Multivariate model for predicting relapse in human brucellosis

Solera, J; Martı́nez-Alfaro, Elisa; Espinosa, Alfredo; Castillejos, María Luisa; Geijo, Paloma; Zapata, Manuel Rodríguez

doi:10.1016/s0163-4453(98)93342-4

Cited by 94 publications

(71 citation statements)

References 12 publications

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“…The percentage of relapses among patients suffering from the disease for more than a month before therapy was higher than that among patients suffering from the disease for less than a month (29). Contradictory to these findings, other studies demonstrated that treatment beginning less than 10 days after disease onset led to higher relapse rates (51,52). In endemic countries, brucellosis may be diagnosed earlier because physicians are familiar with the clinical signs and symptoms and take it more often into consideration as a differential diagnosis.…”

Section: Discussionmentioning

confidence: 89%

Human Brucellosis in Macedonia – 10 Years of Clinical Experience in Endemic Region

Bosilkovski¹,

Krteva²,

Dimzova³

et al. 2010

Croat Med J

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Aim To present our 10-year clinical experience with brucellosis patients at the University Clinic for Infectious Diseases and Febrile Conditions in Skopje, Republic of Macedonia.Methods A total of 550 patients with brucellosis treated between 1998 and 2007 were retrospectively assessed for their demographic, epidemiological, and clinical characteristics and outcomes.Results Of the 550 patients, 395 (72%) were male. The median age was 34.5 years (range, 1-82). Direct contact with infected animals was recorded in 333 (61%) patients and positive family history in 310 (56%). The most frequently seen symptoms were arthralgia (438, 80%), fever (419, 76%), and sweating (394, 72%). The most common signs were fever and hepatomegaly, which were verified in 357 (65%) and 273 (50%) patients, respectively. Focal brucellosis was found in 362 patients (66%) and osteoarticular in 299 (54%). Therapeutic failures were registered in 37 (6.7%) patients. Of the 453 (82%) patients who completed a follow-up period of at least 6 months, relapses occurred in 60 (13%). ConclusionDue to non-specific clinical manifestation and laboratory parameters, brucellosis should be considered one of the differential diagnoses of any patient suffering from obscure involvement of various organs in a brucellosis-endemic region. High percentage of relapses and therapeutic failures in spite of the use of currently recommended therapeutic regimens indicates the seriousness of this zoonosis and the need to control it.

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Section: Discussionmentioning

confidence: 89%

Human Brucellosis in Macedonia – 10 Years of Clinical Experience in Endemic Region

Bosilkovski¹,

Krteva²,

Dimzova³

et al. 2010

Croat Med J

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“…A marked characteristic of brucellosis is its tendency to produce relapses once treatment is concluded (Solera et al, 1998). The clinical symptoms are often misleading and the disease may present hepatosplenic, osteoarticular, gastrointestinal, neurological and/or cardiovascular complications.…”

Section: Resultsmentioning

confidence: 99%

Fluorescence polarization assay for diagnosis of human brucellosis

Lucero

2003

Journal of Medical Microbiology

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Fluorescence polarization immunoassay (FPA) uses molecular rotational properties to measure antibody binding to antigen directly. The potential use of this method was assessed in comparison to a competitive enzyme immunoassay (CELISA) and conventional serological tests for the diagnosis of brucellosis on a total of 587 human sera. Based on 340 sera from asymptomatic blood donors with no evidence of brucellosis, the specificity of the FPA was 97·9 % using a cut-off value of 72 mP. Sera from Brucella-infected patients (11 Brucella melitensis, 32 Brucella abortus, 32 Brucella suis and one Brucella sp.) yielded a sensitivity estimate of 96·1 %. In tests on 84 sera from suspected brucellosis patients, the FPA detected 80 cases. Of 87 sera from patients with probable infection, 15 were detected by both CELISA and FPA, three by CELISA only and four by FPA only. The discrepancies in both groups involved sera with low, declining titres. The FPA uses a sample of 40 ìl serum, takes about 5 min to complete and has been demonstrated to be accurate for the detection of antibodies to B. abortus, B. melitensis and B. suis and for identifying patients suffering relapses. Because of the ease of the procedure, it could be readily adopted for use in clinical laboratories and blood banks.

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“…In addition, Brucella species have been weaponized by several governments and are classified as category B threat agents (6). Because complete eradication of Brucella is unpractical because of its presence in a wide range of wild mammals (7,8), antibiotic treatment is costly, and patients frequently suffer from resurgence of the bacteria (9), vaccination remains the most rational strategy to confer durable protection on populations living in endemic countries and professionals who are frequently exposed to Brucella. Unfortunately, there is no available human brucellosis vaccine; all commercially available animal vaccines are live vaccines that would cause disease in humans (10,11).…”

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confidence: 99%

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

Mambres

Machelart

Potemberg

et al. 2016

The Journal of Immunology

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The mucosal immune system represents the first line of defense against Brucella infection in nature. We used genetically deficient mice to identify the lymphocytes and signaling pathways implicated in the control of primary and secondary intranasal infection with B. melitensis. Our analysis of primary infection demonstrated that the effectors implicated differ at the early and late stages and are dependent on the organ. TCR-δ, TAP1, and IL-17RA deficiency specifically affects early control of Brucella in the lungs, whereas MHC class II (MHCII) and IFN-γR deficiency impairs late control in the lungs, spleen, and liver. Interestingly, IL-12p35−/− mice display enhanced Brucella growth in the spleen but not in the lungs or liver. Secondary intranasal infections are efficiently contained in the lung. In contrast to an i.p. infectious model, in which IL-12p35, MHCII, and B cells are strictly required for the control of secondary infection, we observed that only TCR-β deficiency or simultaneous neutralization of IL-12p35– and IL-17A–dependent pathways impairs the memory protective response against a secondary intranasal infection. Protection is not affected by TCR-δ, MHCII, TAP1, B cell, IL-17RA, or IL-12p35 deficiency, suggesting that CD4+ and CD8+ α/β+ T cells are sufficient to mount a protective immune response and that an IL-17A–mediated response can compensate for the partial deficiency of an IFN-γ–mediated response to control a Brucella challenge. These findings demonstrate that the nature of the protective memory response depends closely on the route of infection and highlights the role of IFN-γ–and IL-17RA–mediated responses in the control of mucosal infection by Brucella.

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Multivariate model for predicting relapse in human brucellosis

Cited by 94 publications

References 12 publications

Human Brucellosis in Macedonia – 10 Years of Clinical Experience in Endemic Region

Human Brucellosis in Macedonia – 10 Years of Clinical Experience in Endemic Region

Fluorescence polarization assay for diagnosis of human brucellosis

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

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