Granulocytic Anaplasmosis in humans and animals 1Elizabeth Lake, 2Nikki Yost, 3Jennifer Johns, DVM, PhD, DACVP Stanford University 1(Class of 2014), 2(Class of 2016) 3Department of Comparative Medicine, Stanford School of Medicine

Introduction Tick vector Disease in animals Prevention Granulocytic Anaplasmosis (GA) is GA is vectored by several species of the GA is a well-known disease of livestock, Ticks are most active between April an emerging infectious disease of Ixodes tick genus in the Ixodidae family with reports of this “tick-borne fever” and September, so prevention is most humans and an established infectious of hard-bodied ticks (figure 2). dating back more than 200 years. Small important during these months. While disease of domestic animals. GA is Ixodes spp. ticks Figure 2. ruminants, horses and dogs most outdoors, people should avoid thick spread by ticks that carry the bacterial transmit a number of commonly develop GA. Clinical signs in brush, apply repellants to clothing (or agent Anaplasma phagocytophilum. infectious diseases to animals include fever, lethargy and use pre-treated clothing and outdoor Like many other tick-borne diseases, humans and animals. lameness; horses additionally develop gear) and use tick preventatives on GA is officially a reportable disease in In the U.S., GA is limb edema and mucosal petechiation4. pets. Prompt removal of ticks is also humans1. Current research is aimed at vital, to disease prevention. Drying vectored by Ixodes Disease in humans better understanding these tick-borne scapularis in the Midwest and clothes on high heat for up to an hour bacterial diseases, as they are Northeast, and by Ixodes pacificus on In contrast to GA in animals, the first will kill any ticks that remain1. progressively spreading throughout theWestcoast(figure3).Thesesame human case of GA was only reported in both the U.S. and the world. tick species carry and transmit Lyme 1994. The first report in Europe soon Current research disease in these locations, along with a followed. The symptoms of GA in Because A. phagocytophilum is an Bacterial pathogen parasitic infection called babesiosis. humans are similar to clinical signs in obligate intracellular bacterium, it Anaplasma phagocytophilum is a Disease transmission generally takes at animals and include fever, malaise, cannot survive outside of cells. A gram-negative bacterium in the family least one day following tick attachment. headache and muscle pain. Respiratory white blood cell-based ‘cell line’ Anaplasmataceae in the order Tick ranges will likely expand in the and gastrointestinal symptoms may (figure 7) is needed to maintain the Rickettsiales2 (figure 1). The genera future due to land use increase and develop. About 40-50% of human GA bacteria in culture for research. Anaplasma and Ehrlichia are climate change, raising concern for patients will require hospitalization and Current work focuses on defining the 5 comprised of tick-borne bacteria that increased spread of tick-borne diseases. 7% will require intensive care . mechanisms by which the bacteria are Preventing able to perturb the host immune primarily infect host blood cells. Diagnosis and treatment Figure 1. tick exposure response, such as altered production will become Hematologic abnormalities in GA of neutrophils and other immune increasingly include thrombocytopenia, the single cells7. The key immune system important in most common finding in animals and regulators in GA differ from those for controlling Figure 3. humans. Morulae (clusters of bacteria) “typical” gram-negative infections, the spread of may be found in neutrophils in the blood supporting the Figure 7. diseases. smear (figure 6). Serology can be useful current concept of for diagnosis but cross-reactivity with a unique host Animal reservoirs Ehrlichia species can necessitate the use immune response 6 Animals reservoirs of GA in many parts of PCR to confirm infection .The to the tick-borne of the U.S. include the white-footed standard treatment is doxycycline. bacteria. mouse (Peromyscus leukopus;figure4) Figure 6. A. phagocytophilum organisms infect and white-tailed deer (Odocoileus References neutrophils (the essential bacterial- virginianus; figure 5). On the west coast, 1. CDC.gov/anaplasmosis killing cells of the immune system). the dusky-footed woodrat (Neotoma 2. Williams KP, Sobral BW, and Dickerman This unusual strategy requires that the fuscipes) and the western grey squirrel AW. J Bacteriol. 2007. 189(13): 4578-86. 3. Keesing F, et al. Emerg Infect Dis. 2012. bacteria disable neutrophil killing (Sciurus griseus) are reservoirs of GA mechanisms to permit their survival 18(12): 2013-6. infection. The relative importance of 4. Borjesson DL, Barthold SW. Comp Med. inside these cells. As the infected each animal reservoir in the spread of GA 2002. 52(5):403-13. neutrophils freely circulate within the is still under investigation3. 5. Dumler JS, et al. Emerg Infect Dis. 2005. body, this survival strategy provides 11(12): 1828-34. Figure 4. A. phagocytophilum the means to 6. CDC MMWR. 55(RR04);1-27. 2006. Diagnosis and Management of Tickborne disseminate throughout the host Rickettsial Diseases. human or animal and establish a nidus 7. Johns JL, et al. Infect Immun. 2009. of infection (often the spleen). Figure 5. 77(9):4070-80.