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Biomedical subjects

E Nordenfelt

Publications and source records attributed to E Nordenfelt.

At least 19 recordsLinked to original sources

A comparison between one first generation and three second generation anti-HCV ELISAs: an investigation in high- and low-risk subjects in correlation with recombinant immunoblot assay and polymerase chain reaction.

One first generation assay (manufactured by Ortho, test I) and 3 second generation anti-HCV ELISAs (manufactured by Ortho, Abbott, and UBI, tests II-IV) were compared. Sera from 4 different sources were used: (1) intravenous drug-users (IVDUs, n = 50), (2) blood donors (n = 1055), (3) all clinical samples from one day of routine anti-HCV testing (n = 89), (4) hemodialysis patients previously found negative by test I but clinically suspected to have a HCV infection (n = 11). Confirmatory anti-HCV tests were carried out with a second generation recombinant immunoblot assay (RIBA II). In sera positive exclusively by test IV, one antibody consumption test (UBI HCV Neutralization EIA) and one further immunoblot assay (INNO-LIA HCV Ab) were used. PCR for HCV RNA was carried out on all hemodialysis patient sera and in the RIBA II positive blood donor sera. The second generation ELISAs discriminated 11 more positive samples than the first generation test (2 IVDUs, 5 blood donors, 4 clinical samples). The 9 sera from blood donors and clinical samples were all RIBA II positive or indeterminate. The second generation tests thus showed increased sensitivity. The second generation tests also showed increased specificity in that 4 samples that were positive by test I but negative by the second generation tests, were also negative by RIBA II. With few exceptions, all RIBA II-positive and most of the indeterminate samples were positive by the second generation ELISAs. With few exceptions, all the RIBA II-negative samples were negative by the second generation ELISAs. Eleven blood donor sera were positive by test IV exclusively where RIBA II and other supplementary assays were negative. The recently introduced second generation anti-HCV ELISAs were found to have a higher sensitivity than the first generation test. The tests also showed a good concordance with the exception of test IV in the group of blood donor sera.

Blood Donors

Hepatitis A in Swedish travellers.

The incidence of hepatitis A is very low in Sweden. It has been shown that the prevalence of antibodies to hepatitis A virus is 6.6% in individuals < 40 years of age and 1% in those < 20 years old. The number of reported cases of hepatitis A infection has declined from 628 in 1985 to approximately 250 during the last four years. The attack rate per 100,000 inhabitants has thus declined from 7.3 to approximately 3 during this period. The number of cases in travellers has been stable at approximately 140 cases per year during the period 1985-1990. About one-third of the cases are associated with travel to either Europe or Asia. Immune globulin has been widely used as prophylaxis but use has declined. Based on travel statistics and estimation of the use of immune globulin, a risk ratio was calculated for the relation between the number of travellers not receiving immune globulin and cases of registered hepatitis A infection. This risk ratio was > 50,000 for travel to the Mediterranean part of Europe, approximately 100 for travel to Africa and approximately 300 for travel to Asia.

Hepatitis A

Acute sporadic viral hepatitis in Ethiopia: causes, risk factors, and effects on pregnancy.

One hundred and ten consecutive cases of acute sporadic hepatitis among Ethiopian patients were studied to define viral causes, identify risk factors, and analyze demographic and clinical data. IgM antibodies to hepatitis A virus were found in nine patients (8%), and hepatitis B surface antigen and IgM antibodies to hepatitis B core antigen were found in 22 (20%); these findings were considered evidence of acute hepatitis A and hepatitis B, respectively. Sera from the remaining 79 patients were tested for antibodies to hepatitis E virus by a blocking fluorescent antibody test. Thirty-six (33%) of these patients were seropositive, as compared to 4 (7%) of 59 healthy control subjects; for 43 patients (39%), the cause of the acute sporadic hepatitis was unidentified. Twenty-one (19%) of the patients had antibodies to hepatitis C virus, as determined by ELISA. Demographic, biochemical, and clinical data (except in regard to sequelae) were comparable for the different types of infections. The study subjects included 32 pregnant women, 19 (59%) of whom had hepatitis E virus infection; these infections caused death in eight of the women (mostly in the third trimester) and 10 fetal complications. Thus, hepatitis E virus is a common cause of acute sporadic viral hepatitis in Ethiopian patients, and its occurrence during pregnancy is associated with high maternal and fetal morbidity and mortality.

Acute Disease

Hepatitis C in chronic liver disease: an epidemiological study based on 566 consecutive patients undergoing liver biopsy during a 10-year period.

We analysed the presence of hepatitis C virus (HCV) antibodies in 566 patients undergoing liver biopsy. While over 20% of the patients were anti-HCV positive according to ELISA, only 13.8% had HCV antibodies when tested with a four-antigen recombinant immunoblot assay (RIBA 2). At the time of inclusion in the study, most patients were asymptomatic, irrespective of whether they were HCV-positive. Histological findings in anti-HCV-positive patients were chronic persistent hepatitis, chronic active hepatitis or cirrhosis in greater than 75% of cases. Only four of the patients who were anti-HCV-positive according to the RIBA 2 had autoimmune chronic active hepatitis. Risk behaviour could be identified in the majority of cases. Community-acquired sporadic cases were rare (12%). Of the 153 patients who died during follow-up, 23 subjects were anti-HCV positive. Although age- and sex-adjusted survival was not shorter in anti-HCV-positive patients than in anti-HCV-negatives, the risk of hepatocellular cancer was higher (P = 0.01). We conclude that HCV infection is associated with chronic liver disease, even when critical evidence of viral aetiology is slight. Truly sporadic cases are rare. Patients infected with HCV are at increased risk of developing hepatocellular cancer.

Adolescent

Hepatitis C virus antibodies and hepatitis C virus RNA in Chinese blood donors determined by ELISA, recombinant immunoblot assay and polymerase chain reaction.

Antibodies to hepatitis C virus (anti-HCV) were determined in Chinese blood donors from the city of Wuhan by a second generation ELISA screening test and a confirmatory recombinant immunoblot assay (RIBA II). Two materials of 281 and 222 sera were sampled under similar conditions in 1989 and 1990, respectively. The first collection of sera was sent to Sweden in lyophilized form, the second directly as fresh unfrozen sera. A high proportion (7.1%) of the lyophilized sera reacted positively in the anti-HCV screening assay, but only seven (2.5%) were positive by the RIBA confirmatory test. In four of these sera HCV-RNA could be detected by polymerase chain reaction (PCR) analysis. In the second material of fresh sera six reacted positively in the screening anti-HCV ELISA, but only one was RIBA positive and four were RIBA indeterminate. None of these sera was positive for HCV-RNA. Thus, the overall prevalence of anti-HCV among the 503 Chinese blood donors, as identified by RIBA, was 1.6%, and of HCV-RNA by PCR 0.8%. The confirmed antibody prevalence is higher than reported from the Western world. Caution about using data from the screening ELISA only, especially if sera have been handled in an unorthodox way, is emphasized.

Adult

Prevalence of antibodies against hepatitis B and C viruses among different groups of medical staff.

The prevalence of antibodies to hepatitis C virus (anti-HCV) among the medical staff of a department of infectious diseases and a dialysis unit was studied (n = 80). Among medical staff from some selected emergency and operating units at elevated risk for blood exposure (n = 231) the prevalence of antibodies to both hepatitis B and C viruses was determined. Three out of 311 staff members tested (0.96%) were positive for anti-HCV, 1 from an emergency unit and 2 from surgery departments. 14/231 tested for anti-HBc (6.1%) were positive. None of these was positive for HBsAg. Thus, the prevalence of anti-HCV among medical staff frequently dealing with anti-HCV positive patients or at elevated risk for blood exposure was low and did not differ considerably from what has been found among healthy blood donors. The prevalence of markers for passed hepatitis B was only slightly augmented compared to what has been reported from the general population.

Hepacivirus

Reactivation of hepatitis B virus infection with an unusual pattern of serological markers.

A 73-year-old man presented with acute hepatitis, judged to be a reactivation of hepatitis B virus infection. His serum samples during a follow-up time of 16 months showed an unusual pattern of serological markers. He was consistently HBeAg positive, HBsAg fluctuated just under the cut-off value and he had a low level of circulating anti-HBs. By electron microscopy numerous aggregates of surface antigen particles, but not complete virions were seen. He was HBV DNA positive by hybridization. The complete precore and core genes and a region of the surface gene were amplified from his serum by PCR. These findings emphasize the need for expanded serological testing in some patients with acute clinical hepatitis.

Acute Disease

Chronic liver disease in Ethiopia: a clinical study with emphasis on identifying common causes.

Between July 1986 and April 1989, 334 hospitalized adult Ethiopian patients with chronic liver disease were studied according to a protocol to define their clinical features and to identify risk factors with the aim of preventive intervention. Of these, 14 had chronic hepatitis, 208 cirrhosis and 112 hepatocellular carcinoma (HCC). Both clinical and histological diagnostic criteria were employed. A detailed questionnaire was used to document demographic and clinical data. A common clinical presentation among patients with chronic hepatitis was darkening of the face and hands with or without hypertrichosis of the face and blisters over the dorsi of the hands. This overt or latent form of porphyrea cutanea tarda (PCT) responds to chloroquine. Patients with cirrhosis of the liver commonly present for the first time with ascites, splenomegaly, haematemesis and/or melena from oesophageal varices, and mental changes due to hepatic encephalopathy. Overt or latent forms of PCT are also common features. Peculiar to these cirrhotics is the rarity of spider naevi, gynaecomastia, testicular atrophy, Dupuytren's contracture, parotid gland enlargement and clubbing of the fingers. Exhaustion, loss of appetite, rapid loss of weight, right upper quadrant and/or epigastric pain (all often of less than 6 months' duration, a big, hard, tender and grossly nodular liver with bruit, signs of portal hypertension, and/or hepatic encephalopathy, in a young male with a rapid down hill course characterize the Ethiopian patient with HCC. Serum anti-nuclear factor, anti-mitochondrial anti-bodies and anti-smooth muscle anti-bodies were absent in those with chronic hepatitis and were uncommon in the cirrhotics and HCC cases. One or more hepatitis B virus markers were found in 86% of chronic hepatitis, 88% cirrhosis and 78% HCC and the HBsAg carrier state was found in 36%, 29% and 23%, respectively. Among the HBsAg carriers, HBeAg positivity was less common than anti-HBe but anti-HDV was significantly higher than in the healthy general population. Alphafetoprotein (AFP) levels greater than 500 mg/ml were present in 16 (8%) cirrhotics and 58 (52%) patients with HCC. Histologically, 3 of the chronic hepatitis patients had progressed to cirrhosis, 8 of the cirrhotic patients had chronic active hepatitis and 85% of HCC cases occurred in a background of macronodular cirrhosis. Three cirrhotics developed HCC during follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Outbreak of acute hepatitis E virus infection among military personnel in northern Ethiopia.

An outbreak of acute hepatitis E virus (HEV) infection occurred from October 1988 to March 1989 in military camps in northern Ethiopia. The epidemic was waterborne and entirely confined to military men, of whom 423 hospitalized, icteric patients were studied. The clinical course was mild and short, without any fulminant hepatitis or death. All sera tested for anti-HAV-IgM were negative and among 54 (13%) patients who were positive for HBsAg, 7 (2%) were positive for anti-HBc IgM. On the other hand, 28 of 30 (93%) patients had antibodies against hepatitis E virus (anti-HEV) in contrast to 1 of 29 (3%) asymptomatic controls (P less than .01). The need for an easily available, inexpensive serologic test for HEV infection, protection of water supplies from fecal contamination, adequate chlorination and/or boiling of drinking water, and health education about personal and environmental hygiene, especially in communities at high risk, is emphasized.

Acute Disease

Hepatitis C virus RNA in blood donor sera detected by the polymerase chain reaction: comparison with supplementary hepatitis C antibody assays.

The low specificity of screening ELISAs for antibodies to hepatitis C virus in blood donors has called for confirmatory tests. Two types of supplementary antibody assays are available, recombinant immunoblot assays (RIBA-1 and RIBA-2) and an antibody consumption test referred to as a neutralization assay. Amplification of viral nucleic acid by the polymerase chain reaction (PCR) provides an antibody independent mode of detecting viral infection. We applied reverse transcription-double PCR to detect an HCV 5'-noncoding viral RNA sequence in serum specimens and compared PCR findings with confirmatory antibody tests. This study includes sera from 37 blood donors found positive by the Ortho anti-HCV (C100-3) ELISA out of 14,591 donations. Of the 37 positive sera, 8 were positive by RIBA-1 and 1 further by RIBA-2. Seven of the RIBA positive sera contained HCV RNA by PCR. Among the 8 indeterminate and the 21 negative donor sera by RIBA-1, no PCR positive serum was found. The 37 anti-HCV positive donor sera identified by Ortho ELISA were also tested by Abbott anti-HCV (C100-3) ELISA whereby 22 were positive. Of these 22 sera plus 1 further with ELISA OD just below cutoff, 8 were positive by the "neutralization assay," (Abbott Laboratories, North Chicago, IL, USA) and 6 of these, including the borderline serum, were PCR positive. One of the two neutralizable but PCR negative sera was RIBA positive and the other was indeterminate. However, one ELISA (Abbott Laboratories) positive (OD 1.99) serum was not neutralizable but nevertheless contained HCV RNA by PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Donors

Antibody to hepatitis-C-virus-related proteins in sera from alanine-aminotransferase-screened blood donors and prospectively studied recipients.

A prospective study of posttransfusion non-A, non-B hepatitis was conducted in Malmö, Sweden, in 1984-1985, in which donors were alanine aminotransferase (ALT) screened but not ALT selected. Among 741 patients studied at 0, 6, and 12 weeks after transfusion, 13 developed non-A, non-B hepatitis, and these were further followed up. Stored sera from the 13 hepatitis patients and their 123 donors were tested for anti-hepatitis C virus (HCV) by ELISA and if positive, analyzed by recombinant immunoblot assay (RIBA). All ALT-elevated blood units (n = 301) and a similar number of ALT-normal units were also tested. Only 4/13 patients with non-A, non-B hepatitis seroconverted to anti-HCV, all with ALT peaks greater than 10 times the upper normal. All seroconversions occurred within 5 months after transfusion and could be confirmed by RIBA. Hepatitis C in recipients occurred both after transfusion of blood that was strongly positive, weakly positive, and/or negative for anti-HCV by ELISA. In donors grouped by ALT levels, the anti-HCV prevalence varied between 0.4 (normal ALT) and 14% (ALT elevated greater than or equal to 2 times). Of the total of 9 donor units positive by ELISA, only 5 were confirmed by RIBA. Of the 5 recipients of the RIBA-positive blood units, 3 went into hepatitis, 1 remained normal at 10.5 weeks, and 1 showed a slight, transient ALT elevation at week 12. The recipients of ELISA-positive but RIBA-negative blood remained healthy.

Alanine Transaminase

Antibody to a hepatitis C virus related protein among patients at high risk for hepatitis B.

Anti-HCV prevalence in treated hemophiliacs, their heterosexual partners, intravenous drug addicts and homosexual men was studied. In hemophiliacs and many of the intravenous drug addicts, greater than or equal to 2 sera drawn 1-18 or 1-17 years apart were available. Anti-HCV testing was performed by ELISA (Ortho). Among patients with severe and moderate hemophilia A, 87% (98/112) were positive for anti-HCV at least once and among patients with severe and moderate hemophilia B, 83% (24/29) were positive for anti-HCV. Seroconversion to anti-HCV was observed in 21% of hemophilia patients. In hemophilia A, HCV infection generally occurred during the first years of life and in hemophilia B somewhat later. Loss of anti-HCV antibody was seen in 12% (17 patients). The rest, 54% (76 patients) were seropositive in first and last samples. All 12 tested spouses to anti-HCV positive men were anti-HCV negative. 80% of the drug addicts (137/172) were seropositive for anti-HCV. In those with greater than 1 serum tested, 8% were consistently negative and 68% consistently positive. 21% seroconverted to anti-HCV while 3% lost antibody. 10% (22/211) of homosexual men were anti-HCV positive. Intravenous transmission of HCV thus seemed highly efficient whereas sexual transmission was much less efficient.

Adolescent

HBsAg/IgM complexes as a prognostic marker of chronicity in acute hepatitis B virus infection.

A simple radioimmunoassay for the detection of HBsAg/IgM complexes is described. 52 patients with acute hepatitis B infection were tested, 35 with self-limiting disease (group I) and 17 who became chronic carriers (group II). In the first sampling, taken during the early clinical phase, 24/35 patients (69%) in group I and 16/17 (94%) impending chronic carriers had detectable HBsAg/IgM complexes. The mean s/n values were significantly higher (p less than 0.01) in the group of chronic carriers. In the second sampling, taken with a mean of 31 and 39 days after the first samples in the first and second group, respectively, 2/35 (6%) and 15/17 (88%) were positive for HBsAg/IgM complexes (p less than 0.001). A comparison of HBsAg/IgM complexes results with the detection of HBeAg/anti-HBe showed that 7/14 (50%) patients with acute self-limiting disease lost their complexes before converting to anti-HBe. In the group of chronic carriers, HBeAg was generally lost before or at the same time as the HBsAg/IgM complexes (2.5 months to greater than 9 years after the onset of infection). The method described is easy to perform and could be entered into routine testing of patients with a newly acquired hepatitis B virus infection as an additional prognostic marker, complementing the HBsAg/anti-HBs and the HBeAg/anti-HBe systems.

Acute Disease

Successful treatment of fulminant hepatitis B and fulminant hepatitis B and D coinfection explained by inhibitory effect on the immune response?

Foscarnet has been shown to inhibit the proliferation of human T and B lymphocytes in vitro. The production of lymphokines was more strongly affected than the DNA synthesis. Monocyte function was only partly inhibited by the highest foscarnet concentration tried. The influence of foscarnet on the immune system could explain the beneficial effect observed in patients with HBV-related fulminant hepatitis treated with foscarnet.

Antiviral Agents

Immunogenicity of hepatitis B vaccine simultaneously administered with the expanded programme on immunisation (EPI).

To assess the immunogenicity of hepatitis B vaccine simultaneously administered with the Expanded Programme on Immunisation (EPI) vaccines, a total of 300 consecutive infants, ranging in age between 6 weeks and 6 months, were alternatively assigned to the revised EPI and to EPI plus plasma-derived hepatitis B vaccine (Hevac B Pasteur). Four dosages (2 mcg or 0.5 ml each) of hepatitis B vaccine were given intramuscularly. HBsAg, anti-HBc, and anti-HBs were determined at day 0 and at day 210 in both groups by radioimmunoassay methods. The anti-HBs titre levels and geometric mean titres (GMTs) were determined at day 180 and day 210. There were three new hepatitis B virus infections in the control group and none in the study group by day 210. The seroconversion rates in the study group were 66% at day 180 and 84% at day 210, the respective GMTs being 116 and 940. Although the duration of observation is short (7 months) and the difference in the rate of infection between the two groups is not statistically significant (P greater than 0.05), the immunogenicity of the vaccine appears to be good. The simultaneous administration of hepatitis B vaccine and the EPI vaccines is logistically ideal. However, we suggest a further study using a larger dose of the Hevac B Pasteur vaccine to find out if a higher seroconversion rate than the 84% observed in this study could be achieved.

Female

Low frequency of hepatitis C antibodies among children from foreign countries adopted in Swedish families.

89 children from 20 countries adopted to Swedish parents between 1984 and 1988 were tested for the presence of hepatitis C antibodies (anti-HCV). Sera taken soon after their arrival to Sweden were retrospectively analyzed. Two children, an 18-month-old boy from Poland and an 8-month-old girl from India, were anti-HCV positive. The girl from India had lost the anti-HCV antibodies in sera taken at the age of 13 and 14 months. These antibodies were probably passively derived from the mother. The Polish boy had a strong positive reactivity and is likely to have had an HCV infection early in life. Thus, there is a low prevalence of anti-HCV positivity among children from foreign countries adopted in Swedish families.

Adoption