Rolf Gustafson

Tick-borne encephalitis in Sweden and climate change

BACKGROUND The incidence of tick-borne encephalitis (TBE) in Sweden has substantially increased since the mid-1980s. During the same period the climate has become milder and ticks have become more abundant. We investigated whether there is a link between the change in climate and the increase in incidence of TBE. METHODS Since the late 1950s all cases of encephalitis admitted in Stockholm County have been serologically tested for TBE. We analysed the period 1960-98 with multiple regressions. The number of days per season with temperatures of known importance for tick prevalence and pathogen transmission were studied. 2 years of temperature data were related to each TBE incidence rate to account for the ticks long life-span. FINDINGS Increases in disease incidence was significantly related (R(2)=0.58; p<0.0001) to a combination of two consecutive mild winters, temperatures favouring spring development (8-10 degrees C) and extended autumn activity (5-8 degrees C) in the year prior to the incidence year, and temperatures allowing tick activity (5-8 degrees C) early in the incidence year. INTERPRETATIONS The findings indicate that the increase in TBE incidence since the mid-1980s is related to the periods change towards milder winters and early arrival of spring. Other factors may have influenced TBE incidence such as more people in endemic locations, and increases in host animal populations; factors which are partly climate related. Access to TBE vaccination since 1986 and increased awareness of ticks might have caused an underestimation of the links found. Our findings also suggest that the incidence of other tick-borne zoonoses might have been affected by the milder climate.

Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs

Immunoglobulins (IgG) as replacement therapy in primary antibody deficiencies can be given as intramuscular injections, or as intravenous or subcutaneous infusions. Our aims were to obtain information on the frequency of adverse systemic reactions during subcutaneous therapy, the occurrence and intensity of tissue reactions at the infusion sites, and serum IgG changes. Furthermore, we compared costs between the different replacement regimes. Our study included 165 patients (69 women, 96 men, aged 13-76 years) with primary hypogammaglobulinaemia or IgG-subclass deficiencies. Data were compiled from questionnaires filled in by the patients and from their medical records. 33,168 subcutaneous infusions (27,030 in home therapy) had been given. 106 (of which 16 were at home) adverse systemic reactions (100 mild, 6 moderate) were recorded in 28 patients (17%). No severe or anaphylactoid reactions occurred. Despite large immunoglobulin volumes given during 434 patient years (28,480 infusions), no signs have been found that indicate the transmission of hepatitis virus. Transient tissue reactions occurred at the infusion sites but were not troublesome to most patients and we found significant increases in mean serum IgG. The use of subcutaneous instead of intravenous infusions at home would reduce the yearly cost per patient for the health-care sector by US

Prevalence of Tick-borne Encephalitis and Lyme Borreliosis in a Defined Swedish Population

10,100 in Sweden alone. We conclude that subcutaneous administration of IgG is a safe and convenient method of providing immunoglobulins. We were able to reach serum IgG concentrations similar to those by the intravenous therapy and we found that the method could also be used successfully in patients with previous severe or anaphylactoid reactions to intramuscular injections.

Two-year survey of the incidence of lyme borreliosis and tick-borne encephalitis in a high-risk population in Sweden

Sera from 346 individuals living on Lisö, an area south of Stockholm, endemic for tick-borne encephalitis (TBE) and Lyme borreliosis, were tested for antibody activity to TBE-virus (TBEV) and Borrelia burgdorferi, using a sonicate antigen, by haemagglutination-inhibition and ELISA, respectively. 10/346 (3%) individuals had a history of previous serologically confirmed TBE with encephalitic symptoms, and 33/346 (10%) had a history of previous erythema chronicum migrans (ECM). Four individuals (1%) had been treated for neuroborreliosis and another 4 (1%) for acrodermatitis chronica atrophicans (ACA). Antibodies to TBEV and B. burgdorferi were detected in 40/346 (12%) and 89/346 (26%) individuals, respectively. The seroprevalence of Lyme borreliosis increased with age, time spent on Lisö, and number of reported tick-bites. For TBE there was a correlation between seropositivity and time spent on Lisö only. In sera from 50 healthy blood-donors, living in a non-endemic area, no antibody activity to TBEV could be detected and only 1/50 (2%) had antibodies to borrelia. In sera from 150 age and sex matched control individuals, living in the city of Stockholm, antibody activity to TBEV and borrelia was found in 8/150 (5%) and 13/150 (9%), respectively.

Prevalence of Borrelia burgdorferi sensu lato infection in Ixodes ricinus in Sweden

A survey was made over a two-year period (September 1987 to August 1989) of a population living in an area endemic for Lyme borreliosis and tick-borne encephalitis in Sweden. For each patient a blood sample was collected and a questionnaire completed annually. All sera were tested for an antibody response toBorrelia burgdorferi in an EIA using sonicated antigen and for an antibody response to the tick-borne encephalitis virus using an EIA and a haemagglutination inhibition test. Antibodies toBorrelia burgdorferi and tick-borne encephalitis virus were detected in 89 (25.7 %) and 40 (11.6 %) respectively of 346 samples collected in August 1987. In the first year of the study 14 of 303 subjects (4.6 %) developed Lyme borreliosis and in the second year 9 of 277 subjects (3.2 %). A significant increase in the antibody titre forBorrelia burgdorferi was seen in 14 of 303 (4.6 %) subjects in the first year and 8 of 277 (2.9 %) subjects in the second year. An earlier episode of Lyme borreliosis or an elevated antibody titre did not seem to protect against reinfection. One case of tick-borne encephalitis was seen each year. Seroconversion for tick-borne encephalitis virus was found in 3 of 258 (1.2 %) subjects in the first year and 5 of 211 (2.4 %) in the second year, excluding subjects who had undergone successful immunisation or had earlier been hospitalised for tick-borne encephalitis. The study thus demonstrated a high yearly incidence of tick-borne infections in a population at risk.

Characterization of Haemophilus influenzae isolates from the respiratory tract of patients with primary antibody deficiencies: evidence for persistent colonizations.

Between 1988-1991, a total of 3,141 Ixodes ricinus ticks, 2,740 adults and 401 nymphs, was collected from different localities in 23 of the 25 provinces of Sweden. The ticks were identified, dissected and examined for the presence of Borrelia spirochetes. Indirect immunofluorescence was performed, using an antiserum obtained from rabbits, immunized with sonicated, whole Borrelia burgdorferi spirochetes isolated from Swedish Ixodes ricinus ticks. Borrelia-positive I. ricinus were found in all 23 provinces. The prevalence of infection in adults ranged from 3% in Jämtland to 23% in Södermanland. In nymphs, the infection prevalence ranged from 0% in 9 provinces to 15% in Södermanland. A significantly greater proportion of the adult ticks were found to be positive for Borrelia in the southern and central parts of Sweden as compared to the northern part (Norrland). No significant difference in prevalence could be demonstrated between the western and eastern parts of Sweden. On average, 10% of the nymphs and 15% of the adult I. ricinus were positive for Borrelia. Of 41 non-I. ricinus ticks, none was positive for Borrelia. This study shows that Borrelia burgdorferi sensu lato is present throughout the distributional area of I. ricinus in Sweden. This should lead to increased awareness of signs and symptoms compatible with Lyme borreliosis in persons living in or visiting areas where I. ricinus is present.

Clinical Manifestations and Antibody Prevalence of Lyme Borreliosis and Tick-borne Encephalitis in Sweden: A Study in Five Endemic Areas Close to Stockholm

A total of 117 consecutive patients with primary antibody deficiencies were followed for up to 5 years with regard to acute respiratory tract infections. Nontypeable Haemophilus influenzae (NTHI) was the sole pathogen in 61% (202/330) of the samples from which a potential pathogen was recovered. Common variable immunodeficiency (CVI) was the most prevalent condition (27/39 patients) in the group where H. influenzae was isolated. In patients where H. influenzae was not found only 9/78 patients had CVI. 49 of these 78 patients had isolated IgG3 or IgA deficiency. Both of these entities seemed to be associated with a lower prevalence of NTHI infections. 13 of 18 patients with at least 2 isolates of NTHI were colonized with the same strain from 3 to 43 months as shown by total genomic DNA-fingerprinting. Recurrent symptomatic infections occurred in these patients despite substitution therapy with gammaglobulins and repeated antibiotic treatments. All but 2 of the 224 H. influenzae isolates were beta-lactamase negative and sensitive to ampicillin. The use of 10 lipopolysaccharide-specific monoclonal antibodies in a whole cell ELISA showed that the LPS-epitopes on the 224 H. influenzae isolates from the hypogammaglobulinemic group were very similar to 499 NTHI isolates from immunocompetent patients with respiratory infections. One may therefore conclude that i) patients with CVI, were prone to be permanently colonized with NTHI, and ii) the colonizing bacteria were ordinary strains showing the same LPS-phenotypes as those strains that cause acute respiratory tract infections in immunocompetent individuals.

Antibody Prevalence and Clinical Manifestations of Lyme Borreliosis and Tick-borne Encephalitis in Swedish Orienteers

Five populations, including 903 individuals living in 5 different areas close to Stockholm, were studied with regard to clinical manifestations and antibody prevalence of Lyme borreliosis (LB) and tick-borne encephalitis (TBE). The study areas involved 4 groups of islands in the Baltic Sea and 1 island in Lake Mälaren. Serum samples from each individual were tested for antibody activity to Borrelia burgdorferi using a sonicated whole spirochete antigen in an ELISA, and to TBE-virus (TBEV) by ELISA and haemagglutination inhibition. A history of LB was reported by 1-21% and antibodies to Borrelia burgdorferi were found in 7-29% of the participants from the various areas. An increasing seroprevalence with age was seen. In sera from 3 different control groups, including 502 individuals living in non-endemic areas, antibodies to Borrelia burgdorferi were detected in 1-2% and from 1 control group including 150 individuals living in the city of Stockholm, in 9%. A history of TBE was reported by 0-6% of the individuals and in non-immunized individuals seropositivity was seen in 4-22%, depending on the area investigated. No antibody activity to TBEV could be detected in sera from persons in the 3 control groups living in non-endemic areas, whereas 5% of the controls from Stockholm were found to be positive. The prevalence rates of antibodies to TBEV in persons vaccinated against TBE were 40%, 53% and 79% after 1, 2 and 3 injections, respectively.

Impact of IgG Replacement Therapy and Antibiotic Treatment on the Colonization of Non-encapsulated Haemophilus Influenzae in the Nasopharynx in Patients with Hypogammaglobulinaemia

Antibody prevalence and clinical manifestations of Lyme borreliosis (LB) and tick-borne encephalitis (TBE) were studied in 362 orienteers from the county of Stockholm during a large relay race in October 1990. From all participating orienteers, a blood sample was collected and a questionnaire completed. Antibody activity to Borrelia burgdorferi was measured using a sonicated whole spirochete antigen in an ELISA, and to TBE virus (TBEV) by ELISA and haemagglutination inhibition (HI) test. A past history of LB was reported by 6% of the orienteers and antibodies to B. burgdorferi were found in 9%. Antibody reactivity to B. burgdorferi was found in 1-2% of the sera from 3 different control groups comprising 502 persons living in non-endemic areas. The corresponding value was 9% in sera from a fourth control group consisting of 150 persons living in the city of Stockholm. A past history of TBE was reported by 1 orienteer (0.3%) and detectable antibodies to TBEV in non-immunized individuals were found in 1%. No antibody activity to TBEV could be detected in sera from the control individuals living in the 3 non-endemic areas, but in 5% of the controls from Stockholm. In this study, there was no indication that frequent or severe manifestations of LB or TBE are common among orienteers in Sweden.

Evaluation of a Bioluminescence Assay for the Detection of Bacteriuria

Non-typable Haemophilus influenzae (NTHI) and Streptococcus pneumoniae are regarded as the main pathogens in patients with humoral immunodeficiency. These patients have been given IgG replacement therapy since the 1950s. However, a number of individuals still suffer from recurrent episodes of respiratory tract infections. Nasopharyngeal cultures were obtained on a regular basis over a 3?6-month period from 11 patients with common variable immunodeficiency disease in 1989 and 1998. The proportion of cultures positive for NTHI decreased from 56% in 1989?90 to 16% in 1998?99 ( p < 0.003). After 9 y of IgG therapy, 7 of the 11 patients were free from NTHI in the nasopharynx. Specific NTHI strains were analysed by pulsed-field gel electrophoresis and compared, with regard to genetic relatedness, on an intra-individual basis. In 1 patient the same NTHI strain was found in both 1989 and 1999. The apparent absence of NTHI from the nasopharynx in most of the patients was assumed to be due to subcutaneous IgG treatment, as well as adequate antibiotic treatment.Non-typable Haemophilus influenzae (NTHI) and Streptococcus pneumoniae are regarded as the main pathogens in patients with humoral immunodeficiency. These patients have been given IgG replacement therapy since the 1950s. However, a number of individuals still suffer from recurrent episodes of respiratory tract infections. Nasopharyngeal cultures were obtained on a regular basis over a 3-6-month period from 11 patients with common variable immunodeficiency disease in 1989 and 1998. The proportion of cultures positive for NTHI decreased from 56% in 1989-90 to 16% in 1998-99 (p < 0.003). After 9 y of IgG therapy, 7 of the 11 patients were free from NTHI in the nasopharynx. Specific NTHI strains were analysed by pulsed-field gel electrophoresis and compared, with regard to genetic relatedness, on an intra-individual basis. In 1 patient the same NTHI strain was found in both 1989 and 1999. The apparent absence of NTHI from the nasopharynx in most of the patients was assumed to be due to subcutaneous IgG treatment, as well as adequate antibiotic treatment.