Mostafa K. Mohamed

The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt

BACKGROUND The population of Egypt has a heavy burden of liver disease, mostly due to chronic infection with hepatitis C virus (HCV). Overall prevalence of antibody to HCV in the general population is around 15-20%. The risk factor for HCV transmission that specifically sets Egypt apart from other countries is a personal history of parenteral antischistosomal therapy (PAT). A review of the Egyptian PAT mass-treatment campaigns, discontinued only in the 1980s, show a very high potential for transmission of blood-borne pathogens. We examine the relative importance of PAT in the spread of HCV in Egypt. METHODS The degree of exposure to PAT by cohort was estimated from 1961-86 Ministry of Health data. A cohort-specific exposure index for PAT was calculated and compared with cohort-specific HCV prevalence rates in four regions. FINDINGS HCV prevalence was calculated for 8499 Egyptians aged 10-50 years. A significant association between seroprevalence of antibodies to HCV and the exposure index (1.31 [95% CI 1.08-1.59]; p=0.007) was identified across four different regions. In all regions cohort-specific HCV prevalence was lowest in children and young adults than in older cohorts. These lower prevalence rates coincided with the gradual and final replacement of PAT with oral antischistosomal drugs at different points in time in the four regions. INTERPRETATION The data suggest that PAT had a major role in the spread of HCV throughout Egypt. This intensive transmission established a large reservoir of chronic HCV infection, responsible for the high prevalence of HCV infection and current high rates of transmission. Egypts mass campaigns of PAT may represent the worlds largest iatrogenic transmission of blood-borne pathogens.

HCV burden of infection in Egypt: results from a nationwide survey.

Summary.  Egypt is the country with the largest hepatitis C virus (HCV) epidemic in the world. In 2008, a Demographic Health Survey (DHS) was carried out in Egypt, providing for the first time a unique opportunity for HCV antibody testing on a nationwide representative sample of individuals. Consenting individuals answered a questionnaire on socio‐demographic characteristics and iatrogenic exposures, before providing a blood sample for HCV antibody testing by enzyme‐linked immunosorbent assay. Factors independently associated with HCV infection were examined through multivariate logistic regression models. Of 12 780 eligible subjects aged 15–59 years, 11 126 (87.1%) agreed to participate and provided a blood sample. HCV antibody prevalence nationwide was 14.7% (95% CI 13.9–15.5%) in this age group. HCV antibody prevalence gradually increased with age, reaching, in the 50–59 years age group, 46.3% and 30.8% in males and females, respectively. It was higher in males compared to females (17.4% versus 12.2%, respectively, P < 0.001), and in rural compared to urban areas (18.3% versus 10.3%, respectively, P < 0.001). In multivariate analysis, age, male sex, poverty, past history of intravenous anti‐schistosomiasis treatment, blood transfusion, and living outside of the Frontier Governorates were all significantly associated with an increased risk of HCV infection. In addition, in urban areas, lack of education and being circumcised for females were associated with an increased risk of HCV infection. This study confirmed on a nationwide representative sample the very high HCV antibody prevalence in Egypt. It stresses the urgent need for strengthening prevention efforts, and bringing down the costs of antiviral drugs for countries like Egypt, where the people in the most precarious situations are also those most likely to be infected by the virus.

Intrafamilial transmission of hepatitis C in Egypt

The incidence of hepatitis C (HCV) infection and associated risk factors were prospectively assessed in a cohort of 6,734 Egyptians from 2 rural villages who were negative for antibodies to HCV (anti‐HCV). Initial and follow‐up sera were tested for anti‐HCV by enzyme immunoassay (EIA), and possible incident cases were confirmed by using the microparticle enzyme immunoassay (MEIA) and tested for HCV RNA. All follow‐up serum samples converting from negative to positive without detectable HCV‐RNA were further tested by recombinant immunoblot assay. Over an average of 1.6 years, asymptomatic anti‐HCV seroconversion occurred in 33 people (3.1/1,000 person‐years [PY]), including 28 (6.8/1,000 PY) in the Nile Delta village (AES), where prevalence was 24% and 5 (0.8/1,000 PY) in the Upper Egypt village (baseline prevalence of 9%). The strongest predictor of incident HCV was having an anti‐HCV–positive family member. Among those that did, incidence was 5.8/1,000 PY, compared (P < .001) with 1.0/1,000 PY; 27 of 33 incident cases had an anti‐HCV–positive family member. Parenteral exposures increased the risk of HCV but were not statistically significant; 67% of seroconverters were younger than 20 years of age, and the highest incidence rate (14.1/1,000 PY) was in children younger than 10 who were living in AES households with an anti‐HCV–positive parent. In conclusion, young children would especially benefit from measures reducing exposures or preventing infection with HCV. (HEPATOLOGY 2005.)

Higher clearance of hepatitis C virus infection in females compared with males

Background and aims: According to the literature, 14–46% of subjects clear hepatitis C virus (HCV) from blood after infection. Controversy exists about sex differences in HCV clearance rates. Patients and methods: We compared HCV clearance in males and females using data from a large population based study on HCV infection in Egypt. Definitions used in the paper were: cleared HCV infection (positive HCV antibody and negative HCV RNA test results) and chronic HCV infection (positive HCV antibody and positive HCV RNA test results). The study sample included 4720 village residents aged 18–65 years recruited through home based visits (n = 2425) or voluntary screening (n = 2295). Results: Overall, HCV antibody prevalence was 910/4720 (19.3% (95% confidence interval 18.2–20.4)). Of those with HCV antibodies (n = 910), 61.5% had chronic HCV infection. Compared with males, females were more likely to have cleared the virus (44.6% v 33.7%, respectively; p = 0.001). Control for age, schistosomiasis history, iatrogenic exposures, and sexual exposure to HCV did not alter the positive association between female sex and viral clearance. Conclusion: This study provides strong evidence in favour of a higher HCV clearance rate in females compared with males.

Metabolic and cardiovascular risk profiles and hepatitis C virus infection in rural Egypt

Background and aim: To investigate the relationship between lipid profiles and diabetes with past and chronic hepatitis C virus (HCV) infection among village residents of Egypt. Patients and methods: Fasting lipids and glucose profiles were compared among adults never infected with HCV (negative HCV antibodies), infected in the past (positive HCV antibodies and negative HCV RNA) and chronically infected (positive HCV antibodies and HCV RNA). Results: Of the 765 participants, 456 (59.6%) were female, and median age was 40 (range 25–88) years. Chronic HCV infection was present in 113 (14.8%) and past infection in 67 (8.8%). After adjustment for age and sex, participants with chronic HCV infection had lower plasma low density lipoproteins (LDL) cholesterol and triglyceride levels compared with those never infected (age and sex adjusted differences (95% CI) were −19.0 (−26.3 to −11.7) mg/dl and −26.2 (−39.0 to −13.3) mg/dl, respectively). In contrast, participants with cleared HCV infection had higher triglyceride levels compared with those never infected (age and sex adjusted difference (95% CI) was +16.0 (0.03 to 31.9) mg/dl). In multivariate analysis, participants with chronic HCV infection were more likely to have diabetes (OR 3.05, 95% CI 1.19 to 7.81) compared with those never infected, independent of LDL cholesterol levels. Conclusion: In conclusion, this community based study has shown that in a single population, chronic HCV infection is associated with glucose intolerance and, despite that, a favourable lipid pattern. An intriguing finding was the high triglyceride levels observed among participants with past infection, suggesting that elevated triglycerides at the time of acute infection may facilitate viral clearance.

Comparison of Cigarette and Water Pipe Smoking Among Female University Students in Egypt

This study investigated behavioral and sociodemographic factors associated with tobacco use among female university students patronizing water pipe cafes in Cairo, Egypt. We interviewed two groups of female university student smokers (100 and 96 students from a public and a private university, respectively). The interviews took place in nine water pipe cafes near the two universities. A logistic regression model was developed to analyze the relationship between tobacco-related knowledge and beliefs and the choice between smoking water pipe or cigarettes. Among these smokers, 27% smoked cigarettes only, 37.8% smoked water pipe only, and 35.2% smoked both types of tobacco. Most of the water pipe smokers (74.1%) preferred this method because they believe it to be less harmful than smoking cigarettes. More than half of the subjects were encouraged to start smoking by other females (56.6%). Curiosity was a significant factor for initiation (OR = 2.8, 95% CI = 1.3-6.2, p<.01). We found no significant differences between water pipe and cigarette smokers regarding current age, age at initiation, quit attempts, knowledge about the hazards of smoking, wanting to be fashionable, or smoking with friends. About one in four (23.7%) attempted to quit, with health cited as a major reason. An urgent need exists for correction of the misperception among this study population that water pipe smoking is safe and less harmful than cigarette smoking.

HCV iatrogenic and intrafamilial transmission in Greater Cairo, Egypt

Objectives To document hepatitis C virus (HCV) intrafamilial transmission and assess its relative importance in comparison to other current modes of transmission in the country with the largest HCV epidemic in the world. HCV intrafamilial transmission was defined as HCV transmission among relatives living in the same household. Design Case–control study. Cases were adult patients with acute hepatitis C diagnosed in two ‘fever hospitals’ of Cairo. Controls were adult patients with acute hepatitis A diagnosed in the same two hospitals, and family members of cases. All consenting household members of cases provided blood for HCV serological and RNA testing. Homology of viral sequences (NS5b region) within households was used to ascertain HCV intrafamilial transmission. Exposures at risk for HCV during the 1–6 months previous to onset of symptoms were assessed in all cases and controls. Results From April 2002 to June 2007, 100 cases with acute hepatitis C, and 678 controls (416 household members and 262 patients with acute hepatitis A) were recruited in the study. Factors independently associated with HCV infection and their attributable fractions (AFs) were the following: having had a catheter (OR=5.0, 95% CI=1.4 to 17.8; AF=6.7%), an intravenous perfusion (OR=5.8, 95% CI=2.5 to 13.3; AF=20.1%), stitches (OR=2.0, 95% CI=1.3 to 6.6; AF=10.7%), gum treatment (OR=3.7, 95% CI=1.1 to 11.9; AF=3.8%) and being illiterate (OR=2.4, 95% CI=1.4 to 4.4). Of the 100 cases, 18 had viraemic HCV-infected household members. Three long-married (>15 years) couples were infected with virtually identical sequences and none of the three index patients reported any exposure at risk, suggesting HCV intra-familial transmission. Conclusion While three new HCV infections out of 100 could be linked to intra-familial transmission, parenteral iatrogenic transmission (dental care included) was accountable for 34.6% of these new infections. Thus, the relative contribution of intrafamilial transmission to HCV spread seems to be limited.

Genotoxic effects of waterpipe smoking on the buccal mucosa cells

Waterpipe smoking is popular in many parts of the world. Micronuclei (MN) evaluation in the exfoliated oral cells of smokers is a non-invasive technique for evaluation of possible tobacco harm. We aimed to assess whether MN levels are higher in waterpipe smokers than in never smokers. We examined oral smears of 128 adult male waterpipe smokers and 78 males who never smoked tobacco in rural Egypt. The total number of MN per 1000 cells per subject, and the number of MN-containing cells per individual were compared. We observed a higher level of total MN in waterpipe smokers (10 +/- 4) than in never smokers (4 +/- 2, p < 0.001). A similar difference was found for the mean number of affected cells per individual (8 +/- 3 vs. 4 +/- 1.62, p < 0.001). MN levels were not significantly dose related. This study is among the first to assess the association between waterpipe smoking and a cytogenetic measure of tobacco harm. The twofold increase in MN level is consistent with previous reports of MN in cigarette smokers. More research is needed to determine if such MN levels are predictive of future health consequences.

Dissection of familial correlations in hepatitis C virus (HCV) seroprevalence suggests intrafamilial viral transmission and genetic predisposition to infection

Objective: Unsafe injections and transfusions used during treatments are considered to be responsible for many cases of transmission of hepatitis C virus (HCV) in developing countries, but cannot account for a substantial proportion of present infections. The aim of the present work was to investigate familial clustering of HCV infection in a population living in a highly endemic area. Design, setting and participants: A large seroepidemiological survey was conducted on 3994 subjects (age range, 2–88 years) from 475 familial clusters in an Egyptian rural area. Epidemiological methods appropriate for the analysis of correlated data were used to estimate risk factors and familial dependences for HCV infection. A phylogenetic analysis was conducted to investigate HCV strain similarities within and among families. Main outcome measures: HCV familial correlations adjusted for known risk factors, similarities between viral strains. Results: Overall HCV seroprevalence was 12.3%, increasing with age. After adjustment for relevant risk factors, highly significant intrafamilial resemblances in HCV seroprevalence were obtained between father–offspring (odds ratio (OR) = 3.4 (95% confidence interval (CI), 1.8 to 6.2)), mother–offspring (OR = 3.8 (95% CI, 2.5 to 5.8)), and sibling–sibling (OR = 9.3 (95% CI, 4.9 to 17.6)), while a weaker dependence between spouses (OR = 2.2 (95% CI, 1.3 to 3.7)) was observed. Phylogenetic analysis showed greater HCV strain similarity between family members than between unrelated subjects, indicating that correlations can be explained, in part, by familial sources of virus transmission. In addition, refined dissection of correlations between first-degree relatives supported the role of host genes predisposing to HCV infection. Conclusions: Current HCV infection in endemic countries has a strong familial component explained, at least partly, by specific modes of intrafamilial viral transmission and by genetic predisposition to infection.

Towards realistic estimates of HCV incidence in Egypt

Accurate incidence estimates are essential for quantifying hepatitis C virus (HCV) epidemic dynamics and monitoring the effectiveness of public health programmes, as well as for predicting future burden of disease and planning patient care. In Egypt, the country with the largest HCV epidemic worldwide, two modelling studies have estimated age‐specific incidence rates that, applied to the age pyramid, would correspond to more than 500 000 Egyptians getting infected annually. This is in contrast to figures of the Egyptian Ministry of Health and Population that estimates new infections to be approximately 100 000 per year. We performed new analyses of nationwide data to examine the modelling assumptions that led to these estimates. Thus, we found that the key assumption of these models of a stationary epidemic is invalid. We propose an alternate approach to estimating incidence based on analysing cohort data; we find that the number of annual new infections is <150 000.