Ehrlichia chaffeensis: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Ehrlichia chaffeensis

Agent type

Bacteria

Taxonomy

Family

Anaplasmataceae

Genus

Ehrlichia

Species

chaffeensis

Synonym or cross-reference

Ehrlichiosis, human monocytic ehrlichiosis (HME), Ehrlichia ewingii, Ehrlichia muris eauclairensis, Rikettsial diseases, undetermined ehrlichiosis/anaplasmosis.

Characteristics

Brief description

Ehrlichia chaffeensis is a tick-borne Gram-negative obligatory intracellular bacterium of the family Anaplasmataceae in the order Rickettsiales^{Footnote 1}. Its genome consists of a single small (1.18 Mbp) circular genome that lacks most genes for amino-acid biosynthesis and intermediary metabolism and consequently, the bacterium depends on host cells for these molecules^{Footnote 2}. In humans, they reside and propagate in bone marrow-derived cells, such as granulocytes, monocytes, erythrocytes, and platelets within vacuoles. These intracytoplasmic clusters of bacteria are found in two forms; as small dense core forms (0.2 to 0.4 µm) or larger forms (0.8 to 1.5 µm) that resemble reticulate bodies^{Footnote 3}. Infection in humans causes a severe flu-like febrile disease called human monocytic ehrlichiosis (HME), which is often accompanied by hematologic abnormalities and signs similar to those of hepatitis^{Footnote 4}.

Properties

As an obligate intracellular bacteria, E. chaffeensis has adaptations that aid in avoiding detection by the host immune system. The bacteria replicates within monocytes and macrophages, which are primary immune cells that recognize pathogen-associated molecular patterns (PAMPs). To avoid detection, E. chaffeensis has lost genes encoding major PAMPs such as lipopolysaccharide, peptidoglycan, flagella, and common pili^{Footnote 5}. E. chaffeensis invasin EtpE (entry-triggering protein of Ehrlichia) binding to the host surface receptor DNase X induces internalization into host cells without activating a phagocytic response. Once inside the host cell, bacterium replicate inside vacuoles which further shields it from the host immune response^{Footnote 6}.

Section II – Hazard identification

Pathogenicity and toxicity

Although ehrlichiosis is a general term used to describe disease caused by E. chaffeensis, Ehrlichia ewingii and Ehrlichia muris eauclairensis, the majority of reported cases in humans are due to infection caused by E. chaffeensis^{Footnote 7}. Symptoms of early illness include fever, chills, dull/severe headaches, myalgia, malaise, nausea, vomiting, diarrhea and loss of appetite^{Footnote 8Footnote 9}. In addition, ehrlichiosis patients may present with symptoms of confusion or changes in mental state and rash^{Footnote 10Footnote 11}. Ehrlichiosis typically manifests with leukopenia, thrombocytopenia, and elevated hepatic transaminases^{Footnote 12}. More severe symptoms can lead to multi-organ failure^{Footnote 11Footnote 13} and manifests in vital organs such as the heart, kidney, liver, spleen and lung and can be accompanied with mental confusion^{Footnote 11}. Additionally, ehrlichiosis may be complicated by hemophagocytic lymphohistiocytosis in rare cases and in immunocompromised situations, such as in transplant patients^{Footnote 11Footnote 13}. The clinical manifestations of E. chaffeensis infections appear to be due to the host inflammatory response to the infection rather than direct damage from the bacteria. Fatality rate as high as 3% is seen for E. chaffeensis infections^{Footnote 14}.

Epidemiology

Ehrlichiosis caused by E. chaffeensis is seen primarily in North America, but there are reports of the disease in Europe and in Asian countries such as China, Japan, and South Korea^{Footnote 14Footnote 15Footnote 16Footnote 17Footnote 18}. Maintenance of tick-borne E. chaffeensis in nature depends upon the presence of appropriate tick vectors and mammalian hosts in the local environment. In North America, E. chaffeensis is maintained in a cycle involving the white-tailed deer (Odocoileus virginianus) and the lone star tick (Amblyomma americanum), which play a role as its primary reservoir and vector, respectively^{Footnote 1}. E. chaffeensis has also been detected in coyotes, foxes, gray wolves, raccoons, opossums, goats and domestic dogs^{Footnote 7Footnote 19}.

As ehrlichiosis is a tickborne disease, it is more common from May through to August^{Footnote 7}. In the United Sates, the number of reported cases on ehrlichiosis caused by E. chaffeensis has steadily increased from 200 cases in the year 2000 up to a peak of 2093 cases in 2019^{Footnote 20}. These figures are likely underestimates, as active surveillance in Tennessee has shown infection rates as high as 330–414 cases per 100,000 population (0.3%–0.4%)^{Footnote 7}. In the United States during the period from 2008 to 2012, 4613 cases of E. chaffeensis infection were reported, corresponding to an incidence rate of 3.2 cases per million persons-years^{Footnote 21}. The hospitalization rate was 57% while the fatality rate was 1%.

Older individuals, patients with comorbidities, and immunocompromised patients are at higher risk for a severe disease if left untreated^{Footnote 14}.

Host range

Natural host(s)

White-tailed deer, humans and domestic animals^{Footnote 15}.

Other host(s)

White-footed mice, hamsters, and red-backed voles have been inoculated but do not show signs of infection, disease or seropositivity^{Footnote 22}. Immunocompromised C3H/HeJ mice have been infected.

Infectious dose

Unknown.

Incubation period

Median incubation period is 9 days^{Footnote 1}.

Communicability

Most people develop ehrlichiosis after a tick bite from an infected tick^{Footnote 1}. In rare cases, E. chaeffeensis may be transmitted through blood transfusion and organ transplantation^{Footnote 23}.

Section III – Dissemination

Reservoir

White tailed deer (Odocoileus virginianus) is the principal animal reservoir of E. chaffeensis. They are persistently bacteremic, but do not develop clinical signs of infection^{Footnote 24Footnote 25}. Dogs, foxes, wolves, coyotes and cats are also known animal reservoirs^{Footnote 9Footnote 26Footnote 27}.

Zoonosis

None.

Vectors

Lone Star tick (Amblyomma americanum); black-legged ticks (Ixodes scapularis and I. pacificus). American dog ticks (Dermacentor variabilis and D. occidentalis) are less common carriers^{Footnote 28}.

Section IV – Stability and viability

Drug susceptibility/resistance

Doxycycline is a wide spectrum antibiotic of choice for ehrlichiosis; early treatment can prevent death and severe illness^{Footnote 9Footnote 11Footnote 16}. Many antibiotics such as b-lactams, cephalosporins, macrolides, and aminoglycosides are ineffective against E. chaffeensis in vitro^{Footnote 7}.

Susceptibility to disinfectants

Susceptible to 1% sodium hypochlorite, 70% ethanol, glutaraldehyde, formaldehyde, and quaternary ammonium disinfectants^{Footnote 29}.

Physical inactivation

Sensitive to moist heat (121°C) for at least 15 minutes and dry heat (160°C–170°C) for at least 1 hour^{Footnote 28Footnote 30}.

Survival outside host

E. chaffeensis is an obligate intracellular bacteria and are sensitive to mechanical stress such as freezing and thawing, and osmolarity changes^{Footnote 1Footnote 29}.

Section V – First aid/medical

Surveillance

Monitor for symptoms of illness; confirmation through diagnostic testing such as Romanowsky stains, PCR, and serological tests (indirect immunofluorescence) which detect Ehrlichia species in blood, cerebral spinal fluid (CSF), tissue, and ticks, or Ehrlichia-specific antibodies in serum^{Footnote 1}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

People bitten by a tick are advised to remove the tick and subsequently watch for signs and symptoms of illness. If signs such as fever, rash, fatigue, or myalgia develop, the recommendation is to see a physician within 14 days of the tick bite. A wide spectrum tetracycline based antibiotic, doxycycline, is the first line of treatment for positive diagnostic tests indicating signs of ehrlichiosis^{Footnote 7}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

No vaccines are available for humans^{Footnote 20}.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

No known post-exposure prophylaxis.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI – Laboratory hazard

Laboratory-acquired infections

No cases of laboratory-acquired infections have been reported.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

Whole blood, CSF, eschar swab or tissue. Cultures and frozen stocks^{Footnote 1}.

Primary hazards

Ingestion, accidental parenteral inoculation, and direct contact with skin or mucous membranes with cultures/infected tissues/body fluids and inhalation of aerosols of contaminated fluids.

Special hazards

Direct contact with an slaughtered infected animal^{Footnote 10}.

Section VII – Exposure controls/personal protection

Risk group classification

Ehrlichia chafeensis is a Risk Group 3 Human Pathogen and Risk Group 2 Animal Pathogen^{Footnote 31}.

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects are to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Proper precautions should be considered when working with infected arthropods. This might include implementing a program to prevent escapes and monitor any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measures^{Footnote 32Footnote 33}.

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time with disinfectant before clean up (Canadian Biosafety Handbook).

Disposal

Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 3 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

An inventory of RG3 pathogens in long-term storage, to be maintained and to include:

• specific identification of the regulated materials
• a mechanism that allows for the detection of a missing or stolen sample in a timely manner

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with Ehrlichia chaffeensis require a Pathogen and Toxin licence issued by the Public Health Agency of Canada. E. chaffeensis is a terrestrial animal pathogen in Canada; therefore, importation of E. chaffeensis requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a Pathogen and Toxin Licence which includes a Human Pathogen and Toxin Licence and an HAR importation permit.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations

Last file update

June, 2024

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, directives and standards applicable to the import, transport, and use of pathogens and toxins in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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