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Biomedical subjects

D Fish

Publications and source records attributed to D Fish.

At least 55 records · Page 3Linked to original sources

Prevention of Borrelia burgdorferi transmission in guinea pigs by tick immunity.

We examined the effect of repeated infestation of guinea pigs with Ixodes scapularis on the capacity of ticks to transmit Borrelia burgdorferi infection. Repeated challenges with nymphs or larvae lead to a reduction in duration of nymphal tick attachment and weight of recovered ticks consistent with the development of tick immunity. Only one of 18 I. scapularis-immune guinea pigs challenged with B. burgdorferi-infected nymphal ticks became infected, whereas 10 of 18 naive guinea pigs similarly challenged became infected. We conclude that tick immunity interferes with borrelial transmission.

Animals↗

Density-dependent factors regulating feeding success of Ixodes scapularis larvae (Acari: Ixodidae).

We studied the effects of different parasite and host densities on the feeding success of larval Ixodes scapularis ticks upon white-footed mice Peromyscus leucopus. Mice were infested daily with 10, 25, 50, or 100 larvae and kept individually or in groups of 2 and 3 to simulate co-nesting in the field. Engorgement weight and molting success of replete larvae did not change during more than 3 wk of continuous infestation, but overall larval feeding success decreased from 24% to 12% with increased infestation density. Grooming was observed in response to unattached, crawling larvae, and grooming of unfed ticks increased with infestation density. Nearly all larvae completed engorgement once attached, although a few were groomed accidentally along with unattached ticks. Co-nesting mice fed 2-3 times fewer ticks than did solitary mice because of increased frequency of self-grooming in the presence of nest-mates, but differences between groups of 2 or 3 mice were not significant. Thus, increased mouse density may reduce the density of the tick population at first, but further increase in the number of co-nesting mice does not affect the feeding success of larval I. scapularis and increased mouse density will increase tick density.

Anesthesia↗

Bilateral parasagittal parietooccipital polymicrogyria and epilepsy.

We describe 9 patients with a bilateral malformation of cortical development, centered around the parasagittal and mesial aspects of the parietooccipital cortex, with magnetic resonance imaging findings suggestive of polymicrogyria. No familial distribution or etiologic factors were identified. Location in a watershed area between anterior and posterior cerebral arteries suggests postmigratory perfusion failure as the underlying cause. In most patients the malformation was detected by magnetic resonance imaging after computed tomography scans with 10-mm-thick sections were considered normal. Seizures, present in all, had started between the ages of 20 months and 15 years (mean, 9 years) and were intractable in 7. Complex partial seizures with or without minor automatisms were the most frequent ictal pattern. In only 4 patients these were preceded by symptoms indicating posterior onset. Interictal electroencephalograms showed both diffuse and bilateral parietooccipital or temporal abnormalities. The range of IQ scores indicated average intelligence to mild retardation. Several patients presented deficits on neuropsychological tasks requiring performance under time constraints, suggesting that the malformation may result in cognitive slowing. Early diagnosis of this malformation may be difficult because of the lack of neurological signs, relatively late seizure onset, difficulty in localizing seizure onset, and inability to recognize the cortical abnormality on computed tomography scans.

Adolescent↗

Transmission of the agent of human granulocytic ehrlichiosis by host-seeking Ixodus scapularis (Acari:Ixodidae) in southern New York state.

Ixodes scapularis Say nymphs collected from a natural focus of human granulocytic ehrlichiosis (HGE) in Westchester County, New York, transmitted the HGE agent to uninfected mice in the laboratory. Infection was demonstrated in 3 of 8 mice by polymerase chain reaction analysis of whole blood and microscopic examination of blood smears for morulae. Two of these mice were also positive by xenodiagnosis. Positive xenodiagnostic larvae maintained infection through molting and transferred infection to 1 of 3 mice. Naturally infected I. scapularis ticks transmit the agent of human granulocytic ehrlichiosis to mice, but both acquisition and transmission of this agent by I. scapularis appear to be less efficient than would be expected for Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, the agent of Lyme disease.

Animals↗

Feeding density influences acquisition of Borrelia burgdorferi in larval Ixodes scapularis (Acari: Ixodidae).

The intensity of Borrelia burgdorferi transmission in nature is dependent upon the efficiency of acquisition of spirochetes by larval Ixodes scapularis Say (= I. dammini Spielman, Clifford, Piesman & Corwin). White-footed mice infected with B. burgdorferi were infested weekly for 5 consecutive weeks with 25 or 250 larval I. scapularis. Prevalence of infection in nymphs derived from larvae fed at high density (25.0-38.9%) was consistently higher than in nymphs derived from larvae fed at low density (6.7-23.5%). Spirochete prevalence in nymphal I. scapularis populations in nature may be influenced by larval population density.

Animals↗

OspA antibodies inhibit the acquisition of Borrelia burgdorferi by Ixodes ticks.

Ixodes ticks are infected by Borrelia burgdorferi when larvae feed on spirochete-infected mice. We studied the acquisition of B. burgdorferi by larval ticks, characterized the production of outer surface protein A (OspA) by spirochetes entering larvae, and examined the effects of OspA antibodies on the establishment of B. burgdorferi infections in ticks. Most larvae were infected by spirochetes 24 to 48 h after placement on mice. OspA antibodies stained the first spirochetes observed in larvae, suggesting that OspA is synthesized early during the colonization of the vector. When OspA antibodies were administered to B. burgdorferi-infected mice and larvae were then placed on the animals, the severity of larval infection and the number of infected ticks (7 of 16) were decreased compared with that of controls (15 of 16). The inhibitory effects of OspA antibodies were observed with passive antibody transfer as well as active host-generated immunity. The lower larval infection rate observed in the presence of OspA antibodies was exacerbated after the larval molt since only 1 of 12 nymphs was infected, and none of the mice that were fed upon by these nymphs became infected with B. burgdorferi. Therefore, an OspA antibody response in mice altered the reservoir competence of the vertebrate host by inhibiting the movement of B. burgdorferi from the host to the vector.

Animals↗

Inhibition of efficient polymerase chain reaction amplification of Borrelia burgdorferi DNA in blood-fed ticks.

Polymerase chain reaction (PCR) analysis is a widely used method for detection of Borrelia burgdorferi DNA in biological specimens, including ticks. Studies have demonstrated that substances present in mammalian blood can inhibit PCR amplification. This would limit the utility of PCR for determination of B. burgdorferi infection in engorged ticks that have taken a blood meal from a human or other animal host. To systematically assess the potential for such inhibition, nymphal Ixodes scapularis, which had acquired B. burgdorferi as larvae, were fed on rats. These engorged ticks were lysed in standard PCR lysis buffer and aliquots were subjected to PCR analysis; 0 of 56 were PCR positive. An equivalent cohort of unfed (unengorged) ticks had an infection rate of 19% (11 of 57) as determined by identical PCR analysis (P = 0.0006, by Fisher's exact test). When lysates from the engorged ticks were spiked with the 500 prelysed B. burgdorferi, none of the samples yielded a positive PCR signal, indicating the presence of inhibitory substances. Consistent with this observation, PCR amplification of the original engorged tick lysates after extraction with a DNA extraction kit, resulted in detection of B. burgdorferi DNA in 13 specimens (23%). Furthermore, when 500 prelysed B. burgdorferi were added to the treated extracts, all samples (56 of 56) were PCR positive. Thus, extraction resulted in removal of inhibitors of PCR amplification present in unprocessed engorged tick lysates. Furthermore, additional titration experiments showed that some inhibitory substances may also be present in unfed ticks, although this inhibition does not completely prevent detection of B. burgdorferi DNA in unprocessed lysates. This study clearly demonstrates that inhibitors of PCR amplification are present in engorged ticks and prevent accurate determination of B. burgdorferi infection rates by this method unless steps are taken to remove such inhibitors.

Animals↗

Landscape characterization of peridomestic risk for Lyme disease using satellite imagery.

Remotely sensed characterizations of landscape composition were evaluated for Lyme disease exposure risk on 337 residential properties in two communities of suburban Westchester County, New York. Properties were categorized as no, low, or high risk based on seasonally adjusted densities of Ixodes scapularis nymphs, determined by drag sampling during June and July 1990. Spectral indices based on Landsat Thematic Mapper data provided relative measures of vegetation structure and moisture (wetness), as well as vegetation abundance (greenness). A geographic information system (GIS) was used to spatially quantify and relate the remotely sensed landscape variables to risk category. A comparison of the two communities showed that Chappaqua, which had more high-risk properties (P < 0.001), was significantly greener and wetter than Armonk (P < 0.001). Furthermore, within Chappaqua, high-risk properties were significantly greener and wetter than lower-risk properties in this community (P < 0.01). The high-risk properties appeared to contain a greater proportion of broadleaf trees, while lower-risk properties were interpreted as having a greater proportion of nonvegetative cover and/or open lawn. The ability to distinguish these fine scale differences among communities and individual properties illustrates the efficiency of a remote sensing/GIS-based approach for identifying peridomestic risk of Lyme disease over large geographic areas.

Animals↗

Detection of Borrelia burgdorferi OspA in Ixodes scapularis larvae by an antigen-capture enzyme-linked immunosorbent assay.

The Borrelia burgdorferi outer surface protein A (OspA) was quantified by an antigen-capture ELISA. The test detected 0.156 ng OspA/B, using purified rabbit IgG as a detection system. Dose-response relationship was described by a three-parameter equation and second degree polynomials. The estimated amount of OspA in host-attached Ixodes scapularis larvae was positively correlated with the tick's engorgement status, whereas the presence of blood in OspA-negative larvae reduced test absorbance. The antigen-capture ELISA can be effectively used in the ecology and epidemiology of Lyme borreliosis. However, host attached larvae should be matched by engorgement level to remove the effect of this variable on test results.

Animals↗

Duration of tick bites in a Lyme disease-endemic area.

Regression equations, based on scutal index (body length/scutal width), were developed to determine the duration of attachment for nymphal and adult female lxodes scapularis ticks. Feeding times were calculated for 444 nymphal and 300 female ticks submitted by bite victims between 1985 and 1989 in Westchester County, New York, an area where Lyme disease is highly endemic. Nymphs were attached for a mean of 34.7 hours, with 26.8% removed after 48 hours, the critical time for transmission of Borrelia burgdorferi. Attachment times increased with victim age class (Kruskal-Wallis test, p < 0.05). Mean duration of attachment for female ticks (28.7 hours) was significantly less (Kruskal-Wallis test, p < 0.05) than that for nymphs, with 23.3% attached for more than 48 hours. The 0- to 9-year age class had the highest proportion (37.1%) of females attached for more than 48 hours. Nymphs remain attached to adult tick-bite victims longer than they remain attached to children. However, children have a high risk of acquiring Lyme disease because they receive more nymphal bites and also because they are less likely to have female ticks removed in time to prevent transmission.

Adolescent↗

Surgical treatment of epilepsy: the problem of lesion/focus incongruence.

BACKGROUND: This study suggests an alternative surgical strategy for treating patients with intractable epilepsy in whom a lesion, visualized by imaging, is found to be at a distance from the maximal electroencephalographic abnormality (focus). METHODS: Sixty patients (divided into three groups of 20), all of whom have had surgical resection for intractable epilepsy, are reviewed. Group A patients, representing the most common situation of a congruent electroencephalographic focus and structural lesion, underwent resection of the lesion/focus. Group B patients, in whom the focus and the lesion are incongruent, underwent resection of the focus only. Group C patients are those where the focus and lesion are incongruent; in this group, the lesion only was resected. RESULTS: Group A patients underwent resection of the lesion/focus (sites: 13 temporal, six frontal, and one parietal) with excellent results. Group B patients, in whom the focus only was resected (lesion sites: 14 temporal, four parietal, and two occipital) obtained poor results. Group C patients had excellent results following resection of the lesion only (lesion sites: 12 temporal, seven frontal, and one parietal). The superior surgical outcome in seizure control of group C is comparable to that seen in group A (Chi2 contingency test; Chi2 = 3.27 p > .05, 3 degrees of freedom) and is in contrast to the poor results seen in group B (Chi2 = 20.59 p < .001, 3 degrees of freedom). CONCLUSION: In those patients where a choice between a focus and a lesion is imperative, the lesion detected by imaging should be given priority in surgical resection.

Brain Diseases↗

Safety, efficacy, and immunogenicity of a recombinant Osp subunit canine Lyme disease vaccine.

A subunit canine Lyme disease vaccine formulated with recombinant lipidated Osp A and OspB and saponin QS21 was assessed for safety, protective efficacy, and immunogenicity. Ten normal beagles were subcutaneously vaccinated twice at age 12 and 16 weeks, respectively. Three months after the second vaccination, the vaccinates and another 10 nonvaccinated control beagles were challenged by feeding ticks on each dog for 5 days using eight field-collected adult female and six adult male Ixodes scapularis infected with Lyme disease spirochetes per dog. Adverse reactions associated with the vaccinations were limited to injection site swellings which occurred within the first 48 h and resolved within a week. The local reaction was independent of vaccination times and tick challenge. On the basis of typical clinical signs, xenodiagnosis, and diagnostic immunoblotting, all 10 controls were infected; five developed lameness and three of them experienced at least two to three episodes of limping during a 10-month monitoring period. In contrast, eight of ten vaccinates were protected and two infected vaccinates, as judged by xenodiagnosis, were asymptomatic. None of the protected vaccinates developed antibodies to diagnostic spirochetal antigens other than OspA and OspB. In contrast, most controls produced antibodies to borrelial antigens, but not to OspA and OspB. Antibody production in vaccinates receiving a third vaccination 10 months postchallenge was greatly boosted; the geometric mean antibody titer was significantly higher (P < 0.0001) than that tested prechallenge. Thus, the subunit canine Lyme disease vaccine was safe and protective and elicited immunological memory. Vaccinated dogs were serologically distinguishable from those naturally exposed.

Animals↗

Suppression of acute Ixodes scapularis-induced Borrelia burgdorferi infection using tumor necrosis factor-alpha, interleukin-2, and interferon-gamma.

Down-regulation of mammalian cytokine production has been demonstrated during tick feeding. To examine the hypothesis that reconstitution of cytokines during tick feeding could facilitate immune containment of Borrelia burgdorferi, the following experiments were done. C3H/HeJ mice were given cytokines for 10 days after Ixodes scapularis attachment. At day 21, ear biopsies were analyzed for B. burgdorferi. Polymerase chain reaction analysis indicated a protection rate of 95% in mice receiving tumor necrosis factor (TNF)-alpha. Mice that received interleukin (IL)-2 or interferon (IFN)-gamma had infection rates of 30%-45% compared with 83% for untreated controls. No correlation was noted between neutralizing antibody, reactivity by Western blot, and subsequent protection. Culture of B. burgdorferi in cytokine-conditioned media indicated that TNF-alpha, IFN-gamma, and IL-2 were not cytotoxic for B. burgdorferi. These data suggest that cytokine-induced protection from B. burgdorferi infection was immune-mediated and that cellular immunity may be associated with protection from I. scapularis-induced infection.

Acute Disease↗