Abstract
Introduction and importance:
Brucellosis is globally acknowledged as the predominant zoonotic infection afflicting humans. Misdiagnosis and underdiagnosis pose significant challenges in the diagnosis of brucellosis due to the potential risk of overlooking or misinterpreting symptoms.
Case presentation:
This article reports a case of a 10-year-old girl with brucellosis, presenting with fever, rash on both lower limbs, and pain in the right ankle joint. The patient underwent 10 days of inaccurate treatment at a local hospital without improvement, and then sought treatment at a provincial hospital. Considering that it was the peak season for Mycoplasma pneumonia infection, she received intravenous cefotaxime combined with oral azithromycin for anti-infection treatment after admission. Six days later, blood cultures showed positive for Brucella, and it was learned that the child’s family raised sheep. She was ultimately diagnosed with brucellosis.
Clinical discussion:
In this case, if medical staff had been fully aware of the relevant issues and promptly conducted corresponding laboratory tests, such as the tube agglutination test (SAT) or the colloidal gold immunochromatographic assay, the patient might have received effective treatment earlier.
Conclusion:
Brucellosis often has nonspecific symptoms that can lead to misdiagnosis or delays in diagnosis. However, early intervention can reduce complications, shorten treatment time, and improve outcomes. Therefore, developing effective diagnostic tests for brucellosis is crucial for timely detection and management. Additionally, healthcare professionals need a thorough understanding of the disease’s clinical signs and diagnostic challenges to ensure accurate and prompt diagnoses.
Keywords: brucellosis, children, delayed diagnosis, misdiagnosis, underdiagnosis
Introduction
Human brucellosis is an often persistent illness mimicking flu-like symptoms, with nonspecific clinical manifestations. This zoonotic disease is still common in many developing countries, especially in areas with widespread agriculture. The main mode of transmission is frequently associated with the consumption of unpasteurized dairy products[1]. Additionally, infection can be contracted through direct contact with infected animals, and there have been reported instances of individuals acquiring the disease following interactions with wildlife[2].
The global prevalence of human brucellosis has significantly changed in the past decade compared to 2006[3]. The epidemic now spans at least 97 countries, including an additional 18 in Europe, 12 in the Americas, 9 in Asia, and 4 in Africa. The Eastern Mediterranean region has the highest reported incidence of brucellosis. Asia bears the highest burden of human brucellosis globally. In China, the incidence rate has witnessed a significant increase from 0.0281/100 000 in 1993 to 5.0553/100 000 in 2021[4].
HIGHLIGHTS
Human brucellosis is a persistent illness with nonspecific clinical symptoms. Often mimicking flu-like symptoms, this zoonotic disease is still common in many developing countries, especially in areas with widespread agriculture.
Asia bears the highest burden of human brucellosis globally.
Misdiagnosis and underdiagnosis pose significant challenges in the diagnosis of brucellosis due to the potential risk of overlooking or misinterpreting symptoms.
This article presents a case study of a 10-year-old female patient diagnosed with Brucellosis, who exhibited symptoms including fever, bilateral lower limb rash, and pain in the right ankle joint. Following 16 days of diagnosis and treatment, the definitive diagnosis of the disease was established. Therefore, medical professionals need to have a thorough understanding of the clinical manifestations and diagnostic challenges of the disease in order to make accurate and timely diagnoses.
Misdiagnosis and underdiagnosis pose significant challenges in the diagnosis of brucellosis due to the potential risk of overlooking or misinterpreting symptoms. The nonspecific nature of symptoms, such as fever, fatigue, and joint pain, can resemble those associated with various other illnesses, potentially leading to delayed initiation of appropriate treatment.
It has previously been observed that 62.5% of brucellosis patients are misdiagnosed during their initial diagnosis[5]. Another study also reported that over half of the brucellosis patients were initially misdiagnosed with other diseases[6]. Recently, Qin et al[7] reported a case of brucellosis patient who was misdiagnosed due to symptoms similar to COVID-19 or flu and delayed treatment during strict COVID-19 prevention and control period. Despite its low mortality rate, brucellosis can result in significant debilitation or impairment[8]. Therefore, prompt diagnosis and treatment are essential for preventing the chronic progression of the disease.
We are reporting a case of a child diagnosed with brucellosis after 16 days after the symptoms appeared. This study aims to contribute to Pediatric brucellosis literature, epidemiological, clinical features, laboratory findings, and treatment.
Case report
On July 13, 2024, a 10-year-old girl came for a medical consultation due to fever, a rash on both lower limbs, and pain in the right ankle joint. The patient had developed a fever 10 days prior, with a maximum temperature of 39°C, accompanied by chills. Despite taking oral antipyretics and undergoing physical cooling, the fever persisted, recurring about three times daily. Oral amoxicillin capsules (0.25 g each, three times a day) proved ineffective after 2 days, leading to the development of scattered hemorrhagic rashes on both lower limbs and pain in the right ankle joint. Following hospitalization at a local facility, it was noted that the peak of the fever had decreased compared to before but still recurred, the rash had slightly reduced, and there was no significant improvement in the right ankle joint. Consequently, the patient was referred to our hospital for further diagnosis and treatment. The blood routine results from XXX Hospital on July 11, 2024, indicated the following: CRP 22.8 mg/L, WBC 4.687 × 109/L, N% 39%, L% 58.5%, M% 2.3%, N# 1.9 × 109/L, HGB 108 g/L, PLT 133 × 109/L. Additionally, the serum amyloid A level was 95.78 mg/L; lactate dehydrogenase level was 677 U/L; alanine aminotransferase level was 42 U/L; and aspartate aminotransferase level was 94 U/L. Kidney function and myocardial enzymes are within normal ranges. However, the serum ferritin level was found to be over 1000 ng/ml. Tests for various viral antibodies all returned negative results. The routine urine analysis is normal. The specific results are detailed in Table 1. Chest X-ray suggests: increased and blurred lung markings in both lungs, and ultrasound indicated splenomegaly (oblique diameter 14.5 cm). In a follow-up examination on July 13, 2024, CRP levels had decreased to 14.65 mg/L, but other indicators remained unchanged.
Table 1.
Laboratory results
| Lab tests | Result | Reference range | |
|---|---|---|---|
| Blood test | C-reactive protein (CRP) | 22.8 mg/L | 0–10 mg/L |
| White blood cells (WBC) | 4.687 × 109/L | 3.50–9.50 × 109/L | |
| Percentage of neutrophils (N%) | 39% | 40.00%–75.00% | |
| Percentage of lymphocytes (L%) | 58.50% | 20.00%–50.00% | |
| Percentage of monocytes (M%) | 2.30% | 3.00%–10.00% | |
| Absolute neutrophil count (N #) | 1.9 × 109/L | 1.80–6.30 × 109/L | |
| Hemoglobin (HGB) | 108 g/L | 115–150 g/L | |
| Blood platelets (PLT) | 133 × 109/L | 125–350 × 109/L | |
| Serum amyloid A (SAA) | 95.78 mg/L | 0–10 mg/L | |
| Alanine aminotransferase (ALT) | 42 U/L | 7–40 U/L | |
| Aspartate aminotransferase (AST) | 94 U/L | 13–35 U/L | |
| AST/ALT(AST/ALT) | 2.23 | 0.5–1.5 | |
| Lactate dehydrogenase (LDH) | 677 U/L | 120–250 U/L | |
| α-hydroxybutyrate dehydrogenase (α-HBDH) | 500.31 U/L | 72–182 U/L | |
| Creatine kinase (CK) | 17.54 U/L | 40–200 U/L | |
| Creatine kinase isoenzyme MB (CK-MB) | 20.34 U/L | 0–24 U/L | |
| Urea | 3.53 mmol/L | 2.6–7.5 mmol/L | |
| Creatinine (Cr) | 31.35 μmol/L | 41–73 μmol/L | |
| Uric acid (UA) | 236.50 μmol/L | 155–357 μmol/L | |
| Serum ferritin (FER) | 1535.54 ng/ml | 10–291 ng/ml | |
| Nucleic acid of influenza A virus | Negative (−) | Negative (−) | |
| Nucleic acid of influenza B virus | Negative (−) | Negative (−) | |
| Respiratory syncytial virus | >40 | CT >40 was considered negative | |
| Adenovirus | >40 | CT >40 was considered negative | |
| Parainfluenza virus type I | >40 | CT >40 was considered negative | |
| Parainfluenza virus type II | >40 | CT >40 was considered negative | |
| Parainfluenza virus type III | >40 | CT >40 was considered negative | |
| Human metapneumovirus | >40 | CT >40 was considered negative | |
| Mycoplasma pneumonia | >40 | CT >40 was considered negative | |
| Urine test | Glucose (GLU) | Norm mmol/L | - |
| Bilirubin (BIL) | Neg µmol/L | - | |
| Urobilinogen (URO) | Norm µmol/L | Normal ~ +/− | |
| PH value (PH) | 8 | 4.5–8.0 | |
| Specific gravity (SG) | 1.018 | 1.003–1.030 | |
| Occult Blood (BLD) | Neg mg/L | - | |
| Nitrite (NIT) | Neg | - | |
| Ketone body (KET) | Neg mmol/L | - | |
| Urinary protein (PRO.) | Neg g/L | - | |
| White blood cells (LEU) | Neg/µl | - | |
| Urinary red blood cells (RBC/HP) | 0.60/HP | 0.00–2.27 /HP | |
| Urine white blood cells (WBC/HP) | 0.90/HP | 0.00–2.73 /HP | |
| Pus cell (U_PC) | 0/µl | 0–9/µl |
Upon admission on July 13, 2024, the physical examination revealed scattered hemorrhagic rashes on both lower limbs. These rashes presented as a mixed distribution of petechiae and ecchymosis, slightly raised above the skin surface, and did not blanch upon pressure. The throat appeared congested, with mild enlargement of both tonsils. The liver was palpated 2 cm below the costal margin, and the spleen was palpated 3 cm below the costal margin, with no tenderness noted upon palpation. The joints of the limbs were normal, except for swelling in the right ankle joint, which had full range of motion. All other examination results were within normal limits. Given that it was the season for an outbreak of Mycoplasma pneumonia, intravenous cefotaxime combined with oral azithromycin was administered for anti-infection treatment after admission. Simultaneously, oral probiotics were given to regulate intestinal flora, along with vitamin C supplementation and appropriate fluid support therapy. On July 14, 2024, venous blood was collected for microbial blood culture testing at 6:30 a.m. On July 15, 2024, a bone marrow aspiration was performed to rule out hematological malignancies. The results of the bone marrow aspiration showed no abnormal cells or blood parasites, indicating a bone marrow picture consistent with secondary anemia. Other examination results were generally similar to those from the local hospital. On July 18, 2024, the blood culture report indicated that the child tested positive for Brucella, and it was discovered that the child’s family raised sheep. By combining clinical symptoms and auxiliary examination results, a diagnosis of brucellosis was confirmed. The treatment plan was adjusted to include the following: (1) Combined intravenous cefotaxime and oral doxycycline for anti-infection. (2) Oral probiotics to regulate intestinal flora. (3) Symptomatic treatment with oral vitamin D and calcium supplements. (4) Nutritional support therapy, including vitamin C supplementation and appropriate fluid replacement. Subsequently, the child’s condition gradually improved. Their general status was good, with no complaints of discomfort, and the child was discharged on 24 July.
Discussion
Brucellae are characterized as small, nonmotile, non-spore-forming, and slow-growing Gram-negative coccobacilli, measuring approximately 0.5–0.7 by 0.6–1.5 µm in size. They belong to the Brucellaceae family, which is classified within the alpha-2 subclass of the Proteobacteria phylum. This family also encompasses the genera Mycoplana, Pseudochrobactrum, Paenochrobactrum, Daeguia, Crabtreella, and Ochrobactrum[9].
The clinical manifestations of human brucellosis encompass a wide range of organ systems, typically presenting with nonspecific symptoms such as general malaise, arthralgia, night sweats, and insidious onset of fever. Osteo-articular involvement (including arthritis, sacroiliitis, or spondylitis) and genitourinary complications (such as orchitis, epididymitis, and abortion in pregnant women) are the most frequently observed manifestations[10]. Cardiovascular complications like endocarditis, myocarditis, pericarditis, or endarteritis are infrequent occurrences (3% of cases). However rare they may be, endocarditis accounts for 80% of deaths among affected individuals[11]. Aortic and iliac involvement primarily in the form of infected aneurysms is even more uncommon in cases of brucellosis[12]. Gastrointestinal symptoms are frequently observed in patients with brucellosis and may present as reduced appetite, nausea, vomiting, abdominal discomfort, diarrhea, and constipation. Additionally, hepatosplenomegaly is evident in approximately 50% of individuals affected by brucellosis. In the presence of gastrointestinal disturbances, it is crucial to consider potential complications. Respiratory manifestations of brucellosis are infrequent. They are predominantly documented as clinical cases encompassing pneumonia, pleurisy, pulmonary nodules, pulmonary granuloma, pleural effusion, lung abscess, thoracic abscess, pneumothorax, lymphadenopathy, and mediastinal involvement[13,14]. Neurobrucellosis is a rare complication of brucellosis, with an incidence ranging from 0.5% to 25% in patients with systemic brucellosis[15]. The first report of neurobrucellosis dates back to Hughes in 1896. Central nervous system involvement occurs in brucellosis, presenting as a serious and heterogeneous clinical manifestation encompassing encephalitis, meningoencephalitis, radiculitis, myelitis, peripheral and cranial neuropathies, intracranial and subarachnoid hemorrhage, as well as psychiatric manifestations[16–18]. The prevalence of brucellosis complicated with skin lesions varies between 5% and 17%[19]. Cutaneous manifestations are nonspecific and include urticaria-like papules and plaques, livedo reticularis, palmar erythema, erythema nodosum[20], cutaneous vasculitis[21–23], and cutaneous cysts[24]. Ocular involvement can occur in cases of brucellosis, although such presentations are rare[25]. All ocular structures may be affected by the disease. Reported cases have demonstrated various ocular and neurological manifestations associated with brucellosis, including uveitis, neuritis, optic neuritis, papilledema, keratitis, and other diverse presentations[26]. The most frequent manifestation is posterior uveitis[27]. Thyroiditis caused by Brucella has been documented, presenting with typical symptoms of thyroid inflammation, such as fever, chills, and neck swelling[28–30].
At present, the detection methods for brucellosis mainly include bacteriological, serological, and molecular biological techniques.
Blood cultures despite the challenges posed by the slow growth characteristics of Brucella organisms, laboratory safety concerns, and reduced sensitivity in prolonged disease and focal infections, isolation of the pathogen remains indisputable evidence for confirming the presence of brucellosis. Detection of Brucella in blood cultures helps confirm its presence in the disease at an early stage, especially when serological tests still show negative or low or borderline antibody titers[31]. Furthermore, the isolation of Brucella can provide a definitive diagnosis in patients who are not clinically suspected of infection but have been identified as carrying the pathogen in blood cultures obtained from routine examinations[32]. Currently, the automated blood culture systems predominantly utilized in laboratories include the Bactec 9000 series, Bactec FX series, and BacT/ALERT system developed by Becton Dickinson Company.
Serological diagnosis for brucellosis indirectly confirms exposure to the pathogen by examining the patient’s immune response for antibodies, rather than directly confirming the presence of microorganisms. Currently, serological methods include the Rose–Bangham test (RBT), the tube agglutination test (SAT), which is the most commonly employed serological assay for diagnosing B. abortus, B. melitensis, and B. suis infections; the 2-mercaptoethanol test (2-ME); the Coombs antiglobulin agglutination test and the Brucella Coombs gel test; the complement fixation test; enzyme-linked immunosorbent assay (ELISA); lateral flow immunochromatography (LFIA), chemiluminescence immunoassay, and time-resolved fluorescence resonance energy transfer detection; as well as fluorescence polarization immunoassay.
Molecular biological detection mainly includes nucleic acid amplification tests (NAATs) and genomic sequencing techniques. Among them, NAATs cover real-time polymerase chain reaction (PCR), quantitative reverse transcription PCR (RT-qPCR), multiplex real-time PCR (M-RT-PCR), and loop-mediated isothermal amplification, among others. Recently, researchers have developed a high-resolution melting-PCR method, which can rapidly screen and directly classify DNA into one of the 12 species within the Brucella genus[33]. Additionally, a droplet digital PCR technology has been established to precisely quantify the Brucella DNA load in whole blood samples and evaluate its significance in the diagnosis, prognosis, and treatment of human brucellosis[34]. Meanwhile, whole-genome sequencing, allele-based typing, and core genome single nucleotide polymorphism techniques have also been widely applied in brucellosis-related research[35,36].
The Brucella detection technology has achieved certain development to a certain extent. Recently, the combined rapid detection of anti-Brucella IgG/IgM can be achieved based on surface-enhanced Raman scattering-LFIA technology[37]. Researchers have discovered that the novel CRISPR/Cas12a probe can be used to rapidly identify Brucella and its species in vitro and on-site[38]. On the other hand, researchers are committed to identifying novel antigens for the diagnosis of brucellosis. Notable examples include periplasmic protein 26 (BP26)[39], multi-epitope fusion proteins[40], and various combinations of serum proteins[41].
In conclusion, the nonspecific symptoms of brucellosis frequently result in misdiagnosis or delayed diagnosis; however, early intervention can significantly mitigate the risk of complications, shorten the treatment duration, and enhance prognosis. It is advisable to conduct bacterial culture or nucleic acid testing for etiological examination. Serological screening tests should encompass RBT, GICA, or ELISA methodologies. Furthermore, SAT, CFT, or Coombs test may be utilized for serological confirmation. Nevertheless, these diagnostic methods possess certain limitations including time consumption and the potential occurrence of false negatives and false positives as well as relatively low sensitivity. Therefore, it is imperative to develop robust diagnostic assays for brucellosis to improve early detection and treatment outcomes of this disease. Furthermore, healthcare professionals are required to possess a thorough understanding of the clinical manifestations and diagnostic complexities associated with brucellosis in order to ensure accurate and timely diagnoses.
Footnotes
C.P., L.L., and T.L. contributed equally to this work and share first authorship.
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Published online 10 April 2025
Contributor Information
Chunsong Pang, Email: pangchunsong2023@163.com.
Lina Liu, Email: lln19880302@163.com.
Ting Liu, Email: liuting7572@163.com.
Nianzhu Zhang, Email: zhangnianzhu0318@foxmail.com.
Lifen Zhao, Email: lifenzhao18@163.com.
Ethical approval
This study was approved by the Ethics Committee of the Second Affiliated Hospital of Dalian Medical University.
Consent
Consent was obtained from the patient, and it is important to note that no patient privacy information has been included in this paper. Written informed consent was obtained from the patient’s parents/legal guardian for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Sources of funding
This research was funded by the Doctoral Research Start-Up Funding of the Second Affiliated Hospital of Dalian Medical University (DY2Y201801) and the Natural Science Foundation of Liaoning Province (2022-BS-254).
Author contributions
Writing – original draft, visualization: C.P.; formal analysis, writing – review and editing; L.L.; writing – review and editing, revise the manuscript: T.L.; resources, writing – review and editing, funding acquisition: N.Z.; resources, writing – review and editing, funding acquisition: L.Z. All authors have read and approved of the final manuscript.
Conflicts of interest disclosure
The authors declare that they have no competing interests.
Research registration unique identifying number (UIN)
Not applicable.
Guarantor
Lifen Zhao.
Provenance and peer review
The paper was not invited.
Data availability statement
The original contributions presented in the study are included in the article. For further inquiries, please contact the corresponding authors.
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References
- [1].Godfroid J, Al Dahouk S, Pappas G, et al. A “One Health” surveillance and control of brucellosis in developing countries: moving away from improvisation. Comp Immunol Microbiol Infect Dis 2013;36:241–48. [DOI] [PubMed] [Google Scholar]
- [2].Fredriksson-Ahomaa M. Wild boar: a reservoir of foodborne zoonoses. Foodborne Pathog Dis. 2019;16:153–65. [DOI] [PubMed] [Google Scholar]
- [3].Pappas G, Papadimitriou P, Akritidis N, et al. The new global map of human brucellosis. Lancet Infect Dis 2006;6:91–99. [DOI] [PubMed] [Google Scholar]
- [4].Liu Z, Gao L, Wang M, et al. Long ignored but making a comeback: a worldwide epidemiological evolution of human brucellosis. Emerg Microbes Infect 2024;13:2290839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Zheng R, Xie S, Lu X, et al. A systematic review and meta-analysis of epidemiology and clinical manifestations of human brucellosis in China. Biomed Res Int 2018;2018:5712920. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [6].Wang Y, Zhang W, Ke Y, et al. Human brucellosis, a heterogeneously distributed, delayed, and misdiagnosed disease in China. Clin Infect Dis 2013;56:750–51. [DOI] [PubMed] [Google Scholar]
- [7].Qin S, Lv D, Duan R, et al. Case report: a case of brucellosis misdiagnosed as coronavirus disease 2019/influenza in China. Front Public Health 2023;11:1186800. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [8].Adetunji SA, Ramirez G, Foster MJ, et al. A systematic review and meta-analysis of the prevalence of osteoarticular brucellosis. PLoS Negl Trop Dis 2019;13:e0007112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Whatmore AM, Koylass MS, Muchowski J, et al. Extended multilocus sequence analysis to describe the global population structure of the genus Brucella: phylogeography and relationship to biovars. Front Microbiol 2016;7:2049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Bosilkovski M, Krteva L, Caparoska S, et al. Osteoarticular involvement in brucellosis: study of 196 cases in the Republic of Macedonia. Croat Med J 2004;45:727–33. [PubMed] [Google Scholar]
- [11].Li X, Wang T, Wang Y, et al. Short- and long-term follow-up outcomes of patients with Brucella endocarditis: a systematic review of 207 Brucella endocarditis cases. Bioengineered 2021;12:5162–72. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12].Cascio A, De Caridi G, Lentini S, et al. Involvement of the aorta in brucellosis: the forgotten, life-threatening complication. A systematic review. Vector Borne Zoonotic Dis 2012;12:827–40. [DOI] [PubMed] [Google Scholar]
- [13].Pappas G, Bosilkovski M, Akritidis N, et al. Brucellosis and the respiratory system. Clin Infect Dis 2003;37:e95–9. [DOI] [PubMed] [Google Scholar]
- [14].Olukman Ö. Pulmonary involvement in childhood brucellosis: a case report. Vector Borne Zoonotic Dis. 2008;8:245–48. [DOI] [PubMed] [Google Scholar]
- [15].Dreshaj S, Shala N, Dreshaj G, et al. Clinical manifestations in 82 neurobrucellosis patients from Kosovo. Mater Sociomed 2016;28:408–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Gul HC, Erdem H, Gorenek L, et al. Management of neurobrucellosis: an assessment of 11 cases. Intern Med 2008;47:995–1001. [DOI] [PubMed] [Google Scholar]
- [17].Yetkin MA, Bulut C, Erdinc FS, et al. Evaluation of the clinical presentations in neurobrucellosis. Int J Infect Dis 2006;10:446–52. [DOI] [PubMed] [Google Scholar]
- [18].Karsen H, Akdeniz H, Kasim Karahocagil M, et al. Toxic-febrile neurobrucellosis, clinical findings and outcome of treatment of four cases based on our experience. Scand J Infect Dis 2007;39:990–95. [DOI] [PubMed] [Google Scholar]
- [19].Jin M, Fan Z, Gao R, et al. Research progress on complications of brucellosis. Front Cell Infect Microbiol 2023;13:1136674. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [20].Mazokopakis E, Christias E, Kofteridis D. Acute brucellosis presenting with erythema nodosum. Eur J Epidemiol. 2003;18:913–15. [DOI] [PubMed] [Google Scholar]
- [21].Massasso D, Gibson K. Brucellosis mimicking Henoch-Schönlein purpura. Med J Aust. 2007;186:602–03. [DOI] [PubMed] [Google Scholar]
- [22].Catakli T, Arikan FI, Acar B, et al. Cutaneous vasculitis in a patient with acute brucellosis. Clin Exp Dermatol 2009;34:e387–8. [DOI] [PubMed] [Google Scholar]
- [23].Albayrak A, Kadi M, Döner N, et al. Two brucellosis cases with vasculitic skin lesions. Rheumatol Int 2014;34:575–76. [DOI] [PubMed] [Google Scholar]
- [24].Raptis L, Pappas G, Akritidis N. A cutaneous cyst caused by brucellosis with a negative serological test. Int J Infect Dis. 2007;11:82–83. [DOI] [PubMed] [Google Scholar]
- [25].Rolando I, Vilchez G, Olarte L, et al. Brucellar uveitis: intraocular fluids and biopsy studies. Int J Infect Dis 2009;13:e206–11. [DOI] [PubMed] [Google Scholar]
- [26].Puig Solanes M, Heatley J, Arenas F, et al. Ocular complications in brucellosis. Am J Ophthalmol 1953;36:675–89. [DOI] [PubMed] [Google Scholar]
- [27].Rolando I, Olarte L, Vilchez G, et al. Ocular manifestations associated with brucellosis: a 26-year experience in Peru. Clin Infect Dis 2008;46:1338–45. [DOI] [PubMed] [Google Scholar]
- [28].Mousa AR, Al-Mudallal DS, Marafie A. Brucella thyroiditis. J Infect. 1989;19:287–88. [DOI] [PubMed] [Google Scholar]
- [29].Azizi F, Katchoui A. Brucella infection of the thyroid gland. Thyroid. 1996;6:461–63. [DOI] [PubMed] [Google Scholar]
- [30].von Graevenitz A, Colla F. Thyroiditis due to Brucella melitensis–report of two cases. Infection. 1990;18:179–80. [DOI] [PubMed] [Google Scholar]
- [31].Shemesh AA, Yagupsky P. Limitations of the standard agglutination test for detecting patients with Brucella melitensis bacteremia. Vector Borne Zoonotic Dis. 2011;11:1599–601. [DOI] [PubMed] [Google Scholar]
- [32].Yagupsky P. Detection of Brucella melitensis by BACTEC NR660 blood culture system. J Clin Microbiol. 1994;32:1899–901. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [33].Girault G, Perrot L, Mick V, et al. High-resolution melting PCR as rapid genotyping tool for Brucella species. Microorganisms 2022;10:336. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [34].Liu J, Song Z, Ta N, et al. Development and evaluation of a droplet digital PCR assay to detect Brucella in human whole blood. PLoS Negl Trop Dis 2023;17:e0011367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [35].Akar K, Brangsch H, Jamil T, et al. Genomic analysis of Brucella isolates from animals and humans, Türkiye, 2010 to 2020. Euro Surveill 2024;29:2400105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [36].An C, Nie S, Luo B, et al. Multiple Brucella melitensis lineages are driving the human brucellosis epidemic in Shaanxi Province, China: evidence from whole genome sequencing-based analysis. Front Cell Infect Microbiol 2024;14:1452143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [37].Zhang Y, Li Z, Zhu A, et al. Combined and rapid detection of anti-Brucella IgG/IgM in clinical samples based on surface-enhanced Raman scattering-lateral flow immunochromatography. J Mater Chem B 2024;12:11012–24. [DOI] [PubMed] [Google Scholar]
- [38].Zhang Y, Lyu Y, Wang D, et al. Rapid identification of Brucella genus and species in silico and on-site using novel probes with CRISPR/Cas12a. Microorganisms 2024;12:1018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [39].Xie Y, Lin S, Guo L, et al. Development and evaluation of the recombinant BP26 protein-based C-ELISA for human brucellosis diagnosis. Front Microbiol 2025;15:1516915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [40].Wu Q, Yuan Y, Guo L, et al. Preparation and application of a Brucella multiepitope fusion protein based on bioinformatics and Tandem Mass Tag-based proteomics technology. Front Immunol 2015;15:1509534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [41].Li X, Wang B, Li X. Analysis and validation of serum biomarkers in brucellosis patients through proteomics and bioinformatics. Front Cell Infect Microbiol. 2025;14:1446339. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
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Data Availability Statement
The original contributions presented in the study are included in the article. For further inquiries, please contact the corresponding authors.