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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 3  |  Issue : 1  |  Page : 46-52

Pulmonary tuberculosis incidence and drug resistance-related factors analysis in North China


1 School of Science, Harbin University of Commerce, Harbin, China
2 Institute of Multidrug-Resistant Control, Heilongjiang Province Center for Tuberculosis Control and Prevention, Harbin, China
3 Department of Infectious, The First Affiliated Hospital of Harbin Medical University, Harbin, China

Date of Submission26-Nov-2018
Date of Decision27-Dec-2018
Date of Acceptance31-Dec-2018
Date of Web Publication13-Mar-2019

Correspondence Address:
Prof. Zheng Qi
School of Science, Harbin University of Commerce, Harbin 150076
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_141_18

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  Abstract 


Background: This study analysis the epidemiological characteristics of incidence, gender, age, occupation, educational level, income, residence location, and timescale of 773 pulmonary tuberculosis patients in Hulin County in North China from 2014 to 2016. Methods: Two hundred and sixty-seven strains were identified and nine drug sensitivity tests against isoniazid (INH), streptomycin (S), ethambutol (EMB), rifampicin (RFP), ofloxacin (OFX), capreomycin, prothionamide, para-aminosalicylic acid (PAS), and kanamycin. Results: The top five drug resistance sequences of nine kinds of anti-TB drugs were S (24.535%) >INH (13.383%) >RFP (8.178%) >OFX (4.089%) >EMB (1.859%). Conclusion: The anti-TB medicine needs to be use under the guidelines to minimize drug resistance, and the elder age and poor also the work focus in the future.

Keywords: First-line drug, resistance rate, second-line drug, tuberculosis incidence


How to cite this article:
Qi Z, Yang W, Wang YF, Liu C. Pulmonary tuberculosis incidence and drug resistance-related factors analysis in North China. Biomed Biotechnol Res J 2019;3:46-52

How to cite this URL:
Qi Z, Yang W, Wang YF, Liu C. Pulmonary tuberculosis incidence and drug resistance-related factors analysis in North China. Biomed Biotechnol Res J [serial online] 2019 [cited 2019 Jul 22];3:46-52. Available from: http://www.bmbtrj.org/text.asp?2019/3/1/46/254096




  Introduction Top


Tuberculosis is the world's first chronic infectious disease caused by Mycobacterium tuberculosis, and China is a high-tuberculosis burden country.[1],[2],[3],[4],[5] According to the WHO report, about nine million new tuberculosis incidence occur each year whole world. In 2016, there were approximately 10.4 million tuberculosis patients worldwide, of which approximately 1.4 million died of tuberculosis. Tuberculosis is one of the top ten diseases, which cause of death in the world. The death is mainly related drug resistance.[6],[7] The tuberculosis incidence in China is among the top five in the world. The WHO estimates that there were approximately 895,000 new pulmonary tuberculosis incidents of China in 2016, mainly caused by the widespread use of resistant drugs.[8] In 2016, there were 600,000 patients resistant to rifampin, of which 490,000 were multidrug-resistance tuberculosis (MDR-TB) and 47% of these MDR-TB patients were from India, China, and Russia.[8] The economic development of North China is relative slower than that of South China, and Heilongjiang province is the most north place in China, there are about 30,000 active tuberculosis patients in Heilongjiang Province each year. The reported tuberculosis incidence in China was 63.42/100000 in 2015. The average reported tuberculosis incidence was 86.64/100 000 in Heilongjiang Province in 2015, which was much higher than the national average. The WHO and UN development goals are to end the global tuberculosis epidemic by 2035, tuberculosis mortality will drop by 90% and the incidence will drop by 80% by 2030 compared with 2015.[9]

Hulin is a relatively poor county in Heilongjiang province, and this study aims to analyze the pulmonary tuberculosis surveillance and drug resistance in Hulin, Heilongjiang Province from 2014 to 2016. It provides a basis to reduce the national average incidence of tuberculosis, also provides a strategy of the prevention and control of drug-resistant tuberculosis all over the world.


  Methods Top


Data sources

From January 2014 to December 2016, 773 cases of tuberculosis patients in Hulin County, Jixi City, Heilongjiang Province selected from registration in the TB Network Special Reporting System. Drug resistance data manually entered. The population information for each year was from the Hulin county National Economic Statistics Yearbook. Epidemiological data on morbidity, gender, age, occupation, education, income, place of residence, and timetable for tuberculosis patients were obtained from questionnaires for each patient and entered manually. The ethical statement is not need in this study. There are human research, but all from system and yearbook. The cases of tuberculosis patients in Hulin County, Jixi City, Heilongjiang Province selected from registration in the TB Network Special Reporting System. Drug resistance data manually entered. The population information for each year was from the Hulin county National Economic Statistics Yearbook.

Statistical analysis

Data analyzed by descriptive epidemiological methods. First, we calculated the incidence of smear-positive pulmonary tuberculosis. Next, we examined this stratified by gender, age, occupation, educational level, income, residence location, and timescale of pulmonary tuberculosis patients in Hulin from 2014 to 2016 were analyzed. Excel 2016 software was used to enter the data and analysis data, SPSS version 19.0 software (SPSS Inc., Chicago, IL) was used for statistical analysis data, statistical analysis using χ2 test, there was statistically significant as P < 0.05.

Ethics approval statement

The data were collected from the Chinese National TB Network Special Reporting System; ethical approval was not required for the study.


  Results Top


Tuberculosis incidence

There were 723 new cases and 47 retreated cases in Hulin County during 2014 to 2016. The annual average incidence proportion was 91.08/100,000. The incidence of 2016 in Hulin county was 92.13/100,000 exceeded average incidence, and the difference was statistically significant (χ2 = 84.120, P < 0.05). The annual average new incidence proportion was 85.07/100,000, and the incidence of 2015 in Hulin county was 83.49/100000 less than average incidence, the difference was not statistically significant (χ2 = 0.211, P > 0.05). The annual average recurrence incidence was 5.54/100,000, the recurrence incidence of 2015 in Hulin county was 2.46/100,000 less than average incidence, the difference was statistically significant (χ2 = 7.319, P < 0.05) [Table 1].
Table 1: Tuberculosis incidence of Hulin County in 2014-2016

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Tuberculosis incidence characteristics of gender

The average incidence proportion was 124.12/100,000 of 529 male patients, and the average incidence proportion was 57.75/100,000 of 244 female patients. The incidence of male patients was about 2.168 times than that of female patients; there was statistical significance (χ2 = 105.078, P < 0.05) [Table 2].
Table 2: Tuberculosis incidence characteristics of gender in Hulin County 2014-2016

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Tuberculosis incidence characteristics of age

There were no preschool patients in Hulin County 2014–2016, the number of tuberculosis patients increased as age growth until 45–54 age group, then decreased. The highest incidence was the age group of 45–54, 55–64, 25–34, the difference was statistically significant (χ2 = 259.113, P < 0.05) [Table 3].
Table 3: Tuberculosis incidence characteristics of age in Hulin County 2014-2016

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Tuberculosis incidence characteristics of occupation

The top three occupations with high-tuberculosis incidence were farmers, unemployed/laid-off staff, retired persons, and the percentages were 45.41%, 18.76%, and 13.97%, respectively. The difference was statistically significant (χ2 = 1360.268, P < 0.05) [Table 4].
Table 4: Tuberculosis incidence characteristics of occupation in Hulin County 2014-2016

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Tuberculosis incidence characteristics of education background

The tuberculosis patients' education background with junior middle school and primary school accounted for 66.88% of total, and the difference was statistically significant (χ2 = 270.176, P < 0.05) [Table 5].
Table 5: Tuberculosis incidence characteristics of education background in Hulin County

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Tuberculosis incidence characteristics of income level

The average income of Hulin in 2014 was 18,228.32 RMB; 19,507.95 RMB in 2015; and 21,051.72 RMB in 2016, which increased year by year. The average tuberculosis patients' income of Hulin in 2014 was 13,510.89 RMB; 17,305.45 RMB in 2015; and 19,736.49 RMB in 2016, which increased year by year. However, it was always lower than the average income of whole Hulin county people, and the difference was statistically significant (χ2 = 1168.200, P < 0.05) [Figure 1].
Figure 1: Income level of tuberculosis patients in Hulin county 2014–2016

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Tuberculosis incidence characteristics of living condition

There were 773 patients in Hulin 2014–2016, where 498 living in rural areas and 275 living in towns. The incidence was 170.012/100,000 in rural areas and 52.285/100,000 in urban in 2014; 181.313/100,000 in rural areas and 47.399/100,000 in urban in 2015; and 206.361/100,000 in rural areas and 41.978/100,000 in urban in 2016. The average incidence of rural and urban was 185.452/100,000 and 47.39910/100,000 in 2014–2016, the rural patients were much more than urban [Figure 2].
Figure 2: Rural and urban tuberculosis incident in Hulin county 2014–2016

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Tuberculosis incidence characteristics of time

The incidence was slightly higher in January each year. From February to August, the incidence raised firstly and then fall down again, which was slightly higher in April and May, the lower in August and September, and the increased again from October [Table 6].
Table 6: Tuberculosis incidence characteristics of time in Hulin County

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Drug-resistance analysis

Two hundred and seventy strains were isolated, one strain failed. Two hundred and sixty-nine strains were successfully conducted to strain identification and drug sensitivity tests. Two hundred and sixty-seven strains (99.257%) were M. tuberculosis complex strains and two strains (0.743%) were nontuberculous mycobacteria. Drug sensitivity tests included: isoniazid (INH), streptomycin (S), ethambutol (EMB), rifampicin (RFP), ofloxacin (OFX), capreomycin (CPM), prothionamide (PTO), para-aminosalicylic acid (PAS), kanamycin (KAM), and nine second-line anti-TB drugs.[10],[11]

Initial treatment means new patients or the patients treated less than 1 month. Retreatment means patients treated for over 1 month or failed initial treatment. Any resistant strains mean one or more drug resistance of the above nine anti-TB drugs. Single-drug resistance means resistance to only one-drug resistance. Multidrug resistance means at least simultaneous resistance to INH and RFP. MDR-TB means resistance to at least two drugs and except resistant to both INH and RFP.[12],[13]

There were 191 patients of 267 were sensitive to drugs, 76 patients were resistant to drugs, the initial resistance rate was 27.542%, and the retreatment resistance rate was 35.484%. According to the group analysis of gender, age, living location, occupation, education background, and income, there was no statistically significant difference (χ2 = 1.528, P = 0.216; χ2 = 1.396, P = 0.706; χ2 = 0.621, P = 0.431; χ2 = 5.398, P = 0.147; and χ2 = 1.852, P = 0.174). There was no statistically significant difference between the initial and retreatment patients (χ2 = 0.778, P = 0.378). There was a statistically significant difference in drug resistance among different occupations (χ2 = 14.445, P = 0.002) [Table 7].
Table 7: Drug-resistance stains analysis

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First-line drug resistance analysis

Sensitive to first-line drugs means sensitive to INH, S, EMB, and RFP drugs. First-line drugs resistance means at least one resistance to INH, S, EMB, and RFP drugs. The resistance rate in Hulin County of first-line drugs was 27.509%, drug resistance rate with initial treatment was 26.891%, and the resistance rate of first-line drugs with retreatment was 25.806% [Table 8].
Table 8: Tuberculosis stains resistance analysis for the first-line drug

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Second-line drug resistance analysis

Sensitivity to second-line drugs means sensitive to OFX, CPM, PTO, PAS, and KAM drugs. Second-line drugs resistance means at least one resistance to OFX, CPM, PTO, PAS, and KAM drugs. The resistance rate in Hulin County of second-line drugs was 4.089%, drug resistance rate with initial treatment was 3.361%, and the resistance rate of second-line drugs with retreatment was 9.677% [Table 9].
Table 9: Tuberculosis stains resistance analysis for second-line drug

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According to nine drugs test of INH, S, EMB, RFPOFX, CPM, PTO, PAS, and KAM, 76 strains of mycobacteria were resistant strains and the total resistance rate was 28.839%. Single-drug resistance was 15.356%, multidrug-resistance rate was 7.116%, and MDR-TB was 5.993% [Table 10].
Table 10: Tuberculosis stains resistance analysis for all drugs

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  Discussion Top


According to the WHO reports, the global tuberculosis incidence in 2015 decreased by 1.5% compared with 2014. Since 2010, the incidence of tuberculosis has been slowly declining year by year, but the total number of patients also increased year by year as the population increased.[14],[15],[16] There were totally 772 patients in Hulin county in 2014–2016. The annual average incidence was 85.07/100,000, of which 529 were male and 244 were female, the average incidence proportion were 124.12/100,000 and 57.75/100,000, respectively, the number and incidence of male patients were higher than female, which was consistent with Sun's conclusions.[17] From the age characters, the incidence of 35–64 age group is highest. The people at this age are the main driving force of the society, and have high-work intensity and stress, also high fatigue and susceptible to M. tuberculosis;[18] The middle-aged and elderly people 45–54, 55–64 age group, immune system degradation, and it is easy to infect M. tuberculosis.[19],[20],[21] People living in rural, such as farmers, low-education background, and low income are susceptible to M. tuberculosis.[22] The incidence is higher in early spring (March and April) and winter (October–January). The winter in Hulin is relative cold, people living in rural need to self-heat in winter, therefore these two periods are dusty and susceptible to M. tuberculosis.[23]

The resistance rate of tuberculosis in China is higher than the global level and ranks among the top in the world.[24],[25] Two hundred and seventy isolates strains were obtained from Hulin country, except one strain failed, the 267 (99.257%) were M. tuberculosis complex strains and two (0.743%) were nontuberculous mycobacteria. Among the 267 strains, 191 were sensitive to drugs, 76 were resistant to drugs, the initial resistance rate was 27.542%, and the retreatment resistance rate was 35.484%. The rate of drug resistance in male higher than female, elder age higher than younger, and the higher the age, the higher the drug resistance rate is. The rate of drug resistance in urban areas is higher than that in rural areas. In general, men smoke more than women, and smoking is associated with drug-resistant tuberculosis, the patients with low-working condition, low-education background, and low income related with tuberculosis drug resistant.[26],[27]

The total drug resistance rate of the first-line drugs was 27.509%, in which the new patients' drug resistance rate was 26.891% and the retreatment patients' drug resistance was 25.806%. Resistance rates of the first-line drugs order were INH > S > EMB > RFP.

The total drug resistance rate of the second-line drugs was 4.089%, in which the new patients' drug resistance rate was 3.361%, and the retreated patients' drug resistance rate was 9.677%. Resistance rates of the second-line drugs order were OFX > CPM > KAM > PAS > PTO. The order of 267 strains of M. tuberculosis complex resistant of nine antituberculosis drugs was: S (24.535%) > INH (13.383%) > RFP (8.178%) > OFX (4.089%) > EMB (1.859%) > CPM (1.859%) > KAM (1.487%) > PAS (1.115%) > PTO (0.000%). The order of 236 strains of M. tuberculosis complex of new patients antituberculosis drugs was: S (23.109%) > INH (10.924%) > RFP (5.462%) > OFX (3.361%) > CPM (1.681%) > PAS (1.261%) > KAM (1.261%) > EMB (0.840%) > PTO (0.000%). Thirty-one strains of M. tuberculosis complex or retreatment patients antituberculosis drugs order were: S (35.484%) > INH (32.258%) > RFP (29.032%) > EMB (9.677%) > OFX (9.677%) > CPM (3.226%) > KAM (3.226%) > PTO (0.000%) > PAS (0.000%). S, INH, RFP, and OFX of the nine antituberculosis drugs was highest resistance rate, and the reason for the higher resistance rate of OFX was because of cross-use as anti-TB drugs.[28]

Drug-resistant tuberculosis is highly persistent and difficult to treat. It is a major problem all over the world, and China is still a “hard-hit area.” The main reason for drug resistance is due to the widespread and irregular use of anti-TB drugs. In addition, the tuberculosis patients' investigation is unclear. This study analyzes the incidence and drug resistance in Hulin County, respectively, it is the first time to analyze the characters in detail of both incidence and drug resistance. The results in this research can be reference for other place in China or worldwide and clarifies the focus of prevention and control in the future.

Acknowledgment

We would like to express sincere thanks to the government for their support and finance supplied by the central financial transfer payment for TB control and thank to the project of Health and Family Planning Commission of Heilongjiang Province (2018191).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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