A total of 13 cases of brucellosis were identified in the above 58-month study period. The clinical details of the patients were summarized in Table 1. Out of the 13 patients, 7 (53.8%) of the patients were male, 6 (46.2%) were female, with age ranging from 29 to 73 years old (median age: 51 years). Five patients (38.5%) came from Guangdong province, and eight patients (61.5%) came from other provinces including Heilongjiang, Inner Mongolia, Fujian, Henan, and Shanxi. The commonest risk factors of acquisition were from consumption of placenta of goat (4 patients, 30.8%) and undercooked beef or goat (4 patients, 30.8%). Other risk factors included handling of animal meat (3 patients, 21.3%) and direct goat contact (3 patients, 21.3%). However, no definite risk factors were identified in the remaining two patients (15.4%). Further statistical analysis revealed that patients from Guangdong province were more likely to have prior handling of animal meat (60.0% vs 0.0%, p = 0.012) and consumption of goat placenta (80.0% vs 0.0%, p = 0.002) when compared with patients from other provinces (Table 2).
Table 1: Summary of the clinical features of the 13 patients with brucellosis.
|
Case
|
Sex/Age
|
Occupation
|
Home town
|
Risk factor(s)
|
Presentation
|
Clinical findings
|
Complication
|
Clinical specimen with positive culture
|
Titer of Brucella Antibody
|
Treatment
|
|
1
|
F/29y
|
Clerk
|
Henan
|
Contacted goat
|
Left hip pain for one month
|
Osteoarticular involvement
|
Arthritis
|
Joint fluid
|
Nil
|
Doxycycline×3 months+Rifampin×3 months+Gentamicin×14 days
|
|
2
|
M/64y
|
Retired farmer
|
Heilongjiang
|
Contacted goat
|
Fever, night sweat and urinary urgency for one month
|
Fever, splenomegaly
|
Nil
|
Blood
|
1:100
|
Doxycycline×6 weeks+Gentamicin×7 days
|
|
3
|
M/29y
|
Businessman
|
Guangdong
|
Consumed goat placenta
|
Fever for 20 days and testicular pain for one week
|
Fever
|
Epididymo-orchitis
|
Blood
|
Nil
|
Doxycycline×3 months+gentamiicin×14 days+Rifampin×3 months+Ceftriaxone×14 days
|
|
4
|
M/59y
|
Unemployed
|
Heilongjiang
|
Nil
|
Fever, abdominal pain and urinary symptoms for one week
|
Fever, lymphadenopathy, splenomegaly
|
Intra-abdominal abscess
|
Blood
|
1:200
|
Doxycycline×2 days+Gentamicin×2 days
|
|
5
|
M/64y
|
Retired worker
|
Guangdong
|
Handled and consumed goat meat
|
Fever with chills and urinary symptoms for one month
|
Fever, lymphadenopathy
|
Spondylitis
|
Blood
|
1:400
|
Doxycycline×3 months+Rifampin×3 months+Gentamicin×7 days
|
|
6
|
M/30y
|
Office worker
|
Inner Mongolia
|
Nil
|
Recurrent fever for 50 days
|
Fever, splenomegaly
|
Nil
|
Blood
|
Negative
|
Doxycycline×6 weeks+Gentamicin×7 days
|
|
7
|
F/51y
|
Retired farmer
|
Guangdong
|
Consumed goat placenta
|
Fever, severe lower back pain for half a year
|
Fever, splenomegaly
|
Nil
|
Blood
|
1:400
|
Doxycycline×6 weeks+Gentamicin×7 days
|
|
8
|
F/31y
|
Cosmetologist
|
Fujian
|
Consumed undercooked beef
|
Fever with low back pain for one month
|
Fever, splenomegaly
|
Spondylitis
|
Blood
|
1:100
|
Doxycycline×4 months+Rifampin×4 months+Gentamicin×14 days
|
|
9
|
F/44y
|
Pork peddler
|
Guangdong
|
Handled and consumed goat placenta
|
Recurrent lower grade fever for three months
|
Fever, lymphadenopathy, splenomegaly
|
Liver and splenic abscess
|
Blood
|
1:100
|
Doxycycline×3 months+Rifampin×3 months+Gentamicin×14 days
|
|
10
|
M/63y
|
Farmer
|
Shanxi
|
Raised goat
|
Fever and back pain for 10 days
|
Fever, lymphadenopathy, splenomegaly
|
Spondylitis
|
Blood
|
1:200
|
Doxycycline×3 months+Rifampin×3 months+Gentamicin×14 days+Ceftriaxone×9 days
|
|
11
|
F/33y
|
Bank clerk
|
Shanxi
|
Consumed undercooked beef
|
Recurrent fever for 17 days
|
Fever
|
Nil
|
Nil
|
1:100
|
Doxycycline×6 weeks+Rifampin×6 weeks
|
|
12
|
F/73y
|
Housewife
|
Guangdong
|
Handled and consumed goat placenta
|
Abdominal pain, low grade fever, dysuria, constipation, low back pain and weight loss one month
|
Fever, lymphadenopathy, splenomegaly
|
Possible abdominal aortitis
|
Blood
|
1:100
|
Doxycycline for long-term+Gentamiicin×14 days+Rifampin×6 weeks+Ceftriaxone×6 weeks
|
|
13.
|
M/56y
|
Salesman
|
Henan
|
Consumed undercooked beef
|
Recurrent fever with low back pain and chest wall pain
|
Fever, lymphadenopathy, splenomegaly
|
Spondylitis, chest wall abscess, osteomyelitis
|
Blood
|
1:200
|
Doxycycline×3 months+Rifampin×3 months+Gentamicin×14 days
|
|
Table 2: Comparison of clinical characteristics between patients from Guangdong province and other provinces
Clinical characteristics
|
Patient from Guangdong province (%)
|
Patient from other provinces (%)
|
P value
|
Demographics
|
|
|
|
Sex (Male)
|
2 (40.0)
|
5 (62.5)
|
0.429
|
Age (Range/ Median)
|
29 – 73 (51)
|
29 – 64 (44.5)
|
0.622
|
Prior exposure/ Risk factors
|
|
|
|
Contact with live animals
|
0 (0.0)
|
3 (37.5)
|
0.118
|
Handling of animal meat
|
3 (60.0)
|
0 (0.0)
|
0.012
|
Consumption of animal meat
|
1 (20.0)
|
3 (37.5)
|
0.506
|
Consumption of goat placenta
|
4 (80.0)
|
0 (0.0)
|
0.002
|
Symptoms and signs
|
|
|
|
Fever
|
5 (100.0)
|
7 (87.5)
|
0.411
|
Abdominal pain
|
1 (20.0)
|
1 (12.5)
|
0.715
|
Urinary symptoms
|
2 (40.0)
|
2 (25.0)
|
0.569
|
Joint pain
|
0 (0.0)
|
1 (12.5)
|
0.411
|
Low back pain
|
2 (40.0)
|
3 (37.5)
|
0.928
|
Splenomegaly
|
3 (60.0)
|
6 (75.0)
|
0.569
|
Lymphadenopathy
|
3 (60.0)
|
3 (37.5)
|
0.429
|
Complications of infection
|
|
|
|
Spondylitis/ Arthritis
|
1 (20.0)
|
4 (50.0)
|
0.279
|
Epididymo-orchitis
|
1 (20.0)
|
0 (0.0)
|
0.188
|
Intra-abdominal abscess
|
1 (20.0)
|
1 (12.5)
|
0.715
|
Abdominal aortitis
|
1 (20.0)
|
0 (0.0)
|
0.188
|
Investigation results
|
|
|
|
Positive culture from clinical specimen
|
5 (100.0)
|
7 (87.5)
|
0.411
|
Total
|
5 (38.5)
|
8 (61.5)
|
|
Concerning the clinical presentation, the most commonly presenting symptoms included fever (92.3%), osteoarticular pain (46.2%) and urinary tract symptoms (30.8%). Other common physical signs in our cohort included splenomegaly (69.2%) and lymphadenopathy (46.2%). The commonest complication in our cohort was spondylodiscitis/ peripheral joint arthritis (5 patients, 38.5%), while extra-osteoarticular complications including abdominal aortitis, hepatosplenic abscess, chest wall abscess, and epididymo-orchitis were observed in 4 other patients, with the remaining 4 patients with no definite focal involvement. No statistically significant differences were observed in terms of clinical presentation and complications when compared between patients from Guangdong provinces and other provinces (Table 2).
Among all of the above complications, the most life-threating complication was abdominal aortitis, as demonstrated by the patient labelled case 12. This patient is an elderly woman, with history of hypertension and cerebral infarction on long term aspirin (acetylsalicylic acid), losartan, metoprolol, and betahistine. She had history of handling and consumption of goat placenta on multiple occasions during the past one year. She first presented to our hospital with constitutional symptoms (fatigue for six months, weight loss of 5 kg in one month and fever), right-sided abdominal pain radiating to the back for 1 week and non-specific symptoms such as cough, dysuria, and constipation. A supine abdominal X-ray revealed multiple air-fluid levels in the small bowel (Figure 1). Computed tomographic angiography (CTA) showed an abdominal infrarenal aortic aneurysm with penetrating ulcer, together with pseudoaneurysm, and presence of lymphadenopathy (Figure 2A and 2B), which were not known prior to this admission. Emergency endovascular repair was successfully performed with a bifurcated stent-graft inserted (Figure 3). Although the above development of aortic aneurysm could be accounted by underlying vascular risk factors, with the development of abdominal symptoms only 1 week prior to admission, presence of lymphadenopathy in CT scan, together with positive blood culture with Brucella melitensis, overall clinical picture suggestive of possible abdominal aortitis secondary to Brucella melitensis. Therefore, she was given intravenous antibiotics for 6 weeks, then antibiotics were subsequently stepped down to oral doxycycline for long term suppressive therapy. Currently the patient is still under follow up in our clinic for one year, with good clinical outcome and no recurrence.
Brucella species was isolated from the blood culture from eleven patients and joint fluid culture from one patient. All 12 strains were identified by MALDI-TOF MS, and visual inspection of these spectra from all the strains revealed a high similarity with reference spectra of Brucella melitensis (Figure 4-5), with common specific peaks for all the strains at 3023 Da, 3696 Da, 4537 Da, 5170 Da, 6674 Da, 7394 Da, 8037 Da, 9074 Da, 9786 Da, 12425 Da and 16060 Da. Brucella melitensis with confidence scores above 2.0 were obtained for all isolates, and if other bacteria such as Ochrobactrum, Pseudomonas and Enterobacteriaceae were included in the final MALDI-TOF MS results table, the confidence scores were less than 1.5. In addition, all strains were further identified by Vitek 2 compact system, with the result compatible with Brucella melitensis.
No positive culture from clinical specimen could be obtained from 1 of the 13 patients, while her Brucella antibody titer was found to be high with her clinical disease responded to doxycycline. Among the remaining eleven patients with serology performed by standard tube agglutination test, ten patients (90.9%) showed a positive titer with the remaining patient (9.1%) having a negative titer despite a positive blood culture.
These patients were treated with various combinations of antibiotics depending on the organ of involvement, side effects, and tolerability of antibiotics. The shortest duration of antibiotics was six weeks for patients with uncomplicated disease, and 3-4 months for osteoarticular involvement, abscess and epididymo-orchitis; with the exception of case 4 who ceased treatment after 2 days of antibiotics. The patient with intravascular infection such as abdominal aortitis after endovascular treatment was put on long term oral suppressive therapy. There were three (23.1%) patients with uncomplicated disease receiving doxycycline plus gentamicin, whereas one (7.7%) received doxycycline plus rifampin; Five (38.5%) patients received a combination of doxycycline, gentamicin plus rifampin, and three (23.1%) patients with more complicated disease received a combination of ceftriaxone and doxycycline, gentamicin plus rifampin.