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Various cultures have practised immunization against a range of infectious diseases for many centuries, but the principles began to gain general acceptance in 1796 when Edward Jenner showed that vaccination against cowpox provided protection against smallpox, which was the most common cause of death among young children at the time. Sweden adopted compulsory vaccination against smallpox in 1816. While vaccination eradicated smallpox in many countries, the need to vaccinate entire populations remained as long as the infection could still be found anywhere in the world. As recently as the early 1960s, a Swedish sailor brought the disease back to the country and gave rise to a national smallpox epidemic. A global vaccination campaign launched against smallpox by the World Health Organization (WHO) in 1967 eradicated the disease within 10 years. Thus, Sweden stopped administering the vaccine in 1976. [ABSTRACT FROM AUTHOR]

Unlabelled: In a retrospective study of neonatal septicaemia and meningitis carried out in 1987-1996 in the Göteborg area of Sweden, 305 cases during the first 28 d of life were found. The incidence was 3.7/1000 live births, which was higher than that found in a study from 1975 to 1986 in the same area, 2.8/1000 live births. The most common pathogens were group B streptococci, aerobic gram-negative rods, Staphylococcus aureus and enterococci. The cases were approximately equally divided between very early, early and late onset infections. The case-fatality rate was lower in the present study (9%) than that in the previous study (15%). The case-fatality rate varied between 23% in neonates with a gestational age of < or = 29 wk and 3% in full-term neonates. Eighty-three very late onset infections occurred between days 28 and 120 after birth, corresponding to an incidence of 1.0/1000 live births. Of those, 47 occurred in preterm neonates. The most common organisms were aerobic gram-negative rods. Coagulase-negative staphylococci (CoNS) were studied separately. This organism was isolated in 60 and 32 cases during the first 28 d of life and between days 28 and 120, respectively, in neonates fulfilling the criteria of the Yale-New Haven Hospital for infections caused by commensal species. The incidence rates of CoNS infections were 0.7 and 0.4/1000 live births, respectively.Conclusion: The incidence of neonatal infections increased and the case-fatality rate decreased in the Göteborg area compared to the findings of a previous study. Very late onset infections should be added to the total burden of neonatal infections. CoNS are important pathogens but their role is difficult to determine since they are both pathogens and contaminants of cultures from blood and cerebrospinal fluid. [ABSTRACT FROM AUTHOR]

Investigates whooping cough in adults in Gothenburg, Sweden. Identification of attack and vomiting; Effects of pertussis vaccine; Recognition of symptoms.

Objectives To study the serotype distributions of group B streptococci (GBS) isolated from blood and cerebrospinal fluid and from the genital tract of pregnant women and to investigate any possible relation between serotype, age and clinical manifestation. Methods Invasive strains were collected from 1988 to 1997 and genital strains from 1995 to 1996. Strains of GBS were serotyped with coagglutination. Clinical data were obtained from hospital notes. Results A total of 144 invasive strains, 78 from neonates and infants and 66 from adults, were serotyped. The most common isolates from neonates and infants were types III (62%), Ia (18%), and V (9%). The most common isolates from adults were types III (29%), Ib (23%), V (21%) and II (15%). A majority of the adults (94%) had an underlying medical condition. The most common serotypes of the 114 strains isolated from the genital tract of pregnant women were types III (32%), V (22%), Ia (13%), Ib (13%) and II (11%). Conclusions Serotype III was the single most frequent GBS isolate from infants and adults. Serotype V, which appeared first in 1992, was the third most frequent isolate. A vaccine containing five GBS capsular polysaccharides appears to be appropriate for the Swedish population. [ABSTRACT FROM AUTHOR]

This study monitored the serotypes ofStreptococcus agalactiae(group B streptococcus; GBS) isolated from invasive infections in western Sweden and investigated possible relationships between serotype, age and clinical manifestations. Invasive GBS isolates were collected prospectively during 1998–2001 at six laboratories, covering two counties with a population of 1.8 million, and were serotyped by coagglutination. Clinical data were obtained from hospital notes. In total, 161 invasive strains (50 from neonates and infants aged< 3 months, and 111 from adults) were serotyped. The commonest serotypes from neonates and infants were serotypes III (60%), V (22%) and Ia (10%), and from adults were serotypes V (42%) and III (25%). Serotype V had doubled in frequency among both children and adults compared to a previous study from the same area in 1988–1997. Most (80%) of the adults had an underlying medical condition. No relationship was found between serotype and clinical manifestations. However, the study demonstrated the importance of active surveillance of GBS serotypes and the difficulties of formulating a multivalent polysaccharide conjugate vaccine against GBS. [ABSTRACT FROM AUTHOR]

Background: The pneumococcal conjugate vaccine PCV7 was introduced in Southwest Sweden in the child vaccination program in 2009, followed by PCV13 in 2010 and PCV10 in 2015. In this retrospective cohort study we assessed the pneumococcal serotype distribution in relation to predisposing factors, clinical manifestations and outcome during seven years after PCV introduction., Methods: Clinical data from 1278 patients with 1304 episodes of invasive pneumococcal disease (IPD) between January 2009 and December 2015 in Region Västra Götaland, Sweden, were retrospectively collected from medical records. Pneumococcal isolates were serotyped by gel diffusion and/or Quellung reactions performed at the Public Health Agency in Sweden. Associations between serotypes and clinical characteristics were statistically evaluated by use of Fisher's exact test, Mann-Whitney U test and Logistic regression analysis, whereas IPD episodes caused by serotypes over time were analyzed by Mantel-Haenszel chi-square test., Results: With the exception of serotype 3, the prevalence of PCV13 serotypes decreased during the study period, from 76% (n = 157) of all IPD episodes in 2009 to 25% (n = 42) in 2015 (p < 0.001) while non-PCV13 serotypes increased, mainly among patients ≥65 years and in patients with predisposing factors, including cardiovascular disease, pulmonary disease and malignancy (p < 0.001 for all). Patients with predisposing factors, including those with malignancy, immune deficiency or renal disease, were more likely to have IPD caused by a serotype not included in PCV13 rather than a vaccine-included serotype. Serotype 3 was associated with intensive care unit admissions while serotype 1 and 7F caused IPD among healthier and younger patients. PCV13 serotypes were associated with invasive pneumonia, and non-PCV13 serotypes were associated with bacteremia with unknown focus and with manifestations other than pneumonia or meningitis., Conclusions: Non-PCV13 serotypes caused the majority of IPD cases in Southwest Sweden, especially in patients ≥65 years and in patients with predisposing factors. Serotype 3, included in PCV13, was prevalent and often caused severe disease., (© 2021. The Author(s).)

Background: The objective of the study was to assess the epidemiology of late-onset (LO) neonatal invasive infections with surveillance covering 43 years, starting from 1975., Methods: Observational epidemiologic, retrospective study including a cohort of infants born in western Sweden in 1997-2017, who had a positive blood and cerebral spinal fluid culture between 3 and 120 days of age. A comparison was made of the incidence between 1997-2007 and 2008-2017. Data on LO infections during 3-27 days of life were assessed from 1975., Results: A total of 473 cases of LO infections were registered in 437 patients. The incidence increased from 2.0 to 3.1/1000 live births (LB) between 1997-2007 and 2008-2017 (P < 0.001). The increase in incidence was most pronounced among infants born <28 weeks gestation (from 255 to 398/1000 LB, P < 0.001). The most frequent pathogens were Staphylococcus aureus (25%), coagulase-negative staphylococci (17%), and Escherichia coli (13%). Infections due to group B Streptococci rose from 0.16/1000 LB to 0.33 (P = 0.03). During the whole surveillance period from 1975 to 2017, there were 579 cases between 3 and 27 days of life. Although the incidence increased in 2008-2017 to 1.9/1000 LB after first declining in 1997-2007, the case-fatality rate continued to decline from 27/284 (9.5%) between 1975 and 1996 to 6/182 (3.3%) in 2008 and 2017 (P = 0.01)., Conclusions: The incidence of LO neonatal invasive infections increased during the study period (1997-2017), but the case-fatality rate remained lower than in the previous surveillance period (1975-1996). Further surveillance and interventions with focus on prevention is critical to counteract the increasing incidence among high-risk infants., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The objective of the study was to evaluate data on early-onset neonatal invasive infections in western Sweden for the period 1997-2017. To identify changes in incidence, etiology and mortality and compare to previous studies from the same area starting from 1975., Methods: Observational epidemiological, retrospective study on infants 0-6 days of age with a positive culture in blood and/or cerebrospinal fluid between 1997 and 2017. A comparison was made of the incidence between 2008 and 2017 compared to 1997-2007. Changes in the incidence of infections due to Group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods were assessed from 1975., Results: The total incidence, including both recognized pathogens and commensals as causative agents, was 1.1/1000 live births. The incidence declined from 1.4/1000 LB in 1997-2007 to 0.9/1000 LB in 2008-2017 but the case-fatality rate remained unchanged, (8/119 vs 7/90), at 7%. Among the 209 patients identified during 1997-2017 with sepsis or meningitis the most common organisms were Group B streptococci (40%, 84/209), S. aureus (16%, 33/209) and E. coli (9%, 18/209). The incidence of Group B streptococci infections went from 0.9/1000 live births 1987-1996 to 0.45/1000 live births 1997-2017 and all cases were within 72 h. The proportion of extremely preterm infants (< 28 weeks gestation) rose steadily during the study period but there was no rise in infections due to Gram-negative organisms. The spectrum of cultured organisms changed after 72 h as commensal organisms started to emerge., Conclusion: There has been a decrease in the incidence of neonatal early-onset infections compared to previous studies in western Sweden. The incidence of GBS infections was not as low as in other reports. Further studies are needed to assess if screening-based intra partum antimicrobial prophylaxis instead of a risk factor-based approach for identifying candidates for intrapartum antimicrobial prophylaxis would be a better option for this study area., Key Notes: This study is one of the longest running follow-ups in the world, a follow-up of 43 years of early-onset neonatal infections.The incidence of early-onset GBS infections is higher in Western Sweden compared to other local reports.No difference in the incidence of early-onset GBS depending on the definition of early-onset being within 72 h or 7 days of life.

Aim: Respiratory syncytial virus (RSV) infections are among the most common lower respiratory tract infections in infants, but few studies have determined the age-specific incidence of hospitalisation in defined populations. This study gathered Swedish data on RSV in Gothenburg and its 10 surrounding municipalities from 2004 to 2011., Methods: Information was obtained from hospital databases of all patients up to five years of age who had a discharge diagnosis of an RSV infection and had a positive antigen detection or polymerase chain reaction test., Results: A total of 1764 children fulfilled the inclusion criteria and 238 of these were preterm. The incidence under one year of age was 17.4/1000/year, and in children aged one to four years it was 0.6/1000/year. RSV patients occupied a mean of 1141 hospital beds per year: 65 were treated in the intensive care unit, 27 needed ventilator support, 19 needed continuous positive airway pressure, 408 (23%) received antibiotics, 399 (23%) received steroids, and all but four patients received a bronchodilator. All children survived., Conclusion: The incidence of RSV infections was high, medication use was high, and complications were low. Preterm infants had a higher risk, but most infants needing hospitalisation for RSV are full term and have no known risk factors., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Unlabelled: The frequency of long-lasting, intensely itching subcutaneous nodules at the injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was investigated in a prospective cohort study comprising 4,758 children who received either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (Infanrix®, Pentavac®) alone or concomitant with a pneumococcal conjugate (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children (0.83 %) with itching granulomas were identified, epicutaneously tested for Al sensitisation and followed yearly. Contact allergy to Al was verified in 85 %. The median duration of symptoms was 22 months in those hitherto recovered. The frequency of granulomas induced by Infanrix® was >0.66 % and by Prevenar >0.35 %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al-adsorbed vaccine was added to the schedule., Conclusion: Long-lasting itching vaccination granulomas are poorly understood but more frequent than previously known after infant vaccination with commonly used diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk increases with the number of vaccines given. Most children with itching granulomas become contact allergic to aluminium. Itching vaccination granulomas are benign but may be troublesome and should be recognised early in primary health care to avoid unnecessary investigations, anxiety and mistrust.

Background: The aim of this prospective cohort study was to estimate the burden of severe disease caused by rotavirus-induced gastroenteritis in Swedish children aged < 5 y., Methods: Rotavirus-positive children admitted to hospitals serving 3 geographical regions with 155,838 children aged < 5 y, were offered inclusion in this 1-year study. Rotavirus strains identified were genotyped using multiplex PCR. Disease progression was documented through interviews and chart reviews., Results: In total, 604 children with rotavirus-induced gastroenteritis were included in the study. Forty-nine of 604 (8.1%) fulfilled the criteria for nosocomial infection. The minimum incidence was 388 per 100,000, with significant variability between study regions, ranging from 280 to 542 per 100,000. In all regions, the peak season occurred in February-April, but the season start varied, with first cases observed in October in the eastern region and December in the northern region. Genotypes identified differed between the regions: G1[P8] was most prevalent in all regions (77%), while the most varied pattern was observed in the western region, with G1[P8] observed in 61%, G4[P8] in 13%, G9[P8] in 10%, G2[P4] in 8%, and G3[P8] in 8% of the children. The median age of hospitalized children was 14 months and the median total duration of diarrhoea was 6.9 days. Sixty-eight percent reported a temperature > 38.5°C upon admission. Complications occurred in > 10% of the children, with hypertonic dehydration (32/604) and seizures (10/604) occurring most frequently., Conclusions: Rotaviruses may cause severe febrile acute gastroenteritis leading to dehydration requiring acute rehydration in hospital. In addition, further complications occurred in > 10% of hospitalized children.

After 16 years of no vaccination against pertussis in Sweden, mass vaccination of infants and catch-up vaccination of children up to 10 years with a monocomponent pertussis toxoid vaccine was performed in the Greater Gothenburg area of Sweden between 1995 and 1999. At the end of the project in February 1999, 56% of all 10 year old children born in the Greater Gothenburg area had received 3 doses of the pertussis toxoid. No booster doses were given. This led to a temporary almost complete elimination of the disease. The aim of the present study was to follow the incidence of pertussis after end of the mass vaccination project (1999-2009) as it is reflected by laboratory verified cases (cultures and/or PCR) and pertussis hospitalizations. A reemergence of pertussis was seen from the end of 1999 with a peak in 2004 followed by a decrease when booster doses to both 6 and 10 year old children were introduced in 2005-2006. From July 1, 1999 through December 31, 2009 a total of 1973 cases were diagnosed with culture or PCR. The disease was prevalent in all age groups. The highest documented incidence was seen in infants younger than 12 months. 450 patients with verified pertussis had received 3 doses of the pertussis toxoid vaccine in the mass vaccination project and some other trials (comprising a total of 69,423 children). The mean time from the last dose to the laboratory verification of pertussis was 5 years in these 450 cases. There were 128 hospitalizations, 106 of which were in infants. In conclusion, pertussis is still not eliminated from the area. Booster doses are needed but the numbers and optimal timing are not known., (Copyright © 2011. Published by Elsevier Ltd.)

Sweden was the only country in the world without any general pertussis vaccination when acellular pertussis (aP) vaccines were introduced. Since 1996 aP vaccines are given at the ages of 3, 5 and 12 months, with a 99% coverage, and until 2007 without a later booster. The long-term effects of aP vaccines, monitored within an enhanced surveillance project, were discussed at an international workshop in Stockholm in November 2008. The unique Swedish experience demonstrates that aP vaccines are capable of achieving the primary goal of a national vaccination programme, i.e., to significantly reduce the burden of pertussis in pre-school children. Throughout the 10-year surveillance period the highest age-specific incidence was reported in unvaccinated infants or those who had received only one dose, with most hospitalisations in this age group and eight deaths among unvaccinated infants. Complementary strategies are needed to achieve further reduction in morbidity from circulation of Bordetella pertussis.

The joint distributions of the six genes bca, bac, epsilon/alp1, alp2, alp3 and rib (encoding alpha-C-protein, beta-C-protein, epsilon/Alp1, Alp2, Alp3, and Rib, respectively) and the proteins alpha-C-protein, beta-C-protein and Rib were investigated in invasive isolates of group B streptococcus (GBS). In total, 297 invasive isolates (123 from neonates, 174 from adults) from south-west Sweden were collected during a 13-year period. Genes were detected using multiplex and specific PCRs, and expression of the surface proteins was demonstrated using monoclonal antibodies. The genes studied were found alone or in combinations in 294 (99%) of the invasive isolates. The most common genes were rib (n = 127 isolates, 43%), alp3 (n = 78, 26%) and epsilon/alp1 (n = 42, 14%). The bac gene was never found alone, but was found in combination with one other gene in 36 isolates. The surface proteins studied were detected alone or in combinations in 152 (51%) isolates, with the most common being Rib (n = 80, 27%), alpha-C-protein (n = 68, 23%) and beta-C-protein (n = 24, 8%). Several genes were associated significantly with particular serotypes (e.g., epsilon/alp1 with serotype Ia; bca and bac with serotypes Ib and II; rib with serotype III; alp3 with serotype V). Overall, it was concluded that demonstration of different genes and surface proteins of GBS strains can be useful in epidemiological studies and in formulation of vaccines, but disappointingly, no single gene or surface protein included in the study was sufficiently common for it to be considered as the basis for a successful GBS vaccine.

The antibiotic susceptibility of 297 invasive isolates of group B streptococci (GBS) to a panel of 12 antibiotics was analysed using the E-test. The isolates (from 123 neonates and 174 adults) were collected from south-west Sweden during the 2 periods 1988-1997 and 1998-2001. The breakpoints of the Clinical and Laboratory Standards Institute were used. All isolates were sensitive to cefotaxime, meropenem, linezolid, vancomycin, moxifloxacin and quinupristin-dalfopristin. Two strains displayed a slightly decreased susceptibility to penicillin G (MIC 0.25 microg/ml) also when tested by the broth dilution method. Two per cent were resistant to erythromycin and 1% to clindamycin. Strains with intermediate sensitivity to erythromycin and clindamycin increased over the 2 study periods. 68% were resistant to doxycycline, and the resistance rate for doxycycline increased over the 2 study periods. No strain was resistant to trimethoprim-sulfamethoxazole. Serotype V dominated among strains with intermediate susceptibility to erythromycin and clindamycin. There were no other relationships between serotypes and decreased sensitivity to any agent. There were no significant differences in susceptibility to any agent tested between strains isolated from neonates and adults. In conclusion, penicillins remain the drug of choice in the region but with the increasing rates of intermediate susceptibility to both erythromycin and clindamycin, antibiotic sensitivity analysis should be performed on the GBS isolates from penicillin-allergic patients.

Invasive disease caused by antibiotic resistant pneumococci is a worldwide problem. All invasive pneumococcal strains in an area of south-west Sweden with 1.7 million inhabitants were collected prospectively during 1998-2001. Minimum inhibitory concentrations (MICs) were determined by E-test and correlated to serotypes and clinical characteristics. Of 827 strains, 744 (90%) were susceptible (S) to all agents tested and 83 (10%) were indeterminate (I) or resistant (R) to at least 1 agent. 22 isolates (2.7%) were I to penicillin (MIC >0.06 to < or = 1.0 mg/l), but none were R (MIC >1.0 mg/l). Numbers and proportions of decreased susceptibility against other agents tested were as follows: erythromycin R: 30 (3.6%), clindamycin R: 6 (0.7%), tetracycline R: 16 (1.9%), moxifloxacin R: 1 (0.1%), cotrimoxazole I: 17 (2%) and R: 31(4%). Non-susceptibility to at least 1 agent was not correlated with age, clinical manifestation, underlying diseases and outcome. The serotype distribution differed between non-susceptible and susceptible strains. The serotypes in the 7-valent pneumococcal conjugate vaccine covered 42% of all infections and 73% of those caused by non-susceptible strains. In conclusion, the impact of antibiotic resistance in invasive pneumococcal disease remains limited in south-west Sweden.

Unlabelled: In an open study, 502 10-year-old children, who had received primary vaccination against diphtheria and tetanus in infancy and had varying histories of pertussis disease and vaccination, were vaccinated with diphtheria-tetanus vaccine (DT) alone or with the addition of 20 microg or 40 microg of pertussis toxoid. Diphtheria toxin neutralising antibodies, pertussis toxin IgG and tetanus toxoid IgG antibodies were measured before and 1 month after the booster. All toxoids were highly immunogenic. In pertussis toxoid recipients, median levels of pertussis toxin IgG increased to 16.5 U/ml (DTaP20) and to 36 U/ml (DTaP40) in children with non-detectable (<1 U/ml) antibodies before vaccination and to >400 U/ml in children (both DTaP20 and DTaP40) with detectable antibodies before vaccination. A total of 60 children (12%) with non-detectable (<0.01 IU/ml) diphtheria antibodies and 36 children (7%) with non-detectable (<0.01 IU/ml) tetanus antibodies before the booster had lower median antibody concentrations post-vaccination than children with detectable antibodies before the booster (diphtheria: 5.12 vs. 20.48 IU/ml; tetanus: 4.0 vs. 10.0 IU/ml). There were no differences in diphtheria and tetanus antibodies after vaccination between children who did and did not receive pertussis toxoid., Conclusion: 10-year-old children with non-detectable diphtheria and tetanus antibodies before the booster had lower post-vaccination antibodies than those with detectable antibodies before the booster indicating a poor immunological memory. Addition of pertussis toxoid to diphtheria-tetanus vaccine did not affect the antibody responses to diphtheria and tetanus toxoids when the three toxoids were combined as a booster. Even though immunity to diphtheria and tetanus was only estimated by surrogate markers (serum antitoxin antibodies) the results indicate that a lower age for the booster dose of diphtheria-tetanus vaccine or diphtheria-tetanus acellular pertussis vaccine should be considered.

Rare cases of persistent pruritic nodules, sometimes associated with aluminium (Al) allergy, have been reported after the use of several Al adsorbed vaccines. During vaccine trials in the 1990s a high incidence of pruritic nodules (645 cases/76,000 recipients), in 77% associated with Al allergy, was observed after the administration of diphtheria-tetanus / acellular pertussis (DT/aP) vaccines from a single producer. In the present report 19 children with pruritic nodules after vaccination with Al hydroxide-adsorbed DTaP/polio+Hib (Infanrix, Pentavac) are described. The children had intensely itching nodules at the injection site, often aggravated during upper respiratory tract infections, and local skin alterations. So far, the symptoms have persisted for up to 7 years. The median time between vaccination and onset of symptoms was 1 month. 16 children were epicutaneously tested for Al, all with positive reactions indicating delayed hypersensitivity to Al. The condition is not commonly known but is important to recognise, as the child and the family may suffer considerably. Future vaccinations with Al-adsorbed vaccines may cause aggravation of the symptoms and the Al allergy. Al-containing skin products, such as antiperspirants, may cause contact dermatitis. Nodules may be mistaken for tumours. Even though the incidence of itching nodules and Al allergy after administration of Infanrix, Pentavac and other Al-adsorbed vaccines is probably low, research to replace Al adjuvants seems appropriate. We conclude that intensely itching subcutaneous nodules, lasting for many years, and hypersensitivity to aluminium may occur after DTaP/polio+Hib vaccination of infants.

Background: Thanks to a successful voluntary vaccination programme, measles, mumps and rubella are rare diseases in Sweden. Coverage among children 18 mo of age has been 99%, but the measles, mumps and rubella vaccination (MMR) has increasingly been questioned among parents., Aim: To study reasons why parents choose not to vaccinate their child against measles, mumps and rubella, and their opinions on vaccines and the diseases themselves. A secondary objective was to compare coverage at 18 mo of age based on parental report with the national statistics based on patient charts., Methods: The official statistics were compared with patient charts for two birth cohorts in the city of Göteborg, Sweden. Out of these children born in 1995 and 1996, 300 unvaccinated and vaccinated children were identified. Their parents received a postal questionnaire assessing the parent's views on vaccines and childhood diseases., Results: The documented vaccine coverage in this study was higher in 1995 and 1996 than official statistics indicated. The major reason, for both groups, for accepting respectively declining vaccination was strengthening the child's immune system. Parents with children unvaccinated against MMR were also more likely to have declined vaccination against diphtheria, polio, tetanus, Haemophilus influenzae and pertussis. One-third of the parents with a child unvaccinated against MMR had not yet made their final decision 3 y after the vaccine offer. Few parents, both with vaccinated and unvaccinated children, had acquired vaccine information from the Internet. Both groups believed that insufficient time was allocated for vaccine information and discussion at the Child Health Centre., Conclusion: Our study indicates that official statistics on MMR vaccination uptake underestimate the number of vaccinated children. Vaccine safety is a major concern for many parents and needs to be addressed by healthcare professionals at institutions offering paediatric vaccinations.

Objectives: To study the incidence, clinical manifestations, concomitant conditions and case-fatality rate in patients with invasive group B Streptococcus (GBS) infections in the Göteborg area (mean population 582,666) of Sweden during 1981-95., Design: Patients were identified from the records of the Department of Clinical Bacteriology. Clinical data were obtained from hospital records., Results: GBS was isolated from blood, cerebrospinal fluid or other sterile body fluids from 211 patients with 215 infectious episodes; 108 in neonates, and 107 in non-neonates. The incidence was 2.4/100,000 per year, with the highest rates in neonates and in persons 65 years old or older. The incidence in neonates was 0.92/1,000 live births. The most common manifestation was septicemia with unknown focus. Of the neonates, 54% were full term and had no underlying conditions. Of the non-neonates, 15% had no underlying conditions. The most common underlying conditions were preterm delivery in neonates, and arteriosclerotic disease and diabetes mellitus in non-neonates. The case-fatality rates were 13% in neonates and 16% in non-neonates., Conclusions: GBS is an important pathogen in neonates and in adults with concomitant conditions. The morbidity and mortality rates necessitate research to develop GBS vaccines both for women of fertile age and for patients with a wide variety of underlying diseases.

Pertussis re-emerged in Sweden with a cumulative incidence of about 60% during the first 10 years of life, when the locally produced cellular vaccine lost its efficacy around 1970 and general vaccination was discontinued in 1979. The epidemiology, clinical features, and immunology of pertussis and a monocomponent pertussis toxoid vaccine were studied in Göteborg, Sweden. After phase 1 and 2 studies, a randomized, double-blind, placebo-controlled trial of pertussis toxoid (PTox), compounded with diphtheria and tetanus toxoids, was administered to 3450 children according to the Swedish schedule at 3, 5, and 12 months of age. After a mean follow-up of 18 months, the efficacy was 71% overall and 75% in household contacts, respectively. A statistically significant correlation was found between the level of PTox-induced antibodies and protection against pertussis. As observed with cellular and with multicomponent acellular vaccines, PTox reduced the severity of disease and the percent of children with positive cultures. Furthermore, vaccination reduced the transmission of Bordetella pertussis to household contacts in the vaccinees compared with the controls who received only diphtheria and tetanus toxoids. Patients with culture-verified Bordetella parapertussis infection reacted with antibodies to pertactin and to filamentous hemagglutinin but not to pertussis toxin, and some subsequently developed pertussis. The antibody responses of patients with pertussis to the surface polysaccharides of B pertussis and to B parapertussis were cross-reactive serologically. Serosurveys showed that only antibodies to pertussis toxin were related to the occurrence of pertussis in the general population: antibodies to filamentous hemagglutinin and pertactin were probably stimulated by antigens of other bacteria as well as Bordetellae. Mass vaccination of Göteborg children born in the 1990s was started in 1995. In February 1999, about 55% had been vaccinated and both B pertussis and pertussis decreased significantly in individuals of all ages (herd immunity). Similar to diphtheria, PTox-induced immunity to pertussis occurs both on an individual and community basis. The apparent greater efficacy of multicomponent acellular pertussis vaccines compared with monocomponent PTox was proposed to be an artifact created when the diagnosis of pertussis was made by the serologic criteria of the World Health Organization only. Our conclusion is that PTox is both an essential and alone sufficient antigen in acellular pertussis vaccines.

During 1979-1995, there was no vaccination against pertussis in Sweden. With the aim of studying the epidemiology and transmission of pertussis, mass vaccination with pertussis toxoid of children born during the 1990s was instituted in the Göteborg area (population, 778,597) in 1995. Infants were offered 3 doses of pertussis toxoid combined with diphtheria and tetanus toxoids. Children aged > or =1 year were offered 3 doses of pertussis toxoid alone. From June 1995 through February 1999, 167,810 doses of pertussis toxoid were given to 61,219 children born during the 1990s (56% received 3 doses). The number of Bordetella pertussis isolates per year declined from 1214 (1993-1995) to 64 (January 1997 through June 1999; P<.0001), and hospitalizations due to pertussis declined from 62 to 5 (P<.0001). Significant decreases in B. pertussis isolates and hospitalizations occurred in all age groups, including adults and nonvaccinated infants. Thus, mass vaccination of children with pertussis toxoid decreases spread of B. pertussis in the population.

In a retrospective study, the incidence, clinical manifestations, concomitant conditions and case fatality rate were studied in patients with invasive pneumococcal infections in the Göteborg area of Sweden during 1981-95, when the pneumococcal polysaccharide vaccine was available but little used. Patients were identified from the records of the Departments of Clinical Bacteriology and from the computer-based hospital discharge registers of the relevant departments. Individual case records were found for 876 patients with invasive pneumococcal infections verified by cultures from blood, cerebrospinal fluid or other sterile body fluids. A study from the same area with the same design covering the years 1964-80 has previously been published. There was an increase in total incidence from 5.3 to 10.3 cases/100,000/y from the previous to the present study. This increase was due to an increase in patients with non-meningitic infections aged > or = 60 y. The incidence of meningitis was virtually unchanged (1.4/100,000/y), as was the incidence of non-meningitic infections in individuals < 60 y. There were no other important changes between the 2 studies, which confirm that invasive pneumococcal infections have the highest incidence rates in children < 2 y and in the elderly, that a wide variety of underlying conditions are seen in the patients and that the case fatality rate, 15% in the present study, is still high.

Swedish infants were vaccinated with diphtheria, tetanus and pertussis toxoids, inactivated poliovirus vaccine and a Haemophilus influenzae type b - tetanus toxoid conjugate vaccine at 2, 4, 6 and 15 months (US vaccination program, 'US arm', n=118) or at 3, 5 and 12 months of age (Swedish vaccination program, 'Swedish arm', n=103). The antigen amounts in the diphtheria and tetanus vaccines were higher in the Swedish than in the US arm while the amounts in the other vaccines were the same in both arms. There were no serious side effects. Local reactions increased with the numbers of doses but did not differ significantly between the groups. Serum was obtained at 2, 7, 15 and 16 months in the US arm and at 3, 6, 12 and 13 months of age in the Swedish arm. A fifth serum was obtained in both groups at 4 yr of age. For vaccines with the same antigen amount the following was observed: a. three doses at 2, 4 and 6 months were more immunogenic than two doses at 3 and 5 months; b. the third dose in the Swedish arm was more immunogenic than the third dose in the US arm; c. the fourth dose in the US arm induced higher antibodies than the third dose in the Swedish arm (except for pertussis toxin antibodies that were similar in both groups) and the differences tended to remain at the age of 4 yr. Children in the Swedish arm received a higher diphtheria toxoid dose (25 Lf) than in the US arm (15 Lf) which led to higher diphtheria toxin antibodies in the Swedish arm at comparable ages. Children in the Swedish arm received a higher tetanus toxoid dose (7 Lf) than in the US arm (6 Lf). Tetanus antibodies were similar at comparable ages. In conclusion, the immunogenicity of vaccines in infancy can be improved by increasing the number of doses, by prolonging the intervals between doses and by increasing the antigen amount in the vaccine.

In the Gothenburg study, 3,450 infants were randomly assigned to receive three subcutaneous injections of acellular pertussis vaccine consisting of peroxide-inactivated pertussis toxin with diphtheria and tetanus toxoids (DTP-toxoids) or DT-toxoids alone under blind conditions at three, five and 12 months of age. Safety of the vaccinations was assessed by direct contact with the families in the week following each injection. No serious vaccine-associated adverse reactions were observed, in either group. The frequency of fever and local reactions increased by dose. Redness and swelling were slightly but significantly more frequent in recipients of DTP-toxoids compared to the DT group.

The incidence, concomitant conditions and case fatality rate of Haemophilus influenzae (Hi) and pneumococcal meningitis and of invasive meningococcal infections were studied retrospectively in Sweden (population 8.4 million) for the years 1987-89, the period before vaccination against Hi type b started. A total of 1,019 cases with culture-verified infection were found. The incidence rates per 100,000 per year were 1.8 for Hi meningitis, 1.2 for pneumococcal meningitis and 1.0 for invasive meningococcal infections. The age-specific incidence was highest in the 3-23 months age group for the 3 bacterial species. Pneumococcal meningitis was common in individuals > or = 60 years and meningococcal infections in the age-group 10-24 years. A serious concomitant condition was known in 57% of all patients with pneumococcal meningitis while this was uncommon for the other organisms. The case fatality rate was 2% for Hi meningitis, 24% for pneumococcal meningitis and 10% for meningococcal infections. All 81 pneumococcal isolates which had been serotyped belonged to serotypes in the 23-valent pneumococcal vaccine. Of the meningococcal isolates, 65% belonged to serogroup B. In conclusion, the high incidence of Hib meningitis justifies general Hib vaccination. Development of a vaccine against N. meningitidis group B should have high priority. Furthermore, improved pneumococcal vaccines are needed for patients with predisposing conditions. The currently available pneumococcal polysaccharide vaccine seems to be underused.

A retrospective study of the incidence, aetiology and case fatality rate of acute epiglottitis in children and adults was performed. The study covered the whole of Sweden (population 8.4 million) during the years 1987-89, before general vaccination against Haemophilus influenzae (Hi) type b was started. Patients were included if it was documented that they fulfilled all 3 of the following criteria: (a) red and swollen epiglottis visualized by indirect laryngoscopy, (b) inspiratory stridor or difficulties in swallowing, and (c) a temperature > or = 38 degrees C. A total of 306 children and adolescents (0-19 years) and 502 adults (> or = 20 years) were found. The age-specific incidence was highest in children aged 0-4 years, (14.7/100,000 per year). The total incidence was 3.2/100,000 per year. In the age group 0-19 years, blood cultures had been obtained from 195 (64%) and Hi was isolated from 154 (79%). In adults (> or = 20 years), 114 of 298 blood cultures yielded Hi, while pneumococci were isolated from 5 and group A streptococci from 3 patients. A total of 220 children (72%) and 114 adults (23%) needed an artificial airway. Five children and 12 adults died. In conclusion, the incidence of acute epiglottis in Sweden is very high. Compared to a previous country-wide study covering the years 1981-83 that used the same methods for case finding and case definition, the incidence in children had decreased while the incidence in adults had increased.

Background: Although many whole-cell vaccines have been effective in preventing pertussis, these vaccines are difficult to standardize and can produce side effects. In Sweden, pertussis became endemic during the 1970s despite vaccination. Because of its limited efficacy, the Swedish-made whole-cell vaccine was withdrawn in 1979., Methods: To evaluate the efficacy of an acellular vaccine consisting of pertussis toxin inactivated by hydrogen peroxide (pertussis toxoid), we conducted a randomized, double-blind, placebo-controlled trial in Sweden. Infants were vaccinated with either diphtheria and tetanus toxoids alone (DT toxoids, 1726 infants) or diphtheria, tetanus, and pertussis toxoids (DTP toxoids, 1724 infants) at 3, 5, and 12 months of age., Results: There were no serious reactions. With the pertussis vaccine there were slightly more local reactions than with the DT toxoids alone, but the rates of postvaccination fever were the same. The main period of surveillance, which began 30 days after the third vaccination, continued for a median of 17.5 months. There were 312 cases of pertussis (72 in the DTP-toxoids group and 240 in the DT-toxoids group) that met the clinical criterion (paroxysmal cough lasting > or = 21 days) and laboratory criteria for pertussis as defined by the World Health Organization. The efficacy of this acellular vaccine was 71 percent (95 percent confidence interval, 63 to 78 percent). The recipients of DTP toxoids who had pertussis had cough of shorter duration than the recipients of DT toxoids, and fewer had whooping and vomiting. The vaccine efficacy after two doses was 55 percent (95 percent confidence interval, 12 to 78 percent), on the basis of 14 cases in the DTP-toxoids group and 31 in the DT-toxoids group that met the definition of the World Health Organization., Conclusions: A pharmacologically inert, acellular pertussis-toxoid vaccine that is easily standardized is safe and confers substantial protection against pertussis.

A cost-benefit analysis of general vaccination of infants with a conjugated Haemophilus influenzae type b (HIB) vaccine was performed. Information on incidence and prognosis of HIB meningitis and acute epiglottitis in children was obtained from nation-wide retrospective studies covering the years 1981-83, when the birth rate was approximately 93,000 per year. The annual cost for hospitalization, neurologic and auditory sequelae and parents' absence from work amounted to 54 million Swedish crowns (SEK). A mean of 6 children died every year. Inclusion of value of lives lost added SEK 72 million to the cost of disease. With vaccine prices (approximately SEK 125/dose) and birth rate (approximately 120,000 per year) prevailing in 1993, vaccine costs would be SEK 45 million, provided that 3 doses are sufficient to offer protection close to 100%. Other costs for vaccination, e.g. physicians' and nurses' time, needles and syringes, are negligible, since the vaccine can be given at the same time as other infant vaccinations at already existing Child Health Centres. In conclusion, general vaccination of infants against HIB is cost-effective, saves lives and reduces human suffering.

In Sweden general vaccination with a whole cell pertussis vaccine was recommended from 1953. In 1979 the recommendation was withdrawn because the Swedish-made vaccine had become ineffective. In order to determine the incidence of the disease in a nonvaccinating country, 400 children born in 1980 were randomly selected from the population register of Göteborg, Sweden. The parents of the children were interviewed in 1990, when the children were 10 years old. The parents of 377 children could be reached, and of those 372 were not vaccinated against pertussis. Of the nonvaccinated children 61% had experienced clinically typical whooping cough; 195 (119 with and 76 without a history of whooping cough) agreed to donate a serum sample for determination of antibodies against pertussis toxin, filamentous hemagglutinin and pertactin. Of the children with a history of whooping cough, 91% had antibodies against pertussis toxin, as had 64% of the children without a history of disease. All but 3 children had antibodies against filamentous hemagglutinin and all 195 children had antibodies against pertactin. The antibody titers against the 2 last mentioned proteins did not differ between children with and without a history of whooping cough or between children with and without antibodies against pertussis toxin.

Serum antibodies against pertactin were found in all samples from 260 nonvaccinated healthy Swedish 1- to 4-year-old children, although 42% had neither a history of clinical pertussis nor antibodies against pertussis toxin or filamentous hemagglutinin. Pertactin antibody levels were, however, higher in children with a history of pertussis than in those without a history of pertussis, and higher in children with antibodies against pertussis toxin and filamentous hemagglutinin than in those without such antibodies.

In a retrospective study of invasive meningococcal infections in Greater Gothenburg, Sweden, 213 cases of culture-verified meningitis or septicaemia were identified during the 15-year period 1975-1989. The annual incidence was 2.0/100,000. Cases were seen in all age-groups with the highest rates in the 0-4 and 15-19 year-old groups, 9.5 and 6.2/100,000 respectively. 20% of the patients were less than 2 years. 91% of the patients had no known risk factors. In only 10 cases (5%) was contact with another case of meningococcal infection known. The main clinical manifestations were meningitis (57%), septicaemia with no sign of focal infection (25%) and septic shock (17%). The case-fatality rate for all the patients was 6.6% and did not change during the 15-year period. One-third of the patients who presented with septic shock died. The serogroup was known for strains from 192 patients. 51% of the strains belonged to serogroup B, 10% to group A and 23% to group C. In conclusion, the incidence of meningococcal infection was low but the relatively high case-fatality rate warrants a search for effective prophylaxis. About 30% of the cases were potentially preventable by the currently available tetravalent (A, C, Y and W135) polysaccharide vaccine, which is immunogenic in children greater than 2 years. Widespread use of antibiotic prophylaxis to close contacts of known cases would not lower the incidence markedly.

In a retrospective study of neonatal septicaemia and meningitis in a defined region of western Sweden 1975-1986, 231 cases were identified. The incidence was 2.8/1000 live births. The case-fatality rate was 15%. thirty-three patients had meningitis. Only 55 patients (24%) had no known risk factors. Preterm delivery was a most important risk factor for both morbidity and mortality. The most common causative organisms were group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods, together isolated from 82% of the patients. The cases were approximately equally divided between very early, early and late onset infections. Group B streptococci were over-represented in very early onset infections in all birthweight groups and aerobic Gram-negative rods were the most common isolates from low birthweight infants with late onset infections. However, group B streptococci, Staphylococcus aureus and Gram-negative rods were found in all birthweight and gestational age groups. Thus, initial antimicrobial therapy must be equally broad in all neonates with suspected septicaemia.

In a retrospective study of the incidence of acute epiglottitis in Sweden, 485 children and 356 adults fulfilled the following criteria: (a) red and swollen epiglottis visualised at laryngoscopy; (b) stridor or difficulties in swallowing own saliva or water; and (c) temperature greater than or equal to 38 degrees C. The age specific incidence in children (0-14 years) was 10 and in adults (greater than or equal to 15 years) 1.8/100,000/year. These incidence rates were higher than the incidence of Haemophilus influenzae meningitis in the same population. Blood cultures were obtained from 290 children (60%) and 185 adults (52%). H influenzae was isolated from 267 blood cultures (92%) from children and 98 blood cultures from adults (53%). Other organisms were isolated from six adults (3%). An artificial airway was established in 352 children (73%) and in 68 adults (19%); the remainder were treated conservatively. Six children and two adults died. Sweden has a high incidence of acute epiglottitis in children and the disease also occurs in adults. The importance of H influenzae in the aetiology of epiglottitis in all age groups is confirmed, but in adults many cases occur without septicaemia. The mortality is currently very low.

The aim of this study was to examine whether there is a correlation between parental information on the child's history of whooping cough and the presence or absence of serum antibodies against two antigens of Bordetella pertussis, pertussis toxin and filamentous hemagglutinin, in nonvaccinated Swedish children. The parents of 266 Swedish children aged 1 to 4 years answered a questionnaire regarding the child's history of whooping cough, and a serum sample was obtained from the child for determination of IgG, IgM, and IgA antibodies to pertussis toxin and filamentous hemagglutinin. The study was performed from 1984 to 1986, five to seven years after the cessation of general vaccination against pertussis in Sweden; none of the children had received pertussis vaccine. Antibodies to both toxin and filamentous hemagglutinin increased with age. Of the children aged 4 years, 50% had antibodies to both antigens. Of all 266 children, 100 had antibodies to both antigens, 6 to toxin alone, and 49 to filamentous hemagglutinin alone. There was a good correlation between the presence of antibodies and a history of whooping cough. Of 91 children with a history of whooping cough, 77 had antibodies against both antigens and 13 against one antigen; only one child lacked detectable antibodies against both antigens. Of the 175 children with no history of whooping cough, 110 lacked detectable antibodies to both antigens, 23 had antibodies to both, 2 to toxin alone, and 40 to filamentous hemagglutinin alone. The data indicate that parental information on a previous history of whooping cough in their nonimmunized child is reliable, and that many infections with B. pertussis are subclinical or atypical. Exposure to other Bordetella species than B. pertussis, which is the only toxin-producing species, might be important for the development of FHA antibodies. A follow-up 2 to 4 years after the collection of serum samples of children without a history of whooping cough but with antibodies to one or both antigens indicated that serum antibodies to toxin, but not to filamentous hemagglutinin, may be protective against disease.

A retrospective analysis of the case records of 494 patients with 508 episodes of pneumococcal infections verified by cultures from blood or from cerebrospinal, pleural, and/or synovial fluid from 1964 through 1980 is presented and discussed in relation to the literature on invasive pneumococcal infections. The documented incidence (1976-1980) of pneumococcal meningitis in a defined area of southwestern Sweden was similar to that reported from the United States; 1.4 cases per 100,000 persons per year; for nonmeningitic infections (mainly bacteremic pneumonia) the incidence was 6.1 per 100,000 per year. The highest age-specific incidence was seen in infants younger than two years. In the vast majority of patients, predisposing conditions (young or old age or severe underlying diseases) were present. In adults, alcoholism was the most important risk factor. The fatality rate was 33% for patients with meningitis and 15% for patients with non-meningitic infections, figures that were strikingly similar to those reported in other studies. Underlying diseases and young or old age contributed significantly to the high mortality rates.

In an open trial, the efficacy of intravenously administered ceftazidime was evaluated in 106 adult patients with urinary or respiratory tract infections, soft tissue infections, osteitis and septicaemia. The most commonly isolated pathogens were Escherichia coli, Pseudomonas spp. and Staphylococcus aureus. Of 85 organisms isolated before treatment, 79% were cleared and 15% were cleared but later relapsed often because of the underlying conditions. Clinical cure was achieved in 70%, improvement occurred in 25% of the patients and 6% failed to respond. Marked increases in serum creatinine occurred in three patients with pre-existing renal impairment treated with ceftazidime in unmodified dosage. Exanthema, diarrhoea or local thrombophlebitis was noted in 13 patients.

Incidence of whooping cough was studied in Göteborg, Sweden, in four random samples of birth cohorts from 1972, 1977, 1978 and 1980. To obtain data a postal questionnaire to parents was used and methodologically explored. Vaccination data were taken from health cards. Four years after stopping vaccination cumulative incidence in the unvaccinated cohort born 1980 had risen to levels of the prevaccination era. Sex differences in susceptibility were not seen. Efficacy of the Swedish manufactured non-adsorbed whole cell pertussis vaccine was low. In a developed country like Sweden a cross-sectional study of random samples from the community with recall data may give useful information on the incidence of a disease like whooping cough at a comparatively low cost.

Haemophilus influenzae meningitis in children 0 to 15 years old was studied retrospectively in a defined region of southwest Sweden from 1971 through 1980; 147 patients with culture-verified H. influenzae meningitis were found. Sixty-seven of them were younger than 18 months and would not have been protected by a purified H. influenzae b polysaccharide vaccine. The age-specific yearly incidence was 27 per 100,000 in the 0- to 4-year age group, 4 per 100,000 in the 5- to 9-year age group and 1 per 100,000 in the 10- to 15-year age group. Predisposing factors were found in only three patients. Two patients died, 3 developed severe neurological sequelae and 19 developed irreversible auditory impairment.