Why entomological antimalaria research should not focus on transgenic mosquitoes.
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Journal Article↗
Biomedical subjects
A Spielman
Publications and source records attributed to A Spielman.
Diagnosis of babesiosis: evaluation of a serologic test for the detection of Babesia microti antibody.
To assess the possibility of standardization of a commonly used indirect immunofluorescent antibody (IFA) test for detection of Babesia microti antibody in human sera, the results from four reference laboratories were compared. Patients with babesiosis from southern New England (n = 25) and subjects with no history of babesiosis from southern New England (n = 55) and Iceland (n = 50) were enrolled in the study. Anti-Babesia antibody titers were determined in a blinded fashion by IFA test. The range of test results in the four laboratories was 88%-96% sensitivity, 90%-100% specificity, 69%-100% positive predictive value, and 96%-99% negative predictive value. Interlaboratory and intralaboratory concordance ranged from 84% to 85% and 94% to 100%, respectively. This B. microti IFA procedure is a sensitive, specific, and reproducible method for diagnosing babesiosis and is suitable for use as a standard in laboratories testing human sera for B. microti antibody.
Adult↗
Cultivation and phylogenetic characterization of a newly recognized human pathogenic protozoan.
An intraerythrocytic protozoan (WA1) recently isolated from a patient in Washington State was shown to be morphologically identical to Babesia microti but biologically and genetically distinct. Continuous growth of WA1 was established in stationary erythrocyte cultures. Hybridization of a chemiluminescent Babesia-specific DNA probe to Southern blots of restriction enzyme-digested genomic DNA showed that WA1 could be distinguished from other Babesia species that were antigenically cross-reactive (Babesia gibsoni and babesial parasites from desert bighorn sheep, Ovis canadensis nelsoni) or known to infect humans (B. microti, Babesia divergens, and Babesia equi), or both. A 1436-bp portion of the nuclear small subunit rRNA gene of WA1 was sequenced and analyzed. Genetic distance analysis showed that WA1 is most closely related to the canine pathogen B. gibsoni and lies within a phylogenetic cluster with Theileria species and B. equi. The methodology described will be useful for improved diagnosis and identification of human protozoal pathogens.
Animals↗
Amplifying role of edible dormice in Lyme disease transmission in central Europe.
To determine whether the presence of edible dormice (Glis glis) amplifies the risk of human infection by the Lyme disease spirochete (Borrelia burgdorferi), the capacity of dormice as reservoir hosts was compared with that of other potential reservoirs in a central European site where risk of human infection is intense. Dormice appeared to be more heavily infested by subadult vector wood ticks (Ixodes ricinus) than were other reservoir hosts. Although their spirochete competence was similar to other reservoir hosts, field-derived dormice infected more ticks than did other rodents in the site, because nymphal ticks most readily feed on them. Spirochetes isolated from dormice appeared identical to those implicated as agents of Lyme disease. Subadult wood ticks become replete and detach from dormice during late afternoon when dormice are at rest in their nests. Thus, the presence of edible dormice in Central Europe amplifies transmission of the agent of Lyme disease and intensifies the risk of human infection.
Animals↗
Detection of Borrelia burgdorferi DNA in museum specimens of Peromyscus leucopus.
To determine whether Borrelia burgdorferi was enzootic within the United States at the beginning of the 20th century, ear skin samples taken from museum specimens of the white-footed mouse (Peromyscus leucopus) were examined for evidence of spirochetal DNA. In total, 280 samples from mice collected between 1870 and 1919 were analyzed by a nested polymerase chain reaction protocol. Of these, 2 specimens from the vicinity of Dennis, Massachusetts, during 1894 were reproducibly positive for B. burgdorferi OspA sequences. The remaining 278, representing both currently endemic and nonendemic sites, were negative for spirochetal DNA. These studies suggest that the agent of Lyme disease was present in a suitable reservoir host in the United States before the turn of the century and provide evidence against a hypothesis of recent introduction of this zoonotic agent to North America.
Animals↗
Incorporation of body components of diverse microorganisms by larval mosquitoes.
A pulse-purge schedule of exposure to labeled microorganisms was used to compare their digestibility by larval mosquitoes. Larvae were placed for an hour in suspensions of diverse axenically grown microorganisms that had been labeled with radioactive carbon (in the form of glucose or glycine). The guts of these mosquitoes were then purged with nonlabeled Sephadex particles for 30 min, and retained radioactivity was measured. Larvae imbibed no dissolved material. Larval mosquitoes differ in their capacity to derive label from algae (sensu lato), and certain algae contribute more label to these mosquitoes than do others. The nature of any algal food, as well as the feeding habits and developmental stage of the larva, influence its capacity to derive label from algae. This pulse-purge method of analysis can assist in the selection of algal "vectors" suitable as vehicles for transgenic larvicide. Although larval mosquitoes fail to assimilate the contents of Palmellacoccus cells with which they are confined, as much as 1/3 of the body contents of a Euglena gracilis cells become incorporated into their bodies. Because larval mosquitoes internalize more material from Euglena than they do from various other algae, these microorganisms provide a promising candidate vehicle for transgenic Bacillus thuringiensis israelensis.
Aedes↗
Transmission of the agent of Lyme disease on a subtropical island.
To determine whether the agent of Lyme disease (Borrelia burgdorferi) perpetuates on a subtropical island, we recorded prevalence of spirochetal infection in Ixodes ricinus ticks collected on Madeira Island and identified local reservoir hosts of both pathogen and vector tick. Spirochetes infect at least 1.3% of the nymphal ticks collected in a particular site. Subadult ticks frequently parasitized Norway as well as black rats on the island, and Lyme disease spirochetes were found in these hosts. Each was competent as reservoir host. Canaries, lizards and domestic ungulates, on the other hand, were incompetent for Madeiran spirochetal isolates. Madeiran spirochetes stimulated rodents to recognize the same antigens as did spirochetes isolated on the European continent. The polymerase chain reaction amplified identical specific sequences of Madeiran spirochetes as of European-derived spirochetes. Rats appear to be the main reservoir hosts of the agent of Lyme disease on Madeira Island, and cattle and sheep serve as definitive hosts of the vector tick. The agent of Lyme disease is enzootic on this subtropical island some 10 degrees of latitude south of the northern Mediterranean coast. Because I. ricinus ticks frequently attack people on Madeira Island, Lyme disease should be considered as a cause of locally acquired human illness.
Animals↗
Risk of infection from and treatment of tick bite.
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Animals↗
Protection against antigenically variable Borrelia burgdorferi conferred by recombinant vaccines.
Due to local variation in the antigenicity of the agent of Lyme disease (Borrelia burgdorferi), a vaccine derived from any one isolate of this spirochete may fail to protect against the heterogeneous population of organisms that may be present in an enzootic focus. Accordingly, we determined whether antigenically variable spirochetes delivered by naturally infected ticks, collected from a site where transmission is intense, may fail to infect mice actively immunized with recombinant glutathione transferase outer surface fusion proteins A or B (OspA and OspB). Virtually all mice vaccinated by either immunogen appeared not to become infected, as determined by culture or histopathology of their tissues. We conclude that Osp vaccination of mice effectively prevents infection by the agent of Lyme disease in a simulated natural cycle of transmission.
Animals↗
Carotenoid-depletion diet for use in long-term studies.
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Adult↗
Norway rats as reservoir hosts for Lyme disease spirochetes on Monhegan Island, Maine.
To determine whether the agent of Lyme disease, Borrelia burgdorferi, may be maintained in the absence of its usual white-footed mouse reservoir host, Ixodes dammini ticks from an island where mice are absent were examined. Prevalence of spirochetal infection was described for ticks removed from mammals, birds, and vegetation on Monhegan Island, Maine. Forty percent of adult I. dammini removed from vegetation were infected. Norway rats were heavily infested with ticks, and > 60% of such ticks contained spirochetes. Other hosts were less frequently infested by ticks, and few such ticks were infected by spirochetes. The prevalence of antibody to B. burgdorferi was 23% in dogs and cats; 4% of island residents had Lyme disease. Thus, rats maintain Lyme disease spirochetes on Monhegan Island, and there may be transmission of this agent by I. dammini to island residents and their pets.
Animals↗
Topical prophylaxis for Lyme disease after tick bite in a rodent model.
To determine whether infection with the Lyme disease spirochete (Borrelia burgdorferi) can be aborted by topical application of antibiotic to the site of tick attachment, individual infected nymphal deer ticks (Ixodes dammini) were permitted to feed on the ears of mice, and various antibiotics were applied to the feeding site at intervals after the replete infecting tick had detached. Infection in each mouse was determined by serology and by xenodiagnosis at 4 weeks after the bite of the infected tick. None of these mice became infected when antibiotic was topically applied to the site of tick attachment within 2 days after the spirochete-infected ticks had detached. In contrast, all nontreated and virtually all solvent-treated mice became persistently infected. Thus, persistent infection by the agent of Lyme disease can be aborted by appropriate topical application of antibiotic.
Administration, Topical↗
Reduced abundance of immature Ixodes dammini (Acari: Ixodidae) following incremental removal of deer.
The abundance of immature Ixodes dammini Spielman, Clifford, Piesman & Corwin was monitored for 9 yr (1983-1991) before and during the controlled, limited hunting of white-tailed deer, Odocoileus virginianus (Zimmerman), at a coastal Massachusetts site. Deer abundance was reduced from an estimated 350 during 1985 to approximately 60 during 1991. Although annual fluctuations were large, mean larval I. dammini abundance declined from 20.8 per white-footed mouse, Peromyscus leucopus (Rafinesque), during 1983-1986 before deer reduction to 10.3 per mouse following deer reduction (1987-1991). Similarly, mean nymphal I. dammini abundance declined from 2.7 per mouse before intervention to 1.6 per mouse after intervention. Immature I. dammini population fluctuations were not associated with those of P. leucopus. The total population of larvae infesting P. leucopus declined from 3,596 ticks before intervention to 1,535 ticks after intervention. Concurrently, the total nymphal population declined from 417 ticks before intervention to 187 ticks after intervention. The number of feeding adult female I. dammini on deer increased as deer density decreased.
Animals↗
Reservoir competence of white-footed mice for Babesia microti.
Although the white-footed mouse, Peromyscus leucopus Rafinesque, has been incriminated as the main reservoir of the agent of human babesiosis, Babesia microti Franca, a quantitative demonstration of reservoir competence has not been presented. Mice captured within an intensely zoonotic site served as host for laboratory-reared larval Ixodes dammini Spielman, Clifford, Piesman, and Corwin, and the resulting nymphal ticks were assayed for evidence of salivary gland infection by the piroplasm. Solely 25% of the mice were patently parasitemic on thin blood smears, but virtually all mice infected ticks with B. microti. Thus, smear positivity correlates poorly with infectivity. Infection in smear-negative mice, however, was demonstrated by the use of the polymerase chain reaction. White-footed mice may be chronically infected by the piroplasm with parasitemias detectable only by the most sensitive methods, yet efficiently serve as a source of infection. We conclude that P. leucopus serves to maintain B. microti in the northeastern United States, as it does the spirochetal agent of Lyme disease.
Animals↗
Time limitation and the role of research in the worldwide attempt to eradicate malaria.
The U.S. Congress established an intense, time-limited, worldwide malaria eradication program in 1958 and assigned operational responsibility to the U.S. Agency for International Development (and its predecessors). When the program was terminated on schedule in 1963, approximately $400 million had been consumed and malaria prevalence had greatly been reduced. Transmission began to increase thereafter. The open-ended WHO global eradication effort began in 1955 ended in 1969 and consumed approximately $15 million during the 1958-1963 period of progress, mainly provided by the United States. Intensified anti-malaria interventions continued after Congress discontinued direct support. Although malariological research was discouraged during the period of time limitation, it was embraced as the conceptual basis for the open-ended period of intervention that followed. This effort saved many lives but expended our ability to intervene against future epidemics and reduced human herd immunity. To avoid the "great gamble" inherent in any ambitious intervention against this disease, future programs should be designed to seek incremental, local antimalaria gains.
Animals↗
Rapid dissemination by the agent of Lyme disease in hosts that permit fulminating infection.
We determined whether the agent of Lyme disease (Borrelia burgdorferi) disseminates more rapidly following deposition in hosts that permit fulminating infection than in hosts in which infection is relatively benign. Thus, individual infected nymphal deer ticks (Ixodes dammini) were permitted to engorge on the ears of C3H mice, and the site of attachment was excised at intervals thereafter. Infection in each mouse was determined by serology and by examining previously noninfected ticks that had engorged on these mice. These results were compared with data obtained similarly by using the CD-1 strain of mice in which the agent is relatively nonpathogenic. When the site of inoculation was ablated within 2 days after the infected tick became replete, dissemination was aborted. Spirochetemia could not be demonstrated in any of these mice. We conclude that Lyme disease spirochetes disseminate from the feeding lesion of an infecting tick more rapidly in certain highly spirochete-susceptible mice than in others in which pathogenesis is less severe.
Animals↗
Accelerated transmission of Lyme disease spirochetes by partially fed vector ticks.
To determine how rapidly Lyme disease spirochetes (Borrelia burgdorferi) can be transmitted by partially fed vector ticks (Ixodes dammini), attached nymphs were removed from their hosts at various intervals post-attachment and subsequently permitted to re-feed to repletion on noninfected mice. We confirm previous reports that ticks deposit Lyme disease spirochetes in the skin of their hosts mainly after 2 days of attachment. Those that have been removed from a host within this interval can reattach and commence feeding. Spirochete-infected nymphs that have previously been attached to a host for 1 day become infectious to other hosts within another day. Noninfected nymphs acquire infection from spirochete-infected hosts within a day of attachment and become infectious to other hosts 3 to 5 days later. Virtually all ticks transmitted infection when reattaching after first feeding for 2 days. We conclude that partially fed nymphal ticks transmit spirochetal infection more rapidly than do ticks that have never been attached to a host and that infected ticks become infectious before they molt.
Animals↗
Standardization of medium for culturing Lyme disease spirochetes.
To standardize the procedure for isolating and culturing Lyme disease spirochetes, we modified the composition of the medium generally used for this purpose (BSK-II) and developed a system for its distribution. This medium contains no gelatin or agarose, and various components are used in proportions that differ from those in BSK-II. Each of the major proteinacious components was screened by substitution in samples of the complete product. The final medium was evaluated for the capacity to grow related spirochetes including Borrelia burgdorferi N40, Guilford, and JD-1 as well as strains of Borrelia hermsii (HS-1) and of Borrelia coriaceae (CO53). Each isolate developed from inocula containing as few as one to five organisms. Doubling time of B. burgdorferi during log-phase growth at 37 degrees C was 10 to 12 h. Lyme disease spirochetes were isolated in this medium from ear punch biopsies and dermal aspirates from naturally infected mice and rabbits, from dermal biopsies from a human patient, and by sampling field-collected deer ticks (Ixodes dammini). Cultured spirochetes remained infective to mice and to ticks. The medium can be stored at -20 degrees C or lower temperatures for at least 8 months without effect on its ability to support growth of small inocula to densities exceeding 10(8) spirochetes per ml. Lyme disease spirochetes remained infective to mice after being stored at -80 degrees C in this medium for at least 8 months. We anticipate that the availability of this standardized medium (Sigma Chemical Co.), supplemented with prescreened rabbit serum, will facilitate comparison of research results between laboratories and may eventually permit definitive clinical diagnosis of Lyme disease based on demonstration of the pathogen. The standardized medium is designated BSK-H.
Animals↗