Hepatitis B seroprevalence in persons attending youth clinics in Stockholm, Sweden in 2008.

Sweden is a low endemicity country for hepatitis B virus (HBV). The previously reported prevalence of chronic HBV is <1% and of overall markers <5%. HBV is not included in the universal childhood vaccination programme. Instead, selected high-risk groups are targeted. Our aim was to examine the HBV seroprevalence in youth clinic clients in Stockholm and identify if this population might be a new target group for vaccination. In total, 515 clients aged 18-22 years were recruited. They completed a risk-assessment questionnaire and 464 (90%) had a serum specimen tested for HBV serology. Chronic HBV was found in 0.6% and 0.9% had previously been infected with HBV. A seroprevalence of 1.8% HBV markers was found among non-vaccinated persons. This is lower than reported from other countries and not different from the general population in Sweden. However, in persons originating from HBV endemic countries (n = 123), the prevalence was higher, 6.5%. Only 14% were vaccinated and the majority hence susceptible to HBV. The target groups are not reached by the present vaccination strategy. Youth clinics are ideal settings for catch-up vaccination.

Performance of three automated fourth-generation combined HIV antigen/antibody assays in large-scale screening of blood donors and clinical samples.

Since the introduction in the mid-1980s, HIV testing has gradually improved both in terms of sensitivity and specificity. The so-called fourth generation of tests, combined HIV antigen/antibody assays, has now been introduced. This study compares three automated combined assays with older third-generation antibody assays in large-scale screening. Serum samples from routine screening of blood and plasma donors and clinical samples were investigated for specificity evaluation. Three fourth-generation combination assays from one manufacturer were compared with three older third-generation antibody assays from the same manufacturer. More than 40 000 samples per assay were included. For sensitivity, selected panels of confirmed HIV-1- and HIV-2-positive samples as well as seroconversion samples (HIV-1) from commercial panels and also from patients who appeared during the evaluation were used. The specificities of the fourth-generation tests were 99.91% (AxSYM), 99.95% (ARCHITECT) and 99.97% (PRISM) after repeated testing. Some specificity variation between reagent batches was observed. All HIV-1-positive samples were reactive by the three fourth-generation systems. HIV-1 seroconversion samples and panels were reactive earlier than by antibody-only tests. As for HIV-2 samples, AxSYM failed to detect one (n = 40), whereas PRISM and ARCHITECT detected all (n = 16 for PRISM and n = 52 for ARCHITECT). The new HIV antigen/antibody combination assay systems were found to have high sensitivity and specificity. The instruments provided a rational and easy way of testing at large scale.

Relevance of a combined HIV antigen/antibody assay to detect early HIV infections in a low prevalence population: case reports.

The AxSYM HIV Ag/Ab Combo assay (Abbott) has proven to possess excellent sensitivity on seroconversion samples. Since its introduction in Sweden and Norway approximately one year ago, eight cases of acute HIV infections were found earlier compared to assays detecting only antibodies either to screen or to confirm an HIV infection. Data of the presented cases indicate that the early detection of primary HIV infection is of benefit to the individual patient and may reduce further spread of the disease. The impact of HIV combo assays on screening and diagnosis in a low prevalence population is discussed.

Population-based rates of severe respiratory syncytial virus infection in children with and without risk factors, and outcome in a tertiary care setting.

UNLABELLED: The aim of this study was to make a population-based estimate of the risk of hospitalization and complications during virologically confirmed respiratory syncytial virus (RSV) infection in relation to established risk factors, and an estimation of additional risk factors and outcome as seen in a tertiary care referral centre. During a period of 12 y, all children with virologically confirmed RSV infection were included. Recorded complications were: admission to the intensive care unit, mechanical ventilation, death and later hospitalization for wheezing. In total, 1503 cases were identified, 1354 of which originated from the population defined by the catchment area. There was a biannual seasonal variation with late small outbreaks alternating with early large ones. The hospitalization rates for infants without risk factors were 0.8 and 1.4% during the 2 epidemic types. They were 1.6-3.2% for infants born preterm (<33 gestational wk), 2.9-7.0% for children under 2 y old with chronic lung disease of prematurity and 2.8-6.4% for infants with congenital heart disease. The presence of siblings in the family more than doubled the risk of hospitalization. Later hospitalization for wheezing occurred in 8.4 and 4.9% of children without risk factors over and under the age of 2 mo, respectively (p < 0.001). CONCLUSION: This study found lower population rates of hospitalization and complications than have previously been reported. The seasonal variation and the presence of siblings in the home influenced these rates by factors of 2.

A randomized study of alpha-interferon plus ribavirin for 6 months or 12 months for the treatment of chronic hepatitis C in patients with bleeding disorders.

Little is known about the optimal treatment in patients with chronic hepatitis C virus (HCV) who were infected by pooled plasma products. The aim of our study was to compare the efficacy of 6 and 12 months of combination therapy with interferon alpha-2b and ribavirin in patients with bleeding disorders and chronic HCV. In a randomized open study, 61 patients with haemophilia or von Willebrand disease received treatment with a combination of interferon alpha-2b and ribavirin at standard dosage for 6 or 12 months. Follow-up was done with analysis of HCV RNA after an additional 6 months. The prevalence of HCV genotype 1 was 67%. Overall, sustained viral response was achieved in 41%; 13 of 30 patients (43%) treated for 6 months vs. 12 of 31 patients (39%) treated for 12 months. The rate of sustained response was 22% in those with HCV genotype 1 and 80% in other genotypes (100% in genotype 2), with no difference between the treatment durations. The number of early discontinuations due to side-effects was 3 and 9, respectively. The study was stopped prematurely due to introduction of a more effective regimen, and the numbers are not sufficient to state equality. We conclude that the efficacy and safety of combination therapy against chronic hepatitis C in patients infected by pooled plasma products is similar to that observed in other populations. Six months of therapy seems sufficient in the case of HCV genotype 2. For other genotypes, the decision regarding duration of therapy has to be based on the tolerance of the individual patient together with experiences from other studies.

Diagnosis of primary HIV-1 infection and duration of follow-up after HIV exposure. Karolinska Institute Primary HIV Infection Study Group.

OBJECTIVE: To determine the sensitivity of 33 currently available and seven earlier tests for the detection of HIV or HIV antibody in primary HIV-1 infection, to estimate the duration of the 'window period' and the influence of early initiated antiretroviral treatment (ART). DESIGN: A prospective cohort study of 38 patients with primary HIV-1 infection. ART was initiated at a median time of 13 (range 0-23) days after the onset of symptoms in 10 patients. MAIN OUTCOME MEASURES: The time from infection to onset of symptoms and from onset of symptoms to the appearance of HIV antibody as measured by 36 different tests, and the start and duration of viraemia, as detected by four different tests. RESULTS: The illness appeared 13-15 days after infection in 12 of 15 determinable cases, and seroconversion was detected within 1-2 weeks after the onset of illness by 27 of 30 currently available tests for HIV antibody, in contrast to the 2-7 weeks or more needed by the old tests. HIV RNA appeared during the week preceding the onset of illness and was detected in all subsequent samples, except when ART had been initiated, which also induced a delay of the antibody response. CONCLUSION: Many tests for HIV or HIV antibody can now be employed for an early confirmation of primary HIV infection (PHI). Currently available screening tests proved much more sensitive than older tests, and seroconversion was usually detected within one month after infection. Consequently, in Sweden we now recommend only 3 months of follow-up after most cases of HIV exposure.

Comparative evaluation of 14 immunoassays for detection of antibodies to the human T-lymphotropic virus types I and II using panels of sera from Sweden and West Africa.

BACKGROUND: A new generation of assays for the detection of human T-lymphotropic virus types I and II (HTLV-I/II) antibodies has been released. These assays incorporate HTLV-I- and HTLV-II-specific antigens, and some are based on new assay principles. Comparative evaluation data that include these new as well as previous assays are limited. STUDY DESIGN AND METHODS: Fourteen HTLV antibody assays were evaluated by using well-characterized panels of sera from Guinea-Bissau, West Africa, and Sweden. The sera included 127 HTLV-I-positive and 62 HTLV-II-positive specimens, as well as 919 consecutive negative samples. RESULTS: The sensitivity for HTLV-I was 100 percent for all assays, except one, which repeatedly missed one sample. The sensitivity for HTLV-II varied between 86 percent and 100 percent. In general, new-generation assays incorporating HTLV-II-specific antigens, and some of which are based on new assay principles, had a higher sensitivity for HTLV-II than previous assays, which mainly are based on HTLV-I antigens. The specificity was generally higher for new assays than for the previous versions. Testing of Swedish blood donor sera gave higher specificities (94-100%) than did that of African specimens (90-99.7%). Most assays had low delta values (DVs), although there was a tendency toward increased DVs for the new generation of assays. Only two of the new generation of assays came close to a combination of high sensitivity for both HTLV-I and HTLV-II, high specificity, positive and negative predictive values, and high DVs. CONCLUSION: The sensitivity for HTLV-I was generally high and appears to have improved for HTLV-II with the introduction of a new generation of assays incorporating HTLV-II-specific antigens. However, some assays still give false-negative results on HTLV-II-positive specimens. The specificities and the DVs were generally higher for the new assays than for the previous versions.

Hepatitis C virus-infected, HCV-RNA-negative patients with bleeding disorders--relationship to age, HIV and treatment.

All 155 anti-hepatitis C-virus (HCV) positive patients with haemostatic disorders at our unit were tested for HCV-RNA in order to determine the prevalence of a negative result. The patients were also characterized in order to find predictors for a negative HCV-RNA test. The prevalence of a negative HCV-RNA test was 15.5% (24 of 155) and this was similar among anti-HIV positive and negative patients. A common denominator for the 4 HIV-infected, HCV-RNA negative haemophiliacs was treatment with azidothymidin prior to the first test. Among the anti-HIV negative patients, those < 40 y of age had a significantly greater chance of being HCV-RNA-negative than the older ones (27.3 vs 3.6%). They also had a lower consumption of plasma products than age-matched HCV-RNA positive cases. Absence of co-infection with hepatitis B was not correlated with a negative HCV-RNA test. Young age and a low requirement for factor concentrates thus seem to be predictors for a negative HCV-RNA test in patients with bleeding disorders.

Vertical transmission of hepatitis C virus infection.

Vertical transmission of hepatitis C virus (HCV) was studied in 58 infants of 55 mothers (3 sets of twins). HCV RNA analyses by the polymerase chain reaction (PCR) and alanine aminotransferase (ALT) were performed on consecutive blood samples from birth to 18 months of age (0, 3, 9 and 18 months). Data on factors possibly influencing mother-to-infant transmission of HCV, such as concomitant human immunodeficiency virus (HIV) and hepatitis B virus infection during pregnancy, maternal HCV RNA status at delivery, mode of delivery, prematurity and breastfeeding habits were collected. In addition, 6 older siblings (age 4-10 years) of the infants were tested once for anti-HCV. Of the 55 mothers 52 (95%) had a history of intravenous drug use (IVDU). Two mothers were HIV positive. 40/54 (75%) tested mothers were HCV RNA positive. 16 (27%) infants were delivered by Caesarean section, and 50 (86%) infants were breastfed. All infants were HCV RNA negative on all occasions and anti-HCV negative at the age of 18 months. Maternally acquired anti-HCV antibodies disappeared and were not detected by 9 months in 78%. One of the 6 older siblings was anti-HCV and HCV RNA positive. We conclude that the risk of vertical HCV transmission is low in infants of HCV-positive/HIV-negative mothers, and that breastfeeding seems to be safe in this group.

Prevention of hepatitis B by immunization of the newborn infant--a long-term follow-up study in Stockholm, Sweden.

In order to assess the present hepatitis B immunization program in Stockholm, Sweden, 212 children of HBsAg carrier mothers were followed up 2-9 years after birth. In babies of HBeAg-positive mothers a combined passive and active immunization schedule with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine was used. Among 25 children to such mothers, 1 HBsAg carrier and 5 children with asymptomatic seroconversion were found. To newborns of HBeAg-negative/anti-HBe-negative mothers, only vaccine was given. Among 15 such children, no HBsAg carrier (but 1 child with an asymptomatic seroconversion) was found. In babies of HBeAg-negative/anti-HBe-positive mothers, immunization was withheld between 1983 and 1987. Among 90 such children, 1 HBsAg carrier and 8 asymptomatic seroconversions were detected. After 1987, newborns in this group were vaccinated whereafter 3 asymptomatic seroconversions were found among 82 children. We conclude that in low prevalence areas a screening program for HBsAg should be offered to pregnant women originating from hepatitis B endemic regions, since immunoprophylaxis gave long-term protection to most children at risk. Children born to HBeAg-positive mothers should receive vaccine in combination with HBIg, whereas for children of mothers lacking HBeAg, vaccination only seems sufficient, at least if a rapid vaccination schedule is used.

Screening for HIV-1 antibodies in pregnancy: results from the Swedish national programme.

OBJECTIVE: To determine the effectiveness of a national screening programme for HIV infection in pregnant women. DESIGN: Observational study. SUBJECTS: All pregnant women presenting to antenatal or abortion clinics. SETTING: Sweden, September 1987 to December 1991. MAIN OUTCOME MEASURES: Number and characteristics of infected women. RESULTS: By the end of the study period 510,000 tests had been performed and 54 women with HIV infection identified (1.06/10,000). Of the 33 women identified in Stockholm, 14 women (4.4/10,000) had attended abortion clinics and 19 antenatal clinics (1.8/10,000; p < 0.05). Three women had been intravenous drug users, one was infected through a blood transfusion, and 50 were probably infected sexually. Of the 20 women who attended antenatal clinics early enough to allow an abortion, 12 continued with their pregnancies. CONCLUSIONS: Testing of all women, not just those perceived to be at risk, probably contributed to the high uptake of HIV testing. With high uptake such screening provides valuable data on spread of HIV in the heterosexual population and presents opportunity for preventing transmission of HIV to children and partners.

Second-generation hepatitis C Elisa antibody tests confirmed by the four-antigen recombinant immunoblot assay correlate well with hepatitis C viremia and chronic liver disease in Swedish blood donors.

Seventy-three Swedish blood donors (52 men, 21 women; median age 36 years) repeatedly reactive for hepatitis C antibodies (anti-HCV C-100-3) were tested with a second-generation (2nd-gen) anti-HCV Elisa and a 4-band recombinant immunoblot assay (RIBA 2). These results were correlated to serum alanine aminotransferase (S-ALAT), liver morphology and viremia as detected by 'nested' polymerase chain reaction (PCR) based on primers from a 5'-noncoding sequence of the HCV genome. Thirty-five of 46 (76%) donors with positive 2nd-gen Elisa tests confirmed by RIBA 2 were PCR positive whereof 27 had histological findings compatible with chronic persistent hepatitis (CPH) and 7 had chronic active hepatitis (CAH). Ten of 56 (18%) 2nd-gen Elisa-positive donors were RIBA 2 negative (or indeterminate) and none of these had chronic hepatitis nor were PCR positive. Seventeen of 73 (23%) donors were 1st-gen Elisa positive but 2nd-gen Elisa negative. All of these were PCR negative and only 1 (6%) had chronic hepatitis (CPH). An elevated S-ALAT level (reference < 0.7 mu kat/l) was found in 26 2nd-gen Elisa and RIBA 2-positive donors of which 18 had CPH and 7 had CAH and all 25 were PCR positive. A normal S-ALAT level was found in 9 of 34 (26%) donors with chronic hepatitis (all had CPH) and positive PCR. We have found that blood donors with positive 2nd-gen anti-HCV Elisa tests confirmed by RIBA-2 and especially with a concomitant elevated S-ALAT are highly likely to be viremic as demonstrated by PCR and to have chronic hepatitis.

HIV-antibody testings among injecting drug users (IDUs) in the Stockholm area, 1984-91: information compiled from testing laboratories.

The available information about testings for HIV antibodies in injecting drug users (IDUs) carried out in Stockholm between 1984 and 1992 has been compiled. These testings were carried out mainly in special settings. The use of codes (the first 2 digits giving the age and the last 4 the 6 and checking figures in the individual's personal identity number) precluded exact identification of individuals; in most cases, however, complementary information made it possible to recognize patients at follow-up. The data indicated that 9,150 persons associated with current or previous drug addiction were tested. The first extensive testings were performed in 1985 and 1986. After this period, 4,500 persons were retested. 11% of the IDUs tested in 1984-85 were found to be HIV-antibody-positive. After 1988, 1% were estimated to seroconvert each year. While in the first phase the heroin users predominated among those infected, in later years the rates of newly diagnosed infections became similar for all types of IDUs. The age profiles of the IDUs tested were similar up to 1988, after which there was an indication that also younger persons had entered the scene. However, the infected IDUs discovered belonged mainly to the 'old' cohort born between 1950 and 1960.

Prevalence of hepatitis B virus markers in Sweden: a community-based serosurvey of 4,000 young Swedish adults.

The influence of age, origin, and region of domicile on the prevalence of hepatitis B virus markers was investigated in a cross-sectional sample of young Swedish adults. Sera and demographic data were prospectively collected from 2,000 male conscripts and 2,000 pregnant women from urban and rural parts of Sweden during 1988-1989. A total of 10 of 4,000 (0.25%) were found to be hepatitis B surface antigen carriers, and 62 (1.6%) were positive for both anti-hepatitis B core antigen and anti-hepatitis B surface antigen, indicating a present or prior hepatitis B virus infection. Origin from a country with high hepatitis B virus endemicity and increasing age were factors associated with serologic signs of a present or prior hepatitis B virus infection, whereas region of domicile was not. In addition, seven individuals positive only for anti-hepatitis B core antigen (blocking greater than 70% in the test) and 39 positive only for anti-hepatitis B surface antigen (with a titer of greater than or equal to 10 international units/liter) were believed to have been exposed to hepatitis B virus. Altogether, these results indicated that 3% of young Swedes had encountered hepatitis B virus and that origin from a country with high hepatitis B virus endemicity was the factor that most strongly was associated with a present or past hepatitis B virus infection.

Intramuscular versus intradermal administration of a recombinant hepatitis B vaccine: a comparison of response rates and analysis of factors influencing the antibody response.

In an open controlled study 286 health care workers in Stockholm, Sweden, received 20 micrograms of a recombinant hepatitis B vaccine (Engerix B) by the intramuscular route, and 383 2 micrograms by the intradermal route. Seroconversion to protective anti-HBs levels (anti-HBs titre greater than or equal to 10 IU/l) was achieved in 94% of the i.m. and 89% of the i.d. vaccinees. Female sex, intramuscular vaccination, young age, and being a non-smoker were associated with a higher response rate and a higher geometric mean anti-HBs titre than male sex, intradermal vaccination, old age and being a smoker. If an acceptable response rate to protective anti-HBs levels of 85% is chosen, intradermal vaccination can be used as a cost reducing strategy for all women and for non-smoking men less than 30 years of age, as estimated in a logistic regression model. Due to the variable antibody response in different individuals, post vaccination testing for anti-HBs titres is recommended in health care workers, regardless of vaccination route.

Seroprevalence and outcome of hepatitis C in liver transplantation.

A recombinant enzyme-linked immunosorbent assay (ELISA) followed by a neutralization test (NT) and recombinant immunoblot assay (RIBA) were used for the detection of antibody to hepatitis C virus (anti-HCV) in 71 patients receiving 84 orthotopic liver grafts between 1984 and 1990. Before the liver transplantation (LTX) anti-HCV was present in six of the 71 recipients (8.5%) who were accepted for LTX because of acute or chronic liver failure. After LTX anti-HCV could not be detected in one of the patients, but it was continuously present in the others for more than 12 months. Detectable HCV antibodies were not present in the three patients who underwent LTX because of clinical evidence of fulminant NANB hepatitis. Two of 48 (4.2%) previously HCV seronegative recipients, who survived more than 3 months, seroconverted 9 and 16 months, respectively, after transplantation. The postoperative seroconversion was probably due to the transfer of virus via perioperative blood transfusions. Thus, these liver recipients may be able to respond by producing anti-HCV despite immunosuppressive therapy. None of the seven post-transplant HCV-seropositive patients developed symptoms such as icterus or fatigue, which would suggest the presence of liver insufficiency due to HCV infection. However, two of them had increased transaminase levels and histological signs of mild hepatitis. No significant difference was found in 1-year survival, prothrombin complex, albumin levels or the risk for retransplantation in post-transplant anti-HCV-seropositive patients, compared with those without detectable HCV antibodies (71% vs 69%, respectively). Thus, during the study period of 1-5 years, the clinical course of HCV infection was milder than that reported for hepatitis B infection in liver recipients.

Seroconversion to hepatitis C virus antibodies in patients with acute posttransfusion non-A, non-B hepatitis in Sweden.

Seventy-four patients in 1978 and 316 in 1986, all transfused during open-heart surgery in Stockholm, Sweden, were studied prospectively for the development of posttransfusion non-A, non-B (NANB) hepatitis, seroconversion to hepatitis C virus antibodies (anti-HCV) (C-100), time lag to seroconversion to anti-HCV and outcome of posttransfusion NANB/C hepatitis. Anti-HCV was tested up to six months after transfusions in patients from 1978 and up to one year after transfusions in patients from 1986. Fifty-four percent of the patients who developed posttransfusion NANB hepatitis seroconverted to anti-HCV, 7/15 (47%) in 1978 and 8/13 (62%) in 1986. Four (27%) of the 15 patients who seroconverted to anti-HCV were anti-HCV reactive within one week, 12 (80%) within eight weeks and all within 18 weeks after the onset of hepatitis. The ELISA optical density/cut-off (OD/CO) ratio was above 4.0 in all patients with hepatitis C who seroconverted. One transfused patient with normal serum aminotransferase levels throughout follow-up seroconverted after six months. He had a temporary positive anti-HCV reactivity with a maximal ELISA OD/CO ratio for anti-HCV of only 1.2, which became negative three years later. Development of chronic hepatitis was noticed in 9/15 (60%) patients who seroconverted to anti-HCV and in 5/13 (38%) patients with posttransfusion NANB hepatitis who did not seroconvert.

Zidovudine in the management of primary HIV-1 infection.

Eleven subjects who presented with a clinical illness characteristic of primary HIV-1 infection were treated with 1 g zidovudine daily for a median period of 56 days (range, 28-111 days). Primary HIV-1 infection was confirmed in each subject by seroconversion and virus isolation. The acute phase of the illness resolved a median of 4 days (range, 3-14 days) from commencement of zidovudine. Six subjects reported symptoms that may have been side-effects of zidovudine, the most common being nausea in four subjects and headache in two. Treatment was discontinued in one subject who had persistent headache and nausea. Haemoglobin, haematocrit and erythrocyte counts decreased and mean corpuscular volume increased significantly during the treatment. None of the subjects developed anaemia and none required dose modification or blood transfusion as a result of haematological side-effects. There were no significant differences in the granulocyte count or the lymphocyte count during any week of treatment when compared with baseline levels. There were no significant differences in T-cell subset numbers of the subjects during treatment compared with a group of historical controls. HIV-1 was isolated from several subjects during and after termination of zidovudine treatment. The results of this investigation indicate that zidovudine is a safe drug to administer to people with primary HIV-1 infection. There was no clear evidence, however, of any clinical benefit in terms of resolution of the acute illness and no indication that the treatment would prevent development of persistent infection.(ABSTRACT TRUNCATED AT 250 WORDS)