Characterization of hepatitis E-specific cell-mediated immune response using IFN-gamma ELISPOT assay.

In developing countries, hepatitis E (HEV) and hepatitis A (HAV) are the major causes of acute viral hepatitis with similar feco-oral modes of transmission. In contrast to the high seroprevalence of hepatitis A infection, a low seroprevalence of HEV among children in endemic areas has been reported. These data suggest the possibility that silent HEV infection is undiagnosed by the current available methods. Many of the serological tests used for HEV diagnosis have poor specificity and are unable to differentiate among different genotypes of HEV. Moreover, the RT-PCR used for HEV isolation is only valid for a brief period during the acute stage of infection. Cell-mediated immune (CMI) responses are highly sensitive, and long lasting after sub-clinical infections as shown in HCV and HIV. Our objective was to develop a quantitative assay for cell-mediated immune (CMI) responses in HEV infection as a surrogate marker for HEV exposure in silent infection. Quantitative assessment of the CMI responses in HEV will also help us to evaluate the role of CMI in HEV morbidity. In this study, an HEV-specific interferon-gamma (IFN-gamma) ELISPOT assay was optimized to analyze HEV-specific CMI responses. We used peripheral blood mononuclear cells (PBMC) and sera from experimentally infected chimpanzees and from seroconverted and control human subjects to validate the assay. The HEV-specific IFN-gamma ELISPOT responses correlated strongly and significantly with anti-HEV ELISA positive/negative results (rho=0.73, p=0.02). Moreover, fine specificities of HEV-specific T cell responses could be identified using overlapping HEV ORF2 peptides.

Schistosoma infection inhibits cellular immune responses to core HCV peptides.

Patients coinfected with hepatitis C virus (HCV) and the trematode, Schistosoma mansoni, have an increased incidence of viral persistence and accelerated fibrosis. To investigate immunological mechanisms responsible for this more aggressive natural history of HCV, the core HCV-specific T-cell responses were analysed in 44 donated blood units rejected because they had antibodies to HCV (anti-HCV). Half also had anti-S. mansoni antibodies, evidence of past or active infection. HCV-specific ELISPOT responses were examined using pools of 180 overlapping 9-mer peptides with offsets of one covering the core of HCV genotype 4a. Comparison of T-cell responses in blood units positive for both anti-HCV and anti-Schistosoma antibodies with blood units positive only for anti-HCV antibodies showed a significant decrease in core-specific T-cell IFN-gamma (505+/- 46 vs. 803 +/- 66 ISC/10(6) cells, P < 0.001), IL-4 (2 +/- 108 vs. 641 +/- 131 ISC/10(6) cells, P < 0.001), and IL-10 (159 +/- 105 vs. 466 +/- 407 ISC/10(6) cells, P < 0.002) responses. In contrast, there was no significant difference in cell-mediated immune response (CMI) to PHA mitogen between these two groups. Therefore, we concluded T cells from persons with anti-Schistosoma have reduced IFN-gamma, IL-4, and IL-10 secreting HCV-specific T-cell responses. This may explain why Schistosoma coinfection increases persistence and severity of HCV infection.

Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results.

BACKGROUND/AIMS: A double-blinded trial evaluating silymarin, an herbal supplement for liver disease, to prevent complications of chronic hepatitis C virus infection has not been done. SUBJECTS: One hundred and seventy-seven consenting residents of an Egyptian village with chronic hepatitis C virus were randomly assigned to receive either silymarin or multivitamin supplements. METHODS: Participants had baseline and follow-up clinical, ultrasound, blood tests and quality-of-life assessments. Community nurses visited weekly to ascertain compliance, distribute supplements and record adverse effects. RESULTS: At 12 months almost all of 141 remaining subjects reported feeling better, although symptoms and quality-of-life scores did not differ between the silymarin and multivitamin groups. Both the silymarin and vitamins were tolerated equally well; and >95% of supplements were taken by >95% of subjects. One in each group had no detectable hepatitis C virus antibodies while two in the silymarin group and three receiving multivitamins had undetectable hepatitis C virus RNA. Serum alanine aminotransferase elevations did not differ between groups. Serum hepatic fibrosis marker, hyaluronic acid and YKL-40, and abdominal ultrasound results were similar in both groups and may have progressed slightly at 12 months. CONCLUSIONS: The recommended dose of silymarin can be safely taken for 1 year and improves symptoms and general well-being, but has no effect upon hepatitis C virus viremia, serum ALT, or serum and ultrasound markers for hepatic fibrosis. More prolonged evaluation and a higher dose may be required to ascertain whether milk thistle supplements prevent complications of chronic hepatitis C virus.

Hepatitis C virus infection in a community in the Nile Delta: risk factors for seropositivity.

The purpose of this study was to identify risk factors for hepatitis C virus (HCV) infection in a rural village in the Nile Delta with a high prevalence of antibodies to HCV (anti-HCV). One half of the village households were systematically selected, tested for anti-HCV, and interviewed: 973 of 3,999 (24.3%) subjects were anti-HCV-positive (reflecting prior HCV infection but not necessarily current liver disease), with nearly equal prevalence among males and females. Anti-HCV prevalence increased sharply with age among both males and females, from 9.3% in those 20 years of age and younger to >50% in those older than 35, suggesting a cohort effect with reduced transmission in recent years. Multivariate regression was used to estimate independent effects of risk factors on seropositivity. Among those over 20 years of age, the following risk factors were significantly associated with seropositivity: age (P <.001); male gender (odds ratio [OR] = 2.5, 95% CI = 1.3-4.7); marriage (OR = 4.1, 2.4-6.9); anti-schistosomiasis injection treatment (OR = 2.0, 1.3-2.9); blood transfusion (OR = 1.8, 1.1-2.9), invasive medical procedure (surgery, catheterization, endoscopy, and/or dialysis) (OR = 1.5, 1.1-1.9); receipt of injections from "informal" health care provider (OR = 1.3, 1.0-1.6); and cesarean section or abortion (OR = 1.4, 1.0-1.9). Exposures not significantly related to anti-HCV positivity in adults included: history of, or active infection with, Schistosoma mansoni, sutures or abscess drainage, goza smoking in a group, and shaving by community barbers. Among those 20 years old or younger, no risk factors were clearly associated with anti-HCV positivity; however, circumcision for boys by informal health care providers was marginally associated with anti-HCV (OR = 1.7, 1.0-3.0). Prevention programs focused primarily on culturally influenced risks in rural Egyptian communities are being implemented and evaluated.

Racial differences in reported Lyme disease incidence.

In the United States, the incidence of Lyme disease is considered to be disproportionately high among Whites because of risk of exposure. For assessment of racial differences in Lyme disease incidence and the role of risk exposure, incidence rate ratios (IRRs) for Lyme disease and its manifestations between Whites and African Americans in Maryland and in its focus of endemicity, the Upper Eastern Shore, were calculated. Calculations were based on reported cases of Lyme disease in Maryland during the years 1992-1996. The IRR for Lyme disease between Whites and African Americans was 6.3 (95% confidence interval (CI): 5.0, 8.0), decreasing to 1.8 (95% CI: 1.2, 2.7) for the Upper Eastern Shore. Statewide, there was a significant difference between the White to African American IRR for erythema migrans and for Lyme disease-associated arthritis, at 17.7 (95% CI: 11.2, 27.8) and 2.3 (95% CI: 1.7, 3.2), respectively. On the Upper Eastern Shore, the IRR for arthritis reversed, indicating higher incidence among African Americans than among Whites: IRR = 5.7 (95% CI: 2.4, 13.9) for erythema migrans and IRR = 0.7 (95% CI: 0.4, 1.1) for arthritis. White patients were more likely to have erythema migrans (risk ratio = 2.8, 95% CI: 1.9, 4.1) and less likely to have arthritis than were African Americans (risk ratio = 0.4, 95% CI: 0.3, 0.5). Among all patients, there was a significant negative association between arthritis and erythema migrans. Although much of the racial disparity in incidence rates diminishes in a rural, endemic area, consistent with exposure risk being responsible for much of the variation, a difference remains. This may be due to failure to recognize early disease (erythema migrans) among African Americans, resulting in increased rates of late manifestations. Geographic spread of the disease warrants efforts to increase awareness of Lyme disease and its manifestations among people of color and the health care providers who serve them.

Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence.

This report describes a cross-sectional survey of the prevalence of antibodies to hepatitis C virus (anti-HCV) in a rural Egyptian community in the Nile Delta. One half of the village households were systematically selected and examined by questionnaire and testing sera for anti-HCV and HCV RNA. Blood samples were obtained from 3, 888 (75.4%) of 5,156 residents >/=5 years of age; an additional 111 samples were obtained from children younger than 5 years. Overall, 973 (24.3%) of 3,999 residents were anti-HCV-positive, and the age- and gender-adjusted seroprevalence was 23.7%. Anti-HCV prevalence increased sharply with age, from 9.3% in those 20 years of age and younger to >50% in those older than 35 years. Currently or previously married individuals were more likely to be seropositive than those never married, controlling for age (Mantel-Haenszel risk ratio = 1.8; 95% CI: 1.3, 2.6). Of the 905 anti-HCV-positive samples tested, 65% were also positive for HCV RNA. Active schistosomal infection was not associated with anti-HCV status; however, history of antischistosomal injection therapy (reported by 19% of anti-HCV positives) was a risk for anti-HCV (age-adjusted risk ratio = 1.3; 95% CI: 1.2, 1.5). This study, the largest community-based survey to date, supports earlier reports of high levels of anti-HCV among adults in rural areas of Egypt, although many of those who are seropositive will not have active liver disease. The large reservoir of HCV infection in the community provides an opportunity to investigate risk factors for transmission, the natural history of infection and effectiveness of preventive methodologies, and raises concern about the prospect of an increasing incidence of chronic liver disease in the coming decades.

The epidemiology of schistosomiasis in Egypt: methods, training, and quality control of clinical and ultrasound examinations.

Morbidity due to schistosomiasis was evaluated in a subpopulation of 14,000 of the randomized sample in the Epidemiology 1, 2, 3 Project. It was measured by using a standardized questionnaire for obtaining medical history and symptoms and by performing standardized physical and ultrasound examinations. Reported herein are descriptions of the methods and training and quality control efforts made to insure that the morbidity data was reliable and consistent when collected by 7 different teams in 9 different governorates.

The epidemiology of schistosomiasis in Egypt: Menofia Governorate.

Health questionnaires and parasitologic examinations of urine and stool were performed upon a stratified random sample of 10,899 individuals from 1,537 households in 27 rural communities in Menofia Governorate in Egypt in 1992 to investigate the prevalence of, risk factors for, and changing pattern of infection with Schistosoma sp. in the governorate. A subset, every fifth household, or 1,480 subjects, had physical and ultrasound examinations to investigate prevalence of and risk factors for morbidity. The prevalence of S. mansoni ranged from 0.3% to 72.9% and averaged 28.5%. The geometric mean egg count was 81.3 eggs/gram of stool. Age-stratified prevalence and intensity of infection was 30-40% and 60-80 eggs/gram of stool from the age of 10 onward; males had higher infection rates and ova counts than females in all age groups > 10 years old. Schistosoma haematobium was rare, being consequential in only 1 community. Risk factors for S. mansoni infection were male gender; age > 10 years; living in smaller communities; exposures to canal water; history of or treatment for schistosomiasis or blood in the stool; detection of splenomegaly by either physical or ultrasound; and ultrasound-detected periportal fibrosis (PPF). The more severe grades of PPF were rarely (21 of 1,450 examinations) detected. Risk factors for morbidity, i.e., ultrasound-detected PPF, were similar to those for infection. Schistosoma mansoni has almost totally replaced S. haematobium in Menofia. The prevalence of S. mansoni in rural communities remains high and average intensities of infection are moderate. The association of morbidity with schistosomal infection was variable and is obviously markedly influenced by both the frequent use of antischistosomal chemotherapy in communities in Menofia and by the prevalence of complications from chronic viral hepatitis in the population: hepatomegaly did not correlate with infection; PPF and splenomegaly, however, were related to S. mansoni infection in both individuals and communities.

The epidemiology of schistosomiasis in Egypt: Gharbia Governorate.

Health questionnaires and parasitologic examinations of urine and stool were performed upon a stratified random sample of 14,344 individuals from 1,952 households in 34 rural communities in Gharbia Governorate of Egypt to investigate the prevalence of, risk factors for, and changing pattern of infection with Schistosoma sp. A subset, every fifth household, of 1,973 subjects had physical and ultrasound examinations to investigate prevalence of and risk factors for morbidity. Community prevalence of Schistosoma mansoni ranged from 17.9% to 79.5% and averaged 37.7%. The geometric mean egg count (GMEC) was 78.9 eggs/gram of feces. The prevalence and intensity of infection was 40-50% and 70-100 eggs/gram of feces in those > or =10 years of age. Schistosoma haematobium was detected in 5 of the 34 communities. The maximum infection rate was 2.8% and mean GMEC in the five communities was 2.1/10 ml of urine. The overall prevalence of S. haematobium in the governorate was 0.3%. Risk factors for infection with S. mansoni were male gender, an age >10 years, living in smaller communities, exposures to canal water, prior therapy for schistosomiasis, or blood in the stool (in children only). Morbidity detected by physical examination or ultrasonography did not correlate with S. mansoni infection in individuals with the exception of periportal fibrosis (PPF, odds ratio [OR] = 1.25). Periportal fibrosis was detected in more than half of the subjects by ultrasonography; 5.3% had grade II lesions and 1.0% had the most severe grade III changes. Risk factors for morbidity as manifested by ultrasonographically detected PPF were similar to those for infection. Periportal fibrosis had a negative relationship with abdominal pain (OR = 0.45) and hepatomegaly detected by physical examination and ultrasonography (ORs = 0.72 and 0.68), but it was associated with splenomegaly (ORs = 4.14 and 3.55). The prevalence of PPF, hepatomegaly, and splenomegaly increased with age. There was no relationship between community burden of schistosomiasis mansoni and any measurements of morbidity with the exception of splenomegaly detected by physical examination (r = 0.40). Schistosoma mansoni has almost completely replaced S. haematobium in Gharbia, which has a high prevalence and moderate intensity of S. mansoni infection. Periportal fibrosis was detected by ultrasonography in more than half of the subjects, and 1 in 16 had grade II and III lesions. The only relationship between PPF and other morbidity findings was its positive relationship with splenomegaly and negative association with hepatomegaly. Hepatic morbidity is common in communities in Gharbia but the role of schistosomiasis mansoni in this is uncertain.

The epidemiology of schistosomiasis in Egypt: Fayoum Governorate.

Health questionnaires and parasitologic examinations of urine and stool were performed upon a stratified random sample of 7,710 individuals from 1,109 households in 21 rural communities in Fayoum Governorate, Egypt in 1992 to investigate the prevalence of, risk factors for, and changing pattern of, infection with Schistosoma sp. in the governorate. A subset, every fifth household, or 1,038 subjects, had physical and ultrasound examinations to investigate prevalence of, and risk factors for, morbidity. The prevalence of S. haematobium ranged from 0% to 27.1% and averaged 13.7%. The geometric mean egg count (GMEC) was 10.0 eggs/10 ml of urine. Age-stratified prevalence and intensity of infection were 18-25% and 10-15 eggs/10 ml of urine in those 5-25 years of age. Schistosoma mansoni were detected in inhabitants of 13 communities, but 78.5% of the infections were focally present in a group of 4 satellite hamlets around a single village. The overall prevalence of S. mansoni in the governorate was 4.3% and the GMEC was 44.0 ova/g of stool. Risk factors for infection with either species were male gender, an age <20 years, living in smaller communities, and exposures to canal water by males. Histories of burning micturation, blood in the urine, or prior schistosomiasis and reagent strip-detected hematuria and proteinuria were risks for S. haematobium, but not for S. mansoni. Both urinary tract and higher grades of hepatic morbidity were rare. Obstructive uropathy was present in 6.3% of the subjects and was more common in males and older people. Ultrasonography-detected bladder lesions were present in 5.2% and correlated with S. haematobium only in younger subjects and in those with hematuria and proteinuria. The prevalences of hepatomegaly, splenomegaly, and periportal fibrosis (PPF) were associated with each other and increased with age and in males. Ultrasonography-detected hepatomegaly and splenomegaly were weakly associated with S. mansoni infections only in children. The prevalence of PPF was greater in the 4 communities with >25% S. mansoni infection rates in comparison with the 17 other villages and ezbas. Transmission of S. mansoni is focally well established in Fayoum, which also has the highest prevalence of S. haematobium in the governorates surveyed by the Epidemiology 1, 2, 3 Project. However, both urinary tract and hepatic morbidity are relatively rare in the governorate. This probably results from the long-standing schistosomiasis control program in Fayoum, which suppressed intensity more than prevalence of infection, leading to less community morbidity.

The epidemiology of schistosomiasis in Egypt: Minya Governorate.

Risk factors, prevalence, and intensity of infection with Schistosoma sp. and prevalence and magnitude of morbidity caused by schistosomiasis was assessed in a stratified random sample of 16,433 subjects from 2,409 households in 33 rural communities in Minya Governorate, Egypt. The prevalence of S. haematobium ranged from 1.9% to 32.7% among the communities and averaged 8.9%. The average intensity of infection was a geometric mean egg count (GMEC) of 8.5 per 10 ml of urine and ranged from 1.6 to 30.9. Prevalence was maximum (18-20%) in those 10-20 years of age and higher in males than in females. Intensity of infection followed the same pattern. Infection with S. mansoni was present almost exclusively in a single village, confirming spread of this species up the Nile River and its focality in Minya. Risk factors for S. haematobium infection were an age from 11 to 20; male gender; males bathing in, women washing clothing or utensils in, and children swimming or playing in canals; and a history of, or treatment for, schistosomiasis. Recent history of burning micturition was associated with infection in children but not in adults, while a history of blood in urine correlated with S. haematobium infection in both age groups. Reagent strip-detected hematuria and proteinuria were highly associated, particularly in children, with S. haematobium infection. The presence of hepatomegaly or splenomegaly on physical examination was not associated with S. haematobium ova in the urine. Hepatomegaly, as measured by ultrasonography in the midclavicular line or the midsternal line, or ultrasonography-detected splenomegaly were not present more frequently in infected subjects than in uninfected subjects. Schistosoma ova were not detected more frequently in urine of subjects with ultrasonography-detected periportal fibrosis than in the urine from subjects without this finding. Ultrasonography-detected urinary bladder wall lesions were detected in only 6 (0.3%) subjects and obstructive uropathy was observed in 54 (2.7%) subjects. The absence of an association between prevalence of urinary tract morbidity and S. haematobium infections was surprising. Two possible explanations are 1) that repeated chemotherapy has reduced the prevalence of urinary tract morbidity and 2) that morbidity was not being detected by the ultrasonographic operators.

The epidemiology of schistosomiasis in Egypt: Assiut governorate.

In the Assiut, Egypt Epidemiology 1, 2, 3 investigation, a sample of 14,204 persons in 10 villages, 31 ezbas (satellite communities), and 2,286 households was drawn from a rural population of 1,598,607. Parasitologic examination of urine and stool were made for Schistosoma haematobium and S. mansoni, and physical and ultrasound examinations were made on a 20% subsample. The overall estimated prevalence of S. haematobium was 5.2 +/- 0.5 (+/- SE). This varied considerably by village and ezba, ranging from 1.5% to 20.9%, with ezbas having a slightly higher overall prevalence than villages. The overall estimated geometric mean egg count was 6.6 +/- 0.5 eggs per 10 ml of urine and was consistently low throughout the communities. Infection with S. haematobium was associated with age (peak prevalence of 10.6 +/- 1.5% in 15-19-year-old age group) males, children playing in the canals, a history of blood in the urine, and reagent strip positivity for hematuria and proteinuria. The prevalence of either hepatomegaly or splenomegaly detected by physical examination was low (4.0% and 1.5%, respectively). The prevalence of hepatomegaly determined by ultrasonography was substantially higher, 24.1%. The prevalence of periportal fibrosis (PPF) was 12.0%, but grade II or III PPF was present in less than 1%. Ultrasonography-determined hepatomegaly, in both the midclavicular line and the midsternal line, increased by age to more than 30%. Periportal fibrosis was more common in the age groups in which infection rates were the highest. At the village and ezba level of analysis, the prevalence of hepatomegaly, splenomegaly, and PPF tended to be higher in communities having the highest prevalence of infection with S. haematobium.

The epidemiology of schistosomiasis in Egypt: summary findings in nine governorates.

Health questionnaires and parasitologic examinations of urine and stool were evaluated from a stratified random sample of 89,180 individuals from 17,172 households in 251 rural communities in 9 governorates of Egypt to investigate the prevalence of, risk factors for, and changing pattern of infection with Schistosoma sp. in Egypt. A subset, every fifth household, or 18,600 subjects, had physical and ultrasound examinations to investigate the prevalence of and risk factors for morbidity. Prevalence of S. haematobium in 4 governorates in Upper Egypt in which it is endemic ranged from 4.8% to 13.7% and averaged 7.8%. The geometric mean egg count (GMEC) ranged from 7.0 to 10.0 ova/10 ml of urine and averaged 8.1. Age stratified prevalence of infection peaked at 15.7% in the 10-14-year-old age group and decreased to 3.5-5.5% in all groups more than 25 years of age. Age-stratified intensity of infection peaked at approximately 10.0 ova/10 ml of urine in the 5-14-year-old age groups and was about half that in all groups more than 25 years of age. Males had higher infection rates and ova counts than females in all age groups. Schistosoma mansoni was rare in Upper Egypt, being consequential in only Fayoum, which had a prevalence of 4.3% and an average intensity of infection of 44.0 ova/g of stool. Risk factors for S. haematobium infection were male gender, an age <21 years old, living in smaller communities, exposures to canal water; a history of, or treatment for, schistosomiasis, a history of burning micturition or blood in the urine, and reagent strip-detected hematuria or proteinuria. The more severe grades (II and III) of ultrasonography-detected periportal fibrosis (PPF) were rare (15 of 906) in these schistosomiasis haematobia-endemic governorates. Risk factors for morbidity (ultrasonography-detected urinary bladder wall lesions and/or obstructive uropathy) were similar to those for infection, with the exception that risk progressively increased with age. Subjects with active S. haematobium infections were 3 times as likely as those without active S. haematobium infections to have urinary tract morbidity. The prevalence of S. mansoni in 5 governorates in Lower Egypt, where it is endemic, ranged from 17.5% to 42.9% and averaged 36.4%. The GMEC ranged from 62.6 to 93.3 eggs/g of stool and averaged 81.3. Age-stratified prevalence of infection peaked at 48.3% in the 15-19-year-old age group, but averaged 35-45% in all groups more than 10 years of age. The intensity of infection was highest in the 10-14-year-old age group, and showed a range of 70-85 eggs/g of stool in those > or =5 years of age. Males had higher infection rates and ova counts than females in all age groups. Schistosoma haematobium was rare in these governorates; Ismailia (1.8%) had the highest infection rate. Risk factors for S. mansoni were male gender, an age >10 years old, living in smaller communities, exposures to canal water, a history of, or treatment for, schistosomiasis or blood in the stool, detection of splenomegaly by either physical examination or ultrasonography, and ultrasonography-detected PPF. The more severe grades (II and III) accounted for 463 (13.3%) of the 3,494 having ultrasonography-detected PPF. Risk factors for morbidity (ultrasonography-detected PPF) were similar to those for infection except that inhabitants of smaller communities were not at increased risk. Active S. mansoni infection increased the odds ratio (OR) of having PPF by 1.37. In comparison with others with normal-size livers, subjects having hepatic enlargement in either the midclavicular line or the midsternal line detected by physical examination or ultrasonography had a reduced risk (ORs = 0.64-0.72) of PPF. The prevalences of lesions detected by ultrasonography were 23.7% for enlargement of right lobe of the liver, 11.3% for enlargement of left hepatic lobe, 20.6% for splenomegaly, and 50.3% for PPF. Schistosoma mansoni has almost totally replaced S. haematobium in Lower E

Prevalence of antibodies to hepatitis E in two rural Egyptian communities.

A population-based serosurvey in two rural Egyptian communities was used to assess age-specific prevalence of antibody to hepatitis E virus (anti-HEV). One community is in the Nile Delta (11,182 inhabitants; 3,997 participants) and the other in Upper Egypt (10,970 inhabitants; 6,029 participants). Samples were tested for anti-HEV with a commercial enzyme-linked immunoassay (ELISA) based on antigens derived from open reading frame (ORF)2 and ORF3. Although there was a clear difference in sensitivity among the lots of the commercial test used, it was still possible to determine the seroprevalence. The seroprevalence of anti-HEV exceeded 60% in the first decade of life, peaked at 76% in the second decade and remained above 60% until the eighth decade. Prevalence of this magnitude is among the highest reported in the world, with an age-specific pattern more similar to hyperendemic hepatitis A virus transmission than generally described. Lot-to-lot variation in the sensitivity of the commercial ELISA kit highlights a problem when comparing seroepidemiologic studies of different populations.

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. Egypt's mass campaigns of PAT may represent the world's largest iatrogenic transmission of blood-borne pathogens.

Hepatitis C in a community in Upper Egypt: I. Cross-sectional survey.

The prevalence of antibody to hepatitis C virus (anti-HCV) was determined in a cross-sectional survey in a village in Upper Egypt. Exposure and demographic characteristics were obtained through a questionnaire. Antibody to hepatitis C virus was assessed using a second generation enzyme immunoassay, and the presence of HCV RNA was tested using a reverse transcriptase-polymerase chain reaction. Collection of blood samples was targeted at those > or = 5 years old, and obtained from 62.8%. This report describes the community, the HCV infection characteristics of the subjects, and evaluates some factors associated with presence of anti-HCV. Of the 6,031 participants, 522 (8.7%) were anti-HCV positive. Prevalence was higher among males than females (11.3% versus 6.5%; P < 0.001). It was greater among those > 30 years of age than among those < or = 30 years of age (20.0% versus 3.6%; P < 0.001). Those who were less educated, farmed, provided health care, and were currently married had a significantly higher anti-HCV prevalence than those who were not; however, these associations were not significant after adjusting for age. Although active infections with Schistosoma haematobium were not associated with anti-HCV, a history of past infection was (age-adjusted risk ratio [RR] = 2.1, 95% confidence interval [CI] = 1.8, 2.4); 134 persons who had a history of receiving parenteral anti-schistosomal therapy had a higher age-adjusted RR (3.0; 95% CI = 2.5, 3.7) for anti-HCV than those who did not. Hepatitis C virus RNA was detected in 62.8% of the anti-HCV positive subjects, without significant variation by age, gender, education, or marital status. The prevalence of anti-HCV in Upper Egypt is high, albeit lower than in Lower Egypt, with continuing but limited transmission indicated by the lower prevalence in residents < or = 30 years old.

Parasite density and malaria morbidity in the Pakistani Punjab.

The relationship between quantitative Plasmodiumfalciparum or P. vivax parasitemia and clinical illness has not been defined in Pakistan or in other areas where malaria transmission is not highly endemic. Standardized questionnaires were given to and physical examinations and parasitologic tests were performed in 8,941 subjects seen in outpatient clinics in 4 villages for 13 consecutive months in the Punjab region of Pakistan. The results, based on multivariable analysis, showed that a clinical diagnosis of malaria, a history of fever, rigors, headache, myalgia, elevated temperature, and a palpable spleen among children were all strongly associated with the presence and density of P. falciparum or P. vivax malaria in a monotonic dose-response fashion. The malaria attributable fraction of a clinical diagnosis of malaria, and the same symptoms and signs also increased with increasing P. falciparum and, to a lesser extent, P. vivax, parasitemia. Unlike in sub-Saharan Africa, clinical illness due to malaria often occurs in the Punjab among adolescents and adults and in patients with parasite densities less than 1,000/microl. Clinical guidelines based upon parasitemia and symptomatology must be adjusted according to the intensity of transmission and be specific for each geographic area.