The epidemiology of lyme borreliosis

The tick-transmitted bacterial infection known as Lyme disease, or Lyme borreliosis, has recently emerged as the leading arthropod-borne disease in Europe and North America. Several thousand new cases of human Lyme disease are reported each year from Europe and the USA. The causative agent, Borrelia burgdorferi, has been isolated from several species of mammals, birds, ticks and insects and, in this article, Thomas Jaenson discusses the geographical differences in the epidemiology of the infection.     

Protective immunity in lyme borreliosis

Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne illness in the USA. Although early infection can be treated with antibiotics, the initial diagnosis is difficult and late disease may be recalcitrant to therapy. A vaccine against Lyme disease is therefore needed, and murine models of Lyme borreliosis have facilitated its development. In this review, Erol Fikrig, Fred Kantor, Stephen Barthold and Richard Flavell focus on the use of Borrelia surface antigens as vaccine candidates for Lyme disease.     

Lectin-binding characteristics of a lyme borreliosis spirocheteBorrelia burgdorferi sensu stricto

Borrelial glycoconjugates were localized by labeled lectins on ultrathin cryosections and on surfaces of intact negatively stained bacteria. Protein-saccharide complexes in these glycoconjugates were partially characterized by means of enzyme deglycosylation and mild alkali pretreatment of cryosections. The results of labeling were examined by transmission electron microscopy. Statistically evaluated results (relative labeling index, chi2 test) of gold labeling indicated that surfaces of Borrelia burgdorferi strain B31 and external (outer) membrane vesicles (MVs) were covered with glycoconjugates containing O-glycosidically linked N-acetyl-D-galactosamine (GalNAc) and N-glycosidically linked N-acetyl-D-glucosamine (GlcNAc). The presence of N-linked GalNAc, sialic acid, mannose and fucose on the surfaces of outer membranes and MVs was probably due to an adherence of BSK-H medium components, especially rabbit serum, to Borrelia surfaces.     

Immunodominant proteins of Borrelia burgdorferi,the etiological agent of lyme borreliosis

Lyme borreliosis, a multisystem disorder involving the skin, the nervous system, the heart, the joints and many other organs, is a worldwide infectious disease which is transmitted by ticks of the Ixodes complex. Most frequently diagnosis is accomplished by detection of antibodies because the Borrelia are difficult to cultivate. Present serodiagnostic methods, however, are impaired by low sensitivity and unspecific reactions. The selection of immunodominant antigens with low cross-reactivity to other bacteria should improve antibody detection. Borrelia burgdorferi proteins have been analysed for cross-reactivity with immune sera from unrelated bacteria, and sera from patients with different stages of the disease. Suitable antigens for improving serodiagnosis have been detected and are reported here. In view of the immunological heterogeneity of Borrelia proteins, sensitivity of antibody detection may possibly be increased by using recombinant antigens derived from different strains. Immunization with recombinant OspA (a flagellum-associated protein) from a North American isolate protected mice from the challenge with three North American isolates. However, for development of an effective vaccine (especially in Europe), the heterogeneity of OspA has to be considered.This paper was presented at the IUMS Symposium on New Developments in Diagnosis and Control of Infectious Diseases held in conjunction with the Eighth International Congress of Virology, Berlin, Germany, 24–31 August 1990.     

Lymphoadenopathy during lyme borreliosis is caused by spirochete migration-induced specific B cell activation

Lymphadenopathy is a hallmark of acute infection with Borrelia burgdorferi, a tick-borne spirochete and causative agent of Lyme borreliosis, but the underlying causes and the functional consequences of this lymph node enlargement have not been revealed. The present study demonstrates that extracellular, live spirochetes accumulate in the cortical areas of lymph nodes following infection of mice with either host-adapted, or tick-borne B. burgdorferi and that they, but not inactivated spirochetes, drive the lymphadenopathy. The ensuing lymph node response is characterized by strong, rapid extrafollicular B cell proliferation and differentiation to plasma cells, as assessed by immunohistochemistry, flow cytometry and ELISPOT analysis, while germinal center reactions were not consistently observed. The extrafollicular nature of this B cell response and its strongly IgM-skewed isotype profile bear the hallmarks of a T-independent response. The induced B cell response does appear, however, to be largely antigen-specific. Use of a cocktail of recombinant, in vivo-expressed B. burgdorferi-antigens revealed the robust induction of borrelia-specific antibody-secreting cells by ELISPOT. Furthermore, nearly a quarter of hybridomas generated from regional lymph nodes during acute infection showed reactivity against a small number of recombinant Borrelia-antigens. Finally, neither the quality nor the magnitude of the B cell responses was altered in mice lacking the Toll-like receptor adaptor molecule MyD88. Together, these findings suggest a novel evasion strategy for B. burgdorferi: subversion of the quality of a strongly induced, potentially protective borrelia-specific antibody response via B. burdorferi's accumulation in lymph nodes.     

Borrelia burgdorferi sensu lato, the agent of lyme borreliosis: life in the wilds

In Europe, Borrelia burgdorferi sensu lato (sl) the agent of Lyme borreliosis circulates in endemic areas between Ixodes ricinus ticks and a large number of vertebrate hosts upon which ticks feed. Currently, at least 12 different Borrelia species belonging to the complex B. burgdorferi sl have been identified among which seven have been detected in I. ricinus: B. burgdorferi sensu stricto (ss), B. garinii, B. afzelii, B. valaisiana, B. spielmanii and B. bissettii. A few dozens of vertebrate hosts have been identified as reservoirs for these Borrelia species. Specific associations were rather early observed between hosts, ticks and borrelia species, like for example between rodents and B. afzelii and B. burgdorferi ss, and between birds and B. garinii and B. valaisiana. The complement present in the blood of the hosts is the active component in the Borrelia host specificity. Recent studies confirmed trends toward specific association between Borrelia species and particular host, but also suggested that loose associations may be more frequent in transmission cycles in nature than previously thought.     

Evaluation of a genotyping method based on the ospA gene to detect Borrelia burgdorferi sensu lato in multiple samples of lyme borreliosis patients

In this study we have developed a new Restriction-Fragment-Length-Polymorphism (RFLP) genotyping method for rapid detection and identification of Borrelia genospecies present as unique species or as co-infection in multiple specimens obtained simultaneously from 29 individual patients affected by early or late Lyme borreliosis (LB). The target of the RFLP-genotyping was the heterogeneous plasmid located ospA gene, thus we developed a method able to detect and differentiate between six clinically relevant Borrelia genospecies circulating in Europe, B. burgdorferi sensu stricto, B. garinii, B. afzelii, B. valaisiana, B. bissettii and B. spielmanii. In this study Borrelia DNA could be detected by PCR in at least one specimen of each patient, except in one case of neuroborreliosis (NB); blood samples gave the highest sensitivity in all patient groups. The genotyping indicated that B. afzelii was present in 8 patients with skin involvement, B. garinii in 2 cases of NB and 4 cases with skin involvement, B. burgdorferi sensu stricto was detected in one patient with skin involvement and another with Lyme arthritis. Different Borrelia species in distinct specimens were identified in one patient with EM. The RFLP analysis of 11 patients revealed mixed patterns, which suggested pluri-infection with different Borrelia species.     

Pericarditis as a manifestation of essential thrombocythemia.

A 58-year-old woman presented with pericarditis and pericardial effusion. Investigation revealed that she was suffering from a thrombocythemic myeloproliferative disorder; she died of massive pulmonary embolism 10 days after admission. Histologic study verified epicardial and pericardial trilineage hematopoiesis. Pericarditis is an unusual feature of essential thrombocythemia and it may occur in direct relation to the abnormal cellular proliferation.     

k-Carrageenan Gel as Agent to Sequester Paralytic Shellfish Poison

The action of k-carrageenan gel to sequester paralytic shellfish poison (PSP) was tested and characterized. When an extract from a Philippine strain of Pyrodinium bahamense var. compressum was used as PSP solution, the PSP-sequestering property of k-carrageenan gel was found to be dependent on gel surface area, interaction time, and polysaccharide concentration. The interaction was also found to be affected by high concentrations of monovalent cations. The characteristics of k-carrageenan as a PSP-sequestering agent all point to cation exchange as its mechanism of action. It is also proposed that the polysaccharide gel can be utilized as an agent to alleviate PSP intoxication.     

Splenic hematoma as a first manifestation of cytomegalovirus infection

Splenic rupture is rare but life threatening complication of mononucleosis syndrome. It has been suggested that subcapsular splenic hematoma formation precedes rupture. The case of 44-year-old, previously healthy, male with splenic hematoma occurring after rising of heavy cargo is reported. Mononucleosis syndrome was suggested based on routine laboratory tests (elevated white blood cell count with predominance of lymphocytes and raised serum transaminases) and CMV infection was confirmed by serological test. Nonoperative management was used since the patient was hemodynamically stable with no further signs of splenic rupture. The same approach has been used in growing number of cases of patients with spontaneous splenic rupture in mononucleosis syndrome. Importance of considering splenic hematoma and/or rupture if abdominal pain occurs in the course of mononucleosis syndrome is outlined as well as importance of routine laboratory tests in suspecting mononucleosis syndrome in otherwise clinically silent patient.     

The vegetative state as a manifestation of a stable pathological state

The results of comprehensive monitoring of the state of 25 patients in the vegetative state (prolonged coma) before and after compensating for the factors of secondary brain damage were analyzed and followed up for no less than six months. The primary results showed that the best recovery of consciousness and cognitive functions was observed if, according to the positron emission tomography data, a diffuse decrease in the glucose metabolism rate (GMR_glu), significantly exceeding the extent of the zones of morphological/anatomical lesions, was present in the brain before treatment, while the minimal improvement was observed if the GMR_glu was sufficiently intact. These and other paradoxical results can be explained if the vegetative state is regarded as a stable pathological state of the brain, which offers new approaches to the treatment of this group of patients.     

Septo-optic dysplasia as a manifestation of valproic acid embryopathy.

BACKGROUND: The use of valproic acid during pregnancy has been associated with adverse fetal outcomes, including major and minor congenital malformations, intrauterine growth retardation (IUGR), hyperbilirubinemia, hepatotoxicity, transient hyperglycemia, and fetal and neonatal distress. In addition, intrauterine exposure to valproic acid has been associated with an increased risk of central nervous system abnormalities, primarily neural tube defects. Optic nerve hypoplasia has been reported in association with other prenatal anticonvulsant exposures, but the occurrence of septo-optic dysplasia as a manifestation of valproic acid embryopathy has not been reported previously. RESULTS: We report on a woman who received Depakote (valproic acid) throughout her pregnancy for the treatment of a seizure disorder. The patient presented with features typical of valproic acid embryopathy, including bitemporal narrowing, hypertelorism, short palpebral fissures, epicanthal folds, microphthalmia, a flat broad nasal bridge, small mouth, hypoplastic nails, mild clinodactyly, and camptodactyly. MRI showed hypoplasia of the optic chiasm and absence of the septum pellucidum. CONCLUSIONS: We report the first case of septo-optic dysplasia associated with maternal exposure to valproic acid throughout pregnancy. This case expands the clinical phenotype of valproate embryopathy.     

Generalized adenopathy as a manifestation of type 2 reactional leprosy

Generalized adenopathy as a manifestation of type 2 reactional leprosy Leprosy patient's reactions are severe clinical manifestations of acute inflammation of chronic lesions, capable of producing irreversible and invalidating damage. We studied a 46 year-old man with a type 2 leprosy reaction, who presented fever, cutaneous nodules, nasal obstruction and generalized adenopathy. The hemogram showed leucocytosis with neutrophilia. None of the initial diagnoses included leprosy. A lymph node biopsy revealed extensive necrotic areas infiltrated with polymorphonuclear lymphocytes, and foamy macrophages. Eosinophylic necrosis and thrombosis of venules with lymphoid nodule depletion was also in evidence. Ziehl Neelsen stain was not done, but the Gomori stain clearly showed Hansen's bacilli. These were were not detected by the pathologist and therefore a final diagnosis was not provided. Twenty months later, the patient presented similar symptoms, but with more generalized lymphadenopathy and presence of cutaneous nodules. Nodule biopsy showed lepromatous leprosy with erythema nodusum leprosum or type 2 reaction. Polychemotherapy treatment and anti-reaction treatment with thalidomide cured the patient. No sequelae were noted in 3 years following the treatment. A literature review of the type 2 reaction in leprosy is provided, including discussion of risk factors, histopathology, differential diagnosis for leprosy adenopathy, pathogenesis, prognosis, and treatment. Type 2 leprosy must be treated immediately upon diagnosis as it can cause serious and permanent tissue damage. As had occurred in the above patient, the disease can proceed with generalized and symptomatic lymphadenopathy.     

Dietary restriction and longevity extension as a manifestation of Hormesis

Restricting the food intake of rats and mice to 60% of ad libitum intake has been shown to significantly slow their aging processes and markedly extend length of life. Evidence is presented that indicates the antiaging action of this dietary restriction is a manifestation of hormesis and acts by enabling the animal to cope with stressors, including the low‐intensity, long‐term intrinsic and extrinsic stressors conjectured to cause aging. A hypothesis is offered for the evolutionarily adaptive basis of the antiaging action of dietary restriction: It proposes that this antiaging action is a byproduct of the evolution of mechanisms that enabled animals living in the wild to survive unpredictable and relatively brief periods of food scarcity. Likely proximate mechanisms of antiaging action of dietary restriction are considered. Enhancement of the stress response genes, particularly the heat shock protein genes, appears to be importantly involved. Evidence indicates that moderate hyperadrenocorticism also plays a significant role. These proximate mechanisms may well be major players in other examples of hormesis.     

Adaptation as a manifestation of informational connections in living systems

The problem of adaptation of living systems in terms of the concept of informational communications is considered. The informational communication means the qualitative evaluation of information and determines correspondence of living systems to concrete conditions of life during interaction of these living systems to the source of the information. The system of the wholeorganism regulatory chemical communication is the main functional basis for the informational communication. Due to it, the transformation of the information signal in biological systems is performed, which results in their adequate response according to this information. The existence of living systems and their adaptation are determined by peculiarities of functioning of elements of their regulatory systems according to the character of the informational communication.     

Pararenal angiosarcoma as a manifestation of sexual dimorphism in carcinogenesis

Pararenal angiosarcoma developed in 42% of CBA male mice injected subcutaneously 1.2-dimethyl hydrazine (DMH) in a dose of 8 mg/kg body weight within 30 weeks. None of 176 CBA female mice given the same treatment developed such tumors. Histologically, the tumors represented various angiosarcomas characterized by a marked invasive growth into the renal parenchyma.     

Increased catabolism of muscle proteins as a manifestation of radiation myopathy

Summary Exposure of the hindquarter of the rat to 1000 rad of gamma-radiation caused a significant increase in the release of glutamine and alanine into the perfusion fluid at 4 h post-irradiation. The extent of the release of glutamine exceeded that of alanine. Furthermore, the exposure to gamma-radiation brought about a significant lowering of the intra-/extracellular concentration gradient with respect to glutamine and alanine.On leave from the University of Rochester, School of Medicine and Dentistry, Department of Biophysics, Rochester, New York, USADedicated to Prof. L.E. Feinendegen on the occasion of his 60th birthday