Human Granulocytic Anaplasmosis—A Systematic Review of Published Cases

Abstract

Anaplasma phagocytophilum is an emerging, Gram-negative, obligate intracellular pathogen that is transmitted by a tick vector. Human infection ranges from asymptomatic to severe disease that can present with pancytopenia, multiorgan failure, and death. The aim of this systematic review is to analyze case reports and case series reported over the last two decades in peer-reviewed journals indexed in the Medline/PubMed database according to the PRISMA guidelines. We found 110 unique patients from 88 case reports and series. The most common mode of transmission was tick bite (60.9%), followed by blood transfusion (8.2%). Infection was acquired by blood transfusion in nearly half (42%) of the immunocompromised patients. Most patients reported fever (90%), followed by constitutional (59%) and gastrointestinal symptoms (56%). Rash was present in 17% of patients, much higher than in previous studies. Thrombocytopenia was the most common laboratory abnormality (76%) followed by elevated aspartate aminotransferase (AST) (46%). The diagnosis was most commonly established using whole-blood polymerase chain reaction (PCR) in 76% of patients. Coinfection rate was 9.1% and Borrelia burgdorferi was most commonly isolated in seven patients (6.4%). Doxycycline was used to treat 70% of patients but was only used as an empiric treatment in one-third of patients (33.6%). The overall mortality rate was 5.7%, and one patient died from trauma unrelated to HGA. The mortality rates among immunocompetent and immunocompromised patients were 4.2% (n = 4/95) and 18.2% (n = 2/11), respectively. Four of the six patients who died (66.6%) received appropriate antibiotic therapy. Among these, doxycycline was delayed by more than 48 h in two patients.

The Obligate Intracellular Bacterial Pathogen Anaplasma phagocytophilum Exploits Host Cell Multivesicular Body Biogenesis for Proliferation and Dissemination

“… A. phagocytophilum infection in humans, termed human granulocytic anaplasmosis (HGA), is the second-most common tickborne disease in the United States and occurs throughout much of Europe and Asia ( 3 , 4 ). HGA can also be transmitted perinatally and via blood transfusion ( 5 ). Hospitalization is required for 36% of HGA cases and admittance to intensive care for 7% ( 4 , 6 ).…”

High diversity of Rickettsia spp., Anaplasma spp., and Ehrlichia spp. in ticks from Yunnan Province, Southwest China

“…Meanwhile, A. phagocytophilum , A. bovis , and A. capra are confirmed human pathogens ( Li H. et al, 2015 ; Ismail and McBride, 2017 ; Lu et al, 2019 ). In the past decades, a total of 110 infection cases of A. phagocytophilum were reported ( Dumic et al, 2022 ). Among Ehrlichia species, E. ruminantium and E. minasensis are known to infect cattle, causing severe fever, anemia, and thrombocytopenia ( Peter et al, 2020 ).…”

Infection of Severe Fever with Thrombocytopenia Syndrome Virus as a Cause of a Child’s Fever of Unknown Origin: A Case Report

“…The differential diagnosis for SFTS encompasses diseases transmitted by the same vector such as Dengue fever, Crimean-Congo hemorrhagic fever (CCHF), typhus, human granulocytic anaplasmosis (HGA), and Lyme disease; however, other zoonoses and non-vector-borne diseases should also be considered, such as Influenza, thrombotic thrombocytopenic purpura (TTP), myelodysplastic syndrome (MDS), and other hematological diseases. 17 …”

“…The differential diagnosis for SFTS encompasses diseases transmitted by the same vector such as Dengue fever, Crimean-Congo hemorrhagic fever (CCHF), typhus, human granulocytic anaplasmosis (HGA), and Lyme disease; however, other zoonoses and non-vector-borne diseases should also be considered, such as Influenza, thrombotic thrombocytopenic purpura (TTP), myelodysplastic syndrome (MDS), and other hematological diseases. 17 Pediatric SFTS infection has a milder clinical course than adult SFTS infection and responds well to treatment. This phenomenon led to the hypothesis that children were immune to infection, possibly due to immaturity of the immune system or a lack of other injury risk factors (such as cigarette smoking).…”