Biomedical subjects

E Nordenfelt

Publications and source records attributed to E Nordenfelt.

At least 19 recordsLinked to original sources

PubMed2000

Continued transmission of hepatitis B and C viruses, but no transmission of human immunodeficiency virus among intravenous drug users participating in a syringe/needle exchange program.

The virological efficacy of a syringe/needle exchange program was evaluated in a cohort incidence study. Of 698 intravenous drug users (IVDUs) initially recruited, 15 (2.1%) were HIV-positive at baseline. Adequate follow-up was possible in 515 (74%) and showed no new cases of HIV infection during a median of 31 months. Most IVDUs had been previously exposed to HBV (anti-HBc-positive 70.1%) and HCV (anti-HCV-positive 90.7%). Of those 159 IVDUs negative at baseline for anti-HBc and/or anti-HCV, 56 (35%) seroconverted to one or both viruses during follow-up, corresponding to 11.7 seroconversions/100 y at risk for HBV and 26.3 seroconversions/100 y for HCV. Multiple logistic regression analysis showed hepatitis seroconversion to correlate with imprisonment during the study (OR 2.2; 95% CI 1.04-4.74), absence of drug-free periods (OR 5.7; CI 1.44-22.3) and frequent syringe/needle exchanges (OR 1.31; CI 1.02-1.7). The absence of HIV spread was probably partly due to the low prevalence of HIV-infected IVDUs in the city. Despite free syringes and needles, both HBV and HCV continued to spread at high rates. Nevertheless, syringe/needle exchange programs, coupled with monitoring of serostatus provide good surveillance and are valuable for further assessment of remaining risks.

Adult↗

PubMed1996

2',3'-dideoxy-3'-fluoroguanosine inhibits duck hepatitis B virus in vivo.

Duck hepatitis B virus (DHBV) belongs to the same virus family as the human hepatitis B virus (HBV). Domestic ducks infected with DHBV can be used as an animal model for chronic hepatitis B virus infection in therapeutic trials. In this study the antiviral effect of the guanosine analogue 2',3'-dideoxy-3'-fluoroguanosine (FLG) was tried in vivo on chronically DHBV-infected ducks. The ducks were either congenitally infected, or inoculated with DHBV immediately post-hatch. FLG was given as intraperitoneal injections twice daily, at different dosages. Serum DHBV levels were determined by DNA dot-blot hybridization. A strong inhibition of serum DHBV DNA was observed with FLG doses down to 1 mg kg-1 day-1, given for 7 to 10 days. With the corresponding thymidine analogue, 2',3'-dideoxy-3'-fluorothymidine; however, no inhibition was obtained. This difference may be due to different phosphorylation mechanisms. Independently of FLG dose, serum DHBV DNA returned to pretreatment levels within a few days after cessation of therapy. After a long-term trial (FLG, 5 mg kg-1 day-1 for 33 days), the same relapse of DHBV production was seen. Thus, FLG is an efficient inhibitor of DHBV replication, and is a candidate for treatment of HBV infections. However, the effect is transient, and therefore combination with other types of anti-HBV drugs should be considered.

Animals↗

PubMed1996

Increasing heterogeneity of the 'a' determinant of HBsAg found in the presumed late phase of chronic hepatitis B virus infection.

To investigate if the concomitant presence of hepatitis B virus (HBV) DNA and antibodies to hepatitis B surface antigen (anti-HBs) is associated with mutations in the HBV envelope gene, selected sequences of the HBV genome in 54 patients with chronic liver disease, collected from the Wuhan district of China, were amplified by polymerase chain reaction (PCR) and the DNA sequences of the products were determined. The part of the S gene coding for the 'a' determinant of HBsAg was found to be prone to diversity. A total of 19 aberations occurring at 11 of the 69 nucleotide positions of this part of the genome were found in sera from 15 HBsAg-negative but anti-HBs-positive patients. One of 13 HBsAg/HBeAg-positive and 8 of 17 HBsAg/anti-HBe-positive samples also showed point mutations in this gene sequence. Most prevalent was a point mutation from adenine to guanine at nucleotide 530 resulting in a change from threonine to alanine at amino acid position 126. This study highlights that the long time course of chronic HBV infection could favour a selection of escape mutants. The occurrence of such HBV variants in patients with chronic liver disease are not detected by conventional HBV serology, and the patients can therefore easily by be misdiagnosed. If viral mutants like those described here can be transmitted to other patients, there will be difficulties in identifying these infections, and conventional HBV vaccination will presumably not be protective against them.

Adolescent↗

PubMed1995

Decline of herpes simplex virus type 2 and Chlamydia trachomatis infections from 1970 to 1993 indicated by a similar change in antibody pattern.

Antibodies to herpes simplex virus type 2 (HSV-2) and Chlamydia trachomatis (Ct) were determined in sera from pregnant women from 1970 and at intervals up to 1993. The trends for HSV-2 and Ct infections were deduced from the observed antibody rates in different age groups during the observation period. Total antibody rates for HSV-2 tended to decline toward the end of the period when age-matched groups were compared, while the Ct antibody rates peaked in 1979 and then declined gradually. Age-specific antibody rates showed declining frequencies in women younger than 20 years for both HSV-2 and Ct over the study period. Women 35 years of age and older in the early 1990s had significantly higher antibody rates than younger women at that time or than women of similar age in the early 1970s. This group of slightly older women with high antibody rates in the 1990s were 15-20 years of age in 1970 when a high antibody frequency was noted in this age group. High antibody rates against both HSV-2 and Ct in older pregnant women in the early 1990s may thus reflect a high incidence of these infections around 1970. The declining rates of antibodies in the youngest women would suggest a declining incidence of primary infections in this group.

Adult↗

PubMed1995

Hepatitis E virus infections in patients with acute hepatitis non-A-D in Sweden.

A total of 12 patients previously treated for acute hepatitis of unknown aetiology were retrospectively found to be anti-hepatitis E virus (HEV) IgG-positive. Four patients were anti-HEV IgM- and IgG-positive consistent with an acute HEV infection. All 4 had travelled to or were immigrants from HEV-endemic countries. One anti-HEV IgM-negative patient seroconverted from anti-HEV IgG-negative to positive and 3 from anti-HEV IgG-positive to negative in 2 consecutive serum samples. Of the remaining 4 patients without anti-HEV IgM, 3 had a history of recent travel to an HEV-endemic country. Most patients were young adults and all but 1 recovered from the hepatitis. One patient with a fulminant hepatitis was anti-HEV IgG-positive when tested 4 months after a journey to Turkey. She died from her fulminant hepatitis shortly after admission. All the other patients but 1 normalized their serum liver enzymes within 1-2 months after the onset of disease.

Acute Disease↗

PubMed1994

Genotyping of hepatitis C virus isolates by a modified polymerase chain reaction assay using type specific primers: epidemiological applications.

A polymerase chain reaction (PCR)-based assay using primers against the hepatitis C core gene has been described [Okamoto et al. (1992a): Journal of General Virology 73:673-679]. Within the two major HCV genotypes 1 and 2, the Okamoto system identifies two subtypes each (1a, 1b and 2a, 2b, respectively). Typing is achieved by a primary PCR with consensus primers followed by a nested PCR with type specific primers. The original assay was modified by addition of a parallel second PCR identifying the recently described major genotype 3. The assay also identifies in duplicate subtype 1b (type II by Okamoto), suggested to respond poorly to interferon. Reaction conditions were reviewed and melting temperatures of all typing primers equalised to increase strigency. The modified system functioned well and typing results were supported by partial core sequencing. The following distribution of genotypes was found in 53 hepatitis C virus (HCV) infected Swedish blood donors: genotype 1a (57%), 3 (19%), 1b (13%), and 2b (11%). In six recipients of HCV infected blood identified in a retrospective study, the recipient HCV genotype was identical to donor HCV genotype. Furthermore, in HCV positive couples identical genotype was observed when only one partner had an external risk factor; whereas genotypes were often diverse if both sex partners had parenteral risk factors. Finally, a cluster of hepatitis C cases in a haemodialysis unit was evaluated retrospectively. Eight patients had genotype 1b, two had mixed 1a and 1b, and one had type 1a. The modified HCV genotyping assay was of value in examining different epidemiological situations and can be expanded presumably to include future genotypes.

Base Sequence↗

PubMed1994

HTLV-I and -II in intravenous drug users from Sweden and Denmark.

693 IVDU (intravenous drug user) sera from Copenhagen, Malmö and Stockholm were tested, 247 retro- and 446 prospectively, for antibodies to human T-lymphotropic virus (HTLV), types I and II, by means of a commercial whole-virus EIA and/or an HTLV-I/-II peptide-based EIA. Positive EIA reactions were checked and typed by electrophoretic immunoblotting, a differential peptide-based EIA and nucleic acid amplification/hybridization with HTLV-I and -II specific primers and probes. 3 (0.7%) of the prospectively tested IVDUs from Malmö, none of 100 from Stockholm and none of 45 from Copenhagen were HTLV-seropositive. The 3 Malmö IVDU cases were a female immigrant from South America, her male native Swedish spouse (both HTLV-I), and a male immigrant Italian heroinist (HTLV-II). We conclude that HTLV was uncommon among intravenous drug users, a sentinel population, in Sweden and Denmark during 1986 and 1989. However, the occurrence of 3 HTLV-positive cases in Malmö 1993 indicates that the situation can change rapidly.

Adult↗

PubMed1993

Hepatitis B virus DNA in serum and liver is commonly found in Chinese patients with chronic liver disease despite the presence of antibodies to HBsAg.

Sera from 410 patients from the Wuhan area in the central part of China with the diagnosis of chronic liver disease were analyzed for markers of hepatitis B, C and D virus infections. All sera, plus liver biopsy specimens from 188 of the patients, were also tested for hepatitis B virus DNA by polymerase chain reaction. Sixty-eight percent were HBsAg positive in serum, whereas 29% showed markers of past hepatitis B virus infection. Hepatitis B virus DNA was detected in all HBeAg-positive sera but also in 58% of patients with HBe antibody. In the liver specimens of the corresponding patient groups, 97% and 78%, respectively, were hepatitis B virus DNA positive. However, more noteworthy was that of the HBsAg-negative/HBs-antibody positive patients 30% had detectable hepatitis B virus DNA in serum and 32% had hepatitis B virus DNA in liver tissue, whereas in a control group of healthy blood donors, of which 90% had HBs antibody, none was hepatitis B virus DNA positive. Our results demonstrate that among patients with chronic liver disease, infections with hepatitis B virus or hepatitis B virus-related virus(es) may frequently occur without being revealed by conventional serological methods. Hepatitis C and D viruses seem to be of only minor importance in the pathogenesis of chronic liver disease in this part of China.

Biomarkers↗

PubMed1993

Correlation of HBeAg/anti-HBe, ALT levels, and HBV DNA PCR results in HBsAg-positive patients.

A highly sensitive polymerase chain reaction (PCR) was used to analyse serum samples from HBsAg-positive patients in Sweden. Forty-two chronic carriers were tested, five of whom were of Swedish origin. Of the total, there were 13 HBeAg-positive and 27 anti-HBe-positive patients, while 1 patient was negative for both HBeAg and anti-HBe and one was positive for both markers. Nine of the 13 HBeAg-positive carriers and only 7 of the 27 anti-HBe-positive carriers had elevated alanine transaminase (ALT) levels (P = 0.01). Two PCR tests of marginally different sensitivity were used on all patient samples. All 13 HBeAg-positive patients and the patients with and lacking both HBeAg and anti-HBe markers, respectively, were positive in both PCR tests. One HBeAg-positive patient was shown to shed hepatitis B virus (HBV) DNA in both saliva and urine. Twelve of the 27 anti-HBe-positive carriers, 6 of whom had elevated ALT levels, were PCR positive. The remaining 15 had no evidence of HBV DNA and all but 1 had normal ALT levels. A positive PCR result was more common in those anti-HBe-positive patients with elevated ALT levels (P < 0.02). The precore gene from 18 samples was sequenced and, with a few exceptions, showed a high degree of conservation. We suggest that in the absence of optimal tests for infectivity of serum from HBsAg-positive patients, and until PCR becomes more widely available, all anti-HBe-positive patients with elevated ALT levels be considered highly infectious.

Acute Disease↗

PubMed1993

Hepatitis C virus infection in hemodialysis patients in southern Sweden: epidemiological, clinical, and diagnostic aspects.

A prevalence of hepatitis C virus (HCV) antibodies of 12% was found in 276 patients from 11 dialysis units. Between zero and 22% of the patients in the different units were anti-HCV positive. The epidemiology of HCV was studied in two units during a 2 year period by antibody assays and the polymerase chain reaction and correlated with clinical manifestations. Two types of epidemiologic patterns were found that may explain the wide difference of HCV prevalence described in different dialysis units. In one unit there was no evidence of spread within the unit, and the prevalence of HCV was dependent on the status of the patients entering for treatment. In the other unit, a clustering of infected patients could be seen in which 13 of 36 were infected during a 3 year period. Some patients who had not received blood transfusions were among the infected. Hepatitis C infection was the most common explanation for repeated abnormal transferase levels. Most of the HCV-infected patients reacted both for anti-HCV and HCV RNA. HCV RNA was in general detected earlier than anti-HCV seroconversion. Among 20 HCV RNA-positive serum samples that were anti-HCV ELISA-positive 18 had indeterminate and two negative reactions by immunoblot (RIBA 2). Thus the RIBA 2 test should be used with caution as a confirmatory antibody test in this group of patients.

Alanine Transaminase↗

PubMed1993

Human papilloma virus types in routine cytological screening and at colposcopic examinations.

Certain types of human papillomaviruses (HPV) play a crucial role in the development of anogenital cellular dysplasia and cancer. We have searched for a broad spectrum of HPV-types by PCR in cervical cell samples from 230 women aged 20-29 years enrolled at routine gynecological health control and 506 women referred to colposcopy due to suspected cytological changes. Thirteen percent of the health control women had HPV DNA of identified types. Half of the colposcopy patients showed benign histology with corresponding HPV DNA prevalence of 18%, while among the patients with cervical intraepithelial neoplasia between 61% and 78% had HPV DNA. Among both women with normal cytology or histology and those with various degrees of cervical dysplasia, cancer-related HPV types represented about 85% of the types found. The strong correlation between HPV infections and development of cervical dysplasia is an argument for HPV DNA testing of certain patient groups.

Adult↗

PubMed1993

Screening for anti-HIV and HBsAg in pooled sera from a clinical chemistry section as a tool for epidemiological survey.

With the aim of estimating the unknown spread of HIV into the general society, a program for testing pooled routine sera from a clinical chemistry laboratory has been tried. Serum samples obtained from the daily inflow of blood tubes at the Clinical Chemistry Laboratory, Malmö General Hospital, and not labelled as risk samples for blood-borne infection(s), were collected and pools of up to ten sera each were constructed according to a special protocol. All serum pools were screened for anti-HIV and HBsAg. During the 32-months period of the study 3,016 serum pools from men and the same number from women were collected and analysed. These pools together contained sera from 26,468 male and 26,891 female patients, respectively. Altogether 33 male and 2 female pools were found anti-HIV positive. Anti-HIV-positive males appeared in all age groups, without significant difference between the groups. Two female pools from the age group 15 to 24 years were anti-HIV positive; these samples were drawn during the last year of testing. HBsAg was detected in 189 male and 129 female pools. From 1989 to the first half of 1991 the mean anti-HIV prevalence among the male samples investigated was 0.10%, with 95% confidence limits from 0 to 0.25%. If the upper confidence limit is exceeded in the future, this could be a warning of increased spread of HIV of in society.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Antibodies to hepatitis C virus 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 ELISA screening tests and confirmatory recombinant immunoblot assay (RIBA). 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 (22%) of the lyophilized sera were positive in the screening assay but only 6 (2.10%) were positive by RIBA with antibodies against both the C100-3 and 5-1-1 peptides. HCV RNA could be detected by polymerase chain reaction (PCR) analysis in 3 of the 6 sera and in one reacting with C100-3 only. In the second material of fresh sera only 3 were positive in the screening anti-HCV ELISA, but none was RIBA or PCR positive. Thus, the overall prevalence of anti-HCV among the 503 Chinese blood donors as identified by RIBA was 1.2%, and that of HCV RNA by PCR was 0.8%. The confirmed antibody prevalence is higher than that reported in the western literature.

Blood Donors↗

PubMed1993

Hepatitis E virus infection in pregnancy in Ethiopia.

Thirty-two pregnant and 34 nonpregnant Ethiopian women between 15 and 45 years of age with sporadic acute viral hepatitis were studied consecutively. Demographic data including family size, monthly income and nutritional status as well as hepatitis virus markers were compared in the pregnant and nonpregnant groups. Only 3 nonpregnant women had hepatitis A infection. Hepatitis B infection was diagnosed in 4 pregnant and 9 nonpregnant women. Nineteen (59%) pregnant women had hepatitis E virus (HEV) infection as compared to 7 (22%) in the nonpregnant group (Relative risk = 2.88; 95% Confidence interval = 1.4-5.9). The remaining 9 pregnant and 15 nonpregnant women had non-A, non-B, non-E (NANBNE) hepatitis. Of a total of 10 maternal deaths, 9 occurred (7 during the third trimester) in the pregnant group, 8 in association with HEV infection. Two deaths, one from each group, were due to NANBNE hepatitis. In addition to 6 foetal losses as a result of maternal death, there were 2 foetal deaths and 7 premature deliveries as a direct result of acute viral hepatitis, all but 2 associated with HEV infection. Comparison of socioeconomic and nutritional status, clinical features, mean aminotransferase and bilirubin levels did not show differences in the two groups. Thus, pregnant women are more at risk to acquire HEV infection than nonpregnant women and HEV infection in this group of Ethiopian pregnant women is associated with high maternal mortality and neonatal complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1993

Hepatitis B virus DNA detected by PCR in sera and liver tissues of Chinese patients with chronic liver diseases.

To investigate the HBV infection and its replication in Chinese patients with chronic liver disease, polymerase chain reaction (PCR) was employed to detect hepatitis B virus DNA in sera of 410 patients with chronic liver disease and liver samples from 188 patients. The HBV DNA detectability in all serum samples was 58%. Among them 100% HBeAg-positive and 58% anti-HBe cases were HBV DNA detectable respectively. However, HBV DNA was also found in 23% HBsAg-negative/anti-HBc positive chronic cases. Furthermore, 30% anti-HBs positive chronic cases who had neutralizing antibody against HBV infection, continued to contain HBV DNA. Our findings indicate that HBV infection and its replication are dominant cause of chronic liver disease and some HBV variants may escape from the protective antibody to induce chronic liver disease, even anti-HBs antibody circulated.

Adolescent↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗