BACKGROUND:

Lyme disease (LD) is a tick-borne zoonosis currently affecting approximately 1000 people annually in the UK (confirmed through serological diagnosis) although it is estimated that the real figures may be as high as 3000 cases. It is important to know what factors may predict correct appraisal of LD symptoms and how the experience of LD might predict preferences for future precautionary actions.

METHODS:

A cross-sectional survey was conducted with early LD patients via the Lyme Borreliosis Unit at the Health Protection Agency. One hundred and thirty participants completed measures of awareness of having been bitten by ticks, knowledge of ticks and LD, interpretation of LD symptoms, suspicions of having LD prior to seeing the General Practitioner (GP), and preferences for precautionary actions during future countryside visits. Chi-square tests and logistic regression were used to identify key predictors of awareness of having been bitten by ticks and of having LD. t-tests assessed differences between groups of participants on suspicions of having LD and preferences for future precautions. Pearson correlations examined relationships between measures of preferences for precautions and frequency of countryside use, knowledge of ticks and LD, and intentions to avoid the countryside in the future.

RESULTS:

73.8% of participants (n = 96) reported a skin rash as the reason for seeking medical help, and 44.1% (n = 64) suspected they had LD before seeing the GP. Participants reporting a direct event in realizing they had been bitten by ticks (seeing a tick on skin or seeing a skin rash and linking it to tick bites) were more likely to suspect they had LD before seeing the doctor. Participants distinguished between taking precautions against tick bites during vs. after countryside visits, largely preferring the latter. Also, the more frequently participants visited the countryside, the less likely they were to endorse during-visit precautions.

CONCLUSIONS:

The results suggest that the risk of LD is set in the context of the restorative benefits of countryside practices, and that it may be counterproductive to overemphasize pre- or during-visit precautions. Simultaneously, having experienced LD is not associated with any withdrawal from countryside.

Erythema of the ear lobe in the context of Lyme disease is caused by either borrelial lymphocytoma or localized erythema migrans. Here we present a case of chondritis limited to the ear cartilage caused by Lyme disease. The patient was treated with ceftriaxone with complete resolution of symptoms.

OPINION STATEMENT: The tick-borne spirochete responsible for Lyme disease is highly antibiotic-sensitive. Treatment related misconceptions can be attributed to confusion in three principal realms: (1) the appropriate approach to diagnosis (who should be treated); (2) necessary and appropriate treatment; and (3) what actually constitutes nervous system infection and to what extent this mandates different treatment. Contrary to often-repeated assertions, laboratory-based diagnosis-in the appropriate setting-is as valid as it is in most other serologically diagnosed infections. Treatment is highly effective in the vast majority of patients, including those with nervous system disease. Nervous system infection, most typically meningitis, cranial neuritis, radiculoneuritis, and other forms of mononeuropathy multiplex, is highly antibiotic responsive. The encephalopathy that can be seen in some patients with active infection represents the same phenomenon that occurs in patients with many other inflammatory disorders, is not evidence of central nervous system (CNS) infection, and does not require any different, more prolonged, or more intensive treatment. In patients with infection not involving the CNS, oral treatment with amoxicillin, cefuroxime axetil, or doxycycline for 2-4 weeks is almost always curative. Despite historic preferences for parenteral treatment with ceftriaxone, cefotaxime, or meningeal dose penicillin, patients with the forms of nervous system involvement listed above are highly responsive to oral doxycycline. Parenteral regimens can be reserved for those very rare patients with parenchymal CNS involvement, other severe forms of infection, or the approximately 5 % of patients who fail to respond to oral regimens.

Lyme disease Borrelia spp. are transmitted by Ixodes ticks, and more than 10 species of borreliae have been identified around the world. Recently another Borrelia sp. has been reported in Asia (Japan, Korea, China, Taiwan and Thailand) as Borrelia valaisiana-related sp. In the present study, we obtained and genetically characterized 19 B. valaisiana-related sp. strains from mammals and ticks. Genetic analyses showed that the Borrelia strains were distinct from B. valaisiana found in Europe. Multilocus sequencing typing revealed that these Borrelia isolates formed a monophyletic group with B. yangtze strains in China. Some of strains were isolated from the bladders of small mammals, and also two strains were experimentally confirmed to be infectious to C3H/HeN mice. We observed that the Borrelia sp. was maintained in Ixodes granulatus tick after molting. These results suggested that small mammals and I. granulatus were possible reservoir hosts and vector tick for the Borrelia sp., respectively. B. valaisiana, originally found in Europe, was transmitted mainly by I. ricinus, and birds were mainly thought to be reservoir hosts. Our results suggested Japanese isolates of B. yangtze (formerly B. valaisiana-related sp.) were distinguishable from B. valaisiana according to the reservoir host and its vector tick. In this study, we also deposited borrelia strain Okinawa-CW62 to bioresource centers as a reference strain of the B. yangtze (=DSM 24625, JCM 17189).

Many pathogenic microorganisms express fibronectin-binding molecules that facilitate their adherence to the extracellular matrix and/or entry into mammalian cells. We have previously described a Borrelia recurrentis gene, cihC that encodes a 40-kDa surface receptor for both, fibronectin and the complement inhibitors C4bp and C1-Inh. We now provide evidence for the expression of a group of highly homologues surface proteins, termed FbpA, in three B. hermsii isolates and two tick-borne relapsing fever spirochetes, B. parkeri and B. turicatae. When expressed in Escherichia coli or B. burgdorferi, four out of five proteins were shown to selectively bind fibronectin, whereas none of five proteins were able to bind the human complement regulators, C4bp and C1-Inh. By applying deletion mutants of the B. hermsii fibronectin-binding proteins a putative high-affinity binding site for fibronectin was mapped to its central region. In addition, the fibronectin-binding proteins of B. hermsii were found to share sequence homology with BBK32 of the Lyme disease spirochete B. burgdorferi with similar function suggesting its involvement in persistence and/or virulence of relapsing fever spirochetes.

It has been proposed that Borrelia burgdorferi infection is associated with ∼25% of children with autism spectrum disorders. Here antibodies against Borrelia burgdorferi were assessed in autistic (n=104), developmentally delayed (n=24) and healthy control (n=55) children. No seropositivity against Borrelia burgdorferi was detected in the children with and without autism. There was no evidence of an association between Lyme disease and autism.

Borrelia burgdorferi spirochetes that cause Lyme borreliosis survive for a long time in human serum because they successfully evade the complement system, an important arm of innate immunity. The outer surface protein E (OspE) of B. burgdorferi is needed for this since it recruits complement regulator factor H (FH) onto the bacterial surface to evade complement-mediated cell lysis. To understand this process at the molecular level we used a structural approach. First, we solved the solution structure of OspE by NMR, revealing a fold that has not been seen before in proteins involved in complement regulation. Next, we solved the X-ray structure of the complex between OspE and the factor H (FH) C-terminal domains 19 and 20 (FH19-20) at 2.83 Å resolution. The structure shows that OspE binds FH19-20 in a way similar to, but not identical with, that used by endothelial cells to bind FH via glycosaminoglycans. The observed interaction of OspE with FH19-20 allows the full function of FH in down- regulation of complement activation on the bacteria. This reveals the molecular basis for how Borrelia burgdorferi evade innate immunity, and suggests how OspE could be used as a potential vaccine antigen.

We review latest developments in knowledge of established and emerging tick-borne infections in the United States other than Lyme borreliosis, emphasizing a clinical and geographic approach to diagnosis and management.The incidence of tick-borne diseases in the United States has increased. New tick-borne diseases have emerged and will likely continue to be identified.Clinicians should maintain suspicion for tick-borne diseases in children with acute infectious illnesses, and consider treating such patients presumptively to prevent complications. Knowledge of common tick vectors in the United States and the infections they transmit will allow pediatricians to appropriately assess and manage patients with tick-borne diseases.

BACKGROUND:

Lyme borreliosis, caused by tick-borne Borrelia burgdorferi, is a multi-phasic, multi-system disease in humans. Similar to humans, C3H mice develop arthritis and carditis, with resolution and periodic bouts of recurrence over the course of persistent infection. Borrelia burgdorferi arthritis-related protein (Arp/BBF01), a highly conserved protein among B. burgdorferi s.s. isolates, has been shown to be antigenic in humans with Lyme borreliosis, and a target for antibody-mediated disease resolution in the mouse model.

RESULTS:

A mutant strain of B. burgdorferi s.s. deficient of the arp gene and a complemented version of that mutant were created and examined for phenotypic effects in mice compared to wild-type B. burgdorferi. Deletion of arp did not abolish infectivity, but did result in a higher infectious dose compared to wild-type B. burgdorferi, which was restored by complementation. Spirochete burdens in tissues of C3H-scid mice were lower when infected with the arp mutant, compared to wild-type, but arthritis was equally severe. Spirochete burdens were also lower in C3H mice infected with the arp mutant, but disease was markedly reduced. Ticks that fed upon infected C3H mice were able to acquire infection with both wild-type and arp mutant spirochetes. Arp mutant spirochetes were marginally able to be transmitted to naive hosts by infected ticks.

CONCLUSION:

These results indicated that deletion of BBF01/arp did not abrogate, but diminished infectivity and limited spirochete burdens in tissues of both immunocompetent and immunodeficient hosts, and attenuated, but did not abolish the ability of ticks to acquire or transmit infection.