Reference Point Recognition of the threat of Ehrlichia ruminantium infection in domestic and wild ruminants in the continental United States Thomas R. Kasari, DVM, MVSc, DACVIM, DACVPM; Ryan S. Miller, MSC; Angela M. James, PhD; Jerome E. Freier, DVM, PhD isease attributable to Ehrlichia ruminantium (for- ABBREVIATION Dmerly Cowdria ruminantium) infection was first de- scribed in South Africa in 1838 as a nervous condition FAD Foreign animal disease of sheep that developed after a substantial infestation of ticks.1 It is an infectious but noncontagious tick-borne trophils and endothelial cells and replicates by binary disease (ie, heartwater) that affects domestic and wild fission and, less frequently, by budding. The number of ruminants. Infection often causes the death of clinically replicated organisms inside these cells can range from 1 affected ruminants. In 2009, many sub-Saharan African to several thousand.4,6 countries and the island of Guadeloupe in the Carib- Different strains of E ruminantium may not induce bean reported clinical cases of heartwater in their do- homologous or heterologous cross-protection, with this mestic ruminant populations.2 Additionally, livestock lack of immune induction potentially attributable to have died of heartwater on the islands of Marie-Galante antigenic diversity.4 Antigenic diversity also impacts the and Antigua in the Caribbean.3 degree of pathogenicity of various strains of E ruminan- On the basis of the proximity of the United States tium in Africa and the Caribbean islands. Whereas some mainland to the Caribbean islands, the ultimate concern strains are highly virulent, others appear to be non- for animal health officials, members of the livestock in- pathogenic.7,8 Remarkably, a less pathogenic strain of dustry, and other stakeholders may not be what should E ruminantium, which is referred to as Panola Mountain be done to keep heartwater from being introduced into Ehrlichia, may exist in the central, southeastern, and the continental United States, but rather what can be eastern United States; preliminary characterization of done to limit the extent of an outbreak when this in- this pathogen by investigators indicates that this strain cursion transpires. A key element to controlling the is genetically and antigenically more closely related to extent of a disease outbreak is early recognition of the E ruminantium than to any other Ehrlichia spp.9,10 In a disease in an animal population. Therefore, the pur- goat with experimentally induced disease,9 the Panola pose of the information reported here is to describe the Mountain Ehrlichia bacteria caused a transient illness salient features of heartwater and to promote increased with a mild febrile condition that was followed by a disease awareness among veterinarians, livestock own- chronic latent infection. The lack of reports of heartwa- ers, wildlife biologists, and other stakeholders. It is ter or heartwaterlike disease in domestic or wild rumi- our hope that this awareness will translate into a more nants from areas in which Panola Mountain Ehrlichia rapid detection of disease and the ability to limit the organisms have been detected provides further indirect extent of an outbreak should it occur in the continental support that this bacterium has low pathogenicity in United States. infected animals.10 Ehrlichia ruminantium does not survive for long Pathogen Characteristics periods outside of a host. Blood exposed to sunlight will lose infectivity in ≤ 5 minutes.11 In a dead animal, Ehrlichia ruminantium is an aerobic, gram-negative, 12 nonmotile, coccoid- to ellipsoidal-shaped organism in the organism will typically begin to die in ≤ 6 hours. 4 However, infectivity may be prolonged for as long as 72 the order Rickettsiales and family Anaplasmataceae. 13 This organism is typically transmitted to a susceptible hours under cold conditions (4°C [39.2°F]). Ehrlichia 5 ruminantium is also susceptible to treatment with anti- host through infective blood. Once inside the host, this 5 obligate intracellular agent typically resides inside in- microbials, particularly tetracycline derivatives. tracytoplasmic inclusions (diameter, ≤ 4.0 µm) in neu- Epidemiology From the National Surveillance Unit (Kasari) and Center for Ani- Tick vector—Amblyomma spp ticks must be pres- mal Health Information and Analysis (Miller, James, Freier), ent in a geographic area to transmit E ruminantium to Centers for Epidemiology and Animal Health, Veterinary Ser- susceptible ruminant hosts during and after an out- vices, APHIS, USDA, 2150 Centre Ave, Building B, Fort Collins, CO 80526. break of heartwater. This tick species is categorized as Address correspondence to Dr. Kasari ([email protected]. a 3-host tick; therefore, each life stage of the tick (ie, gov). larva, nymph, and adult) feeds on a different host and 520 Vet Med Today: Reference Point JAVMA, Vol 237, No. 5, September 1, 2010 may require as few as 5 months or up to 4 years to com- water buffalo [Bubalus bubalis]) are also susceptible to plete the tick life cycle.14,15 Infection can be transmitted disease.26 Sheep and goats typically have more severe by each life stage of the tick.16 Infective organisms can clinical disease than do cattle. Bos indicus breeds of cattle endure in these various life stages for an extended pe- typically are more resistant to infection than are B taurus riod (eg, ≤ 15 months).15,17 breeds.27 Similarly, indigenous breeds of goats and sheep In Africa, there are 5 native species of Ambly- in heartwater-endemic areas appear to be more resistant omma spp ticks (Amblyomma variegatum, Amblyomma to disease, compared with resistance of other nonindig- hebraeum, Amblyomma lepidum, Amblyomma astrion, enous breeds of goats and sheep.27 Additionally, young and Amblyomma pomposum) considered natural vec- lambs and kids during the first week after birth and tors of heartwater. These 5 species have transmitted calves during the first month after birth typically have E ruminantium under field conditions to susceptible ani- resistance to overt clinical disease after infection.28–30 mal species, and transmission has caused clinical signs Although heartwater has been the suspected cause of disease.18,19 In experimental conditions, 5 other spe- of death in many species of ungulate ruminant wild- cies of Amblyomma spp ticks (Amblyomma cohaerens, life, only 12 species indigenous to Africa and 3 non– Amblyomma gemma, Amblyomma tholloni, Amblyomma African-origin species are proven to be susceptible to in- sparsum, and Amblyomma marmoreum) indigenous to fection by E ruminantium26,31–42 (Table 1). All 15 species Africa are capable of transmitting E ruminantium to ru- are present in the continental United States as captive (eg, minants.18 Three Amblyomma spp ticks (Amblyomma farmed) or free-ranging populations.33–35 Although these maculatum, Amblyomma cajennense, and Amblyomma species can function as a sentinel species for heartwater, americanum) indigenous to North America are sus- this disease is likely to be observed first in white-tailed ceptible to infection with E ruminantium,19,20 but only deer (Odocoileus virginianus) or axis deer (Axis axis). A maculatum appears to be efficient at transmitting White-tailed deer are an important sentinel species be- heartwater to susceptible ruminants.19,20 Amblyomma cause of their ubiquitous geographic distribution36 and americanum also serves as a natural vector for the E ru- potential interaction with heartwater-infected domestic minantium–like Panola Mountain Ehrlichia organisms9,10 ruminants. Although they lack the extensive range of initially identified in the southeastern United States.9 white-tailed deer, there are free-ranging populations of Amblyomma dissimile, which was introduced into Florida axis deer in Texas, California, and Washington35,38; axis and typically parasitizes reptiles and amphibians,21,22 has deer are a popular farmed species in many southern and also transmitted E ruminantium to goats in experimental midwestern states.33–35,37 Several other ungulate rumi- conditions.23 Despite being found occasionally on cattle nant wildlife species have been introduced into the con- in natural conditions, researchers23 believe it is unlikely tinental United States as captive and free-ranging popu- that A dissimile plays a substantial role in the transmis- lations33–35,37–42 and are suspected to be susceptible to sion of heartwater among ruminants. E ruminantium infection.31,32 However, studies are need- The tropical bont tick (A variegatum) and bont tick ed to confirm the susceptibility of these introduced spe- (A hebraeum) are considered to be the most important cies to E ruminantium infection. vectors of heartwater because of their adaptation to do- mestic ruminant livestock, ease with which they trans- Transmission—The typical life cycle of E ruminan- mit E ruminantium among ruminants, and geographic tium includes a phase in which the organism is transmit- distribution.24,25 However, given the widespread distri- ted between successive life stages of Amblyomma spp ticks bution of the tropical bont tick in the Caribbean islands, before transmission to a susceptible vertebrate host. Ad- this tick may be the arthropod vector that is eventually ditionally, the organism may be transmitted iatrogenically. responsible for the first outbreak of heartwater in the United States. Consequently, veterinarians, livestock TICK-tO-tICK tRANSMISSION owners, and wildlife biologists should be familiar with Miniscule amounts of E ruminantium–infected