Cross reactive cellular immune response to HCV genotype 1 and 4 antigens among genotype 4 exposed subjects.

BACKGROUND: Hepatitis C Virus (HCV) infection is a global health burden particularly in Egypt, where HCV genotype 4a (GT-4a) predominates. The prevention and control of HCV infection will remain a challenge until the development of an effective vaccine that protects against different genotypes. Several HCV GT-1-based vaccines are in different stages of clinical trials, but antigenic differences could make protection against other genotypes problematic. In this regard, data comparing the cell-mediated immune (CMI) response to different HCV genotypes are limited. We aimed to ex vivo investigate whether GT-1-based vaccine may protect against HCV GT-4 infections. This was carried out on samples collected from genotype 4 infected/exposed subjects. METHODS/PRINCIPAL FINDINGS: The CMI responses of 35 subjects; infected with HCV GT-4/or who had spontaneously-resolved the infection and 10 healthy control subjects; to two sets of seven HCV overlapping 15-mer peptide pools derived from both genotypes; and covering most of the viral proteins; were evaluated. This was carried out using an interferon gamma (IFNγ) enzyme-linked immunospot (ELISpot) assay. Peripheral blood mononuclear cells (PBMC) from 17 subjects (48%) responded to at least one peptide pool derived from GT-1b/GT-4a with 13 subjects responding to peptide pools from both genotypes. A strong correlation was found in the responses to both genotypes (r = 0.82, p<0.001; 95% confidence interval = 0.562-0.933). The average IFNγ total spot forming cells (SFC)/10(6) PBMC (±SE) from the responding subjects for GT-1b and GT-4a was 216±56 and 199±55, respectively (p = 0.833). Also, there were no significant differences between those who cleared their HCV infection or who remained HCV-RNA positive (p = 0.8). CONCLUSION/SIGNIFICANCE: Our data suggest that an effective GT-1b vaccine could protect from GT-4a infection. These data could help in HCV rationale vaccine design and efficacy studies and further our understanding of HCV cross protection against different genotypes.

Incidence of hepatitis C virus infection among Egyptian healthcare workers at high risk of infection.

BACKGROUND: Hepatitis C virus (HCV) is a global health threat with Egypt having the highest worldwide prevalence. Evaluation of the efficacy of a preventive HCV vaccine, such as those currently in Phase I/II trials, requires a cohort with a high-risk exposure to HCV. OBJECTIVE: To identify a reliable cohort for evaluating preventive HCV vaccines, we studied HCV incidence among HCW in a hospital where almost 85% of patients are HCV-infected. STUDY DESIGN: Of 717 HCW negative for HCV-antibodies (anti-HCV) at baseline, 651 were followed up and tested for seroconversion twice annually for an average of 504 ± 154 days. Those reporting a needle-stick injury were additionally tested for both HCV antibodies and RNA monthly for a total of four months. RESULTS: Two subjects (0.31%) had anti-HCV and HCV-RNA seroconversion with an overall incidence of 2.04/1000 person-years and a 4.8% incidence among the 21 subjects who reported a needle-stick injury. Two additional subjects had viremia without detectable anti-HCV. Two of the four subjects were among 21 with reported needle-stick injuries (9.5%) and another had surgery. All four were nurses providing direct patient care. CONCLUSIONS: Our results show that both transient and persistent viremia were detectable in this high-risk cohort of HCW and suggest that absence of anti-HCV in two of the subjects may be due to low-dose viral exposures. These data indicate that HCV infections acquired from documented injuries during direct patient care are frequent in Egypt and can guide selection of eligible HCW suitable for preventive HCV vaccine trials.

Hepatitis C virus-specific cell-mediated immune responses in children born to mothers infected with hepatitis C virus.

OBJECTIVE: To investigate the association between hepatitis C virus (HCV)-specific cell-mediated immunity (CMI) responses and viral clearance in children born to mothers infected with HCV. STUDY DESIGN: A cross-sectional study of children from a mother-infant cohort in Egypt were enrolled to detect CMI responses to recombinant core and nonstructural HCV antigens (nonstructural segments NS3, NS4a/b, and NS5 of the HCV genome) using an interferon-gamma enzyme-linked immunospot assay. Children born to mothers with chronic HCV were enrolled into 3 groups: transiently viremic (n = 5), aviremic (n = 36), and positive control (n = 6), which consisted of 1 child with chronic HCV from this cohort and another 5 children with chronic HCV from a companion study. Children without HCV born to mothers without HCV (n = 27) served as a negative control group. Wilcoxon rank sum test was used to compare the magnitude of CMI responses between groups. RESULTS: None of the 6 control children who were positive for HCV responded to any HCV antigen, and 4 (80%) of 5 children with transient viremia responded to at least one HCV antigen, compared with 5 (14%) of 36 and 3 (11%) of 27 children in the aviremic and negative control groups, respectively. Children with transient viremia elicited stronger responses than did negative controls (P = .005), positive controls (P = .011), or children without HCV viremia (P = .012), particularly to nonstructural antigens. CONCLUSIONS: HCV-specific CMI responses were significantly higher in magnitude and frequency among transiently infected children compared with those persistently infected. This suggests CMI responses may be associated with past viral clearance and can identify children at high risk of infection, who can be targeted for health education, screening, and follow-up.

Risk factors for hepatitis C virus infection among Egyptian healthcare workers in a national liver diseases referral centre.

Little is known about the prevalence of hepatitis C virus (HCV) among healthcare workers (HCW) in Egypt, where the highest worldwide prevalence of HCV exists. The prevalence of HCV, hepatitis B virus and Schistosoma mansoni antibodies was examined in 842 HCWs at the National Liver Institute in the Nile Delta, where >85% of patients are HCV antibody-positive. The mean age of HCWs was 31.5 years and they reported an average of 0.6±1.2 needlesticks/HCW/year. The prevalence of anti-HCV, hepatitis B surface antigen (HBsAg) and co-infection was 16.6%, 1.5% and 0.2%, respectively. HCV-RNA was present in 72.1% of anti-HCV-positive HCWs, and all but one subject were infected with HCV genotype 4. Schistosoma mansoni antibodies were present in 35.1%. The anti-HCV rate increased sharply with age and employment duration, but not among those with needlestick history. After adjusting for other risk factors, the anti-HCV rate was higher among older HCWs [P<0.001; risk ratio (RR) = 1.086, 95% CI 1.063-1.11], males (P=0.002; RR=1.911, 95% CI 1.266-2.885) and those with rural residence (P<0.001; RR=2.876, 95% CI 1.830-4.52). Occupation (P=0.133), duration of employment (P=0.272) or schistosomal antibody positivity (P=0.152) were not significant risk factors for anti-HCV positivity. In conclusion, although one in six HCWs had been infected with HCV, the infections were more likely to be community-acquired and not occupationally related.

Strong hepatitis C virus (HCV)-specific cell-mediated immune responses in the absence of viremia or antibodies among uninfected siblings of HCV chronically infected children.

BACKGROUND: Cell-mediated immune (CMI) responses to hepatitis C virus (HCV) antigens in adults without seroconversion or viremia are biomarkers for prior transient infection. We investigated HCV-specific CMI responses in seronegative children living with HCV-infected siblings. METHODS: Children 3-18 years of age living with HCV-infected siblings were screened for HCV antibodies and HCV RNA. Peripheral blood mononuclear cells (PBMCs) were evaluated for HCV-specific CMI responses by interferon γ (IFN-γ) enzyme-linked immunospot assay using 3 recombinant HCV protein antigens. Flow cytometry phenotypically characterized IFN-γ-secreting cells. RESULTS: Forty-five seronegative children and 5 seropositive viremic siblings had functionally viable PBMCs. Among the 45 seronegative siblings, 15 (33.3%) had positive HCV-specific IFN-γ responses, and subsequent RNA testing revealed that 3 were viremic. Compared with the 5 seropositive viremic children, the median number of HCV-specific spot-forming units was significantly higher in the 12 seronegative aviremic children (P = .002) and in the 3 seronegative viremic children (P = .025). Flow cytometric analysis revealed that IFN-γ was synthesized mainly by CD4(+) T cells. CONCLUSION: Strong HCV-specific CD4(+) T cell responses were detectable in higher frequency among seronegative, aviremic children compared with persistently infected siblings. Further studies are needed to determine whether these immune responses are protective against HCV infection.

Incidence and risk factors for community-acquired hepatitis C infection from birth to 5 years of age in rural Egyptian children.

A prospective study in three Egyptian villages (A, B and C) having a high prevalence of hepatitis C virus (HCV) infection examined incidence of community-acquired HCV infection in children; 2852 uninfected infants were prospectively followed from birth for up to 5.5 years. Fifteen seroconverted for either HCV antibodies and/or HCV-RNA (incidence of 0.53%). Ten had both anti-HCV and HCV-RNA; four had only anti-HCV; and one had HCV-RNA in the absence of antibody. The incidence rate at all ages was 2.7/1000 person-years (PY). It was 3.8/1000 PY during infancy and 2.0/1000 PY for the 1-5-years age group. Hospitalization and low birth weight increased the risk of infection; while living in village B, the family having a higher socioeconomic status, and advanced maternal education were protective. Six of eight HCV-infected infants reported iatrogenic exposures (e.g. hospitalization, therapeutic injections, ear piercing) prior to infection whereas only 2/7 children older than 1 year reported these exposures. Having an HCV-positive mother was the only other reported risk in two of these older children. The virus cleared in six (40%) children by the end of follow-up. Health education targeting iatrogenic exposures and focusing on risk factors could reduce HCV infection in children in high-risk populations.

Prospective cohort study of mother-to-infant infection and clearance of hepatitis C in rural Egyptian villages.

Although persistent transmission of hepatitis C virus (HCV) from infected mothers to their infants is reported in 4-8%, transient HCV perinatal infection also occurs. This prospective cohort study determined perinatal HCV infection- and early and late clearance-rates in 1,863 mother-infant pairs in rural Egyptian villages. This study found 15.7% and 10.9% of pregnant women had HCV antibodies (anti-HCV) and HCV-RNA, respectively. Among 329 infants born of these mothers, 33 (10.0%) tested positive for both anti-HCV and HCV-RNA 2 months following birth-29 (12.5%) having HCV-RNA positive mothers and 4 (with transient infections) having mothers with only anti-HCV. Fifteen remained HCV-RNA positive at one and/or 2 years (persistent infections), while 18 cleared both virus and antibody by 1 year (transient infections). Among the 15 persistent cases, 7 cleared their infections by 2 or 3 years. At 2- to 6- and at 10- to 12-month maternally acquired anti-HCV was observed in 80% and 5% of infants, respectively. Four perinatally infected and one transiently infected infant were confirmed to be infected by their mothers by the sequence similarity of their viruses. Viremia was 155-fold greater in mothers of infants with persistent than mothers of infants with transient infections. Maternal-infant transmission of HCV is more frequent than generally reported. However, both early and late clearance of infection frequently occurs and only 15 (4.6%) and 8 (2.4%) infants born of HCV-RNA positive mothers had detectable HCV-RNA at one and 2-3 years of age. Investigating how infants clear infection may provide important information about protective immunity to HCV.

A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis.

PURPOSE: Milk thistle or its purified extract, silymarin (Silybum marianum), is widely used in treating acute or chronic hepatitis. Although silymarin is hepatoprotective in animal experiments and some human hepatotoxic exposures, its efficacy in ameliorating the symptoms of acute clinical hepatitis remains inconclusive. In this study, our purpose was to determine whether silymarin improves symptoms, signs and laboratory test results in patients with acute clinical hepatitis, regardless of etiology. METHODS: This is a randomized, placebo-controlled trial in which participants, treating physicians and data management staff were blinded to treatment group. The study was conducted at two fever hospitals in Tanta and Banha, Egypt where patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase (ALT) levels >2.5 times the upper limit of normal were enrolled. The intervention consisted of three times daily ingestion of either a standard recommended dose of 140 mg of silymarin (Legalon, MADAUS GmbH, Cologne, Germany), or a vitamin placebo for four weeks with an additional four-week follow-up. The primary outcomes were symptoms and signs of acute hepatitis and results of liver function tests on days 2, 4 and 7 and weeks 2, 4, and 8. Side-effects and adverse events were ascertained by self-report. RESULTS: From July 2003 through October 2005, 105 eligible patients were enrolled after providing informed consent. No adverse events were noted and both silymarin and placebo were well tolerated. Patients randomized to the silymarin group had quicker resolution of symptoms related to biliary retention: dark urine (p=0.013), jaundice (p=0.02) and scleral icterus (p=0.043). There was a reduction in indirect bilirubin among those assigned to silymarin (p=0.012), but other variables including direct bilirubin, ALT and aspartate aminotransferase (AST) were not significantly reduced. CONCLUSIONS: Patients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion. Despite a modest sample size and multiple etiologies for acute clinical hepatitis, our results suggest that standard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process.

Usefulness of clinical algorithm as screening process to detected malaria in low-to-moderate transmission areas of scarce health related resources.

INTRODUCTION: In areas of low-to-moderate risk of malaria transmission, the World Health Organization recommends parasitic confirmation before treatment. Such areas have usually low budget for health care and malaria diagnosis is mostly based on clinical assumption. Algorithms have been developed to improve health care providers' identification of clinical malaria and could be used as screening to reduce the number of individuals requiring parasitic confirmation before treating. METHODS: Prospective clinical and parasitological data were collected from inhabitants of four villages from March 1984 through March 1985. Symptoms and signs recorded by physicians were used in multivariate models to test the best predictors of malaria. Sensitivity and specificity were calculated for various cut-offs of scores and compared to clinical diagnosis. RESULTS: A total of 8.941 individuals were evaluated during the 1-year period of data collection. The overall prevalence of malaria parasitemia was 19.7% (n=1762). Of the 4280 people evaluated during the high season period, 24% (n=1024) presented any parasitemia, 55.3% (566/1024) due to Plasmodium falciparum. The final clinical algorithm included history of fever, rigors, headache, absence of myalgia, backache or cough, nausea or vomiting, and splenomegaly on examination as predictable variables. At a cut-off score of 2.0, the sensitivity of the algorithm was higher for the entire sample (57% vs. 43%), for high season period (70% vs. 53%), for children less than 6 years of age (59% vs. 40%), for individuals with parasitemia due to P. falciparum (65% vs. 48%), and for high P. falciparum parasitemic individuals at high season (84% vs. 68%). However, specificity was usually lower unless a higher cut off was used, in which case the gain in sensitivity by using the algorithm was reduced. CONCLUSION: In low-to-moderate transmission areas in which health related resources are scarce, a clinical algorithm increases the identification of real cases of malaria and could be used as screening for further parasitic identification.

Incidence and risk factors for hepatitis C infection in a cohort of women in rural Egypt.

A prospective cohort study of the incidence and risk factors for hepatitis C virus (HCV) infection was performed in 2171 pregnant women in three rural Egyptian villages who were HCV antibody (anti-HCV) and RNA (HCV-RNA) negative at baseline. During an average of 2.2 years follow up, 25 incident cases were observed, giving an estimated HCV incidence of 5.2/1000 person-years (PY). The infection rate correlated with community anti-HCV prevalence in pregnant women, while the perinatal incidence rate of 11.2/1000 PY was almost five times that of the non-perinatal rate (2.3/1000 PY). The data suggested iatrogenic perinatal risk factors were associated with infection in one village, while health education reduced infections in another. Among the 25 incident cases, eight were HCV-RNA negative when they were first found to be anti-HCV positive and one-third of the 15 viraemic cases with follow-up data available cleared their HCV-RNA after an average of 1.3 years. None of the 25 incident cases were jaundiced or had symptoms of hepatitis but elevated serum alanine aminotransferase levels confirmed hepatitis in nine. Our data suggest that asymptomatic HCV infections frequently occurred during the perinatal period but often cleared and that educating medical personnel on safe practices possibly reduced HCV transmission.

Hepatitis C vaccine: supply and demand.

Despite difficulties associated with extreme variability and mutability of hepatitis C virus (HCV), several vaccines that prevent initial infection or viral persistence, or that clear viraemia in individuals with chronic HCV infections, are currently in development. At least one vaccine that may prevent chronic persistent infections will soon be available for testing. We review the widespread importance of HCV infection and disease, the immune response to HCV and correlates of protection, prevention strategies and vaccine candidates, and groups that will need the vaccine and provide suitable populations for assessing vaccine safety and efficacy. The evaluation of prophylactic vaccines is particularly problematic since distribution must focus upon individuals at high risk of exposure-for example, intravenous drug users and health-care providers in areas with high HCV prevalence. Although there is a huge need for therapeutic vaccines, further immunological hurdles must be cleared before one becomes available.

HIV-positive poor women may stop breast-feeding early to protect their infants from HIV infection although available replacement diets are grossly inadequate.

Little is known about mothers' perspectives and experiences of early breast-feeding cessation as a strategy to reduce postnatal HIV transmission in rural, resource-constrained settings. We conducted in-depth interviews (IDI) with 15 HIV-positive breast-feeding mothers of infants aged 3-5 mo about their plans for feeding their infants after age 6 mo. We also conducted IDI with 12 HIV-positive mothers who intended to stop breast-feeding after receiving their infant's HIV-PCR negative test result at age 6 mo. Twenty-four-hour dietary recalls were conducted with the same 12 mothers and 16 HIV-negative or status unknown mothers who were breast-feeding their 6- to 9-mo-old infants. Of the 12 mothers who intended to stop breast-feeding, 11 did so by 9 mo. Median energy intake (percent requirement) was 1382 kJ (54%) among weaned infants compared with 2234 kJ (87%) among breast-feeding infants. Median intakes were <67% of the recommended levels for 9 and 7 of the 12 micronutrients assessed for weaned and breast-feeding infants, respectively. Factors facilitating early breast-feeding cessation were mothers' knowledge about HIV transmission, family support, and disclosure of their HIV status; food unavailability was the primary barrier. HIV-positive mothers in resource-constrained settings may be so motivated to protect their child from HIV that they stop breast-feeding early even when they cannot provide an adequate replacement diet. As reflected in the new World Health Organization guidance, HIV-positive mothers should continue breastfeeding their infants beyond 6 mo if replacement feeding is still not acceptable, feasible, affordable, sustainable, and safe.

Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma.

Egypt has one of the world's highest prevalences of hepatitis C virus (HCV) infection, with a majority of genotype 4 infections. To explore the genetic diversity of HCV in Egypt, sera from 131 Egyptians [56 from community studies, 37 chronic hepatitis patients, 28 hepatocellular carcinoma (HCC) patients and 10 patients with non-Hodgkin's lymphoma] were genotyped by restriction fragment-length polymorphism and phylogenetic analyses of sequences from the mid-core and non-structural 5B regions. The different genotyping methods showed good agreement. The majority of the viruses (83 of 131; 63%) were of subtype 4a, but five other subtypes within genotype 4 were also observed, as well as three genotype 1b, five genotype 1g and one genotype 3a samples. Interestingly, subtype 4o, which was easily identifiable in all three genomic regions, showed an association with HCC (P=0.017), which merits further investigation.

Evaluation of serum biomarkers of fibrosis and injury in Egyptian patients with chronic hepatitis C.

BACKGROUND/AIMS: We evaluated whether surrogate serum biomarkers for liver injury are comparable to liver biopsy in Egyptian patients with hepatitis C virus (HCV) infection. SUBJECTS: Two hundred and twenty Egyptian patients, 91% infected with genotype-4 HCV, undergoing liver biopsy during evaluation for interferon/ribavirin therapy. METHODS: Liver biopsy scored by the Ishak method was compared to biochemical tests, platelet count and two fibrosis biomarkers: hyaluronic acid (HA) and YKL-40. Univariate and logistic regression analyses determined independent predictors of fibrotic, inflammatory, and fatty changes. Biomarkers were evaluated for ability to differentiate between severe fibrosis/cirrhosis and no/mild fibrosis. RESULTS: Although increasing age, HA, YKL-40, AST, reduced platelet count, and AST and HA/platelet count ratios were associated with fibrosis by univariate analysis, the other variables were not significant after controlling for HA (p=0.0001) and age (p=0.004). Although age and some biomarkers were associated with inflammation, none remained significant after controlling for fibrosis. YKL-40 (p=0.04) and aspartate aminotransferase (p=0.05) remained associated with steatosis after controlling for fibrosis. CONCLUSIONS: In Egyptians with chronic HCV, young patients with low levels of HA are at very low risk of fibrosis. This can limit the number of liver biopsies to those whose clinical findings conflict with the biomarker results.

Transmission of hepatitis C virus between parents and children.

Egyptian children with infected parents are at high risk of infection with hepatitis C (HCV). Analysis of data collected during surveys of rural communities show children whose parents had antibodies to HCV (anti-HCV) were at higher risk for having anti-HCV than children whose parents did not. The association was greater with mothers than fathers and when the parent had HCV RNA. For instance, 87 (14%) of 612 children had anti-HCV whose mothers had HCV RNA compared with 28 (7%) of 401 whose mothers only had anti-HCV and 79 (2.6%) of 3,086 whose mothers were seronegative. These associations persisted after controlling for age, parenteral exposures, and serologic status of the other parent. Sequencing isolates from 13 families with parent(s) and children having HCV RNA showed 10 of 18 had genetically similar viruses. These findings suggest Egyptian children are at high risk of being infected with HCV by their parents and identification of the transmission routes would allow for preventive measures.

Liver disease in Egypt: hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors.

In Egypt, schistosomiasis was traditionally the most important public health problem and infection with Schistosoma mansoni the major cause of liver disease. From the 1950s until the 1980s, the Egyptian Ministry of Health (MOH) undertook large control campaigns using intravenous tartar emetic, the standard treatment for schistosomiasis, as community-wide therapy. This commendable effort to control a major health problem unfortunately established a very large reservoir of hepatitis C virus (HCV) in the country. By the mid-1980s, the effective oral drug, praziquantel, replaced tartar emetic a s treatment f o r schistosomiasis in the entire country. This both reduced schistosomal transmission and disease and interrupted the "occult" HCV epidemic. It was evident when diagnostic serology became available in the 1990s that HCV had replaced schistosomiasis as the predominant cause of chronic liver disease. Epidemiological studies reported a high prevalence and incidence of HCV, particutarly within families in rural areas endemic for schistosomiasis. Clinical studies showed 70% to 90% of patients with chronic hepatitis, cirrhosis, or hepatocellular carcinoma had HCV infections. Co-infections with schistosomiasis caused more severe liver disease than infection with HCV alone. Schistosomiasis was reported to cause an imbalance in HCV-specific T-cell responses leading to increased viral load, a higher probability of HCV chronicity, and more rapid progression of complications in co-infected persons. As complications of HCV usually occur after 20 years of infection, the peak impact of the Egyptian outbreak has not yet occurred. Efforts have been initiated by the Egyptian MOH to prevent new infections and complications of HCV in the estimated 6 million infected persons.

Active surveillance for acute viral hepatitis in rural villages in the Nile Delta.

BACKGROUND: Acute viral hepatitis is less frequent in Egypt than serum antibody levels suggest. Because acute viral hepatitis has a wide clinical spectrum, we tested the hypothesis that many cases are undetected because of mild illness caused by initial, early-childhood exposure to hepatitis viruses. METHODS: During active case detection among 20,000 inhabitants of rural villages in Egypt, we screened 1715 symptomatic patients for serum alanine aminotransferase (ALT) levels. Viral hepatitis markers were tested in 47 subjects who had ALT levels that were least twice the normal level. RESULTS: Of the 47 individuals tested, 4 children aged 3-5 years had immunoglobulin M (IgM) antibodies to hepatitis A virus (anti-HAV IgM). One also had a possible false-positive result to a test for IgM antibodies to hepatitis E virus. None had serological evidence of acute hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. However, 33 of the remaining 43 had active HCV infection, having both antibodies to HCV (anti-HCV) and HCV RNA. Four others anti-HCV without HCV RNA, and 2 others had seroconversion to anti-HCV during follow-up. Two patients who were positive for hepatitis B surface antigen had chronic HBV infection. Only 3 with elevated ALT levels had no evidence of acute or chronic infections with known hepatitis viruses. Immunoglobulin G antibodies to hepatitis E virus was detected in 40 patients. CONCLUSION: Active surveillance covering approximately 50,000 person-years detected only 4 cases of acute HAV infection. Almost all persons with mild symptoms and elevated ALT levels had serological evidence of chronic viral hepatitis, most often associated with HCV. Many of these cases were probably "flare-ups" of HCV infection or incidental illness in patients with chronic HCV infection, but some could have been caused by difficult-to-confirm initial HCV infections. Although serological evidence for exposures was highly prevalent, hepatitis viruses seldom caused acute viral hepatitis in these communities.

Prevalence of and risk factors for hepatitis C in rural pregnant Egyptian women.

Prevalence and risk factors for hepatitis C virus (HCV) infection were studied in 2,587 pregnant women from three rural Egyptian villages in the Nile Delta being admitted to a prospective cohort study of maternal-infant transmission; 408 (15.8%) had antibodies to HCV (anti-HCV) and 279 (10.8%) also had HCV-RNA. Fewer than 1% gave a history of jaundice or liver disease. Risk factors for anti-HCV included increasing age, low socioeconomic status and a history of blood transfusion or injection therapy for schistosomiasis. Sub-analyses after stratification of subjects by village revealed risks associated with specific venues for medical care, having a previous delivery attended by a traditional birth assistant (TBA), receiving medical care in a temporary clinic located in a mosque, overnight admission to a private doctor's clinic, and circumcision by a TBA or a 'health barber'. Our results suggest HCV causes very little detected illness in young adult Egyptian women and some sources of HCV transmission in rural Egypt in the past were associated with the provision of medical care and varied by location. Prevention should be focused on providing appropriate resources and health education should be given to formal and informal health care providers and should be sufficiently broad to adjust for local variations in exposures.