Jarmo Oksi

Complement Evasion by Borrelia burgdorferi: Serum-Resistant Strains Promote C3b Inactivation

ABSTRACT The most characteristic features of the Lyme disease pathogens, theBorrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of time, despite elevated levels of borrelia-specific antibodies in serum and other body fluids. Our aim in the present study was to determine whether B. burgdorferi is able to interfere with complement (C) at the level of C3 by accelerating C3b inactivation and thus to inhibit the amplification of the C cascade. Strains belonging to different genospecies (Borrelia garinii, B. burgdorferi sensu stricto, and Borrelia afzelii) were compared for their sensitivities to normal human serum and abilities to promote factor I-mediated C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains were found to be serum resistant. When the spirochetes were incubated with radiolabeled C3b, factor I-mediated degradation of C3b was observed in the presence of C-resistant B. afzelii(n = 3) and B. burgdorferi sensu stricto (n = 1) strains but not in the presence of C-sensitive B. garinii (n = 7) strains or control bacteria (Escherichia coli,Staphylococcus aureus, and Enterococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors factor H and factor H-like protein 1 (FHL-1) from growth medium and human serum. A novel surface protein with an apparent molecular mass of 35 kDa was found to preferentially bind to the N terminus region of factor H. Thus, the serum-resistant B. burgdorferi s.l. strains can circumvent C attack by binding the C inhibitors factor H and FHL-1 to their surfaces and promoting factor I-mediated C3b degradation.

Elimination of Epidemic Methicillin- Resistant Staphylococcus aureus from a University Hospital and District Institutions, Finland

From August 1991 to October 1992, two successive outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) occurred at a hospital in Finland. During and after these outbreaks, MRSA was diagnosed in 202 persons in our medical district; >100 cases involved epidemic MRSA. When control policies failed to stop the epidemic, more aggressive measures were taken, including continuous staff education, contact isolation for MRSA-positive patients, systematic screening for persons exposed to MRSA, cohort nursing of MRSA-positive and MRSA-exposed patients in epidemic situations, and perception of the 30 medical institutions in that district as one epidemiologic entity brought under surveillance and control of the infection control team of Turku University Hospital. Two major epidemic strains, as well as eight additional strains, were eliminated; we were also able to prevent nosocomial spread of other MRSA strains. Our data show that controlling MRSA is possible if strict measures are taken before the organism becomes endemic. Similar control policies may be successful for dealing with new strains of multiresistant bacteria, such as vancomycin-resistant strains of S. aureus.

Prevalence of Chlamydia pneumoniae and Mycoplasma pneumoniae immunoglobulin G and A antibodies in a healthy Finnish population as analyzed by quantitative enzyme immunoassays.

ABSTRACT Chlamydia pneumoniae and Mycoplasma pneumoniae immunoglobulin G (IgG) and IgA antibody seroprevalence rates and antibody levels related to age and gender were studied. The samples (n = 742) were collected during a nonepidemic period and analyzed by quantitative enzyme immunoassays (EIAs). Seroprevalence to C. pneumoniae was found to increase sharply in young children, and in the 15- to 19-year-old group it reached levels as high as 70 and 60% for IgG and IgA, respectively. After adolescence, seroprevalence showed a transient decrease and then continued to increase, although less dramatically than in early childhood. In the elderly the seroprevalence of IgG antibodies reached 75 and 100% in women and men, respectively. The corresponding rates of IgA antibodies were 73 and 100%. When a randomly selected subgroup of samples (n = 66) was analyzed in parallel by a microimmunofluorescence test and an EIA for C. pneumoniaeIgA antibodies, similar seroprevalence rates were obtained (36 versus 35%). Seroprevalence to M. pneumoniae was already found to increase very sharply in 2- to 4-year-old children, reaching 16% for IgG and 8% for IgA. Seroprevalence to M. pneumoniae also continued to increase in adolescence, but in contrast to that toC. pneumoniae, the increase leveled off at about 40 to 50% in adulthood. In subjects aged over 65 years, prevalence did not exceed 60% for IgG or 35% for IgA. The seroprevalence patterns as well as the medians and variations of levels of C. pneumoniae andM. pneumoniae IgG antibodies were similar to those of corresponding IgA antibodies. Compared to IgG antibodies, IgA antibodies do not seem to be of additional value in the diagnosis of infections caused by these pathogens when single serum specimens are studied.

Anti—Tumor Necrosis Factor—α Treatment Activates Borrelia burgdorferi Spirochetes 4 Weeks after Ceftriaxone Treatment in C3H/He Mice

BACKGROUND The effect of anti-tumor necrosis factor (TNF)-alpha treatment in Borrelia burgdorferi-infected and ceftriaxone-treated C3H/He mice was evaluated. METHODS Mice were infected with B. garinii A218 or B. burgdorferi sensu stricto N40. At 2 weeks of infection, one group was treated simultaneously with ceftriaxone and anti-TNF-alpha, whereas another received ceftriaxone at 2 weeks and anti-TNF-alpha 4 weeks later. One group received ceftriaxone treatment only. Infected and noninfected control groups were sham treated. RESULTS At 14 weeks of infection, B. burgdorferi could not be detected by cultivation or by polymerase chain reaction in tissue samples of any mouse treated with ceftriaxone only. However, spirochetes grew from the tissue samples of one-third of the mice treated with anti-TNF-alpha simultaneously or 4 weeks after ceftriaxone. These activated spirochetes showed ceftriaxone sensitivity rates, plasmid profiles, and virulence rates similar to those of bacteria used to infect the mice. All infected control mice and mice given anti-TNF-alpha only were culture positive. CONCLUSIONS This report shows that, after ceftriaxone treatment for 5 days, a portion of B. burgdorferi-infected mice still have live spirochetes in their body, which are activated by anti-TNF-alpha treatment.

Early dissemination of Borrelia burgdorferi without generalized symptoms in patients with erythema migrans

The diagnosis of erythema migrans (EM) is not always easy, and reports of culture‐ or PCR‐confirmed diagnosis as well as reports of EM with simultaneous disseminated disease are few. Characteristics and incidence of EM in addition to frequency of early dissemination of B. burgdorferi were studied in the archipelago of South‐Western Finland prospectively using questionnaires, skin biopsies and blood samples. Clinical EM was recognized in 82 patients (incidence 148/100000 inhabitants/year). Of skin biopsy samples, 35.5% were positive by PCR (the majority B. garinii), and 21.5% by cultivation (all B. garinii). Of blood samples, 3.8% were positive by PCR, and 7.7% by cultivation. Of the patients, 30.9% were seropositive at the first visit, and 52.9% 3 weeks later. Of the patients with laboratory confirmed diagnosis, the EM lesion was ring‐like in 31.8% and homogenous in 65.9%. Dissemination of B. burgdorferi, based on culture or PCR positivity of blood samples, was detected in 11.0% of the patients. The frequency of generalized symptoms was nearly the same in patients with as in those without dissemination (22.2% vs 27.4%). Only 21.4% of the patients with culture‐positive EM recalled a previous tick bite at the site of the EM lesion. We conclude that EM lesions are more often homogenous than ring‐like. B. burgdorferi may disseminate early without generalized symptoms.

Prevalence of granulocytic Ehrlichia and Borrelia burgdorferi sensu lato in Ixodes ricinus ticks collected from Southwestern Finland and from Vormsi Island in Estonia

Altogether, 343 adult and 111 nymphal Ixodes ricinus ticks collected from parks in Turku and suburban and rural islands of the Turku archipelago, Finland, and 100 adult I. ricinus ticks collected from Vormsi Island, Estonia, were included in this study. Using the polymerase chain reaction the ticks were examined for 16S rDNA of the Ehrlichia phagocytophila genogroup and for Borrelia burgdorferi sensu lato recA and flagellin genes. None of the Finnish ticks was found to be infected with E. phagocytophila, whereas 3% of the Estonian ticks were positive for this organism. The rate of Finnish ticks infected with B. burgdorferi sensu lato varied from 0% to 11.6% (mean 5%; 9% for adult and 4% for nymphal ticks). The corresponding rate for Estonian ticks was 15%. Borrelia afzelii was the most common genospecies in both Finnish (2.6%) and Estonian (12%) ticks. B. burgdorferi sensu stricto was detected in 2.0% of the Finnish ticks, but in none of the Estonian ticks. These results suggest that the E. phagocytophila genogroup is very rare in Finnish ticks, although the ticks were collected from an area endemic for Lyme borreliosis. In Estonia, E. phagocytophila is found in ticks and may cause disease.

Persistence of borrelial DNA in the joints of Borrelia burgdorferi-infected mice after ceftriaxone treatment.

Yrjänäinen H, Hytönen J, Hartiala P, Oksi J, Viljanen MK. Persistence of borrelial DNA in the joints of Borrelia burgdorferi‐infected mice after ceftriaxone treatment. APMIS 2010; 118: 665–73.

18 F-FDG positron emission tomography/computed tomography in infective endocarditis

BackgroundThe diagnosis of infective endocarditis (IE), especially the diagnosis of prosthetic valve endocarditis (PVE) is challenging since echocardiographic findings are often scarce in the early phase of the disease. We studied the use of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in IE.MethodsSixteen patients with suspected PVE and 7 patients with NVE underwent visual evaluation of 18F-FDG-PET/CT. 18F-FDG uptake was measured also semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). The modified Duke criteria were used as a reference.ResultsThere was strong, focal 18F-FDG uptake in the area of the affected valve in all 6 cases of definite PVE, in 3 of 5 possible PVE cases, and in 2 of 5 rejected cases. In all patients with definite PVE, SUVmax of the affected valve was higher than 4 and TBR higher than 1.8. In contrast to PVE, only 1 of 7 patients with NVE had uptake of 18F-FDG by PET/CT in the valve area. Embolic infectious foci were detected in 58% of the patients with definite IE.Conclusions18F-FDG-PET/CT appears to be a sensitive method for the detection of paravalvular infection associated with PVE. Instead, the sensitivity of PET/CT is limited in NVE.

Cat Scratch Disease Caused by Bartonella grahamii in an Immunocompromised Patient

ABSTRACT Bartonella grahamii colonizes rodents worldwide and has been detected in questing Ixodes ricinus ticks. Here, the first human B. grahamii infection confirmed by multilocus sequence typing is reported. The route of transmission and clinical picture of the patient are similar to those seen in patients with cat scratch disease, which is typically diagnosed as a Bartonella henselae infection.

Borreliosis : recent research, diagnosis, and management

Lyme borreliosis (LB) is a tick‐borne infection caused by the spirochete Borrelia burgdorferi sensu lato. The disease covers a wide spectrum of clinical manifestations affecting the skin, nervous and musculoskeletal systems, the heart, and the eyes. The diagnosis must be based on clinical suspicion and on symptoms and signs observed during a thorough interview and examination of the patient. Laboratory results either support or oppose the conclusions that are drawn from history and clinical examination. Antibiotic therapy is curative in most patients with LB. Unfortunately, some patients develop chronic symptoms, such as arthritis, that do not respond to antibiotics. In these patients, treatment with non‐steroidal anti‐inflammatory drugs or corticosteroids is recommended, while the role of immunomodulatory drugs, such as tumour necrosis factor (TNF)‐α inhibitors, remains open. In this review we focus, after presenting the history and basics of LB, on the pathogenesis, diagnosis, and treatment of LB, as well as on recent advances in selected aspects of the field.