Doa'a A. Saleh

Hepatitis C Virus-Specific Cell-Mediated Immune Responses in Children Born to Mothers Infected with Hepatitis C Virus

Objective To investigate the association between hepatitis C virus (HCV)-specific cell-mediated immunity (CMI) responses and viral clearance in children born to mothers infected with HCV. Study design A cross-sectional study of children from a mother-infant cohort in Egypt were enrolled to detect CMI responses to recombinant core and nonstructural HCV antigens (nonstructural segments NS3, NS4a/b, and NS5 of the HCV genome) using an interferon-gamma enzyme-linked immunospot assay. Children born to mothers with chronic HCV were enrolled into 3 groups: transiently viremic (n = 5), aviremic (n = 36), and positive control (n = 6), which consisted of 1 child with chronic HCV from this cohort and another 5 children with chronic HCV from a companion study. Children without HCV born to mothers without HCV (n = 27) served as a negative control group. Wilcoxon rank sum test was used to compare the magnitude of CMI responses between groups. Results None of the 6 control children who were positive for HCV responded to any HCV antigen, and 4 (80%) of 5 children with transient viremia responded to at least one HCV antigen, compared with 5 (14%) of 36 and 3 (11%) of 27 children in the aviremic and negative control groups, respectively. Children with transient viremia elicited stronger responses than did negative controls (P = .005), positive controls (P = .011), or children without HCV viremia (P = .012), particularly to nonstructural antigens. Conclusions HCV-specific CMI responses were significantly higher in magnitude and frequency among transiently infected children compared with those persistently infected. This suggests CMI responses may be associated with past viral clearance and can identify children at high risk of infection, who can be targeted for health education, screening, and follow-up.

Reliability of risk-based screening for hepatitis C virus infection among pregnant women in Egypt

OBJECTIVESnThe Centers for Disease Control and Prevention (CDC) only recommends risk-based HCV screening for pregnant women in the United States. This study sought to determine the reliability of risk-based versus universal HCV screening for pregnant women in Egypt, a country with the worlds highest HCV prevalence that also relies on risk-based screening, and to identify additional characteristics that could increase the reliability of risk-based screening.nnnMETHODSnPregnant women attending the Cairo University antenatal clinic were tested for anti-HCV antibodies and RNA, and demographic characteristics and risk factors for infection were assessed.nnnRESULTSnAll 1250 pregnant women approached agreed to participate (100%) with a mean age of 27.4xa0±xa05.5 years (range:16-45). HCV antibodies and RNA were positive in 52 (4.2%) and 30 (2.4%) women respectively. After adjustment, only age (OR:1.08, 95%CI:1.002-1.16, pxa0<xa00.01), history of prior pregnancies (OR:1.20, 95%CI:1.01-1.43, pxa0<xa00.04), and working in the healthcare sector (OR:8.68, 95%CI:1.72-43.62, pxa0<xa00.01), remained significantly associated with chronic HCV infection.nnnCONCLUSIONSnUniversal antenatal HCV screening was widely accepted (100%) and traditional risk-based screening alone would have missed 3 (10%) chronically infected women, thereby supporting universal screening of pregnant women whenever possible. Otherwise, risk-based screening should be modified to include history of prior pregnancy and healthcare employment.

GSTM1, GSTT1 Null Variants, and GPX1 Single Nucleotide Polymorphism Are Not Associated with Bladder Cancer Risk in Egypt

Background: Bladder cancer is the most common male malignancy in Egypt, consists predominantly of urothelial cell carcinoma (UCC) and squamous cell carcinoma (SCC), and disparities in incidence exist between men and women regardless of geographic region. Tobacco smoke exposure and Schistosoma haematobium (SH) infection and the presence of GSTM1, GSTT1, and GPX1 genotypes, as modulators of the carcinogenic effect of reactive oxidative species, were hypothesized to modify bladder cancer risk and possibly explain these gender differences. Methods: We evaluated the association between bladder cancer risk and functional polymorphisms in the GSTM1, GSTT1, and GPX1 genes in 625 cases and 626 matched population-based controls in Egypt and assessed for potential interactions between these candidate genes and environmental exposures, such as smoking and SH infection. We analyzed the risk for developing UCC and SCC separately. Results: None of these functional polymorphisms were significantly associated with bladder cancer risk. There were no significant interactions between genotypes and smoking or SH infection in this population, nor was any difference detected in genotypic risk between men and women. Conclusions: Our findings suggest that common genetic variations in GSTM1, GSTT1, and GPX1 are not associated with bladder cancer risk overall and that well-known environmental risk factors, such as smoking and SH infection, do not interact with these genes to modulate the risk. Impact: Our data indicate that common genetic variations in GSTM1, GSTT1, and GPX1 were not associated with bladder cancer risk. Cancer Epidemiol Biomarkers Prev; 20(7); 1552–4. ©2011 AACR.

Agricultural Workers and Urinary Bladder Cancer Risk in Egypt

ABSTRACT The authors examined the associations between farming and the risk for squamous cell (SCC) or urothelial cell (UC) carcinoma of the urinary bladder among Egyptians. The authors used data from a multicenter case-control study (1,525 male and 315 female cases, and 2,069 male and 547 female age- and residence-matched, population-based controls) to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Men in farming and who never smoked had increased risk for either SCC or UC (AOR [95% CI]: 4.65 [2.59–8.36] and 6.22 [3.82–10.15], respectively). If they ever smoked, their risks were 2.27 (1.75–2.95) and 1.93 (1.58–2.35), respectively. Women in farmer households were at increased risk for SCC (1.40 [0.93–2.09] and UC [1.25 (0.82–1.89]), although not statistically significant. Occupational and environmental exposures to farming increased the risk for bladder cancer among Egyptians.

Genetic polymorphisms in NQO1 and SOD2: Interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt

BACKGROUNDnBladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms innnnNAD(P)Hnquinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individuals susceptibility to these carcinogenic exposures and hence the risk of bladder cancer.nnnMETHODSnWe assessed the effects of potential interactions between functional polymorphisms in the NQO1 and SOD2 genes and exposure to smoking and SH infection on bladder cancer risk among 902 cases and 804 population-based controls in Egypt. We used unconditional logistic regression to estimate the odds ratios (OR) and confidence intervals (CI) 95%.nnnRESULTSnWater pipe and cigarette smoking were more strongly associated with cancer risk among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86-10.42]) as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97-6.74]). Conversely, the risk associated with SH infection was higher among the latter (OR [CI 95%] = 3.59 [2.21-5.84]) than among the former (OR [CI 95%] = 1.86 [1.33-2.60]). Polymorphisms in NQO1 genotype showed a similar pattern, but to a much lesser extent. The highest odds for having bladder cancer following SH infection were observed among individuals with the CC genotypes for both NQO1 and SOD2 (OR [CI 95%] = 4.41 [2.32-8.38]).nnnCONCLUSIONnOur findings suggest that genetic polymorphisms in NQO1 and SOD2 play important roles in the etiology of bladder cancer by modulating the effects of known contributing factors such as smoking and SH infection.

Safety and Efficacy of Combined Treatment with Pegylated Interferon Alpha-2b and Ribavirin for HCV Genotype 4 in Children

Combined treatment with pegylated interferon (PEG-IFN)-α2b and ribavirin (RBV) is the only currently approved treatment for hepatitis C virus (HCV) infection in children. The aim of this study was to assess the safety and efficacy of combined treatment with PEG-IFN-α2b and RBV in Egyptian children and adolescents with genotype 4 (GT4) HCV infection. The study included 66 patients (3-17 years of age), of both sexes, infected with HCV GT4, treated with PEG-IFN-α2b (60 μg/m(2)), subcutaneously once weekly plus RBV (15 mg/kg/day) in 2 divided oral doses. Efficacy was assessed by achievement of sustained virological response (SVR). Safety was assessed by questionnaires directed to the patients at specific intervals, growth assessment and laboratory tests. SVR was achieved in 28 patients (42.4%). Nonresponders had significantly commoner history of treated malignancies (P = 0.03), baseline lower absolute neutrophil count (ANC; P = 0.009), higher gamma glutamyl transpeptidase (GGT; P = 0.003), and higher viral load (P = 0.03). Fever was the most frequently reported side effect occurring in 98.5% of the patients followed by musculoskeletal symptoms. Neutropenia was observed in 36 patients (54.6%) and necessitated treatment discontinuation in 1 patient. Decline in both weight and height percentiles was observed in 70% of children who received the combined therapy for a total of 48 weeks. In conclusion, the currently available treatment for HCV GT4 in pediatric patients has modest SVR with numerous adverse events necessitating meticulous monitoring to optimize care of the patients. Side effects could be managed with dose modifications and specific treatment when necessary.

A bio inspired fuzzy k-modes clustring algorithm

This paper proposes a bio inspired fuzzy K-Modes clustering algorithm using fuzzy particle swarm optimization (FPSO) and fuzzy k-modes (FK-Modes) algorithm for clustering categorical data. It integrates concepts of FK-Modes algorithm to handle the uncertainty phenomena and FPSO to reach global optimal solution of clustering optimization problem. The proposed FPSO-FK-Modes algorithm was implemented and evaluated using slandered benchmark data sets and performance measures. Experimental results showed that the proposed FPSO-FK-Modes algorithm performed well compared with FK-modes and Genetic FK-modes (GA- FK-modes) algorithm using adjusted rand index.

Substance Use by Egyptian Youth: Current Patterns and Potential Avenues for Prevention

Background. Substance abuse in Egypt is a serious public health threat. Recent studies have demonstrated increases in the prevalence of the use of tobacco, illegal drugs, and over-the-counter drugs, particularly among youth. Methods. We conducted focus groups with a total of 40 male and female youth participants, ages 12–14 and 15–18, recruited from two different areas (Cairo and Alexandria) in 2012. We investigated their knowledge and perceptions regarding current substance use, its sources, and promoting and protecting factors, broadly addressing the use of tobacco products, illicit and prescription drugs, inhaled substances such as glue and solvents, and alcohol. Results. Our findings suggest that: (1) youth in Egypt had access to and were actively using substances encountered in similar research worldwide, including tobacco, alcohol, illicit drugs, glue sniffing, and pharmaceutical agents; (2) smoking cigarettes and using hashish were the most common practices, and Tramadol was the most commonly used pharmaceutical drug; (3) peer pressure from friends stood out as the most common reason to start and continue using substances, followed by adverse life events and having a parent or family member who used substances; (4) strict parenting, religiosity, and having non-user friends were among the factors perceived by youth to prevent substance use or help them quit using substances; (5) most youths were aware of the adverse health effects of substance use. Conclusion. These findings will inform the design of quantitative surveys aimed at estimating the prevalence of specific behaviors related to substance use among youth and potential avenues for prevention.

Abstract 3752: GSTT1 and GSTM1 null genotypes may increase risk of HCV-associated HCC

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLnnIntroduction: Oxidative stress plays an important role in hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC). Glutathione S-transferases (GSTs) prevent oxidative stress associated cellular damage, catalyzing the conjugation of electrophilic compounds with glutathione. Partial or complete deletions of GST theta 1 (GSTT1) and mu 1 (GSTM1) have been associated with chronicity of HCV infection. However, data on the role of these null genotypes in progression to HCC is lacking. We investigated whether GSTT1 and GSTM1 modify the association between HCV and HCC in a case-control study in Egypt.nnMethods: Participants were recruited at the National Cancer Institute of Cairo University. Cases of HCC were confirmed on pathology, alpha-fetoprotein levels and imaging. Non-cancer controls, representative of the general population with respect to HCV prevalence, were frequency matched to cases on age, sex, and area of residence. HCV antibodies were measured in blood samples by enzyme-linked immunosorbent assay, and HCV RNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). Homozygous deletions in GSTT1 and GSTM1 were determined by separate multiplex PCR methods. For these analyses, participants with active HBV were excluded. Logistic regression was used to analyze the risk of HCC associated with HCV after stratifying by GSTT1 and GSTM1 genotype. Additive interaction of HCV and null GST genotypes in HCC risk were determined by calculating the interaction contrast ratio (ICR). All analyses were adjusted for age, sex, current smoking, alcohol intake, urban/rural status, and pesticide use.nnResults: Compared to controls, HCC cases were more likely to be older, married, non-smokers, living in rural areas, and exposed to agricultural pesticides. HCV infection was a strong risk factor for HCC in this population [adjusted odds ratio (aOR): 13.6, 95% confidence interval (CI): 9.7-18.9]. GSTT1 and GSTM1 polymorphisms alone were not associated with HCC risk. However, the association of HCV with HCC was markedly stronger in patients with null GSTT1 genotype [aOR (95% CI): 23.9 (12.8-44.9) for null vs. 11.4 (7.6-17.1) for non-null]. The observations were similar for GSTM1 genotype [aOR (95% CI): 17.7 (11.1-28.5) for null vs. 10.0 (6.2-16.1) for non-null]. Additive positive interaction, as determined by an ICR value greater than zero, between HCV and null GSTT1 was significant for HCC risk [ICR (95% CI): 10.9 (2.6-41.9)]. However, the ICR for GSTM1 and HCV interaction was not statistically significant [ICR (95% CI): 2.9 (−1.7-11.1)].nnConclusions: Chronic HCV carriers with null GST genotypes are more likely to have HCC as compared to those with non-null genotypes. Studies are needed to confirm these findings and investigate the exact mechanisms underlying HCC susceptibility associated with the null GST genotypes in chronic HCV patients.nnCitation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3752. doi:10.1158/1538-7445.AM2011-3752