### 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 infection 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 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 in reindeer and caribou, nearly causing 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 it 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 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. [^23] ### Syndromes *[[Brucella]]* 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 is not uncommon; especially [[Uveitis]]. [[Faget's Sign]], aka pulse-temperature disassociation, may be a hint. > Hepatic brucelloma is chronic form of *[[Brucella]]* 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, and 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 occurred 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) [Word History](http://www.pusware.com/PW1/WordHistory.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop.173.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 *[[Brucella]]* 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). *[[Brucella]]* 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 *[[Brucella]]* 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 *[[Brucella]]*. 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 *[[Brucella]]*. 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 *[[Brucella]]* 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 *[[Brucella]]*. 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 *[[Brucella]]* 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. *[[Brucella]]* 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/*[[Brucella]]* [^26]: D'Anastasio R, Zipfel B, Moggi-Cecchi J, Stanyon R, Capasso L. Possible *[[Brucella]]* 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.