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Biomedical subjects

A Spielman

Publications and source records attributed to A Spielman.

At least 73 records · Page 4Linked to original sources
PubMed1995

Discriminating between Ixodes ticks by means of mitochondrial DNA sequences.

Ticks of the genus Ixodes have recently assumed prominence because they frequently serve as vectors of important zoonoses, including Lyme disease and babesiosis. The morphological characteristics that have been used in their identification often are ambiguous and are useful solely at a particular stage of development. Here we report the DNA sequence of the mitochondrially encoded 16S rRNA gene of nine different Ixodes ticks and an outgroup from another genus, Dermacentor. The sequences readily discriminate between these ticks. Samples of I. dammini from the northeastern and upper midwestern United States differ from southeastern I. scapularis at about 2% of the nucleotides. This difference is about half that separating other members of the I. ricinus group of species, but exceeds typical levels of intraspecific variation. Two major clades exist within the I. ricinus complex. One includes I. cookei, I. hexagonus, and I. angustus. The other includes I. persulcatus, I. pacificus, I. muris, I. ricinus, I. scapularis, and I. dammini. We conclude that mtDNA sequences are useful for unravelling the systematics of these important vectors of human disease.

Animals↗
PubMed1995

Early murine Lyme carditis has a macrophage predominance and is independent of major histocompatibility complex class II-CD4+ T cell interactions.

To compare the role of macrophages and CD4+ T lymphocytes in early Lyme carditis, immunohistochemical techniques were used to analyze cardiac infiltrates in immunocompetent mice infected with Borrelia burgdorferi spirochetes. Macrophages predominated in the infiltrate during the first 4 weeks after infection. CD4+ and CD8+ lymphocytes each constituted < 5% of the infiltrate; B lymphocytes were rare. Infected mice deficient in class II major histocompatibility complex (MHC) antigen and depleted of CD4+ lymphocytes developed similar infiltrates, suggesting that class II MHC-CD4+ lymphocyte interactions do not play a critical role in disease initiation. Expression of mRNA encoding JE within areas of cardiac inflammation implicates this chemokine in the recruitment and activation of macrophages in this disease. These data demonstrate that early murine Lyme carditis requires neither class II antigen expression nor presentation of antigen to CD4+ T lymphocytes and suggest a direct response of macrophages to cardiac tissue invasion by B. burgdorferi.

Animals↗
PubMed1995

Nondifferentiation between Lyme disease spirochetes from vector ticks and human cerebrospinal fluid.

To determine whether Lyme disease neuropathogenesis may result from infection by a particular segment of the locally extant population of spirochetes, genetic markers of spirochetes found in cerebrospinal fluid (CSF) of 12 pediatric patients were compared with those in spirochetes from 40 vector ticks sampled in the vicinity of their homes. The primary structure of the outer surface protein A served as the marker of variation; a fragment of the corresponding gene was amplified by nested polymerase chain reaction and the products sequenced. Tick-derived variants clustered in seven distinct categories, of which four were present in CSF. One of the CSF variants differed from any found in ticks. Coinfection by different spirochete variants was infrequent in ticks and absent in human samples. Spirochetal neuropathology in children in our study site does not correlate with a particular segment of the tickborne pathogens present in nature.

Amino Acid Sequence↗
PubMed1995

Efficacy of human Lyme disease vaccine formulations in a mouse model.

Although immunization with recombinant outer surface protein A (OspA) appears to protect mice against infection by the agent of Lyme disease, all reported experiments have involved formulations that would not be suitable for use in humans or have not used realistic challenges. This study was designed to determine whether vaccines prepared and used in a phase I human trial, including one currently being used for a phase II trial in sites with endemic Borrelia burgdorferi, conferred protection in the C3H/HeJ mouse model. The challenge was ticks collected from a major site of the trial. None of the vaccinated mice became infected or developed disease, whereas 60% of unvaccinated mice became infected. Spirochetes were destroyed within the guts of virtually all recovered challenge ticks. These preparations of recombinant OspA effectively induced immunity to protect mice from Lyme disease when bitten by ticks collected from a field trial site.

Adjuvants, Immunologic↗
PubMed1995

Sensitive and specific colorimetric dot assay to detect eastern equine encephalomyelitis viral RNA in mosquitoes (Diptera: Culicidae) after polymerase chain reaction amplification.

A sensitive and specific colorimetric dot assay following polymerase chain reaction (PCR) method has been developed to detect 0.1 pg of eastern equine encephalomyelitis viral (EEEV) RNA. The assay is 250-fold more sensitive than analysis by electrophoresis and is based on converting a 291-nucleotide sequence of the viral coat protein amino terminus into a double-stranded DNA (dsDNA) and amplifying the DNA using a specific primer pair and PCR. The amplified complementary DNA (cDNA) is denatured adsorbed onto a nylon strip, baked, and detected with a digoxigenin-labeled probe. Dots with viral cDNA are stained dark red, whereas controls do not stain or stain lightly. The assay is very specific and sensitive and detects only EEEV. RNA of Venezuelan equine encephalitis, St. Louis encephalitis, Keystone, Flanders, Tensaw, and western equine encephalitis viruses were not detected. EEEV (Ten Broeck) RNA was detected at the 10-ng level, indicating that the prototype we used may have different nucleotides in the region where the primer pair binds. The PCR amplified EEEV cDNA that was 92% homologous to the consensus sequence of EEEV. The detection of EEEV in the liver of an infected Emu bird and in field-collected mosquitoes from Florida and Massachusetts that were analyzed concurrently as blind samples by tissue culture plaque assay and by PCR dot analysis proved that the assay is sensitive and can be used to detect infected mosquitoes. The assay can detect at least 1 infected mosquito in a pool of 1,000 uninfected mosquitoes.

Animals↗
PubMed1995

Nonvascular delivery of St. Louis encephalitis and Venezuelan equine encephalitis viruses by infected mosquitoes (Diptera: Culicidae) feeding on a vertebrate host.

We determined whether mosquitoes infected with the viruses St. Louis encephalitis (SLE) or Venezuelan equine encephalitis inoculate virus extravascularly or directly into the vascular system. Infected mosquitoes fed on the distal 3rd of the tails of suckling mice. Significantly more mice whose tails were amputated at the midpoint within 10 min of mosquito feeding survived than did siblings whose tails remained intact. Even when tails were amputated 1-6 h after SLE virus-infected mosquitoes fed, the median time to death was significantly longer in mice with amputated tails (7.1 d) than in mice with intact tails (5.8 d). We concluded that mosquitoes inoculated virus primarily extravascularly, rather than directly into the vascular system, while feeding on a vertebrate host. Extravascular, rather than intravascular, delivery of pathogens by mosquitoes may affect disease pathogenesis and vaccine efficacy.

Aedes↗
PubMed1995

Antibody response of the mouse reservoir of Borrelia burgdorferi in nature.

To determine whether the white-footed mouse reservoir host (Peromyscus leucopus) of the agent of Lyme disease (Borrelia burgdorferi) naturally mounts an immune response against the full range of antigens expressed by this zoonotic pathogen, we analyzed the pattern of immunoreactivity of these rodents at sites in which the intensity of transmission differs. Although the incidence of seroconversion within the reservoir population relates proportionally to the density of subadult deer ticks (Ixodes dammini), seroprevalence appears constant. About a fifth as many juvenile mice recognize spirachete antigens as do adult mice. Virtually all reservoir mice in nature recognize the p20, p35.5, p39, and p58 antigens, regardless of the intensity of transmission. Seropositive mice retain reactivity to a wide range of spirochetal antigens. Few mice recognize flagellin, OspB, and OspC. Although a third of serum samples include reactivity to a 31-kDa band, this reaction is irregular and may represent an uncharacterized antigen that comigrates with OspA. Mice captured where transmission is intense recognize the same spectrum of antigens as do mice captured where vector ticks are scarce.

Age Factors↗
PubMed1995

Differential spirochetal infectivities to vector ticks of mice chronically infected by the agent of Lyme disease.

We determined whether the infectivity of the Lyme disease spirochete (Borrelia burgdorferi) to vector ticks varies with the duration of infection in laboratory mice. Thus, noninfected nymphal deer ticks were permitted to feed on two strains of early (2 months after infection) and late (8 months after infection) spirochete-infected mice. The attached ticks were removed from their hosts at specified time intervals and were thereafter examined for spirochetes by direct immunofluorescence microscopy. Spirochetes can be acquired by nymphal ticks as fast as 8 h after attachment. More than 80% of the attached ticks acquired spirochetal infection within 48 h after feeding on early spirochete-infected mice. In contrast, spirochetal infectivity to ticks was less than 50% after feeding on late spirochete-infected mice. The overall infectivity of spirochete-infected mice to ticks correlated with the duration of tick attachment. In addition, there was no adverse effect on the spirochetal infectivity to ticks by high levels of host antibody against spirochetes, and no obvious differences in infectivity to ticks was observed by the site of tick feeding. We conclude that the span of spirochetal infectivity to ticks varies with the duration of infection in mice and suggest that spirochetes may persist and may be evenly distributed in the skin of infected hosts, regardless of prominent host immunity.

Animals↗
PubMed1995

Effect of ambient temperature on competence of deer ticks as hosts for Lyme disease spirochetes.

We determined whether the temperature of extrinsic incubation affects the competence of vector ticks as hosts for Lyme disease spirochetes (Borrelia burgdorferi). Larval Ixodes dammini ticks that had engorged on spirochete-infected C3H mice were incubated continuously at various temperatures, and the gut contents of the resulting nymphs were examined for spirochetes by direct immunofluorescence microscopy. Spirochetes were present in virtually all nymphs kept at 27 degrees C or less for 6 months, in only 10% of those kept at 33 degrees C, and in none kept at 37 degrees C. Spirochetes became undetectable within 8 weeks when nymphs were warmed from 27 to 33 degrees C beginning at the time of molting. Nymphs became virtually noninfective for mice after incubation at temperatures higher than 27 degrees C for 2 weeks or longer. We conclude that ambient temperatures in excess of 27 degrees C are not permissive for transmission of the agent of Lyme disease.

Animals↗
PubMed1995

Short report: mode of action of protective immunity to Lyme disease spirochetes.

To determine whether protective immunity against the agent of Lyme disease may be expressed mainly within its tick vector prior to transmission, we passively immunized mice at various intervals after infected ticks had attached, and assayed such mice for evidence of spirochetal infection by xenodiagnosis one month after challenge. Groups of CD-1 mice were intraperitoneally infused with 0.5 ml of hyperimmune rabbit or mouse serum, reagents and quantities previously determined to protect against syringe-challenge with 10(6) low-passage JD1 spirochetes 12 hr after passive transfer. Comparison groups received normal rabbit serum or saline. All mice were protected from infection when infused no more than one day after infective ticks were allowed to attach. However, if infused three or five days post-tick attachment, 60-100% of the mice became infected. All mice became persistently infected when infused with saline or normal rabbit serum. We conclude that antibody is protective against tick-transmitted spirochetal infection only when passively administered before the spirochetes are deposited in the skin of the host. Ingested antibody may destroy spirochetes or interfere with activation and replication within the tick gut, or with dissemination to the salivary glands. Lyme disease vaccines may thus be uniquely effective because of the vulnerability of the spirochetal agent within its vector.

Animals↗
PubMed1995

The economic burden imposed by a residual case of eastern encephalitis.

To estimate the economic burden imposed by eastern encephalitis (EE), we identified a series of residents of eastern Massachusetts who had survived EE infection and enumerated any costs that could be attributed to their experience. The records of three people who suffered only a transient episode of disease were analyzed as well as those of three who suffered severe residual sequelae. Transiently affected subjects mainly required assistance for direct medical services; the average total cost per case was $21,000. Those who suffered persistent sequelae remained at home and seemed likely to live a normal span of years, but without gainful employment. Early in the course of their chronic illness, costs ranged as high as $0.4 million per year, but plateaued at about $0.1 million after three years. Hospital costs, which dominated early in the disease experience, approached $0.3 million per patient. Educational costs tended to replace hospital costs after two years as the dominant economic burden and totaled about $0.3 million per patient during the first six years. Total costs then averaged almost $0.8 million. By the time that these subjects will have reached 22 years of age, disease-related costs will have totaled about $1.5 million. Institutionalization will impose an additional lifetime cost of $1.0 million. Insecticidal interventions designed to avert outbreaks of human EE infection cost between $0.7 million and $1.4 million, depending on the extent of the treated region. The direct costs of an intervention are less than the $3 million imposed on one person suffering residual sequelae of EE.

Adolescent↗
PubMed1995

Short report: density of Lyme disease spirochetes within deer ticks collected from zoonotic sites.

We determined whether the density of Lyme disease spirochetes varied between individual host-seeking deer ticks. Guts were dissected from 30 adult Ixodes dammini collected from three intensely zoonotic coastal Massachusetts sites, and the number of Borrelia burgdorferi present was estimated by a modified counting technique using indirect immunofluorescence. A median of 1,925 spirochetes was observed; ticks from the three sites contained similar numbers of spirochetes. No tick contained more than 4,500 spirochetes. Initial experimental reports establishing the efficiency of spirochetal transmission may have been based on ticks with a uniform spirochetal density, and extrapolations from these studies may thus overestimate the infectivity of host-seeking ticks in nature.

Animals↗
PubMed1995

A nestable fiber pot for sampling resting mosquitoes.

To enhance the effectiveness of an arbovirus monitoring program, we evaluated a commercially available device for sampling resting vector mosquitoes. Diverse Anopheles, Culiseta, and Culex mosquitoes were taken in these nestable fiber pots. The pots sample about as many Culiseta melanura mosquitoes per device as do conventional resting boxes, but fewer than do boxes fitted with expanded frames. More Cs. melanura, and more bloodfed mosquitoes, but fewer species of mosquitoes are harvested with fiber pots than with CDC light traps. Fiber pots are more readily used, transported, and stored and are less expensive than conventional resting box devices or CDC light traps. A monitoring program based on the use of fiber pots, therefore, expends fewer resources than one using conventional resting boxes and collects about as many vector mosquitoes.

Animals↗
PubMed1994

The emergence of Lyme disease and human babesiosis in a changing environment.

This pattern of spread of Lyme disease and its vectors in the northeastern United States and Europe derives from the recent proliferation of deer, and the abundance of deer derives from the process of reforestation now taking place throughout the North Temperate Zone of the world. Residential development seems to favor small tree-enclosed meadows interspersed with strips of woodland, a "patchiness" much prized by deer, mice, and humans. As a result, increasingly large numbers of people live where risk of Lyme disease and babesiosis is intense. The agents of these infections, that once were transmitted enzootically by an exclusively rodent-feeding vector, have become zoonotic.

Animals↗
PubMed1994

Emergence of eastern encephalitis in Massachusetts.

The 20th century emergence in Massachusetts of zoonotic eastern encephalitis was interpreted in terms of recorded environmental change. The main mosquito vector of the infection, Cs. melanura, appears to have been scarce in eastern North America before the 1930s. Its relative scarcity resulted from destruction of the swamps that had been lumbered or drained for farming in the 18th and 19th centuries. When swamps matured once again early in the 1900s, the formation of subsurface pools of water beneath mature trees would have increased the availability of breeding sites for this mosquito. Transmission would have further been enhanced by the simultaneous proliferation of wetland-roosting robins and the extinction of such vagile birds as the passenger pigeon. Although numerous horses were maintained in Massachusetts at the time, no outbreaks of "equine sleeping sickness" came to public notice between the 1830s and the 1930s, when mature trees were scarce and the fauna was most disturbed. The severity of the first major outbreak in 1938 may have been potentiated by the absence of herd-immunity in a rapidly proliferating population of reservoir birds. These considerations suggest that recent landscape and faunal changes caused zoonotic EE to emerge in Massachusetts after waning for a century.

Animals↗
PubMed1994

Virulence of vector-borne pathogens. A stochastic automata model of perpetuation.

To determine how virulence may be perpetuated in populations of vector-borne pathogens, we simulated their fitness in a stochastic simulation based on cellular automata. Thereby, directly transmissible pathogens that differed in virulence were permitted to compete for hosts with similarly virulent pathogens that could infect hosts remotely because they were vector-borne. Fitness was defined as the proportion of the host population infected with each pathogen at equilibrium. Virulent, directly transmitted pathogens prevailed solely when their infectivity was transient. When duration of infectivity exceeded that of host survival, the less virulent pathogen invariably prevailed. Although remotely transmitted virulent pathogens persisted somewhat longer than did virulent pathogens that were transmitted directly, they never perpetuated themselves. We conclude that populations of vector-borne pathogens may retain pathogenicity somewhat longer than do those that are directly transmitted, but that both kinds of pathogens tend to become nonvirulent.

Animals↗