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Title: Trends and Characteristics of Drug-resistantTuberculosis in Rural Shandong, China
Authors: Ning-ning Tao, Xiao-chun He, Xian-xin Zhang, YaoLiu, Chun-bao Yu, Huai-chen Li
PII: S1201-9712(17)30243-6DOI: https://doi.org/10.1016/j.ijid.2017.09.019Reference: IJID 3042
To appear in: International Journal of Infectious Diseases
Received date: 25-5-2017Revised date: 17-9-2017Accepted date: 18-9-2017
Please cite this article as: Tao Ning-ning, He Xiao-chun, Zhang Xian-xin, LiuYao, Yu Chun-bao, Li Huai-chen.Trends and Characteristics of Drug-resistantTuberculosis in Rural Shandong, China.International Journal of Infectious Diseaseshttps://doi.org/10.1016/j.ijid.2017.09.019
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Trends and Characteristics of Drug-resistant Tuberculosis in Rural
Shandong, China
Ning-ning Taoa#, Xiao-chun Heb, Xian-xin Zhangc, Yao Liua, Chun-bao
Yud, and Huai-chen Lia*
a.Department of Respiratory Medicine, Shandong Provincial Hospital
Affiliated to Shandong University, Jinan;
b.Department of Respiratory Medicine, Baoji Central Hospital, Baoji,
Shaanxi, China;
c.Department of Respiratory Medicine, Shandong Provincial Chest
Hospital, Jinan, China;
d.Katharine Hsu International Research Center of Human Infectious
Diseases, Shandong Provincial Chest Hospital, Jinan, China;
#This author is first author on this work.
*Correspondence and requests for materials should be addressed to
Huai-chen Li. Mailing Address: Shandong Provincial Hospital Affiliated
to Shandong University, 324 Jingwuweiqi Road, Huaiyin District, Jinan,
China 250021.
E-Mail: lihuaichen@163.com
Highlights:
The increasing prevalence of MDR TB has led to new challenges.
Studying of DR TB and MDR TB in rural areas is vital to TB
control in China.
Increasing MDR TB especially primary MDR TB characterize DR
TB cases in rural China.
Abstract
Objectives: We aim to describe the secular trends for drug-resistant
tuberculosis (DR TB) and to identify unique characteristics of
multidrug-resistant TB (MDR TB) in rural China.
Methods: A retrospective study of TB data collected from 36
tuberculosis prevention and control institutions serving rural populations
in Shandong Province, China, from 2006 to 2015 was conducted.
Results: Approximately 8.3% of patients suffered from MDR, among
which 70% were new treated patients, and this rate has increased at a
yearly rate of 1.3% during the last decade. An increase in the percentage
of overall first-line drug resistance against isoniazid (INH), rifampin
(RFP), ethambutol (EMB), and streptomycin (SM) was confirmed
(P<0.05). The percentage of MDR TB in new and previously treated
cases increased at yearly rates of 9.9% and 11.1%, respectively. MDR TB
patients were more likely to be female (OR, 1.58; 95% CI, 1.32-1.89),
smoking (OR, 1.75; 95% CI, 1.47-2.07), having recent TB contact (OR,
1.58; 95% CI, 1.04-2.42), and retreated (OR, 2.89; 95% CI, 2.46-3.41).
Conclusions: Increasing MDR TB and rates of primary MDR TB
characterize DR TB cases in rural China. Persistent efforts need to be
made among MDR TB patients in future TB control strategies.
Keywords: multidrug-resistant tuberculosis; primary transmission; rural;
epidemiology
Introduction
Microbial drug resistance has become a major public health concern
worldwide [1]. Due to persistent international efforts to combat
tuberculosis (TB), both the global mortality rate and incidence rate have
decreased over the past two decades [2]. However, the increasing
prevalence of drug-resistant tuberculosis (DR TB) has led to new
challenges [3]. As an expanding threat, it is estimated that MDR TB,
defined as resistance to isoniazid (INH) and rifampin (RFP), has grown to
480,000 new cases (2015 cohort) with 210,000 deaths/year (2013 cohort)
[2]. With catastrophic cost, poor adherence, prolonged treatment duration
and inadequate effective drugs, MDR TB has been associated with worse
treatment outcomes than drug-susceptible TB [4-7]. The serious epidemic
of MDR TB places patients just one step away from having extensively
drug-resistant (XDR) and also increases the rate of treatment failure and
causes enormous social and economic disruption [8].
China has the second highest number of TB cases and accounts for
25% of the MDR TB population in the world [9]. As China has the largest
agricultural population in the world, approximately 64.9% of TB patients
and 80% of MDR TB patients in China live in rural areas [10-11]. Due to
poor regional socioeconomic status (living conditions, health and
nutritional status, money to pay for health care and access to health
services) [12], more and more patients have delayed or received
inappropriate treatments, which have consequently increased the
prevalence and mortality rate of TB in poor rural areas compared with
economically developed urban areas [13]. With economic development
and urbanization, an increasing population, up to 211 million in 2010,
migrated from rural to urban areas in China, leading to the spreading of
TB nationwide [14]. Thus, studying of DR TB specifically MDR TB in
rural areas is of key importance for monitoring and controlling TB in
China. Previous studies on TB in rural areas were limited by the short
time span and small sample size of culture-positive TB in China [15-16].
Shandong is a province located on the east coast of China with a
population of 95 million and a rural population of 57 million according to
the Sixth National Census. An estimated 211,900 people in Shandong
were infected with TB with 66.7% of the cases being rural residents
according to the Fifth National TB Epidemiological Survey in Shandong
province [11]. The purpose of the present study was to summarize the
changes between different drug-resistant patterns over time on the basis
of drug susceptibility testing (DST) for first-line drugs among the rural
population in Shandong Province, China, in the last decade, to provide
effective intervention strategies for the prevention and control of DR TB
in similar populations.
Materials and Methods
Study population and data collection
We collected information from consecutive culture-confirmed TB cases
among the rural population in Shandong Province from the China
Information System for Disease Control and Prevention (CISDCP) from
2006 to 2015. Two province-level hospitals, Shandong Provincial
Hospital and Shandong Provincial Chest Hospital (SPCH), and 21
county-level and 13 municipal-level local health departments in
Shandong Province constituted the 36 monitoring sites in this
retrospective study. Monitoring sites were selected based on convenience
and to reflect a range of TB burdens and clinical capacity. In 2004, the
Center for TB Control and Prevention of Shandong province, including
SPCH, set up the provincial health department Katharine Hsu
International Research Center of Human Infectious Diseases (KICID),
where the patients’ information was collected and recorded by trained
researchers on standard case report forms. KICID has been responsible
for laboratory quality assurance and TB surveillance in Shandong
province since its inception.
Mycobacterium tuberculosis was identified by culturing and
susceptibility to INH, RFP, ethambutol (EMB), and streptomycin (SM)
was identified by using DST. Sociodemographic data for all of the
patients including age, sex, smoking history, excess alcohol consumption,
TB contact history and prior TB treatment history were collected and
recorded.
Laboratory Methods
All samples available were processed for smear and culture. Tissue
samples were also examined for the presence of granulomas. By using
Ziehl-Neelsen staining, the presence of acid-fast bacilli (AFB) was
confirmed. Culturing was performed on Lowenstein-Jensen (LJ) culture
medium. After thorough assessment of all the evidence derived from
growth characteristics, morphologic characteristics of the colony, and the
result for inhibition by P-nitrobenzoic acid, M. tuberculosis was selected
[9]. Furthermore, the samples containing non-tuberculosis mycobacteria
(NTM) were rejected.
Acid buffer LJ medium DST was performed using the proportion
method with the following antibiotic concentrations: (1) INH (0.2 μg/mL),
(2) RFP (40 μg/mL), (3) EMB (2.0 μg/mL), and (4) SM (4.0 μg/mL).
Resistance was defined as more than 1% growth for any anti-TB drug.
Laboratory Quality Control
External quality assessment (EQA) for smear, culture and DST in
county and district level laboratories was conducted by the prefectural
and provincial TB laboratories, accordingly, EQA in the provincial
reference laboratories and the National Tuberculosis Reference
Laboratory (NTRL) was conducted by the Supranational Tuberculosis
Reference Laboratory (STRL) based on the WHO guideline [17]. Blinded
re-testing of a random selection of approximately 10% of the isolates
from each laboratory by a superior laboratory was essential.
Data inclusion and definitions
All of the TB cases in rural areas that had a positive M. tuberculosis
culture with DST results and demographic and clinical information were
included. TB patients with non-tuberculous mycobacteria (NTM) as well
as HIV (in China HIV-positive patients are immediately transferred to an
HIV-specialized hospital) were excluded.
Drug-susceptible TB was defined as TB isolates susceptible to all the
four tested first-line drugs. MDR TB was defined as TB resistant to at
least INH and RFP. A “new case” is defined as a patient who had never
been treated for TB or had taken <1 month of anti-TB drugs in the past; A
“previously treated case” is defined as a patient who had received ≥1
month of anti-TB drugs in the past [17].
Statistical analysis
The changes in the proportions of different resistance patterns over
time were confirmed using the Chi-Square test for trends and linear
regression. Pearson’s X2 test was used to compare categorical variables
for univariable analysis. Multivariable logistic regression analysis was
used to identify unique characteristics of MDR TB. The odds ratios (OR),
95% confidence interval (CI) and P value for individual variables were
obtained using a logistic regression model, and P<0.05 was considered to
be statistically significant. We used SPSS software version 17.0 for the
statistical analysis.
Results
Case Estimates
A total of 10,977 cases were identified with M. tuberculosis in rural
Shandong during the last decade. First, we excluded 1198 (10.9%)
patients without DST result and 35 (0.3%) patients without demographic
or clinical information. Then, we excluded 171 (1.6%) patients with
NTM. Finally, sum to 9,573 (87.2%) cases were included. The average
age of these patients was 51.0 (mean±SD, 51.0±19.3) years old and
79.1% were male.
Drug Resistance Patterns
Among the 9,573 TB cases, the resistance rate for SM was 17.7%,
followed by INH (16.5%), RFP (10.0%), and EMB (4.4%). The
prevalence of MDR was 794 (8.3%), while another 951 (9.9%) patients
had resistance to either INH or RFP (but not both). A total of 2,037
(24.1%) cases were resistant to at least one first-line drug and 289 (3.0%)
cases were resistant to all the four tested first-line drugs.
MDR TB was confirmed in 6.8% of new cases and 17.1% of
previously treated cases. Another 9.2% and 14.3% of new and previously
treated TB cases, respectively, were resistant to either INH or RFP (but
not both). An estimated 21.8% and 37.1% of new and previously treated
TB cases, respectively, were resistant to at least one of the four first-line
anti-tuberculosis drugs (Table 1).
Trends Overtime
Among the included patients (9573 cases), it is noteworthy that the
percentage of drug-susceptible TB decreased from 78.6% in 2006 to
71.9% in 2015, decreasing at a yearly rate of 1.0% (R2=0.5611;
Chi-square test for trends: X2=29.242, P<0.001). In contrast, the
percentage of overall first-line drug resistance for INH, RFP, EMB and
SM, and MDR TB increased significantly (P<0.001) over the past decade
(X2=22.831 for INH resistance, increasing at a yearly rate of 4.8%
(R2=0.47) from 12.6% to 19.2%; X2=62.297 for RFP resistance,
increasing at a yearly rate of 8.2% (R2=0.69) from 6.4% to 13.1%;
X2=38.933 for EMB resistance, increasing at a yearly rate of 18.0%
(R2=0.68) from 1.5% to 6.6%; X2=36.392 for SM resistance, increasing at
a yearly rate of 5.1% (R2=0.74) from 14.7% to 22.9%; and X2=43.629 for
MDR TB, increasing at a yearly rate of 9.4% (R2=0.53) from 4.9% to
11.1%) (Figure 1 and Figure 2). Moreover, mono-resistance analysis
showed a statistically significant increase in the RFP mono-resistance
(RMR) proportion (X2=9.017, P=0.003), though INH, EMB, and SM
mono-resistance showed no statistically significant changes during the
last decade.
To better understand the epidemic trends in TB cases with different
treatment histories, a further breakdown of new and previously treated
TB cases was conducted. This breakdown estimated that there was an
increasing yearly rate of 9.9% (R2=0.53) for new treated MDR TB and
11.1% (R2=0.71) for previously treated MDR TB cases during the last
decade; these changes were statistically significant (P<0.001) using the
Chi-square test for trends (X2=51.279 and 60.481, respectively) (Figure
2).The percentage of new treated MDR TB among MDR TB patients
increased from 67.5% in 2006 to 76.0% in 2015, increasing at a yearly
rate of 1.3% (R2=0.38; Chi-square test for trends: X2=12.291, P<0.001)
(Figure 3). We also analyzed trends for other drug resistance patterns in
new and previously treated TB cases. We found that the overall drug
resistance rate was increasing significantly at a yearly rate of 4.9%
(R2=0.40), 8.8% (R2=0.56), 18.0% (R2=0.65), and 5.2% (R2=0.67) for
INH, RFP, EMB, and SM, respectively, in new TB cases during our study
period (Chi-square test for trends: X2=19.699, P<0.001; X2=53.892,
P<0.001; X2=36.196, P<0.001; and X2=35.933, P<0.001, respectively).
Coincidentally, in previously treated TB cases, the overall drug resistance
rate increased significantly at a yearly rate of 6.6% (R2=0.69), 10.0%
(R2=0.76), 19.7% (R2=0.44), and 5.4% (R2=0.53) for INH, RFP, EMB,
SM, respectively, during our study period (Chi-square test for trends:
X2=14.805, P<0.001; X2=30.753, P<0.001; X2=9.112, P=0.003; and
X2=10.369, P=0.001, respectively). The mono-resistance analysis showed
an increasing yearly rate of 9.3% (R2=0.55) for new treated RMR TB and
14.0% (R2=0.45) for previously treated RMR TB cases; these changes
were statistically significant using the Chi-square test for trends
(X2=4.506, P=0.034; and X2=8.222, P=0.004, respectively). In contrast,
INH mono-resistance in previously treated TB cases and EMB and SM
mono-resistance in both new and previously treated TB cases showed no
statistically significant changes. The percentage of INH mono-resistance
in new TB cases decreased significantly from 4.4% to 2.2%, decreasing at
a yearly rate of 7.4% (R2=0.30; Chi-square test for trends: X2=6.261,
P=0.012).
Demographic and Clinical Characteristics
Table 2 shows the characteristics of patients with or without MDR TB
in detail. Univariable comparison showed that the following
characteristics were associated with the presence of MDR TB: (1) female,
(2) smoking, (3) recent TB contact and (4) TB treatment history. Patients
aged 15-24 years were less likely to have MDR TB. On the basis of the
variables included in the univariable comparison, the final multiple
logistic regression model predicted MDR TB based on the following
characteristics: (1) female (OR, 1.58; 95% CI, 1.32-1.89), (2) smoking
(OR, 1.75; 95% CI, 1.47-2.07), (3) recent TB contact (OR, 1.58; 95% CI,
1.04-2.42) and (4) TB treatment history (OR, 2.89; 95% CI 2.46-3.41).
Discussion
This retrospective study attempted to systematically investigate the
secular trends of DR TB and to identify characteristics of MDR in M.
tuberculosis strains from TB patients in rural settings in Shandong, the
second largest province located on the eastern coast of China. To our
knowledge, this is one of the largest retrospective study from the aspect
of both time span and sample size for culture-positive TB that describes
the epidemiology of DR TB among rural populations in Shandong, China
over the past decade.
In 2009, the Chinese government established the rural New
Cooperative Medical Scheme (NCMS), a health insurance scheme for
rural patients, and devised a plan for MDR TB prevention and control
[18-19]. Although these efforts appear to be helpful, with low
reimbursement rates for in-patients and no reimbursement rates for
out-patients, this strategy may not be sufficient for TB treatment and
control in rural China and may run into bottlenecks. In this study, the
percentage of drug susceptible TB in new and previously treated cases
and INH mono-resistance TB in new cases decreased during the last
decade. In contrast, an increase in the percentage of overall first-line drug
resistance for INH, RFP, EMB and SM, RMR and MDR TB with new
and previously treated cases in rural areas during the last decade was
confirmed.
During the study periods, the percentage of new treated MDR TB
among MDR TB patients increased from 67.5% in 2006 to 76.0% in 2015,
increasing at a yearly rate of 1.3%. This indicates ongoing primary
transmission of MDR TB strains in rural China. Consistent with previous
surveys, patients who had a recent TB contact history were more likely to
have MDR TB [20-21]. To make matters worse, the percentage of recent
TB contact as a sensitive indicator for primary transmission was greatly
underestimated due to a lack of diagnosis and unawareness of the disease
for those infected as well as disguising of TB status for the susceptible
population [22]. Delays (patient, provider, diagnostic, and treatment
delays) for suspected TB patients affected the percentage of infection
among close contacts and contributed to the emergence of drug resistance,
particularly for MDR [23-24]. This phenomenon may be even more
serious in rural areas, which harbor a higher burden of TB/MDR TB and
have much poorer living conditions, poorer health and nutritional status,
less money to pay for health care, insufficient laboratory facilities, and
fewer qualified health professionals [12, 25]. Up to 70% of the patients
with MDR TB had diseases that were resistant to at least INH and RFP
before they received standard first-line short-course treatment in this
study. With poor and even no standard TB infection control (IC) measures
in some undeveloped regions in China, the primary spread of M.
tuberculosis within the general population and cross-infection between
TB patients particularly in health-care facilities are quite serious [26].
Continuous efforts are urgently needed to control the on-going primary
transmission of MDR TB in rural China.
Shandong province has implemented directly observed treatment
strategy (DOTS) therapy since 1992, the strategy has universally covered
TB patients at the county level since 1995, the cure rate of active TB
cases by DOTS reached over 90% at the county level according to
mid-evaluation on carrying out “TB control planning of China
(2001-2010)” in Shandong Province [27]. However, the prevalence and
continual rise of DR TB and MDR TB stands to derail the
implementation and completion of DOTS in rural China [28]. During the
study period, MDR TB with prior anti-TB treatment history which may
occurred by acquisition, re-infection or re-current increased from 8.4% in
2006 to 21.8% in 2015, increasing at a yearly rate of 11.1%. The
widespread and inappropriate use of anti-TB drugs might enable the
selection of drug-resistant strains, which also accelerated the occurrence
of acquired MDR [9, 29-30]. A previous study demonstrated that INH or
RMR was an independent predictor for acquired MDR TB [9]. An
increase in the overall resistance rate to INH, RFP, and RMR was
confirmed in this study. An estimated 9.2% of new and 14.3% of
previously treated TB patients had resistance to either INH or RFP (but
not both), placing them just one step away from having MDR TB. The
government provided “free” TB treatment for all TB patients covering
only some diagnostic tests and first-line anti-mycobacterial medications,
however catastrophic second-line anti-mycobacterial medications and
“out of pocket” expenditures, such as transport, additional food,
symptom-relieving medicines, or indirect expenses associated with lost
income, lead to more and more patients, especially those living in poor
rural areas, dropping out of and/or discontinuing treatment even under
DOTS [31-33]. These inadequate (poor regimens) treatment, irregular
(poor compliance) and incomplete (defaulting) treatments can exacerbate
treatment failure and increase the risk of MDR TB [5-7]. The already
serious situation of DR TB in China could easily be much worse if
increasing populations migrated from rural to urban areas [34]. Thus,
controlling MDR in rural areas may be one of the most significant factors
in future TB control strategies.
Similar to previous studies, we identified several characteristics of
MDR TB among rural TB cases. In this study, special attention should be
paid to TB patients who are female [35-36], smokers [37-38], previously
treated [20, 35] and in contact with other TB patients [20-21].
This is the first study devoted to assessing the changes in different DR
TB patterns from a retrospective perspective and identifying unique MDR
TB case characteristics in rural China. The results imply that the DR TB
situation in China could easily deteriorate if MDR TB and primary
transmission of MDR strains increase in rural areas.
This study did have some limitations. First, because only one province
on the eastern coast of China was examined, the economic and regional
disparities limited the generalizability of the results. Second, according to
the National Survey of Drug-Resistant TB in 2007, one third of patients
with MDR TB were resistant to either ofloxacin or kanamycin [9],
placing them one step away from XDR TB. However, the lack of DST for
second-line drugs impeded us from further understanding the extent of
drug-resistant, extremely DR and totally DR TB that were associated with
treatment outcomes much worse than MDR TB [39-41]. Third, because
all of the patients were culture-confirmed HIV-seronegative TB cases
with little information on their education, incomes, and living conditions
accessible from the medical records, we failed to show the relationships
between these factors and the DR TB epidemic. Finally, the lack of
genotyping, a gold standard for identifying the origin of resistant isolates,
impeded us from correlating the mutations in the prevalent strains with
observed resistance in this region of study with observations in other
parts of China and the world.
In conclusion, we demonstrated an increase in MDR TB in rural China
over the last decade. MDR TB strains are mainly transmitted by airborne
infection in rural China. Effective TB IC strategies are urgently needed to
control the on-going primary transmission of MDR TB, especially among
people grouped closely with diagnosed TB patients. DST for both first-
and second-line anti-TB drugs is essential for more individualized
anti-TB regimens. Additionally, on-going reforms for financing DOTS
(TB diagnosis and treatment) in rural areas will be essential components
of effective interventions for TB prevention and control in China.
Acknowledgements
We would like to express our deep appreciation to all the individuals
who contributed to this work. This work was supported by the Science
and technology development plan of Shandong Province (Grant Number:
2009GG10002054).
Ethical clearance
This study was approved by the Ethics Committee of Shandong
Provincial Hospital, which is affiliated to Shandong University. Patient
records were anonymized and de-identified before analysis.
Conflict of interest
None.
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Figure legends
Figure 1. Drug-resistance pattern trends among 9,573 culture-confirmed
TB cases in rural China from 2006 to 2015.
For INH resistance (X2=22.831, P<0.001; linear regression formula:
R2=0.47, x-coefficient=0.006, SE=0.130); for RFP resistance (X2=62.297,
P<0.001; linear regression formula: R2=0.69, x-coefficient=0.008,
SE=0.051); for EMB resistance (X2=38.933, P<0.001; linear regression
formula: R2=0.68, x-coefficient=0.005, SE=0.017); and for SM resistance
(X2=36.392, P<0.001; linear regression formula: R2=0.74,
x-coefficient=0.008, SE=0.131).
EMB=ethambutol, INH=isoniazid, RFP=rifampin, SE=standard error,
SM=streptomycin, and TB=tuberculosis.
Figure 2. Trends for MDR TB in rural China from 2006 to 2015.
For MDR (X2=43.629, P<0.001; linear regression formula: R2=0.53,
x-coefficient=0.006, SE=0.043); for MDR among new treated patients
(X2=51.279, P<0.001; linear regression formula: R2=0.53,
x-coefficient=0.007, SE=0.027); and for MDR among previously treated
patients (X2=60.481, P<0.001; linear regression formula: R2=0.71,
x-coefficient=0.015, SE=0.094).
MDR-TB=multidrug-resistant tuberculosis and SE=standard error.
Figure 3. Trends for the new treated MDR TB proportion among MDR
TB cases in rural China from 2006 to 2015.
(X2=12.291, P<0.001; linear regression formula: R2=0.38,
x-coefficient=0.027, SE=0.511).
MDR TB=multidrug-resistant tuberculosis and SE=standard error.
Figure 1
Figure 2
Figure 3
Table 1 Drug resistance to first-line drugs among new and previously treated patients in rural areas of Shandong, China
from 2006-2015
Drug resistance New treated patients (n=8155) Previously treated patients (n=1418) Total (n=9573)
n % n % n %
Any resistance to first-line drug 1781 (825) 21.8 (10.1) 526 (182) 37.1 (12.8) 2307 (1007) 24.1 (10.5)
INH 1196 (282) 14.7 (3.5) 386 (69) 27.2 (4.9) 1582 (351) 16.5 (3.7)
RFP 657 (64) 8.1 (0.8) 300 (31) 21.2 (2.2) 957 (95) 10.0 (1.0)
EMB 315 (24) 3.9 (0.3) 105 (5) 7.4 (0.4) 420 (29) 4.4 (0.3)
SM 1317 (455) 16.2 (5.6) 377 (77) 26.6 (5.4) 1694 (532) 17.7 (5.6)
Resistance to 2 drugs
INH+RFP 62 0.8 37 2.6 99 1.0
INH+SM 305 3.7 62 4.4 367 3.8
RFP+SM 31 0.4 23 1.6 54 0.6
Resistance to 3 drugs
INH+RFP+EMB 11 0.1 6 0.4 17 0.2
INH+RFP+SM 267 3.3 122 8.6 389 4.1
INH+EMB+SM 39 0.5 13 0.9 52 0.5
RFP+EMB+SM 7 0.1 3 0.2 10 0.1
At least INH/RFP 749 9.2 202 14.3 951 9.9
MDR, overall 552 6.8 242 17.1 794 8.3
Resistance to 4 drugs 212 2.6 77 5.4 289 3.0
EMB, ethambutol; INH, isoniazid; MDR, multidrug-resistant; RFP, rifampin; SM,streptomycin.
Numbers and rates of mono-first-line drug resistant cases are shown in parentheses.
Table 2 Univariable and multivariable logistic regression analyses of unique characteristics for MDR-TB among TB cases in
rural China from 2006 to 2015
Characteristics Non-MDR
TB
(n=8779)
MDR-
TB
(n=79
4)
Univariable
analysis
OR (95%CI)
P value
Multivariable
analysis
OR (95%CI)
P value
Age groups
0-14 63 (0.7) 3 (0.4) 0.53
(0.16-1.68)
0.27
15-24 1198
(13.6)
86
(10.8)
0.77
(0.61-0.97)
0.03
25-44 1818 174 1.08 0.42
(20.7) (21.9) (0.90-1.28)
45-64 3304
(37.6)
322
(40.6)
1.13
(0.98-1.31)
0.10
≥65 2396
(27.3)
209
(26.3)
0.95
(0.81-1.12)
0.56
Sex
Male 6982
(79.5)
592
(74.6)
Reference
Female 1797
(20.5)
202
(25.4)
1.33
(1.12-1.57)
0.00
1
1.58
(1.32-1.89
)
<0.0
01
aExcess alcohol 1243 104 0.91 0.41
consumption (14.2) (13.1) (0.74-1.13)
Smoker 1846
(21.0)
166
(20.9)
1.54
(1.31-1.81)
<0.0
01
1.75
(1.47-2.07
)
<0.0
01
bTB contact 163 (1.9) 27
(3.4)
1.86
(1.23-2.82)
0.00
3
1.58
(1.04-2.42
)
0.03
TB retreatment 1176
(13.4)
242
(30.5)
2.83
(2.41-3.34)
<0.0
01
2.89
(2.46-3.41
)
<0.0
01
a Excess alcohol consumption means ≥ 2 standard alcohol beverages per day.
b TB contact defined as contact with family members, schoolmates, or colleagues with TB.
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