Assessment of hepatitis E virus (HEV) in the edible goat products pointed out a risk for human infection in Upper Egypt.

Hepatitis E virus (HEV) infection is endemic in developed and developing countries. Although the seroprevalence of HEV among the Egyptians is high, the sources of HEV infection in Egypt are not completely identified. Zoonotic HEV transmission among Egyptians is underestimated. Recently, we detected HEV in the milk of cows, this suggests the possibility of HEV transmission through the ingestion of contaminated milk. However, the role of small ruminants especially the goats in HEV epidemiology in Egypt remains unclear. Herein, we screened HEV markers in the edible goat products, mainly the milk and liver and we assessed the risk factor for HEV infection to the goat owners. A total of 280 goat milk samples were collected from 15 villages in the Assiut governorate. Anti-HEV IgG and HEV Ag were detected in 7.14% and 1.8% of the samples, respectively. HEV RNA was detected in 2 milk samples, cladogram analysis revealed that the isolated viruses belonged to HEV-3 subtype 3a. One viral isolate showed high homology to HEV recently isolated from the cow milk in the same geographic area. The level of anti-HEV IgG and HEV Ag were comparable in the milk and matched blood samples. While the urine and stool of HEV seropositive goats tested negative for HEV markers. HEV RNA was also detectable in the fresh goat liver samples (n = 2) derived from HEV seropositive goats. Finally, we analyzed HEV seroprevalence in households (n = 5) that owned the seropositive goats and households (n = 5) that owned the seronegative goats. Interestingly, anti-HEV IgG was recorded in 80% of households owned and frequently consumed the products of HEV seropositive goats, while HEV markers were not detectable in the owners of the seronegative goats. In conclusion: Here, we report HEV in the milk and liver of goats distributed in the villages of Assiut governorate. Higher HEV seroprevalence was recorded in the households that owned the seropositive goats. Investigation of the goat products is pivotal to assess the risk factor of HEV transmission to villagers in the Assiut governorate.

MORBIDITY AND MORTALITY ASSESSMENT IN ACUTE HEPATITIS-E.

BACKGROUND: Hepatitis-E is an enterically transmitted virus causing acute hepatitis. Mostly it is a self-limiting clinical course, but can be life threatening in certain high risk groups. Pakistan is endemic for Hepatitis-E with limited published literature. The aim of this study is to evaluate the predictors of mortality in patients with acute Hepatitis-E. METHODS: We analyzed the medical records of 369 adult patients with Hepatitis-E infection admitted at Aga khan University Hospital, from January 1996 to December 2010. Details of their laboratory investigations, clinical course and complications such as FHF and mortality were noted. The outcome was compared, and determinants of mortality were evaluated in important patient subgroups. RESULTS: Out of 369 patients with Hepatitis-E, 326 (88.3%) were discharged after full recovery. Out of these 22 (6%) patients had chronic liver disease CLD in this study, of whom 10 (2.7%) expired (p-value <0.001). There were about 67 (18%) pregnant patients, with a mean gestational age of 29.19 +/- 7.68 weeks and 5 (1.4%) pregnant patients died (p-value=0.23). A total of 58 (15.7%) patients were coinfected with other hepatotropic virus, and a comparison did not find an increased risk of mortality in this group. CONCLUSION: This study showed that Hepatitis-E is significantly associated with mortality in patients suffering from pre-existing chronic liver disease. Pregnancy was not a determinant of mortality in Hepatitis-E patients in this study, and neither was coinfection with other Hepatotropic viruses.

Cost-effectiveness analyses of hepatitis A vaccine: a systematic review to explore the effect of methodological quality on the economic attractiveness of vaccination strategies.

Hepatitis A vaccines have been available for more than a decade. Because the burden of hepatitis A virus has fallen in developed countries, the appropriate role of vaccination programmes, especially universal vaccination strategies, remains unclear. Cost-effectiveness analysis is a useful method of relating the costs of vaccination to its benefits, and may inform policy. This article systematically reviews the evidence on the cost effectiveness of hepatitis A vaccination in varying populations, and explores the effects of methodological quality and key modelling issues on the cost-effectiveness ratios.Cost-effectiveness/cost-utility studies of hepatitis A vaccine were identified via a series of literature searches (MEDLINE, EMBASE, HSTAR and SSCI). Citations and full-text articles were reviewed independently by two reviewers. Reference searching, author searches and expert consultation ensured literature saturation. Incremental cost-effectiveness ratios (ICERs) were abstracted for base-case analyses, converted to $US, year 2005 values, and categorised to reflect various levels of cost effectiveness. Quality of reporting, methodological issues and key modelling issues were assessed using frameworks published in the literature.Thirty-one cost-effectiveness studies (including 12 cost-utility analyses) were included from full-text article review (n = 58) and citation screening (n = 570). These studies evaluated universal mass vaccination (n = 14), targeted vaccination (n = 17) and vaccination of susceptibles (i.e. individuals initially screened for antibody and, if susceptible, vaccinated) [n = 13]. For universal vaccination, 50% of the ICERs were <$US20 000 per QALY or life-year gained. Analyses evaluating vaccination in children, particularly in high incidence areas, produced the most attractive ICERs. For targeted vaccination, cost effectiveness was highly dependent on the risk of infection.Incidence, vaccine cost and discount rate were the most influential parameters in sensitivity analyses. Overall, analyses that evaluated the combined hepatitis A/hepatitis B vaccine, adjusted incidence for under-reporting, included societal costs and that came from studies of higher methodological quality tended to have more attractive cost-effectiveness ratios. Methodological quality varied across studies. Major methodological flaws included inappropriate model type, comparator, incidence estimate and inclusion/exclusion of costs.

Screening travelers for hepatitis A antibodies: an observational cost-comparison study of vaccine use.

OBJECTIVES: To measure the seroprevalence of antibodies to hepatitis A virus (anti-HAV) in a health plan population of travelers and to determine whether prevaccination screening for anti-HAV can reduce unnecessary vaccination and thus promote the most effective, economic use of hepatitis A vaccine. DESIGN: Observational, cost-comparison study. SETTING: Central injection clinic of a health maintenance organization medical center. SUBJECTS: Five hundred twenty-seven adults who denied having previous hepatitis A or vaccination. MAIN OUTCOME MEASURES Subgroups with the greatest prevalence of anti-HAV seen between June 1995 and April 1996 for immunizations before traveling to nonindustrialized countries. Relative costs of their screening and immunization. RESULTS: The presence of anti-HAV precluded the need for vaccination in 148 subjects (28.1%). The highest prevalence of anti-HAV (82.7%) was found in subjects born in nonindustrialized countries (62/75), in subjects who had previously traveled to areas of endemic hepatitis A (32.1% [135/420]), and in subjects born before 1945 (29.2% [92/315]). Costs of screening and vaccinating travelers were cheapest if prevaccination antibody sera testing was limited to subjects born in nonindustrialized countries and those born before 1945. CONCLUSIONS: Prevaccination screening of travelers for hepatitis A can be done selectively on the basis of age and country of origin. This strategy could lead to a more economic use of the vaccine and clinic resources.

Cost-effective analysis of hepatitis A prevention in Ireland.

OBJECTIVE: The purpose of this study was to determine the most cost-effective prevention strategy against hepatitis A virus (HAV) infection for healthcare workers and the general population at risk in Ireland. METHODS: Four prevention strategies were compared: active immunization with Havrix Monodose (1440E.U); screening for anti-HAV antibody and then vaccinating; passive immunization; screening for anti-HAV antibody and then passive immunization. The cost-effective ratio was calculated for each prevention strategy. Threshold analysis, sensitivity analysis, and model extension to include indirect cost from work days lost and secondary attack rates through horizontal transmission were also derived. RESULTS: The medical costs were lowest and the infection rate highest when no preventive action was taken. Vaccination was most cost effective when the prevalence of immunity was 45% or less, reducing the infection rate by 98% when compared to nonprevention. Screening before vaccination was most cost effective when the prevalence of immunity was greater than 45%. Passive immunization and screening before passive immunization were not comparable to the other strategies in cost effectiveness. Sensitivity analysis showed that the cost-effective ratio for vaccination was dependent on vaccine price, incidence of HAV, and prevalence of immunity in the target group. Extending the model to include indirect costs further increased the cost effectiveness of vaccination. CONCLUSION: The best cost-effective strategy relates to target group immunity. Where HAV immunity is 45% or less, vaccination is the strategy of choice and when immunity is greater than 45%, then screening followed by vaccination should be used. This study can be used to provide a framework within which choices can be made to achieve better health for less cost.

Cost-effectiveness analysis of hepatitis A vaccination strategies for adults.

Our objective in this study was to determine the cost-effectiveness of hepatitis A vaccination strategies in healthy adults in the United States. We constructed a decision model simulating costs and health consequences for otherwise healthy adults with respect to hepatitis A prevention. Three strategies were compared: (1) no intervention, (2) vaccination against hepatitis A, and (3) testing for antibodies to hepatitis A and vaccinating those without antibodies. Costs and probabilities were obtained from the published literature. One- and two- way sensitivity analyses were performed. Under baseline conditions, the "test" strategy cost $230,100 per life-year saved compared with the "no intervention" strategy. The incremental cost-effectiveness of the "vaccination" strategy compared with the "test" strategy was $20.1 million per life-year saved. The "test" strategy was cost-effective when the hepatitis A case fatality rate exceeded 17% (baseline 2.7%). The "vaccination" strategy was cost-effective when 1 dose of vaccine cost $7 or less (baseline $57). Under baseline conditions, neither the "test" nor the "vaccination" strategies are considered cost-effective according to current standards. Large changes in hepatitis A incidence, mortality rates, or vaccine cost are required for either of the intervention strategies to approach potentially cost-effectiveness. Such conditions may occur in areas in which hepatitis A is endemic, and/or under mass-vaccination scenarios.

Assessment of a hepatitis C virus antibody assay in saliva for epidemiological studies.

The performance of a commercially available assay for detection of hepatitis C virus (HCV) antibody in saliva samples was assessed. Samples of saliva were collected from 270 individuals whose HCV antibody status was determined by serum assay (161 HCV-positive, 109 HCV-negative). The saliva samples were tested for the presence of HCV antibodies using a modified protocol. The sensitivity was 94.4% (95% CI, 89.3-97.2%) and the specificity 99.1% (95% CI, 94.3-100%). Although the optical density in tests on HIV-positive individuals was lower than that among HIV-negative individuals, the HIV status had no significant influence on the results of the HCV assay in saliva. These findings suggest that tests on saliva can be useful in epidemiological studies for estimating the prevalence of HCV in populations that are difficult to reach.

The prevalence of hepatitis A antibodies among Israeli travellers and the economic feasibility of screening before vaccination.

BACKGROUND: Hepatitis A (HA) is the most common vaccine-preventable disease among travellers. The probability of contracting the disease depends on the endemicity in both the destination and country of origin of the traveller. The introduction of the new highly effective but expensive inactivated HA vaccine necessitates a re-evaluation of HA prevention policy. In highly developed countries all travellers require vaccination. In highly endemic areas the entire population is immune. In Israel, HA seroprevalence declined from 94% in the early 1970s to < 60% in the mid 1980s. Living in a country in which the HA endemicity is changing, we studied the current situation of HA seroprevalence among travellers and the cost-benefit of screening for HA IgG before vaccination. METHODS: Israeli travellers of all ages, (range 22-74 years) expecting to spend a considerable time abroad presented to the travel clinic for pre travel advice and vaccination. A brief medical history was taken, including history of jaundice. Blood for HA IgG testing was drawn. RESULTS: In the present study, 389 Israeli travellers were screened for HA IgG. Overall, 46% were seropositive: 26% in the 21-30 group (n = 102); 37% in the 31-40 group (n = 145); 62% in the 41-50 group (n = 62); and 79% in the > 50 group (n = 80). CONCLUSIONS: In countries where hepatitis A endemicity is changing, an evaluation of seroprevalence and then a cost benefit calculation should be made. In Israel, assuming a current cost of $130 for vaccination and $30 for the IgG test, it is economically valid to screen Israeli travellers > 30 years old for HAV IgG before vaccination. A formula is presented for calculating the cost benefit ratio in any country, based on local endemicity according to age group.

Hepatitis A vaccination by intracutaneous low dose administration: a less expensive alternative.

We investigated the immune response to three different intracutaneous (i.c.) doses of inactivated hepatitis A vaccine: 72, 144, and 216 ELISA units (EU). The response was measured using a quotient score derived from a commercial enzyme-linked immunosorbent assay (HAVAB Abbott) and translated to IU per liter using a World Health Organization standard serum for hepatitis A virus antibody. The results were compared with the results obtained after an intramuscular (i.m.) full dose, i.e. 1,440 EU, at 0 and 6-12 months. As estimated from antibody concentration, 3 lots of 144 EU i.c. with 100% or two lots of 216 EU i.c. with 98% seroconversion results in at least as good early protection as the standard immunization with one lot of 1,440 EU i.m., (79% with our method). Indeed, only two doses of 144 EU vaccine (90% seroconversion) seem to give results comparable to the standard procedure. After the booster dose the median antibody concentration is 1,290 IU/l for the 144 EU vaccine and 837 for the 216 EU one, compared with an antibody response of 990 IU/l for the standard 1,440 EU i.m. vaccination. In conclusion, three doses of 144 EU vaccine i.c. or, as an alternative, two doses of 216 EU at monthly intervals give good early protection (e.g. before travel). After the booster dose, which is given 6 months to 1 year later, the serological response is comparable to the standard procedure of two doses of the 1,440 EU vaccine given i.m. and with 100% seroconversion in all three programs.

Cost effectiveness of hepatitis A prevention in France.

A spreadsheet simulation model of hepatitis A disease was developed to evaluate the cost effectiveness of an inactivated [corrected] hepatitis A vaccine ('Havrix', SmithKline Beecham) in high risk groups in France. Gammaglobulin prophylaxis, systematic vaccination without screening and vaccination of nonimmune persons after systematic screening were compared with the reference situation of no prevention over a 10-year period. It was found that both vaccination strategies would prevent 98% of new cases of hepatitis A, and would generate savings of FF4.2 to FF4.7 million ($US1 = FF5, 1995) in alternative service volunteers [initial seroprevalence (IS) 26%] stationed in countries with high hepatitis A endemicity. The cost per symptomatic case avoided [i.e. the cost-effectiveness ratio (CER)] was found to vary from FF177,612 with screening to FF281,463 without screening in adult tourists (IS 77%). In hospital workers, screening before vaccination (CER = FF65,108) would be about half as costly as systematic vaccination (IS 55 to 79%). Recommendations for vaccination should take into account the specific collective or individual risk, age, seroprevalence and probability of compliance with the prevention protocol.

Hepatitis A antibodies in attenders of London Travel Clinics: cost-benefit of screening prior to hepatitis A immunisation.

The seroprevalence of hepatitis A antibodies in travellers attending London Travel Clinics increases with age and screening may eliminate the need for vaccination at present for approximately 40% of adults. The duration of protection by current hepatitis A vaccine(s) is still to be established.

Prospective assessment of incidence of fulminant hepatitis in post-transfusion hepatitis: a study of 504 cases.

The incidence of posttransfusion hepatitis and "fulminant" hepatitis was investigated by a plan devised at our hospital in December 1982. Of 2959 blood recipients between January 1982 and December 1988, 504 (22.5%) developed posttransfusion hepatitis, with a mean transfusion volume of 10.2 units. Of the 504 cases of posttransfusion hepatitis, "icteric" (T-Bil > 2.0 mg/dl) and "overt icteric" hepatitis (T-Bil > 5.0 mg-dl) developed in 111 cases (22.0%) and 28 cases (5.6%), respectively. Of the 28 overt icteric hepatitis cases, 13 (2.8%) were thought to be true overt icteric posttransfusion hepatitis because the icterus was caused by other reasons in the other 15 cases (seven neonatal jaundice, four hemolytic anemia, one radiation hepatitis, one halothane-induced hepatitis; two other cases were excluded because chronic liver disease was diagnosed by imaging procedures despite serum ALTs in the normal range before transfusion). The anti-HCV serostatus was investigated in five of the 13 true overt icteric posttransfusion hepatitis patients using blood specimens taken 180 days or more following the onset of posttransfusion hepatitis. Anti-HCV seroconversion occurred in three of the five cases (60%). HCV seroconversions were not seen in the cases in which the icterus was due to other reasons.

Prospective assessment of donor blood screening for antibody to hepatitis C virus and high-titer antibody to HBcAg as a means of preventing posttransfusion hepatitis.

Since December 1989, the Japan Red Cross Blood Bureau has screened blood donors for hepatitis C virus antibody on the basis of enzyme-linked immunosorbent assay and high titers of antibody to HBc antigen. To elucidate the effectiveness of the new screening tests in preventing posttransfusion hepatitis, the incidence of posttransfusion hepatitis after the introduction of the new tests (December 1989 to December 1990) was compared with the incidence before their introduction (January 1982 to December 1988). The incidence of posttransfusion hepatitis was 9.8% (219 of 2240), with a mean transfusion volume of 10.2 units, before the screening and 3.7% (12 of 326), with a mean transfusion volume of 14.7 units, after the introduction of the new tests. Statistical analysis revealed a significant decrease of incidence of posttransfusion non-A, non-B hepatitis after the introduction of the new tests (X2 = 10.9, p < 0.01). Posttransfusion hepatitis B occurred in 3 of 2,240 recipients (0.13%) before the introduction of HBc antibody testing. No cases of posttransfusion B viral hepatitis developed after the introduction of the new tests. Hepatitis C virus antibody status was investigated in 7 of 12 posttransfusion hepatitis patients who contracted the disease after the new screening tests were initiated. Hepatitis C virus antibody seroconversion occurred in three of the seven cases (43%), as detected on first- and second-generation hepatitis C virus antibody assays and reverse-transcription polymerase chain reaction.

Prospective assessment of donor blood screening for antibody to hepatitis C virus and high-titer antibody to hepatitis B core antigen as a means of preventing post-transfusion hepatitis.

Since November 1989, the Japan Red Cross has been screening blood donors for hepatitis C virus antibody (anti-HCV) with 1st generation assay and high-titer antibody to hepatitis B virus core antigen (HBcAb). To clarify the effectiveness of the new screening tests for the prevention of post-transfusion hepatitis, the incidence of post-transfusion hepatitis after the introduction of new tests (December 1989 to September 1990) was compared with the incidence before the in introduction (January 1982 to December 1987). The incidence of "definite" post-transfusion hepatitis was 10.3% (205/1991) with a mean transfusion volume of 10.2 units before the screening, and 3.9% (11/282) with a mean transfusion volume of 14.6 units after the introduction of the new screening tests. Statistical analysis revealed a significant decrease of post-transfusion non-A, non-B hepatitis after the introduction of new tests (chi 2 = 10.9, P < 0.01). The incidence of "probable" post-transfusion hepatitis was 12.4% (246/1991) and 11.7% (33/282) respectively. No significant change was observed between the rates of "probable" post-transfusion hepatitis before and after the introduction of the new tests. It was concluded that anti-HCV and high-titer anti-HBc screening of volunteer blood donors could contribute to the prevention of the post-transfusion non-A, non-B hepatitis in Japan.

Simple haemadherence test for the detection of class-specific immunoglobulins to hepatitis A virus.

The ability of hepatitis A virus (HAV) to agglutinate human erythrocytes was used to develop IgM and IgG antibody capture haemadherence tests (MACHAT and GACHAT). Haemadherence was dependent on the pH of the red cell suspension and was best in the pH range 5.4 to 5.8. The tests were applied to serum, urine, and saliva specimens from individuals susceptible to, or with recent or past infection with HAV. Haemadherence test reactivities were compared with results obtained with IgM and IgG antibody capture radioimmunoassay (MACRIA and GACRIA) and competitive radioimmunoassay (COMPRIA). For 339 serum specimens examined, the sensitivity and specificity of MACHAT were 98.2% and 99.6%, respectively, and of GACHAT 99.1% and 100.0%. For 303 urine specimens, the sensitivity and specificity of MACHAT were 99.1% and 100.0%, and of GACHAT 100% for both. On initial testing, accuracy on saliva specimens was considerably less. For 2,819 saliva specimens, the sensitivity and specificity of MACHAT were 85.7% and 97.2% and of GACHAT 90.4% and 94.7%. The haemadherence test is a simple, inexpensive method which is satisfactory for use on serum and urine specimens. MACHAT and GACHAT can be used for epidemiological investigations, e.g., hepatitis A outbreaks and, in conjunction with a confirmatory test, for clinical diagnostic testing.

Clinical assessment and incidence of hepatitis C RNA in 50 consecutive RIBA-positive volunteer blood donors.

OBJECTIVES: (i) To assess evidence of liver disease in 50 consecutive volunteer blood donors who were anti-hepatitis C virus (anti-HCV) antibody positive and who were referred to one hepatologist; (ii) to assay for viral RNA in serum in these patients. SETTING: Royal Prince Alfred Hospital, a teaching hospital of the University of Sydney. PATIENTS: Fifty people who were detected by the NSW Red Cross Blood Transfusion Service to be anti-HCV antibody positive and to have a positive result on recombinant immunoblot assay (RIBA) were assessed by one hepatologist for symptoms, signs and biochemical evidence of hepatic dysfunction. These patients were consecutive referrals from this source. Sixteen of these patients also consented to liver biopsy assessment. All patients had serum assayed for viral RNA by polymerase chain reaction with a combination of 3' and 5' primers. RESULTS: The 50 blood donors consisted of 28 men and 22 women, with a mean age of 34.5 years. Forty-six patients were asymptomatic. Only six had a past history of hepatitis while 14 had minor signs of chronic liver disease. In 28, injecting drug use was thought the most likely source of exposure to HCV. The minimal mean time since exposure to HCV in these patients was 8.8 +/- 5.2 years. Eight patients had received a blood transfusion at a mean time of 15.0 +/- 9.8 years from the time of consultation. The mean maximum level of alanine aminotransferase (ALT) in all 50 patients was 102.8 U/L. Five patients had persistently normal ALT levels; another 22 had at least one normal ALT level. Liver biopsies indicated chronic persistent hepatitis in 11 patients, mild chronic active hepatitis in three patients and more severe chronic active hepatitis in one. One patient had cirrhosis on biopsy. Forty-two patients had viral RNA detected in serum. CONCLUSION: Chronic infection with HCV in blood donors was invariably asymptomatic; 78% of patients had no signs of chronic liver disease and 68% had a maximum hepatic transaminase level of less than 100 U/L. Although severe liver disease was seen in two of 16 biopsies, the majority of these patients have mild liver disease despite a mean of about 10 years since exposure to the virus. Eighty-four per cent of patients had evidence of viral RNA in serum.

Detection of hepatitis C virus antibodies with new recombinant antigens: assessment in chronic liver diseases.

A new serological assay to detect antibodies against hepatitis C, based on a recombinant protein (BHC10) which incorporates structural and non-structural viral antigens, was tested in 67 healthy subjects and 409 patients with various forms of liver disease. Results were compared with the current assay based on the recombinant non-structural viral antigen c100 and with the recently introduced second-generation assay, Ortho2. None of the healthy subjects was positive by any of the assays. In patients with chronic non-A, non-B hepatitis the prevalence of anti-BHC10 was 96.8%, higher than anti-c100 (83.3%, p less than 0.001) and similar to Ortho2 (94.3%). False-positive results were less frequently found when BHC10 was used. These findings show that assays incorporating structural and non-structural antigens provide higher sensitivity to detect hepatitis C virus infection and they define an almost exclusive role of hepatitis C virus in the genesis of chronic non-A, non-B hepatitis.