Keys to Prevent Human Monocytic Ehrlichiosis
Abstract
Rationale: Human monocytic ehrlichiosis (HME) is an emerging disease caused by infection with the bacterium Ehrlichia chaffeensis (Ech). HME is a severe systemic flu-like illness accompanied by hematologic abnormalities and mild hepatitis. Unlike most other bacteria, Ech infects and replicates inside human cells, similar to human immunodeficiency virus. The disease is not contagious, but transmitted to humans by the bite of infected ticks. Ticks acquire Ech infection by sucking the blood of infected animals. The Lone Star tick that transmits Ech is abundant in the US, and due to global warming, deforestation, and urbanization, the chances of tick bite and transmission of Ech are increasing. Military training and exercises expose troops to tick-infested habitats where Ehrlichia spp. are highly endemic. Since 1989, the US Army has had a Tick Surveillance program in place to track exposure of Soldiers to various tick-borne diseases, including HME, at military installations in the mid-Atlantic, south, northeast, and upper midwest regions. Indeed, the Ech was first isolated from a Soldier stationed at Fort Chaffee, Arkansas and named after Fort Chaffee. Studies of Soldiers in military training exercises carried out in areas where Ech is endemic have shown a high prevalence of seropositivity to Ech and related pathogens. Importantly, tick-borne diseases such as HME are considered a health threat to US personnel stationed around the world because human ehrlichiosis is endemic or potentially endemic in 26 countries in Europe, Asia, Africa, and South America. It is also possible that Soldiers could contract Ech via blood transfusion or organ transplantation, even by exposure to the blood from infected humans or animals. Moreover, Ech has been shown to survive for more than a week in refrigerated blood. An even higher risk of exposure to vector-borne disease exists for the US military working dogs during training and global deployment. Dogs are highly susceptible to tick-borne pathogens including Ech, and thus can serve as sentinels as well as useful animal models. The current therapy of choice is the broad-spectrum antibiotic doxycycline, but it is effective only if initiated early because delayed therapy initiation; for example, under battle circumstances in the field, it can lead to severe complications or death. Also, the presence of underlying illness or injury, stress, immunosuppression, and/or co-infection with other tick-borne pathogens can lead to severe complications or death with a mortality rate of 2%-5%. No vaccines exist for HME. Our laboratory recently discovered that a unique Ech surface protein, which we named Entry triggering protein of Ehrlichia (EtpE), is required for this bacterium to infect human cells. Antibody against EtpE greatly inhibited Ech infection of human cells in culture. Moreover, immunization of mice against EtpE significantly inhibited infection induced by syringe inoculation of Ech, suggesting it may be feasible to similarly vaccinate high-risk humans against HME, significantly improving prevention. The project is relevant to the Fiscal Year 2016 Tick-Borne Diseases Research Program (TBDRP) Focus Areas of Pathogenesis and Prevention. Scientific Objective: The objectives of our study are to investigate whether antibody against EtpE can block Ech transmission from tick to human cells, and to test whether vaccination of susceptible animals can block Ech infection from the bite of infected ticks. Aims of the Proposed Project: We have two specific aims. Specific Aim 1 is to determine whether EtpE protein is produced by Ech-infected tick cells and whether antibody against EtpE can prevent Ech transmission from tick cells to human cells in cell culture. Specific Aim 2 is to investigate whether EtpE is produced by Ech-infected salivary glands of ticks and whether immunization with EtpE-C can block Ech transmission from infected ticks to dogs by allowing Ech-infected ticks to
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710519
Entities
People
- Yasuko Rikihisa
Organizations
- Ohio State University
- United States Army