Brucella melitensis

De kiem

Brucellose bij kleine herkauwers wordt voornamelijk veroorzaakt door Brucella melitensis, een klein Gram­-negatief staafje. Bij B. melitensis zijn drie stammen van belang, namelijk de biovars 1, 2 en 3. Alle drie veroorzaken ze ziekte bij kleine herkauwers, maar ze verschillen in geografische verspreiding. Zo komt biovar 3 het meest voor in landen rond de Middellandse Zee en het Midden-­Oosten, terwijl biovar 1 meer in Midden-­Amerika voorkomt. Kleine herkauwers kunnen ook geïnfecteerd raken met B. abortus en B. suis, maar ze zullen dan maar in zeldzame gevallen klinische verschijnselen vertonen.

Gevoelige diersoorten

Volksgezondheid

Overleving

Klinische verschijnselen

Morbiditeit/mortaliteit

Uitscheiding van de kiem

Mensen raken veelal besmet na direct contact met de bacterie via de slijmvliezen, beschadigde huid of via opname van de bacterie door het eten of drinken van besmette melk en/of besmette melkproducten. De ziekte wordt ook wel een beroepsziekte genoemd, omdat veehouders, dierenartsen, handelaren, slachthuispersoneel en andere personen die veel in aanraking komen met kleine herkauwers een verhoogd risico lopen. Ook laboratoriumpersoneel dat werkt met de bacterie kan gemakkelijk besmet raken. De transmissie van B. melitensis bij kleine herkauwers gaat meestal via contact met placentamateriaal, de foetus en vaginale uitscheiding van besmette dieren. Uitscheiding van besmettelijk materiaal kan via vaginale uitvloeiing bij schapen weken en bij geiten tot maanden doorgaan. Uitscheiding via de melk kan bij geiten levenslang doorgaan. De meeste dieren raken besmet door orale opname of via slijmvliezen van de oropharynx, de voorste luchtwegen of de conjunctivae, maar besmetting via beschadigde huid is ook mogelijk. Daarnaast kunnen in utero­infecties en dekinfecties optreden.

• Chlamydia abortus
• Coxiella burnetii
• Toxoplasma gondii
• Listeria spp.
• Campylobacter spp.
• Salmonella spp.
• Yersinia pseudotuberculosis
• Border disease virus (BDV)
• Leptospira spp.
• Rift Valley fever/Akabane virus/Cache Valley virus (niet in Nederland)
• Bluetongue virus (BTV)
• Brucella melitensis
• Trueperella pyogenes
• Arcanobacterium pluranimalium
• Overige bacteriën en virussen die bacteriaemie of viraemie kunnen veroorzaken

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Diagnose van Brucella melitensis

Monitoring

Nederland is officieel vrij van Brucella melitensis sinds het begin van de jaren negentig van de vorige eeuw: op basis van het feit dat nooit een infectie met Brucella melitensis is bevestigd, vaccinatie niet was toegestaan en een serologische screening geen positieve bevindingen opleverde, heeft Nederland de vrije status gekregen. Dit is om meerdere redenen gunstig: schapen- en geitenhouders en andere personen die in contact komen met kleine herkauwers en producten van kleine herkauwers lopen geen risico om Maltakoorts of Middellandsezeekoorts op te lopen en de kosten van dierbeweging binnen de EU zijn beperkt omdat geen nader onderzoek op brucellose hoeft plaats te vinden bij dieren die aan het intraverkeer deelnemen. Hetzelfde geldt bij export van dierlijke producten. Jaarlijks vindt, op basis van een Europese richtlijn, monitoring plaats om deze vrije status te behouden. Deze richtlijn schrijft voor dat jaarlijks ten minste 1.475 bedrijven in Nederland moeten worden onderzocht. GD voert deze monitoring uit en krijgt daartoe een bestand aangeleverd van de Rijksdienst voor Ondernemend Nederland (RVO) die elk jaar een willekeurige selectie maakt uit de bedrijven met kleine herkauwers die staan geregistreerd in de centrale I&R-database van het ministerie van LNV. GD benadert deze houders en hun praktiserend dierenarts om per bedrijf van maximaal dertien dieren van zes maanden en ouder bloedmonsters in te sturen voor onderzoek. Deze bloedmonsters werden tot eind 2012 onderzocht middels een ELISA en CBR. Sinds 1 januari 2013 wordt de Rose Bengaltest weer gebruikt.

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Prevalentie van Brucella melitensis

Historie en beschikbare beschrijvingen uitbraken

Europa

Antibiotica

Maatregelen bij ernstige verdenking en bij besmetting

Preventie van Brucella melitensis

In Nederland worden jaarlijks ongeveer 15.000 kleine herkauwers serologisch onderzocht op B. melitensis: zie Monitoring onder Diagnostiek Brucella melitensis.
In een koppel schapen of geiten waar een abortusstorm plaatsvindt, is het belangrijk om zeer zorgvuldig met de algemene hygiënemaatregelen om te gaan. Daarnaast moeten placenta’s, vruchtwater-­ en vruchtvliezen en geaborteerde vruchten zorgvuldig worden afgevoerd. Bezoekers mogen niet meer bij mogelijk geïnfecteerde dieren in de buurt komen. Consumptie van ongepasteuriseerde melk en melkproducten is niet zonder risico en moet worden vermeden. Bij de omgang met besmette dieren moeten handschoenen, masker en bescherming voor de ogen worden gedragen.
Abortus bij kleine herkauwers is meldingsplichtig.

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Regelgeving

Regelgeving en wettelijke basis voor de brucellabewaking en -bestrijding ligt in:

Europees recht:

• Richtlijn 64/432/EEG: 
  • (gewijzigd door RL 97/12/EG en RL 98/46/EG
  • Bijlage AII: officieel brucellosevrij-bepalingen
  • Bijlage C: brucellose-laboratoriumbepalingen
    
     
• Richtlijn 88/407/EEG, bijlage B, Hoofdstuk II, punt 1: jaarlijkse controle spermawincentra
• Richtlijn B 1999/466/EG: officieel brucellosevrij-erkenning; Nederland is hierin opgenomen per 01.08.1999.

Internationaal:

• OIE Terrestrial Animal Code article 1.1.3.: van Brucella melitensis dient binnen 24 uur per telegram, fax of e-mail aangifte gedaan te worden bij de OIE.

Nederlands recht:

• Gezondheids- en welzijnswet voor dieren (GWWD):
  • Artikel 19, lid 1. Indien een dier verschijnselen van een besmettelijke dierziekte vertoont, geeft de houder hiervan terstond kennis aan de burgemeester van de gemeente waar het dier zich bevindt.
  • Artikel 19, lid 2. De burgemeester stelt een door Onze Minister aangewezen ambtenaar alsmede, voorzover de dierziekte is aangewezen in overeenstemming met Onze Minister van Welzijn, Volksgezondheid en Cultuur, een door Onze Minister van Welzijn, Volksgezondheid en Cultuur aangewezen ambtenaar, onmiddellijk op de hoogte indien zich in zijn gemeente een geval voordoet, als bedoeld in het eerste lid.
  • Artikel 100. De dierenartsen zijn verplicht van alle door hen opgemerkte gevallen van dierziekten waarop afdeling 3 van Hoofdstuk II van toepassing is, alsmede van gevallen van andere door Onze Minister aangewezen dierziekten onverwijld kennis te geven aan een door Onze Minister aangewezen ambtenaar en aan de burgemeester van de gemeente waar het dier zicht bevindt.
  • Regeling aanwijzing besmettelijke dierziekten artikel 2, onderdeel n.
  • Regeling aanwijzing besmettelijke dierziekten artikel 10, onderdeel b: kennisgeving van abortus;
  • Besluit verdachte dieren artikel 3, onderdeel f.
  • Besluit bescherming tegen bepaalde zoönosen en bestrijding besmettelijke dierziekten artikel 8a: percentages tot verlaging van de tegemoetkoming in de schade. 

Websites en literatuur

Websites

Literatuur

Zie voor een Nederlandse beschrijving van Brucella melitensis het Handboek schapeziekten van P. Vellema (ISBN 90 6255 546 2).

J Bacteriol. 2012 Nov;194(22):6321. doi: 10.1128/JB.01595­12.

Complete Genome Sequence of Brucella melitensis Biovar 3 Strain NI, Isolated from an Aborted Bovine Fetus. Liu W, Jing Z, Ou Q, Cui B, He Y, Wu Q.

Source

Key Laboratory of Animal Epidemiology and Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.

Abstract

From an aborted bovine fetus in China, a bacterial strain named NI was isolated and identified as Brucella melitensis by a PCR assay. Strain NI was further characterized as B. melitensis biovar 3 using biochemical assays. Here we report the complete genome sequence of strain NI.

J Bacteriol. 2012 Oct;194(19):5489. doi: 10.1128/JB.01293­12.

Genome sequences of Brucella melitensis 16M and its two derivatives 16M1w and 16M13w, which evolved in vivo. Ke Y, Yuan X, Wang Y, Bai Y, Xu J, Song H, Huang L, Chen Z.

Source

Department of Infectious Disease Control, Beijing Institute of Disease Control and Prevention, Beijing, People's Republic of China.

Abstract

Brucella melitensis is an intracellular pathogen that induces chronic infection in humans. Here, we report the genome sequences of 16M and its two derivatives, 16M1w and 16M13w, which were allowed to adapt in vivo for 1 and 13 weeks, respectively. Our findings contribute to the investigation of adaptive mutations and mechanisms of chronic infection by B. melitensis.

J Bacteriol. 2012 Oct;194(19):5451. doi: 10.1128/JB.01202­12.

Genome sequence of Brucella melitensis S66, an isolate of sequence type 8, prevalent in China. Ke Y, Yuan X, Zhen Q, Wang Y, Li T, Sun Y, Song H, Huang L, Wang D, Cui B, Mao K, Chen Z.

Source

Department of Infectious Disease Control, Beijing Institute of Disease Control and Prevention, Beijing, People's Republic of China.

Abstract

Brucella melitensis is the most­represented Brucella species causing human brucellosis in China. Here we report the complete genome sequence of B. melitensis strain S66, a representative strain of sequence type 8 (ST8), which is prevalent in China, making it possible to compare the genome sequences of isolates from different countries.

PLoS One. 2012;7(8):e42514. doi: 10.1371/journal.pone.0042514. Epub 2012 Aug 14.

MLVA16 typing of Portuguese human and animal Brucella melitensis and Brucella abortus isolates. Ferreira AC, Chambel L, Tenreiro T, Cardoso R, Flor L, Dias IT, Pacheco T, Garin­Bastuji B, Le Flèche P, Vergnaud G, Tenreiro R, de Sá MI.

Source

Laboratório Nacional de Investigação Veterinária, Instituto Nacional de Recursos Biológicos, IP, Lisboa, Portugal. cristina.ferreira@lniv.minagricultura.pt

Abstract

To investigate the epidemiological relationship of isolates from different Portuguese geographical regions and to assess the diversity among isolates, the MLVA16(Orsay) assay (panels 1, 2A and 2B) was performed with a collection of 126 Brucella melitensis (46 human and 80 animal isolates) and 157 B. abortus field isolates, seven vaccine strains and the representative reference strains of each species. The MLVA16(Orsay) showed a similar high discriminatory power (HGDI 0.972 and 0.902) for both species but panel 1 and 2A markers displayed higher diversity (HGDI 0.693) in B. abortus compared to B. melitensis isolates (HGDI 0.342). The B. melitensis population belong to the "Americas" (17%) and "East Mediterranean" (83%) groups. No isolate belonged to the "West Mediterranean" group. Eighty­five percent of the human isolates (39 in 46) fit in the "East­Mediterranean" group where a single lineage known as MLVA11 genotype 116 is responsible for the vast majority of Brucella infections in humans. B. abortus isolates formed a consistent group with bv1 and bv3 isolates in different clusters. Four MLVA11 genotypes were observed for the first time in isolates from S. Jorge and Terceira islands from Azores. From the collection of isolates analysed in this study we conclude that MLVA16(Orsay) provided a clear view of Brucella spp. population, confirming epidemiological linkage in outbreak investigations. In particular, it suggests recent and ongoing colonisation of Portugal with one B. melitensis lineage usually associated with East Mediterranean countries.

J Med Microbiol. 2012 Sep;61(Pt 9):1335­7. doi: 10.1099/jmm.0.038612­0. Epub 2012 Jun 8.

Isolation of Brucella melitensis biotype 3 from epidural empyema in a Bosnian immigrant in Germany.

Tappe D, Melzer F, Schmoock G, Elschner M, Lâm TT, Abele­Horn M, Stetter C. Source:

Institute of Hygiene and Microbiology, University of Würzburg, Josef­Schneider­Str. 2, 97080 Würzburg, Germany. dtappe@hygiene.uniwuerzburg.de Abstract:

Brucellosis is a regionally emerging infectious disease in Mediterranean countries with an increasing number of human cases and high morbidity rates. Here, we describe a case of severe B. melitensis biotype 3 infection in an immigrant who had contact with ruminants during a short­term stay in Bosnia before he returned to Germany. The patient developed thoracic spondylodiscitis accompanied by a large epidural empyema and neurological deficits. The isolated strain was characterized and compared to other strains from the Mediterranean region by multiple locus variable number of tandem repeat analysis, showing minor differences between emerging strains from neighbouring geographical areas.

Euro Surveill. 2012 Mar 15;17(11). pii: 20116.

Outbreak investigation of brucellosis in Thassos, Greece, 2008.

Karagiannis I, Mellou K, Gkolfinopoulou K, Dougas G, Theocharopoulos G, Vourvidis D, Ellinas D, Sotolidou M, Papadimitriou T, Vorou R. Source:

Hellenic Center for Disease Control and Prevention, Athens, Greece. Abstract:

In spring 2008, the Hellenic Center for Disease Control and Prevention was notified about human brucellosis cases in Thassos, a Greek island that had been up to that point under a brucellosis eradication programme. Following the verification of the outbreak a 1:1 case– control study was conducted in the island. The study revealed that consumption of locally produced raw cheese was a risk factor for Brucella melitensis infection (odds ratio (OR): 15.1, 95% confidence interval (CI): 6.56–34.7). Brucella melitensis biotype 3 was identified in two clinical samples. As a result of the outbreak, the island is no longer officially considered as an area with farms free of brucellosis and is currently under a brucellosis control programme. The investigation of this outbreak demonstrated that control and eradication of brucellosis is not only a question of designing a strategy, but rather of ensuring its continuous, strict implementation. Furthermore, it revealed the lack of appropriate education of the public regarding the risks associated with raw, non heat­treated cheese consumption.
 

Rev Sci Tech. 2011 Dec;30(3):809­19.

The first International Standard anti­Brucella melitensis Serum.

McGiven J, Taylor A, Duncombe L, Sayers R, Albert D, Banai M, Blasco JM, Elena S, Fretin D, Garin­Bastuji B, Melzer F, Muñoz PM, Nielsen K, Nicola A, Scacchia M, Tittarelli M, Dias IT, Walravens K, Stack J. Source:

Animal Health Veterinary Laboratories Agency (OIE/FAO Reference Laboratory), Woodham Lane, Addlestone, Surrey KT15 3NB, United Kingdom.

Abstract:

The World Organisation for Animal Health (OIE) requested an International Standard anti­Brucella melitensis Serum (ISaBmS) to standardise diagnostic tests and reagents for sheep and goats. The agreed criteria were the highest dilution (in negative serum) of the standard which must give a positive result and the lowest dilution (in negative serum) which must simultaneously give a negative result. The two dilutions for each assay were, respectively: indirect enzyme­linked immunosorbent assay (iELISA) 1/64 and 1/750, competitive ELISA (cELISA) 1/8 and 1/300, fluorescent polarisation assay (FPA) 1/16 and 1/200, Rose Bengal test (RBT) 1/16 and 1/200. The OIE International Standard Serum (OIEISS) will remain the primary standard for the RBT; the ISaBmS is an additional standard. It was impossible to set criteria for the complement fixation test, therefore the OIEISS will remain the primary standard. The ISaBmS can be used to standardise iELISA, cELISA and FPA to diagnose sheep and goat brucellosis. This standard should facilitate harmonisation of tests used for brucellosis surveillance and international trade in these species.

J Hosp Infect. 2012 Apr;80(4):321­5. Epub 2012 Jan 9.

A large exposure to Brucella melitensis in a diagnostic laboratory.

Sam IC, Karunakaran R, Kamarulzaman A, Ponnampalavanar S, Syed Omar SF, Ng KP, Mohd Yusof MY, Hooi PS, Jafar FL, Abubakar S.

Source:

Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. jicsam@ummc.edu.my Abstract:

Background

Brucella species are easily transmitted by aerosols and can be acquired in the laboratory.

Aim

To report the management of a large exposure to Brucella melitensis that occurred over six days in a hospital diagnostic laboratory.

Methods

Fifty­one exposed staff were managed according to Centers for Disease Control and Prevention guidelines. A further 96 non­exposed laboratory staff were tested for seroprevalence. Testing was carried out using the Brucella sp. serum agglutination test.

Findings

Twenty­seven people had high­risk exposure and 24 had low­risk exposure. High­risk staff were offered post­exposure prophylaxis. Twelve (44.4%) agreed to this, of whom eight (66.7%) completed the course. Overall compliance with serological follow­up at baseline, 2, 4, 6 weeks and 8 months was 45.9%. Despite this poor compliance there were no clinical brucellosis cases and no seroconversion in the 47.1% of staff tested at 8 months. Brucella sp. seroprevalence among all staff tested was 3/147 (2.0%).

Conclusion

Lack of experience with Brucella spp. and lack of policies for handling potentially hazardous organisms contributed to this prolonged exposure. As compliance with current recommendations may be poor, the optimum frequency of serological follow­up and target groups for prophylaxis should be reassessed. Laboratories in low­ or non­endemic areas must prepare for potential isolation of Brucella spp. The impact of human brucellosis in Malaysia requires further study.

J Infect Dev Ctries. 2011 Dec 13;5(12):893­5.

Acute renal failure due to Brucella melitensis.

Dagli O, Dokur M, Guzeldag G, Ozmen Y. Source:

Department of Clinic for Infectious Disease, Kilis State Hospital, Kilis, Turkey. drozgurdagli@yahoo.com Abstract:

We present the case of a 42­year­old male patient who applied to the emergency department of our hospital with clinical nephritis, orchitis, acute renal failure without endocarditis, and a low­grade fever. Brucella agglutinin titers were 1:160, Rose Bengal test was positive and Brucella melitensis was isolated from urine and blood cultures. A combination of oral rifampin (600 mg/day) and doxycycline (200 mg/day) was administered along with supportive treatment leading to resolution of his clinical status by eight weeks. This was a rare complication of severe renal involvement due to brucellosis which resolved with antibiotic treatment.

Foodborne Pathog Dis. 2011 Dec;8(12):1257­61.

Brucella melitensis survival during manufacture of ripened goat cheese at two temperatures.

Méndez­González KY, Hernández­Castro R, Carrillo­Casas EM, Monroy JF, López­Merino A, Suárez­Güemes F.

Source:

Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Coyoacán, México.

Abstract:

The aim of the current work was to assess the influence of two temperatures, 4°C and 24°C, on pH and water activity and their association with Brucella melitensis survival during the traditional manufacture of ripened goat cheese. Raw milk from a brucellosis­free goat herd was used for the manufacture of ripened cheese. The cheese was inoculated with 5×10(9) of the B. melitensis 16M strain during the tempering stage. The cheeses were matured for 5, 20, and 50 days at both temperatures. To assess Brucella survival, the pH and a(w) were recorded at each stage of the process (curd cutting, draining whey, immersion in brine, ripening I, ripening II, and ripening III). B. melitensis was detected at ripening stage III (1×10(3) colony­forming unit [CFU]/mL) from cheeses matured at 4°C with a pH of 5.0 and a(w) of 0.90, and at a ripening stage II (1×10(4) CFU/mL) from cheeses ripened at 24°C with a pH of 4.0 and a(w) of 0.89. The remaining stages were free from the inoculated pathogen. In addition, viable B. melitensis was recovered in significant amounts (1­2×10(6) CFU/mL) from the whey fractions of both types of cheese ripened at 24°C and 4°C. These results revealed the effects of high temperature (24°C vs. 4°C) on the low pH (4) and a(w) (0.89) that appeared to be associated with the suppression of B. melitensis at the early stages of cheese ripening. In the ripened goat cheeses, B. melitensis survived under a precise combination of temperature during maturation, ripening time, and a(w) in the manufacturing process.

BMC Microbiol. 2011 Nov 22;11:256.

MLVA genotyping of Chinese human Brucella melitensis biovar 1, 2 and 3 isolates.

Jiang H, Fan M, Chen J, Mi J, Yu R, Zhao H, Piao D, Ke C, Deng X, Tian G, Cui B. Source:

State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping, Beijing 102206, PR China. Abstract:

Background

Since 1950, Brucella melitensis has been the predominant strain associated with human brucellosis in China. In this study we investigated the genotypic characteristics of B. melitensis isolates from China using a multiple­locus variable­number tandem­repeat analysis (MLVA) and evaluated the utility of MLVA with regards to epidemiological trace­back investigation.

Results

A total of 105 B. melitensis strains isolated from throughout China were divided into 69 MLVA types using MLVA­16. Nei's genetic diversity indices for the various loci ranged between 0.00 ­ 0.84. 12 out 16 loci were the low diversity with values < 0.2 and the most discriminatory markers were bruce16 and bruce30 with a diversity index of > 0.75 and containing 8 and 7 alleles, respectively. Many isolates were singlelocus or double­locus variants of closely related B. melitensis isolates from different regions, including the north and south of China. Using panel 1, the majority of strains (84/105) were genotype 42 clustering to the 'East Mediterranean' B. melitensis group. Chinese B. melitensis are classified in limited number of closely related genotypes showing variation mainly at the panel 2B loci.

Conclusion

The MLVA­16 assay can be useful to reveal the predominant genotypes and strain relatedness in endemic or non­endemic regions of brucellosis. However it is not suitable for biovar differentiation of B. melitensis. Genotype 42 is widely distributed throughout China during a long time. Bruce 16 and bruce 30 in panel 2B markers are most useful for typing Chinese isolates.

Zoonoses Public Health. 2011 Nov;58(7):489­92. doi: 10.1111/j.1863­2378.2011.01399.x. Epub 2011 Feb 22.

Brucella melitensis infection following military duty in Iraq. Bechtol D, Carpenter LR, Mosites E, Smalley D, Dunn JR.

Source:

University of Tennessee, Knoxville, TN, USA. Abstract:

Brucellosis is a common zoonotic disease worldwide; however, few cases are reported in the US. Brucella melitensis infections are primarily acquired via consumption of high­risk foods or travel to endemic areas. We describe a case of B. melitensis infection in a Tennessee soldier following deployment in Iraq. Initial symptoms included knee and back pain. Culture of an aspirate of the left sacroiliac joint yielded B. melitensis. Genetic analysis indicated that this isolate came from the Middle East. Investigation of laboratory workers identified risky exposures and positive serology prompting post­exposure prophylaxis. Military personnel and other travellers should be advised to reduce risk regarding food consumption and animal contact in endemic areas. Additionally, medical providers should remain vigilant for non­endemic zoonoses among recent travellers.

Rev Sci Tech. 2005 Dec;24(3):973­9.

Abortion due to Brucella abortus in sheep in Nigeria.

Ocholi RA, Kwaga JK, Ajogi I, Bale JO.

Source:

Brucellosis Research Unit, Bacterial Research Department, National Veterinary Research Institute, Vom, Plateau State, Nigeria.

Abstract:

This paper reports on a sporadic, naturally acquired infection of sheep with Brucella abortus on a privately owned farm in Toro near Bauchi, Nigeria. The abortions, which occurred in a flock of 28 Yankassa sheep, involved five ewes at the third month of gestation. Serum and milk samples from the flock were examined for Brucella antibodies by the Rose Bengal plate test, serum agglutination test (SAT) and milk ring test (MRT). The proportion shown as positive by SAT was 14.3%. All the five milk samples examined by MRT were positive. A total of seven isolates of Brucella were obtained from three milk samples and four vaginal swabs collected from aborting ewes. All isolates were identified and biotyped as B. abortus biovar 1. This biovar was also isolated from cattle maintained on the farm in association with the sheep. The infection was attributed to the animal husbandry practices employed on the farm.

Emerg Infect Dis. 1997 Apr­Jun;3(2):213­21.

Brucellosis: an overview.

Corbel MJ.

Source:

National Institute of Biological Standards and Control, South Mimmas, Potters Bar, Hertfordshire, United Kingdom. mcorbel@nibsc.ac.uk Abstract:

Brucellosis remains a major zoonosis worldwide. Although many countries have eradicated Brucella abortus from cattle, in some areas Brucella melitensis has emerged as a cause of infection in this species as well as in sheep and goats. Despite vaccination campaigns with the Rev 1 strain, B. melitensis remains the principal cause of human brucellosis. Brucella suis is also emerging as an agent of infection in cattle, thus extending its opportunities to infect humans. The recent isolation of distinctive strains of Brucella from marine mammals has extended its ecologic range. Molecular genetic studies have demonstrated phylogenetic affiliation to Agrobacterium, Phyllobacterium, Ochrobactrum, and Rhizobium. Polymerase chain reaction and gene probe development may provide more effective typing methods. Pathogenicity is related to production of lipopolysaccharides containing a poly N­formyl perosamine O chain, CuZn superoxide dismutase, erythrlose phosphate dehydrogenase, stress­induced proteins related to intracellular survival, and adenine and guanine monophosphate inhibitors of phagocyte functions. Protective immunity is conferred by antibody to lipopolysaccharide and T­cell­mediated macrophage activation triggered by protein antigens. Diagnosis still centers on isolation of the organism and serologic test results, especially enzyme immunoassay, which is replacing other methods. Polymerase chain reaction is also under evaluation. Therapy is based on tetracyclines with or without rifampicin, aminoglycosides, or quinolones. No satisfactory vaccines against human brucellosis are available, although attenuated purE mutants appear promising.

PLoS One 2014 Apr 14;9(4):e94168. doi: 10.1371/journal.pone.0094168. eCollection 2014.

Brucella melitensis in France: persistence in wildlife and probable spillover from Alpine ibex to domestic animals.

Mick V, Le Carrou G, Corde Y, Game Y, Jay M, Garin­Bastuji B.

Can J Infect Dis. 1995 May-Jun; 6(3): 153–155. Human to human transmission of Brucella melitensis

Patrice Vigeant, MD FRCPC, Jack Mendelson, MD MS FRCPC, and Mark A Miller, MD MSc FRCPC

Abstract

Human brucellosis is acquired mainly through contact with infected animal tissues, ingestion of unpasteurized dairy products or infected aerosols. Person to person transmission is still considered uncertain. The case of a woman diagnosed with proven brucellosis after her husband suffered a relapse of bacteremia with Brucella melitensis biotype 3, which was originally acquired abroad by eating goat cheese, is described. It was postulated that person to person spread of brucellosis is a likely mode of transmission in this case.

Clinical Infectious Diseases, Volume 51, Issue 2, 15 July 2010, Pages e12–e15, https://doi.org/10.1086/653608

Sexually Transmitted Brucellosis in Humans 

Eyal Meltzer Yechezkel Sidi Gill Smolen Menachem Banai Svetlana Bardenstein Eli Schwartz

Human brucellosis is acquired mainly through contact with infected animal tissues, ingestion of unpasteurized dairy products or infected aerosols. Person to person transmission is still considered uncertain. The case of a woman diagnosed with proven brucellosis after her husband suffered a relapse of bacteremia with Brucella melitensis biotype 3, which was originally acquired abroad by eating goat cheese, is described. It was postulated that person to person spread of brucellosis is a likely mode of transmission in this case.

Can J Microbiol. 2017 Aug;63(8):719-729. doi: 10.1139/cjm-2017-0179. Epub 2017 May 8.

Brucella melitensis M5-90Δbp26 as a potential live vaccine that allows for the distinction between natural infection and immunization.

Li T, Tong Z, Huang M, Tang L, Zhang H, Chen C.

Brucella is Gram-negative intracellular bacterial pathogen that infects humans and animals and contributes to great economic losses in developing countries. Presently, live attenuated Brucella vaccines (Brucella melitensis M5-90) are the most effective means of brucellosis control and prevention in animals. However, these vaccines have several drawbacks, such as an inability to distinguish between a natural infection and immunization and an association with abortions in pregnant animals. Therefore, this study constructed a Brucella M5-90Δbp26 mutant and evaluated its virulence. The survival of the M5-90Δbp26 mutant was attenuated in human placenta trophoblastic 8 cells (HPT-8 cells) and in BALB/c mice, with a high immunoprotectivity noted in mice. Furthermore, safety tests showed that the M5-90Δbp26 mutant was less virulent than the M5-90 vaccine strain. Additionally, an indirect enzyme-linked immunosorbent assay (ELISA) screening was shown to detect the presence of Brucella protein 26 (BP26) with high sensitivity, with M5-90Δbp26 inoculation accompanied with a lack of BP26 expression, and was further confirmed by western blotting. Together, the M5-90Δbp26 mutant and the indirect ELISA can be employed to distinguish vaccinated livestock from infected animals.

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