exposing humans to larval ixodes scapularis to study host response to tickborne diseases and tick bites

Human Exposure to Larval Ticks for Tickborne Disease Research

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 feeding1,2,3. Animal studies have demonstrated that non-permissive hosts acquire resistance to tick bites with repeated tick exposures, which can lead to a decreased ability to transmit a pathogen, while ticks can repeatedly parasitize permissive hosts. Acquired tick resistance is dependent on the nature of the host immune response4,5,6,7.
Tickborne diseases are an increasing threat in the United States (US), with the number of reported cases more than doubling between 2004 and 20168,9. Due to climate change, the geographic ranges of different ticks continue to expand10,11. The leading tickborne diseases in the US include Lyme disease, anaplasmosis, ehrlichiosis, spotted fever rickettsiosis, babesiosis, tularemia, and Powassan virus disease8. Lyme disease, caused by infection with Borrelia burgdorferi sensu lato, is the most common tickborne disease in the US and Europe12. With approximately 476,000 individuals diagnosed with Lyme disease annually in the US, there is both a public health and economic burden to individuals and to society13,14,15.
Ixodes scapularis (the black-legged or deer tick) is the primary vector for Lyme disease, as well as anaplasmosis, babesiosis, Borrelia miyamotoi disease, and Powassan virus disease in the US. Other medically important tick species in the US include Amblyomma americanum (Lone star tick), Dermacentor variabilis (American dog tick), Ixodes pacificus (Western black-legged tick), Dermacentor andersoni (Rocky Mountain wood tick), Ixodes cookei (Groundhog tick), Dermacentor occidentalis (Pacific Coast tick), Rhipicephalus sanguineus (brown dog tick), and Amblyomma maculatum (Gulf Coast tick)16.
Developing a method to expose research volunteers to tick bites supports studies using the natural vector to search for evidence of infection, a procedure known as xenodiagnosis17,18,19,20,21, and to learn more about immunity induced by exposure to ticks, which can contribute to the discovery of an anti-tick vaccine5,6,7. The procedure described here was developed and used in the first human research study using laboratory-reared Ixodes scapularis larva for xenodiagnosis of B. burgdorferi infection after antibiotic therapy (NCT01143558), published in 201419. The system has been successfully used in a phase 2 study investigating whether a positive xenodiagnosis correlated with the persistence of symptoms after antibiotic treatment of Lyme disease (NCT02446626) and in a study exploring the host response to tick bites (NCT05036707).
This procedure protocol describes the process for creating the containment dressing, the tick placement procedure, and the tick removal procedure, as well as the site care needed to maintain the containment dressing. The details regarding the pathogen-free I. scapularis tick colony and tick exposure procedures used for the above-cited studies have been previously described19,22. This methodology offers a flexible research tool that can be adapted to studying different aspects of the human host response to tick bites, the effectiveness of tick prevention medications, as well as Lyme disease and other tickborne illnesses.

Author Spotlight: Controlled Human Exposure Model for Tick Research and Lyme Disease Studies

Un modelo para la exposición experimental de humanos a larvas de garrapatas Ixodes scapularis

This protocol offers an effective method for a controlled exposure of humans to ticks. For research, the protocol can be used to study the human immune response tick bites, as well as the development of diagnostics and preventions against tick-borne diseases. There were no published procedures for placing ticks on human research volunteers.The challenge was to develop a system that allowed the ticks to feed for days while also being comfortable for the participants. This model contains the ticks for the duration of the feeding and allow the research participants to proceed with their daily activities with minor lifestyle adjustments.

Exposición de humanos a larvas de Ixodes scapularis para estudiar la respuesta del huésped a las enfermedades transmitidas por garrapatas y las picaduras de garrapatas

Para comenzar, cree un campo visible colocando una hoja blanca alrededor del área de colocación. Use una gasa de cuatro por cuatro pulgadas, humedecida con agua limpia o solución salina, para limpiar la piel del sitio de colocación. Seque el sitio con una gasa limpia.Tome el apósito de contención preparado y retire el revestimiento adhesivo del lado hidrocoloide. Fije el apósito a la piel en el sitio de colocación. Rompe el hisopo de madera por la mitad para exponer los extremos irregulares.Ahora abra el frasco de garrapatas con cuidado. Use el extremo dentado del hisopo de madera para transferir las garrapatas activas del vial a la piel dentro del apósito de contención. A continuación, retire el revestimiento adhesivo de la capa de malla del apósito de contención y cierre la capa de malla sobre la abertura, asegurándose de que el adhesivo esté bien adherido.Aplique el apósito hidrocoloide extra delgado preparado de cuatro por cuatro pulgadas sobre el apósito de contención para mayor seguridad. Proporcione una cubierta de barrera contra el agua y cinta hipoalergénica de dos pulgadas al participante de la investigación. Revise periódicamente la adherencia de los bordes del apósito a la piel.Aplique cinta adhesiva adicional para reforzar los bordes según sea necesario. Perfore los orificios en la tapa del frasco con una aguja de calibre 20 si es necesario preservar las garrapatas vivas. Use malla de nailon o poliéster y la tapa para sellar el vial.Etiquete los viales de recolección de garrapatas con los identificadores requeridos. Para mantener la humedad, coloque el frasco de garrapatas en una bolsa hermética con una esponja húmeda. Coloque sábanas blancas alrededor del sitio del vendaje.Con toallitas con alcohol, retire con cuidado el vendaje de la piel. Coloque el vendaje retirado en el recipiente de recolección y examínelo para detectar la presencia de garrapatas desprendidas. Evalúe la piel en el sitio de colocación para ver si hay garrapatas adheridas.Use pinzas de punta fina para quitar las garrapatas adheridas. En el primer estudio de xenodiagnóstico humano se realizaron un total de 43 procedimientos. En comparación con el número de ticks colocadas, el porcentaje medio de recuperación de ticks adheridos fue de aproximadamente el 45%

Research

JoVE Journal

Immunology and Infection

Exposing Humans to Larval Ixodes scapularis to Study Host Response to Tickborne Diseases and Tick Bites

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

Tickborne diseases are a significant public health problem in the United States and worldwide. Ticks are obligate blood-feeding arthropods; an ixodid tick ...

Investigación

Inmunología e Infección

Dressing Preparation for Tick Placement and Containment to Study Human Response to Tick Bites

Preparación de apósitos para la colocación y contención de garrapatas para estudiar la respuesta humana a las picaduras de garrapatas