Abstract
Background
Human brucellosis remains a significant public health concern in northeastern Türkiye and is among the leading causes of visits to infectious disease clinics. In this study, we aimed to describe the clinical characteristics and laboratory findings of patients with brucellosis in high-burden regions, with a particular focus on identifying diagnostic indicators of complicated disease.
Methods
We conducted a retrospective study of patients with positive serology for brucellosis who were admitted to Harakani State Hospital in Kars between September 2022 and December 2023. Patients were grouped based on whether they had complicated or uncomplicated brucellosis. Potential diagnostic indicators of complicated brucellosis were identified using univariate and multivariate logistic regression.
Results
The study included 97 patients with a median age of 42 years; 41.2% were female. Rose Bengal and Brucellacapt/Coombs Wright (BC/CW) tests were positive in 94.8% and 98.9% of patients, respectively. Cases were classified as acute (55.7%), subacute (28.9%), and chronic (15.5%). Complicated brucellosis was identified in 33 patients (34%). In univariate analyses, complicated brucellosis was associated with thrombocytopenia (OR: 5.53; 95% CI: 1.01–30.29), elevated C-reactive protein (CRP) (OR: 5.9; 95% CI: 2.31–15.15), elevated erythrocyte sedimentation rate (ESR) (OR: 3.23; 95% CI: 1.14–9.18), and a BC/CW titer >1:320 (OR: 2.76; 95% CI: 1.13–6.72). Elevated CRP levels were observed in 43.3% of patients and remained independently associated with complicated brucellosis in multivariable analysis (adjusted OR: 4.36; 95% CI: 1.60–11.87). Relapse occurred in 13 patients (13.4%) within six months.
Conclusions
The presence of thrombocytopenia, high CRP and ESR levels, and high BC/CW titers was a diagnostic indicator of complicated brucellosis. Early identification of high-risk patients using combined clinical and laboratory parameters may improve follow-up strategies and clinical outcomes.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1186/s12879-026-13983-3.
Keywords: Brucellacapt, Brucellosis, Complicated brucellosis, Coombs Wright, Focal involvement
Introduction
Brucellosis is one of the most common zoonotic diseases worldwide, with approximately 500,000 new cases reported annually. Countries with the highest annual incidence of human brucellosis (> 100 cases per million population) include Syria, Mongolia, Kyrgyzstan, Iraq, Iran, Saudi Arabia, Tajikistan, North Macedonia, Kazakhstan, and Türkiye [1]. Despite substantial progress achieved through national control programs, brucellosis remains endemic in Türkiye. National surveillance data showed that the incidence increased from 5.3 to 12.3 cases per 100,000 population between 2015 and 2019 [2]. Consistent with these findings, a recent meta-analysis reported a pooled human brucellosis seroprevalence of 4.5%, highlighting the ongoing burden of the disease, particularly among rural populations and high-risk occupational groups [3].
Brucellosis is transmitted to humans through the consumption of contaminated, unpasteurized dairy products or by contact with tissues or fluids of infected animals. It is also an occupational disease among shepherds, veterinarians, and microbiology laboratory personnel [4]. There are significant challenges in diagnosing brucellosis, particularly in selecting appropriate diagnostic methods and identifying patients who require further evaluation for complicated disease that may require prolonged treatment. Kars, a province in northeastern Türkiye with one of the highest brucellosis incidence rates in the country, provides a valuable opportunity to identify challenges in disease management and improve clinical practices.
This study aimed to assess the number of serological tests used for diagnosis and their positivity in an endemic region, describe the clinical characteristics and laboratory findings of patients with brucellosis, analyze the side effects of treatment, and identify diagnostic indicators of complicated brucellosis.
Methods
Study design
This retrospective study was conducted between September 2022 and December 2023 at Harakani State Hospital (HSH) in Kars, a province in northeastern Türkiye. There were two microbiology laboratories in Kars, located at HSH and Kafkas University School of Medicine Hospital (KUH). During the study period, samples from district state hospitals and family health centers throughout Kars were sent to the microbiology laboratory at HSH, so most Brucella serology samples in the province were analyzed there. KUH did not have an infectious disease (ID) outpatient clinic during the study period.
This study evaluated the number of Brucella serology tests conducted at the HSH microbiology laboratory over a 15-month period. Patients with positive Brucella serology results who visited the HSH ID outpatient clinic, as well as those referred from other regional hospitals, were included in the study for further evaluation. Patients diagnosed with brucellosis were included in further analysis. This study was approved by the Kafkas University Clinical Research Ethics Committee (protocol number: 80576354-050-99/366).
Study population
The inclusion criteria were as follows:
Adult patients (18 years of age or older),
Positive results in one of the following serological tests: Brucellacapt (BC) ≥ 1:160, Coombs Wright (CW) ≥ 1:160, Brucella abortus immunoglobulin G (IgG) in cerebrospinal fluid (CSF) or growth of Brucella spp. in blood or sterile body fluid cultures,
Those who had not received treatment for brucellosis within the six months prior to application,
Those who have completed the prescribed treatment process,
Those with positive Brucella serology who underwent testing at hospitals other than HSH and subsequently sought treatment at our outpatient clinic.
The excluded patients were those who transferred from another hospital after initiating treatment, those who did not seek treatment after a positive Brucella serology result, those who were lost to follow-up without receiving treatment for a sufficient time (at least six weeks), and those who received treatment for brucellosis in the six months before application.
Data on patients’ demographic characteristics (age, sex, place of residence, occupation, and potential routes of brucellosis transmission), comorbidities, clinical manifestations, and physical examination findings were collected from medical records. Initial laboratory evaluations included a complete blood count, alanine aminotransferase (ALT), renal function tests, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).
Microbiological study
The Brucella slide agglutination test (Rose Bengal, RB; BioMedica Diagnostics, Canada) was performed on patients with at least one symptom of brucellosis, including arthralgia, fatigue, sweating, and weight loss. As part of the routine diagnostic algorithm, the BC test (Metser Lab Biological Products, Türkiye) was performed in all patients with a positive RB test, and a BC titer ≥ 1:160 was considered positive. In patients with high clinical suspicion of brucellosis, samples were referred to the Microbiology Reference Laboratories of the General Directorate of Public Health in Ankara for CW testing when the RB test was positive, but the BC test was negative. Likewise, when the RB test was negative in a patient with high clinical suspicion for brucellosis, the BC test was performed, and patients with negative BC results were further evaluated with CW testing.
Investigation of complicated brucellosis
Complications of brucellosis were not routinely investigated in patients with the disease. If the patient had severe back or hip pain, contrast-enhanced magnetic resonance imaging was requested to evaluate for spondylodiscitis and sacroiliitis. Diagnosis of peripheral arthritis was based on clinical findings of limited joint motion, redness, and swelling. Blood or tissue culture was not routinely performed. Arthrocentesis was performed on patients with arthritis of large joints, and blood cultures were collected from patients with acute fever. Scrotal ultrasonography was performed on patients presenting with scrotal pain or swelling. Individuals exhibiting symptoms such as neck stiffness, confusion, depression, personality alterations, or neurological manifestations underwent a lumbar puncture. Subsequently, B. abortus IgG levels in CSF were measured. Thyroid function tests were performed on patients exhibiting sensitive thyroid tissue.
Treatment schedules
The patients were initiated on dual or triple combination antibiotic therapies. The preferred antibiotic regimens were doxycycline 100 mg twice daily, rifampin 600 mg once daily, intramuscular streptomycin 1000 mg once daily, intramuscular or intravenous gentamicin 5 mg/kg once daily, ciprofloxacin 750 mg twice daily, co-trimoxazole 800 mg/160 mg twice daily, and intravenous ceftriaxone 2 g twice daily. Patients were monitored every 2 to 3 weeks, and antibiotic side effects were recorded.
Definitions
Patients were divided into three groups based on the duration of symptoms before admission to the hospital:
Acute brucellosis: <2 months.
Subacute brucellosis: 2–12 months.
Chronic brucellosis: >12 months.
The presence of focal involvement was defined as complicated brucellosis [5]. Relapse was defined as the recurrence of symptoms or an increase in previously declining agglutinating antibody titers within six months after treatment [5, 6]. Thrombocytopenia was defined as a platelet count < 150 × 10⁹/L. High ESR was defined as values exceeding half the patient’s age in males and half the patient’s age plus 10 in females.
Statistical analysis
Data analyses were performed using the Jamovi software version 2.5 (The Jamovi project; retrieved from https://www.jamovi.org). For continuous variables with non-normal distributions, medians and interquartile ranges (IQRs) were calculated. The chi-square test or Fisher’s exact test was used for categorical variables. Bonferroni correction was applied for multiple comparisons. The t-test was used as a parametric test for continuous variables, and the Mann-Whitney U test was used as a non-parametric test. The Kruskal-Wallis test was used to compare more than two continuous variables with a non-normal distribution. A p-value of < 0.05 was considered statistically significant. The study calculated odds ratios (ORs) and 95% confidence intervals (CIs) for possible diagnostic indicators of complicated brucellosis using univariate logistic regression. Variables with a p value < 0.20 in the univariable analysis were considered for inclusion in the multivariable logistic regression model. Final variable selection was guided by both statistical significance and clinical relevance, with particular attention to avoiding collinearity, overadjustment, and redundancy among predictors.
Results
The microbiology laboratory at HSH analyzed a total of 8462 samples for Brucella serology (RB and BC) between September 2022 and December 2023, comprising 7192 patients (6310 adults and 882 children). The positivity rate for the RB test was 6.3% (483 of 7578 samples) and 27.9% (247 of 884 samples) for the BC test. Of the positive BC tests (belonging to 188 patients), 164 were from adult patients with a median age of 42.2 years, and 56.7% (n = 93) of the adult patients were male (Fig. 1).
Fig. 1.

Study design
The number of adult patients exhibiting at least one symptom of brucellosis who were referred to the HSH ID outpatient clinic was 1013. We excluded 862 patients with negative serology or repetitive testing and 65 patients with positive serology who did not meet the inclusion criteria. Eleven patients with positive test results from other microbiology laboratories were included in this study, along with 97 patients in total (Supplementary Fig. 1). The median age of the patients was 42 years (IQR: 33–52), and 58.8% (n = 57) were male. The most common comorbidities were hypertension (12.4%), diabetes mellitus (7.2%), and pulmonary disease (6.2%). Out of 97 cases, 72.2% lived in rural areas, 86.6% worked in husbandry, and 58.8% consumed unpasteurized dairy products. Thirty-six patients (37.1%) had a history of brucellosis at least six months prior to their inclusion in the study, and fifteen (15.5%) had a family history of brucellosis.
Based on symptom duration before hospital admission, 54 (55.7%) cases were classified as acute, 28 (28.9%) as subacute, and 15 (15.5%) as chronic. The most common symptoms reported at presentation were fatigue (82.5%), arthralgia (77.3%), and sweating (69.1%), with no statistical differences between the groups. The patients’ symptoms are outlined in Table 1.
Table 1.
Symptoms and laboratory findings of brucellosis cases
| Symptoms n (%) |
Acute brucellosis n = 54 |
Subacute brucellosis n = 28 |
Chronic brucellosis n = 15 |
Total n = 97 |
p |
|---|---|---|---|---|---|
| Fever | 29 (53.7) | 16 (57.1) | 8 (53.3) | 53 (54.6) | 0.9 |
| Sweating | 38 (70.4) | 21 (75) | 8 (53.3) | 67 (69.1) | 0.3 |
| Fatigue | 43 (79.6) | 26 (92.9) | 11 (73.3) | 80 (82.5) | 0.1 |
| Loss of appetite | 23 (42.6) | 19 (67.9) | 5 (33.3) | 47 (48.5) | 0.04 |
| Arthralgia | 39 (72.2) | 22 (78.6) | 14 (93.3) | 75 (77.3) | 0.2 |
| Back pain | 33 (61.1) | 20 (71.4) | 7 (46.7) | 60 (61.9) | 0.2 |
| Myalgia | 21 (38.9) | 13 (46.4) | 7 (46.7) | 41 (42.3) | 0.7 |
| Hip pain | 22 (40.7) | 14 (50) | 6 (40) | 42 (43.3) | 0.6 |
| Weight loss | 20 (37) | 17 (60.7) | 3 (20) | 40 (41.2) | 0.02 |
| Nausea | 18 (33.3) | 9 (32.1) | 1 (6.7) | 28 (28.9) | 0.1 |
| Headache | 22 (40.7) | 15 (53.6) | 7 (46.7) | 44 (45.4) | 0.5 |
| Laboratory Findings | |||||
| Leukocytosis‡ | 5 (9.3) | 2 (7.1) | 3 (20) | 10 (10.3) | 0.3 |
| Thrombocytopenia‡ | 4 (7.4) | 2 (7.1) | 1 (6.7) | 7 (7.2) | 0.9 |
| ALT > 33 U/L | 18 (33.3) | 6 (21.4) | 1 (6.7) | 25 (25.8) | 0.09 |
| CRP > 5 mg/L | 27 (50.9) | 10 (37) | 5 (33.3) | 42 (43.3) | 0.3 |
| Median CRP (IQR) | 6.29 (1.5–21.6) | 3 (1.27–20.7) | 2.9 (0.7–7.16) | 4.24 (1.2–19.7) | 0.2 |
| ESR elevation | 13 (27.1) | 5 (22.7) | 2 (16.7) | 20 (24.4) | 0.7 |
| Median ESR (IQR) | 11.5 (8–21.5) | 12.5 (7.25–18.8) | 11 (7.5–16.3) | 12 (8–20.8) | 0.7 |
ALT: Alanine aminotransferase, CRP: C-reactive protein, ESR: Erythrocyte sedimentation rate, IQR: Interquartile range.‡Leukocytosis > 10,000/mm3; thrombocytopenia < 150,000 /mm3
The most common laboratory findings in patients with brucellosis were high CRP levels (> 5 mg/L; 44.2%), elevated ALT levels (> 33 U/L; 25.8%), and elevated ESR (24.4%). Although no statistically significant differences were observed, high levels of CRP, ESR, and ALT were more common in acute cases (Table 1). Rose Bengal tests were positive in 94.8% (n = 92) of patients, and BC or CW tests were positive in 98.9% (n = 96). Seven patients had positive RB and negative BC but positive CW tests. Four patients had negative RB and BC but positive CW tests. One neurobrucellosis case had negative RB, BC, and CW tests; only B. abortus IgG in CSF was positive. Thirty-three patients (34%) had BC or CW titers higher than 1:320. Complicated brucellosis, sweating, elevated ALT, and high CRP were more commonly observed among patients with high titers (> 1:320) in BC or CW (p < 0.05). Blood cultures were obtained from 13 patients with acute fever, but all were sterile. Brucellosis grew in the synovial fluid culture of a patient with knee arthritis.
Thirty-three patients (34%) were diagnosed with complicated brucellosis. The most common type of focal involvement was osteoarticular (23.7%), followed by epididymo-orchitis (8.2%). Osteoarticular involvement included spondylitis (13.4%), peripheral arthritis (7.2%), and sacroiliitis (6.2%). All patients with epididymo-orchitis were acute cases. CRP and ESR levels were significantly higher in patients with complicated brucellosis (p < 0.001). High CRP levels (> 5 mg/L) were observed in 71.9% of patients with complicated brucellosis, compared with 30.2% of patients with uncomplicated brucellosis (p < 0.001). An elevated ESR was observed in 39.3% of patients with complicated brucellosis and 16.7% with uncomplicated brucellosis (p = 0.02). Univariate logistic regression analyses revealed that diagnostic indicators of complicated brucellosis included thrombocytopenia (OR: 5.53; 95% CI: 1.01–30.29), high CRP (OR: 5.9; 95% CI: 2.31–15.15), elevated ESR (OR: 3.23; 95% CI: 1.14–9.18), and BC/CW titer > 1:320 (OR: 2.76; 95% CI: 1.13–6.72). High CRP (> 5 mg/L), observed in 43.3% of patients, was an independent predictor of focal involvement, increasing the odds more than fourfold in the adjusted model (adjusted OR 4.36, 95% CI 1.60–11.87) (Table 2).
Table 2.
Logistic regression analyses of potential diagnostic indicators for complicated brucellosis
| Diagnostic Indicators | Complicated disease N = 33 (%) |
Uncomplicated disease N = 64 (%) |
Univariate analyses | Multivariate analyses | |||
|---|---|---|---|---|---|---|---|
| OR | 95% CI | p | Adjusted OR | 95% CI | |||
| Age (years), median (IQR) | 43 (36–45) | 41 (29.8–54.5) | 1.00 | 0.97–1.03 | 0.8 | ||
| Delayed treatment (days), median (IQR) | 2 (0–4) | 1.5 (0–8.5) | 1.03 | 0.97–1.07 | 0.2 | ||
| Sex (male) | 20 (60.6) | 37 (57.8) | 1.12 | 0.47–2.64 | 0.7 | ||
| Previous brucellosis | 10 (30.3) | 26 (40.6) | 0.6 | 0.2–1.55 | 0.3 | ||
| Family history of brucellosis | 5 (15.2) | 10 (15.6) | 0.9 | 0.3–3.1 | 0.9 | ||
| Symptoms | |||||||
| Fever | 20 (60.6) | 33 (51.6) | 1.45 | 0.61–3.39 | 0.3 | ||
| Sweating | 26 (78.8) | 41 (64.1) | 2.08 | 0.78–5.54 | 0.1 | * | |
| Fatigue | 29 (87.9) | 51 (79.7) | 1.85 | 0.55–6.2 | 0.3 | ||
| Loss of appetite | 17 (51.5) | 30 (46.9) | 1.2 | 0.51–2.79 | 0.6 | ||
| Arthralgia | 24 (72.7) | 51 (79.7) | 0.68 | 0.25–1.81 | 0.4 | ||
| Back pain | 19 (57.6) | 41 (64.1) | 0.76 | 0.32–1.8 | 0.5 | ||
| Myalgia | 11 (33.3) | 30 (46.9) | 0.56 | 0.23–1.36 | 0.2 | ||
| Hip pain | 15 (45.5) | 27 (42.2) | 1.14 | 0.49–2.66 | 0.7 | ||
| Weight loss | 14 (42.4) | 26 (40.6) | 1.08 | 0.46–2.52 | 0.8 | ||
| Nausea | 13 (39.4) | 15 (23.4) | 2.12 | 0.85–5.26 | 0.1 | * | |
| Headache | 14 (42.4) | 30 (46.9) | 0.83 | 0.35–1.95 | 0.6 | ||
| Scrotal pain | 8 (40) | 0 | 51 | 2.74–94 | < 0.001 | * | |
| Laboratory findings | |||||||
| Leukocytosis‡ | 4 (12.1) | 6 (9.4) | 1.33 | 0.34–5.1 | 0.6 | ||
| Thrombocytopenia‡ | 5 (15.2) | 2 (3.1) | 5.53 | 1.01–30.29 | 0.04 | 4.75 | 0.73–30.65 |
| ALT > 33 U/L | 10 (30.3) | 15 (23.4) | 1.42 | 0.55–3.64 | 0.4 | ||
| CRP > 5 mg/L | 23 (71.9) | 19 (30.2) | 5.9 | 2.31–15.15 | < 0.001 | 4.36 | 1.60-11.87 |
| ESR elevation | 11 (39.3) | 9 (16.7) | 3.23 | 1.14–9.18 | 0.02 | * | |
| BC or CW titer > 1/320 | 16 (50) | 17 (26.6) | 2.76 | 1.13–6.72 | 0.02 | 1.88 | 0.68–5.16 |
CI: Confidence interval, OR: Odds ratio, ALT: Alanine aminotransferase, CRP: C-reactive protein, ESR: Erythrocyte sedimentation rate, IQR: Interquartile range, BC: Brucella capture, CW: Coombs Wright‡Leukocytosis > 10,000/mm3; thrombocytopenia < 150,000 /mm3*Variables with p < 0.20 in univariate analysis were evaluated for inclusion in the multivariable model. Nonspecific symptoms (sweating and nausea), variables representing focal disease manifestations (scrotal pain), and highly correlated inflammatory markers (ESR and CRP) were not entered simultaneously into the model
Thirteen patients (13.4%) experienced a relapse of the disease within six months after the treatment ended. Although no statistically significant difference was found, the relapse rate was higher in patients with complicated brucellosis than in patients with uncomplicated brucellosis (18.2% vs. 10.9%).
The median time from hospital admission to the initiation of treatment was 2 days (IQR: 0–7). The most preferred combination of antibiotics was doxycycline + rifampin (84.5%), followed by doxycycline + rifampin + streptomycin (9.3%) (Supplementary Table 1). The median duration of therapy was 8 weeks (IQR: 6–12). Side effects related to antibiotic treatment were observed in 28 patients (28.9%). Reported side effects included nausea or vomiting (n = 12), epigastric pain (n = 6), diarrhea (n = 4), rash (n = 3), glossitis (n = 2), dysphagia/esophagitis (n = 2), and hepatotoxicity (n = 1). The median duration to change treatment due to side effects was 14 days (IQR: 14–28).
Discussion
Brucellosis causes substantial economic losses in both public health, such as workforce reduction and treatment costs, and animal production, including abortion and decreased milk production. Brucellosis remains an endemic disease in Türkiye, particularly in provinces where animal husbandry is a major source of income. According to the Ministry of Health report, Kars had the third-highest incidence rate among these provinces in 2019, with 109.7 cases per 100,000 population [2]. Over a 15-month period, patients with brucellosis who visited the ID outpatient clinic in Kars were included in the study. Complicated brucellosis was identified in 34% of the patients. Thrombocytopenia, elevated CRP and ESR levels, and high BC or CW titers were found to be diagnostic indicators of complicated disease.
Human brucellosis most commonly occurs in individuals living in areas where the disease is endemic in animals, such as cattle, goats, and sheep. In a study, a total of 400 sera were obtained from 16 different flocks of sheep from various regions of Kars, which had a history of abortion and were not vaccinated against Brucella. The serum agglutination test was found to be positive in 36.7% of the sera [7]. In another study, milk samples were collected from 334 cows that had a history of abortion or shared the same barn in urban and rural areas of Erzurum, neighboring Kars. Polymerase chain reaction analyses revealed that the B. abortus gene was detected in 273 (82%) of the milk samples [8]. Complete prevention of brucellosis in humans is possible by preventing the infection in animals. Deficiencies in veterinary support services and animal husbandry practices in Türkiye have facilitated the spread of infection. An animal vaccination project was launched in 2012 with the goal of eradication, but vaccination coverage has not yet reached the target level [2].
Serological assays are the most commonly used tests in the laboratory diagnosis of brucellosis. Serologic results should be interpreted together with clinical presentation and epidemiologic data. The RB test is an optimal screening tool due to its ease of application, rapid turnaround time, high sensitivity, and cost-effectiveness. Concerns have been raised regarding the performance of RB, including its low sensitivity in chronic cases and its low specificity in endemic regions [9, 10]. In our study, five patients with brucellosis had negative RB results. A positive result should be confirmed by more specific tests, especially in areas where brucellosis is endemic. The CW test detects incomplete, blocking, or non-agglutinating IgG antibodies, making it suitable for complicated and chronic cases [11]. The BC is based on an immunocapture agglutination technique and exhibits diagnostic effectiveness similar to that of the CW test [12]. In our study, 98.9% of patients had positive BC or CW test results. Enzyme-linked immunosorbent assay is another option for complicated, localized, and chronic cases. Moreover, the enzyme-linked immunosorbent assay can be used for the serodiagnosis of neurobrucellosis in CSF samples [13]. In our study, RB, BC, and CW tests were negative in a case of neurobrucellosis; only Brucella IgG was positive in CSF. It is important to recognize that false-positive and false-negative test results may occur, particularly in endemic regions. Therefore, additional serological tests should be performed to confirm or exclude the diagnosis.
In a meta-analysis of 57 studies, the most common clinical symptoms of brucellosis in adults were malaise (81%), fever (73%), and arthralgia (65%) [14]. Another meta-analysis found that fever (99%) was the most common clinical symptom, followed by muscle pain (76%) and fatigue (64%); leukocytosis, anemia, and thrombocytopenia were the common abnormal laboratory tests [15]. The most common symptoms in our study were fatigue and arthralgia; however, fever was observed in approximately 50% of patients. Variations in symptoms and laboratory characteristics among patients across studies may be ascribed to factors such as symptom duration or focal involvement. In a retrospective study, the most observed symptoms in acute cases included lack of appetite, weight loss, fever, cough, and splenomegaly [16]. Similarly, in our study, lack of appetite and weight loss were observed most frequently in acute cases.
Previous studies have reported the prevalence of complicated brucellosis ranging from 36% to 90% [16, 17]. Older age, agricultural occupation, underlying comorbidities, delayed diagnosis, subacute or chronic disease presentation, musculoskeletal symptoms, elevated leukocyte and neutrophil counts, and increased inflammatory markers, particularly CRP and ESR, have been associated with complicated brucellosis in recent studies [18–21]. In our study, thrombocytopenia, high CRP levels (> 5 mg/L), elevated ESR, and high BC/CW titers were associated with complicated brucellosis. Based on the multivariable analysis, high CRP levels may help clinicians more effectively identify patients at increased risk of complicated brucellosis, who may require closer monitoring and extended treatment.
The ability of Brucella species to survive within macrophages and thereby prevent the host from accessing them may explain relapse and increasing chronicity. Relapse occurs in 5% to 30% of patients, usually within the first 6 months after the initial infection [22]. The relapse rate was 13.4% in our study.
Our study has several limitations. First, the diagnostic evaluation was based primarily on the serological tests available at our institution, namely the Rose Bengal and Brucellacapt assays. Culture confirmation was not performed systematically in all patients, and blood cultures were generally obtained only from patients presenting with acute febrile illness. Second, imaging studies were performed according to clinical indications; therefore, asymptomatic or subclinical focal involvement may have been underrecognized. Finally, the geographically dispersed population created challenges in maintaining continuity of diagnostic evaluation, follow-up, and treatment. Consequently, patients who did not complete the diagnostic or treatment process could not be included in the final analysis, potentially limiting the generalizability of our findings.
Conclusions
Brucellosis continues to pose a substantial public health burden in northeastern Türkiye. Our findings suggest that thrombocytopenia, elevated CRP and ESR levels, and high BC/CW titers may serve as useful indicators of complicated disease. Recognition of these factors may improve risk stratification and facilitate earlier identification of patients requiring closer evaluation for focal involvement and other complications. Broader availability of serological diagnostic tools in endemic regions may contribute to more timely diagnosis and treatment.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
None.
Abbreviations
- ALT
Alanine aminotransferase
- BC
Brucellacapt
- CI
Confidence interval
- CRP
C-reactive protein
- CSF
Cerebrospinal fluid
- CW
Coombs Wright
- ESR
Erythrocyte sedimentation rate
- HSH
Harakani State Hospital
- ID
Infectious disease
- IgG
Immunoglobulin G
- IQRs
Interquartile ranges
- KUH
Kafkas University School of Medicine Hospital
- OR
Odds ratio
Author contributions
Concept – Ö.A.; Design – Ö.A.; Supervision – Ö.A.; Materials – B.Ç., Ö.A.; Data Collection and/or Processing – Ö.A., B.Ç.; Analysis and/or Interpretation – Ö.A.; Literature Review – Ö.A.; Writer – Ö.A.; Critical Reviews – Ö.A., B.Ç.
Funding
The authors declared that this study has received no financial support.
Data availability
The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.
Declarations
Ethics approval and consent to participate
This study was approved by Kafkas University Clinical Research Ethics Committee on 31.01.2024 with decision number 80576354-050-99/366, and the research strictly adhered to the ethical standards of the World Medical Association Declaration of Helsinki. Due to the retrospective design of the study, the requirement for informed consent was waived by the ethics committee.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.
