Orientia tsutsugamushi: Infectious substances pathogen safety data sheet 

Section I: Infectious agent

Name

Orientia tsutsugamushi

Agent type

Bacteria

Taxonomy

Family

Rickettsiaceae

Genus

Orientia

Species

tsutsugamushi

Synonym or cross-reference

Also known as Rickettsia tsutsugamushi^{Footnote 1}. O. tsutsugamushi is the causative agent of scrub typhus, also known as "tropical typhus" and "tsutsugamushi disease"^{Footnote 2}.

Characteristics

Brief description

O. tsutsugamushi is a gram-negative, coccobacilli bacterium measuring 0.5 μm by 1.2-3.0 μm^{Footnote 3}. The cell wall of the bacterium lacks lipopolysaccharide and contains minimal peptidoglycan^{Footnote 4}. The genome contains large proportions of mobile genetic elements. O. tsutsugamushi cannot be grown in media as it is an obligate intracellular pathogen and must be cultured in vitro^{Footnote 5}. O. tsutsugamushi can be cultured within the yolk sac of chicken embryos or in cell lines, such as HeLa, Vero, BHK, or L929^{Footnote 3},^{Footnote 6}. O. tsutsugamushi can also be cultivated in mice^{Footnote 3}.

Properties

O. tsutsugamushi enters host cells by induced phagocytosis and replicates by binary fission in the cytoplasm of eukaryotic host cells. After replicating in host cells, O. tsutsugamushi is released from host cells in a manner similar to budding of enveloped viruses^{Footnote 7}.

Section II: Hazard identification

Pathogenicity and toxicity

O. tsutsugamushi is the causative agent of scrub typhus. Symptoms may include general malaise, coughing, headache, fever persisting 9 to 19 days, rash, and lymphadenopathy^{Footnote 6},^{Footnote 8},^{Footnote 9}. Other characteristics of the disease include focal or disseminated vasculitis and perivasculitis, involving the lungs, heart, liver, spleen, and the central nervous system^{Footnote 8}. The disease can lead to complications, such as pneumonia, myocarditis, meningoencephalitis, acute renal failure, or gastrointestinal bleeding^{Footnote 8}. O. tsutsugamushi is transferred through mite bites and an eschar can develop at the site of the bite, beginning as a red papule which later ulcerates and blackens^{Footnote 6}.

The mortality rate varies from less than 1% to 50%^{Footnote 9},^{Footnote 10},^{Footnote 11}; median mortality rate for untreated patients is 6% and 1.4% for treated patients^{Footnote 12}. Mortality rates are higher in cases involving complications, including acute respiratory distress syndrome^{Footnote 13},^{Footnote 14}, pneumonitis^{Footnote 15},^{Footnote 16}, thrombocytopenia^{Footnote 2}, pancreatitis, renal failure, aseptic meningitis, meningoencephalitis, gastrointestinal bleeding, and multi organ failure^{Footnote 8},^{Footnote 13},^{Footnote 17}.

Virulence varies among different strains mostly due to the variable surface antigens across different O. tsutsugamushi strains^{Footnote 3},^{Footnote 18},^{Footnote 19}.These surface antigens can cause O. tsutsugamushi to persist in humans after the disease is resolved, as antibodies no longer recognize the changed surface antigens^{Footnote 20},^{Footnote 21}. Relapses after completion of antibiotic treatment have been reported^{Footnote 21},^{Footnote 22}.

Epidemiology

O. tsutsugamushi is endemic to 'tsutsugamushi triangle', which includes northern Japan, Korea, Southeast Asia, Southwest Pacific, and eastern Russia^{Footnote 17}. Scrub typhus incidence varies in different countries from 1 to 60 cases per 100,000 people per year^{Footnote 12}. Numerous outbreaks of scrub typhus have been documented^{Footnote 17}. Recent outbreaks include two Camp Fuji outbreaks in 2000 and 2011 with 9 and 8 cases, respectively^{Footnote 10},^{Footnote 17}; Maldives in 2002 with 168 confirmed cases^{Footnote 10},^{Footnote 17}; Thailand in 2006-2007 in which scrub typhus was suspected in 142 febrile children^{Footnote 17}; and two outbreaks in Rajasthan, India in 2012 and 2013^{Footnote 17}. Sporadic cases of scrub typhus have been reported in areas outside the tsutsugamushi triangle, including United Arab Emirates, Chile and parts of Africa^{Footnote 17}.

Animals do not appear to show symptoms of the disease caused by O. tsutsugamushi despite being infected, as determined by the presence of serum antibodies.

Individuals living or working in areas where the mite vectors are highly prevalent are more susceptible to scrub typhus^{Footnote 23}. Elderly individuals afflicted by scrub typhus are more at risk of developing complications^{Footnote 13}. Additional risks for pregnant women include increased chance of miscarriage and premature delivery^{Footnote 13}.

Host range

Natural host(s)

Humans. Rodents and other infected mammals are dead-end hosts. Antibodies to O. tsutsugamushi have been found in wild monkeys and dogs^{Footnote 29},^{Footnote 30}, although the disease is not known to occur naturally in animals^{Footnote 31}.

Other host(s)

Chickens, goats, horses, and calves were susceptible to infection by O. tsutsugamushi in vaccine research^{Footnote 29}. Monkeys infected in an experimental setting developed clinical signs and symptoms that resembled human scrub typhus^{Footnote 32}.

Infectious dose

Varies for different strains^{Footnote 33}. The 50% mouse infectious dose (MID₅₀) for different O. tsutsugamushi strains was determined by intraperitoneal inoculation in mice; MID₅₀ ranged between 6.2 and 7.8 (log₁₀) depending on strain virulence^{Footnote 33}.

Incubation period

5 to 20 days^{Footnote 6}.

Communicability

Transmission from animal to human hosts occurs in nature via bites from infected Leptotrombidium mites (also known as 'chiggers') that are vectors for O. tsutsugamushi. Mites require 36-72 hours for attachment to the host's skin and infection to occur^{Footnote 8}. Once inside the host, the bacteria can enter the bloodstream^{Footnote 24}. Vertical transmission from mother to baby is unlikely but has been observed^{Footnote 25}. Human to human transmission is rare but can occur via blood transfusion^{Footnote 26},^{Footnote 27}.

There is potential for the bacterium to enter a host through damaged skin. Contact of O. tsutsugamushi with mucous membranes via inhalation of infectious aerosols in a laboratory setting has resulted in scrub typhus pneumonitis^{Footnote 28}. Laboratory workers have also acquired O. tsutsugamushi infection via rat bites, needle-stick injuries or auto-inoculation^{Footnote 28}.

Section III: Dissemination

Reservoir

Leptotrombidium mites^{Footnote 17}. After the disease is resolved, the bacterium can persist in human and animal hosts without symptoms^{Footnote 20},^{Footnote 21}.

Zoonosis

None. Infected animals can transmit O. tsutsugamushi to humans via bites, but this phenomenon is not common in nature^{Footnote 5}.

Vectors

Larval trombiculid mite species of the genus Leptotrombidium are vectors for O. tsutsugamushi^{Footnote 2},^{Footnote 34}. The bacteria are transmitted to hosts via mite 'bites'. Mites attach to skin and feed using host pores or hair follicles but do not pierce the skin. O. tsutsugamushi are injected into the host as the mite feeds. Mites feed once during the larval stage of their life cycle^{Footnote 2}.

Section IV: Stability and viability

Drug susceptibility/resistance

Tetracyclines (e.g., doxycycline), chloramphenicol, macrolides (e.g., azithromycin)^{Footnote 10},^{Footnote 35}, rifampicin^{Footnote 36}, and telithromycin^{Footnote 37} are effective against O. tsutsugamushi.

Doxycycline and chloramphenicol resistance have been reported^{Footnote 25},^{Footnote 38}.

Susceptibility to disinfectants

Information specific to O. tsutsugamushi is not available. Generally, rickettsiae are susceptible to 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde, formaldehyde, and quaternary ammonium compounds^{Footnote 39}.

Physical inactivation

Moist heat (121°C for 15 min) and dry heat (170°C for 1 hour) are effective against O. tsutsugamushi^{Footnote 39}. Treatment of blood products with riboflavin and light is effective at reducing O. tsutsugamushi^{Footnote 40}.

Survival outside host

O. tsutsugamushi can survive for 7 days in blood at room temperature^{Footnote 41}, and up to 10 days in blood stored at 4°C^{Footnote 27}.

Section V: First aid/medical

Surveillance

Diagnosis is accomplished through the monitoring of clinical symptoms, patient history, and laboratory tests^{Footnote 17}. Patient serum can be tested for O. tsutsugamushi using ELISA-based tests^{Footnote 42}, indirect fluorescent antibody testing or indirect immunoperoxidase testing^{Footnote 17}. These are rapid methods that have high specificity for identification of O. tsutsugamushi antigens. PCR of DNA from eschar swabs and blood samples collected during the acute phase of the disease can also be used to diagnose O. tsutsugamushi^{Footnote 43},^{Footnote 44},^{Footnote 45}.

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 (CBH).

First aid/treatment

Doxycycline and azithromycin are commonly used to treat scrub typhus^{Footnote 10},^{Footnote 39}. Antibiotics may be given orally or parenterally depending on the severity of the illness^{Footnote 17}. Early treatment results in better patient outcomes.

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 CBH.

Immunization

No vaccine is currently available; however, vaccine development is ongoing^{Footnote 10}.

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

Prophylaxis

Antibiotics such as chloramphenicol and tetracycline protect against scrub typhus. The World Health Organisation recommends prophylactic treatment under special circumstances^{Footnote 31}.

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

Section VI: Laboratory hazard

Laboratory-acquired infections

There are 9 known documented cases of laboratory-acquired scrub typhus^{Footnote 28},^{Footnote 46}. Exposure to O. tsutsugamushi in a laboratory setting during a procedure involving cell homogenization resulted in one lab worker developing scrub typhus pneumonitis^{Footnote 28}. The worker was not wearing a protective mask^{Footnote 28}. Laboratory workers have also acquired O. tsutsugamushi infection via rat bites, and needle-stick or glassware injuries^{Footnote 28}.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Blood, biopsy specimens.

Primary hazards

Inhalation of airborne or aerosolized infectious material, bites/scratches of an infected animal, and autoinoculation with infectious material.

Special hazards

None.

Section VII: Exposure controls/personal protection

Risk group classification

O. tsutsugamushi is a Risk Group 3 human pathogen^{Footnote 47} and a Risk Group 2 animal pathogen.

Containment requirements

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

Protective clothing

Wear protective clothing to prevent mite bites when working or residing in Leptotrombidium mite habitats. The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the CBS is 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

Thorough cleaning of skin and clothing with detergent after a potential encounter with Leptotrombidium mites can reduce risk of O. tsutsugamushi infection^{Footnote 17}. Insect repellents can be used to prevent mite bites^{Footnote 17}. 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 considered with work involving animals or large scale activities.

Section VIII: Handling and storage

Spills

Allow aerosols to settle. Wearing protective clothing, 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 before clean up (CBH).

Disposal

Regulated materials, as well as all items and waste are 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 (CBH).

Storage

The applicable Containment Level 3 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone are 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 and RG4 pathogens, and SSBA toxins in long-term storage, to be maintained and to include:

1. specific identification of the regulated materials; and
2. 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 O. tsutsugamushi require a Human Pathogens and Toxins Licence issued by the Public Health Agency of Canada.

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

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Regulations

Last file update

August, 2019

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, guidelines and standards applicable to the import, transport, and use of pathogens 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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