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An ecological approach to preventing human infection: vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle.

Many pathogens, such as the agents of West Nile encephalitis and plague, are maintained in nature by animal reservoirs and transmitted to humans by arthropod vectors. Efforts to reduce disease incidence usually rely on vector control or immunization of humans. Lyme disease, for which no human vaccine is currently available, is a commonly reported vector-borne disease in North America and Europe. In a recently developed, ecological approach to disease prevention, we intervened in the natural cycle of the Lyme disease agent (Borrelia burgdorferi) by immunizing wild white-footed mice (Peromyscus leucopus), a reservoir host species, with either a recombinant antigen of the pathogen, outer surface protein A, or a negative control antigen in a repeated field experiment with paired experimental and control grids stratified by site. Outer surface protein A vaccination significantly reduced the prevalence of B. burgdorferi in nymphal blacklegged ticks (Ixodes scapularis) collected at the sites the following year in both experiments. The magnitude of the vaccine's effect at a given site correlated with the tick infection prevalence found on the control grid, which in turn correlated with mouse density. These data, as well as differences in the population structures of B. burgdorferi in sympatric ticks and mice, indicated that nonmouse hosts contributed more to infecting ticks than previously expected. Thus, where nonmouse hosts play a large role in infection dynamics, vaccination should be directed at additional species.

Animals↗

[The activity of cyfluthrin and cypermethrin-based preparations against the vector of the causative agent of tick-borne relapsing fever].

Laboratory tests have established a high activity and long-term persistence of some cipermethrin isomers (fendone, fastac) and cifluthrin (zolfac) against the tick Ornithodoros papillipes, a carrier of tick-borne relapsing fever. These indices are considerably superior to those of an isomer mixture of cipermethrin (cimbush, ripkord). This can be applied to deltamethrin and cigalothrin. The findings suggest that these agents are highly promising in controlling the carrier of tick-borne relapsing fever along with a significant reduction in the ecological pesticidal load in the focus.

Animals↗

Prevention of borreliosis in persons bitten by infected ticks.

A study on prevention of borreliosis in humans bitten by infected ticks was performed in 1992-1994 in the Perm' region of Russia. Adult Ixodes persulcatus ticks were removed from the study subjects, and live preparations made from the material obtained from the gut of each tick were microscopically analyzed (up to 250 microscopic fields per preparation). Persons were divided into experimental and control groups (261 and 97 persons, respectively). The experimental group received doxycycline (100 mg twice daily) for 3-5 days after the tick bite. In the control (untreated) group, 12 persons contracted borreliosis. In the experimental group, the disease was diagnosed in three subjects. Morbidity per 100 patients in the experimental group was 1.1, i.e. 11 times lower than that in the control group. Identification of Borrelia in ticks by microscopic analysis, followed by a short-term treatment with antibiotics according to microbiological indications, is an efficient method for preventing persons from contracting borreliosis.

Animals↗

Infestation with pathogen-free nymphs of the tick Ixodes scapularis induces host resistance to transmission of Borrelia burgdorferi by ticks.

Female BALB/c mice were infested four times with pathogen-free Ixodes scapularis nymphs prior to infestation with nymphs infected with Borrelia burgdorferi B31. Each infestation was separated by a 14-day tick-free period. Mean weights of fed ticks and percentage reaching repletion did not indicate development of acquired resistance. Only 16.7% of mice repeatedly infested with pathogen-free ticks prior to infected I. scapularis nymph challenge became positive for B. burgdorferi. One hundred percent of control mice infested only with infected ticks were culture positive for B. burgdorferi.

Animals↗

Modulation of Borrelia burgdorferi stringent response and gene expression during extracellular growth with tick cells.

Borrelia burgdorferi N40 multiplied extracellularly when it was cocultured with tick cells in L15BS medium, a medium which by itself did not support B. burgdorferi N40 growth. Growth of B. burgdorferi N40 in the presence of tick cells was associated with decreased production of (p)ppGpp, the stringent response global regulator, a fourfold decrease in relA/spoT mRNA, an eightfold net decrease in bmpD mRNA, and a fourfold increase in rpsL-bmpD mRNA compared to growth of B. burgdorferi in BSK-H medium. As a result, the polycistronic rpsL-bmpD mRNA level increased from 3 to 100% of the total bmpD message. These observations demonstrate that there are reciprocal interactions between B. burgdorferi and tick cells in vitro and indicate that the starvation-associated stringent response mediated by (p)ppGpp present in B. burgdorferi growing in BSK-H medium is ameliorated in B. burgdorferi growing in coculture with tick cell lines. These results suggest that this system can provide a useful model for identifying genes controlling interactions of B. burgdorferi with tick cells in vitro when it is coupled with genetic methods to isolate and complement B. burgdorferi mutants.

Animals↗

Immune protection conferred by the baculovirus-related glycoprotein of Thogoto virus (Orthomyxoviridae).

The coding region of segment 4 of Thogoto (THO) virus, a tick-borne member of the Orthomyxoviridae, was expressed in a baculovirus system under the control of the polyhedrin promoter. This construct expressed authentic envelope glycoprotein as determined by size and antigenic reactivity with a panel of monoclonal antibodies (MAbs). Immunization of hamsters with Spodoptera frugiperda (Sf21) cells infected with the recombinant baculovirus induced neutralizing and protective antibodies against virus challenge; control hamsters developed clinical disease with high-titer viremia 3 days postchallenge. In contrast to hamsters, guinea pigs are comparatively resistant to THO virus infection but support nonviremic transmission between cofeeding infected and uninfected ticks. However, when uninfected ticks fed on guinea pigs immunized with the baculovirus recombinant, only 2% became infected following virus challenge of the animals compared to 26% of ticks on control nonimmune guinea pigs. Furthermore, neutralizing MAbs specific for THO viral glycoprotein protected mice against lethal challenge with THO virus; nonneutralizing MAbs specific for the glycoprotein, which inhibit THO viral agglutinating activity, did not induce a protective response. Thus at least in the murine model, protective immunity is conferred by antibodies directed against the neutralizing epitope(s) of the baculovirus-related glycoprotein of THO virus.

Animals↗

Vaccination against worm parasites of animals.

The 1990s have seen the culmination of decades of painstaking research with the registration and launch of Tickgard (Hoechst), a recombinant vaccine against Boophilus microplus, and the provisional registration of a Taenia ovis vaccine. Research continues to hold promise for immunological control of Echinococcus, Fasciola, Haemonchus, Trichostrongylus and Ostertagia. Blood-sucking parasites (e.g. ticks and H. contortus) are susceptible to control by vaccines containing 'novel' or 'concealed' antigens where serum antibodies in blood meals attack targets in the gut. Antibodies also provide protection in taeniid models, whereas the protective response to be sought in Fasciola remains unclear. More problematic are formulations and delivery strategies to induce expulsion of gastrointestinal nematodes, using vaccines containing recombinant 'conventional' antigens. The use of computer models to simulate vaccine efficacy in worm control and challenges to the concept of 'hypo-responsiveness' of young lambs will encourage cautious optimism and lively debate as to the prospects for integrated worm control using parasite vaccines. This review covers the aspirations, current success and problems faced by researchers in the parasite arena.

Animals↗

Transovarial transmission of African swine fever virus in the argasid tick Ornithodoros moubata.

The aim of this study was to determine filial infection prevalence of experimentally infected colony Ornithodoros moubata Walton (Ixodoidea: Argasidae) ticks for African swine fever virus (ASFV). Three groups of ticks were used: an uninfected control group, one group orally infected with the VIC T90/1 isolate and another group orally infected with the LIV 13/33 isolate of ASFV. The results show that filial infection prevalences were not constant but were highly variable between egg batches from different ticks and between successive egg batches from the same tick. Filial infection prevalences ranged from 1.8% to 31.8% for ticks infected with the VICT90/1 isolate and from 1.2% to 35.5% for ticks infected with the LIV 13/33 isolate. A similar pattern was noted after the third feed. Immunohistochemisty showed that virus replicates in the developing larval cells and not in the yolk sac cells or within the outer layers of the eggs. The results show that ASFV can replicate to a high titre (10(5.1)log10HAD50) within the larval cells of the developing egg.

African Swine Fever↗

Tick-borne relapsing fever: an interstate outbreak originating at Grand Canyon National Park.

During the 1973 summer season, 27 employees and 35 overnight guests at the North Rim, Grand Canyon National Park, Arizona, acquired febrile illnesses compatibel with relapsing fever. Sixteen cases were confirmed by finding Borrelia spirochetes in peripheral blood smears or inoculated Swiss mice. Retrospective surveys of 278 employees and 7247 guests at the park revealed that acquisition of illness was significantly associated with the persons sleeping in rustic log cabins and acquiring bites of "unknown" insects. From rodent nesting materials found in the walls and attics of cabins where cases had occurred, infective Ornithodoros hermsi ticks were recovered. Exceptional activity of ticks in human populations appeared to have resulted from a decreased population of the ticks' usual rodent hosts. Vector control activities consisted of spraying the cabins with residual insecticide, removing nesting materials, and "rodent proofing." This outbreak, the largest yet identified in North America, extends the known range of a principal vector and establishes the North Rim as an endemic source of tick-borne relapsing fever.

Adult↗

Tick-borne encephalitis virus transmission between ticks cofeeding on specific immune natural rodent hosts.

To determine whether the portion of a vertebrate host population having specific immunity to tick-borne encephalitis (TBE) virus can participate in the TBE virus transmission cycle, natural hosts immunized against TBE virus were challenged with infected and uninfected ticks. Yellow-necked field mice (Apodemus flavicollis) and bank voles (Clethrionomys glareolus) were either immunized with TBE virus by subcutaneous inoculation of the virus, or they were exposed to virus-infected Ixodes ricinus ticks. One month later, when serum neutralizing antibody was detectable, the animals were infested with infected (donor) adult female ticks and uninfected (recipient) nymphal ticks; recipients were allowed to feed either in close contact (chamber 1) or physically separated (chamber 2) from the infected donor ticks. Following challenge with infected (and uninfected) ticks, viremia developed in all the control, nonimmune animals, whereas viremia was undetectable in all those animals naturally immunized by previous exposure to infected ticks. Despite the presence of neutralizing antibodies in all the immunized animals, 89% (24/ 27) immune animals supported virus transmission between infected and uninfected cofeeding ticks. Most transmission was localized, occurring within chamber 1; disseminated transmission from chamber 1 to chamber 2 was reduced. Immunization by tick bite was more effective than immunization by syringe inoculation in blocking cofeeding virus transmission. Nevertheless 76% (9/12) animals with "natural" immunity still supported transmission. The results demonstrate that natural hosts having neutralizing antibodies to TBE virus (and no detectable viremia) can still support virus transmission between infected and uninfected ticks feeding closely together on the same animal. These observations have important epidemiological implications relating to the survival of TBE virus in Nature.

Animals↗

[Ixodidae ticks in Bishkek].

The fauna of Ixodidae ticks was studied in Bishkek in 1998-2004. The city is situated in the center of the Chuisk valley, at the foot of the Kirghiz ridge, at the boundary of a submountain-plain-arid region and a plain-piedmont-semiarid one with steppe fragments. The ticks were gathered on a flag from small mammalians caught by Gero traps, from birds, domestic and agricultural animals. A total of 648 animals of 13 species were examined. The bites of ticks were registered in 98 persons in the city. A total of 1085 ticks of all developmental phases were gathered. The faunal complex of Ixodidae ticks was represented by the following species: Ixodes persulcatus Sch (domination index (DI) = 0.45), Haemaphysalis punctata Can. Et Fanz (DI = 21.93), Haemaphysalis erinacei Paves (DI = 1.0), Dermacentor marginatus Sulter (DI = 0.27), Rhipicephaluspumilio Sch. (DI = 0.84), Rhipicephalus sanguineus Latr. (DI = 0.56), Rhipicephalus turanicus Pom (DI = 74.85), Hyalomma anatolicum Koch (DI = 0.87). The regional and climatic conditions of Bishkek and the presence of profeeders in the private sector (domestic and agricultural animals, synanthropic rodents, and birds) favor the existence of the R. turanicus population. The mosaic pattern of a cultural region in the center of the city permits small populations of several species of ticks to exist.

Agriculture↗

Sequencing a new target genome: the Boophilus microplus (Acari: Ixodidae) genome project.

The southern cattle tick, Boophilus microplus (Canestrini), causes annual economic losses in the hundreds of millions of dollars to cattle producers throughout the world, and ranks as the most economically important tick from a global perspective. Control failures attributable to the development of pesticide resistance have become commonplace, and novel control technologies are needed. The availability of the genome sequence will facilitate the development of these new technologies, and we are proposing sequencing to a 4-6X draft coverage. Many existing biological resources are available to facilitate a genome sequencing project, including several inbred laboratory tick strains, a database of approximately 45,000 expressed sequence tags compiled into a B. microplus Gene Index, a bacterial artificial chromosome (BAC) library, an established B. microplus cell line, and genomic DNA suitable for library synthesis. Collaborative projects are underway to map BACs and cDNAs to specific chromosomes and to sequence selected BAC clones. When completed, the genome sequences from the cow, B. microplus, and the B. microplus-borne pathogens Babesia bovis and Anaplasma marginale will enhance studies of host-vector-pathogen systems. Genes involved in the regeneration of amputated tick limbs and transitions through developmental stages are largely unknown. Studies of these and other interesting biological questions will be advanced by tick genome sequence data. Comparative genomics offers the prospect of new insight into many, perhaps all, aspects of the biology of ticks and the pathogens they transmit to farm animals and people. The B. microplus genome sequence will fill a major gap in comparative genomics: a sequence from the Metastriata lineage of ticks. The purpose of the article is to synergize interest in and provide rationales for sequencing the genome of B. microplus and for publicizing currently available genomic resources for this tick.

Animals↗

Postexposure treatment with doxycycline for the prevention of tick-borne relapsing fever.

BACKGROUND: Tick-borne relapsing fever (TBRF) is an acute febrile illness. In Israel, TBRF is caused by Borrelia persica and is transmitted by Ornithodoros tholozani ticks. We examined the safety and efficacy of postexposure treatment to prevent TBRF. METHODS: In a double-blind, placebo-controlled trial, 93 healthy subjects with suspected tick exposure (52 with signs of tick bites and 41 close contacts--those without signs but with a similar risk of contact with ticks) were randomly assigned to receive either doxycycline (Dexxon, in a dose of 200 mg the first day and then 100 mg per day for four days) or placebo after presumed exposure to TBRF. Cases of TBRF were defined by fever and a positive blood smear. Serologic analysis for cross-reactivity to Borrelia burgdorferi and polymerase chain reaction (PCR) for the borrelia glpQ gene were also performed. RESULTS: After randomization, 47 subjects (26 with signs of tick bites and 21 close contacts) received doxycycline. Forty-six other subjects (26 with signs of tick bites and 20 close contacts) received placebo. All 10 cases of TBRF identified by a positive blood smear were in the placebo group of subjects with signs of a tick bite (P<0.001). These findings suggested a 100 percent efficacy of preemptive treatment (95 percent confidence interval, 46 to 100 percent). PCR for the borrelia glpQ gene was negative at baseline for all subjects and subsequently positive in all subjects with fever and a positive blood smear. Seroconversion was detected in eight of nine cases of TBRF. PCR and serum samples were negative for all of the other subjects tested. No major treatment-associated adverse effects were identified. CONCLUSIONS: Treatment with doxycycline is safe and efficacious in preventing TBRF after suspected exposure to ticks in a high-risk environment. (ClinicalTrials.gov number, NCT00237016 [ClinicalTrials.gov].).

Adult↗