Transmission of Hepatitis C between Spouses An Epidemiological
Transkript
Transmission of Hepatitis C between Spouses An Epidemiological
Med. J. Cairo Univ., Vol. 82, No. 1, June: 297-308, 2014 www.medicaljournalofcairouniversity.net Transmission of Hepatitis C between Spouses An Epidemiological Study at National Liver Institute Hospital WESAM S. MORAD, M.D. 1 ; MOHAMED K. EL-SOBKY, M.D.2 ; GAAFAR M. ABDEL-RASOUL, M.D. 2 ; EMAN A. REWISHA, M.D. 3 ; OLFAT M. HENDY, M.D. 4 and MANAL A. EL-BATANONY, M.D. 2 The Departments of Community Medicine, National Liver Institute 1 , Faculty of Medicine 2 , Hepatology 3 and Clinical Pathology4, National Liver Institute, Menoufiya University Abstract single subtype, 4a, which responds less successfully to interferon therapy than other subtypes [6-8] . Background/Aims: In Egypt, relatively higher rates of sexual transmission have been reported and reflect the higher background prevalence in this country. In rural Egypt, sexual transmission between monogamous spouses ranged between 3 and 34%. It was said that Egypt has one of the highest HCV prevalence rates in the world. About one in every 10 persons has the virus. It is widely believed that mass therapy of Egypt’s rural population against schistosomiasis (bilharziasis) in the 1960s and 1970s, which did not follow rigorous hygiene standards, are responsible for the current rates of hepatitis C. Bilharziasis, a water-borne disease, and was at one time endemic in Egypt. Also he blames the high HCV rates on bad hygiene habits, the population’s ignorance of the virus and lack of a vaccine against the virus. Also it can come from children playing with scissors, teenage boys borrowing someone’s razor to shave or even a toothbrush. These persons don’t have any manifestations, they don’t feel anything, and it is often discovered by accident [9] . Methods: This is a cross sectional hospital based study evaluated the non-sexual and sexual risk factors of HCV infection transmission from male and female index cases to their spouses. This study documented previously uncertained lifestyle risk factors for HCV transmission between spouses, confirmed the high prevalence of HCV infection (17% to 26%) in Egypt which is higher than other parts of the world, and provided evidence of sexual transmission of HCV (30). Results: HCV transmission from wife to husband including sexual relationship occurred in 46% of cases while from husband to wife was 25% and 35.5% overall HCV transmission between spouses. Sexual intercourse of positive HCV female more than 4 times per month is 66 times risky to transmit HCV infection to her husband. Conclusion: This study emphasize that transmission between spouses significantly occur due to sexual contact but we can’t ignore the significant role of non sexual risk factors of HCV transmission among married couples. In Egypt, relatively higher rates of sexual transmission have been reported and reflect the higher background prevalence in this country. In rural egypt, sexual transmission between monogamous spouses ranged between 3 and 34% (95% CI 0-49) [10] . Key Words: Spouses – Sexual transmission – Hepatitis C virus – Obstetric risk factors – Cross-sectional studies – Roc curve. Taken together, although some cases of acute HCV have been related to sexual transmission, the degree to which sexual transmission of HCV occurs is controversial because sexual transmission is difficult to confirm given that partners might have other risk factors for HCV transmission such as Intravenous drugs users. Phylogenetic analysis to identify genetic relatedness of HCV viral isolates in partners is required to confirm sexual transmission. All studies on the sexual transmission of hepatitis C are limited by the potential of the confounding variable of IDU or shared items such as razors and other Introduction EGYPT has possibly the highest HCV prevalence in the world; 10-20% of the general population are infected and HCV is the leading cause of HCC and chronic liver disease in the country [1-5] . Approximately 90% of Egyptian HCV isolates belong to a Correspondence to: Dr. Wesam S. Morad, E-mail: wesammorad@yahoo.com 297 300 items among sexual partners. Large studies directed at evaluating HCV infected persons with multiple sexual partners are needed for accurate estimates of sexual transmission [11] . In a study among spouses in Egypt, it was estimated that wife to husband transmission was 34% and 10% for Anti HCV positive wives with and without detectable HCV RNA respectively. The probability of husband to wife transmission was estimated to be 3% and 0% for Anti HCV positive husband with and without detectable HCV RNA respectively. Overall, 6% were estimated to have contracted HCV from their spouse [10] . Early studies found the rate of HCV positivity in partners increased with the longer duration of marriage, suggesting risk of sexual transmission correlated with frequency of contact [12] . However, subsequent studies adjusting for age did not find a consistent relationship between the duration of the sexual relationship and HCV positivity in partners [13] . Some other studies indicate that sexual transmission from men to women is more efficient than transmission from women to men. Since HCV is spread through blood, the risk of sexual transmission may be higher when a woman is having her menstrual period [14] . HIV co-infection is associated with higher rates of anti-HCV in persons engaged in higher-risk sexual practices, Additionally, in studies of STD clinic attendees and men having sex with men, other STDs (herpes simplex virus, Trichomonas, gonorrhea) and sexual practices that may traumatize the mucosa (e.g., anal receptive sex) are more frequent in anti-HCV positive than anti-HCV negative individuals’. Suggesting these factors increase the sexual transmission of HCV [15,16] . Many people are very worried about getting or giving hepatitis C to others that they live with. However, it would be very hard to give or get HCV unless there is direct blood to-blood contact. Things like razors, toothbrushes, nail clippers and other personal hygiene items can spread HCV, but it is very difficult to do so. For example, in order for someone to get HCV from a tooth brush there would have to be blood from someone who has HCV on the toothbrush then someone would have to take that same toothbrush and brush their teeth. Next there would have to be an open cut or wound in the mouth for the HCV infected blood to get into the bloodstream. The bottom line is that this just doesn’t happen very Transmission of Hepatitis C between Spouses easily. In fact, there has never been a proven case of this happening [14] . In order to eliminate other possible risk factors for hepatitis C that could measure the link between sexual intercourse and HCV transmission, John interviewed each spouse about risk factors other than sexual intercourse. Each spouse also underwent an antibody test for HCV, when antibodies specific to HCV are detected, it tells the doctor that the patient has the viral infection [17] . We know that blood-borne viruses can be transmitted through certain types of sexual activity. HCV has rarely been detected in semen and vaginal fluids. However, most studies suggest that the virus is not often found in these body fluids, or that it is present in very low amounts and the virus particles may be non-infectious [14] . Some people feel more secure knowing that they are doing everything; they can prevent sexual transmission of HCV. Safer sex practices can also help to prevent the spread of hepatitis A and B, HIV, and other STDs. A decision to use safe sex methods depends on the nature of the sexual relationship [18] . To reduce the risk of HCV transmission during oral sex or deep kissing, practice regular good oral hygiene-healthy teeth and gums may be the best defense against the spread of diseases through the mouth. Many experts recommend that people avoid brushing or flossing their teeth right before or after oral sex or deep kissing, since these can cause bleeding gums and tiny abrasions [14] . Prevention messages for persons with sexual practices: Persons who are at risk for sexually transmitted diseases should be advised: That the surest way to prevent the spread of human immunodeficiency virus infection and other sexually transmitted diseases is to have sex with only one uninfected partner or not to have sex at all. - - - To use latex condoms correctly and every time to protect themselves and their partners from diseases spread through sexual activity. To get vaccinated against hepatitis B, and if appropriate, hepatitis A [19] . While sexual transmission of HCV remains somewhat controversial, most studies indicate that transmission through sexual activity is uncommon, and most experts believe the risk of sexual transmission is low. According to Maryl and National Institutes of Health, people in stable, monogamous Wesam S. Morad, et al. relationships do not need to change their current sexual practices, although they should discuss safer sex options if either partner is concerned about sexual transmission. People with multiple sex partners should practice safer sex, in particular the use of latex condoms [14] . Material and Methods Study population: On April 1, 2007 till September 30 2008, there were 200 HCV patients (110 females and 110 males) at NLI hospital, Prior to the interview 20 HCV patients (10 females and 10 males) (pilot study sample) were interviewed and tested for the efficiency of data collection forms, to detect deficiencies and remodeling them, Estimating the time needed to collect the required data and Exploring the obstacles found to know the appropriate methods to deal with them, leaving 200 HCV eligible patients for the study all were approached and asked to participate in the study provided informed consent. The study protocol was approved by the Medical Ethics Review Board of the Faculty of Medicine at the Menoufiya University. Participants were interviewed by the same interviewer using a questionnaire comprising demographic, life-style variables, medical history, non sexual risk factors, and sexual history. The demographic variables included age, residence, education and occupation. Medical variables included a history of blood transfusions or donations, hospital admission, surgery, invasive hospital procedures (venous or urinary catheterization and liver biopsy) and endoscopy, bilharsiasis history, chronic diseases history, wound sutures, skin tattoo, teath treatment or extraction, ear piercing, circumcision, abortion or caesarean section, delivery method, person and site and HCV family member at home. Life-style factors, including injection drug use, common teath brush, common face and hand towels, sharing shaving blades and/or nail cutters, skin tattoo and using condom during sexual intercourse. Sexual history included age at marriage, marital duration, sexual relationship length, history of sexually transmitted diseases sexual activity were also requested. Conforming with ethics requirements, patients were not obligated to answer every question on the questionnaire. Consequently, there were some missing responses, especially for “sensitive” life-style questions, although this represented no more than 8 percent for any one variable. Also high costs of investigations needed for each couple especially HCV RNA PCR and Hepatitis B markers to exclude hepatitis viruses other than hepatitis “C” virus as a 301 cause of hepatitis was one of the obstacles faced at the study. Laboratory methodology: Serum specimens from both hepatitis “C” patients and either their spouses, all cases were screened using a third generation ELISA using kit from Biocheme. Immunosystem Inc. It qualitatively determined the presence of antibodies to four recombinant HCV proteins in serum, serum Hbs Ag done by a test based on enzyme linked immunosorbant assay (ELIZA) by kit from Sorine Biomedica Co. and Serum from for both index male and female patients HCV infection was confirmed by detection of circulating HCV-RNA using qualitative reverse transcription-polymerase chain reaction technique (PCR) by Amplicor hepatitis C virus (HCV) from Roche. It is a direct DNA probe test that utilizes a nucleic acid amplification technology called polymerase chain reaction (PCR) and nucleic acid hybridization for the detection of HCV-RNA in human serum and plasma. Statistical analysis: Statistical analyses were performed using SPSS (SPSS, Inc., Chicago, Illinois), Epilnfo (CDC, Atlanta, Georgia), and LogXact (Cytel Software Corporation, Cambridge, Massachusetts). Associations between index male and female HCV status and dichotomous variables were assessed with the chi-square statistic. Chi-square for linear trend was used for associations between categorical variables and HCV status. When the expected number in any cell was less than five, a two-tailed Fisher’s exact test was used. When comparing two-sample means, Student’s t-test was used for normally distributed variables, while non-parametric Mann Whitney test was done for non-normally distributed variables. Odds ratio (OR) was used to calculate the risk of exposure long with 95% confidence interval and both were done to measure the strength of association. Roc curve (Receiver operating characteristic curve) was to determine cut levels of both marital duration and average number of sexual intercourse per month where at this level there were the best sensitivity and specificity and above these levels there were risk of HCV transmission. The validity of the model was measured by means of the concordance© statistic (equivalent to the area under the Roc curve). A model with a c value above 0.7 was considered useful while a c value between 0.8 and 0.9 indicated excellent diagnostic accuracy. The percentage of transmission of HCV infection from index males and females to their spouses was estimated. 302 Transmission of Hepatitis C between Spouses ROC Curve of sexual intercourse numbers of husbands of index females 1.0 Results 0.8 Sensitivity Sexual intercourse numbers above 5 of husbands of index females is more risky to acquire HCV infection from their wives with a sensitivity and specificity of (76.1&71.2%) respectively and AUC of 0.78 (Table 1). Husbands of HCV positive wives with sexual intercourse numbers more than 5 times per month is 12 times risky to acquire HCV infection than others (93.0 vs 7.0% OR, 11.75; 95% CI, 4.1-34.4) (Table 2). 0.6 0.4 0.2 0.0 0.2 0.0 0.4 0.6 Specificity - 1 Fig. (1) 1.0 0.8 Table (1): Sensitivity, specificity and accuracy of sexual intercourse numbers. Studied variables .Sexual intercourse no Cut level 5 times/month Sensitivity Specificity AUC Accuracy SE CI 76.1% 71.2% 0.78 78.6% 0.05 **(0.87 – 0.68) Highly significant ** . Table (2): Significant Sexual risk factors differences among male spouses of index females regarding HCV transmission Total No. of patients Sexual risk factors Sexual intercourse no times/month 5≥ times/month 5> 51 49 Anti HCV positive male spouses % .no 93.0 7.0 37 9 or CI 95% 11.75 ** (34.4 – 4.1) Highly significant **. It was found that the mean age of Anti HCV positive male spouses was (51.8±9.7), 93.5% endoscopic instrumentation, 87% usage of face and hand towels in common, 82.6% of past history of teeth treatment or extraction. 58.7% of past history of bilharsiasis mean age at marriage was (25.8±5.2) and mean sexual intercourse length of (23.4±10.4) (Table 3). Table (3): Non significant demographical, non-sexual and sexual risk factors among male spouses of index females .regarding HCV transmission Total No. of patients risk factors Anti HCV positive male spouses No. p value % – X±SD Demographical RF age in years: 0.14 ** 51.8±9.7 Education: Illiterate up to basic education Secondary education and above 59 41 26 20 21.7 78.3 0.6 Occupation: Specialized work non specialized work 51 49 21 25 45.7 54.3 0.32 Common teeth brush: yes 10 6 13.0 0.51 * Common face and hand towels: yes 82 40 87.0 0.23 Sharing shaving blades and/or nail cutters: yes 63 31 67.4 0.4 Goza and cigarette smoking: yes 70 34 73.9 0.43 Wesam S. Morad, et al. 303 Table (3): Count. Non Sexual RF Anti HCV positive male spouses Total No. of patients risk factors No. % p value Previous operations: yes 45 22 74.8 0.6 Hospital admission: yes 50 26 65.5 0.23 Endoscopy: yes 89 43 93.5 0.19 I.V. injections: yes 13 6 13.0 0.99 Mosquito, fleas and tics bites: yes 34 15 32.6 0.96 Chronic diseases: yes 41 21 45.7 0.38 Bilharsiasis: yes 55 27 58.7 0.49 Wound sutures: yes 32 17 37.0 0.33 Skin tattoo: yes 8 4 8.7 * 1.0 Teeth treatment or extraction: yes 74 38 82.6 0.07 Blood transfusion: yes 8 5 11.1 *0.46 Blood donation: yes 35 16 34.8 0.97 HCV infected member at home: yes 9 4 8.7 * 1.0 Using condom during intercourse: yes 1 0 0.0 * 1.0 Sexual RF _ X±SD Age at marriage in years: 46 marital duration: 46 23.5±9.8 Sexual relationship length: 46 23.4±10.4 ** 0.47 *** 0.52 25.8±5.2 * Yates corrected. ** t-test. *** mann whitney test. ROC Curve of sexual intercourse numbers among wives of index males 1.0 0.8 Sensitivity Sexual intercourse numbers above 4 of index husbands is more risky to transmit HCV infection to wives with a sensitivity and specificity of (100.0 and 76.4%) respectively and AUC of 0.96 (Table 4). Husbands of HCV positive wives with sexual intercourse numbers more than 4 times per month is 66 times risky to transmit HCV infection than others (96.0 vs 26.7% OR, 66; 95% CI, 8.461396.4) (Table 5). 0.6 0.4 0.2 0.0 0.0 Fig. (2) 0.2 0.4 0.6 Specificity - 1 0.8 1.0 304 Transmission of Hepatitis C between Spouses Table (4): Sensitivity, specificity and accuracy of sexual intercourse numbers per month. Studied variables Sensitivity Specificity AUC Accuracy SE CI 100.0% 76.4% 0.96 96.0% 0.02 ** (0.99–0.92) Sexual intercourse No. Cut level 4 times/month Table (5): Significant demographical, non-sexual and sexual risk factors among female spouses of index males regarding HCV transmission Demographical RF risk factors Total No. of patients .no % or CI %95 Occupation: 2.67 * (7.94–0.9) 20.0 6 * (35.3–1.11) 11 44.0 2.9 * (8.48–1.1) 73 14 56.0 75 23 92.0 5.09 * (34.1–1.03) ≥4 times/month 44 24 96.0 66 ≥4 times/month 56 1 4.0 Working 25 10 40.0 Housewife 75 15 60.0 8 5 By midwives 27 By others Blood transfusion: yes Non Sexual RF Anti HCV positive female spouses Ear piercing: Sharing shaving blades and/or nail cutters: Sexual RF yes *Yates corrected. Sexual intercourse number: * Significant. ** (1396.4–8.46) ** Highly significant It was found that the mean age of Anti HCV positive male spouses was (37.5±9.5), 100% circumcision, 92% past history of IV injections, 88.0% usage of face and hand towels in common, 92.0% of past history of teeth treatment or extraction. 64% of past history of bilharsiasis, mean age at marriage was (20.2±6.1) and mean sexual intercourse length of (16.9±10.2) (Table 6). Table (6): Non-significant demographical, non-sexual, obstetric and sexual risk factors among female spouses of index males regarding HCV transmission. Anti HCV positive female spouses Total No. of patients risk factors No. % p value Demographical RF X±SD :Age in years 37.5±9.5 25 **0.19 Education: Illiterate up to basic education Secondary education and above 42 58 12 13 48.0 52.0 0.48 Common teeth brush: yes 8 3 12.0 * 0.4 Common face and hand towels: yes 93 22 88.0 *0.36 Wesam S. Morad, et al. 305 Table (6): Count. Non Sexual RF risk factors Obestatric RF Anti HCV positive female spouses Total No. of patients No. % p value Previous operations: yes 52 14 56.0 0.64 Hospital admission: yes 68 19 76.0 0.32 Endoscopy: yes 9 3 12.0 * 0.16 I.V. injections: yes 95 23 92.0 * 0.59 Mosquito, fleas and tics bites: yes 81 19 76.0 * 0.56 Chronic diseases: yes 32 11 44.0 0.14 Bilharsiasis: yes 77 16 64.0 0.07 Wound sutures: yes 37 10 40.0 0.72 Circumcision: yes 97 25 100.0 * 0.57 Teeth treatment or extraction: yes 85 23 92.0 * 0.5 Blood donation: yes 3 2 8.0 * 0.15 HCV infected member at home: yes 11 5 20.0 * 0.14 Method of delivery: normal labor: Caesarean section 94 6 23 2 89.3 10.7 *0.63 Who delivery the mother?: Doctor midwives 78 22 16 9 42.3 57.7 0.05 Delivery site: At home At hospital 47 53 14 11 57.7 42.3 0.29 abortion: yes 43 11 42.3 0.91 Sexual RF – X±SD *Yates corrected. Age at marriage in years: marital duration: Sexual relationship length: ** t-test. 225 25 25 *** mann whitney test 20.2±6.1 18.2±10.3 16.9±10.2 *** 0.5 *** 0 . 19 *** 0.16 306 Transmission of Hepatitis C between Spouses It was found that High to very high PCR viremia is 17 and 30 times risky for HCV transmission from index wives and index husbands to their spouses respectively (63.0 vs 36.9% OR, 16.7; 95% CI, 5.1- 59.1) and (92.0 vs 8.0% OR, 29.6; 95% CI, 5.91199.7) of index wives and husbands respectively (Table 7). .Table (7): PCR viremia among index males and females regarding HCV transmission Total No. of patients PCR viremia Anti HCV positive index cases No. % or CI 95% Index females: High to very high viremia mild to moderate viremia 34 66 29 17 63.1 36.9 16.7 ** (59.1–5.1) Index males: High to very high viremia mild to moderate viremia 44 56 23 2 92.0 8.0 29.6 ** (199.7–5.91) **Highly significant. - (Mild viremia (600-250.000 IU). - (High viremia (2.500.000-5.000.000 IU) - (Moderate viremia (250.000-2.500.000 IU). - (Very high viremia (>5.000.000 IU). - (NLI-PCR department). frequency of HCV transmission was 46.0% from Anti HCV positive wives to their husbands and 25.0% from Anti HCV positive husbands to their wives (Fig. 3). Percentage frequency of HCV transmission between spouses 50 45 40 35 30 25 20 15 10 5 0 46 25 Husband to Wife transmission Wife to husband transmission Fig. (3): frequency of HCV transmission in both index males and index females Discussion This study was conducted to provide representative data for NLI, as well as to supply data for HCV transmission risk factors between spouses. HCV infection is a natural problem in Egypt; its prevalence rate is from 17% to 26% [20] which is higher than other parts of the world. It was 3% worldwide. In addition, the proportionate morbidity rate of HCV disease in NLI during the period of the study was 80%. There are many risk factors known which facilitate HCV transmission. In this work, we found that the risk of contracting HCV among index female and index male patients was significantly as- sociated with Demographic, non-sexual, sexual risk factors. In this study HCV, transmission from wife to husband including sexual relationship occurred in 46% of cases while from husband to wife was 25%. In a previous study among spouses in Egypt, it was estimated that wife to husband transmission was 34% and 10% for Anti HCV positive wives with and without detectable HCV RNA respectively. The probability of husband to wife transmission was estimated to be 3% and 0% for Anti HCV positive husband with and without detectable HCV RNA respectively [10] . Study risk factors for HCV transmission among spouses: The only seen association that carries a significant risk was due to no of sexual intercourse / month in both female and male spouses and in addition non-sexual factors including occupation, blood transfusion, circumcision, ear piercing and sharing shaving blades in male spouses. This non-sexual risk factors operating among male spouses may in part be related to exposure particularly to female including trauma during labor. In this study mean age of HCV positive spouses of index females or male were [(37.5±9.2 yrs) or (51.8±9.7 yrs)] higher than that of HCV negative ones [(49.2±1 1.1 yrs) or (35.4±9.2 yrs)] respectively though the difference was not significant any how this could be explained that older age results into increase marital duration so increasing incidence of HCV transmission. In similar study the mean age was higher for HCV-positive spouses (57.7 vs 49.6 yr) than for HCV negative spouses ( p-value <0.01) Wesam S. Morad, et al. [21] . Regarding Nicotine smoking (Cigarette and Goza) although the difference was non-significant but higher percent was found in HCV positive husbands of index female (73.9%) thus, we can’t ignore nicotine consumption role as a risk factor in HCV infection. This could be explained in part that sharing Goza might result into increasing risk of HCV infection especially in cases of diseased HCV cases with bleeding gums. In similar study, it was found that nicotine consumption was also higher (41.0%) in husbands of index female [22] . History of sharing shaving blades and/or nail clippers showed no significant difference in HCV infected husbands of index female versus HCV negative ones (67.4 vs 59.2%) but again higher percent was found in HCV positive than HCV negative ones on the other hand it showed significant difference (p-value <0.05) in HCV infected wives of index males versus HCV negative ones (92.0 vs 69.3% OR, 5.09; 95% CI, 1.03–34.1) respectively. It is possible that, dry blood on shaving blades or nail cutters might be a source of HCV infection when shared with others. In similar study it was found that (87.5%) were sharing nail clippers and (58.3%) of them were sharing manicure cutters [23] . Although using teeth brush in common didn’t show association between significant HCV transmission among spouses but still carry a higher percent among HCV positive spouses compared with their negative ones. This could be explained by brush contamination from bleeding gums of HCV index cases. Terrault, [24] stated that differences between risk groups although in some cases was not significant yet it may reflect different rates of exposure to non-sexual sources of HCV, such as sharing nail clippers, manicure cutters or toothbrushes. In this research endoscopy wasn’t a significant factor among HCV positive index spouses versus HCV negative ones, this reflect different rates of exposure to non-sexual sources of HCV as a higher percent was found in HCV positive spouses (93.5 vs. 85.2% and 12.0 vs. 8.0%). In similar work done, Centers for Disease Control and Prevention reported that Patient to patient transmission of HCV occurred via endoscopy [25] . Past history of IV injections were found equal (13.0%) between HCV positive husbands of index females versus their HCV negative ones, while higher percent was found in HCV negative wives of index male versus their HCV positive ones (75.8% vs. 92.0%). This again can reflect difference in exposure rate between female and male spouses. In similar study it showed that the percentage of couples sharing glass syringes was significantly higher 307 among those with both partners infected (65.6% vs 12.9%; OR=12.9; 95% CI=5.4–31.4) [21] . History of Bilharziasis had no significant difference in positive HCV spouses compared with their negative ones although still more recorded by positive HCV female spouses compared with their HCV negative ones and high in HCV negative male spouses compared with their HCV positive ones (58.7 vs. 51.9% and 81.3 vs. 64.0%) respectively. In other study, it was reported that Egypt has the highest HCV prevalence worldwide and the use of parenteral antishistosomal therapy has been implicated in this high rate of infection [26] . Past history of blood transfusion was still more recorded by positive HCV infected spouses (20.0%) in females (11.1%) in males compared with HCV negative ones but the difference was not significant in male spouses of index females while, it was carried 6 times more risk in HCV transmission in female spouses of index males than those with negative history respectively. It might be explained that blood transfusion via inadequate sterilized equipments in street campaigns was a risk factor of HCV transmission. In similar study it was reported that (37.5%) of positive HCV spouses gave past history of blood transfusion [23] . In this study, it was found that no significant difference (p-value >0.05) was found regarding practicing unprotected sex (sex without condoms) among HCV positive husbands of index females compared with their negative ones (100% vs. 98.2%). This reflects monogamous relationships between spouses which, carry less violence or through vaginal candiasis risk for HCV transmission while sex with more than one partner carries high risk of HCV infection if not well protected. In agreement with that was found (96.0%) of husbands of positive spouses were conducted unprotected sexual intercourse [13] . In agreement with other authors average duration of marriage in this study was longer among HCV positive spouses of index females and males compared with their HCV negative ones (23.5±9.8 vs. 21.9±13.3 and 18.2±10.3 yrs vs. 14.8±8.3 yrs) respectively. This could be explained by that, marriage usually includes a sexual relationship, but also other kinds of body contact and exposure to other risk factors (i.e. sharing the same personal tools such as toothbrushes, razors and others) may increase risk of HCV transmission between spouses. Homology analysis on HCV nucleotide sequence is important in study of sexual transmission of HCV, but we did not perform homology analysis in this study because of cost burden so it was not easy to 308 explain the increased rate of HCV infection in couples married for a longer time. In similar study average duration of marriage was (1521±506.7) & (1532.4±670.2) weeks (p>0.05) [27] . In other study, it was found that spouses of antiHCV positive patients were more likely to be infected with HCV than other family members and the infection rate increased with duration of marriage. In particular, a significant difference was found in the prevalence of positive anti-HCV between spouses married for more than 15 years and those married for a shorter time [28] . On the contrary, another study done showed that there is no prevalence of HCV infection between sexual partners married for 13 years or more. This discrepancy might be due to differences in studied samples or due to differences in sexual behavior or non-sexual risky exposure [29] . Although average length of sexual relationship of HCV positive female and male spouses was longer than that of their HCV negative ones (23.4±10.4 vs. 21.6±11.8 and 16.9±10.2 yrs vs. 14.3±7.9 yrs) respectively but still not a significant risk factor for HCV transmission. In this study, it was found that higher percent of positive HCV female and male spouses gave history of sexual intercourse more than 4 up to 5 times per month than HCV negative ones and that they were more risky to had HCV infection than those practicing sex in fewer times (93.0% vs 7.0%; p-value <0.01; OR, 11.75; 95% CI, 4.14-34.4 and 96.4% vs 25.9%; p-value <0.01; OR, 77.32; 95% CI, 10.11619) respectively. All couples denied practicing anal intercourse or sex during menstruation. In similar study it was reported that The mean length of sexual relationship was 21.4 years in which 94.0% of couples were sexually active and 6.0% didn’t and the average rate of sexual intercourse was 1.6 times per week (6.4 times per month) as estimated for the whole period of partnership [13] . In other study, the risk of sexual transmission of hepatitis C virus infection was evaluated among 895 monogamous heterosexual partners of HCV chronically infected individuals were followed for 10 years in a long-term prospective study. It was found that the average weekly rate of sexual intercourse was 1.8 [30] . A highly significant association ( p-value <0.0 1) was found between PCR viremia degrees in index females or males and transmission of HCV to their Transmission of Hepatitis C between Spouses spouses. Index females and males with high up to very high viremia transmit HCV infection (63.1 and 92.0%) to their spouses respectively while those with low up to moderate viremia (36.9 and 8.0%) respectively. In addition, those index female and male cases with high viremia had greater risk in transmission of HCV infection to their spouses than those with lower viremia (OR, 16.7; 95% CI, 5.1–59.1 and OR, 29.6; 95% CI, 5.91–199.7) respectively. On the other hand no significant association was found between HCV positive index females and males versus their HCV negative ones ( p-value >0.05), regarding the rest of risk factors; age, Education, occupation, common teeth brush, use of common hand and face towels, sharing shaving blades and/or nail cutters, Cigarette and Goza smoking, past history of previous operations, hospital admission, endoscopy, mosquito, fleas and tics bites, chronic diseases history, bilharsiasis, wound sutures, ear piercing, blood donation, I.V. injections, teeth treatment or extraction, presence of HCV infected family member at home, using condom at intercourse, sexual diseases, methods of delivery, delivery site, who deliver mother, abortion, place of beard shaving, age at marriage, marital duration and length of sexual relationship. Although in HCV positive spouses higher percent was found regarding positive HCV cases versus lower percent in HCV negative ones thus these risk factors though not playing seen role in transmission between spouses yet we can’t exclude completely their role in HCV transmission among them. In this study it was found that overall percentage of HCV transmission between spouses was (35.5%) where (46.0%) transmission from wife to husband and (25.0%) from husband to wife. In a study among spouses in Egypt, it was estimated that wife to husband transmission was 34% and 10% for Anti HCV positive wives with and without detectable HCV RNA respectively. The probability of husband to wife transmission was estimated to be 3% and 0% for Anti HCV positive husband with and without detectable HCV RNA respectively [13] . These later percentage is much lower than that detected in this study where the overall HCV transmission was (35.5%) this difference in the overall HCV transmission can be due to the change in the prevalence of HCV in Egypt possibly increasing by time also the finding that (80-90%) of female and male spouses were practicing sex more than 3-4 times/month may increase the likelihood of transmission between spouses. Moreover the significant Wesam S. Morad, et al. 309 association between degree of viremia among male and female index groups and the percent of spouses infected by HCV and the significant relationship between no of sexual intercourse and percentage of transmission of HCV infection among spouses, emphasize that transmission between spouses significantly occur due to sexual contact but we can’t ignore the significant role of non sexual risk factors of HCV transmission among married couples such as type of occupation, sharing clippers or nail cutters and blood transfusion. Acknowledgments: This study was supported by cooperation of all patients and their spouses who responded to my questionnaire and supplied me with the needed data that were included in this work. References 1- ARTHUR R.R., HASSAN N.F., ABDALLAH M.Y., EL SHARKAWY M.S., SAAD M.D., HACKBART B.G. and IMAM I.Z.: “Hepatitis C antibody prevalence in blood donors in different governorates in Egypt.” Trans. R. Soc. Trop. Med. Hyg., 91: 271-274, 1997. 9- AL-SAYED HAMDY M.: “Egypt: Poor hygiene, ignorance blamed for prevalence of hepatitis C.” Cairo, 6 march (IRIN). http://wwwjrinnews.org/Report.aspx? ReportId= 77141, 2008. 10- MAGDER FIX A.D., MIKHAIL N.N., MOHAMED M.K., ABDEL-HAMID M. ABDEL-AZIZ F., MEDHAT A. and STRICKL G.T.: “Estimation of the risk of transmission of hepatitis C between spouses in Egypt based on seroprevalence data.” International Journal of Epidemiology, 34: 160-165, 2005. 11 - SANAA M. KAMAL: “Sexual Transmission of HCV between Spouses.” The American Journal of Gastroenterology, 10.1111/j.1572-0241, 2005. 12- AKAHANE Y., KOJIMA M., SUGAI Y., SAKAMOTO M., MIYAZAKI Y., TANAKA T. and TSUDA F.: “Hepatitis C virus infection in spouses of patients with type C chronic liver disease.” Annual Internal Medicine, 120: 748752, 1994. 13- NEUMAYR G., PROPST A., SCHWAIGHOFER H., JUDMAIER G. and VOGEL W.: “Lack of evidence for the heterosexual transmission of hepatitis C.” Q. J. Med., 92: 505-508, 1999. 14- JEREMIAH DONOVAN: “Sex and the C Virus” HCV ADVOCATE journal. http://www.hcvadvocate.org , 2008. 2- EL-ZAYADI A., H. ABAZA, S. SHAWKY, M.K. MOHAMED, O. SELIM and H.M. BADRAN: “Prevalence and epidemiological features of hepatocellular carcinoma in Egypt, a single centre experience.” Hepatology, 19: 170179, 2001. 15- HERSHOW R.C., KALISH L.A., SHA B., TILL M., COHEN M., GIULIANI M. and CAPRILLI F.: “Hepatitis C virus infection in Chicago women with or at risk for HIV infection: evidence for sexual transmission.” Sex Transm Dis., 25: 527-532, 1998. 3- HABIB M., MOHAMED M., ABDEL-AZIZ F., MAGDER L,. ABDEL-HAMID M., GAMIL F., MADKOUR S., MIKHALL N., ANWAR W., STRICKLAND G., FIX A. AND SALLAM I.: “Hepatitis C Virus Infection in a Community in the Nile Delta: Risk Factors for Seropositivity.”Hepatol., 33: 248-253, 200 1. 16- THOMAS D., ZENILMAN J., ALTER H., SHIH J., GALAI N., CARELLA A. and QUINN T.: “Sexual transmission of hepatitis C virus among patients attending sexually transmitted diseases clinics in Baltimore: An analysis of 309 sex partnerships.” J. Infect. Dis., 171: 768-775, 1995. 4- HASSAN M., ZAGHLOUL A.S., EL-SERAG H.B., SOLIMAN O., PATT Y.Z., CHAPPELL C.L., BEASLEY R.P. and HWANG L.Y.: “The role of hepatitis C in hepatocellular carcinoma-a case control study among Egyptian patients.” J. Clin. Gastroenterology, 33: 123-126, 2001. 17- JOHN S. JAMES: “Hepatitis C and unsafe sex: There is some risk” AIDS Treatment News, 2005. 18- ALTER M.: “Sexual transmission of Hepatitis A, B, and C. (Plenary I) Thirteenth Meeting of the International Society for Sexually Transmitted Diseases Research” Hepatitis C Council of NSW, 2002. 5- NAFEH M.A., MEDHAT A., SHEHATA M., MIKHAIL N.N., SWIFEE Y., ABDEL-HAMID M., WATTS S., FIX A.D., STRICKLAND G.T., ANWAR W. and SALLAM I.: “Hepatitis C in a community in upper Egypt: I. Cross-sectional survey.” Am. J. Trop. Med. Hyg., 63: 236-241, 2000. 19- Centers for Disease Control and Prevention (CDC): “Recommendations for Prevention and control of hepatitis C virus (HVC) infection and HCV-related chronic disease.” Morbidity and Mortality Weekly Report, 47: 1-39, 1998. 6- ANGELICO M., RENGANATHAN E. and GANDIN C. G.: “Chronic liver disease in the Alexandria governorate, Egypt: Contribution of schistosomiasis and hepatitis virus infections.” J. Hepatology, 26: 236-243, 1997. 20- YEN TOMMY M.D., KEEFFE EMMET B. M.D. and AHMED AIJAZ M.D.: “The Epidemiology of Hepatitis C Virus Infection.” Journal of Clinical Gastroenterology, 36 (1): 47-53, 2003. 7- EL-ZAYADI A., P. SIMMONDS, H. DABBOUS, L. PRESCOTT, O. SELIM and A. AHDY: “Response to interferon-of Egyptian patients infected with hepatitis C virus genotype 4.” J. Viral Hepatitis, 3: 261-264, 2006. 21- STROFFOLINI T., LORENZONI U., MENNITI-IPPOLITO F., INFANTOLINO D. and CHIARAMONTE M.: “Hepatitis C virus infection in spouses: Sexual transmission or common exposure to the same risk factors?” Am. J. Gastroenterology, 96: 3138-3141, 2001. 8- KAMAL S.M., MADWAR M .A., PETERS T., FAWZY R. AND RASENACK J.: “Interferon therapy in patients with chronic hepatitis C and schistosomiasis.” J. Hepatology, 32: 172-174, 2000. 22- NEUMAYR G.: “Sexual Transmission of Hepatitis C Lack of evidence for the heterosexual transmission of hepatitis C.” Q. J. Med., 92: 505-508, 2007. 310 23- CAVALHEIRO N.P. and NORMA DE PAULA: “Hepatite C: transmissdo entre casais / Hepatitis C: Transmission between couples.” São. Paulo., 34: 69-82, 2004. 24- TERRAULT N.A.: “Sexual activity as a risk factor for hepatitis C.” Hepatology, 36: 599-5105, 2002. 25- Centers for Disease Control and Prevention (CDC): “HCV infection should be tested for HCV and counseled about the risk of sexual and perinatal transmission.” http://www.cdc. gov/hepatitis/HCV/PDFs/HRSA-HIV-HCV, 2006. Transmission of Hepatitis C between Spouses Hepatitis C Support Project, Version 2.0., 2008. 28- HAJIANI E., MASJEDIZADEH R., HASHEMI J., AZMI M. AND RAJABI T.: “Hepatitis virus transmission and its risk factors within families of patients infected with hepatitis C virus in southern Iran: Khuzestan.” World J. Gastroenterology, 12 (43): 7025-7028, 2006. 26- ELREFAEI M., EL-SHEIKH N., KAMAL K. and CAO H.: “Analysis of T cell responses against hepatitis C virus genotype 4 in Egypt.” J. Hepatology, 40: 313-318, 2004. 29- ESKANDAR HAJIANI, MASJEDIZADEH RAHIM, HASHEMI JALAL, MEHRDAD AZMI and TAHEREH RAJABI: “Hepatitis C virus transmission and its risk factors within families of patients infected with hepatitis C virus in southern Iran: Khuzestan.” World J. Gastroenterology, 12 (43): 7025-7028, 2006. 27- VEYSEL TAHAN, CETIN KARACA, BEYTULLAH YILDIRIM, AYSUN BOZBAS, RESAT OZARAS, KADIR DEMIR, EROL AVSAR, ALI MERT, FATIH BESISIK, SABAHATTIN KAYMAKOGLU, HAKAN SENTURK, YILMAZ CAKALOGLU, CEM KALAYCI, ATILLA OKTEN and NURDAN TOZUN: “Hepatitis C transmission.” 30- VANDELLI C., RENZO F., ROMANO L., TISMINETZKY S,. DE PALMA M., STROFFOLINI T., VENTURA E. and ZANETTI A.: “ Lack of evidence of sexual transmission of hepatitis C among monogamous couples: Results of a 10-year prospective follow-up study.” Am. J. Gastroenterol., 99 (5): 855-859, 2004.