Ragnar Norrby

An Epidemiologic Study of Lyme Disease in Southern Sweden

BACKGROUND Lyme disease is the most common vector-borne infection in some temperate regions of the Northern Hemisphere. However, for most areas of endemic disease reliable epidemiologic data are sparse. METHODS Over a one-year period, we conducted a prospective, population-based survey of cases of Lyme disease in southern Sweden. The diagnosis was made on the basis of the presence of erythema migrans at least 5 cm in diameter or characteristic clinical manifestations such as arthritis, neuroborreliosis, and carditis. RESULTS We identified 1471 patients with Lyme disease, for an overall annual incidence of 69 cases per 100,000 inhabitants. The incidence varied markedly according to geographic region, and there were several areas where disease was widely prevalent. The incidence varied according to age, with the highest rates among people 5 to 9 and 60 to 74 years of age, but not according to sex. The most frequent clinical manifestation was erythema migrans (seen in 77 percent of all cases), followed by neuroborreliosis (16 percent) and arthritis (7 percent). Carditis was rare. A preceding tick bite was reported by 79 percent of the patients. Bites in the head and neck region were more common among children than among adults and were associated with an increased risk of neuroborreliosis. CONCLUSIONS Lyme disease is very common in southern Sweden, with a relatively high frequency of neurologic complications and arthritis. With the exception of the low incidence of carditis, the pattern of disease we found in Sweden was similar to that reported in the United States.

Characterization of Lyme Borreliosis Isolates from Patients with Erythema Migrans and Neuroborreliosis in Southern Sweden

ABSTRACT Southern Sweden is an area of Lyme borreliosis (LB) endemicity, with an incidence of 69 cases per 100,000 inhabitants. The most frequent clinical manifestations are erythema migrans (77%) and neuroborreliosis (16%). There was no record of humanBorrelia strains being isolated from patients in this region before the prospective study reported here. Borreliaspirochetes were isolated from skin and cerebrospinal fluid (CSF) from LB patients living in the region. A total of 39 strains were characterized by OspA serotype analysis, species-specific PCR, and signature nucleotide analysis of the 16S rRNA gene. Of 33 skin isolates, 31 (93.9%) were Borrelia afzelii strains and 2 (6.1%) were Borrelia garinii strains. Of six CSF isolates, five (83.3%) were B. garinii and one (16.7%) wasB. afzelii. Neither Borrelia burgdorferisensu stricto strains nor multiple infections were observed. TheB. afzelii isolates were of OspA serotype 2. ThreeB. garinii strains were of OspA serotype 5, and the remaining four strains were of OspA serotype 6. All of theB. garinii strains belonged to the same 16S ribosomal DNA ribotype class. Our findings agree with earlier findings from other geographic regions in Europe where B. afzelii and B. garinii have been recovered predominately from skin and CSF cultures, respectively. To further study the possible presence in Sweden of the genotype B. burgdorferi sensu stricto, which is known to be present in Europe and to occur predominately in patients with Lyme arthritis, molecular detection of Borrelia-specific DNA in synovial samples from Lyme arthritis patients should be performed.

Symptomatic urinary tract infection in women in primary health care: Bacteriological, clinical and diagnostic aspects in relation to host response to infection

OBJECTIVE To evaluate rapid diagnostic tests for bacteriuria in women with symptoms of urinary tract infection (UTI), and to analyse bacteriological and clinical findings in relation to host response to infection. DESIGN Prospective study of symptomatic UTI in women. SETTING Primary health care centres. PATIENTS 819 women with signs and symptoms suggestive of UTI. MAIN OUTCOME MEASURES History of UTI and clinical findings were recorded. After randomization but before antibiotic treatment, urine specimens were analysed for pyuria by sediment microscopy and for nitrite using a test strip, and cultures were performed. The systemic inflammatory response was assessed by C-reactive protein (CRP), erythrocyte sedimentation rate, and total white blood cell count. RESULTS The combined use of tests for pyuria and nitrite resulted in a high sensitivity (0.93) and efficacy (0.85) when the prevalence of bacteriuria was 0.89. Escherichia coli and Staphylococcus saprophyticus accounted for 93% of the urinary isolates. Significantly more patients infected with S. saprophyticus than E. coli complained of dysuria (p < 0.05), frequency (p < 0.05) or flank pain (p < 0.01). CRP agreed best with the clinical diagnosis of acute pyelonephritis. CONCLUSIONS In women with a high probability of bacteriuria, i.e. those with symptoms of lower UTI, examination for pyuria and urinary nitrite offers high diagnostic efficacy. If either or both tests are positive urine cultures can be omitted.

Three major Lyme Borrelia genospecies (Borrelia burgdorferi sensu stricto, B. afzelii and B. garinii) identified by PCR in cerebrospinal fluid from patients with neuroborreliosis in Sweden.

The Lyme Borrelia genospecies Borrelia afzelii and B. garinii have previously been isolated using a culture method in Swedish patients with Lyme borreliosis (LB). There are reports suggesting that the genospecies distribution in human tissue specimens as determined by molecular methods is different from that obtained by culture. In the present study, we developed a nested PCR for detection of Lyme Borrelia-specific DNA in cerebrospinal fluid from Swedish patients with LB. The genospecies were subsequently identified by sequence analysis in a total of 7 PCR-positive patients. Two sequences were identified as B. burgdorferi sensu stricto (s. s.), 1 as B. afzelii and 4 as B. garinii. These are the first reported cases in which B. burgdorferi s. s. has been shown to be the causative agent of human LB in Sweden. The results of our study confirm that the use of direct molecular analytical methods for Borrelia genospecies identification in clinical specimens can provide epidemiological information additional to that obtained by culture.

Differentiation of human serum samples by surface plasmon resonance monitoring of the integral glycoprotein interaction with a lectin panel

Bacterial infection and inflammation result in massive changes in serum glycoproteins. These changes were investigated by the interaction of the saccharide glycoprotein moiety with lectins. A panel of eight lectins (Canavalia ensiformis, Bandeiraea simplicifolia BS-I, Arachis hypogaea, Phytolacca americana, Phaseolus vulgaris, Artocarpus integrifolia, Triticum vulgaris and Pisum sativum) was used to differentiate human serum glycoproteins obtained from patients with various bacterial infections. Lectin functionalised sensing layers were created on gold-coated wafers and lectin-glycoprotein interactions were monitored by surface plasmon resonance. The interaction of the lectin panel with serum glycoproteins produces unique patterns. Principal component analysis (PCA) was used to analyse the patterns. The actual panel of eight lectins enabled discrimination between sera obtained from patients sick with bacterial infection and healthy patients. Extended lectin panels have the potential to distinguish between types of bacterial infection and identify specific disease state. (Less)

Serotype Distribution of Streptococcus pneumoniae Strains Isolated from Blood and Cerebrospinal Fluid in Sweden

215 strains of Streptococcus pneumoniae isolated from blood or cerebrospinal fluid at 3 different laboratories in Sweden were serotyped by coagglutination and subtyped by the capsular reaction test. 78% of the strains belonged to serotypes which are included in or completely cross-immunogenic with serotypes included in the 14-valent vaccine while serotypes included in the 23-valent vaccine covered 89% of the isolates. Types 7F, 14 and 33F, which cannot be detected by counterimmunoelectrophoresis constituted 19% of all strains.

Microflora Changes with Norfloxacin and Pivmecillinam in Women with Recurrent Urinary Tract Infection

ABSTRACT Similar changes in the periurethral and vaginal microflora were observed in 19 women with recurrent urinary tract infection following treatment with norfloxacin (NOR) or pivmecillinam (PIV). Escherichia coli strains were suppressed by both treatments. Staphylococcus spp. and enterococci colony counts increased following PIV treatment in the periurethral flora but remained stable with NOR.

Differential Immune Response to the Variable Surface Loop Antigen of P66 of Borrelia burgdorferi Sensu Lato Species in Geographically Diverse Populations of Lyme Borreliosis Patients

ABSTRACT We have studied the immune response to a variable surface-exposed loop region of the P66 outer membrane protein from Borrelia burgdorferi sensu lato by using an enzyme immunoassay. Lyme borreliosis populations found in North America and Sweden were preferentially more seroreactive to P66 from their respective regional species, namely, B. burgdorferi sensu stricto and B. garinii and B. afzelii, respectively.

Renal concentrating capacity in female outpatients with symptomatic urinary tract infection

Objective. Renal concentrating capacity (RCC) has been used as a tool in the diagnosis of the site of urinary tract infection (UTI). In this study, RCC was measured in women with symptoms of UTI in relation to the clinical picture and the bacterial species isolated. Material and methods. In 633 outpatients aged ≥18 years with symptoms of UTI, a renal concentration test with desmopressin was performed at baseline. The test was repeated after antibiotic treatment in a subset of patients with osmolality values below the reference levels at entry. The bacterial species were identified and patients were classified as having either pyelonephritis or cystitis. Results. RCC was reduced in patients infected with Escherichia coli or Staphylococcus saprophyticus compared to those who had negative urine cultures and increased after antibiotic treatment. Patients with symptoms of both pyelonephritis and cystitis had reduced RCC: 44/68 (65%) and 205/457 (45%), respectively. Conclusions. These findings demonstrate a considerable overlap in RCC between patients with pyelonephritis and cystitis, making the osmolality test unreliable for the purpose of diagnosis of the site of UTI.