Update on laboratory diagnosis of human brucellosis
Section snippets
Brucella species
Brucella spp. are small (0.5–1.5 μm), facultative, intracellular Gram-negative coccobacilli that lack capsules, flagellae, endospores or native plasmids. They are aerobic, do not ferment sugars and are positive in a few oxidative metabolic tests. They can grow on a wide range of culture media and colonies generally appear after 24–48 h incubation [11], [12].
To date, six terrestrial and three marine Brucella species have been recognized: B. melitensis (preferred hosts are goats, sheep, camels), B.
Antigenic components
Several antigenic components have been identified and determined to be involved in a variety of roles, including pathogenesis and the immune response, and are potentially useful in diagnosis of the disease. Lipopolysaccharide (LPS) is the major antigen and can exist in two partially shared antigenic epitopes: A (B. abortus) and M (B. melitensis). The O-specific side chains of the LPS molecule are considered the cause of the reported cross-reactions in both the agglutination and complement
Transmission
Ingesting unpasteurized animal milk (goat, sheep, cow or camel) or its products, e.g. soft cheese, account for most cases worldwide [4], [5], [22]. Occupational infection (mostly in veterinarians, workers in clinical, research and production laboratories, and abattoir workers) is primarily associated with respiratory, conjunctival and skin routes of infection, e.g. through inhalation, sprays and aerosols; abrasions, accidental inoculation or cuts; and mishandling and misidentification of the
Virulence and pathogenesis
The virulence and pathogenesis of Brucella infection and the bacterium's avoidance of the immune system remain to be clarified and resolved [24]. The incubation period is variable, but generally is 1–4 weeks. Its intracellular survival within polymorphonuclear and mononuclear phagocytes, escaping phagosome–lysosome fusion and the immune response, is facilitated by factors including its ability to produce urease, which offers protection from stomach acid, Brucella-containing vacuoles, where the
Clinical features
The clinical diagnosis of brucellosis remains a considerable challenge, and to the unaware physician the diagnosis becomes a protracted problem for months and sometimes years. This difficulty can be attributed to several aspects of infection, including the prolonged and variable incubation period, its frequent presentation as a non-specific febrile syndrome in adults and children (periodic or undulant fever, including muscle aches, back pain, sweating and fatigue), the varied evolution (acute,
Focal complications and conservative cost estimates
The most commonly encountered focal complications are osteoarticular (10–70%, mostly joints), genital in both males (6–8%) and females (2–5%), neurological (3–5%), cardiac (1–3%), pulmonary (1–2%) and renal (<1%). Mortality is very low (<1%) and almost exclusively results from cardiac complications [5], [6], [27], [28], [29], [30], [31], [32], [33]. It is noteworthy that in some patients who have undergone even simple surgeries, like cholecystectomy and hernia repair, unexplained protracted
Laboratory diagnosis
The diagnosis of a patient with possible brucellosis requires the combination of several approaches, including medical history, clinical examination, routine haematological and biochemical laboratory tests, radiological investigation and, most importantly, established and newly available Brucella-specific culture, serological and molecular tests, as described in this article.
The routine haematological investigations used in the diagnosis of brucellosis are mainly complete blood count,
Conclusions
Many improvements have been made towards better understanding of the clinical, epidemiological, pathogenetic, diagnostic, therapeutic and other aspects of human brucellosis, a historic zoonotic disease. However, several challenges remain to be addressed: (1) to define specific serological diagnostic and prognostic markers, (2) determine purified, specific and relevant antigenic epitope predictors of each disease stage (e.g. acute, active, relapse, chronic, cure), (3) carry out follow-up studies
References (76)
- et al.
The new global map of human brucellosis
Lancet Infect Dis
(2006) - et al.
Bacterial pathogens as biological weapons and agents of bioterrorism
Am J Med Sci
(2002) - et al.
Category B potential bioterrorism agents: bacteria, viruses, toxins, and foodborne and waterborne pathogens
Infect Dis Clin North Am
(2006) Current understanding of the genetic diversity of Brucella, an expanding genus of zoonotic pathogens
Infect Genet Evol
(2009)- et al.
Immunization of mice with recombinant L7/L12 ribosomal protein confers protection against Brucella abortus infection
Vaccine
(1996) - et al.
Human brucellosis
Lancet Infect Dis
(2007) Brucella: a Mr “Hide” converted into Dr Jekyll
Microb Infect
(2008)Overview
- et al.
Review of clinical and laboratory features of human brucellosis
Indian J Med Microbiol
(2007) - et al.
Evaluation of Brucella MLVA typing for human brucellosis
J Microbiol Methods
(2007)
Rose Bengal test: diagnostic yield and use for the rapid diagnosis of human brucellosis in emergency departments in endemic areas
Clin Microbiol Infect
The value of ELISA vs negative Coombs findings in the serodiagnosis of human brucellosis
Serodiag Immunother Infect Dis
Profiles of Brucella-specific immunoglobulin G subclass in serum of patients with acute and chronic brucellosis
Serodiag Immunother Infect Dis
Indirect fluorescent antibody test versus enzyme linked immunosorbent assay and agglutination tests in the serodiagnosis of patient with brucellosis
Serodiag Immunother Infect Dis
The evaluation of a user-friendly lateral flow assay for the serodiagnosis of human brucellosis in Kazakhstan
Diagn Microbial Infect Dis
Development and evaluation of real-time polymerase chain reaction assays on whole blood and paraffin-embedded tissues for rapid diagnosis of human brucellosis
Diagn Microbiol Infect Dis
Utility of an immunocapture–agglutination test and an enzyme-linked immunosorbent assay test against cytosolic proteins from Brucella melitensis B115 in the diagnosis and follow-up of human acute brucellosis
Diagn Microbiol Infect Dis
Serum levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) as a predictor of outcome in brucellosis
J Infect
Note on the discovery of a microorganism in Malta Fever
Practitioner
Sir Themistocles Zammit: His honors and an annotated bibliography of his medical work
Maltese Med J
Human brucellosis revisited: a persistent saga in the Middle East
BMJ (Middle East)
Human brucellosis in Kuwait: a prospective study of 400 cases
Quart J Med
An overview of human brucellosis
Clin Infect Dis
Brucellosis and international travel
J Travel Med
From the discovery of the Malta fever's agent to the discovery of a marine mammal reservoir, brucellosis has continuously been a re-emerging zoonosis
Vet Res
Techniques for the brucellosis laboratory
Brucellosis: an overview
Emerg Infect Dis
Brucella ceti sp. nov. and Brucella pinnipedialis sp. nov. for Brucella strains with cetaceans and seals as their preferred hosts
Int J Syst Evol Microbiol
Human exposure to Brucella recovered from a sea mammal
Vet Rec
Human neurobrucellosis with intra-cerebral granuloma caused by a marine mammal Brucella spp
Emerg Infect Dis
Characterisation of a Brucella sp. strain as a marine-mammal type despite isolation from a patient with spinal osteomyelitis in New Zealand
J Clin Microbiol
Afipia clevelandensis antibodies and cross-reactivity with Brucella spp. and Yersinia enterocolitica O:9
Clin Diag Lab Immunol
Characterization of an 18-kilodalton Brucella cytoplasmic protein which appears to be a serological marker of active infection of both human and bovine brucellosis
J Clin Microbiol
Structure and properties of the outer membranes of Brucella abortus and Brucella melitensis
Int Microbiol
Laboratory exposures to Brucellae and implications for bioterrorism
Emerg Infect Dis
Brucellosis: III. Psychologic aspects of delayed convalescence
AMA Arch Intern Med
The nature of brucellosis
A study of brucellosis in childhood
Clin Pediatr
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2022, Annals of Diagnostic PathologyCitation Excerpt :Currently, a consensus about the diagnostic criteria for BS is scant. Besides the gold standard of bacteria culture [10], the diagnosis of BS also relies on the contact tracing, clinical manifestations and laboratory tests [11]. It is generally considered that a serological test for identifying antibodies against Brucella is the first choice for diagnosing brucellosis [12].
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