Biosafety considerations for rickettsial pathogen research

As with all human pathogens, culture of Orientia spp or Rickettsia spp in vitro or in vivo carries the intrinsic hazard of infection of laboratory and ancillary staff (known as laboratory-acquired infections [LAIs]) via parental inoculation by accidental self-inoculation or needle-stick incident, animal bite, or inhalation of infectious aerosols generated during laboratory procedures or incidents. A recent review of scrub typhus and murine typhus LAIs by Blacksell et al (2019a) determined that scrub typhus LAIs were documented in 25 individuals, from 1931 to 2000 with 8 (32%) deaths during the preantibiotic era. There were 35 murine typhus LAI reports and no deaths. Results indicated that the highest-risk activities were working with infectious laboratory animals involving significant aerosol exposures, accidental self-inoculation, or bite-related infections.

Orientia spp or Rickettsia spp are currently classified as risk group (RG) 3 pathogens. There is conjecture however that the basis for this classification is not fully justified and consideration should be given to the risk-group reclassification of selected Rickettsia spp. using a risk-based approach. The recent study by Blacksell et al (2019b) has recommended the recommend the reclassification of Orientia spp. to RG2 based on the classification of RG2 pathogens as being moderate individual risk and low community risk. Furthermore, using a risk-based approach, we recommend that low risk activities can be performed within a BSC located in a BSL2 core laboratory (i.e., heightened containment measure laboratory) and high-risk activities, such as those involving aerosol generation or high bioburden of bacteria, would require the use of BSL3 laboratory facilities. The majority of animal activities involving Orientia spp. would still require ABSL3 containment. A risk-based biosafety approach for in vitro and in vivo culture of O. tsutsugamushi and R. typhi would require that only high-risk activities (animal work or large culture volumes) be performed in high-containment biosafety level (BSL) 3 laboratories. We argue that relatively low-risk activities including inoculation of cell cultures or the early stages of in vitro growth using low volumes/low concentrations of infectious materials can be performed safely in BSL-2 laboratories within a biological safety cabinet.

Further consultation is underway to fully determine the risks associated with research into rickettsial pathogens such that suitable and sufficient risk mitigation strategies can be implemented in low resource settings where rickettsial pathogens are prevalent.

Blacksell SD, Robinson MT, Newton PN, Ruanchaimun S, Salje J, Wangrangsimakul T, et al. Biosafety and biosecurity requirements for Orientia spp. diagnosis and research: recommendations for risk-based biocontainment, work practices and the case for reclassification to risk group 2. BMC Infect Dis. 2019;19(1):1044.

Blacksell SD, Robinson MT, Newton PN, Day NPJ. Laboratory-acquired Scrub Typhus and Murine Typhus Infections: The Argument for a Risk-based Approach to Biosafety Requirements for Orientia tsutsugamushi and Rickettsia typhi Laboratory Activities. Clin Infect Dis. 2019;68(8):1413-9.