Human granulocytic anaplasmosis

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Human granulocytic anaplasmosis
Other namesHuman granulocytic ehrlichiosis (HGE) [1] [2]
Anaplasma phagocytophilum cultured in human promyelocytic cell line HL-60.jpg
Anaplasma phagocytophilum cultured in a human promyelocytic cell line, arrows point to cells containing prominent bacterial morulae
Specialty Infectious diseases   OOjs UI icon edit-ltr-progressive.svg

Human granulocytic anaplasmosis (HGA) is a tick-borne, infectious disease caused by Anaplasma phagocytophilum , an obligate intracellular bacterium that is typically transmitted to humans by ticks of the Ixodes ricinus species complex, including Ixodes scapularis and Ixodes pacificus in North America. These ticks also transmit Lyme disease and other tick-borne diseases. [3]

Contents

The bacteria infect white blood cells called neutrophils, causing changes in gene expression that prolong the life of these otherwise short-lived cells. [4]

Signs and symptoms

Signs and symptoms may include:[ citation needed ]

Symptoms may be minor, as evidenced by surveillance studies in high-risk areas. Gastrointestinal tract symptoms occur in less than half of patients and a skin rash is seen in less than 10% of patients. [5] It is also characterized by a low number of platelets, a low number of white blood cells, and elevated serum transaminase levels in the majority of infected patients. [5] Even though people of any age can get HGA, it is usually more severe in the aging or immune-compromised. Some severe complications may include respiratory failure, kidney failure, and secondary infections.[ citation needed ]

Cause

A. phagocytophilum is transmitted to humans by Ixodes ticks. These ticks are found in the US, Europe, and Asia. In the US, I. scapularis is the tick vector in the East and Midwest states, and I. pacificus in the Pacific Northwest. [6] In Europe, the I. ricinus is the main tick vector, and I. persulcatus is the currently known tick vector in Asia. [7]

The major mammalian reservoir for A. phagocytophilum in the eastern United States is the white-footed mouse, Peromyscus leucopus. Although white-tailed deer and other small mammals harbor A. phagocytophilum, evidence suggests that they are not a reservoir for the strains that cause HGA. [8] [9] A tick that has a blood meal from an infected reservoir becomes infected themselves. If an infected tick then latches onto a human the disease is then transmitted to the human host and A.phagocytophilum symptoms can arise. [10]

Anaplasma phagocytophilum shares its tick vector with other human pathogens, and about 10% of patients with HGA show serologic evidence of coinfection with Lyme disease, babesiosis, or tick-borne meningoencephalitis. [11]

While it is rare, it is possible for HGA to be transmitted human-to-human via a blood transfusion, in which case it is called Transfusion-Transmitted Anaplasmosis (TTA). [12]

Major surface proteins

Many major surface proteins (MSPs) are found in Anaplasma and those which interact with Anaplasma can mainly be found in A. marginale and A. phagocytophilum. [13] There are many different phenotypic traits that are associated with MSPs, because each MSP can only infect certain animals in certain conditions. [13] A. phagocytophilum infects the most vast array of living things, including humans, and all around the world. [13] A. marginale evolved to be more specific in infecting animals, such as deer and cattle in the subtropics and tropics. [13] The main difference between these two MSPs is that the host cell for A. phagocytophilum is the granulocyte, while the host cell for A. marginale is erythrocytes. [13] It is likely that these MSPs coevolved, because they had previously interacted via tick-pathogen interaction. [13]

Anaplasma MSPs can not only cooperate with vertebrates, but also invertebrates, which make these phenotypes evolve faster than others, because they have a lot of selective forces acting on them. [13]

Diagnosis

Clinically, HGA is essentially indistinguishable from human monocytic ehrlichiosis, the infection caused by Ehrlichia chaffeensis , and other tick-borne illnesses such as Lyme disease may be suspected. [14] As Ehrlichia serologies can be negative in the acute period, PCR is very useful for diagnosis. [15]

Prevention

Currently, there is no vaccine against human granulocytic anaplasmosis, so antibiotics are the only form of treatment. [7] The best way to prevent HGA is to prevent getting tick bites. [16]

Treatment

Doxycycline is the treatment of choice. If anaplasmosis is suspected, treatment should not be delayed while waiting for a definitive laboratory confirmation, as prompt doxycycline therapy has been shown to improve outcomes. [14] Presentation during early pregnancy can complicate treatment. Doxycycline compromises dental enamel during development. [17] Although rifampin is indicated for post-delivery pediatric and some doxycycline-allergic patients, it is teratogenic. Rifampin is contraindicated during conception and pregnancy. [18]

If the disease is not treated quickly, sometimes before the diagnosis, the person has a high chance of mortality. [7] Most people make a complete recovery, though some people are intensively cared for after treatment. [7] A reason for a person needing intensive care is if the person goes too long without seeing a doctor or being diagnosed. [7] The majority of people, though, make a complete recovery with no residual damage. [7]

Epidemiology

From the first reported case in 1994 until 2010, HGA's rates of incidence have exponentially increased. [19] This is likely because HGA is found where there are ticks that carry and transmit Lyme disease, also known as Borrelia burgdorferi, and babesiosis, which is found in the northeastern and midwestern United States, which has seemingly increased in the past couple of decades. [19] Before 2000, there were less than 300 cases reported per year. In 2000, there were only 350 reported cases. [19] From 2009-2010, HGA experienced a 52% increase in the number of cases reported. [19]

History

The first outbreak of Human Granulocytic Anaplasmosis (HGA) in the United States began with a patient in early 1990 in Wisconsin. He was kept in the hospital in Minnesota for testing, but died without a diagnosis. [7] Over the next couple of years, many people within the same area of Wisconsin and Minnesota had come down with the same symptoms. [7] It was discovered in 1994 that it was Human Granulocytic Ehrlichiosis (HGE), later to be known as HGA. [10]

Terminology

Although the infectious agent is known to be from the Anaplasma genus, the term "human granulocytic ehrlichiosis" (HGE) is often used, reflecting the prior classification of the organism. E. phagocytophilum and E. equi were reclassified as Anaplasma phagocytophilum.[ citation needed ]

See also

Related Research Articles

Ehrlichiosis is a tick-borne disease of dogs usually caused by the rickettsial agent Ehrlichia canis. Ehrlichia canis is the pathogen of animals. Humans can become infected by E. canis and other species after tick exposure. German Shepherd Dogs are thought to be susceptible to a particularly severe form of the disease; other breeds generally have milder clinical signs. Cats can also be infected.

<span class="mw-page-title-main">Lyme disease</span> Infectious disease caused by Borrelia bacteria, spread by ticks

Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by Borrelia bacteria, which are spread by ticks in the genus Ixodes. The most common sign of infection is an expanding red rash, known as erythema migrans (EM), which appears at the site of the tick bite about a week afterwards. The rash is typically neither itchy nor painful. Approximately 70–80% of infected people develop a rash. Early diagnosis can be difficult. Other early symptoms may include fever, headaches and tiredness. If untreated, symptoms may include loss of the ability to move one or both sides of the face, joint pains, severe headaches with neck stiffness or heart palpitations. Months to years later, repeated episodes of joint pain and swelling may occur. Occasionally, shooting pains or tingling in the arms and legs may develop. Despite appropriate treatment, about 10 to 20% of those affected develop joint pains, memory problems, and tiredness for at least six months.

<span class="mw-page-title-main">Babesiosis</span> Malaria-like parasitic disease caused by infection with the alveoate Babesia or Theileria

Babesiosis or piroplasmosis is a malaria-like parasitic disease caused by infection with a eukaryotic parasite in the order Piroplasmida, typically a Babesia or Theileria, in the phylum Apicomplexa. Human babesiosis transmission via tick bite is most common in the Northeastern and Midwestern United States and parts of Europe, and sporadic throughout the rest of the world. It occurs in warm weather. People can get infected with Babesia parasites by the bite of an infected tick, by getting a blood transfusion from an infected donor of blood products, or by congenital transmission . Ticks transmit the human strain of babesiosis, so it often presents with other tick-borne illnesses such as Lyme disease. After trypanosomes, Babesia is thought to be the second-most common blood parasite of mammals. They can have major adverse effects on the health of domestic animals in areas without severe winters. In cattle, the disease is known as Texas cattle fever or redwater.

Tick-borne diseases, which afflict humans and other animals, are caused by infectious agents transmitted by tick bites. They are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa. The economic impact of tick-borne diseases is considered to be substantial in humans, and tick-borne diseases are estimated to affect ~80 % of cattle worldwide. Most of these pathogens require passage through vertebrate hosts as part of their life cycle. Tick-borne infections in humans, farm animals, and companion animals are primarily associated with wildlife animal reservoirs. Many tick-borne infections in humans involve a complex cycle between wildlife animal reservoirs and tick vectors. The survival and transmission of these tick-borne viruses are closely linked to their interactions with tick vectors and host cells. These viruses are classified into different families, including Asfarviridae, Reoviridae, Rhabdoviridae, Orthomyxoviridae, Bunyaviridae, and Flaviviridae.

<span class="mw-page-title-main">Erythema migrans</span> A rash in several vector-borne diseases

Erythema migrans or erythema chronicum migrans is an expanding rash often seen in the early stage of Lyme disease, and can also be caused by southern tick-associated rash illness (STARI). It can appear anywhere from one day to one month after a tick bite. This rash does not represent an allergic reaction to the bite, but rather an actual skin infection of one of the Lyme bacteria species from the genus Borrelia. The rash's name comes from Neo-Latin for "Redness migrating."

<i>Dermacentor variabilis</i> Species of tick

Dermacentor variabilis, also known as the American dog tick or wood tick, is a species of tick that is known to carry bacteria responsible for several diseases in humans, including Rocky Mountain spotted fever and tularemia. It is one of the best-known hard ticks. Diseases are spread when it sucks blood from the host. It may take several days for the host to experience symptoms.

<i>Anaplasma phagocytophilum</i> Species of bacterium

Anaplasma phagocytophilum is a Gram-negative bacterium that is unusual in its tropism to neutrophils. It causes anaplasmosis in sheep and cattle, also known as tick-borne fever and pasture fever, and also causes the zoonotic disease human granulocytic anaplasmosis.

<span class="mw-page-title-main">Anaplasmosis</span> Medical condition

Anaplasmosis is a tick-borne disease affecting ruminants, dogs, and horses, and is caused by Anaplasma bacteria. Anaplasmosis is an infectious but not contagious disease. Anaplasmosis can be transmitted through mechanical and biological vector processes. Anaplasmosis can also be referred to as "yellow bag" or "yellow fever" because the infected animal can develop a jaundiced look. Other signs of infection include weight loss, diarrhea, paleness of the skin, aggressive behavior, and high fever.

<span class="mw-page-title-main">Ehrlichiosis</span> Medical condition

Ehrlichiosis is a tick-borne bacterial infection, caused by bacteria of the family Anaplasmataceae, genera Ehrlichia and Anaplasma. These obligate intracellular bacteria infect and kill white blood cells.

<i>Anaplasma</i> Genus of bacteria

Anaplasma is a genus of gram-negative bacteria of the alphaproteobacterial order Rickettsiales, family Anaplasmataceae.

<i>Ehrlichia</i> Genus of bacteria

Ehrlichia is a genus of Rickettsiales bacteria that are transmitted to vertebrates by ticks. These bacteria cause the disease ehrlichiosis, which is considered zoonotic, because the main reservoirs for the disease are animals.

<i>Ixodes scapularis</i> Species of tick

Ixodes scapularis is commonly known as the deer tick or black-legged tick, and in some parts of the US as the bear tick. It was also named Ixodes dammini until it was shown to be the same species in 1993. It is a hard-bodied tick found in the eastern and northern Midwest of the United States as well as in southeastern Canada. It is a vector for several diseases of animals, including humans and is known as the deer tick owing to its habit of parasitizing the white-tailed deer. It is also known to parasitize mice, lizards, migratory birds, etc. especially while the tick is in the larval or nymphal stage.

Neuroborreliosis is a disorder of the central nervous system. A neurological manifestation of Lyme disease, neuroborreliosis is caused by a systemic infection of spirochetes of the genus Borrelia. Symptoms of the disease include erythema migrans and flu-like symptoms.

<i>Ehrlichia ewingii</i> Species of bacterium

Ehrlichia ewingii is a species of rickettsiales bacteria. It has recently been associated with human infection, and can be detected via PCR serological testing. The name Ehrlichia ewingii was proposed in 1992.

<span class="mw-page-title-main">Human monocytotropic ehrlichiosis</span> Medical condition

Human monocytotropic ehrlichiosis is a form of ehrlichiosis associated with Ehrlichia chaffeensis. This bacterium is an obligate intracellular pathogen affecting monocytes and macrophages.

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Ehrlichiosis ewingii infection is an infectious disease caused by an intracellular bacteria, Ehrlichia ewingii. The infection is transmitted to humans by the tick, Amblyomma americanum. This tick can also transmit Ehrlichia chaffeensis, the bacteria that causes human monocytic ehrlichiosis (HME).

Borrelia miyamotoi is a bacterium of the spirochete phylum in the genus Borrelia. A zoonotic organism, B. miyamotoi can infect humans through the bite of several species of hard-shell Ixodes ticks, the same kind of ticks that spread B. burgdorferi, the causative bacterium of Lyme disease. Ixodes ticks are also the primary vector in the spread of babesiosis and anaplasmosis.

<i>Ixodes persulcatus</i> Species of tick

Ixodes persulcatus, the taiga tick, is a species of hard-bodied tick distributed from Europe through central and northern Asia to the People's Republic of China and Japan. The sexual dimorphism of the species is marked, the male being much smaller than the female. Hosts include wild and domestic ungulates, man, dog, rabbit, and other small mammals, including the dormouse, Amur hedgehog, and occasionally birds.

Anaplasma bovis is gram negative, obligate intracellular organism, which can be found in wild and domestic ruminants, and potentially a wide variety of other species. It is one of the last species of the Family Anaplasmaceae to be formally described. It preferentially infects host monocytes, and is often diagnosed via blood smears, PCR, and ELISA. A. bovis is not currently considered zoonotic, and does not frequently cause serious clinical disease in its host. This organism is transmitted by tick vectors, so tick bite prevention is the mainstay of A. bovis control, although clinical infections can be treated with tetracyclines. This organism has a global distribution, with infections noted in many areas, including Korea, Japan, Europe, Brazil, Africa, and North America.

References

  1. ↑ Malik A, Jameel M, Ali S, Mir S (2005). "Human granulocytic anaplasmosis affecting the myocardium". J Gen Intern Med. 20 (10): C8–10. doi:10.1111/j.1525-1497.2005.00218.x. PMC   1490240 . PMID   16191146.
  2. ↑ "Human Anaplasmosis Basics - Minnesota Dept. of Health". Archived from the original on 2018-03-14. Retrieved 2009-04-13.
  3. ↑ Holden, K.; Boothby, J. T.; Anand, S.; Massung, R. F. (2003). "Browse BioOne Complete". Journal of Medical Entomology. 40 (4): 534–9. doi: 10.1603/0022-2585-40.4.534 . ISSN   0022-2585. PMID   14680123.
  4. ↑ Lee HC, Kioi M, Han J, Puri RK, Goodman JL (September 2008). "Anaplasma phagocytophilum-induced gene expression in both human neutrophils and HL-60 cells". Genomics. 92 (3): 144–51. doi:10.1016/j.ygeno.2008.05.005. PMID   18603403.
  5. 1 2 Murray, Patrick R.; Rosenthal, Ken S.; Pfaller, Michael A. Medical Microbiology, Fifth Edition. United States: Elsevier Mosby, 2005
  6. ↑ Dumler JS, Madigan JE, Pusterla N, Bakken JS (July 2007). "Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment". Clinical Infectious Diseases. 45 (Suppl 1): S45–51. doi:10.1086/518146. PMID   17582569. S2CID   25167899.
  7. 1 2 3 4 5 6 7 8 Bakken, Johan S.; Dumler, J. Stephen (2006-10-01). "Clinical Diagnosis and Treatment of Human Granulocytotropic Anaplasmosis". Annals of the New York Academy of Sciences. 1078 (1): 236–247. Bibcode:2006NYASA1078..236B. doi:10.1196/annals.1374.042. ISSN   1749-6632. PMID   17114714. S2CID   33910710.
  8. ↑ "Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever, Ehrlichioses, and Anaplasmosis --- United States A Practical Guide for Physicians and Other Health-Care and Public Health Professionals". www.cdc.gov. Retrieved 2015-10-21.
  9. ↑ Massung RF, Courtney JW, Hiratzka SL, Pitzer VE, Smith G, Dryden RL (October 2005). "Anaplasma phagocytophilum in white-tailed deer". Emerging Infectious Diseases. 11 (10): 1604–6. doi:10.3201/eid1110.041329. PMC   3366735 . PMID   16318705.
  10. 1 2 Dumler, J. Stephen; Choi, Kyoung-Seong; Garcia-Garcia, Jose Carlos; Barat, Nicole S.; Scorpio, Diana G.; Garyu, Justin W.; Grab, Dennis J.; Bakken, Johan S. (2005). "Human Granulocytic Anaplasmosis and Anaplasma phagocytophilum". Emerging Infectious Diseases. 11 (12): 1828–1834. doi:10.3201/eid1112.050898. PMC   3367650 . PMID   16485466.
  11. ↑ Dumler JS, Choi KS, Garcia-Garcia JC, et al. (December 2005). "Human granulocytic anaplasmosis and Anaplasma phagocytophilum". Emerging Infectious Diseases. 11 (12): 1828–34. doi:10.3201/eid1112.050898. PMC   3367650 . PMID   16485466.
  12. ↑ Goel, Ruchika; Westblade, Lars F.; Kessler, Debra A.; Sfeir, Maroun; Slavinski, Sally; Backenson, Bryon; et al. (August 2018). "Death from transfusion-transmitted anaplasmosis". Emerging Infectious Diseases . 24 (8): 1548–1550. doi:10.3201/eid2408.172048. PMC   6056119 . PMID   30016241.
  13. 1 2 3 4 5 6 7 de la Fuente, José; Kocan, Katherine M.; Blouin, Edmour F.; Zivkovic, Zorica; Naranjo, Victoria; Almazán, Consuelo; Esteves, Eliane; Jongejan, Frans; Daffre, Sirlei (2010-02-10). "Functional genomics and evolution of tick–Anaplasma interactions and vaccine development". Veterinary Parasitology. Ticks and Tick-borne Pathogens. 167 (2–4): 175–186. doi:10.1016/j.vetpar.2009.09.019. hdl: 10261/144221 . PMID   19819630.
  14. 1 2 Hamburg BJ, Storch GA, Micek ST, Kollef MH (March 2008). "The importance of early treatment with doxycycline in human ehrlichiosis". Medicine. 87 (2): 53–60. doi: 10.1097/MD.0b013e318168da1d . PMID   18344803. S2CID   2632346.
  15. ↑ Prince LK, Shah AA, Martinez LJ, Moran KA (August 2007). "Ehrlichiosis: making the diagnosis in the acute setting". Southern Medical Journal. 100 (8): 825–8. doi:10.1097/smj.0b013e31804aa1ad. PMID   17713310. S2CID   31487400.
  16. ↑ Wormser, Gary P.; Dattwyler, Raymond J.; Shapiro, Eugene D.; Halperin, John J.; Steere, Allen C.; Klempner, Mark S.; Krause, Peter J.; Bakken, Johan S.; Strle, Franc (2006-11-01). "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases. 43 (9): 1089–1134. doi: 10.1086/508667 . ISSN   1058-4838. PMID   17029130.
  17. ↑ Muffly T, McCormick TC, Cook C, Wall J (2008). "Human granulocytic ehrlichiosis complicating early pregnancy". Infect Dis Obstet Gynecol. 2008: 1–3. doi: 10.1155/2008/359172 . PMC   2396214 . PMID   18509484.
  18. ↑ Krause PJ, Corrow CL, Bakken JS (September 2003). "Successful treatment of human granulocytic ehrlichiosis in children using rifampin". Pediatrics. 112 (3 Pt 1): e252–3. doi:10.1542/peds.112.3.e252. PMID   12949322.
  19. 1 2 3 4 "Statistics | Anaplasmosis | CDC". www.cdc.gov. Retrieved 2015-11-08.
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