We conducted a literature search to identify articles published during January–August 2020 describing ehrlichiosis and anaplasmosis in solid organ transplant or blood transfusion recipients in the United States. We used PubMed search terms “ehrlichiosis AND transfusion,” “ehrlichiosis AND transplant,” “anaplasmosis AND transfusion,” and “anaplasmosis AND transplant.” We included articles describing case reports, case series, or other clinical descriptions related to Ehrlichia and Anaplasma spp. infections in the setting of solid organ transplantation or transfusion of blood products in the United States. We excluded infections in hematopoietic stem cell recipients because these are not reported to a national notifiable disease system. For articles meeting inclusion criteria, we further reviewed references to identify any case reports or case descriptions not found in the initial PubMed search. Duplicate cases were only counted once for this review. We summarized transplant- and transfusion-associated cases as presented in the literature; we made no additional exclusions based on diagnostic criteria, and we only determined cases to be donor-derived if the authors presented them as such in the literature or investigations.

In the United States, all suspected or confirmed cases of donor-derived diseases are reported to the Organ Procurement and Transplantation Network and are investigated by the Disease Transmission Advisory Committee (DTAC). Nationally notifiable diseases such as ehrlichiosis and anaplasmosis are referred to the Centers for Disease Control and Prevention (CDC) for investigation and determination of whether the infection was transmitted from a donor to a recipient. We also included cases of transplant-associated ehrlichiosis and anaplasmosis identified as part of these DTAC investigations by CDC if not already accounted for in the peer-reviewed literature (Figure 1). From each reviewed article or CDC-led case investigation, we collected available information on geographic region, recipient characteristics, Ehrlichia or Anaplasma species, transmission route, age of blood component transfused or type of organ transplanted, time between transplantation and infection, symptoms and clinical details, diagnostic methods, donor and recipient histories of tick exposure, donor characteristics, likely source of infection, and whether the recipient survived or died.

This study reviewed ehrlichiosis and anaplasmosis cases among transfusion and solid organ transplant recipients described in published literature and reports from 6 CDC investigations. During the study period, 12 cases of transfusion-transmitted ehrlichiosis or anaplasmosis were reported, 2 of which resulted in death. In addition, 8 cases of organ donor–derived ehrlichiosis were reported (7 kidney transplant recipients and 1 liver recipient), 2 of which resulted in death. A. phagocytophilum was the most common causative agent among transfusion-derived infections. In contrast, among transplant recipients, E. chaffeensis was the most common causative agent. Donor-derived infections were observed among patients of a broad range of ages (5–85 years). Although children are not considered a high-risk group for anaplasmosis in particular, pediatric infection should not be discounted among transfusion and transplant recipients. Time from transplant or transfusion to the development of signs and symptoms varied widely and in most cases was longer than the typical incubation period for a tick-transmitted infection. Delays in symptom onset might be affected by the colony size and the site of the inoculated bacteria. Transfusion- or transplant-transmitted ehrlichiosis and anaplasmosis are rare but can result in severe outcomes including the death of the recipient.

Although known cases of transfusion- and transplant-transmitted ehrlichiosis or anaplasmosis are uncommon, studies of asymptomatic infection among blood donors and the survivability of infection in blood suggest the risk of transmission is greater than previously recognized. In endemic areas, seroprevalence studies found 11.3% of blood donors in New York, 0.5% in Wisconsin, and 3.5% in Connecticut had detectable antibodies against A. phagocytophilum (24,25). In Iowa, ≈1% of blood donors studied were seropositive for and displayed symptoms of ehrlichiosis after blood donation, although recipient lookback reported by physicians indicated that these transfusions did not result in transfusion-transmitted illnesses (26). However, serosurveys do not report active or incident infections, only the proportion of participants previously exposed to an Ehrlichia or Anaplasma agent. Some studies also examined the survivability of Ehrlichia and Anaplasma species in donor blood. Blood from anaplasmosis patients in 2 studies found viable A. phagocytophilum survived under refrigerated storage conditions for up to 18 days in whole blood (27,28). One in vitro study reported E. chaffeensis remained viable for up to 11 days within refrigerated packed red blood cells (29).

Donor-derived ehrlichiosis and anaplasmosis highlight the importance of donor risk mitigation strategies in the setting of blood transfusion and solid organ transplantation and the potential role of laboratory-based screening. Recognizing and diagnosing tickborne diseases is complicated by long incubation periods and potential asymptomatic or mildly symptomatic infections. Although several laboratory tests are used to diagnose ehrlichiosis and anaplasmosis, no tests have been approved by the US Food and Drug Administration (FDA) to screen blood or organ donors for these diseases. Furthermore, serologic screening of donors might not identify active Ehrlichia or Anaplasma infections or could exclude healthy donors (28). PCR testing would more accurately screen contaminated blood and organ products, but no FDA-licensed test is available. Donor deferral on the basis of travel or residence would be impractically broad because of the widespread endemicity of ehrlichiosis and anaplasmosis across regions of the United States. To minimize blood supply disruptions based on travel deferrals for Zika virus and babesia, FDA previously recommended universal antibody testing and regional nucleic acid testing in states with the highest rates of risk for infection (30,31). Similar screening may eventually be necessary for ehrlichiosis and anaplasmosis as the prevalence and incidence of these infections increases in the United States. CDC will continue to monitor the occurrence of transfusion- or transplant-transmitted ehrlichiosis and anaplasmosis.

Among this study’s limitations, for sources identified through the literature we were limited to the information provided in the case reports, which might not always have represented a full account of the patient experience. Data on donor demographics were extremely limited. Donor state of residence might have provided a more accurate insight on likelihood of donor infection by state which might have broader implications for blood and organ screening criteria. Next, for the purposes of this evaluation, we relied on the characterizations by the original authors or investigators to categorize cases as donor- or transplant-derived ehrlichiosis or anaplasmosis. Finally, we included only cases published in peer-reviewed literature or reported to CDC, possibly underreporting transfusion- and transplant-associated infections. In 2019, the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, CDC, added questions relating to recent transfusion and organ transplant to their tickborne rickettsial disease surveillance system (https://www.cdc.gov/ticks/forms/Tick_TBRD_FILL_508.pdf) to better track donor-derived infections.

Because Ehrlichia and Anaplasma species primarily infect leukocytes, leukoreduction has been presumed to reduce risk for ehrlichiosis and anaplasmosis through passive removal (23,32,33). However, 83% (10/12) of components implicated in transfusion-transmitted cases in this study were leukoreduced. In cell culture models, because of their presence in plasma also, E. chaffeensis survived in red blood cells stored in additive solution, suggesting leukoreduction alone will not prevent transmission of Ehrlichia and Anaplasma species (29). Adopting pathogen reduction technology, such as psoralen and ultraviolet light to inactivate infectious agents, for platelet and plasma products would provide additional safety measures to reduce risk for transfusion-transmitted Ehrlichia and Anaplasma infections. Pathogen-reduced plasma has demonstrated a ≥3.6-log reduction in viable A. phagocytophilum (34). However, this method has not been approved for red blood cell products, which were implicated in 8 of 12 cases of transfusion-transmitted ehrlichiosis and anaplasmosis in this study.

Identifying risk factors for Ehrlichia and Anaplasma infections among deceased organ donors is challenging because clinical, demographic, and social information about deceased donors is often obtained from family members, who might not have access to or recall all historical details (35). Also, routine laboratory screening of organ donors, required for multiple infectious diseases, including HIV/AIDS, does not yet include testing for infection with Ehrlichia and Anaplasma species. In addition, the number of posttransplant infections reported in this review highlights the risk among blood product or organ recipients. Therefore, clinicians must closely monitor recipients of blood transfusions or solid organs during long-term management and consider these pathogens when recipients develop signs or symptoms of infection. Because the prevalence of tickborne disease infections is rising, additional risk mitigation interventions will likely be necessary to enhance blood and organ safety.