A Model for Experimental Exposure of Humans to Larval Ixodes scapularis Ticks

Summary

This article presents the methodology for exposing humans to larval Ixodes scapularis for clinical research. The technique is relatively simple, tolerable by the research volunteers, and can be modified according to experimental needs. Such research involving human subjects must be conducted under clinical study protocols approved by the appropriate regulatory authorities.

Abstract

Tickborne diseases are a significant public health problem in the United States and worldwide. Ticks are obligate blood-feeding arthropods; an ixodid tick must remain attached to the skin of the host and complete its multi-day feeding process to acquire its blood meal. Exposing animals to ticks is a common practice for studying host responses to tick bites and tickborne diseases. We developed the procedure, conducted the first human research study, and published the findings on exposing human volunteers to uninfected larval Ixodes scapularis ticks. This article describes the methodology used to construct the containment dressing, how to apply and secure the ticks to the host, how to maintain the dressing, and how to remove the ticks from the host. Exposing volunteers to tick bites is an experimental procedure and must be performed under a clinical research protocol approved by the appropriate regulatory authorities. This method allows for translational research to better understand the human response to tick bites and foster the development of diagnostics, prevention, and therapies for tickborne diseases.

Introduction

Hard ticks (Ixodidae: Acari) are obligate blood-feeding ectoparasites that occur worldwide and are capable of transmitting a broad range of pathogens, including bacteria, viruses, and parasites, of major medical and veterinary importance. Ixodid ticks must remain attached to the host for days to complete a blood meal, and they have the capacity to stay attached to the skin while avoiding recognition, preventing local blood coagulation, and facilitating long-term feeding^1,2,3. Animal studies have demonstrated that non-permissive hosts acquire resistance to tick bites with repe....

Protocol

Exposing volunteers to tick bites is an experimental method and must be conducted under a clinical research protocol approved by the relevant regulatory authorities. The clinical studies (NCT01143558, NCT02446626, and NCT05036707) were approved by the respective institutional review boards, conducted under investigational device exemptions granted by the US Food and Drug Administration, and carried out in accordance with Good Clinical Practice guidelines. Additionally, these studies were registered with ClinicalTrials.go.......

Discussion

While animal studies involving exposures to ticks^4,5,6,7,21 have been invaluable in increasing our understanding of host response to tickborne diseases and tick bites, these models have limitations in how well they predict the human host response. This model, which describes the methodology for exposing humans to tick bites in a controlled manner, can be easil.......

Materials

Name	Company	Catalog Number	Comments
20 G needle	Any brand		For puncturing the vial cap.
3" x 3" containment dressing	Monarch Labs Names	LeFlap	https://www.monarchlabs.com/ordering
4" x 4" extra-thin hydrocolloid dressing	ConvaTec	DuoDerm	https://www.convatec.com/products/advanced-wound-care/brand-names/pc-wound-duoderm-granluflex/duoderm-extra-thin-dressing/
4" x 4" gauze	Monarch Labs Names		For cleaning skin
Clean water or saline			For cleaning skin
Moisture barrier (e.g. 7" x 7")	AquaGuard	TIDI	For showering, ttps://www.tidiproducts.com/product-listing/aquaguard-shower-cover-sheets
Non-adhesive foam dressing	Coloplast	Biatain	https://www.coloplast.us/biatain-non-adhesive-en-us.aspx
Roll of 2" hypoallergenic tape	Monarch Labs Names	Durapore	For reinforcing containment dressing.
Roll of adhesive tape			For trapping ticks
Vials for collection (e.g. cryovials)	Ependorf	ECC200