A case of histologically diagnosed tick infestation on the scalp of a Korean child

A scalp mass surgically excised from a 4-year-old Korean boy was identified as a tick through histological observations. In sections of the mass, characteristic features of a tick, including its gross contour, cuticular structures, well developed musculature and salivary glands, and the capitulum, were discovered. In particular, the capitulum is anteriorly protruded, which strongly suggests that the specimen be a hard tick of family Ixodidae. However, the present histological features were not enough to determine the genus and species of the tick, because information on sectional morphologies of different tick species is unavailable. This is a rare case of tick infestation on the scalp diagnosed in histological sections.     

Clinical Characteristics Associated with Borrelia burgdorferi Sensu Lato Skin Culture Results in Patients with Erythema Migrans

Clinical characteristics associated with isolation of Borrelia burgdorferi sensu lato from skin have not been fully evaluated. To gain insight into predictors for a positive EM skin culture, we compared basic demographic, epidemiologic, and clinical data in 608 culture-proven and 501 culture-negative adult patients with solitary EM. A positive Borrelia spp. skin culture was associated with older age, a time interval of >2 days between tick bite and onset of the skin lesion, EM ≥5 cm in diameter, and location of the lesion on the extremities, whereas several other characteristics used as clinical case definition criteria for the diagnosis of EM (such as tick bite at the site of later EM, information on expansion of the skin lesion, central clearing) were not. A patient with a 15-cm EM lesion had almost 3-fold greater odds for a positive skin culture than patients with a 5-cm lesion. Patients with a free time interval between the tick bite and onset of EM had the same probability of a positive skin culture as those who did not recall a tick bite (OR=1.02); however, the two groups had >3-fold greater odds for EM positivity than patients who reported a tick bite with no interval between the bite and onset of the lesion. In conclusion, several yet not all clinical characteristics used in EM case definitions were associated with positive Borrelia spp. skin culture. The findings are limited to European patients with solitary EM caused predominantly by B. afzelii but may not be valid for other situations.     

A case of Amblyomma testudinarium tick bite in a Korean woman

A case of tick bite was found in the inguinal region of a 74-year-old Korean woman. She was attacked by the tick while working in her vegetable garden in the vicinity of mountain located in Suncheon City, the southern coastal area of the Korean Peninsula. On admission she complained of mild discomfort and itching around the bite area. The causative tick was 23 mm long and had slender pedipalps. The scutum was quite ornate and had eyes at the edge. The genital aperture was located anterior to the level of the coxa II. The spiracular plate was comma-shaped and the anus was surrounded posteriorly by the anal groove. The coxa I had subequal 2 spurs; the external one slightly larger. The spur of coxa IV was slightly longer than those of coxae II and III. The tarsus IV had 2 distinct subapical ventral spurs. It was identified as the fully engorged adult female of Amblyomma testudinarium. This is the first human case of Amblyomma bite in Korea.     

Cytologic features of cerebrospinal fluid in Lyme disease

The cytomorphologic findings in the cerebrospinal fluid (CSF) of four patients with lymphocytic meningoradiculitis (Lyme disease) related to a tick bite (due in at least two cases to Borrelia burgdorferi) are reported. In all cases, the May-Grünwald-Giemsa-stained centrifuge preparations of the CSF showed a cellular pattern consisting of a lymphocytic pleocytosis composed mainly of immunoblasts and plasma cells associated with numerous foamy macrophages. Direct immunofluorescence studies in one case showed the polyclonal pattern of the immunoblasts and the plasma cells. These CSF findings can be considered as suggestive of the spirochetal origin of a lymphocytic meningitis following a tick bite.     

Two human cases of tick bite caused by Ixodes nipponensis

We report two human cases of tick bite. A 63-year-old male had a pruritic pea-sized brownish nodule on the left popliteal area. Another 41-year-old male had an asymptomatic bean-sized black nodule in the pubic area. The ticks were identified as Ixodes nipponensis, which are the 18th and the 19th cases in Korea.     

Repellent effect of sweet basil compounds on Ixodes ricinus ticks

Diseases transmitted by ticks are causing increasing concern in Europe and all around the world. Repellents are an effective measure for reducing the risk of tick bite; products based on natural compounds represent an interesting alternative to common synthetic repellents. In this study the repellency of sweet basil (Ocimum basilicum L.) was tested against the tick Ixodes ricinus L., by using a laboratory bioassay. A bioassay-assisted fractionation allowed the identification of a compound involved in the biological activity. Eugenol appeared to be as repellent as DEET at two tested doses. Linalool, which was identified in the active fraction too, failed to give any response. Repellency of eugenol was proved also in the presence of human skin odour using a convenient and practical bioassay.     

Creatine phosphokinase elevation in a case of tick paralysis

The results of studies on a case of tick paralysis in a female child are described. The patient was paralysed by a single female specimen of Dermacentor andersoni Stiles attached to the left temporal area of the scalp. Paralysis of the lower limbs, incoordinate respiration and weakness of the arms were evident.The findings on physical examination and the results of diagnostic laboratory procedures are reported and the possible significance of the results is discussed. The only abnormal laboratory finding was an elevated level of plasma creatine phosphokinase (CPK) activity occurring during the paralytic phase and persisting for 10 days.     

Ticks and the pediatrician

The match between ticks and pediatricians in Italy is usually a seasonal event related to the spring and summer trips and to the increasing of outdoor activity that sun and warm weather allow, both for children and ticks. So cared parents reach emergencies asking for tick removal but more often after the tick has yet been removed by empirical manoeuvres and after the killing and the destruction of the "enemy". We have scheduled, in the years 2002-2003, the 167 children that reached our unit for a tick bite; they where 92 males (mean age four years) and 75 females (mean age five years). Two of them had only a questionable tick bite but one had erythema on the lateral side of the left ankle, fever of obscure origin and weakness with generalised malaise. She was six years old and she lived with a dog on which, in more instances, ticks where found, but she never noticed ticks on her body. The dog had positive levels of anti rickettsial and anti borrelia antibodies but no evidence of conclamate illness. In this girl we found high titers of anti borrelia antibodies that WB testing confirmed to be anti B. burgdoferi. We diagnosed Lyme disease and treated the girl with amoxicillin (50 mg/kg/day) for three weeks achieving the complete relief of symptomatology till today. Three children with conclamate tick bite had positive levels of anti Rickettsia conorii antibodies with increasing levels at a twenty days control; two (aged four and five years) of them had a full symptomatology (tache noire, satellite lymphadenopathy, fever, and maculopapular erythema) for Meditarranean spotted fever; the latter (three years old) had an atypical form with the complete absence of maculopapular erythema. The therapy was clarithromycin (15 mg/kg/day) for three weeks. In Campania, in the years 2002/2003 on 167 children with tick bite that reached our unit, we found only four pathological correlable events; so are our ticks not infected? But we don't know how many children where tick bited and if there were other children with Lyme disease or Rickettsial disease because of the lack of a pediatric reference centre for "tick bite diseases" and the incomplete and late diffusion of knowledge on these diseases. Other Italian regions and such as Trentino Alto Adige, Veneto, and Friuli Venezia Giulia had a remarkable officially notified number of cases of Lyme disease and in Sicilia, Sardegna and Lazio there were numerous officially notified Rickettsial diseases. So we hope that Campania may be an happy island but we also think that a more effective cooperation between pediatricians and veterinarians and the creation of regional reference centres for tick bite diseases may arise a surveillance net to prevent the diffusion of these world wide emerging diseases and so that parents can achieve an univoque and useful information, the only way to defeat the fear of ignorance.     

Presence and indigenous nature of Lyme disease in southern Italy

Lyme disease is very common in the countries of the northern hemisphere. In Italy it is endemic in some regions of the northern part of the country and it is more frequent during summer. In Calabria (south Italy) no cases have been reported. To document the presence and indigenous nature of Lyme disease in this territory we conducted a study from 1999 to 2002. We defined as indigenous cases those with erythema migrans with the following characteristics: dimensions equal to or greater than 5 cm; localization on an area of the skin where there was a tick bite; appearance between 4 and 30 days after the tick bite; appearance in patients who had not resided out of Calabria in the previous 3 months. We found 23 patients with the necessary characteristics to be defined indigenous cases. Since 15 of these cases (65.2%) were observed in the October - December trimester and no case was found in the July - September trimester, we suspect that in Calabria the disease follows a seasonal distribution which differs with respect to countries where it is historically endemic.     

Neurologic Abnormalities in Two Dogs Suspected Lyme Disease

A 2-year-old mongrel dog developed neurological signs following tick bite. These included astasia, persistent tonic convulsions and hyper-reflexia. Both serum IgG and IgM antibody titers against Borrelia burgdorferi were positive in enzyme-linked immunosorbent assay (ELISA). The neurological signs subsided after high-dose penicillin and streptomycin treatment. A strain of spirochetes (P427a) was isolated from the midgut of Ixodes persulcatus feeding on the dog. Morphological characteristic, immunological property and protein profile revealed that the isolate was B. burgdorferi. Similarly, a 2-year-old Labrador retriever dog developed neurological signs after tick bite and showed a positive IgG antibody titer against B. burgdorferi. Antibiotic treatment was effective also in this case. These findings suggest that neurological symptoms shown in both dogs were caused by infection with B. burgdorferi.     

Aplasia cutis congenita with skull defect in a monozygotic twin after exposure to methimazole in utero

BACKGROUND: Aplasia cutis congenita (ACC) is a condition in which localized or widespread areas of skin are absent at birth. Defective lesions show complete absence of all layers of skin, occasionally extending to skull or dura. ACC is etiologically heterogeneous; many different etiologies including teratogens have been documented. CASE: We describe the first reported case of a monozygotic twin with ACC after exposure to methimazole in utero. The female patient was born at 36 weeks gestation as the first child of monozygotic twins. The mother received methimazole between the 11th and 17th weeks of pregnancy because of transient hyperthyroidism. The second child did not have ACC. The patient had defects of the scalp, skull, and dura (7 x 5 cm) on the sagittal line of the parieto-occipital region. No other malformations were noted. The scalp defect has been treated daily with sterile physiological saline and petrolatum dressing in addition to intravenous antibiotics. Trafermin, a recombinant human fibroblast growth factor, was sprayed from day 6 to promote epithelialization of the scalp defect. On day 21, she had high fever due to infection of the defect lesion, which was controlled by povidone iodine dressing and intravenous antibiotics. The defect of the scalp was well healed after 6 weeks, but the skull defect remained unclosed. CONCLUSIONS: We describe a rare case of a monozygotic twin with ACC and skull defect after methimazole exposure in utero. The findings of our case suggest that methimazole is a potential teratogen of ACC.     

Inactivation of Genes for Antigenic Variation in the Relapsing Fever Spirochete Borrelia hermsii Reduces Infectivity in Mice and Transmission by Ticks

Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host’s acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete’s alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector.     

The structure of OMCI, a novel lipocalin inhibitor of the complement system

The complement (C) system is a potent innate immune defence system against parasites. We have recently characterised and expressed OmCI, a 16 kDa protein derived from the soft tick Ornithodoros moubata that specifically binds C5, thereby preventing C activation. The structure of recombinant OmCI determined at 1.9 A resolution confirms a lipocalin fold and reveals that the protein binds a fatty acid derivative that we have identified by mass spectrometry as ricinoleic acid. We propose that OmCI could sequester one of the fatty acid-derived inflammatory modulators from the host plasma, thereby interfering with the host inflammatory response to the tick bite. Mapping of sequence differences between OmCI and other tick lipocalins with different functions, combined with biochemical investigations of OmCI activity, supports the hypothesis that OmCI acts by preventing interaction with the C5 convertase, rather than by blocking the C5a cleavage site.     

Seroprevalence study of Tick-borne encephalitis, Borrelia burgdorferi, Dengue and Toscana virus in Turin Province

Tick borne encephalitis virus (TBEV) is present in some European countries and it is transmitted by a tick bite. Ixodes ricinus is the main vector of the infection in Italy, where fortunately clinical neurological manifestations, typical of the more serious phase of the disease, are very rarely observed. This behaviour is different from other endemic Euroasiatic areas where numerous cases of encephalitis are described. However TBE transmission has not been widely investigated in Italy and available epidemiological data have been obtained only by studies performed in Central and Northern Regions of the country. In addition seroepidemiological researches were made prevalently on subjects at high risk of tick bite, such as hunters or forest guards from Trentin and Central Italy. No precise information about TBE virus diffusion was available in the Piedmont before our investigations. We found that hunters and wild boar breeders seem to be particularly exposed to the risk of TBE virus infection in Turin Province and in particular in the Susa valley, although no neurological involvement was observed in our population. In particular a seroprevalence of about 5% was detected by the use of purified antigens ELISA test, amongst the subjects at high risk of tick bite. Moreover low risk individuals showed a seroprevalence of below 2%. In addition a parallel seroepidemiological study was performed in Turin Province for Borrelia burgdorferi, the aetiological agent of Lyme disease, also transmitted by tick bite (e.g. Ixodes ricinus), for Dengue and Toscana (TOS) arboviruses, respectively transmitted by Aedes mosquitoes and phlebotomes. Data reported here demonstrate only a sporadic presence in our population of antibodies against Borrelia and Dengue infection. Moreover using an ELISA test performed with viral purified nucleoprotein, we reported a total percentage of about 3% of subjects positive for TOSV.     

An uncommon severe clinical course of European tick-borne encephalitis

Tick-borne encephalitis (TBE) is the major European arbovirosis. Man is often infected by the tick bite; laboratory infections as well as infections after consumption of nonpasteurized milk have occasionally been reported. TBE typically takes a biphasic course. After an incubation period (7-14 days usually), the prodromal symptoms occur. The first stage of the disease lasts 1-8 days. After an afebrile asymptomatic interval of approximately 1-week the second stage develops, in which TBE may manifest as isolated meningitis, meningoencephalitis, meningoencephalomyelitis and/or radiculitis. The mortality rate is 0-3.3%. There is high frequency of sequelae. Patients who have suffered from a TBE infection are immune for the rest of their lives. At present there is no effective antiviral therapy and management is strictly supportive. Active immunization against TBE is recommended for all subjects living in and travelling to areas of risk. Passive immunization is recommended only within 48 hours after a tick bite. The authors present the case report of 75-years old female subject, who suffered from the uncommon severe clinical course of TBE--with the development of consciousness impairment, tetraplegia, and dyspnoea (demanding ventilatory support). Her state was complicated by the transient left side faciobrachial motor Jackson's convulsions, blood pressure instability, heart arrhythmia, respiratory infection, anemia, and by the development of critical illness neuropathy. Although she made slow progress during treatment, she died on the 114th day because of suspected aspiration.     

Ixodes ricinus tick saliva modulates tick-borne encephalitis virus infection of dendritic cells

Tick-borne encephalitis virus is an important human pathogen, naturally delivered into host skin via a tick bite. To examine the effects of the virus on dendritic cell biology, we cultured dendritic cells with two tick-borne encephalitis virus strains of different virulence in the presence of Ixodes ricinus tick saliva. Tick saliva treatment increased proportion of virus-infected cells, led to a decrease in virus-induced TNF-α and IL-6 production and to reduced virus-induced apoptosis. Our data indicate that tick saliva modulate virus-mediated alterations in dendritic cells, thus probably being involved in the early infection process in the host.     

Functional analysis of the Borrelia burgdorferi bba64 gene product in murine infection via tick infestation

Borrelia burgdorferi, the causative agent of Lyme borreliosis, is transmitted to humans from the bite of Ixodes spp. ticks. During the borrelial tick-to-mammal life cycle, B. burgdorferi must adapt to many environmental changes by regulating several genes, including bba64. Our laboratory recently demonstrated that the bba64 gene product is necessary for mouse infectivity when B. burgdorferi is transmitted by an infected tick bite, but not via needle inoculation. In this study we investigated the phenotypic properties of a bba64 mutant strain, including 1) replication during tick engorgement, 2) migration into the nymphal salivary glands, 3) host transmission, and 4) susceptibility to the MyD88-dependent innate immune response. Results revealed that the bba64 mutant's attenuated infectivity by tick bite was not due to a growth defect inside an actively feeding nymphal tick, or failure to invade the salivary glands. These findings suggested there was either a lack of spirochete transmission to the host dermis or increased susceptibility to the host's innate immune response. Further experiments showed the bba64 mutant was not culturable from mouse skin taken at the nymphal bite site and was unable to establish infection in MyD88-deficient mice via tick infestation. Collectively, the results of this study indicate that BBA64 functions at the salivary gland-to-host delivery interface of vector transmission and is not involved in resistance to MyD88-mediated innate immunity.     

Enzyme activities of Lyme disease and relapsing fever borreliae

Activities of glycosidases ( n = 8), esterases ( n = 10), arylamidases ( n = 63), acid phosphatase, alkaline phosphatase and phosphoamidase were tested in 47 Borrelia strains. Forty-four were B. burgdorferi strains; 22 of which were isolated from human specimens (skin 13, cerebrospinal fluid six, and one each from blood, heart muscle and synovia), 13 were isolated from various organs of laboratory animals infected via tick bite or with human isolates, and nine from ticks. The remaining three were the relapsing fever strains B. coriaceae , B. hermsii , and B. turicatae. Strains were of low and high passage but the number of subcultures did not influence the enzyme patterns obtained by utilization of chromogenic substrates of constitutive enzymes. Glycosidase activity was absent in almost all strains tested. Esterase activity was high on molecules of chain length 9 carbons. 2-Naphthylamide derivatives were utilized by strains of human, rodent or tick origin in a range of 66.6 to 83.1%. Almost all strains utilized substrates for acid and alkaline phosphatase and phosphoamidase. Chymotrypsin activity was only found in three and two strains from specimens of human and rodent origin, respectively; and γ-glutamyltransferase activity only in three human skin isolates. No strain tested displayed trypsin activity. Overall, the specific activities of constitutive enzymes of the Borrelia strains tested are widely similar. Thus, the enzyme profiles did not discriminate between human, animal and tick isolates, or between human isolates of Borrelia whether cultivated from cerebrospinal fluid or from skin biopsy of Lyme borreliosis patients.     

BBE31 from the Lyme disease agent Borrelia burgdorferi,known to play an important role in successful colonization of the mammalian host,shows the ability to bind glutathione

Lyme disease is a tick-borne infection caused by Borrelia burgdorferi sensu lato complex spirochetes. The spirochete is located in the gut of the tick; as the infected tick starts the blood meal, the spirochete must travel through the hemolymph to the salivary glands, where it can spread to and infect the new host organism. In this study, we determined the crystal structures of the key outer surface protein BBE31 from B. burgdorferi and its orthologous protein BSE31 (BSPA14S_RS05060 gene product) from B. spielmanii. BBE31 is known to be important for the transfer of B. burgdorferi from the gut to the hemolymph in the tick after a tick bite. While BBE31 exerts its function by interacting with the Ixodes scapularis tick gut protein TRE31, structural and mass spectrometry data revealed that BBE31 has a glutathione (GSH) covalently attached to Cys142 suggesting that the protein may have acquired some additional functions in contrast to its orthologous protein BSE31, which lacks any interactions with GSH. In the current study, in addition to analyzing the potential reasons for GSH binding, the three-dimensional structure of BBE31 provides new insights into the molecular details of the transmission process as the protein plays an important role in the initial phase before the spirochete is physically transferred to the new host. This knowledge will be potentially used for the development of new strategies to fight against Lyme disease.     

Molecular interactions that enable movement of the Lyme disease agent from the tick gut into the hemolymph

Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted to humans by bite of Ixodes scapularis ticks. The mechanisms by which the bacterium is transmitted from vector to host are poorly understood. In this study, we show that the F(ab)(2) fragments of BBE31, a B.burgdorferi outer-surface lipoprotein, interfere with the migration of the spirochete from tick gut into the hemolymph during tick feeding. The decreased hemolymph infection results in lower salivary glands infection, and consequently attenuates mouse infection by tick-transmitted B. burgdorferi. Using a yeast surface display approach, a tick gut protein named TRE31 was identified to interact with BBE31. Silencing tre31 also decreased the B. burgdorferi burden in the tick hemolymph. Delineating the specific spirochete and arthropod ligands required for B. burgdorferi movement in the tick may lead to new strategies to interrupt the life cycle of the Lyme disease agent.