Brucella


B abortus1
B canis1
B ceti1
B inopinata1
B melitensis1
B microti1
B neotomae1
B ovis1
B papionis1
B pinnipedialis1
B suis2
B vulpis1

Brucella is a genus of Gram-negative bacteria,34 named after David Bruce 1855–1931 They are small 05 to 07 by 06 to 15 µm, nonencapsulated, nonmotile,5 facultatively intracellular coccobacilli

Brucella is the cause of brucellosis, which is a zoonosis transmitted by ingesting contaminated food such as unpasteurized milk products, direct contact with an infected animal, or inhalation of aerosols Transmission from human to human, for example through sexual intercourse or from mother to child, is exceedingly rare, but possible6 Minimum infectious exposure is between 10 and 100 organisms

The different species of Brucella are genetically very similar, although each has a slightly different host specificity Hence, the NCBI taxonomy includes most Brucella species under B melitensis

The many names of brucellosis include human disease/animal disease:

  • Malta fever/Bang's disease
  • Undulant fever/enzootic abortion
  • Mediterranean fever/epizootic abortion
  • Rock fever of Gibraltar/slinking of calves
  • Gastric fever/ram epididymitis
  • Contagious abortion/spontaneous abortion7

Contents

  • 1 Human brucellosis
  • 2 Transmission
  • 3 Human disease
  • 4 Characteristics
  • 5 Clinical manifestations
  • 6 Diagnosis
  • 7 Treatment
  • 8 Host specificity and animal brucellosis
  • 9 The plague of Thebes
  • 10 Genomics
  • 11 Effect of blue light
  • 12 References
  • 13 External links

Human brucellosisedit

The Italian doctor and pathologist Aldo Castellani, discovered evidence of Trypanosomas in the liquor cerebrospinalis of ill patients8 Sir David Bruce isolated B melitensis from British soldiers who died from Malta fever in Malta After exposure to Brucella, humans generally have a two- to four-week latency period before exhibiting symptoms, which include acute undulating fever >90% of all cases, headache, arthralgia >50%, night sweats, fatigue, and anorexia9 Later complications may include arthritis or epididymo-orchitis, spondylitis, neurobrucellosis, liver abscess formation, and endocarditis, the latter potentially fatal10

Human brucellosis is usually not transmitted from human to human; people become infected by contact with fluids from infected animals sheep, cattle, or pigs or derived food products, such as unpasteurized milk and cheese Brucellosis is also considered an occupational disease because of a higher incidence in people working with animals slaughterhouse cases People may also be infected by inhalation of contaminated dust or aerosols, and as such, the CDC has labeled Brucella species as highly weaponizable Human and animal brucellosis share the persistence of the bacteria in tissues of the mononuclear phagocyte system, including the spleen, liver, lymph nodes, and bone marrow Brucella can also target the male reproductive tract9

Globally, an estimated 500,000 cases of brucellosis occur each year9

Malta fever was a major health problem to British troops in Malta in the 19th and early 20th centuries, resulting in over 6000 cases and 574 deaths11 In 1860, JA Maraston, assistant surgeon in the British Army in Malta, gave the first accurate description of the disease he called "Mediterranian gastric remittent fever" In 1897, AE Wright, a pathologist in British army, developed the agglutination test, diagnostic of the disease

In 1905, Zammit, a Maltese physician, identified goats as the source of infection E Bang, a Danish veterinarian, described the intracellular pathogen causing abortion in cattle in 1897, and named it Bacillus abortus In 1918, A Evans, an American microbiologist, made the connection between B abortus and Micrococcus melitensis, and placed them in the Bacteriaceae

In 1914, Mohler isolated an organism from the liver and spleen of pigs, B suis B neotome, B ovis, and B canis were described in 1957, 1963, and 1966, respectively11

Transmissionedit

Zoonosis affecting domestic animals is caused by contact with milk, urine, and genital organs, which concentrate the causative organisms Some reservoirs include buffalo and other animals, but mostly cattle12 In humans, the disease is acquired from unpasteurised milk and products or undercooked meat consumers, laboratory inhalation lab workers, accidental skin penetration or abrasion farmers, slaughterhouse workers, and veterinarians and rarely conjunctival contact, blood transfusion, transplacental, and person-to-person13

Human diseaseedit

Brucellosis can affect any organ or organ system, and 90% of patients have a cyclical undulant fever Though variable, symptoms can also include these clinical signs: headache, weakness, arthralgia, depression, weight loss, fatigue, and liver dysfunction Foul-smelling perspiration is considered a classical sign Between 20 and 60% of cases have osteoarticular complications - arthritis, spondylitis, or osteomyelitis Hepatomegaly may occur, as can gastrointestinal complications

Up to 20% of cases can have genitourinary involvement; orchitis and epididymitis are most common Neurological symptoms include depression and mental fatigue Cardiovascular involvement can include endocarditis resulting in death

Chronic brucellosis is hard to define; length, type, and response to treatment are variable Localized infection can occur Blood donations of infected persons should not be accepted

Congenitally infected infants can exhibit low birth weight, failure to thrive, jaundice, hepatomegaly, splenomegaly, respiratory difficulty, and general signs of sepsis fever, vomiting Some cases are asymptomatic14

Characteristicsedit

Brucella species are small, Gram-negative, facultative coccobacilli, most lacking a capsule, endospores, or native plasmids They are intracellular within the host organism, and show environmental persistence outside the host They survive extremes in temperature, pH, and humidity, and in frozen and aborted materials They infect many species, but with some specificity2

Clinical manifestationsedit

The gastrointestinal tract is affected in about 70% of cases, including: anorexia, abdominal pain, vomiting, diarrhea, constipation, hepatomegaly, and splenomegaly The liver is involved in most cases, but function tests are normal or mildly abnormal Granulomas B abortus, hepatitis B melitensis and abscesses B suisare seen

The skeletal system is affected in 20–60% of cases, including: arthritis hip, knee, and ankle, spondylitis, osteomyelitis, and sacroiliitis most common Lumbar vertebrae can be affected showing the classical radiological sign of vertebral erosion Neurological symptoms include meningitis, encephalitis, radiculopathy, and peripheral neuropathy, intracerebral abscesses, and acute or chronic neck rigidity <50%, and the cerebrospinal fluid can show lymphocytic pleocytosis, low sugar, increased protein, positive bacterial culture <50%, and agglutination positive in >95%

Cardiovascular involvement is low endocarditis at 2%, but is the major cause of mortality Often, valve replacement and antibiotics are needed Pericarditis and myocarditis are seen, too

Pulmonary infection can be from inhalation or hematogenous sources, and can cause any chest syndrome Rarely is Brucella isolated from sputum Genitourinary infection can include epidydemoorchitis or pyonephrosis rare Cutaneous involvement is not specific Hematological signs include anemia, leukopenia, and thrombocytopenia15

Diagnosisedit

1416 Brucella is isolated from a blood culture on Castaneda medium or from bone marrow Prolonged incubation up to six weeks may be required, as they are slow-growing, but on modern automated machines, the cultures often show positive results within seven days On Gram stain, they appear as dense clumps of Gram-negative coccobacilli and are exceedingly difficult to see In recent years, molecular diagnostic techniques based on the genetic component of the pathogen have become more popular4

Differentiating Brucella from Salmonella is crucial, the latter could also be isolated from blood cultures and is Gram-negative Testing for urease would successfully accomplish the task; it is positive for Brucella and negative for Salmonella Brucella can also be seen in bone marrow biopsies

Laboratory-acquired brucellosis is common17 This most often happens when the disease is not thought of until cultures become positive, by which time the specimens have already been handled by a number of laboratory staff The idea of preventive treatment is to stop people who have been exposed to Brucella from becoming ill with the disease Polymerase chain reaction PCR shows promise for rapid diagnosis of Brucella species in human blood specimens Positive PCR at the completion of treatment is not predictive of subsequent relapse PCR testing for fluid and tissue samples other than blood has also been described A history of animal contact is pivotal; in endemic area, it should be in the diagnosis of any nonspecific febrile illness

In the laboratory, biochemical tests can be diagnostic15 Oxidase and catalase tests are positive for most members of the genus Brucella

Test B melitensis B abortus B suis B neotomae B ovis B canis
Need to CO2 - + - - + -
production of H2S - + + + - -
Growth on basic fushin 0002% + + - - + -
Growth on thionin 0004% - - + - + +
Growth on thionin 0002% + - + + + +
Destroy withTb phage - + - - - -

Serum agglutination with a titer > 1:160 in the presence of a compatible illness supports the diagnosis of brucellosis Demonstration of a four-fold or greater increase or decrease in agglutinating antibodies over four to 12 weeks provides even stronger evidence for the diagnosis

ELISA is probably the second-most common serologic method18 The sensitivity of the ELISA was 100% when compared with blood culture, but only 44% compared with serologic tests other than ELISA The specificity was >99% In a study including 75 patients with brucellosis, five patients with positive ELISA had a negative tube agglutination test

In the setting of Brucella arthritis, the synovial-fluid white blood cell count does not generally exceed 15,000 cells/μl18 In brucellosis, lymphocytes frequently predominate in contrast to septic arthritis due to other bacteria, in which polymorphonuclear leukocytes frequently predominate

The prognosis19 for brucellosis before the use of antibiotics had a mortality of 2%, mainly due to endocarditis, and morbidity was high, especially with B melitensis Permanent nerve deafness and spinal cord damage often occurred

Prevention18 now includes:

  • Control of disease in domestic animals by immunization using B abortus strain 19 and B melitensis strain Rev 1: Vaccination in young cattle helps in protection, but does not offer full effectiveness
  • Routine pasteurization of milk
  • In labs, strict biosafety precautions

Treatmentedit

No clinical trials exist to be relied on as a guide for optimal treatment, but an at least six-week course of rifampicin or gentamicin and doxycycline twice daily is the combination most often used, and appears to be efficacious;17202122 the advantage of this regimen is that it is oral medication with no injections; however, a high rate of side effects nausea, vomiting, loss of appetite has also been reported22

As of August 2013, Allison Rice-Ficht, PhD at Texas A&M University and her team claim to be close to creating a human vaccine It would primarily be used to immunize members of the military in case of exposure to weaponized Brucella on the battlefield23

Host specificity and animal brucellosisedit

Brucella species have been found primarily in mammals:9

Species Host
B melitensis goats and sheep
B abortus cattle
B canis dogs
B suis pigs
B ovis sheep
B neotomae desert woodrat Neotoma lepida
B pinnipedialis seal
B ceti dolphin, porpoise, whale
B microti common vole Microtus arvalis
B inopinata unknown
Brucella sp NVSL 07-0026 baboon

Pathogenic Brucella species can cause abortion in female animals by colonization of placental trophoblasts, and sterility in male animals24 Drugs with effects against Brucella include tetracyclines, aminoglycosides streptomycin, since 1947, gentamicin, netilmicin, rifampicin, quinolones ciprofloxacin and third-generation cephalosporins Treatment for uncomplicated brucellosis includes:

  • Streptomycin + doxycycline for 6 weeks
  • TMP/SMX + doxycycline for 6 weeks

Rifampicin + doxycycline for 6 weeks

Treatment of complicated brucellosis endocarditis, meningitis has no uniform agreement, but usually uses three anti-Brucella drugs for three months

The plague of Thebesedit

Brucellosis caused by B abortus best fits the characteristics of the plague described in Oedipus Rex Although the disease progression of brucellosis in modern times may make it seem unlikely, it was at least one agent in what may have been a multicomponent plague, along with Salmonella enterica serovar Typhi or another pathogen, or that the ancestral versions of Brucella may have been more lethal25

Genomicsedit

The Brucella genome includes two chromosomes; the first chromosome codes mostly for genes related to metabolism, meanwhile the second smaller one includes several genes related to pathogenicity The genomes of most Brucella species have been sequenced,26 and typically encode 3,200 to 3,500 open reading frames ORFs Examples include:

  1. Brucella abortus A13334, 3,401 ORFs
  2. Brucella canis ATCC 23365, 3,408 ORFs
  3. Brucella melitensis 16M, 3,279 ORFs
  4. Brucella microti CCM 4915, 3,346 ORFs
  5. Brucella ovis ATCC 25840, 3,193 ORFs
  6. Brucella pinnipedialis B2/94, 3,505 ORFs
  7. Brucella suis 1330, 3,408 ORFs

Genome data for these and other Brucella strains are available in the GOLD26 and PATRIC27 databases Also, a public and editable spreadsheet of B abortus 2308W genome annotation has been created, in order to be updated based on new discoveries

Bacterial small RNAs sRNA are an important class of regulatory molecules Many Brucella sRNAs have been identified

Effect of blue lightedit

Infection of macrophages by B abortus is stimulated by blue light in the wild type, but is limited in photochemically inactive and null mutants, indicating a flavin-containing histidine kinase functions as a photoreceptor regulating B abortus virulence Conversely, depriving Brucella of the blue wavelengths dropped its reproductive rate by 90%2829

Referencesedit

  1. ^ a b c d e f g h i j k Parte, AC "Brucella" wwwbacterionet 
  2. ^ a b MulemeM , MugabiR ," BRUCELLOSIS OUTBREAK INVESTIGATIONS"Sakran et al, 2006
  3. ^ Ryan KJ, Ray CG, eds 2004 Sherris Medical Microbiology 4th ed McGraw Hill ISBN 0-8385-8529-9 
  4. ^ a b Lopez-Goni, I 2012 O'Callaghan, D, ed Brucella: Molecular Microbiology and Genomics Caister Academic Press ISBN 978-1-904455-93-6 
  5. ^ Ferooz J, Letesson JJ 2010 "Morphological analysis of the sheathed flagellum of Brucella melitensis" BMC Res Notes 3 333 PMC 3017070  PMID 21143933 doi:101186/1756-0500-3-333 
  6. ^ "Diagnosis Management of Acute Brucellosis in Primary Care" PDF Brucella Subgroup of the Northern Ireland Regional Zoonoses Group August 2004 Archived from the original PDF on 2007-10-13 
  7. ^ XavierMN, PaixãoTA,"Pathogenesis of Brucella spp" The Open Veterinary Science Journal, 2010, 4, 109–118
  8. ^ Bruce, D 2011 "discoverer of brucellosis" Singapore Med J 52 3: 138 
  9. ^ a b c d Atluri, V L; Xavier, M N; De Jong, M F; Den Hartigh, A B; Tsolis, R E M 2011 "Interactions of the Human PathogenicBrucellaSpecies with Their Hosts" Annual Review of Microbiology 65: 523–541 PMID 21939378 doi:101146/annurev-micro-090110-102905 
  10. ^ Gorvel, J P 2008 "Brucella: A Mr "Hide" converted into Dr Jekyll" Microbes and Infection 10 9: 1010–1013 PMID 18664389 doi:101016/jmicinf200807007 
  11. ^ a b ArizaJ , BosilkovskiM , "Perspectives for the Treatment of Brucellosis in the 21st Century:The Ioannina Recommendations",2007, PLoS Medicine, Volume 4 ,Issue 12 , 317
  12. ^ http://wwwcdcgov/brucellosis/clinicians/brucella-specieshtml
  13. ^ Ertem M, Kurekci AE," Brucella Species",2009, APPENDIX 2,Volume 49
  14. ^ a b Poester 2010 "Diagnosis of Brucellosis" The Open Veterinary Science Journal 4: 46–60 doi:102174/1874318801004010046 
  15. ^ a b HoferE,"Microbiological diagnosis of Brucella spp and Austrian epidemiology of brucellosis B suis biovar 2 ",2009, Institute for Veterinary Disease Control, Mödling
  16. ^ Gopaulk 2008 "Rapid identification of Brucella isolates to the species level by real time PCR-based single nucleotide polymorphism SNP analysis" BMC Microbiology 8: 86 doi:101186/1471-2180-8-86 
  17. ^ a b Robichaud S, Libman M, Behr M, Rubin E 2004 "Prevention of laboratory-acquired brucellosis" Clin Infect Dis 38 12: e119–22 PMID 15227634 doi:101086/421024 
  18. ^ a b c CorbelMJ," Brucellosis in humans and animals",2006, WHO/CDS/EPR, ISBN 92-4-154713-8
  19. ^ Blasco JM," CONTROL AND ERADICATION STRATEGIES FOR BRUCELLA MELITENSIS INFECTION IN SHEEP AND GOATS",2010, Contributions, Sec Biol Med Sci, 145–165
  20. ^ E Torok et al Oxford Handbook Infect Dis and Microbiology, 2009
  21. ^ Gilbert DN et al The Sanford guide to antimicrobial therapy 2013
  22. ^ a b Maley MW, Kociuba K, Chan RC 2006 "Prevention of laboratory-acquired brucellosis: significant side effects of prophylaxis" Clin Infect Dis 42 3: 433–4 PMID 16392095 doi:101086/499112 
  23. ^ Williamson, Blair "Victory in the Battle against Brucella: From bench to battlefield" Vital Record: News from Texas A&M HSC 
  24. ^ Corbel, MJ 1997 "Brucellosis: an overview" Emerg Infect Dis 3: 213–221 doi:103201/eid0302970219 
  25. ^ Kousoulis, AA; Economopoulos, KP; Poulakou-Rebelakou, E; Androutsos, G; Tsiodras, S 2012 "The plague of Thebes, a historical epidemic in Sophocles' Oedipus Rex" Emerging Infectious Diseases 18: 153–157 doi:103201/eid1801AD1801 
  26. ^ a b "GOLD Database" Retrieved 1 October 2012 
  27. ^ "Brucella genomes in PATRIC" PATRIC Retrieved 22 October 2012 
  28. ^ "Deadly in the Daylight" August 23, 2007 in ScienceNOW Daily News Accessed September 8, 2007
  29. ^ "Blue-Light-Activated Histidine Kinases: Two-Component Sensors in Bacteria" Science 317 5841: 1090–1093 doi:101126/science1144306 

External linksedit

  • Brucella genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID
  • Brucella Genome Projects from Genomes OnLine Database
  • Comparative Analysis of Brucella Genomes at DOE's IMG system
  • Brucella Bioinformatics Portal
  • Brucellosis subject guide of the University of Navarra


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