Naglaa Arafa

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.

Is the hepatitis C virus epidemic over in Egypt? Incidence and risk factors of new hepatitis C virus infections.

Objectives: To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV transmission with emphasis on the role of living with infected household family members in rural Egypt.

Effect of preventive and curative interventions on hepatitis C virus transmission in Egypt (ANRS 1211): a modelling study

BACKGROUND Most hepatitis C virus (HCV) transmission in Egypt is related to medical injections and procedures. To control the spread of HCV, the Egyptian Ministry of Health initiated awareness and education campaigns, strengthened infection control in health-care facilities, and subsidised anti-HCV treatment. We aimed to investigate the effect of these interventions on the spread of HCV by mathematical modelling. METHODS We developed a mathematical model of HCV transmission in Zawyat Razin, a typical rural community. Our model assumes that each individual has two distinct types of medical procedures: injections and more invasive medical procedures. To quantify the severity of the spread of HCV, we used the notion of the basic reproduction number R0, a standard threshold parameter signalling whether transmission of an infectious disease is self-sustained and maintains an epidemic. If R0 is greater than 1, HCV is self-sustained; if R0 is 1 or less, HCV transmission is not self-sustained. We investigated whether heterogeneity in the rate of injection or invasive medical procedures is the determinant factor for HCV transmission and whether most iatrogenic transmission is caused by a small group of individuals who receive health-care interventions frequently. We then assessed whether interventions targeted at this group could reduce the spread of HCV. FINDINGS The R0 of the spread of HCV without treatment was 3·54 (95% CI 1·28-6·18), suggesting a self-sustained spread. Furthermore, the present national treatment programme only decreased R0 from 3·54 to 3·03 (95% CI 1·10-5·25). Individuals with high rates of medical injections seem to be responsible for the spread of HCV in Egypt; the R0 of the spread of HCV without treatment would be 0·64 (95% CI 0·41-0·93) if everybody followed the average behaviour. The effect of treatment on HCV transmission is greatly enhanced if treatment is provided a mean of 2·5 years (95% CI 0·1-9·2) after chronic infection and with drug regimens with more than 80% efficacy. With these treatment parameters, preventive and curative interventions targeting individuals with high rates of medical injections might decrease R0 below 1 for treatment coverage lower than 5%. INTERPRETATION Targeting preventive and curative interventions to individuals with high rates of medical injections in Egypt would result in a greater reduction the spread of HCV than would untargeted allocation. Such an approach might prove beneficial in other resource-limited countries with health-care-driven epidemics. FUNDING Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS 1211), ANR grant Labex Integrative Biology of Emerging Infectious Diseases.

A novel method to identify routes of hepatitis C virus transmission.

Background We propose a new approach based on genetic distances among viral strains to infer about risk exposures and location of transmission at population level. Methods We re-analysed 133 viral sequences obtained during a cross-sectional survey of 4020 subjects living in a hepatitis C virus (HCV) endemic area in 2002. A permutation test was used to analyze the correlation between matrices of genetic distances in the NS5b region of all pairwise combinations of the 133 viral strains and exposure status (jointly exposed or not) to several potential HCV risk factors. Results Compared to subjects who did not share the same characteristics or iatrogenic exposures, the median Kimura genetic distances of viral strains were significantly smaller between brothers and sisters (0.031 versus 0.102, P<0.001), mother and child (0.044 versus 0.102, P<0.001), father and child (0.045 versus 0.102, P<0.001), or subjects exposed to periodontal treatment (0.084 versus 0.102, P = 0.02). Conversely, viral strains were more divergent between subjects exposed to blood transfusions (0.216 versus 0.102, P = 0.04) or tooth filling or extraction (0.108, versus 0.097, P = 0.05), suggesting acquisition of the virus outside of the village. Conclusion This method provided insights on where infection took place (household, village) for several socio-demographic characteristics or iatrogenic procedures, information of great relevance for targeting prevention interventions. This method may have interesting applications for virologists and epidemiologists studying transmission networks in health-care facilities or among intravenous drug users.

Women in Cairo, Egypt and their risk factors for unmet contraceptive need: a community-based study

Background and methodology Although modern family planning methods are readily available in Egypt at low cost, a considerable proportion of women still have an unmet contraceptive need. The aim of this study was to detect the risk factors of unmet contraceptive need among married women in the childbearing period in an underprivileged area in Cairo with high population density. A survey of 2340 women in the Marg district of Eastern Cairo was conducted by means of home interviews. For every woman identified as having an unmet contraceptive need (n=174), the next two women identified with met contraceptive need were selected as controls (n=348). Results The prevalence of unmet need was 7.4%. Risk factors identified were: belief that contraception is religiously prohibited (OR 2.08, 95% CI 1.06–4.09); poor interspousal communication about the desired number of children (OR 2.59, 95% CI 1.40–4.79); husband opposition to contraceptive use (OR 2.96, 95% CI 1.47–5.97); a previous history of unwanted pregnancy (OR 2.98, 95% CI 1.73–5.14); and experiencing side effects from previous contraceptive use (OR 5.69, 95% CI 3.46–9.37). Conclusions The authors propose training physicians to identify and counsel women who experience contraceptive side effects and/or a previous unwanted pregnancy, as well as the transmission of clear media messages on the religious acceptability of contraceptive use.

Evidence for a dominant major gene conferring predisposition to hepatitis C virus infection in endemic conditions

Hepatitis C virus (HCV), infecting 170 million people worldwide, is a major public health problem. In developing countries, unsafe injections and blood transfusions are thought to be the major routes of transmission. However, our previous work in a population from Egypt, endemic for HCV, revealed highly significant familial correlations, strongly suggesting the existence of both familial transmission of the virus and genetic predisposition to HCV infection. We investigated the hypothesis of genetic predisposition by carrying out a segregation analysis of HCV infection in the same population. We used a logistic regression model simultaneously taking into account a major gene effect, familial correlations and relevant risk factors. We analyzed 312 pedigrees (3,703 subjects). Overall HCV seroprevalence was 11.8% and increased with age. The main associated risk factors were previous parenteral treatment for schistosomiasis and blood transfusions. We found strong evidence for a dominant major gene conferring a predisposition to HCV infection. The frequency of the predisposing allele was 0.013, reflecting a strong predisposition to HCV infection in 2.6% of the subjects, particularly those under the age of 20. This study provides evidence for the involvement of host genetic factors in susceptibility/resistance to HCV infection in endemic conditions.

Excess mortality rate associated with hepatitis C virus infection: A community-based cohort study in rural Egypt

BACKGROUND & AIMS >80% of people chronically infected with hepatitis C virus (HCV) live in resource-limited countries, yet the excess mortality associated with HCV infection in these settings is poorly documented. METHODS Individuals were recruited from three villages in rural Egypt in 1997-2003 and their vital status was determined in 2008-2009. Mortality rates across the cohorts were compared according to HCV status: chronic HCV infection (anti-HCV antibody positive and HCV RNA positive), cleared HCV infection (anti-HCV antibody positive and HCV RNA negative) and never infected (anti-HCV antibody negative). Data related to cause of death was collected from a death registry in one village. RESULTS Among 18,111 survey participants enrolled in 1997-2003, 9.1% had chronic HCV infection, 5.5% had cleared HCV infection, and 85.4% had never been infected. After a mean time to follow-up of 8.6years, vital status was obtained for 16,282 (89.9%) participants. When compared to those who had never been infected with HCV in the same age groups, mortality rate ratios (MRR) of males with chronic HCV infection aged <35, 35-44, and 45-54years were 2.35 (95% CI 1.00-5.49), 2.87 (1.46-5.63), and 2.22 (1.29-3.81), respectively. No difference in mortality rate was seen in older males or in females. The all-cause mortality rate attributable to chronic HCV infection was 5.7% (95% CI: 1.0-10.1%), while liver-related mortality was 45.5% (11.3-66.4%). CONCLUSIONS Use of a highly potent new antiviral agent to treat all villagers with positive HCV RNA may reduce all-cause mortality rate by up to 5% and hepatic mortality by up to 40% in rural Egypt.