Tick Bites, Tick Resistance
Conditions
Keywords
Tick resistance in naturally exposed individuals, tick resistance in tick-naive individuals
Brief summary
Tick-borne diseases are increasing worldwide, and there are currently few effective ways to prevent them. One promising new strategy is to develop a vaccine that targets the tick itself ("anti-tick vaccine") to block the transmission of multiple pathogens. Some animals naturally develop resistance to ticks after repeated tick bites. There are indications that a similar form of acquired tick resistance (ATR) may also occur in humans who have been heavily exposed to ticks. This study investigates whether humans can naturally develop tick resistance and how this affects tick feeding. The investigators will compare people with a long history of tick bites and self-reported signs of tick resistance to people who are tick-naïve. The investigators will also include a small group of volunteers who previously participated in an experimental human tick challenge to evaluate what their reaction on tickbites is 1-2 years after their initial exposures.
Detailed description
Study Objectives Primary Objective To determine whether humans develop naturally acquired tick resistance by measuring tick feeding success, specifically the weight of ticks after feeding. Secondary Objectives To measure additional tick feeding parameters (tick mortality, attachment rate, duration of feeding, and molting). To assess clinical skin reactions such as itch and redness. To study immune responses (antibodies and immune cells) against tick saliva proteins in all groups. To identify tick salivary antigens that may be useful for future anti-tick vaccine development. Study Design Single-center, open-label human experimental tick challenge study. Three groups: ATR group: 11 adults with extensive prior tick exposure and self-reported signs of tick resistance. Control group: 11 adults with no significant tick exposure. Follow-up challenge group: Up to 4 adults previously challenged in the "TICK ME" study. Outcome measures Primary Outcome Measure Post-feeding tick weight Secondary Outcome Measures Tick mortality, attachment rate, days attached, and molting success Clinical skin responses (itch, redness) Immune responses to tick salivary proteins Skin biopsy analyses
Interventions
OTHERTick challenge
uninfected ixodes scapularis ticks will be placed underneath a closed dressing
Sponsors
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Naturally acquired self-reported tick resistant individuals: * Age: 18 - 70 years; * History of repeated tick bites * Local reaction (like redness or itch) at place of previous tick bites and/or signs of impaired tick feeding after bite (anamnestic) Controls: • Age: 18 years - 70 years; Experimentally acquired tick resistant individuals: * Previous participant in the TICK ME study that has completed all 4 challenges * Age: 18 years - 70 years;
Exclusion criteria
* Current suspicion of any tick-borne disease * Diagnosed with tick-borne disease within the last year * Chronic skin condition affecting the skin of the arm; * Inability to maintain the dressing for any reason; * Known immunodeficiency or autoimmune disease; * Use of systemic immunomodulating drugs or chemotherapy, current or in the past; * Chronic use of antibiotics; * Unable to give informed consent or do not have a thorough command of the Dutch language; * Refusal to participate in specimen collection and storage for future study related use; * Pregnant or breastfeeding women; * Not willing to use adequate contraception during the study period; * Red meat allergy (both medically confirmed and self-reported); * Use of investigational therapy and devices during the time of the study; * Any other condition that, in the opinion of the investigator, would make the patient unsuitable for enrolment or could interfere with the patient participating in and completing the study. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tick feeding: tick weight | From the start of the tick challenge until feeding to repletion of the ticks (max 10 days) | Tick weight measured in mg after complete feeding of the tick |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tick feeding: tick mortality | From the start of the tick challenge until feeding to repletion of the ticks (max 10 days) | Tick mortality in % of fed ticks |
| Host reaction: redness | Redness will be monitored at day 2 and the last day of the tick challenge | Redness (using a standardized clinical erythema (CEA) score (scale 0-4) which is scored by physicians using photographs of tick bite lesions) |
| Host reaction: itch | Itch is measures daily during the tick challenge (From the start of the tick challenge until feeding to repletion of the ticks (max 10 days) | Itch (using Visual Analogue Scale 0-100) as a sign of a clinical reaction of the host |
| Host immune response: humoral | From the start of the challenge, day 2, day 5, final day of challenge (day 5-10) depending upon tick feeding, 3-5 weeks after the challenge and 10-12 weeks after the challenge | Humoral (qualitative by characterizing antibodies recognizing anti-tick antigens using a yeast surface display expressing tick salivary gland proteins) |
| Host immune response: cellular | From the start of the challenge, day 2, day 5, final day of challenge (day 5-10) depending upon tick feeding, 3-5 weeks after the challenge and 10-12 weeks after the challenge | Cellular (immunophenotyping of the different immune subsets in collected PBMCs at the specified time points) of immune responses in blood |
Countries
Netherlands
Contacts
PRINCIPAL_INVESTIGATORJoppe W Hovius, Prof. Dr.
Amsterdam UMC
Outcome results
None listed