Review

Authors: Pablo Yagupsky, Pilar Morata, Juan D Colmenero...

The clinical presentation of brucellosis in humans is variable and unspecific, and thus, laboratory corroboration of the diagnosis is essential for the patient's proper treatment. The diagnosis of brucellar infections can be made by culture, serological tests, and nucleic acid amplification assays. Modern automated blood culture systems enable detection of acute cases of brucellosis within the routine 5- to 7-day incubation protocol employed in clinical microbiology laboratories, although a longer incubation and performance of blind subcultures may be needed for protracted cases. Serological tests, though they lack specificity and provide results that may be difficult to interpret in individuals repeatedly exposed to organisms, nevertheless remain a diagnostic cornerstone in resource-poor countries. Nucleic acid amplification assays combine exquisite sensitivity, specificity, and safety and enable rapid diagnosis of the disease. However, long-term persistence of positive molecular test results in patients that have apparently fully recovered is common and has unclear clinical significance and therapeutic implications. Therefore, as long as there are no sufficiently validated commercial tests or studies that demonstrate an adequate interlaboratory reproducibility of the different homemade PCR assays, cultures and serological methods will remain the primary tools for the diagnosis and posttherapeutic follow-up of human brucellosis.

Topics: Brucella; Brucellosis; Clinical Laboratory Techniques; Humans; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Serologic Tests

PubMed: 31722888
DOI: 10.1128/CMR.00073-19

Review

Authors: Marcela Suárez-Esquivel, Esteban Chaves-Olarte, Edgardo Moreno...

organisms are responsible for one of the most widespread bacterial zoonoses, named brucellosis. The disease affects several species of animals, including humans. One of the most intriguing aspects of the brucellae is that the various species show a ~97% similarity at the genome level. Still, the distinct species display different host preferences, zoonotic risk, and virulence. After 133 years of research, there are many aspects of the biology that remain poorly understood, such as host adaptation and virulence mechanisms. A strategy to understand these characteristics focuses on the relationship between the genomic diversity and host preference of the various species. Pseudogenization, genome reduction, single nucleotide polymorphism variation, number of tandem repeats, and mobile genetic elements are unveiled markers for host adaptation and virulence. Understanding the mechanisms of genome variability in the genus is relevant to comprehend the emergence of pathogens.

Topics: Animals; Brucella; Brucellosis; Evolution, Molecular; Genome, Bacterial; Genomics; Humans; Phylogeny; Polymorphism, Single Nucleotide; Virulence

PubMed: 33092044
DOI: 10.3390/ijms21207749

Meta-Analysis

Authors: Mariana Lourenço Freire, Tália Santana Machado de Assis, Sarah Nascimento Silva...

BACKGROUND

Brucellosis, a widely spread zoonotic disease, poses significant diagnostic challenges due to its non-specific symptoms and underreporting. Timely and accurate diagnosis is crucial for effective patient management and public health control. However, a comprehensive comparative review of available diagnostic tests is lacking.

METHODOLOGY/PRINCIPAL FINDINGS

This systematic review addressed the following question: 'What is the accuracy of the available tests to confirm human brucellosis?' Two independent reviewers examined articles published up to January 2023. The review included original studies reporting symptomatic patients with brucellosis suspicion, through any index test, with sensitivity and/or specificity as outcomes. As exclusion criteria were considered: sample size smaller than 10 patients, studies focusing on complicated brucellosis, and those lacking essential information about index or comparator tests. Sensitivity and specificity were assessed, with consideration for the index test, and 'culture' and 'culture and standard tube agglutination test (SAT)' were used as reference standards. Bias assessment and certainty of evidence were carried out using the QUADAS-2 and GRADE tools, respectively. A total of 38 studies reporting diagnostic test performance for human brucellosis were included. However, the evidence available is limited, and significant variability was observed among studies. Regarding the reference test, culture and/or SAT are deemed more appropriate than culture alone. Rose Bengal, IgG/IgM ELISA, and PCR exhibited equally high performances, indicating superior overall diagnostic accuracy, with very low certainty of the evidence.

CONCLUSIONS/SIGNIFICANCE

This systematic review underscores the potential of the Rose Bengal test, IgG/IgM ELISA, and PCR as promising diagnostic tools for brucellosis. However, the successful implementation and recommendations for their use should consider the local context and available resources. The findings highlight the pressing need for standardization, improved reporting, and ongoing advancements in test development to enhance the accuracy and accessibility of brucellosis diagnosis.

Topics: Brucellosis; Humans; Sensitivity and Specificity; Brucella; Diagnostic Tests, Routine; Agglutination Tests

PubMed: 38452046
DOI: 10.1371/journal.pntd.0012030

Review

Authors: Hui Yu, Xinyi Gu, Danfeng Wang...

consists of gram-negative bacteria that have the ability to invade and replicate in professional and non-professional phagocytes, and its prolonged persistence in the host leads to brucellosis, a serious zoonosis. Toll-like receptors (TLRs) are the best-known sensors of microorganisms implicated in the regulation of innate and adaptive immunity. In particular, TLRs are transmembrane proteins with a typical structure of an extracellular leucine-rich repeat (LRR) region and an intracellular Toll/interleukin-1 receptor (TIR) domain. In this review, we discuss infection and the aspects of host immune responses induced by pathogens. Furthermore, we summarize the roles of TLRs in infection, with substantial emphasis on the molecular insights into its mechanisms of action.

Topics: Humans; Toll-Like Receptors; Brucellosis; Brucella; Immunity, Innate

PubMed: 38533384
DOI: 10.3389/fcimb.2024.1342684

Authors: Araceli Contreras-Rodríguez, Cristina Majalca-Martínez, M Guadalupe Aguilera-Arreola...

Topics: Anti-Bacterial Agents; Culture Media; Ochrobactrum anthropi

PubMed: 30534931
DOI: 10.4067/s0716-10182018000400431

Authors: Consuelo Borie, Nicolás Galarce

Topics: Brucella canis

PubMed: 26065455
DOI: 10.4067/S0716-10182015000300011

Authors: Edgardo Moreno, Earl A Middlebrook, Pamela Altamirano-Silva...

Bacteria of the genus Brucella are facultative intracellular parasites that cause brucellosis, a severe animal and human disease. Recently, a group of taxonomists merged the brucellae with the primarily free-living, phylogenetically related spp. in the genus Brucella. This change, founded only on global genomic analysis and the fortuitous isolation of some opportunistic spp. from medically compromised patients, has been automatically included in culture collections and databases. We argue that clinical and environmental microbiologists should not accept this nomenclature, and we advise against its use because (i) it was presented without in-depth phylogenetic analyses and did not consider alternative taxonomic solutions; (ii) it was launched without the input of experts in brucellosis or ; (iii) it applies a non-consensus genus concept that disregards taxonomically relevant differences in structure, physiology, population structure, core-pangenome assemblies, genome structure, genomic traits, clinical features, treatment, prevention, diagnosis, genus description rules, and, above all, pathogenicity; and (iv) placing these two bacterial groups in the same genus creates risks for veterinarians, medical doctors, clinical laboratories, health authorities, and legislators who deal with brucellosis, a disease that is particularly relevant in low- and middle-income countries. Based on all this information, we urge microbiologists, bacterial collections, genomic databases, journals, and public health boards to keep the Brucella and genera separate to avoid further bewilderment and harm.

Topics: Ochrobactrum; Brucella; Terminology as Topic; Phylogeny; Brucellosis; Humans; Opportunistic Infections

PubMed: 37395662
DOI: 10.1128/jcm.00438-23

Review

Authors: M J Corbel

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 N-formyl perosamine O chain, CuZn superoxide dismutase, erythrlose phosphate dehydrogenase, stress-induced proteins related to intracellular survival, and adenine and guanine monophosphate inhibitors of phagocyte functions. Protective immunity is conferred by antibody to lipopolysaccharide and T-cell-mediated 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.

Topics: Animals; Antigens, Bacterial; Brucella; Brucellosis; Cattle; Humans

PubMed: 9204307
DOI: 10.3201/eid0302.970219

Review

Authors: Gamal Wareth, Ahmed Hikal, Mohamed Refai...

Brucellosis is a highly contagious zoonosis that affects the public health and economic performance of endemic as well as non-endemic countries. In developing nations, brucellosis is often a very common but neglected disease. The purpose of this review is to provide insight about brucellosis in animal populations in Egypt and help to understand the situation from 1986 to 2013. A total of 67 national and international scientific publications on serological investigations, isolation, and biotyping studies from 1986 to 2013 were reviewed to verify the current status of brucellosis in animal populations in Egypt. Serological investigations within the national surveillance program give indirect proof for the presence of brucellosis in cattle, buffaloes, sheep, goats, and camels in Egypt. Serologic testing for brucellosis is a well-established procedure in Egypt, but most of the corresponding studies do not follow the scientific standards. B. melitensis biovar (bv) 3, B. abortus bv 1, and B. suis bv 1 have been isolated from farm animals and Nile catfish. Brucellosis is prevalent nationwide in many farm animal species. There is an obvious discrepancy between official seroprevalence data and data from scientific publications. The need for a nationwide survey to genotype circulating Brucellae is obvious. The epidemiologic situation of brucellosis in Egypt is unresolved and needs clarification.

Topics: Animals; Animals, Domestic; Brucella; Brucellosis; Catfishes; Egypt; Seroepidemiologic Studies

PubMed: 25390047
DOI: 10.3855/jidc.4872

Authors: Maite Loperena-Barber, Aitor Elizalde-Bielsa, Miriam Salvador-Bescós...

The genus Pseudochrobactrum encompasses free-living bacteria phylogenetically close to Ochrobactrum opportunistic pathogens and to Brucella, facultative intracellular parasites causing brucellosis, a worldwide-extended and grave zoonosis. Recently, Pseudochrobactrum strains were isolated from Brucella natural hosts on Brucella selective media, potentially causing diagnostic confusions. Strikingly, P. algeriensis was isolated from cattle lymph nodes, organs that are inimical to bacteria. Here, we analyse P. algeriensis potential virulence factors in comparison with Ochrobactrum and Brucella. Consistent with genomic analyses, Western-Blot analyses confirmed that P. algeriensis lacks the ability to synthesize the N-formylperosamine O-polysaccharide characteristic of the lipopolysaccharide (LPS) of smooth Brucella core species. However, unlike other Pseudochrobactrum but similar to some early diverging brucellae, P. algeriensis carries genes potentially synthetizing a rhamnose-based O-polysaccharide LPS. Lipid A analysis by MALDI-TOF demonstrated that P. algeriensis LPS bears a lipid A with a reduced pathogen-associated molecular pattern, a trait shared with Ochrobactrum and Brucella that is essential to generate a highly stable outer membrane and to delay immune activation. Also, although not able to multiply intracellularly in macrophages, the analysis of P. algeriensis cell lipid envelope revealed the presence of large amounts of cationic aminolipids, which may account for the extremely high resistance of P. algeriensis to bactericidal peptides and could favor colonization of mucosae and transient survival in Brucella hosts. However, two traits critical in Brucella pathogenicity are either significantly different (T4SS [VirB]) or absent (erythritol catabolic pathway) in P. algeriensis. This work shows that, while diverging in other characteristics, lipidic envelope features relevant in Brucella pathogenicity are conserved in Brucellaceae. The constant presence of these features strongly suggests that reinforcement of the envelope integrity as an adaptive advantage in soil was maintained in Brucella because of the similarity of some environmental challenges, such as the action of cationic peptide antibiotics and host defense peptides. This information adds knowledge about the evolution of Brucellaceae, and also underlines the taxonomical differences of the three genera compared.

Topics: Phylogeny; Animals; Virulence Factors; Brucellaceae; Brucella; Lipopolysaccharides; Genome, Bacterial; Ochrobactrum; Cattle; Brucellosis; Lipid A

PubMed: 38906517
DOI: 10.1016/j.meegid.2024.105625