Association of genetic polymorphisms of chemokines and their receptors with clearance or persistence of hepatitis C virus infection.

BACKGROUND: Polymorphisms of certain genes may have an effect on either persistence of infection or spontaneous clearance of hepatitis C virus (HCV). We hypothesized that one or more variants of chemokines (CCL2 and CCL5) and chemokine receptors (CC chemokine receptor type 2 [CCR2]) genes are associated with the susceptibility to HCV infection. METHODS: We recruited 1460 patients with chronic HCV (CHC), 108 subjects with spontaneous virus clearance (SVC) and 1446 individuals as a healthy control group. All were genotyped for single nucleotide polymorphisms: rs13900 C/T of CCL2, rs3817655 T/A of CCL5 and rs743660 G/A and rs1799864 G/A of CCR2 using allelic discrimination real-time PCR technique. RESULTS: The carriage of the A allele of CCR2 rs743660 was significantly higher in CHC compared to SVC (odds ratio [OR] 4.03) and to controls (1.42) and in controls compared to SVC (2.85) (all P < 0.01). Similarly, the A allele of CCR2 rs1799864 was significantly higher in the CHC group when compared with both SVC (1.97) and controls (2.13) (both P < 0.01), but the OR between controls and SVC was not significant (1.08, P = 0.723). Carriage of C allele of CCL2 rs13900 and the T allele of CCL5 rs3817655 were significantly higher in SVC group when compared with both CHC (OR = 0.19 and OR = 0.24, respectively) and control groups (OR = 0.65 and OR = 0.45, respectively [all P < 0.01]). CONCLUSIONS: Susceptibility to HCV infection is associated with A alleles of both (rs743660 and rs1799864 G/A) of CCR2 while spontaneous clearance of HCV is associated with the C allele of rs13900 of CCL2 and T allele of rs3817655 of CCL5.

The association of single nucleotide polymorphisms of Toll-like receptor 3, Toll-like receptor 7 and Toll-like receptor 8 genes with the susceptibility to HCV infection.

BACKGROUND: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are linked with functional modification of cytokine responses. In chronic hepatitis C virus (HCV) infection, studies of TLR polymorphisms have primarily targeted receptor pathways implicated in viral immune responses. We hypothesized that one or more variant(s) of TLR3, TLR7 and TLR8 are associated with different outcomes of HCV infection. MATERIALS & METHODS: A total of 3368 subjects from 850 families were recruited and divided into three main groups categorized as chronic HCV CHC spontaneous viral clearance (SVC), and controls. All individuals were genotyped for three SNPs for TLR3, two SNPs for TLR7, and two SNPs for TLR8 using allelic discrimination real-time PCR. RESULTS: Carriage of the C allele in three SNPs of TLR3 (rs3775290, rs3775291, and rs5743312), the C allele in TLR7 (rs3853839) in females only, and the C allele in TLR8 (rs3764879) in males only were significantly higher in SVC group than CHC group (P < 0.001), while carriage of the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both males and females were significantly higher in CHC infection more than SVC group (P < 0.001). CONCLUSION: The C allele is protective of HCV in TLR3, TLR7 (rs3853839) in females only, and TLR8 (rs3764879) in males only, while risk of infection is linked to the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both sexes.

Associations of human leucocyte antigen class II-DQB1 alleles with hepatitis C virus infection in Egyptian population: a multicentre family-based study.

Hepatitis C infection is a global pandemic. HLA-DQB1 alleles are believed to have an effective role in immune response against HCV including susceptibility to or protection from this infection. The aim of this study was to investigate the contribution of HLA-DQB1 alleles in the outcome of HCV genotype-4 infection through a family-based association study. Egyptian families with HCV (324) were recruited for this study (324 index positive for RNA-HCV, 225 positive relatives representing chronic hepatitis C cases and 582 family members negative for HCV-RNA [control], 63 of whom spontaneously cleared the virus. All subjects were genotyped for HLA-DQB1 alleles by sequence-specific primers (SSP-PCR) and sequence-based typing (SBT) methods. The frequency of DQB1*02:01:01 carriage was significantly higher in infected patients when compared to controls and those who spontaneously cleared virus (OR=5.47, P<.0001 and OR= 6.5234, P<.0001, respectively), and the carriage of the DQB1*03:01:01:01 allele was significantly higher in those who cleared and controls when compared to the infected patients (OR=0.2889, P<.0001 and OR=0.3016, P<.0001, respectively). On the other hand, the frequency of DQB1*06:01:01 and QB1*05:01:01:01 alleles was not associated with infection (comparison of infected and cleared patients showed OR of 2.1598 [P<.01]), but it becomes nonsignificant after adjustments with the Bonferroni formula (PC >0.05) and OR= 1.3523, P>.05, respectively. This study shows that clearance of HCV is associated with DQB1*03:01:01:01 allele and chronicity of HCV infection associated with the risk allele: DQB1*02:01:01.

Surveillance of lymphatic filariasis 5 years after stopping mass drug administration in Menoufiya Governorate, Egypt.

The World Health Organization recommends that before lymphatic filariasis elimination in an area can be confirmed, an additional survey should be performed at least 5 years after stopping mass drug administration. The current study aimed to determine the status of lymphatic filariasis 5 years after cessation ofthe mass drug administration in 3 sentinel Egyptian villages in Menoufiya Governorate. The rapid immunochromatographic card test (ICT) and a new commercial antibody detection kit (CELISA®) were used. All 1321 primary-school children aged 6-7 years old were ICT negative but 27 children were antibody positive. All households surveyed in one village with the highest antibody prevalence were ICT negative, indicating an absence of lymphatic filariasis. The CELISA antibody kit needs more standardization and development to be useful under field conditions. We conclude that lymphatic filariasis is no longer a public health problem in these villages and other villages with similar epidemiological conditions.

Impact of polystyrene beads as a mosquito control measure to supplement lymphatic filariasis elimination activities in Socotra Island, Yemen.

Lymphatic filariasis (LF) is targeted for worldwide elimination. In Yemen, all mainland implementation units met the WHO criteria for stopping mass drug administration (MDA) after 5 rounds. However, in Socotra Island these criteria were not met. Our study evaluated the efficacy of applying expanded polystyrene beads (EPBs) on the Culex population and the effect on LF transmission. Human and mosquito surveys were conducted in 40 randomly selected households in Hadibo (capital of Socotra) before and after application of EPBs. The EPBs intervention resulted in a reduction in mosquito density of 80% and a 64.3% reduction in microfilaria prevalence. The majority of interviewed households (98%) thought EPBs considerably reduced the mosquito population. After the intervention all collected pools tested negative. Application of EPBs is an effective supplement to MDA for achieving the goal of LF elimination.

Bancroftian filariasis in Egypt: visualization of adult worms and subclinical lymphatic pathology by scrotal ultrasound.

The purpose of this study was to explore the value of scrotal ultrasound as a means of evaluating Bancroftian filariasis. Color Doppler ultrasound examinations were performed to look for subclinical hydroceles and motile adult filarial worms (dancing worms) in dilated lymphatics. Sixty-one male subjects from a filariasis-endemic area in Egypt were studied including 19 clinically normal microfilaria (MF) carriers (seven with dancing worms and eight with subclinical hydroceles), 13 MF-negative subjects with positive filarial antigen test results (three with dancing worms and seven with subclinical hydroceles), 22 exposed subjects with no MF and negative antigen test results (no dancing worms, four subclinical hydroceles), and seven subjects with clinical filariasis (no dancing worms, seven hydroceles). Thus, all men tested with clinical filariasis and most clinically normal subjects with either microfilaremia or filarial antigenemia had abnormal ultrasound examination results. Ultrasound findings often changed after therapy with diethylcarbamazine, with disappearance of dancing worms and development of new scrotal calcifications or hydroceles. This study confirms the value of scrotal ultrasound as a means of noninvasively visualizing adult filarial worms and assessing subclinical lymphatic damage in Bancroftian filariasis.

A longitudinal study of Bancroftian filariasis in the Nile Delta of Egypt: baseline data and one-year follow-up.

We initiated a longitudinal study of Bancroftian filariasis to improve understanding of dynamics and risk factors for infection in villages near Cairo, Egypt. Baseline prevalence rates for microfilaremia and filarial antigenemia for 1,853 subjects more than 9 years of age were 7.7% and 11.2%, respectively. Microfilaria counts, antigen levels, and microfilaremia incidence over a 1-year period were all significantly lower in older people. These findings suggest that humans develop partial immunity to Wuchereria bancrofti over time. One-year incidence rates for microfilaremia and antigenemia were 1.8% and 3.1%, respectively. Filarial antigenemia, IgG4 antibody to recombinant antigen BmM14, and household infection were all significant risk factors for microfilaremia incidence. Microfilaria counts and parasite antigen levels were significantly reduced by diethylcarbamazine therapy, but many infected subjects refused treatment, and most treated people were still infected one year later. Incident infections approximately balanced infections lost to produce an apparent state of dynamic equilibrium.

Lymphatic filariasis in the Eastern Mediterranean Region: current status and prospects for elimination.

Lymphatic filariasis (LF) represents a major public health problem in tropical and subtropical regions of the world. The disease is endemic or suspected in several countries of the Eastern Mediterranean Region. Recent advances in diagnosis and therapy led the World Health Assembly to pass a resolution in 1997 calling for "the elimination of lymphatic filariasis as a public health problem." The elimination strategy is based on rounds of mass drug administration of an annual single-dose of combined drug regimens for 5-6 consecutive years. Subsequent steps included formation of a Regional Programme Review Group to orient national LF control programmes towards the concept of elimination, provide advice, review each national plan of action and review annual reports. To date, Egypt and the Republic of Yemen have active national LF elimination programmes, however, elimination activities in the Republic of Yemen are still restricted to certain identified endemic regions. Other countries in the Region are on their way to verifying the situation and if LF is proved to be endemic, will start mapping endemic localities. This review sheds light on the status of LF elimination activities in the Region and highlights some of the major accomplishments.

A retrospective hospital study of human cystic echinococcosis in Egypt.

We performed a retrospective study to determine annual clinical incidence of human cystic echinococcosis (CE) in 14 Egyptian hospitals between January 1997 and December 1999. From 492 353 records examined, 133 (0.027%) new human CE cases were recorded. Of these, 50 (37.6%) were from Alexandria and Matrouh hospitals, 33 (24.8%) from Giza Chest Hospital and 50 from other regions. Matrouh governorate had the highest annual clinical incidence (1.34-2.60 per 100 000) followed by Giza governorate (0.80-1.16 per 100 000). About a third of those affected were aged < or = 20 years. Liver and lungs were the organs most affected. Although human CE is of low endemicity in Egypt, it may-represent a public health concern in Matrouh and Giza governorates.

Diabetic nephropathy as a cause of end-stage renal disease in Egypt: a six-year study.

The prevalence of diabetic nephropathy as a cause of end-stage renal disease (ESRD) in Egypt has been examined in small cross-sectional studies, with conflicting results. The need for a large-scale study prompted us to perform this 6-year multiple cross-sectional study. A sample of ESRD patients enrolled in the Egyptian renal data system was evaluated during the period 1996-2001 for the prevalence of diabetic nephropathy. Prevalence gradually increased from 8.9% in 1996, to 14.5% in 2001. The mean age of patients with diabetic nephropathy was significantly higher than that of patients with ESRD from other causes. Mortality was also significantly higher in diabetic patients with ESRD.

Assessment of tobacco dependence in waterpipe smokers in Egypt.

SETTING: Waterpipe smoking is increasing worldwide. Nevertheless, little is known about nicotine dependence in tobacco smokers who use waterpipes. OBJECTIVE: To assess evidence of dependence among non-cigarette smoking waterpipe smokers in Egypt. METHODS: A total of 154 male exclusive current waterpipe smokers were enrolled for the present study. We adapted the Fagerström test for nicotine dependence and the Reasons for Smoking (RFS) scales and related these to smoking behavior. RESULTS: The mean age of the subjects was 47 ± 14 years, the mean age at smoking initiation was 22 ± 9 years, and average daily consumption was 4 ± 8 hagars (tobacco units). The time to the first smoke of the day (P < 0.001), smoking even when ill (P = 0.003), time to tobacco craving (P < 0.001), and hating to give up the first smoke of the day (P = 0.033) were each significantly associated with the number of hagars smoked per day. The RFS subscales of addictive smoking, smoking to relieve negative affect, and smoking for stimulation were also associated with these variables. CONCLUSION: The overall findings suggest that waterpipe smokers exhibit many of the same features of nicotine dependency attributed to cigarette smokers.