Niveen Saudy

Exponential Spread of Hepatitis C Virus Genotype 4a in Egypt

Hepatitis C virus (HCV) infects >10% of the general population in Egypt, in which intravenous injection with an antimony compound for endemic schistosomiasis in the past has been implicated. To simulate the epidemic history of HCV in Egypt, sera were obtained from 3608 blood donors at 13 governorates in or surrounding the Nile valley during 1999. The prevalence of antibody to HCV (anti-HCV) and genotypes was determined in them, and the molecular evolutionary analysis based on the neutral theory was applied to HCV isolates of genotype 4a, which is outstandingly prevalent in Egypt and indigenous there. Of 3608 sera, 317 (8.8%) were positive for anti-HCV. The molecular evolutionary analysis on 47 HCV genotype 4a isolates of carriers from various districts in Egypt indicated that the spread of HCV-4a would have increased exponentially during the 1940s through 1980 when oral medications became available. In conclusion, the estimated spread time is consistent with the duration of intravenous antimony campaigns in Egypt.

Protective Effect of Vaccination with Toxoplasma Lysate Antigen and CpG as an Adjuvant against Toxoplasma gondii in Susceptible C57BL/6 Mice

Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems to both humans and livestock and of great economic impact worldwide. Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote Th1 responses, an adjuvant activity that is desirable for vaccination against intracellular pathogens. We investigated the feasibility of using CpG as an adjuvant combined with Toxoplasma lysate antigen (TLA) as a vaccine against toxoplasmosis. Genetically susceptible C57BL/6 mice were vaccinated with TLA with or without CpG ODN as an adjuvant and then challenged with 85 cysts of the moderately virulent RRA (Beverley) strain of T gondii. Prior to challenge infection, immunization with TLA plus CpG ODN directed cellular and humoral immunity toward a Th1 pattern, characterized by enhanced INF7 production by splenic cells in response to TLA, and enhanced production of toxoplasma‐specific IgG and IgG2a antibodies. Consequently, CpG/TLA‐treated mice showed prolonged survival and 64% reduction in brain parasite burden compared to non‐CpG/TLA treated group. Our results suggest that CpG ODN would provide a stable and effective adjuvant for use in vaccination against toxoplasmosis.

BMI1 gene expression in myeloid leukemias and its impact on prognosis.

BACKGROUND BMI1 is a polycomb group (PcG) protein and is overexpressed in leukemia. It plays a key role in the self-renewal of stem cells. Leukemic cells lacking BMI1 underwent proliferation arrest and showed signs of differentiation and apoptosis. AIM This study was aimed to investigate the expression and impact of BMI1 in myeloid leukemias. Expression levels of BMI1 in 100 acute myeloid leukemia (AML), 100 chronic myeloid leukemia (CML) patients and 20 healthy controls were measured by real time quantitative polymerase chain reaction (RQ-PCR). RESULTS The results showed that the expression of BMI1 was significantly higher in AML and CML versus control subjects (p<0.001 for both). The 2-year overall and disease free survival rates were significantly lower in patients expressing higher BMI1. Multivariate analysis showed that BMI1 was independent prognostic factor for OS for AML cases (p=0.015, HR=3.204, 95% CI=1.250-8.212). Accelerated and blastic phases in CML cases expressed higher BMI1 than chronic phase (p<0.001). CONCLUSION We concluded that detecting BMI1 is helpful for predicting the survival in AML patients and monitoring the aggressiveness and progression in patients with CML.

Vaccination with Toxoplasma lysate antigen and CpG oligodeoxynucleotides: comparison of immune responses in intranasal versus intramuscular administrations

Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoan parasites on earth and highly prevalent in most warm-blooded vertebrates. There are no drugs that target the chronic cyst stage of this infection; therefore, development of an effective vaccine would be an important advance in disease control. Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote T-helper 1 (Th1) responses, an adjuvant activity that is desirable for vaccination against intracellular pathogen. In this study, we compare the immune responses of Toxoplasma susceptible C57BL/6 mice following intranasal and intramuscular vaccination with Toxoplasma lysate antigen (TLA) with or without CpG ODN as adjuvant. Immunized and control non-immunized mice were challenged with 85 cyst of the moderately virulent Beverley strain of T. gondii. Intranasal vaccination gave significantly a higher protection compared to other groups as indicated by prolonged survival and significantly reduced brain cyst burden (P < 0.01). Intranasal vaccination stimulated cellular immunity towards Th1 response characterized by significant INF-γ production (P < 0.01). Furthermore, fecal IgA antibody levels as an indicator of mucosal immune responses were significantly higher (P < 0.05) in intranasal vaccinated group before the challenge compared to all other groups. Intranasal vaccination was not able to upgrade the Th1 humoral arm. In contrast, intramuscular vaccination enhanced humoral immunity towards a type Th1 pattern characterized by a significant increase of specific IgG and Ig2a. Our results suggest that intranasal administration of CpG/TLA would provide a stable, pronounced, and effective vaccine against toxoplasmosis through stimulation of Th1 cellular immunity and mucosal IgA.

Diagnostic Performance of an Immunoassay for Simultaneous Detection of Hcv Core Antigen and Antibodies among Haemodialysis Patients.

Nosocomial transmission of HCV is a concern in haemodialysis (HD) units worldwide. Diagnosis of HCV infection among dialysis patients is currently based on the detection of anti HCV antibodies by ELISA, and is confirmed by HCV RNA. The average window period between HCV infection and seroconversion with new generations of HCV antibody tests remains approximately 70 days with more prolonged period among dialysis patients. In this study we assessed the diagnostic performance of an immunoassay designed for simultaneous detection of anti HCV antibodies and core antigen in one step in comparison to qualitative RT-PCR and anti HCV antibodies detection test among Egyptian haemodialysis patients. The studied patients were 39 chronic renal failure patients on maintenance haemodialysis. The results obtained in the present study revealed HCV infection of 56.4%. Combined Ag/Ab test detected 3 out of the 4 anti-HCV negative viraemic patients who were in the window period. The sensitivity, specificity and accuracy of the test were higher than that of anti HCV antibodies detection test (95.45%, 94.1% and 94.87% versus 81.8%, 88.23% and 84.6%) and they were raised to 100% on combining its positivity with liver enzymes elevation results. Therefore, this simple combined Ag/Ab test can be applied for early detection of HCV infection during window period among HD patients as an alternative to HCV RNA detection.

Genotyping and Clinicoepidemiological Characterization of Rotavirus Acute Gastroenteritis in Egyptian Children

Group A rotavirus (RVA) acute gastroenteritis (AGE) is a common cause of severe childhood diarrhea. The dominant circulating RVA genotypes in a given region may vary between and within the geographic regions and from year to year. Our cross-sectional study was designed to determine the burden of RVA genotypes among children with AGE admitted to referral Children Hospital at Egypt prior to implementation of the vaccine. Stool samples with clinico-epidemiological data were collected from 92 children ≤ 3 years-old with AGE. RVA G and P typing were performed with type-specific primers. RVA was detected in 48.9% of patients. Higher rates of RVA infections, 73.3% were detected in infants < 1 year-old. Breast-fed infants were significantly fewer in RVA positive group (P = 0.0006). Non-breastfeeding was a major risk factor for RVA AGE (OR 0.3, P = 0.02). RVA diarrhea occurred mostly in autumn and winter months (55.4% and 26.6%) with a significant difference in autumn (P = 0.0005) and was associated with vomiting and dehydration (OR; 1.66, P = 0.021 & 1.4, P = 0.03). RVA genotypes G1P[8] (26.7%), G9P[8] (20%) and G3P[8] (15.6%) were accounting for 62.3% of RVA AGE. G9 was significantly associated with mucus diarrhea, than G1 or G3 which were associated with watery diarrhea (P = 0.025). Also, G9 was significantly associated with loose stool for > 5 days (P = 0.006) and 54.4% of G9 patients had severe dehydration. The diversity of RVA strains detected in Nile Delta Egypt and emergence of G9 RVA highlight the need to apply vaccines against this genotype in Egypt.

Impact of ApoE genotypes variations on Toxoplasma patients with dementia

BACKGROUND Toxoplasma deprives host neuron cells from cholesterol and leads to its ability to potentiate dementia. ApoE intermediates neuronal transmission of cholesterol, which is a key constituent for axonal development, redesigning occasions that are important for education and synaptic arrangement, development of memory and repair of neuron. The aim of this work is to investigate the effect of ApoE genotypes on dementia associated with neurodegeneration in latent Toxoplasma gondii in elderly population. METHODS This study comprised: 133 patients with dementia (78 were positive for toxoplasma IgG and 55 were negative) and 95 subjects as control group without dementia (30 were positive for toxoplasma IgG and 65 were negative). All of them were subjected to a cognitive assessment, T. gondii seropositivity (ELISA) and determination of ApoE allelic forms (PCR). RESULTS The ApoE genotype distribution shows that the most predominant genotype is ApoE3/3 and the most widely recognized allele is E3. Both patients and control were further divided into Toxoplasma IgG positive group (n=108) and Toxoplasma IgG negative group (n=120). ApoE4 non carrier, ApoE 2/3 and ApoE 3/3 alleles have highly significant differences (P<0.001) between dementia and non-dementia patients in Toxoplasma infected patients in comparison to non-infected ones. CONCLUSION Toxoplasma positive patients have more risk to develop dementia regardless ApoE4 carriage.