%-51.2%]) at six months. The sustained virological response (SVR) rate among the 17 patients who started treatment 4-6 months after onset of symptoms was 15/17 = 88.2% (95%CI [63.6%-98.5%]). CONCLUSION: Spontaneous viral clearance was high (41.5% six months after the onset of symptoms) in this population with symptomatic acute hepatitis C. Allowing time for spontaneous clearance should be considered before treatment is initiated for symptomatic acute hepatitis C.