| 1. |
- Garpenholt, Örjan
(författare)
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Vaccination against Haemophilus influenzae type b in Sweden : Aspects of epidemiology, economy and the process of introduction
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since 1992-1993 vaccination against Haemophilus influenzae type b (Hib) with conjugated vaccines is included in the general Swedish childhood vaccination programme. In this thesis the introduction of Hib vaccination has been evaluated.The epidemiology and clinical spectrum of invasive H. influenzae disease was prospectively studied during the pre-vaccination period in a well-defined population of Sweden 1987-1992. The incidence (cases/100 000/personyear) was 5.9 for all ages and 55 in children 0 to 4 years of age. Serotype b was the dominating type, especially in children. Three patients died in connecting with illness and six developed permanent sequelae.In national studies, the incidence before and after introduction of the Hib vaccination programme was compared. The source for the studies was the report system from the clinical microbiology laboratories to the Swedish Institute of Infectious Disease Control. Already within one year after introduction a decreased incidence was observed. In the prevaccination period the incidence was 34 in 0 to 4 years old children. In 1998 the incidence had decreased to 1.6 in the same age group. Thirteen children were identified with invasive Hib disease in spite of vaccination. Effectiveness, which take in account both direct and indirect effects of vaccination in 0 to 4 years old children was calculated to 96.0% (95 %Cl, 94.2-97.4). To study the impact of Hib vaccination in the on the diagnosis epiglottitis a national register of all patients treated at Swedish hospitals was used. In the age group 0-4 year the incidence decreased with 95 % after introduction of Hib vaccination. Even in older ages a decrease was observed but this trend did not reach statistically significance.An evaluation of the economic consequences of a general childhood vaccination programme against Hib in Sweden was conducted. A retrospective prevaccination annual cohort of 0-4 year old children was compared with an annual cohort of the same age group after a completely implemented vaccination programme against Hib. The cost analysis shows that vaccination against Hib is cost saving when indirect costs are included in the analysis. In the cost-benefit analysis it is shown that society will gain -88 million Swedish Crowns annually when Hib vaccination is totally implemented.The process of introducing general childhood Hib vaccination was studied. The critical factors for implementation of the immunisation programme were found to be the vaccine product, conception of the disease, government economy and public decision-making. Five activity systems were found to be involved in the implementation process, the systems of vaccine production, government administration, news distribution, science, and disease prevention. To structure the results a theoretical framework was used, Culture Historical Activity Theory. The study shows that a broad range of aspects must be considered before an intervention such as a general vaccination programme can be implemented in society.
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| 2. |
- Hedin Skogman, Barbro, 1967-
(författare)
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Neuroborreliosis in childhood : Clinical, immunological and diagnostic aspects
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lyme Borreliosisis is a multi-organ infectious disease caused by the spirochete Borrelia burgdorferi. The spirochete is transmitted to humans by tick bites. Neuroborreliosis (NB) is a disseminated form of the disease, in which the spirochetes invade the nervous system. In children, subacute meningitis and facial nerve palsy are typical clinical manifestations of NB.The aim of this thesis was to study clinical, immunological and laboratory characteristics in children being evaluated for NB in a Lyme endemic area of Sweden, in order to identify factors of importance for prognosis and clinical recovery. A total of 250 patients and 220 controls were included during 1998-2005, with a prospective and a retrospective part.Less than half (41%) of children with signs and symptoms indicative of NB get the diagnosis confirmed by detection of Borrelia specific flagella antibodies in CSF (clinical routine method). Surprisingly few patients were diagnosed as having other infectious or neurologic diseases and consequently, many patients ended up with an uncertain diagnosis. However, four new Borrelia antigens (DbpA, BBK32, OspC, IR6) were evaluated and performed well in laboratory diagnostics. If they were combined in a panel, together with the flagella antigen, the sensitivity was 82% and the specificity 100%, leading to improved diagnostic accuracy in children with NB, as compared to using the routine flagella antibody test alone.Clinical recovery at the 6-month follow-up (n=177) was generally good and nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. No patient was found to have recurrent or progressive neurologic symptoms.However, permanent facial nerve palsy was found in 22% of patients at the 2-year follow-up, with consequences such as eye-closing problems, excessive tear secretion, pronunciation difficulties and cosmetic complaints.When cellular immune responses were investigated, the number of Borrelia-specific IL-4 and IFN-γ secreting cells in CSF was found to be more prominent in children with NB than in controls. Furthermore, a much stronger IL-4 response in CSF was seen in children as compared to adults with NB. This cytokine profile of children with NB is believed to represent an effective and balanced type1/type2 response in a relevant compartment, and could contribute to the less severe course of the disease seen in children as compared to adults with NB.No prognostic factors were found to influence the outcome in patients with “Confirmed NB” or facial nerve palsy. Nor was any specific cytokine profile, or antibody response to new Borrelia antigens in CSF, correlated to a less favorable clinical outcome.An NB prediction score test, based on clinical variables at admission, is suggested to help physicians to determine whether to start early antibiotic treatment, before results from Borrelia antibody tests are available.Results in this thesis support the notion that mononuclear pleocytosis in CSF, in patients being evaluated for NB, indicates that they are true NB cases despite the fact that an antibody response cannot yet be visualized. with the routine flagella test. Consequently, early antibiotic treatment in NB seems to be the correct course of action and over-treatment is not a substantial problem.
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| 3. |
- Normann, Erik, 1966-
(författare)
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Chlamydia pneumoniae in Children - Epidemiology and Clinical Implications
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chlamydia pneumoniae is a human respiratory tract pathogen. Seroepidemiological studies indicate that C. pneumoniae infection is most common in school-aged children and infrequently detected in younger children.The aims of this study were to further elucidate the prevalence of C. pneumoniae in paediatric populations and to describe the clinical implications of these infections.The study population consisted of 367 children with respiratory tract diseases, 453 presumed healthy children at day-care, 69 children undergoing adenoidectomy and 1585 children from a population based cohort. Family members to infected day-care children were investigated. The laboratory methods used were polymerase chain reaction (PCR) on specimen from upper respiratory tract, serology by microimmunofluorescence (MIF), and immunohistochemistry (IHC) on adenoid tissue specimen. Personal data and medical history were obtained by the means of questionnaires and by the study of patient records.In children younger than five years, the prevalence of C. pneumoniae was 17% as detected by PCR. This prevalence started to increase with increasing age from two years of age. The corresponding increase in serology as detected by MIF started at the age of four years. The prevalence at day-care centres varied from 4 to 39%. Both PCR and MIF underestimated the prevalence of C. pneumoniae detected by IHC. Families to infected children were investigated: mothers were more often infected than fathers were.Most C. pneumoniae infections in small children were confined to the upper respiratory tract. These infections were usually mild or asymptomatic. Symptomatic disease may be of prolonged nature. No subsequent illness after C. pneumoniae infection was detected at follow-up after four years. In general, no association between C. pneumoniae and asthma was found, but C. pneumoniae may be of importance for asthma in some susceptible individuals. Previous C. pneumoniae infection reduced the risk for later atopy.In conclusion, C. pneumoniae is a common finding in small children and most often causes relatively mild disease. If the acquisition of this infection early in life will have any implications for future health remains to be investigated.
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