[Interferon inductors in treatment of associative forms of tick-borne infection in children].

Thirty three children with associative forms of thick-borne infection (thick-borne encephalitis with ixodic borreliosis) were clinically observed. The disease was characterized by subfebrile temperature, moderate intoxication, rare erythema (39.5%) and frequent cardiovascular disorders with development of Lyme carditis (32.6 +/- 7.2%) and further rise of hepatomegalia in the diseases dynamics and development of meningeal symptoms. There were observed changes in the cytokine spectrum, characterized by INF-gamma high levels, and hypersecretion of the whole spectrum cytokines in the dynamics, that provided the Th2 type immune response. High clinicoimmunological efficacy of the complex therapy with cycloferon as an immunomodulator providing more balanced production of pro- and anti-inflammatory cytokines (IL-1alpha, INF-gamma and IL-10) was shown.

Anti-interleukin-15 prevents arthritis in Borrelia-vaccinated and -infected mice.

We showed previously that interleukin-17 (IL-17) plays a significant role in the induction of arthritis associated with Borrelia vaccination and challenge. Little information, however, is available about the chain of immunologic events that leads to the release of IL-17. The production of IL-17 has been linked to stimulation of memory cells by IL-15. Therefore, we hypothesized that IL-15 is involved in the induction of arthritis associated with Borrelia vaccination and infection of mice. Here we present evidence that treatment of Borrelia-vaccinated and -infected mice with anti-IL-15 antibody prevents swelling of the hind paws. More importantly, both anti-IL-15 antibody- and recombinant IL-15 receptor alpha-treated Borrelia-vaccinated and -infected mice were free of major histopathologic indications of arthritis, including hyperplasia, hypertrophy, and vilus formation of the synovium. Similarly, the synovial space and perisynovium were free of inflammatory cells. By contrast, the synovium of nontreated Borrelia-vaccinated and -infected mice had overt hyperplasia, hypertrophy, and vilus formation. Moreover, the synovial space and perisynovium were infiltrated with neutrophils, macrophages, and lymphocytes. Finally, we show that recombinant IL-15 stimulates the release of IL-17 from lymph node cells obtained near the arthritic site. These results suggest that IL-15 plays a major role in orchestrating IL-17 induction of arthritis associated with Borrelia-vaccinated and -infected mice.

In vitro culture of Borrelia garinii results in loss of flagella and decreased invasiveness.

A virulent, low-passage culture of a tick-derived strain of Borrelia garinii was subjected to serial in vitro passages, from which inoculations were made into C3H/HeN mice. A full display of pathogenicity was observed through passage 4, as measured by cultures of ear punch biopsy samples and internal organs and determination of tibiotarsal joint swelling. Decreased dissemination through skin and infection of internal organs were observed beginning at passage 6. These losses correlated with both the selection of clones harboring 21% less flagella than the parent strain, as seen by electron microscopy, and loss of the motility of the higher passages, as demonstrated by a swarm assay. However, during the chronic phase (3 months after infection), spirochetes were cultured from the bladder and kidney of a mouse inoculated with passage 12. The kidney isolate had the same number of flagella and motility as the original low-passage isolate. Although we can't exclude the possibility that other subtle variations may be arising given the uncloned nature of the isolate, we have found a strong association between loss of flagella and decreased invasiveness. Arthritogenicity progressively decreased with passages, so that only 12.5% of chronically infected mice inoculated with passage 29 still presented with joint swelling, concurrent with a decrease in the staining intensity in a Southern blot with a vlsE-based probe. These results suggest a multifactorial model in which the number of flagella drives the invasiveness of this agent, while plasmid-associated factors are responsible for triggering arthritogenicity.

Borrelia lonestari infection after a bite by an Amblyomma americanum tick.

Erythematous rashes that are suggestive of early Lyme disease have been associated with the bite of Amblyomma americanum ticks, particularly in the southern United States. However, Borrelia burgdorferi, the causative agent of Lyme disease, has not been cultured from skin biopsy specimens from these patients, and diagnostic serum antibodies usually have not been found. Borrelia lonestari sp nov, an uncultured spirochete, has been detected in A. americanum ticks by DNA amplification techniques, but its role in human illness is unknown. We observed erythema migrans in a patient with an attached A. americanum tick. DNA amplification of the flagellin gene flaB produced B. lonestari sequences from the skin of the patient that were identical to those found in the attached tick. B. lonestari is a probable cause of erythema migrans in humans.

Neuroborreliosis.

Neuroborreliosis, a manifestation of infection with the spirochete Borellia burgdorferi, has become the most frequently recognised arthropod-borne infection of the nervous system in Europe and the USA. The best criterion of an early infection with B. burgdorferi is erythema migrans (EM), but this is present in only about 40-60% of patients with validated borreliosis. Therefore use of the duration of the disease as a classification criterion for neuroborreliosis is increasing, the chronic form being distinguished from the acute when symptoms persist for more than 6 months. The diverse manifestations of neuroborreliosis require that it be included in the differential diagnosis of many neurological disorders. In Europe, meningopolyradiculoneuritis (Bannwarth's syndrome) represents the most common manifestation of acute neuroborreliosis, with the facial nerve being affected much more frequently than the other cranial nerves. Clinical symptoms affecting the central nervous system are rarely observed and then mostly in chronic courses. By far the most common manifestation of chronic neuroborreliosis is encephalomyelitis with spastic-ataxic disturbances and a disturbance of micturition. The current diagnosis of neuroborreliosis is a clinical one, which has to be confirmed by laboratory testing. In most patients, examination of the cerebrospinal fluid (CSF) reveals lymphocytic pleocytosis, damage to the blood-CSF-barrier and an intrathecal synthesis immunoglobulin (Ig) M, IgG, and sometimes IgA. Confirmation of a borrelial infection of the nervous system requires demonstration of an intrathecal synthesis of borrelial-specific antibodies in the CSF or detection of borrelial DNA in the CSF by polymerase chain reaction (PCR). There is no generally accepted therapeutic regime for the treatment of neuroborreliosis, but recent studies have shown ceftriaxone 2 g/day and cefotaxime 6 g/day to be effective in acute and chronic courses. Penicillin G 20 mega units/day and doxycycline 200 mg/day may be suitable for uncomplicated meningopolyneuritis, without involvement of the central nervous system. The durationof treatment--at least 2 weeks in the acute forms and 3 weeks in the chronic forms of neuroborreliosis--is very important for successful treatment. Corticosteroids are recommended only for patients with severe pain that does not respond to antibiotics an analgesics.

T cell response to Borrelia garinii, Borrelia afzelii, and Borrelia japonica in various congenic mouse strains.

The infectivity and T cell response to Borrelia garinii SIKA2, Borrelia afzelii BFOX, and Borrelia japonica 0612, the organisms that cause Lyme disease in Japan, were examined in various inbred and congenic strains of mice. Infectivity differed among the species: B. garinii SIKA2 and B. afzelii BFOX were each able to infect 90% to 100% of C3H/He mice; B. japonica 0612 was able to infect only 20% of C3H/He mice. The pattern of infectivity to various inbred and congenic strains of mice may influence the pathogenicity of the organism and the clinical signs of Lyme disease. Cross-reactivity between Borrelia antigens was observed, but there was no cross-reactivity between Borrelia antigens and Leptospira antigens. We evaluated the genetic control of the delayed-type hypersensitivity (DTH) reaction in the form of footpad swelling produced by Borrelia antigens using viable or sonicated bacteria as sensitization. Differences in strains of mice infected by viable antigen were observed. However, all strains of mice showed a strong DTH reaction using sonicated antigens without genetic background. A DTH reaction in the form of footpad swelling did not appear to be associated with genetic background. The footpad reaction was mediated by CD4+8- and Ia- T cells, as revealed by in vitro monoclonal antibody treatment. However, CD8+ T cells did not suppress footpad swelling. These results indicate that many antigenic epitopes of the Borrelia spirochete can stimulate the DTH reaction.

[The role of ticks and small mammals in propagation of Borrelia burgdorferi and Babesia microti]. / Rola kleszczy i drobnych ssaków w szerzeniu sie zakazen Borrelia burgdorferi i Babesia microti.

In the present article, the role of ticks and small mammals in the epidemiology of Borrelia burgdorferi and Babesia microti is reviewed. Contrary to other European countries, the zoonotic reservoir of both potogens in Poland is unknown. In particular a preliminary analysis of B. burgdorferi and B. microti infections of rodents in District of Mazury Lake is presented.

Epidemiology and clinical similarities of human spirochetal diseases.

Lyme disease, first identified in 1975, is the most recently recognized of the seven human spirochetal diseases; the evolving clinical picture of Lyme disease indicates it shares many features with the other diseases. These similarities are striking in view of the diverse epidemiology of the seven diseases, which are caused by Treponema species (spread by human-to-human contact) or Leptospira or Borrelia species (zoonoses). These similarities include the following: (1) skin or mucous membrane as portal of entry; (2) spirochetemia early in the course of disease, with wide dissemination through tissue and body fluid; and (3) one or more subsequent stages of disease, often with intervening latent periods. Lyme disease shares with many spirochetal diseases a tropism for skin and neurologic and cardiovascular manifestations, whereas chronic arthritis is unique to Lyme disease. These similarities and dissimilarities offer opportunities to discover which properties unique to the pathogenic spirochetes are responsible for clinical manifestations and suggest that certain clinical features of patients with spirochetal diseases other than Lyme disease may someday be recognized in patients with Lyme disease.

[Ocular findings in tick borreliosis]. / Augenbefunde bei Zecken-Borreliose.

Tick-transmitted borreliosis is by no means a rare infectious disease. It is found especially in southern parts of Germany. Eyes are seldom affected. The disease can lead to nerve palsy of the eye muscles. One case of panophthalmitis and one of optic disk edema have been described. The authors found a bilateral palsy of the abducens nerve in one patient with tick-transmitted borreliosis. Motility normalized under therapy with highly-dosed penicillin.

Prospects for suppressing transmission of Lyme disease.

A variety of methods have been developed to prevent human infection by the Lyme disease spirochete in the northeastern United States, mainly based on the observations that nymphal Ixodes dammini serve as vector, that deer serve as hosts for the reproductive stage of this tick, that white-footed mice serve as the reservoir of infection, and that nymphs are most abundant in early summer and must attach for 2 days before infection is transmitted. Methods for personal protection included seasonal avoidance of infested sites, the use of repellants, and prompt removal of attached ticks. Destruction of mouse habitat, but not of mice, was locally effective. Nondestructive acaricidal treatment of deer proved ineffective, but the elimination of these hosts resulted in reduced transmission after several years. Treatment of mice by means of acaricide-impregnated bedding material effectively reduced transmission.

[Borrelia burgdorferi encephalomyelitis]. / Formes encéphalomyélitiques de l'infection a Borrelia burgdorferi.

We report two patients with chronic encephalomyelitis due to Borrelia burgdorferi in whom the definite diagnosis was delayed because of atypical clinical features. The first patient presented with chronic spastic paraparesis, slight ataxia and nystagmus of several years' duration. A tentative diagnosis of multiple sclerosis was made in spite of important abnormalities of the CSF biological characteristics. The second patient presented with an acute aphasia and a bilateral Babinski's sign. He was thought to suffer from benign herpetic meningoencephalitis. Several months later, as the patient experienced relapses with cerebellar and spinal cord involvement, falsely positive tests for syphilis were found and an antibiotic treatment was given. High protein content, low glucose levels, pleocytosis and oligoclonal bands were observed in all CSF samples, but the definite diagnosis was based on the detection of serum and CSF antibodies against B. burgdorferi.