Table 2.
Detailed pathogen biosafety evidence for Brucella melitensis
| Method | Details | Evidence (direct quote where available) | Reference | Evidence gap? (yes/no) |
|---|---|---|---|---|
| Route of inoculation | Subcutaneous/percutaneous transfer | “Direct contact through skin abrasions with infected animal tissues (as in slaughterhouse workers) is also implicated…” | 49 | No |
| “Transmission of brucellosis to humans occurs…through direct contact with infected animal parts (such as the placenta by inoculation through ruptures of skin and mucous membranes)” | 58 | |||
| “Transmission to humans occurs through opened skin exposed to animal secretions…, inoculation into the conjunctival sac…” | 57 | |||
| “Percutaneous infection through skin abrasions or by accidental inoculation has frequently been demonstrated.” | 56 | |||
| “Common routes of infection include inoculation through cuts and abrasions in the skin or via the conjunctival sac of the eyes…” | 74 | |||
| Inhalation | “…is airborne transmission. Brucella can be easily aerosolized, and when in air, can be easily transmitted through the airways and induce disease, while staying for a protracted period in this virulent form.” |
49
|
No | |
| “Transmission of brucellosis to humans occurs…through the inhalation of infected aerosolized particles” | 58 | |||
| “Transmission to humans occurs through…infected aerosols…” “Laboratorians have acquired brucellosis by inhalation.” | 57 | |||
| “Inhalation of aerosols containing the bacteria, or aerosol contamination of the conjunctivae, is another route.” | 56 | |||
| “Common routes of infection include…inhalation of infected aerosols…” | 74 | |||
| Infectious dose | Inhalation 10–100 microorganisms | “…10 to 100 aerosolized organisms are needed to cause disease…” | 57 | No |
| “…small inoculum needed to induce human disease, traditionally described in the levels of 10–100 microorganisms.” | 49 | |||
| “As few as 10–100 bacteria may cause disease when inhaled.” | 59 | |||
| Cutaneous | No evidence | Yes | ||
| Percutaneous | No evidence | Yes | ||
| Oral | No evidence | Yes | ||
| Ocular | No evidence | Yes | ||
| LAIs | Top percentile of LAIs worldwide | “Mycobacterium tuberculosis, Coxiella burnetii, hantaviruses, arboviruses, hepatitis B virus, Brucella spp., Salmonella spp., Shigella spp., hepatitis C virus, and Cryptosporidium spp. accounted for 1074 of the 1267 infections” | 46 | No |
| “4079 LAIs were caused by 159 biological agents, although ten agents caused infections accounting for 50% of cases (brucellosis, Q fever, hepatitis, typhoid fever, tularemia, tuberculosis, dermatomycoses, Venezuelan equine encephalitis, psittacosis, and coccidioidomycosis)” | 46 | |||
| “Brucellosis is one of the main causes of LAIs and between 1979 and 2015, brucellosis was reported as causing 378 LAIs” | 61 | |||
| Survey of 23 laboratories (up to Biosafety level 4) Two cases of Brucella melitensis |
“Only four of the 23 surveyed laboratories reported 15 LAIs caused by four different pathogenic organisms. Bacterial infections predominated, particularly biosafety level 3 bacteria belonging to the following species: Mycobacterium tuberculosis (ten cases), Coxiella burnetii (two cases), and Brucella melitensis (two cases)” | 75 | No | |
| 71 LAIs found from global literature review (1982–2007) | “In the 28 laboratory exposure case reports, 167 workers were potentially exposed to Brucella spp., 71 (43%) of whom developed LAB” | 45 | No | |
| LAI reports literature review (1982–2016) Asia Pacific region Three cases of Brucella spp. |
“A total of 27 LAI reports were published between 1982 and 2016…The most commonly reported pathogens causing LAIs were dengue virus (3 reports), severe acute respiratory syndrome coronavirus (SARS-CoV) (3 reports), Brucella spp. (3 reports) …” | 76 | No | |
| BSAT TLR reports in United States, 2004–2010 received by CDC Four cases B. melitensis |
“There were 11 laboratory acquired infections (LAIs) that resulted from the incidents described in the 639 release reports received between 2004–2010. These LAIs were associated with exposures to Brucella melitensis (4 cases), B. suis (2 cases), Francisella tularensis (4 cases) and Coccidioides immitis/posadasii (1 case)” | 77 | No | |
| Brucella spp. at a veterinary vaccine plant in Spain the attack rate was 39.5% for staff | “An outbreak of acute brucellosis infection was detected among the employees of a biologicals manufacturing laboratory located in Girona, Spain. A clinical and epidemiologic investigation conducted among the 164 employees found 22 patients with clinical symptoms and positive serology, and six patients detected by serology only (attack rate: 17.1 per cent). Employees working in areas with open windows above the laboratory air extracting system had an attack rate of 39.5 per cent, substantially higher than those working in other locations. When vaccine was manufactured again, an electric oven reaching 300 degrees C had been installed in the air extracting system just before its exit to the exterior. Appropriate culture medium plates were exposed to the laboratory air before and after passing through the oven.” | 62 | No | |
| Inactivation | Heat inactivation | “In our experiment, complete elimination of viable Brucella bacteria (B. abortus, B. suis, and B. melitensis) within 30 to 60 minutes required temperatures approaching boiling, whereas lower temperatures required much longer heating times (hours)” “Heat inactivation appears to be highly influenced by temperature with heating to near 100°C required for rapid killing of all bacteria within samples” |
69 | No |
| Sodium hydroxide/bleach | “Sodium hypochlorite and sodium hydroxide are preferred with dirty conditions or at low temperatures. Actually, the two disinfectants are often selected due to its lower price and low toxicity” | 68 | Yes | |
| “In general, the present results suggested that in the process of brucellosis prevention and control, sodium hydroxide is preferred for animal housing environment and field disinfection, and sodium hypochlorite is preferred for laboratory, biological material, medical supplies, and smooth surface disinfection.” | 67 | |||
| Hypochlorite solutions | “Sodium hypochlorite and sodium hydroxide are preferred with dirty conditions or at low temperatures. Actually, the two disinfectants are often selected due to its lower price and low toxicity” | 68 | Yes | |
| “…should be washed down with an approved disinfectant (hypochlorite, iodophor or phenolic disinfectant at recommended working strength)” | 48 | |||
| “In general, the present results suggested that in the process of brucellosis prevention and control, sodium hydroxide is preferred for animal housing environment and field disinfection, and sodium hypochlorite is preferred for laboratory, biological material, medical supplies, and smooth surface disinfection.” | 67 | |||
| Phenolic disinfectants | “Phenolic disinfectants were also highly effective in quickly inactivating Brucella in solutions” | 69 | Yes | |
| “…should be washed down with an approved disinfectant (hypochlorite, iodophor or phenolic disinfectant at recommended working strength)” | 48 | |||
| “it may be concluded that all these disinfectant types including aldehydes, halogens, quaternary ammonium compound, phenolics, and alkalines could be selected for disinfection to prevent brucellosis” | 67 | |||
| Nano disinfectants | “By trying of some types of Nano disinfectants to evaluate its efficacy against B. melitensis the result was as following; the effect of Dettol and Glutaraldehyde was increased when combined with silver-NPs while calcium-NPs had lower effect especially with presence of organic matters” “Nano disinfectants had good reduction rate at low temperature even with presence of organic matters specially Glutaraldehyde with silver-NPs and Dettol with silver-NPs which had the highest reduction rate” |
68 | Yes | |
| Alkaline disinfectants | “Alkaline disinfectants as…have excellent efficacy against Brucella spp. even in presence of organic matters” | 68 | Yes | |
| “…bacterial efficacy of alkaline disinfectants solution was not comparable with the average results of three commercial farm disinfectants but treatment of up to 1:20 dilution of alkaline disinfectant solution was sufficient to exert bactericidal activity” | 78 | |||
| “…it may be concluded that all these disinfectant types including aldehydes, halogens, quaternary ammonium compound, phenolics, and alkalines could be selected for disinfection to prevent brucellosis” | 67 | |||
| Iodophor/halogens/quaternary ammonium compound | “…it may be concluded that all these disinfectant types including aldehydes, halogens, quaternary ammonium compound, phenolics, and alkalines could be selected for disinfection to prevent brucellosis” | 67 | Yes | |
| “…should be washed down with an approved disinfectant (hypochlorite, iodophor, or phenolic disinfectant at recommended working strength)” | 48 | |||
| 10% Neutral formalin | “Buffered neutral formalin (10% concentration) was highly effective in inactivating Brucella bacteria by 4 hours from tissue sections that had high levels of colonization” | 69 | No | |
| Aldehydes | “it may be concluded that all these disinfectant types including aldehydes, halogens, quaternary ammonium compound, phenolics, and alkalines could be selected for disinfection to prevent brucellosis” | 67 | No | |
| Thermal | Electric oven at 300°C added to veterinary vaccine manufacturing plant exhaust | Appropriate culture medium plates were exposed to the laboratory air before, and after passing through the oven. | 62 | No |
BSAT, biological select agent and toxin; LAI, laboratory-acquired infection; SARS-CoV, severe acute respiratory syndrome coronavirus; TLR, theft, loss or release.