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Biomedical subjects

Andrew Spielman

Publications and source records attributed to Andrew Spielman.

At least 19 recordsLinked to original sources

Confirmation of tick bite by detection of antibody to Ixodes calreticulin salivary protein.

Ticks introduce a variety of pharmacologically active molecules into their host during attachment and feeding in order to obtain a blood meal. People who are repeatedly exposed to ticks may develop an immune response to tick salivary proteins. Despite this response, people usually are unaware of having been bitten, especially if they are not repeatedly exposed to ticks. In order to develop a laboratory marker of tick exposure that would be useful in understanding the epidemiology of tick-borne infection and the immune response to tick bite, we developed an enzyme-linked immunosorbent assay (ELISA) to detect antibody to a recombinant form of calreticulin protein found in the salivary glands of Ixodes scapularis, a member of a complex of Ixodes ticks that serve as the vectors for Lyme disease, human babesiosis, and human granulocytic anaplasmosis. Using this assay, we tested sera obtained from C3H/HeN and BALB/c mice before and after experimental deer tick infestation. These mice developed antibody to Ixodes calreticulin antigen after infestation. We then used the same assay to test sera obtained from people before and after they experienced deer tick bite(s). People experiencing deer tick bite(s) developed Ixodes calreticulin-specific antibody responses that persisted for up to 17 months. This Ixodes recombinant calreticulin ELISA provides objective evidence of deer tick exposure in people.

Animals↗

Community-based rice ecosystem management for suppressing vector anophelines in Sri Lanka.

Sri Lanka is one of the Asian countries most affected by mosquito-borne diseases, especially malaria. This 18-month study assessed the effectiveness of a new community-based ecosystem management programme to control mosquito vectors in the country's rice ecosystem. Farmers in a malaria-prone village were educated and motivated to engage in source reduction as well as measures to restore and maximise rice ecosystem functions. Over the course of the programme, the impact of farmers' ecosystem management on local mosquito ecology was also examined. Although little impact was detected on Culex and Aedes densities, adult Anopheles density was significantly suppressed in the southwest monsoon season. Rice farmers who manage their ecosystems can reduce the burden of Anopheles mosquitoes, interrupt malaria transmission and prevent the destruction of ecosystems.

Adolescent↗

Efficacy of resmethrin aerosols applied from the road for suppressing Culex vectors of West Nile virus.

We determined whether aerosol applications of resmethrin, delivered from the road, suppress the reproductive activity of Culex pipiens pipiens and Cx. restuans mosquitoes in suburban sites located near Boston. Oviposition implies a prior blood-feeding event and hence a potential West Nile virus (WNV) transmission-related event. Droplet size, rate of delivery and meteorological conditions were monitored. The target populations proved to be fully susceptible to the insecticide that was used. The roads in the test sites generally gave adequate opportunity for insecticidal coverage. We found that the aerosol plume may have failed to contact the target mosquitoes and conclude that such insecticidal aerosols, delivered from the road, may not effectively reduce the force of transmission of WNV in our test sites.

Aerosols↗

Babesia microti primarily invades mature erythrocytes in mice.

Babesia microti is a tick-borne red blood cell parasite that causes babesiosis in people. Its most common vertebrate reservoir is the white-footed mouse. To determine whether B. microti invades reticulocytes, as does the canine pathogen B. gibsoni, we infected the susceptible inbred mouse strains C.B-17.scid and DBA/2 with a clinical isolate of B. microti. Staining of fixed permeabilized red blood cells with 4',6'-diamidino-2-phenylindole or YOYO-1, a sensitive nucleic acid stain, revealed parasite nuclei as large bright dots. Flow cytometric analysis indicated that parasite DNA is primarily found in mature erythrocytes that expressed Babesia antigens but not the transferrin receptor CD71. In contrast, CD71-positive reticulocytes rarely contained Babesia nuclei and failed to express Babesia antigens. Accordingly, the frequency of YOYO-1-positive, CD71-negative cells strongly correlated with parasitemia, defined as the frequency of infected red blood cells assessed on Giemsa-stained blood smears. Importantly, the absolute numbers generated by the two techniques were similar. Parasitemia was modest and transient in DBA/2 mice but intense and sustained in C.B-17.scid mice. In both strains, parasitemia preceded reticulocytosis, but reticulocytes remained refractory to B. microti. In immunocompetent C.B-17 mice, reticulocytosis developed early, despite a marginal and short-lived parasitemia. Likewise, an early reticulocytosis developed in resistant BALB/cBy and B10.D2 mice. These studies establish that B. microti has a tropism for mature erythrocytes. Although reticulocytes are rarely infected, the delayed reticulocytosis in susceptible strains may result from parasite or host activities to limit renewal of the mature erythrocyte pool, thereby preventing an overwhelming parasitemia.

Animals↗

Ethical dilemmas in malaria control.

Because the term "malaria control" specifies an anti-malaria activity rather than an outcome of that action, progress has been evaluated in terms of the effort expended. Plans that specify goals and time lines tend to lack irreversible endpoints. Anti-malaria interventions that are stimulated by economic considerations focus on sites in which the residents enjoy some employment advantage, while interventions based on humanitarian objectives serve the neediest residents of broad regions. Site-specific interventions are conducted by industrial or municipal agencies, while regional interventions are conducted by public agencies. Industry contributes an element of sustainability by injecting the possibility of gainful employment into the site. Efforts that distribute assets mainly to the richest-of-the-poor may fail to preserve lives that would otherwise have been preserved, while those that serve the poorest-of-the-poor may fail to create sustainable cycles of health and wealth. Progress in relieving the burden imposed by malaria requires economically motivated as well as humanitarian contributions, and both should specify realistically time-limited goals that ultimately permit deintensification.

Chemical Industry↗

Impact of education on knowledge, agricultural practices, and community actions for mosquito control and mosquito-borne disease prevention in rice ecosystems in Sri Lanka.

Mosquito-borne diseases are a major public health threat in Sri Lanka. A 20-week pilot education program to improve community knowledge and mosquito control with participatory and non-chemical approaches was developed, implemented, and evaluated using pre-educational and post-educational surveys in two intervention and two comparison villages. Correlates of baseline knowledge were sex, number of family members, ratio of family members with malaria history, school education level, and availability of electricity at the residence. Participation in the educational program led to improved knowledge of mosquito ecology and disease epidemiology, changes in agricultural practices, and an increase in environmentally sound measures for mosquito control and disease prevention. The variety of actions at the post-educational stage were determined by improved knowledge, but not by sociodemographic characteristics. Such community-based educational interventions are effective in increasing understanding and active involvement in mosquito control and disease prevention in rice ecosystems regardless of sociodemographic characteristics.

Adult↗

Reinfection and relapse in early Lyme disease.

To determine whether recurrent episodes of appropriately treated Lyme disease are caused by reinfection or relapse, we monitored pertinent clinical manifestations and serology of residents of an endemic site each year for 14 years. Of 253 episodes of early Lyme disease recorded among 213 residents, we observed 40 recurrent episodes. Virtually all included an erythema migrans (EM) rash that appeared at body sites that differed from those of the initial rash, no subjects produced detectable levels of specific antibody between sequential episodes, all episodes occurred a year or more after the initial EM episode, and all occurred during late spring and early summer. People experiencing recurrent episodes tended to have frequent contact with vector ticks. Prompt administration of standard antibiotic therapy for early Lyme disease reliably eliminates persistent infection and prevents relapse.

Animals↗

Hypersensitivity to ticks and Lyme disease risk.

Although residents of Lyme disease-endemic regions describe frequent exposure to ticks, Lyme disease develops in relatively few. To determine whether people who experience cutaneous hypersensitivity against tick bite have fewer episodes of Lyme disease than those who do not, we examined several factors that might restrict the incidence of Lyme disease among residents of Block Island, Rhode Island. Of 1,498 study participants, 27% (95% confidence interval [CI] 23%-31%) reported > or = 1 tick bites, and 17% (95% CI 13%-21%) reported itch associated with tick bite in the previous year. Borrelia burgdorferi infected 23% (95% CI 20%-26%) of 135 nymphal Ixodes scapularis (I. dammini) ticks. The likelihood of Lyme disease infection decreased with >3 reports of tick-associated itch (odds ratio 0.14, 95% CI 0.94-0.03, p = 0.01). Prior exposure to uninfected vector ticks protects residents of disease-endemic sites from Lyme disease.

Animals↗

Age-associated decline in resistance to Babesia microti is genetically determined.

BACKGROUND: Although infection by the protozoan Babesia microti is rarely symptomatic in immunocompetent young people, healthy individuals aged >50 years may experience life-threatening disease. To determine the basis for this age relationship, we developed a mouse model of babesiosis using a novel clinical isolate of B. microti. METHODS: Mice were infected at 2, 6, 12, or 18 months. Parasitemia was monitored on Giemsa-stained blood smears or by flow cytometry. RESULTS: In DBA/2 mice, early and persistent parasitemias increased with age at infection. BALB/c and C57BL/6 mice were resistant, regardless of age, which indicates that allelic variation determines resistance to B. microti. Unlike immunocompetent mice, SCID mice, which retain an innate immune system but lack the lymphocytes needed for adaptive immunity, developed high and persistent levels of parasitemia that were markedly reduced by transfer of naive BALB/c or DBA/2 splenocytes. BALB/c cells reduced the persistent parasitemia to a greater extent than did age-matched DBA/2 cells. Of importance, there was an age-associated loss of protection by cells of both strains. CONCLUSION: The resistance to B. microti infection conferred by the adaptive immune system is genetically determined and associated with age. We postulate that there are age-related differences in the expression of alleles critical for adaptive immunity to B. microti.

Aging↗

Adaptation of diverse lyme disease spirochetes in a natural rodent reservoir host.

We compared the relative reservoir competence of European wood mice for two genospecies of Lyme disease spirochetes by analyzing susceptibility, intrinsic incubation period, and degree and duration of infectivity. Borrelia afzelii, specializing in particular reservoir hosts, is better adapted to those hosts than is the more generalist genospecies B. burgdorferi sensu stricto.

Adaptation, Physiological↗

A global index representing the stability of malaria transmission.

To relate stability of malaria transmission to biologic characteristics of vector mosquitoes throughout the world, we derived an index representing the contribution of regionally dominant vector mosquitoes to the force of transmission. This construct incorporated published estimates describing the proportion of blood meals taken from human hosts, daily survival of the vector, and duration of the transmission season and of extrinsic incubation. The result of the calculation was displayed globally on a 0.5 degrees grid. We found that these biologic characteristics of diverse vector mosquitoes interact with climate to explain much of the regional variation in the intensity of transmission. Due to the superior capacity of many tropical mosquitoes as vectors of malaria, particularly those in sub-Saharan Africa, antimalaria interventions conducted in the tropics face greater challenges than were faced by formerly endemic nations in more temperate climes.

Animals↗

The malaria gap.

Although the correlation between malaria and poverty is apparent, the nature of the linkages in terms of directions and mechanisms of causation is less so, and different methodologic approaches provide widely divergent perspectives concerning the impact of the disease. Certain macroeconomic studies find that in highly endemic countries, malaria may be responsible for reducing economic growth by more than one percentage point a year. Microeconomic studies, which aggregate the cost per case, find a considerably smaller impact, generally less than one percent of annual per capita gross domestic product. The large gap between these estimates suggests economic externalities associated with malaria that make the burden much greater than the sum of the costs of individual cases. Both the magnitude of the burden and the channels through which malaria affects reduces income are important for policymakers. We explore this gap, examining diverse mechanisms through which malaria can affect long-term economic development.

Africa↗

A readily constructed lard-can trap for sampling host-seeking mosquitoes.

Although lard-can traps have been used for sampling host-seeking mosquitoes for at least a half-century, the materials from which they originally were constructed no longer are available. We therefore devised a method for constructing such devices from parts available in the ventilation industry. These traps, baited with birds and mounted near the tops of trees, were employed to monitor the host-seeking activity of Culex spp. mosquitoes. Lard-can traps, constructed in this manner, are economical and sturdy and effectively sample the Culex mosquitoes that appear to perpetuate West Nile virus in North America.

Animals↗

Reduced variation among northern deer tick populations at an autosomal microsatellite locus.

To determine whether genes flow freely between populations of the Ixodes ricinus-like ticks of eastern North America, and to determine whether the abundant northerly populations of these vectors of Lyme disease and other zoonotic infections may have arisen recently from a small cohort of ancestral founders, we characterized the nuclear IR27 microsatellite alleles in ticks sampled from the geographic extremes of their ranges. These microsatellite alleles differentiated populations located in the southeastern, northcentral and northeastern United States, respectively. Although evident heterozygous genotypes are about as frequent as would be expected in randomly mating populations, particular microsatellite alleles and diploid genotypes occur more frequently in certain populations than in others. Ticks from the Northeast and upper Midwest are markedly more related to each other than to ticks from the Southeast. Patterns of diversity present in this nuclear microsatellite marker correspond to those evident at a mitochondrial locus and indicate that the deer ticks of the Northeast and upper Midwest are genetically isolated from those in the Southeast. The Ixodes ricinus-like ticks that impose a public health burden in the northeastern and northcentral United States originated recently in a common founder population.

Animals↗

Research approaches in the development of interventions against vector-borne infection.

The conceptual basis of public health entomology developed at the turn of the twentieth century with the seminal experiments that guided the first vector-directed interventions. Within 50 years, technological advances built confidence in the power of research to resolve threats posed by vector-borne pathogens. Hope that the resulting diseases might be eliminated by time-limited interventions, however, soon became remote, thereby intensifying research efforts in vector biology. Beginning in the 1960s, US investigator-initiated grant proposals in vector biology were reviewed by a panel of the National Institutes of Health (NIH) that considered all proposals relating to 'Tropical Medicine and Parasitology' (TMP). Following the recommendation of a conference held in 1978, proposals relating to insect physiology came to be reviewed by TMP. A standing 'ad hoc entomology' study section was formed in 1982 to deal with this influx of proposals. Another conference, held in 1993, encouraged consideration of proposals relating to vector transgenics by that study section. By 1994, this diversion caused the community of US public health entomologists to petition, in vain, for a return to the original concept of vector biology. By 2003, so many molecular proposals were submitted that entomological studies containing a field component were removed to an epidemiological study section distinct from TMP. In 2002, only half as many vector biology training programs could be identified in the US as in 1982, with a proportionate loss of associated faculty. A conference convened by the Institute of Medicine in 2003 concluded that the 'human resource capacity' in the US suitable for dealing with vector-related issues in health should be rebuilt. Although the development of such a discipline would depend largely on the system of investigator-initiated research proposals awarded by NIH, private donors and foundations seem likely to play an important role in this dynamic. The meld of vector biology, insect physiology and vector transgenics that will characterize the faculty that produces this new generation of public health entomologists remains to be defined.

Animals↗

A component of maize pollen that stimulates larval mosquitoes (Diptera: Culicidae) to feed and increases toxicity of microbial larvicides.

To explain how larval Anopheles arabiensis Patton feed effectively in the turbid water in which they frequently develop, we determined whether an extractable component of maize, Zea mays L., pollen enhances feeding by these mosquitoes. Maturing maize produces a copious amount of wind-borne pollen that is nutritious enough and produced over a sufficient period to support the development of at least one generation of anopheline mosquitoes. Larval An. arabiensis readily ingest the contents of maize pollen or the intact pollen grains themselves. An aqueous extract of maize pollen markedly accelerates the rate at which larval An. arabiensis ingest inert particles and strongly enhances the effectiveness of Bti against larval An. arabiensis. We conclude that the ability of larval anopheline mosquitoes to feed on maize pollen in turbid water is enhanced by the release from these pollen grains of a water-soluble phagostimulatory component (or components), which may be used to increase ingestion of microbial entomotoxins.

Animals↗