Anaplasmosis

This section will provide information related to Anaplasma phagocytophilum. 

In 2012, there were 517 confirmed and probable reported cases of human granulocytic anaplasmosis or HGA in Wisconsin. This pathogen is transmitted by blacklegged ticks, also known as deer ticks.  Approximately 70% of all cases in the US occur in Wisconsin and Minnesota (http://www.cdc.gov/anaplasmosis/stats/). 

Where does Anaplasmosis occur in Wisconsin?

Figure 1.  Infection rates in ticks collected through passive surveys of animals brought to veterinary clinics, human societies or animal rehabilitators.

Anaplasma_passive

Ana cases 2012

 

Figure 2.  Incidence and distribution of human anaplasmosis cases in Wisconsin for 2012.  Map courtesy of the Wisconsin Department of Health Services.  Historical data as well as the most recent data available can be found at http://www.dhs.wisconsin.gov/communicable/tickborne/AandE/index.htm

 

 

 

 

 

 

 

What is Anaplasmosis?

Anaplasmosis or human granulocytic anaplasmosis (HGA) is a tick-borne disease caused by the gram-negative, obligate intracellular bacterium Anaplasma phagocytophilum. This means it can only reproduce inside living cells. It was formerly known as human granulocytic ehrlichiosis (HGE) and later renamed human granulocytic anaplasmosis (HGA) in 2001. It is a bacterium that undergoes development within white blood cells, specifically of the granulocytic type (Dahlgren et al. 2011; Chapman et al. 2006; Dumler et al. 2001).

  • Anaplasma phagocytophilum was first diagnosed as a veterinary pathogen in 1932 and later recognized as a human pathogen in 1990 in a Wisconsin patient who died of a severe febrile illness after being bitten by a tick. Over the next few years, 13 cases with similar clinical and laboratory features were identified in the same region of northwestern Wisconsin and eastern Minnesota. In 1994, through the use of molecular techniques and DNA sequencing, the causative pathogen was recognized as distinct from Ehrlichia chaffeensis, a bacteria which causes human monocytic ehrlichiosis (HME). It was subsequently named human granulocytic ehrlichiosis (HGE) and classified as an Ehrlichia species, but further morphological and serologic studies demonstrated a close or identical relationship to the veterinary pathogens, Ehrlichia equi and Ehrlichia phagocytophila. In 2001, all three agents  E. equi, E phagocytophila and HGE were reclassified into a different genus as a single species, Anaplasma phagocytophilum. The genera Ehrlichia and Anaplasma contain all pathogens in the family that are transmitted by ticks and most commonly infect peripheral or circulating blood cells, including leukocytes (white blood cells), platelets, and erythrocytes (red blood cells). (Dahlgren et al. 2011; Dumler et al. 2007; Demma et al. 2005; Dumler et al. 2005; Dumler et al. 2001). 

How is Anaplasma phagocytophilum transmitted?

The bacteria is transmitted most commonly by the bite of an infected blacklegged tick (Ixodes scapularis) in the northeast and upper Midwestern United States. In general, the tick vector must be attached for 12-24 hours to transmit A. phagocytophilum (des Vignes et al. 2001; Hodzic et al. 1998; Katavolos et al. 1998).

Although everyone is susceptible to Anaplasma phagocytophilum, people who spend time outdoors in areas where ticks which carry this disease-causing organism are at a higher risk of exposure.

Tick infection is established after an infectious blood meal is taken from an infected reservoir host. Three mammalian species are considered important reservoirs for Anaplasma phagocytophilum: the white-footed mouse (Peromyscus leucopus), the  raccoon (Procyon lotor), and the gray squirrel (Sciurus carolinensis), although serologic and molecular evidence has indicated that other small mammals may be competent reservoirs as well.  White-tailed deer (Odocoileus virginianus)  harbor a variant or strain of the bacteria which is not associated with causing disease in humans (Dumler et al. 2005; Massung et al. 2005) but does infect the same tick species. 

Since Anaplasma phagocytophilum infects white blood cells circulating in the blood stream, there is the potential for transmission via other routes. Although extremely rare, alternative methods of transmission have been reported including transplacental infection (from mother to fetus via the placenta) and via blood transfusion. Several cases of human anaplasmosis have been reported associated with the blood transfusions donated from asymptomatic (with no clinical signs or symptoms) or acutely infected donors (Annen et al. 2012).

What are the Clinical Signs and Symptoms of Human Anaplasmosis?

In humans, symptoms of anaplasmosis typically begin 7-21 days after being bitten by a tick infected with the bacteria. Tick bites are often painless and many people do not recall being bitten by a tick. Symptoms vary from person to person and few people with the disease will develop all symptoms but more commonly a combination of the most commonly reported symptoms with this disease. Reported symptoms in humans include:

  • Fever
  • Headache
  • Muscle pain
  • Malaise
  • Chills
  • Nausea / Abdominal pain
  • Cough
  • Confusion
  • Rash – a rash with anaplasmosis is rarely reported and literature suggests that the presence of a rash in patients diagnosed with anaplasmosis are often co-infected (infection with more than one pathogen at the same time) with either the bacteria which causes Lyme disease (Borrelia burgdorferi) or Rocky Mountain Spotted Fever (Rickettsia rickettsii) (Dahlgren et al 2011; Dumler et al. 2007; Chapman et al. 2006; Demma et al. 2005; Dumler et al. 2005).
  • The National Institute of Allergy and Infectious Diseases (NIAID) supported studies of mice found that co-infection with human granulocytic anaplasmosis resulted in more severe Lyme disease (Thomas et al. 2001). Contrastingly, when mice were co-infected with Babesia microti (the pathogen that causes human Babesiosis) and Borrelia burgdorferi (the pathogen that causes Lyme disease in humans), neither pathogen affected how each individual infection progressed. (Coleman et al. 2005). Determining the presence of a co-infection is critical because it may affect antimicrobial choice. Certain antibiotics which are effective in treating early stage Lyme disease, such as amoxicillin, are not effective for HGA (Chapman et al. 2006).
  • Persons with compromised immune systems, such as those undergoing immunosuppressive therapies (e.g., corticosteroids (e.g. prednisone), cancer chemotherapy, or long term immunosuppressive therapy following organ transplant), with HIV infection or splenectomy (without a spleen), appear to be more susceptible to severe infection with Anaplasma phagocytophilum and case fatality rates (i.e., the proportion of persons who die as a result of their infection) for these individuals are usually higher than those reported for the general population. 
How is Human Anaplasmosis Diagnosed?
If you think you may have a tick-borne illness or may have been exposed to the tick vector please contact your physician or medical provider. Diagnosis of anaplasmosis in humans is based on a thorough medical history, possible exposure to established high-risk areas for anaplasmosis and other tick-borne diseases where you live or spend time outdoors and physician observed clinical signs and symptoms as well as accompanying diagnostic laboratory methods to support the diagnosis. 
Anaplasmosis can be challenging for medical providers to diagnose and treat.  As previously stated, symptoms vary from patient to patient and can be difficult to distinguish from other diseases. The diagnosis of anaplasmosis (HGA) must initially be made by a physician based on a thorough medical history and clinical signs and symptoms. Specialized confirmatory laboratory tests can be performed later to validate the initial physician based diagnosis.
For more information click link below: Chapman AS, et al. (2006) MMWR; 55;(RR04):1-27. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5504a1.htm
Laboratory Detection: 
It is important to note, since infection with anaplasmosis in humans may be rapidly progressive and in some instances fatal, antibiotic treatment should never be delayed pending laboratory test results, or be withheld on the basis of an initial negative finding for Anaplasma phagocytophilum.
Diagnostic laboratory tests which may be used for the direct detection of the bacterial organism which causes human anaplasmosis include examination of a sample of a person’s blood under the microscope called a peripheral blood smear, molecular diagnosis by polymerase chain reaction (PCR) or culturing the organism from a sample of  blood or cerebrospinal fluid (CSF). 
The bacteria can also be detected indirectly by what is called serodiagnosis or serologic testing which is considered one of the most sensitive methods for detection. Serologic testing is based on looking for evidence of your body’s reaction to exposure to an infectious agent such as bacteria or a virus. In some cases when the body’s immune system is exposed to infectious agents, it mounts a response in the form of the production of what are called antibodies. Certain laboratory tests can be used to measure the level of response or production of antibodies by an individual to determine if they have been exposed to an infectious agent (Dumler et al. 2007) 

How is Human Anaplasmosis Treated? The antibiotic, doxycycline is the first choice for treatment for anaplasmosis infection in both adults and children of all ages and should be initiated immediately whenever anaplasmosis is suspected and diagnosed by a healthcare provider. Both human anaplasmosis and ehrlichiosis are serious illnesses which can be fatal if not treated correctly, even in previously healthy individuals (Hamburg et al. 2008; Dumler et al. 2007). 

The use of doxycycline to treat suspected anaplasmosis in children is the standard of care recommended by both CDC and the American Academy of Pediatrics (AAP) Committee on Infectious Diseases. (See link to online Redbook; Section 3: Ehrlichia and Anaplasma infections for more information)

 

References:

Annen K, Friedman K, Eshoa C, Horowitz M, Gottschall J, Straus T. (2012). Two cases of transfusion-transmitted Anaplasma phagocytophilum. Am J Clin Path; 137: 565-65. http://ajcp.ascpjournals.org/content/137/4/562.full.pdf

Chapman AS, Bakken JS, Folk SM, Paddock CD et al. (2006). Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever, Ehrlichiosis, and Anaplasmosis—United States. MMWR; 55;(RR04):1-27. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5504a1.htm

Coleman JL, LeVine C, Thill C, Kuhlow C, Benach JL. (2005). Babesia microti and Borrelia burgdorferi follow independent courses of infection in mice. J Infec Dis; 192(9):1634-41. http://jid.oxfordjournals.org/content/192/9/1634.full.pdf+html

Dahlgren FS, Mandel EJ, Krebs JW, Massung RF, McQuiston JH. (2011). Increasing Incidence of Ehrlichia chaffeensis and Anaplasma phagocytophilum in the United States, 2000–2007. Am. J. Trop. Med. Hyg., 85(1):124–131 doi:10.4269/ajtmh.2011.10-0613

Demma LJ, Holman RC, McQuiston JH, Krebs JW, Swerdlow DL. (2005). Epidemiology of human ehrlichiosis and anaplasmosis in the United States, 2001-2002. Am. J. Trop. Med. Hyg., 73(2): 400–409

des Vignes F, Piesman J, Heffernan R, et al. (2001). Effect of tick removal on transmission of Borrelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis nymphs. J Infect Dis; 183(5):773-778.

Dumler JS, Madigan JE, Pusterla N, Bakken JS. (2007). Ehrlichioses in Humans: Epidemiology, Clinical Presentation, Diagnosis, and Treatment. Clinical Infectious Diseases;45:S45–51. DOI: 10.1086/518146

Dumler JS, Choi KS, Garcia-Garcia JC, Barat NS, Scorpio DG, Garyu JW, Grab DJ, Bakken JS. (2005). Human granulocytic anaplasmosis and Anaplasma phagocytophilum. Emerging Infectious Diseases; 11(12): 1828-34. http://wwwnc.cdc.gov/eid/article/11/12/pdfs/05-0898.pdf

Dumler JS, Barbet AF, Bekker CPJ, Dasch GA, Palmer GH, Ray SC, Rikihisa Y, Rurangirwa FR, 2001. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and ‘HGE agent’ as subjective synonyms of Ehrlichia phagocytophila. Int J Syst Evol Microbiol 51: 2145–2165.

Hamburg BJ, Storch GA, Micek, ST, Kollef MH. (2008). The importance of early treatment with doxycycline in human ehrlichiosis. Medicine (Baltimore); 87(2):53-60.       DOI: 10.1097/MD.0b013e318168da1d

Hodzic E, Fish D, Maretzki CM, et al. (1998). Acquisition and transmission of the agent of human granulocytic ehrlichiosis by Ixodes scapularis ticks. J Clin Microbiol;  36(12):3574-8

Katavolos P, Armstrong PM, Dawson JE, et al. (1998). Duration of tick attachment required for transmission of granulocytic ehrlichiosis. J Infect Dis; 177:1422-1425. http://jid.oxfordjournals.org/content/177/5/1422.full.pdf

Massung RF, Courtney JW, Hiratzka SL, Pitzer VE, Smith G, Dryden RL. (2005). Anaplasma phagocytophilum in White-tailed deer. Emerging Infectious Diseases; 11(10): 1604-1606. http://wwwnc.cdc.gov/eid/article/11/10/pdfs/04-1329.pdf

Redbook Online: Section 3. Summaries of Infectious Diseases: Ehrlichia and Anaplasma Infections: (Human Ehrlichiosis and Anaplasmosis). http://aapredbook.aappublications.org/cgi/content/full/2009/1/3.37?cookietest=yes#Diagnostic_Tests

Thomas V, Anguita J, Barthold SW, Fikrig E. (2001). Coinfection with Borrelia burgdorferi and the agent human granulocytic ehrlichiosis alters murine immune responses, pathogen burden and, severity of lyme arthritis. Infect. Immun; 69(5):3359-3371. http://iai.asm.org/content/69/5/3359.full.pdf

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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