### Microbiology *Brucella* are gram-negative short rods. *B*. *abortus*, *B*. *canis*, *B*. *melitensis*, *B*. *suis*, *B*. *neotomae*. They can be very slow to grow, as a fellow I had one blood culture turn positive on the 42nd day of incubation. **Let the lab know you are looking for *Brucella*** in part as it is hard to grow but more importantly it is one of those organisms the lab tech can catch from the cultures.  It is the most common infection for a lab tech to catch. There is also serology for making the diagnosis. ### Epidemiologic Risks Worldwide in range, *Brucella* is found many in many animals. People acquire the infectionn from exposure to animals, often by way of milk: farmers, veterinarians, slaughterhouse workers, travel to Mexico (US cases), abattoir workers, hunters, eating unpasteurized dairy products, especially cheese. [^1] *B*. *abortus*: cattle, buffalo, and camels, often from the milk. [^2] Humans can get the vaccine strain, *Brucella* *abortus* cattle vaccine strain RB51, from drinking raw milk. [^3] There was one case case where a veterinarian got ill after a needle stick from the *Brucella* abortus RB51 Vaccine strain. [^4] *B*. *canis*: found primarily in dogs all over the world (Americas, Asia, and Africa) and occasionally passed on to humans, with dog seropositivity ranging from 6 to 35%. [^5] *B*. *canis* found in at least 30% kennel dogs, at least in Canada. [^6] *B*. *melitensis*: goats and sheep, less often camels, cattle herds in Israel, badgers in China. [^7] *B*. *suis* biovars 1-3: domestic and wild swine in the US, dogs in the US South, and cattle.[^8] *B*. *suis* biovar 4 reindeer and caribou, nearly caused the death of Santa, at least that is what I tell my kids as the reason why they did not get any Christmas presents: Santa had undulant fever. I use the same reason for why we have rabbit as our traditional Easter dinner. Hare carcasses from Argentina, which are approved for human and animal consumption, caused a *B*. *suis* infection in a dog, which was fed a raw hare, in the Netherlands. But could be a risk for humans as well. [^9] So be careful when splitting hares. Bison and elk spread *B*. *suis* to livestock [^10] as can feral pigs. Good name for a band. Feral Pigs. Thrash metal for sure. If you are hunting feral swine in the south, and kill one, the preparation of the carcass can lead to B. suis infection [^11] as can the ritual the ritual slaughter of animals. [^12] *B*. *neotomae*, found in woodrats, infected two humans in Costa Rica. [^13] *Brucella* can be spread sexually male to female, although why someone would have sex with active orchitis is beyond me ([PubMed](http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=20550455&dopt=Abstract)). [^23] ### Syndromes Brucellosis has many names, including remitting fever, undulant fever, Mediterranean fever, Maltese fever, Gibraltar fever, Crimean fever, goat fever, and Bang disease. Bang disease? > Danish veterinarian Bernhard Bang isolated a bacillus as the agent of heightened spontaneous abortion in cows, and the name "Bang's disease" was assigned to this condition. Bang considered the organism rod-shaped and classified it as a bacillus. At the time no one knew that this bacillus had anything to do with the causative agent of Malta fever.[^25] A nonspecific febrile syndrome 2 - 4 weeks after exposure. Depression is common, and the illness can be acute, subacute and local suppurative complications can occur anywhere, especially osteoarticular[^14], liver [^15], central nervous system [^16], spleen, testicles, or kidneys. Eye involvement with chronic disease not uncommon; especially uveitis. Faget's sign, aka pulse-temperature disassociation, may be a hint. > Hepatic brucelloma is chronic form of brucellosis arising up to 40 years after initial infection.[^17] There are two cases of endocarditis in IVDA with no animal exposure risks.[^18] >  Focal involvement was observed in 98 (42.6%) patients. The variables that differed significantly between groups were age (_P_ < 0.001), fever (_P_ = 0.016),  pain (_P_ < 0.001), leukocyte (P = 0.012), neutrophil (P = 0.004), platelet (P = 0.002), mean platelet volume (MPV) (P = 0.043) and erythrocyte sedimentation rate (ESR) (P = 0.001). Older age (>45 years) and back pain were found to be independent risk factors for predicting focal involvement (_P_ = 0.036 and _P_ < 0.001)[^19] ### Treatment The treatment of *Brucella* requires multiple antibiotics for a prolonged period of time, depending on the syndrome. Tetracyclines, aminoglycosides, quinolones are all used with added rifampin. CNS infections may require longer courses of therapy.[^27] For orchitis (oooooohhhhh) > doxycycline for 2 months and streptomycin for 14 to 21 days appears to be adequate and could avoid unnecessary orchiectomy." [^20] I always want to avoid unnecessary orchiectomy, although my one patient with testicular *Brucella*, a professional goat milker from Mexico, did not. Spinal osteomyelitis is associated with poor outcomes and should be treated with at least three months of therapy. [^21] ### Notes Beta-lactam antibiotics are active in vitro, don't believe it, also can't trust third-generation cephalosporins or quinolones. The best antibiotics are antibiotics that achieve good intracellular levels, where Brucella likes to live. *Brucella* DNA can be found in treated patients YEARS after therapy stops. I am not certain what to make of that, except to note > The 3 patients who experienced relapse did not exhibit any statistically significant difference in their bacterial load at any stage of disease or during follow-up.[^22] Making PCR problematic as a marker for cure. There is a case of *Brucella* reactivating 28 years after initial infection.[^24] I was involved in a case that occured years after leaving an endemic area (see below). Goats were a source of nutrition on the hoof in the days before preservation. It was a problem for the British on the Rock of Gibraltar, where it was called Rock Fever and Mediterranean Fever amount others. A 1905 report found 15% of goats were seropositive. And a *Brucella* spinal infection has been found in a 2.5 million-year-old human fossil. [^26] ### Puswhisperers [Goat Cheese](http://www.pusware.com/PW1/GoatCheese.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop77.mp3) [Ursine Questions](http://www.pusware.com/PW4/UrsineQuestions.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop569.mp3) [This Little Piggie](http://www.pusware.com/PW3/ThisLittlePiggie.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop709.mp3) [Surprise Follow Up](http://www.pusware.com/PW8/SurpriseFollowUp.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop983.mp3) ### Rationalizations [^1]:  Pereira CR, Cotrim de Almeida JVF, Cardoso de Oliveira IR, Faria de Oliveira L, Pereira LJ, Zangerônimo MG, et al. (2020) Occupational exposure to _Brucella_ spp.: A systematic review and meta-analysis. PLoS Negl Trop Dis 14(5): e0008164. https://doi.org/10.1371/journal.pntd.0008164 [^2]: Rhodes HM, Williams DN, Hansen GT. Invasive human brucellosis infection in travelers to and immigrants from the Horn of Africa related to the consumption of raw camel milk. Travel Med Infect Dis. 2016 May-Jun;14(3):255-60. doi: 10.1016/j.tmaid.2016.03.013. Epub 2016 Mar 30. PMID: 27038818. [^3]:  Cossaboom CM, Kharod GA, Salzer JS, et al. _Notes from the Field:_ _Brucella abortus_ Vaccine Strain RB51 Infection and Exposures Associated with Raw Milk Consumption — Wise County, Texas, 2017. MMWR Morb Mortal Wkly Rep 2018;67:286. DOI: [http://dx.doi.org/10.15585/mmwr.mm6709a4 ](http://dx.doi.org/10.15585/mmwr.mm6709a4) [^4]: Hatcher SM, Shih D, Holderman J, Cossaboom C, Leman R, DeBess E. Notes from the Field: Adverse Event Associated with Unintentional Exposure to the Brucella abortus RB51 Vaccine - Oregon, December 2017. MMWR Morb Mortal Wkly Rep. 2018 Jul 6;67(26):747. doi: 10.15585/mmwr.mm6726a4. PMID: 29975674; PMCID: PMC6048979. [^5]: Hensel, M. E., Negron, M., & Arenas-Gamboa, A. M. (2018). Brucellosis in Dogs and Public Health Risk. _Emerging Infectious Diseases_, _24_(8), 1401-1406. https://doi.org/10.3201/eid2408.171171. [^6]: Weese, J., Hrinivich, K., & Anderson, M. (2020). Brucella canis in Commercial Dog Breeding Kennels, Ontario, Canada. _Emerging Infectious Diseases_, _26_(12), 3079-3080. https://doi.org/10.3201/eid2612.201144. [^7]: Liu, X., Yang, M., Song, S., Liu, G., Zhao, S., Liu, G....Jiang, H. (2020). Brucella melitensis in Asian Badgers, Northwestern China. _Emerging Infectious Diseases_, _26_(4), 804-806. https://doi.org/10.3201/eid2604.190833. [^8]: Ramamoorthy S, Woldemeskel M, Ligett A, Snider R, Cobb R, Rajeev S. Brucella suis infection in dogs, Georgia, USA. Emerg Infect Dis. 2011 Dec;17(12):2386-7. doi: 10.3201/eid1712.111127. PMID: 22172146; PMCID: PMC3311166. [^9]: van Dijk MAM, Engelsma MY, Visser VXN, Spierenburg MAH, Holtslag ME, Willemsen PTJ, Wagenaar JA, Broens EM, Roest HIJ. Brucella suis Infection in Dog Fed Raw Meat, the Netherlands. Emerg Infect Dis. 2018 Jun;24(6):1127-1129. doi: 10.3201/eid2406.171887. PMID: 29774845; PMCID: PMC6004839. [^10]: Rhyan, J. C., Nol, P., Quance, C., Gertonson, A., Belfrage, J., Harris, L....Robbe-Austerman, S. (2013). Transmission of Brucellosis from Elk to Cattle and Bison, Greater Yellowstone Area, USA, 2002–2012. _Emerging Infectious Diseases_, _19_(12), 1992-1995. https://doi.org/10.3201/eid1912.130167. [^11]: Centers for Disease Control and Prevention (CDC). Brucella suis infection associated with feral swine hunting - three states, 2007-2008. MMWR Morb Mortal Wkly Rep. 2009 Jun 12;58(22):618-21. PMID: 19521334. [^12]: Fuchs I, Osyntsov L, Refaely Y, Ciobotaro P, Zimhony O. Ritual Slaughter as Overlooked Risk Factor for Brucellosis. Emerg Infect Dis. 2016 Apr;22(4):746-8. doi: 10.3201/eid2204.151192. PMID: 26981642; PMCID: PMC4806964. [^13]: Suárez-Esquivel, M., Ruiz-Villalobos, N., Jiménez-Rojas, C., Barquero-Calvo, E., Chacón-Díaz, C., Víquez-Ruiz, E....Guzmán-Verri, C. (2017). Brucella neotomae Infection in Humans, Costa Rica. _Emerging Infectious Diseases_, _23_(6), 997-1000. https://doi.org/10.3201/eid2306.162018. [^14]: Adetunji SA, Ramirez G, Foster MJ, Arenas-Gamboa AM. A systematic review and meta-analysis of the prevalence of osteoarticular brucellosis. PLoS Negl Trop Dis. 2019 Jan 18;13(1):e0007112. doi: 10.1371/journal.pntd.0007112. PMID: 30657765; PMCID: PMC6355028. [^15]: Sahinturk H, Baran B, Sisman G, Altun R. Liver involvement is associated with blood culture positivity and high agglutination titre in patients with brucellosis in Turkey. J Med Microbiol. 2018 Aug;67(8):1078-1082. doi: 10.1099/jmm.0.000791. Epub 2018 Jul 4. PMID: 29972349. [^16]: Guven T, Ugurlu K, Ergonul O, Celikbas AK, Gok SE, Comoglu S, Baykam N, Dokuzoguz B. Neurobrucellosis: clinical and diagnostic features. Clin Infect Dis. 2013 May;56(10):1407-12. doi: 10.1093/cid/cit072. Epub 2013 Feb 27. PMID: 23446629. [^17]: Amsilli, M., Epaulard, O., Brion, J., Pavese, P., Letoublon, C., Pelloux, I....Maurin, M. (2019). Hepatic Brucelloma Diagnosis and Long-Term Treatment, France. _Emerging Infectious Diseases_, _25_(5), 1021-1023. https://doi.org/10.3201/eid2505.180613. [^18]: John M Cafardi and others, _Brucella_ Endocarditis in Persons Who Inject Drugs, _Open Forum Infectious Diseases_, Volume 7, Issue 4, April 2020, ofaa063, [https://doi.org/10.1093/ofid/ofaa063](https://doi.org/10.1093/ofid/ofaa063) [^19]: Demirdal T, Sen P. Risk factors for focal involvement in brucellosis. Diagn Microbiol Infect Dis. 2020 May;97(1):115003. doi: 10.1016/j.diagmicrobio.2020.115003. Epub 2020 Jan 29. PMID: 32037038. [^20]: Colmenero JD, Muñoz-Roca NL, Bermudez P, Plata A, Villalobos A, Reguera JM. Clinical findings, diagnostic approach, and outcome of Brucella melitensis epididymo-orchitis. Diagn Microbiol Infect Dis. 2007 Apr;57(4):367-72. doi: 10.1016/j.diagmicrobio.2006.09.008. Epub 2006 Dec 1. PMID: 17141451. [^21]: Colmenero JD, Ruiz-Mesa JD, Plata A, Bermúdez P, Martín-Rico P, Queipo-Ortuño MI, Reguera JM. Clinical findings, therapeutic approach, and outcome of brucellar vertebral osteomyelitis. Clin Infect Dis. 2008 Feb 1;46(3):426-33. doi: 10.1086/525266. PMID: 18181740. [^22]: Vrioni G, Pappas G, Priavali E, Gartzonika C, Levidiotou S. An eternal microbe: Brucella DNA load persists for years after clinical cure. Clin Infect Dis. 2008 Jun 15;46(12):e131-6. doi: 10.1086/588482. PMID: 18462106. [^23]: Meltzer E, Sidi Y, Smolen G, Banai M, Bardenstein S, Schwartz E. Sexually transmitted brucellosis in humans. Clin Infect Dis. 2010 Jul 15;51(2):e12-5. doi: 10.1086/653608. PMID: 20550455. [^24]: Ögredici Ö, Erb S, Langer I, Pilo P, Kerner A, Haack HG, Cathomas G, Danuser J, Pappas G, Tarr PE. Brucellosis reactivation after 28 years. Emerg Infect Dis. 2010 Dec;16(12):2021-2. doi: 10.3201/eid1612.100678. PMID: 21122256; PMCID: PMC3294561. [^25]: https://en.wikipedia.org/wiki/Brucellosis [^26]: D'Anastasio R, Zipfel B, Moggi-Cecchi J, Stanyon R, Capasso L. Possible brucellosis in an early hominin skeleton from sterkfontein, South Africa. PLoS One. 2009 Jul 30;4(7):e6439. doi: 10.1371/journal.pone.0006439. PMID: 19649274; PMCID: PMC2713413. [^27]: Guven T, Ugurlu K, Ergonul O, Celikbas AK, Gok SE, Comoglu S, Baykam N, Dokuzoguz B. Neurobrucellosis: clinical and diagnostic features. Clin Infect Dis. 2013 May;56(10):1407-12. doi: 10.1093/cid/cit072. Epub 2013 Feb 27. PMID: 23446629.