Staffan Sylvan

Prevalence of antibodies to hepatitis E virus among hemodialysis patients in Sweden.

In order to study the prevalence of antibody to hepatitis E virus (HEV) among hemodialysis patients and to evaluate whether chronic hemodialysis is associated with an increased risk of exposure to HEV in developed countries, the IgG anti‐HEV was determined in serum samples obtained from 182 patients on chronic hemodialysis and 349 statistically selected, healthy Swedish control subjects. Serum specimens from 11 of the 182 (6.0%) hemodialysis patients and from 18 of the 349 (5.2%) control subjects were repeatedly positive for HEV antibodies (the difference was not significant: P= .67). Analysis of serial serum samples obtained at the initiation of hemodialysis and consecutively during follow‐up periods of several years demonstrated no IgG anti‐HEV seroconversion during chronic hemodialysis. The seroprevalence of anti‐HEV antibody in the adult Swedish population was associated significantly with age. In persons younger than 40 years, the percentage of seropositive individuals was 2.5%, whereas the seroprevalence rate of anti‐HEV was 7.4% in subjects older than 40 years (P< .05). This study indicates that nosocomial transmission of HEV to patients on maintenance hemodialysis was non‐existent in three dialysis centers in Sweden (a developed country) and that chronic hemodialysis is not associated with an increased risk of exposure to HEV infection in this region. J. Med. Virol. 54:38–43, 1998.

Carriage of Multiresistant Streptococcus pneumoniae Among Children Attending Day-care Centres in the Stockholm Area

To determine the prevalence of the asymptomatic carriage of drug-resistant Streptococcus pneumoniae (DRSP) by children attending day-care centres in the Stockholm area, nasopharyngeal swabs were cultured from 1129 children and 308 day-care personnel in 36 day-care centres during a 3-week period, from March to April 1995. Approximately 36% of the children were asymptomatic carriers of S. pneumoniae sensitive to penicillin and other antibiotics. The highest prevalence of nasopharyngeal carriage was found in the 2-year-old group (50%), whereas among the 4-year-old children colonization was observed in 42%, and among the 7-year-old children 21% were asymptomatic carriers of penicillin-sensitive S. pneumoniae. In 2 day-care centres, 4 and 5 children, respectively, were found to have DRSP strains in the nasopharynx. The same serotype of DRSP strain was found among the children attending the same day-care centre. During the same period, none of the staff were found to harbour DRSP in the nasopharynx, but 3% were asymptomatic carriers of penicillin-sensitive S. pneumoniae. The patterns of nasopharyngeal colonization by Haemophilus influenzae, Moraxella catarrhalis and Group A streptococci were also studied in 635 children during the same period. 42% of the nasal cultures yielded Moraxella, 32% H. influenzae and 2% Streptococcus pyogenes.

Antibody responses to preS components after immunization of children with low doses of BioHepB.

BioHepB is a recombinant, hepatitis B vaccine derived from a mammalian cell line and containing HBs as well as preS1 and preS2 antigens, in their glycosylated and non-glycosylated forms. The vaccine was administered intramuscularly to 18 children aged 5 months to 11 years at 0, 1 and 6 months. One hundred percent seroconversion and seroprotection rates were achieved after primary and secondary immunization with the 2.5 microg doses of BioHepB. Ten out of the 18 children (56%) responded with the appearance of anti-preS1 and/or anti-preS2 antibodies in circulation, when analyzed 1, 2, 6, 7 and 12 months after the initiation of vaccination. In comparison with the emergence of the anti-HBs response, early (month 2, after two injections) or late (month 7, after three injections) peak responses were noted for the kinetics of anti-preS1 and anti-preS2 production during the course of immunization, demonstrating that the anti-preS1 and anti-preS2 responses are differently regulated, compared with the anti-HBs response. At month 6, just prior to the final injection, BioHepB caused significantly higher anti-HBs responses (GMT) in preS1-reactive children than in children without preS1 antibodies (P<0.005). Moreover, a significantly higher, anti-HBs response in GMT was also noted for anti-preS2-reactive children compared with anti-preS2-negative children (P<0.05). These findings demonstrated that recognition of the preS epitopes contained in the experimental preS1/preS2/S vaccine is accompanied by a more rapid onset and pronounced antibody response to the S-gene-derived protein in healthy children.

Effect of influenza and pneumococcal vaccines in elderly persons in years of low influenza activity.

BackgroundThe present prospective study was conducted from 2003–2005, among all individuals 65 years and older in Uppsala County, a region with 300 000 inhabitants situated close to the Stockholm urban area.The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay (LOHS) even during periods of low influenza activity. The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons.ResultsIn 2003, the total study population was 41,059, of which 12,907 (31%) received influenza vaccine of these, 4,447 (11%) were administered the pneumococcal vaccine. In 2004, 14,799 (34%) individuals received the influenza vaccine and 8,843 (21%) the pneumococcal vaccine and in 2005 16,926 (39%) individuals were given the influenza vaccine and 12,340 (28%) the pneumococcal vaccine.Our findings indicated that 35% of the vaccinated cohort belonged to a medical risk category (mainly those persons that received the pneumococcal vaccine). Data on hospitalisation and mortality during the 3-year period were obtained from the administrative database of the Uppsala county council.During the influenza seasons, reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort (below 80 years of age). For individuals who also had received the pneumococcal vaccine, a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia. Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine, despite that the pneumococcal vaccinated mainly belonged to a medical risk category. Reduction of death from all causes was observed during the influenza season of 2004, in the 75–84-year old age group and in all age-groups during the influenza season 2005.ConclusionThe present study confirmed the additive effect of the two vaccines in the elderly, which was associated with a reduced risk in hospitalisation and a reduction in mean LOHS in seasons with low influenza activity.

Severe group A streptococcal infections in Uppsala County, Sweden: clinical and molecular characterization of a case cluster from 2006 to 2007.

This study describes a recent cluster of 30 patients (median age 52 years) with serious group A streptococcal (GAS) infections in Uppsala County, Sweden, from December 2006 to May 2007. Patients hospitalized with a severe GAS infection, i.e. cases with either invasive GAS (iGAS) disease or patients with a positive non-sterile site culture/rapid antigen test for GAS and clinically considered as having a critical disease, were included in the study. Common clinical presentations were skin and soft tissue infections (53%) and pneumonia (17%). Eight patients (27%) were diagnosed with streptococcal toxic shock syndrome. In 40% of the cases no relevant underlying disease was reported. Among the 16 patients with soft tissue infections, the upper chest, neck or upper arm area was frequently affected and the infection was associated with severe pain. Among the 20 collected isolates, the T1/emm1 type dominated (80%). The majority (86%) of 7 analysed acute sera lacked neutralizing activity against superantigens produced by the patients’ own infecting isolate. The study underscores the association between T1/emm1 and outbreaks of serious GAS infections. This highlights the importance of surveillance for prompt identification of more aggressive isolates in the community, thereby increasing awareness among healthcare professionals of these life-threatening infections.

Screening and genotyping of genital Chlamydia trachomatis in urine specimens from male and female clients of youth-health centers in Stockholm County.

Background The current study was conducted in the context of the current increase in cases of Chlamydia trachomatis infections, the development of new diagnostic strategies, and an outreach to community-based youth center screening sites. Goal The goal was to define the prevalence of genital C trachomatis infection among clients of youth-health clinics and to evaluate the feasibility of implementing genotyping as a tool for epidemiologic studies with use of urine specimens. Study Design This was a prospective pilot study at two community-based youth-health clinics for teenagers and adolescents. Enrollment followed a high school educational program and public advertising campaign on the common occurrence of nonsymptomatic or only mildly symptomatic chlamydial infection among sexually active young people. Voluntary, confidential, free screening of first-void urine was provided, and the samples were tested by polymerase chain reaction (PCR). Demographic and behavioral data were obtained. Positive samples were differentiated into genovars by genotyping with restriction fragment length polymorphism analysis of the PCR–amplified omp 1 gene. Results The prevalence of nonsymptomatic or mildly symptomatic chlamydial infection was 6.0% among women and 9.3% among men. A significant increase in the risk of infection was associated with a history of sexually transmitted disease (STD) (P < 0.01). There was no statistical risk correlating with partner change during the past year, infrequent or inconsistent condom use during the past year, present use of contraceptive pills, smoking habits, or recent alcohol consumption. Genotype E was most common (60%) among both sexes. Genotypes F and K were second most prevalent for men (20%), and genotype D was second most prevalent for women (15%). Genotype K or F was found in 23% of cases. Conclusion Screening programs targeting sexually active adolescents attending youth-health clinics are important for detection of C trachomatis. Genotyping might become an efficient tool in epidemiologic studies. The impact of educational school- and community-based programs on STD among young people needs further evaluation.

PreS1 epitope recognition in newborns after vaccination with the third-generation Sci-B-Vac™ vaccine and their relation to the antibody response to hepatitis B surface antigen

BackgroundSci-B-Vac™ is a recombinant, hepatitis B vaccine derived from a mammalian cell line and containing hepatitis B surface antigen (HBsAg) as well as preS1 and preS2 antigens. Few studies have been performed on the antibody responses to preS1 in relation to the antibody to hepatitis B surface antigen (anti-HBs) response during immunisation of healthy children with preS-containing vaccines.ResultsIn this study 28 healthy newborns were randomly selected to receive either 2.5 ug or 5.0 ug of the Sci-B-Vac vaccine. Children received three doses of vaccine according to a 0-, 1-, 6-month scheme. Antibodies against the S-protein and three synthetic peptides mimicking three B-cell preS1 epitopes, (21–32 amino acid epitope), (32–47 amino acid epitope) and the C-terminal (amino acid epitope 94–117) were determined at 6 and 9 months. Fourteen (50%) of the 28 newborns had detectable levels of anti-preS1 (21–32) antibodies; 15 (54%) were anti-preS1 (32–47) reactive and 12 (43%) were anti-preS1 (94–117) reactive at 6 or 9 months after initiation of the vaccination. Significantly higher levels of anti-HBs were observed in the sera of patients with detectable anti-preS1 (32–47) reactivity (24 550 ± 7375 IU/L, mean ± SEM) as compared with the non-reactive sera (5991 ± 1530 IU/L, p < 0.05). The anti-HBs levels were significantly lower if none (p < 0.05) or one (p < 0.025) of the preS1 (21–32, 32–47, 94–117) peptides were recognised compared with the anti-HBs levels if two or three peptides were recognised.ConclusionRecognition of several preS1 epitopes, and in particular, the epitope contained within the second half of the hepatocyte binding site localised in the hepatitis B surface protein of the third-generation hepatitis B vaccine is accompanied by a more pronounced antibody response to the S-gene-derived protein in healthy newborns.

Impact of a vaccination campaign on adult immunity to diphtheria

OBJECTIVES to raise the level of immunity to diphtheria in the adult population of Stockholm by a vaccination campaign. The rationale behind the campaign, conducted during 1995-1996, was the re-emergence of epidemic diphtheria in the countries of the former Soviet Union and earlier surveys of immunity to diphtheria showing low levels of protection in adults. DESIGN AND MAIN OUTCOME MEASURES the impact of the vaccination campaign was measured by recording the age and sex of vaccinees, the type and number of vaccine doses given and any side-effects. The effect on immunity was evaluated in 1998-1999 by measuring the neutralising antibodies in blood samples from 1863 inhabitants, chosen by random stratified sampling. Vaccines and vaccinations: three doses of diphtheria (D) or diphtheria-tetanus (DT) vaccine were given to those without documented previous vaccination; others received a booster dose. The DT vaccine, with the D component purified before toxoiding, contained 15 Lf of D and 7.5 Lf of T per ml, and was given in 0.5 ml doses for the two priming doses and 0.25 ml as booster. RESULTS 184969 doses of D or DT vaccine were given to 99939 individuals. Of the vaccinees, 65% were 50 years of age or older and 60% were women. The highest rates of reported local reactions were 1.8-5.4% and of systemic reactions, such as fever, 0.2-0.8%. The campaign resulted in a significant increase in antitoxin concentrations in the age cohorts targeted, and especially in women, less well protected than men. CONCLUSIONS a vaccination campaign, targeting the adult part of a population, can result in a major improvement in immunity to diphtheria with only a few and minor side-effects with a DT vaccine where the D component was purified prior to toxoiding. Extending national immunisation programmes to include adults would, however, seem preferable.

Drug-resistant Streptococcus pneuomoniae in day-care centres in Stockholm County

Between January 1994 and July 1995, 40 pre-school children were found to have drug-resistant Streptococcus pneumoniae(DRSP), i.e. reduced sensitivity to penicillin (minimum inhibitory concentration, MIC, > or =0.1) and resistance to at least two other antibiotic drugs. Twenty-five of the children were index cases with symptoms of respiratory disease, and 15 children were carriers discovered in contact-tracing in connection with an index case. Children attending the same group in the day-care centre as an index child were routinely screened. Thirteen of the index children were attending day-care centres. In 11 of these day-care centres, contact-tracing and nasopharyngeal swabs from 424 children and 128 day-care personnel identified an additional 13 asymptomatic children who were carriers of DRSP. In all but one case, the same serotype as the index case was discovered. No day-care personnel were carriers of the DRSP strain. Sixteen (64%) of the 25 children with symptoms caused by DRSP were 1 year old or younger, whereas eight (61%) of the 13 children who were carriers of DRSP were 3-4 years old. In conclusion, when a child attending a day-care centre is discovered to have respiratory disease caused by DRSP, there is a great probability that additional children will be identified in the group with the same DRSP strain.

Demonstration of an association between detection of IgG antibody reactivity towards the C-terminal region of the preS1 protein of hepatitis B virus and the capacity to respond to interferon therapy in chronic hepatitis B

Background and Aim:  The treatment of hepatitis B virus (HBV) remains complex, with somewhat unpredictable responses. The aim of this study was to determine the predictive value of the pretreatment presence of circulatory antibodies towards a synthetic peptide mimicking the amino acids 94–117 of the preS1 protein of HBV and the capacity to respond to alpha‐inteferon (IFN‐alpha) treatment.