| BackgroundTB is an old disease. According to the study MTB was found in the human skull from the Mid-Stone Age in the UK, which came from about 2200 yeasrs ago. At the 403 BC, symptoms about TB had been documented in the "Huang Di Nei Jing Su Wen" in China. In the 19 th century, TB was a pandemic in Europe and North America, due to the lack of effective treatment, resulted in a large number of patients died. WHO reported that the death due to TB was over three million in the worldwide each year, one person died every 10 seconds. According to the WHO Global TB Report 2012, China is one of the countries with a high burden of TB, second only to India, came in second place, the incidence rate is about 50-149 per 100,000 people. The Global Tuberculosis report 2015 from WHO showed that China was still a country with high burden of TB, third to India and Indonesia. The incidence rate is about 63-73 per 100,000 people. In addition the report displayed that the mortality fell to 1-3.9 per 100,000 people in 2014 from 4.5-4.9 per 100,000 people in 2011. Although the annual incidence decreased from 1990 to 2014, the number of extra-pulmonary TB was 6540 in 2011 that increased to 32348 in 2014. Meanwhile, per capita cost in the treatment of tuberculosis with first-line anti-TB drugs is increasing every year, from about $200 in 2011 to $500 in 2014.In extrapulmonary tuberculosis cases involving the skeletal system was about 10%, of which 50% of patients were spinal tuberculosis. In China the 3%-6% new cases and 12%-30% treated of patients was DR-TB. So it is important to determinate the characteristics of spinal tuberculosis. Currently, most researches have focused on characteristics about pulmonary tuberculosis, and these studies on the epidemiological characteristics of tuberculosis were summarized; investigation, analysis and research were on MTB genotypes in the different regions and populations; molecular epidemiology of MTB genotypes was summarized in different regions of the world and in China; and a detailed analysis of specific genotype about DR-TB provided an important reference for tuberculosis treatment. Although the research of tuberculosis has been very thorough and specific, STB research is still at a relatively early stage. Thus, the characteristics of epidemiology and genotype of spinal tuberculosis are not an in-depth study.Objective1. To determinate the epidemiological characteristics of STB.2. To determinate the characteristics of patients with STB of DR and non-DR.3. To determinate the molecular characteristics of TB from STB and relationships between molecular type and clinical symptoms, and physical sign.Methods and Material1. The medical records of consecutive patients with spinal tuberculosis were retrospectively reviewed from January 1999 to December 2013.2. Inclusion criteria: 1) the presence of osteomyelitis in one or more vertebral segments; 2) MTB isolated from an abscess or tissue biopsy specimen, and 3) histology of a tissue specimen demonstrating caseating granuloma or granulomatous inflammation with a positive acid-fast bacillus smear. Patients who fulfilled criterion(1) plus criterion(2) or(3) were included in this study. Exclusion criteria: patients with non- spinal disease caused by Mycobacterium tuberculosis infection.3. The demographic data, chief complain, medical history, symptoms, physical signs, laboratory examination, image examination, indications and treatment of patients with STB from January 1999 to December 2013 in the orthopedic department of Southwest hospital were recorded and imput into the database.4. Bacterial strains were from patients with STB from January 2006 to December 2013. Drug susceptibility testing was performed using the proportional method recommended by the World Health Organization, and the concentrations of drugs in media were as follows: isoniazid 0.2μg/ml, rifampicin 40μg /ml, ethambutol 2μg /ml, streptomycin 4μg /ml, rifapentine 40μg /ml, para-aminosalicylic acid 1.0μg /ml, amikacin 30μg /ml, capreomycin 40μg /ml, kanamycin 30μg /ml, levofloxacin 2μg /ml, protionamide 40 μg /ml and dipasic 0.1μg/ml. A strain was declared resistant to a drug when the growth rate was >1% compared with the control. The characteristics of DR-STB were analyzed.5. Bacterial strains were from patients with STB from January 2006 to December 2013. Drug susceptibility testing was performed using the proportional method recommended by the World Health Organization, and the concentrations of drugs in media. Using boiling method extracted the genomic DNA of non DR-STB. The identification of genomic deletions in region of difference 105(RD105) was performed by PCR to distinguish Beijing type from non-Beijing type. 12 MIRU-VNTR genetic loci were to identify genotyping of MTB from spinal tuberculosis. BioNumerics(version 5.0, Applied Maths, Sint-Martens-Latem, Belgium) was used to construct the Minimal Spanning Trees(MSTs) based on VNTR data. A dendrogram was constructed based on the unweighted-pair group method using average linkages and the software package MEGA, version 6.0, as described previously.Result1. Total number of hospitalized patients with spinal tuberculosis who were treated in our hospital is 967 including 473 women and 494 men, with a mean age of 35.86±15.68 years. The most common presentation of spinal tuberculosis was back pain followed by night sweat and fever. The thoracic spine was the most commonly involved level followed by the lumbar spine and cervical spine. The mean number of involved vertebrae per patient is 2.57±1.52. There were 33 patients with skip lesions. The most common findings were disk space narrowing. Abscesses were visible by CT and MRI in 617 including para-spinal abscess in 538 and pre-vertebral abscess in 79. Epidural compression was visible in 322 patients. 740 patients were successfully treated with surgery and anti-tuberculosis medications.2. There were 675 patients from January 2006 to December 2013. The culture positive specimens and non-pollution were 211 patients including 49 drug-resistant patients and 162 non-resistant patients. In drug-resistant patients, the patients with pain accounted for 83.7%, 44.9% of patients were fever, patients with night sweats accounted for 38.8%, kyphosis accounted for 40.8%, neurological impairment accounted for 30.6% and abscess accounted for 67.3%; in non-resistant patients, pain accounted for 98.8%, 72.8% were fever, night sweats accounted for 74.1%, 52.5% in kyphosis, neurological impairment accounted for 64.2% and abscess accounted for 85.2%. There were significant differences on pain, fever, night sweats, nerve damage and abscess between the resistant and non-resistant patients(P <0.05) and no difference on kyphosis(P > 0.05).3. 49 were found to have drug-resistant strains to at least one anti-tubercular drug. 24 patients had MDR strains and 2 had XDR strains. Among the first-line drugs, maximum resistance was found to isoniazid(63.27%) followed by rifampicin(59.18%) and streptomycin(48.98%). Among the second-line drugs, maximum resistance was found against levofloxacin(32.65%) and rifapentine(30.61%). Least resistance was against amikacin(2.0%) and kanamycin(4.1%). Among the non-MDR group, maximum resistance was found against isoniazid, streptomycin and rifapentine.4. In 162 patients with non-drug-resistant spinal tuberculosis, 148 patients were "Beijing-type" strains TB and 14 were “non- Beijing-type" strains. In the "Beijing-type" strain of patients, pain accounted for 99.3%, 75.0% patients with fever, night sweats patients accounted for 76.4%, 56.8% in kyphosis and neurological impairment patients accounted for 66.2% and 85.8% in abscess formation; in the "non-Beijing-type" strain patients, pain accounted for 92.9%, 50.0% in fever, night sweats accounted for 50.0%, 7.7% in kyphosis, neurological impairment accounted for 42.9% and abscess formation in 78.6%. There was significant difference on kyphosis between the resistant and non-resistant patients(P <0.05) and no differences on pain, fever, night sweats, abscess formation and nerve damage(P > 0.05). There were significant differences on pain, fever, night sweats, abscess formation and nerve damage between the patients with “Beijing†genotype and non-“Beijing†genotype(P <0.05) and no difference on kyphosis(P > 0.05).5. Genotyping revealed 162 MIRU-VNTR types, with 29 isolates(17.9%) being clustered and 133 isolates(82.1%) having unique genotypes. There were 11 clusters with the minimal cluster including 2 isolates and maximal cluster including 7 isolates.Conclusion1. From 1999 to 2013, in our hospital the number of patients with spinal tuberculosis was on the rise. The incidence of male was close to female patients. Patients from 21 to 50 years old were the main onset age. The number of rural patients was more than the urban. The number of thoracic vertebral body involved was more than lumbar, but the number of patients with lumbar spinal tuberculosis was more than patients with thoracic spinal tuberculosis. The numbers of vertebrae involved in the most patients were 2 or more. Pain is the main symptom of spinal tuberculosis; activity limitations and percussive pain was physical sign. 1/3 of all patients were nerve dysfunction. The diagnosis delay was due to patients mainly.2. The most common resistant drugs are isoniazid and levofloxacin in the first and second line anti-tuberculosis drugs respectively. The pain, fever, night sweats, abscess formation and nerve damage are common symptoms in the non-resistent drug spinal tuberculosis.3. Beijing family genotype is predominant and highly epidemic spinal TB. The kyphosis is common symptom in the “Beijing-type†strain spinal tuberculosis. The non-drug resistance MTB is obvious cluster in Chongqing of China. |
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