Human Granulocytic Anaplasmosis PDF

Human Granulocytic A n apla s mo s i s Douglas MacQueen, a,b, *, MD, MS Felipe Centellas, MD a KEYWORDS  Anaplasmosis  Ixodes  Deer tick  Tick-borne  Leukopenia  Thrombocytopenia  Doxycycline KEY POINTS  Anaplasmosis is transmitted by the bite of Ixodes ricinus complex ticks, which includes...

Human Granulocytic A n apla s mo s i s Douglas MacQueen, a,b, *, MD, MS Felipe Centellas, MD a KEYWORDS  Anaplasmosis  Ixodes  Deer tick  Tick-borne  Leukopenia  Thrombocytopenia  Doxycycline KEY POINTS  Anaplasmosis is transmitted by the bite of Ixodes ricinus complex ticks, which includes the black-legged or deer tick (Ixodes scapularis) in north central and eastern North America, and the western black-legged tick (Ixodes pacificus) in western North America.  Symptoms of anaplasmosis include fever, headache, malaise, loss of appetite, and aches.  Illness can be mild and self-limited or progress to severe illness and death, particularly in older individuals and those with comorbid conditions.  Laboratory findings may include leukopenia, thrombocytopenia, and elevated hepatic transaminases.  The probability of anaplasmosis increases with a history of Ixodes tick/habitat exposure and the presence of typical symptoms and can be confirmed with polymerase chain reaction testing.  A patient with compatible illness and epidemiologic exposures should be treated with doxycycline. Continue treatment if they improve while on doxycycline, regardless of confirmatory test results. INTRODUCTION Human granulocytic anaplasmosis (HGA) is a vector-borne bacterial infection caused by Anaplasma phagocytophilum. It has one of the most rapidly increasing incidences of tick-borne infections in the United States.1 It is transmitted to humans when infected nymphal or adult Ixodes ricinus complex (black-legged or deer) ticks take a blood meal.2 These ticks are found in north central and eastern North America and the West coast of North America. Related I ricinus complex ticks transmit HGA in much of Eurasia and eastern Asia. In the United States, HGA was first described in 1994 in the upper Midwest3,4 and then in multiple areas of the Northeast.5,6 The illness was initially known as human granulocytic ehrlichiosis because the pathogen was named Ehrlichia phagocytophilum at the time. Subsequent work involving 16s rRNA a Cayuga Medical Center, 101 Dates Drive, Ithaca, NY 14850, USA; * Corresponding author. E-mail address: [email protected] Infect Dis Clin N Am 36 (2022) 639–654 https://doi.org/10.1016/j.idc.2022.02.008 0891-5520/22/ª 2022 Elsevier Inc. All rights reserved. b Weill Cornell Medicine id.theclinics.com Descargado para Anonymous User (n/a) en Pontifical Bolivarian University de ClinicalKey.es por Elsevier en febrero 07, 2024. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2024. Elsevier Inc. Todos los derechos reservados. 640 MacQueen & Centellas gene sequences led to realignment of families in the order Rickettsiales and renaming of the bacteria as Anaplasma phagocytophilum.7 Members of the genera Anaplasma cause infections in humans and animals. In addition to HGA, A phagocytophilum causes canine and equine granulocytic anaplasmosis, and tick-borne fever in cattle and sheep.8,9 BACKGROUND A phagocytophilum is an obligate intracellular gram-negative bacterium in the order Rickettsiales, family Anaplasmataceae.10 It multiplies in vacuoles called morulae in the cytoplasm of mammalian host neutrophils. In tick vectors, the organism initially lives in cells of the midgut and then migrates to salivary glands where it develops.11–13 A phagocytophilum has been found in the salivary glands of infected ticks that have yet to begin a blood meal,11 suggesting the possibility of faster transmission than occurs with other organisms, such as Borrelia burgdorferi.14 A phagocytophilum is able to interfere with molecular pathways in both tick and host cells to evade the immune response in each. This allows the organism to infect tick midgut cells, evade mammalian host cell defenses, and cause infection.15 There are distinct genetic variants of A phagocytophilum that have specificity for the host in which they are maintained, and for the type of host in which they cause infection. In North America, genetic variant Ap-ha, which causes HGA in humans, is maintained in a white-footed mouse (Peromyscus leucopus) and Eastern chipmunk (Tamias striatus) reservoir.16 Ap-V1, which is found in white-tailed deer (Odocoileus virginianus), is not pathogenic to humans. An abundance of Ap-ha–infected host-seeking ticks in the environment is predictive of human anaplasmosis case distribution and incidence based on data from New York State (Melissa Prusinksi, personal communication, January 5, 2022) and other parts of eastern North America.17 VECTOR-BORNE TRANSMISSION A phagocytophilum is transmitted primarily by the bite of I ricinus complex ticks.2 It is important to be familiar with the range of these ticks in order to assess a patient’s risk for acquiring HGA. In the eastern and Midwest United States and south central and south eastern Canada, the vector is Ixodes scapularis, commonly called the blacklegged (deer) tick.18–20 In the western United States and Canada, it is Ixodes pacificus.21 Throughout much of the United Kingdom and Eurasia, I ricinus is the vector.22–24 I persulcatus is the vector in Japan, Korea, and eastern portions of Russia and China.25 I ricinus complex ticks are not infected as larvae by transovarial transmission.26 Instead, larval and nymph forms of these ticks may acquire A phagocytophilum when they take a blood meal from an infected host. These ticks feed and acquire a blood meal over the course of several days during the same “bite.” Mammalian models suggest that 24 hours or more of tick attachment is needed to transmit enough A phagocytophilum to cause an infection in hosts. I ricinus complex ticks required at least 2 days of feeding to cause symptomatic tick-borne fever owing to A phagocytophilum in sheep.27 Infected I ricinus ticks that fed on dogs began transmission of A phagocytophilum within hours, but more than 48 hours of feeding was needed to transmit a sufficient inoculum of the organism to cause infection.28 Depending on the study, nymphal I scapularis ticks that fed on mice typically required 24 to 48 hours to transmit A phagocytophilum to the mouse.29–32 Some models showed the presence of A phagocytophilum DNA in hosts after feeding by infected ticks in less than 24 hours, but those hosts did not develop antibodies against A Descargado para Anonymous User (n/a) en Pontifical Bolivarian University de ClinicalKey.es por Elsevier en febrero 07, 2024. Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2024. Elsevier Inc. Todos los derechos reservados. Human Granulocytic Anaplasmosis 641 phagocytophilum. This suggests that insufficient inoculum had been transmitted to cause infection during more brief feeding periods. BLOOD TRANSFUSION AND ORGAN TRANSPLANT–RELATED TRANSMISSION HGA can be transmitted by both red blood cell and platelet transfusion as well as organ transplantation. Several transfusion-related cases have been reported, including some that were fatal.33–35 A review of the cases that occurred between 1997 and 2020 identified 10 transfusion-related cases of HGA and 7 solid organ transplant–related cases.36 The blood supply is not screened for HGA.37 Leukoreduced blood units may reduce, but not eliminate, the risk of transfusion-related HGA. EPIDEMIOLOGY HGA is an emerging disease in parts of North America, East Asia, and Eurasia.38–40 The geographic range of HGA and overall incidence are increasing.41–44 The rate of increase is higher than has been seen with other tick-borne infections, and it is estimated that the actual number of cases may be 11 times higher than is reported by public health departments.45 Seroprevalence of antibodies against A phagocytophilum in asymptomatic humans varies by region and exposure type. They were found in 36% of forest workers in Poland,46 14.9% of northwestern Wisconsin residents with no known preceding tick bite,47 and 23% of potential organ donors in Manitoba, where the presence of I scapularis had only recently been described.48 This increase in HGA cases is multifactorial. Elias and colleagues40,41 postulated that case recognition and testing for HGA in individuals with compatible illnesses have increased because of better public and clinician awareness of HGA as well as widespread availability of accurate molecular testing. Other factors include the increased population density and range of I ricinus complex ticks,49 and new areas in that range that questing ticks carry A phagocytophilum.17,50 For example, in New York State, the percentage of adult I scapularis (black-legged or deer) ticks that were positive for A phagocytophilum increased from 4.0% to 9.2% (P