Ehrlichiosis infection mimicking thrombotic microangiopathy syndrome early after kidney transplantation

Abstract

Human ehrlichiosis and anaplasmosis is a tick-borne infection identified in both immunocompromised and immunocompetent individuals 1-13 and can present in different clinical forms. Ehrlichia chaffeensis is a small gram-negative bacillus that causes human monocytic ehrlichiosis (HME). 8-10 Anaplasma phagocytophilum causes human granulocytotropic anaplasmosis (HGA), previously known as human granulocytotropic ehrlichiosis. 1,4,13,14 Human monocytic ehrlichiosis and HGA are quite different in their geographical distribution. While HME is predominant in the South-central and Southwestern United States, HGA is more common in the Northeastern and Midwestern United States. 2,3,5 The clinical presentation of HME and HGA varies from self-limited febrile illness to fatal disease 2,3,7,11,12 that can be even more variable and results in more serious infection in immunocompromised patients. Human monocytic ehrlichiosis and HGA may present with fever, headache, myalgia, thrombocytopenia, leukopenia, and elevated liver enzymes. Renal dysfunction is more often present in transplant recipients than in immunocompetent patients with Ehrlichia infection. 11 Transplant patients present with more gastrointestinal symptoms such as nausea, vomiting, and diarrhea compared to immunocompetent patients. 11 The majority of infected patients may need hospitalization, and 13% of immunocompromised patients may require intensive care unit admission. 11 Thomas et al. reviewed cases of ehrlichiosis in transplant recipients (n = 15) and immunocompetent patients (n = 43), who presented to three hospitals in Nashville, Tennessee, between 1998 and 2006. In that study, the median time of infection since transplantation was 3.9 years, and 80% of the patients were at least 1 year post-transplantation. 11 Similarly to this study, most of the previously described cases was detected in the late post-transplant period. However, early HME and HGA infection may raise the concern for donor driven infection, 15 particularly if donor lives in an endemic area. Human ehrlichiosis was also reported after treatment (Solumedrol, rituximab, and anti-thymocyte globulin) of acute cellular rejection in a living donor kidney transplant recipient. 12

Ehrlichia effector TRP120 manipulates bacteremia to facilitate tick acquisition

“…The hallmark of human ehrlichiosis is white blood cell abnormalities that mimic the signs of leukemia, lymphoma, or endotoxemia, and consequently, cases are sometimes misdiagnosed as hematological malignancies, thrombotic thrombocytopenia purpura, or sepsis, causing delay in treatment ( 1 , 9 , 49 – 52 ). As shown in previous ( 16 , 24 , 25 , 53 ) and current studies, E. japonica causes systemic infection and severe thrombocytopenia and increases serum alanine and aspartate aminotransferase abundance in infected mice, indicators that are similar to those observed for patients that progress to fatal HME ( 9 ).…”

Complement in Secondary Thrombotic Microangiopathy

“…reviewed and are listed below: • Shigatoxin (STEC-HUS) producing enterobacteria: E. coli is the most common, the others include Shigella dysenteriae, Campylobacter jejuni, Moraxella osloensis • Viral infections: cytomegalovirus, Epstein-Barr virus, varicella zoster virus, parvovirus B19, human immunodeficiency virus, influenza virus • Respiratory tract infection agents: Bordetella pertussis, Streptococcus pneumoniae(16), Mycoplasma pneumoniae(93).• Protozoa: Toxoplasma gondii.• Rare agents: erlichiosis(94), Capnacytophaga canimorsus(95,96), Plasmodium vivax (malaria)(97), snakebites (Bothrops jararaca)(98), dengue fever(99)(100)(101), West Nile virus(102); Chikungunya Fever(103,104).• Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) Mechanisms of TMA-associated with infectious diseases are complex and include direct endothelial injury, development of ADAMTS13 inhibitors and complement activation inJ o u r n a l P r e -p r o o f different levels and magnitude. As an illustration, putative mechanisms of TMA in influenza infection are production of neuraminidase (although lower than seen with Streptococcus pneumoniae), direct infection of endothelial cells leading to apoptosis, activation of platelets and generation of thrombin.…”