Cross Infections Among Brucella Infected Guinea Pigs

Phillips, Gerald B.; Broadwater, Grover C.; Reitman, Morton; Alg, Robert L.

doi:10.1093/infdis/99.1.56

Cited by 13 publications

(8 citation statements)

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“…During the housing of infected animals, airborne cross infection may affect the validity of the experiment (8). For instance, studies in our laboratories have shown that, during a test, cross infection of animals may be important in brucellosis (26) but, in the absence of aerosol challenge, is of no significance in vaccinia or Japanese B encephalitis. This permits caging requirements to be tailored to circumstances.…”

Section: Microbiological Techniquementioning

confidence: 99%

Control of Laboratory Airborne Infection

Wedum¹

1961

Bacteriological Reviews

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The control of laboratory airborne infection depends more on administrative and human factors than on the development of new procedures and equipment. The major problem is one of communication and conviction. Much more is known about control of potential airborne infection than is applied. ADMINISTRATION In microbiological units, safety against laboratory-acquired infection is not practiced fully because of lack of agreement on the danger by the administrators and lack of awareness by the

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Section: Microbiological Techniquementioning

confidence: 99%

Control of Laboratory Airborne Infection

Wedum¹

1961

Bacteriological Reviews

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“…The dose titration study indicated a dose of at least 10 6 CFU was required to induce temperature elevations although systemic infection developed in the majority of the guinea pigs inoculated with 10 3 CFU. Previous aerosol studies in guinea pigs delivered a dose of between 4.5×10 3 /ml to 5.0×10 5 /ml, which generated an estimated dose range of 48-2800 CFU [13, 16, 17, 27]. The majority of the early aerosol studies utilized the Henderson apparatus for generating aerosols, which is a mask that fits over the head and neck of the guinea pig to create a small aerosol chamber [13, 16, 17, 28].…”

Section: Discussionmentioning

confidence: 99%

Characterization of a novel intratracheal aerosol challenge model of Brucella melitensis in guinea pigs

Hensel

García-González

Chaki

et al. 2018

Preprint

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B. melitensis is considered the most virulent of the Brucella species, and a need exists for an improved laboratory animal model of infection that mimics natural transmission and disease. Guinea pigs are highly susceptible to infection with Brucella spp. and develop a disease syndrome that mimics natural disease after aerosol inoculation. Intratracheal inoculation is a targeted means of generating aerosols that offer advantages over aerosol chamber delivery. To establish this delivery method, female, Hartley guinea pigs were infected via intratracheal inoculation with PBS or 16M B. melitensis at low dose (101 to 103) or high dose (106 to 108) and monitored for 30 days for signs of disease. Guinea pigs in the high dose groups developed fever between 12-17 days post-inoculation. Bacteria were recovered from the spleen, liver, lymph nodes, lung, and uterus at 30-days post-inoculation and demonstrated dose dependent mean increases in colonization and pathologic changes consistent with human brucellosis. To study the kinetics of extrapulmonary dissemination, guinea pigs were inoculated with 107 CFU and euthanized at 2-hours post inoculation and at weekly intervals for 3 weeks. 5.8×105 to 4.2×106 CFU were recovered from the lung 2 hours post-inoculation indicating intratracheal inoculation is an efficient means of infecting guinea pigs. Starting at 1-week post inoculation bacteria were recovered from the aforementioned organs with time dependent mean increases in colonization. This data demonstrates that guinea pigs develop a disease syndrome that models the human manifestation of brucellosis, which makes the guinea pig a valuable model for pathogenesis studies.Author summaryBrucellosis is caused by a gram-negative, intracellular bacterial pathogen with a worldwide distribution and affects up to half a million people per year. It is a neglected zoonosis that impacts not only animal welfare, but also exert economic pressure on afflicted individuals through loss of wages and decreased productivity. In people, recurrent fever, malaise, and anorexia accompanied by enlargement of the spleen and lymph nodes are common clinical symptoms of infection. The mouse model has been used extensively to study the pathogenesis of brucellosis, but there are drawbacks to extrapolating studies in mice to develop vaccines or therapeutics for people. Mice are frequently inoculated via intraperitoneal injection, which is an artificial means of producing disease that does not mimic natural transmission or disease features, such as fever. An animal model is needed that can be infected through natural transmission routes and subsequently develop a syndrome that matches clinical disease seen in people in order to study the pathogenesis of disease and to develop vaccines and therapeutics. The guinea pig offers an improvement on the mouse model because it can be infected via aerosol inoculation and develops fever, a humoral immune response, systemic colonization, and macroscopic and microscopic lesions of disease. As such, guinea pigs could be used a more biologically relevant model for evaluation of host-pathogen interactions.

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“…For example, atmospheric sampling studies performed at Fort Detrick demonstrated that significant aerosolization of organisms occurred from performing routine laboratory procedures such as removing lids or stoppers (e.g., from Waring Blenders or a shaken culture), flaming inoculation needles, pipetting fluids, lyophilization, animal inoculation, egg inoculation and harvesting, and disturbing contaminated animal cage litter. 1,3,4,9,11,[14][15][16][17][22][23][24] Consequently, a number of other interventions may have resulted in decreases in exposures and infections, including the discontinuation of mouth pipetting, stricter requirements for wearing longsleeve operating gowns, use of nonbreakable plastic Petri dishes, and use of Luer-Lok syringes (to prevent exposures resulting from the separation of the syringe and needle). 4,11,23 Occupational illnesses occurring in biodefense research today are expected to be less frequent than observed in the offensive biological warfare program for several reasons.…”

Section: Figure 5 Vee Cases Diagnosed At Fort Detrick From 1943 To 1mentioning

confidence: 99%

Risk of Occupationally Acquired Illnesses from Biological Threat Agents in Unvaccinated Laboratory Workers

Rusnak

Kortepeter

Hawley

et al. 2004

Biosecurity and Bioterrorism: Biodefense Strategy, Practice, an

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Many vaccines for bioterrorism agents are investigational and therefore not available (outside of research protocol use) to all at-risk laboratory workers who have begun working with these agents as a result of increased interest in biodefense research. Illness surveillance data archived from the U.S. offensive biological warfare program (from 1943 to 1969) were reviewed to assess the impact of safety measures on disease prevention (including biosafety cabinets [BSCs]) before and after vaccine availability. Most laboratory-acquired infections from agents with higher infective doses (e.g., anthrax, glanders, and plague) were prevented with personal protective measures and safety training alone. Safety measures (including BSCs) without vaccination failed to sufficiently prevent illness from agents with lower infective doses in this high-risk research setting. Infections continued with tularemia (average 15/year), Venezuelan equine encephalitis (1.9/year), and Q fever (3.4/year) but decreased dramatically once vaccinations became available (average of 1, 0.6, and 0 infections per year, respectively). While laboratory-acquired infections are not expected to occur frequently in the current lower-risk biodefense research setting because of further improvements in biosafety equipment and changes in biosafety policies, the data help to define the inherent risks of working with the specific agents of bioterrorism. The data support the idea that research with these agents should be restricted to laboratories with experience in handling highly hazardous agents and where appropriate safety training and precautions can be implemented.

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Cross Infections Among Brucella Infected Guinea Pigs

Cited by 13 publications

References 0 publications

Control of Laboratory Airborne Infection

Control of Laboratory Airborne Infection

Characterization of a novel intratracheal aerosol challenge model of Brucella melitensis in guinea pigs

Risk of Occupationally Acquired Illnesses from Biological Threat Agents in Unvaccinated Laboratory Workers

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