Anaplasmosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Faizan Sheraz, M.D. [2]

This article is about the ruminant disease. For anaplasmosis in dogs, see Ehrlichiosis (canine). For anaplasmosis in humans, see Human granulocytic ehrlichiosis.

Introduction

Human Granulocytic Anaplasmosis(HGA) is a disease caused by a rickettsial parasite of ruminants, Anaplasma phagocytophilum previously known by other names, including Ehrlichia equi and Ehrlichia phagocytophilum. The organism occurs in the erythrocytes and is transmitted by natural means through by a number of haematophagous species of ticks most commonaly by black-legged deer tick Ixodes scapularis and Ixodes pacificus. It can also be transmitted iatrogenically by the use of surgical, dehorning, castration, and tattoo instruments and hypodermic needles that are not disinfected between uses. HGA is a notifiable disease in the USA. [1] . In the United States, anaplasmosis is notably present in the south and west where the tick hosts Dermacentor spp. are found. Although vaccines have been developed, none are currently available in the United States. Early in the 20th century, this disease was considered one of the major economic consequences in the western United States. In the 1980s and 1990s, control of ticks through new acaricides and practical treatment with prolonged-action antibiotics, notably tetracycline, has led to the point where the disease is no longer considered a major problem.

Epidemiology

In the USA the annual incidence is 6.3 million per year and it is rising. [2] The endemic area of HGA is the upper midwestern and northeastern United States, eight states (Vermont, Maine, Rhode Island, Minnesota, Massachusetts, Wisconsin, New Hampshire, and New York) have the highest annual incidence of HGA according to the Center for Diseases (CDC). This geographic area coincides with the distribution of black-legged deer tick Ixodes scapularis. There is a seasonal variation of the reported incidence, with the highest rate in summer months, most commonly June and July.

People at risk

The highest incidence of reported cases occurs in males above age 40, with immunocompromised patients (HIV positives, cancer patients on chemotherapy, patients with transplanted organs) are at risk of severe disease with high mortality.

Transmission

Vector

A. phagocytophilum is transmitted by I. scapularis, which also transmit the causative agent of Lyme disease caused by Borrelia burgdorferi and Babesiosis caused by Babesia microti. The coinfection of I. scapularis tick by these organisms and a patient can have HGA, Lyme disease, and Babesiosis simultaneously.


Reservior

The principal animal reservoirs of HGA are white-tailed deer and white-footed mice.


Other modes of transmission

Even though tick bite is a common mode of transmission of A. phagocytophilum, it can also occasionally be transmitted by blood transfusion and maternal-fetal transmission.


Clinical features

The average incubation period of HGA is 5.5 days after a tick bite.[3] Anaplasmosis, caused by Anaplasma phagocytophilum, causes symptoms of fever, headache, and myalgia, with GI symptoms occurring in less than half of the patients and a macular, maculopapular of patechial skin rash in less than 10% of patients. Patients who are immunocompromised and on immunosuppressive drugs like corticosteroids and chemotherapeutic medications have severe illness.


Lab findings It is characterized by thrombocytopenia, leukopenia, and elevated serum transaminase and LDH levels in the majority of infected patients, also, anemia and increased serum creatinine can be seen. The causative bacterium is transmitted to humans via ticks.[4]

Diagnosis The decision to start treatment depends on the history of a tick bite, and sign and symptoms of HGA in patients living in endemic areas along with lab features of thrombocytopenia, leukopenia. However, to obtain a definitive diagnosis serological tests such as ELISA, PCR, and examination of peripheral blood for the characteristic intracytoplasmic morulae can be done.

Lifecycle

The organism can go through a complete lifecycle in the gut of certain species of ticks but the flies appear to be only a mechanical vector, thus, not as important in the maintaining the disease in any given area. The disease causes severe anemia and wasting in adult cattle which are infected. Young cattle and most other ruminants will not show clinical signs if infected but may serve as carriers. Since the organism "hides" from the body's immune system in red blood cells, it is difficult if not impossible for an infection to be totally cleared. As the immune response wanes, the organism again builds up and the host relapses.


Treatment

Treatment is indicated in all symptomatic patients.

  • Human granulocytic anaplasmosis, suspected or symptomatic [5]
  • Preferred regimen: Doxycycline 100 mg PO bid (or IV for those patients unable to take oral medication) for 10 days
  • Alternative regimen: Rifampin 300 mg PO bid for 7–10 days (For patients with mild illness due to HGA who are not optimally suited for doxycycline treatment because of a history of drug allergy, pregnancy, or age <8 years)
  • Pediatric regimen:
  • Children ≥ 8 years of age
  • Preferred regimen: Doxycycline 4 mg/kg/day PO bid (Maximum, 100 mg/dose) (or IV for children unable to take an oral medication) for 10 days
  • Children < 8 years of age
  • Preferred regimen: Rifampin 10 mg/kg bid (Maximum, 300 mg/dose) for 4-5 days
  • Note (1): If the patient has concomitant Lyme disease, then Amoxicillin 50 mg/kg/day in 3 divided doses (maximum of 500 mg per dose) OR Cefuroxime axetil 30 mg/kg per day in 2 divided doses (maximum of 500 mg per dose) should be initiated at the conclusion of the course of Doxycycline to complete a 14-day total course of antibiotic therapy
  • Note (2): Rifampin is not effective therapy for Lyme disease, patients coinfected with B. burgdorferi should also be treated with Amoxicillin OR Cefuroxime axetil

Treatment of pregnant patients

Generally tetracyclins are considered as a contraindication during pregnancy due to hepatotoxicity to the mother, and adverse effect on fetal bones on teeth formation, however, Doxycyclin rarely causes these side effects. [6]

Alternatively, Rifampin can be used in pregnant patients.[7]

Prevention

  1. The best way to prevent infection with A. phagocytophilum is the use of insect repellents such as DEET (N, N-diethyl-3-methylbenzamid) or permethrin.
  2. Thorough bating after outdoor activities, the prompt examination of the skin, and removal of the tick.
  3. Wearing protective clothing for outdoor activities or avoiding outdoor activities in endemic areas.
  4. Use of prophylaxis antibiotics such as Doxycyclin is not recommended, and there is no vaccine available for the prevention of HGA.

References

  1. Khatri, Akshay; Lloji, Amanda; Doobay, Richard; Wang, Guiqing; Knoll, Bettina; Dhand, Abhay; Nog, Rajat (2019). "Anaplasma phagocytophilum presenting with orchitis in a renal transplant recipient". Transplant Infectious Disease. 21 (4). doi:10.1111/tid.13129. ISSN 1398-2273. line feed character in |title= at position 26 (help)
  2. F. Scott Dahlgren, Kristen Nichols Heitman, Naomi A. Drexler, Robert F. Massung & Casey Barton Behravesh (2015). "Human granulocytic anaplasmosis in the United States from 2008 to 2012: a summary of national surveillance data". The American journal of tropical medicine and hygiene. 93 (1): 66–72. doi:10.4269/ajtmh.15-0122. PMID 25870428. Unknown parameter |month= ignored (help)
  3. ME Aguero-Rosenfeld, HW Horowitz, GP Wormser, DF McKenna, J. Nowakowski, J. Munoz & JS Dumler (1996). "Human granulocytic ehrlichiosis: a case series from a medical center in New York State". Annals of internal medicine. 125 (11): 904–908. doi:10.7326 / 0003-4819-125-11-199612010-00006 Check |doi= value (help). PMID 8967671. Unknown parameter |month= ignored (help)
  4. Murray, Patrick R.; Rosenthal, Ken S.; Pfaller, Michael A. Medical Microbiology, Fifth Edition. United States: Elsevier Mosby, 2005
  5. Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS; et al. (2006). "The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America". Clin Infect Dis. 43 (9): 1089–134. doi:10.1086/508667. PMID 17029130.
  6. Cross R, Ling C, Day NP, McGready R, Paris DH (2016). "Revisiting doxycycline in pregnancy and early childhood--time to rebuild its reputation?". Expert Opin Drug Saf. 15 (3): 367–82. doi:10.1517/14740338.2016.1133584. PMC 4898140. PMID 26680308.
  7. Dhand A, Nadelman RB, Aguero-Rosenfeld M, Haddad FA, Stokes DP, Horowitz HW (2007). "Human granulocytic anaplasmosis during pregnancy: case series and literature review". Clin Infect Dis. 45 (5): 589–93. doi:10.1086/520659. PMID 17682993.

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