Discussion
Brucellosis is the most common bacterial laboratory-acquired infection worldwide, owing in part to the low infectious dose and high attack rate following a laboratory exposure (Blaney, Bosserman, Bui, Guerra, & Stoddard, 2009). It is also easily aerosolized and has the potential to cause acute and chronic illness (D L Sewell, 1995). Humans are usually infected by occupational exposure to infected animals, the consumption of unpasteurized dairy products from infected animals, or inhalation of infectious aerosols. Clinical laboratory workers have failed to recognize suspicious isolates and have manipulated unknown isolates on open benches, using procedures that could aerosolize brucellae, increasing their exposure risk to biology hazards (Ackelsberg et al., 2020). In the present study, eight laboratory-acquired infection events were found in the southern region, a brucellosis emerging area (Beijing city). Another event was observed in Ningxia province, which is historically an area of brucellosis. In the past, more than 90% of human brucellosis cases in China appeared in the northern animal husbandry provinces (Shang, Xiao, & Yin, 2002). However, since 2010, human brucellosis has occurred or reappeared in all provinces in southern China (Yang et al., 2020). Southern China is an emerging area of brucellosis with the lowest incidence of brucellosis, but the incidence is increasing (Yang et al., 2020). In the southern regions, clinical microbiology laboratories are frequently unfamiliar with the genus of Brucella, and there is a low index of suspicion by physicians or failure to notify the laboratory that the handled specimens might yield a hazardous organism. Typically, clinicians do not consider brucellosis until notified that bacteremia with Brucella was suspected. Moreover, the misidentification of the organism by commercial systems, unsafe laboratory practices, and laboratory accidents have been responsible for many cases of exposure to the organism and laboratory-acquired disease in recent years (Yagupsky & Baron, 2005). In the United States, fewer than 150 cases of brucellosis have been reported annually since 1986, but brucellosis is among the most commonly reported laboratory-acquired bacterial infections (Pike, 1976). In Indiana and Minnesota, two cases of brucellosis in microbiologists at two clinical laboratories were reported to state health departments in 2006. The results of that investigation showed that Brucella spp. pose a risk of aerosol-transmitted infection (”Laboratory-acquired brucellosis–Indiana and Minnesota, 2006,” 2008). Unknown isolates manipulated and/or tested on open benches was the main risk factor in the laboratory-acquired infection of brucellosis. In this study, the problematic current practices when handling blood culture bottles from patients with fever of unknown origin were the main reason for these infectious events, and the transmission in our cases was probably due to aerosol contamination. Similarly, most critical exposures involved catalase testing or isolate vortexing, both of which may generate infectious aerosols (Stephanie et al., 2004). In New York City, during the 2015–2017 period, over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including procedures that could generate infectious aerosols (Ackelsberg et al., 2020). In Turkey, where biosafety cabinets do not exist in most hospital laboratories, many laboratory-acquired Brucella infection events have been reported (Sayin-Kutlu et al., 2012). In our study, we observed a high risk of developing laboratory-acquired brucellosis in microbiological laboratory workers. In Spain, a total of 75 works have suffered from laboratory-acquired brucellosis, 57% (43/75) of whom were microbiologists (Bouza, Sánchez-Carrillo, Hernangómez, & González, 2005). Thus, Brucella spp. have persisted as biological hazards to clinical laboratory workers manipulating unknown clinical isolates. This suggests that we should improve the ability of clinicians to diagnose brucellosis, especially in the southern region. Furthermore, it is essential to promote the use of biosafety level 3 (BSL-3) facilities when handling specimens from patients suspected of brucellosis infections and also unidentified isolates. Moreover, the following practices should be followed: timely exposure risk identification, information sharing, postexposure prophylaxis (PEP), and appropriate follow-up of potentially exposed workers, in combination with worker training to maximize awareness and observance of proper safety practices. Definitions for the laboratory exposure risk toBrucella spp. and recommendations for PEP have been developed and applied to the laboratory-acquired brucellosis cases that occurred in Indiana and Minnesota (Pien, Saah, Miller, & Woods, 2006). Finally, we consider that the use of gloves, masks, goggles, and a biosafety cabinet, and also the continuous strengthening of the education on biosafety of individuals with high infection risk is significant for preventive laboratory-acquired brucellosis events.
The B. suis strain S2 is a widely used live vaccine in China, which was isolated from a swine fetus at the Institute of Inspection for Veterinary Medicine in 1952 (H. Jiang et al., 2018). A study suggested that the S2 vaccine is of low virulence, stimulates good humoral and cellular immunity, and protect animals against infection by heterologous, virulent Brucella species (Zhu et al., 2016). In the present study, more than 50 individuals infected in the context of S2 vaccination had clinical manifestations, and 180 persons had no clinical symptoms. Another study confirmed that the S2 vaccine had low residual virulence, and the immunity against the B. melitensis strain induced by S2 had declined after 150 days more than those of S19 and Rev.1 (Bosseray & Plommet, 1990). The low residual virulence of S2 may be the main reason why the patients had no obvious clinical symptoms. Similarly, a B. abortus S19 vaccine strain was isolated from four persons; all four infected individuals were employed as milkers and did not have apparent manifestations of the disease (Osman, Hassan, Ali, Abdoel, & Smits, 2015). Moreover, human illness associated with the vaccine strain RB51 has been documented from inadvertent needle sticks or inoculation of the conjunctiva or open wounds with RB51 (Ashford et al., 2004; Cossaboom et al., 2018; Hatcher et al., 2018). The first case of human brucellosis in Bosnia and Herzegovina was caused by live attenuated Brucella melitensis Rev.1 strain (Arapovic et al., 2020). Although the vaccine strain may be transmitted to the human population and may persist in the blood sometimes without causing overt disease, protective measures remain important to prevent exposure from vaccine strains. Moreover, more than 100 grassroots animal epidemic prevention officers from Ulanqab of Inner Mongolia were diagnosed as having brucellosis from short-time period, but the conventional serological tests used did not allow to distinguish between vaccine-associated infection and infections by contact with infected animals.