SUMMARY
SETTING
During 2000–2006, a regional anti-tuberculosis drug resistance surveillance study was conducted in Shanghai, China.
OBJECTIVE
To determine the prevalence, trends and risk factors for drug resistant tuberculosis (TB) in Shanghai, China.
DESIGN
A retrospective study of all pulmonary TB patients reported in Shanghai during 2000–2006 was performed.
RESULTS
Of 8419 pulmonary TB patients, 16.6% had resistance to any first-line anti-tuberculosis drug and 4.0% had multi-drug resistance (MDR). The percentage of TB patients with resistance to any first-line anti-tuberculosis drug and MDR significantly increased during 2000–2003 (P = 0.01 and P<0.01, respectively). After improvements in the TB control programme in 2004, the increasing trend in drug resistance was contained. Age 30–59 years old, being an urban migrant and residence in an urban area of Shanghai were independently associated with resistance to any first-line drug and MDR in new cases, while age 30–59 years and being an urban migrant were independently associated with resistance to any first-line drug and MDR in previously treated cases.
CONCLUSIONS
Drug-resistant TB and MDR-TB pose a challenge for TB control in Shanghai. Improved case management, including DOTS and appropriate treatment regimens, should be sustained to prevent further transmission and development of drug-resistant TB in this setting.
Keywords: tuberculosis, drug resistance, MDR-TB, epidemiology
INTRODUCTION
The emergence of drug-resistant tuberculosis (TB), especially multidrug-resistant (MDR) TB1–3 and extensively drug-resistant (XDR) TB,4,5 poses a substantial threat to TB control programmes worldwide. In China, drug-resistant TB remains a serious public health problem. The World Health Organization (WHO) estimated that China had nearly 140,000 MDR-TB patients in 2004, the largest number of MDR-TB cases in the world.6,7 In some provinces of China, the prevalence of MDR-TB among new cases and previously treated cases was above 10% and 30%, respectively.1–3
The proportion of drug-resistant TB cases can be a useful indicator for assessing the performance of a TB control programme. Periodic assessment of trends in drug resistance is helpful for informing changes and adjustments in the approach to disease control. A low proportion of drug-resistant TB is associated with good management practices, such as DOTS. However, current levels of drug-resistant TB in China are still poorly known.
Previous studies identified several risk factors for drug-resistant TB.8–11 However, the risk factors reported by different study populations were heterogeneous, depending on patient characteristics and their geographical location as well as the epidemiological study design and sampling frame. For example, male sex was strongly associated with drug-resistant TB in some studies,11–13 but the association was weak and non-significant in other studies.8,10 The risk factors for drug-resistant TB in China are largely unknown.
To determine the prevalence, trends and risk factors for drug-resistant TB and MDR-TB in Shanghai, China, anti-tuberculosis drug resistance surveillance was conducted during 2000–2006.
STUDY POPULATION AND METHODS
Study population and setting
Shanghai had approximately 17 million inhabitants in 2005, of which 4–5 million were urban migrants (defined as poor individuals from rural areas of China who had moved to the metropolitan area).14 The notification rate of pulmonary TB in Shanghai in 2005 was 39.4 per 100 000 persons for the entire population, 29.3 per 100 000 among permanent residents and 70.6 per 100 000 among urban migrants.
In Shanghai, all suspected cases of pulmonary TB detected in a general hospital or a community health centre were referred to a specialised TB hospital or TB clinic, where the diagnosis was made by sputum smear, culture and chest radiography. All of the pretreatment positive cultures in each laboratory were sent to the Tuberculosis Reference Laboratory (TRL) at Shanghai Municipal Center for Disease Control and Prevention (Shanghai CDC), where drug susceptibility testing (DST) and specimen identification were performed. DST was routinely performed on isolates of Mycobacterium tuberculosis by the absolute concentration method (minimum inhibitory concentration [MIC]: isoniazid [INH] 1 ug/ml, rifampin [RMP] 50 ug/ml, streptomycin [SM] 10 ug/ml, ethambutol [EMB] 5 ug/ml) prior to 2004 and in 2005, or the proportion method (MIC: INH 0.2 ug/ml, RMP 40 ug/ml, SM 4 ug/ml, EMB 2 ug/ml) in 2004 and 2006. For this study, we included all culture-positive TB patients reported in Shanghai during 2000–2006.
Data analysis
We determined the prevalence of drug resistance among new TB cases and previously treated TB cases. A new TB case is defined as a patient who has never been treated or was treated for <1 month. A previously treated TB case is defined as a patient who has been treated for ≥1month. We used the χ2 test for trends to detect significant trends of drug resistance over time. Separate univariate and multivariate analyses were performed to determine the characteristics of the TB patients that were associated with resistance to at least one anti-tuberculosis drug and MDR-TB (defined as resistance to at least INH and RMP). A P value <0.05 was considered statistically significant. All analyses were performed using Stata statistical software (version 8.0SE, Stata Corporation, College Station, TX, USA).
Ethical approval
The study was approved by the Committee for Medical Research Ethics at Shanghai CDC and the University of California, Davis, CA, USA.
RESULTS
Study Population
During 2000–2006, a total of 27 304 pulmonary TB patients were diagnosed at the TB hospitals and clinics in Shanghai, of whom 18 346 (67.2%) had a sputum culture result available. Of 8841 (88.9%) patients who had an isolate available, 422 (4.8%) were infected with mycobacteria other than M. tuberculosis (MOTT) and were excluded from the analysis. There were 8419 (95.2%) patients infected with M. tuberculosis with DST results available comprised the study population used for analysis (Figure 1).
Figure 1.
Study population of drug-resistant tuberculosis in Shanghai, 2000–2006. For each step in the flow diagram, the percentage was calculated by dividing n by the value of n in the preceding step. PTB = Pulmonary tuberculosis; MOTT = mycobacteria other than M. tuberculosis.
Among the study population of 8419 TB patients, the median age was 48 years and 74.9% were male. Most patients (83.0%) were sputum smear-positive, 32.2% had a cavity on their initial chest radiograph and 10.9% of patients had a diagnosis of diabetes at the time of TB diagnosis. Two thirds (66.0%) of the patients lived in a rural or suburban area of Shanghai, and 16%had previously been treated with anti-tuberculosis drugs. In addition, 58.1% (348/599) of the previously treated TB patients who were residents of Shanghai from 2004 to 2006 TB were treated for their first episode of TB before 1990, before the initiation of family-member DOTS in Shanghai.
Prevalence and secular trends of drug resistance and MDR
Of the total 8419 patients, 16.6% had resistance to any of the four first-line anti-tuberculosis drugs, and 4.0% had MDR-TB. We also determined the percentage of cases with resistance to INH (10.3%), RMP (5.6%), SM (11.1%) and EMB (1.2%). The percentage of cases with resistance to any first-line drug and MDR was much higher among previously treated cases than among new cases (Table 1); 72.5% (1016/1401) of patients with resistance to any first-line drug and 59.8% (199/333) of patients with MDR did not report a history of previous TB treatment.
Table 1.
Percentage of TB cases with resistance to first-line anti-tuberculosis drugs in Shanghai, 2000–2006
| Year | P value | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
||||||||||||||||||
| 2000 | 2001 | 2002 | 2003 | 2004 | 2005 | 2006 | Total | |||||||||||
| n | (%) | n | (%) | n | (%) | n | (%) | n | (%) | n | (%) | n | (%) | n | (%) | 2000– 2003 |
2004– 2006 |
|
| All cases, n* | 970 | 941 | 1063 | 1074 | 1377 | 1507 | 1487 | 8419 | ||||||||||
| Resistant to any first-line drug | 131 | (13.5) | 150 | (15.9) | 161 | (15.1) | 193 | (18.0) | 252 | (18.3) | 251 | (16.7) | 263 | (17.7) | 1401 | (16.6) | 0.01 | 0.68 |
| Resistant to INH | 71 | (7.3) | 99 | (10.5) | 98 | (9.2) | 134 | (12.5) | 178 | (12.9) | 127 | (8.4) | 161 | (10.8) | 868 | (10.3) | <0.01 | 0.12 |
| Resistant to RMP | 48 | (4.9) | 34 | (3.6) | 44 | (4.1) | 64 | (6.0) | 103 | (7.5) | 92 | (6.1) | 87 | (5.9) | 472 | (5.6) | 0.19 | 0.09 |
| Resistant to SM | 85 | (8.8) | 94 | (10.0) | 113 | (10.6) | 128 | (11.9) | 170 | (12.3) | 172 | (11.4) | 175 | (11.8) | 937 | (11.1) | 0.02 | 0.64 |
| Resistant to EMB | 14 | (1.4) | 6 | (0.6) | 10 | (0.9) | 6 | (0.6) | 22 | (1.6) | 11 | (0.7) | 30 | (2.0) | 99 | (1.2) | 0.09 | 0.33 |
| MDR-TB | 24 | (2.5) | 26 | (2.8) | 36 | (3.4) | 49 | (4.6) | 81 | (5.9) | 55 | (3.6) | 62 | (4.2) | 333 | (4.0) | <0.01 | 0.04 |
| New cases, n | 801 | 782 | 931 | 914 | 1121 | 1207 | 1279 | 7035 | ||||||||||
| Resistant to any first-line drug | 92 | (11.5) | 111 | (14.2) | 126 | (13.5) | 144 | (15.8) | 178 | (15.9) | 162 | (13.4) | 203 | (15.9) | 1016 | (14.4) | 0.02 | 0.95 |
| Resistant to INH | 47 | (5.9) | 68 | (8.7) | 71 | (7.6) | 90 | (9.8) | 123 | (11.0) | 79 | (6.5) | 120 | (9.4) | 598 | (8.5) | <0.01 | 0.22 |
| Resistant to RMP | 31 | (3.9) | 22 | (2.8) | 32 | (3.4) | 39 | (4.3) | 56 | (5.0) | 52 | (2.3) | 55 | (4.3) | 287 | (4.1) | 0.50 | 0.42 |
| Resistant to SM | 63 | (7.9) | 75 | (9.6) | 90 | (9.7) | 96 | (10.5) | 121 | (10.8) | 115 | (9.5) | 130 | (10.2) | 690 | (9.8) | 0.08 | 0.63 |
| Resistant to EMB | 11 | (1.4) | 4 | (0.5) | 7 | (0.8) | 3 | (0.3) | 9 | (0.8) | 4 | (0.3) | 18 | (1.4) | 56 | (0.8) | 0.03 | 0.09 |
| MDR-TB | 16 | (2.0) | 17 | (2.2) | 26 | (2.8) | 26 | (2.8) | 44 | (3.9) | 32 | (2.7) | 38 | (3.0) | 199 | (2.8) | 0.15 | 0.21 |
| Previously treated cases, n | 165 | 159 | 132 | 160 | 256 | 300 | 208 | 1380 | ||||||||||
| Resistant to any first-line drug | 39 | (23.6) | 39 | (24.5) | 35 | (26.5) | 49 | (30.6) | 74 | (28.9) | 89 | (29.7) | 60 | (28.8) | 385 | (27.9) | 0.14 | 0.99 |
| Resistant to INH | 24 | (14.5) | 31 | (19.5) | 27 | (20.5) | 44 | (27.5) | 55 | (21.5) | 48 | (16.0) | 41 | (19.7) | 270 | (19.6) | <0.01 | 0.56 |
| Resistant to RMP | 17 | (10.3) | 12 | (7.5) | 12 | (9.1) | 25 | (15.6) | 47 | (18.4) | 40 | (13.3) | 32 | (15.4) | 185 | (13.4) | 0.104 | 0.334 |
| Resistant to SM | 22 | (13.3) | 19 | (11.9) | 23 | (17.4) | 32 | (20.0) | 49 | (19.1) | 57 | (19.0) | 45 | (21.6) | 247 | (17.9) | 0.05 | 0.52 |
| Resistant to EMB | 3 | (1.8) | 2 | (1.3) | 3 | (2.3) | 3 | (1.9) | 13 | (5.1) | 7 | (2.3) | 12 | (5.8) | 43 | (3.1) | 0.82 | 0.81 |
| MDR-TB | 8 | (4.8) | 9 | (5.7) | 10 | (7.6) | 23 | (14.4) | 37 | (14.5) | 23 | (7.7) | 24 | (11.5) | 134 | (9.7) | <0.01 | 0.32 |
The history of previous TB treatment was unknown for four patients.
TB = tuberculosis; INH = isoniazid; RMP = rifampicin; SM = streptomycin; EMB = ethambutol; MDR = multidrug resistance (defined as resistance to at least INH and RMP).
In 2004, the TB control programme in Shanghai initiated some improvements. Standard diagnostic procedures such as sputum smear examinations, culture, chest radiography procedures, DST and specimen identification were made free for all pulmonary TB patients, first-line anti-tuberculosis drugs were provided to pulmonary TB patients free of charge and family-member DOTS was available for urban migrants as well as residents. To evaluate the effect of the improvements initiated in 2004, we analysed the trends of drug resistance for the periods 2000–2003 and 2004–2006.
Table 1 shows the drug resistance patterns separately for all cases, new cases, and previously treated cases during 2000–2006. From 2000 to 2003, the percentage of all cases with resistance to any first-line drug increased significantly, from 13.5% to 18.0% (P = 0.01), while the percentage of all MDR-TB cases increased significantly, from 2.5% to 4.6% (P < 0.01). From 2004 to 2006, the percentage of all cases with resistance to any first-line drug was stable, and the percentage of all MDR-TB cases decreased by 28.8%, from 5.9% in 2004 to 4.2% in 2006 (P = 0.04). Among new cases, the percentage of cases with resistance to any first-line drug increased significantly (P = 0.02) from 2000 to 2003, and was stable (P = 0.95) from 2004 to 2006. The percentage of MDR-TB cases increased non-significantly from 2000 to 2003 (P = 0.15), and decreased non-significantly from 2004 to 2006 (P = 0.21). Among previously treated cases, the percentage of cases with resistance to any first-line drug increased non-significantly (P = 0.14) from 2000 to 2003, and was stable from 2004 to 2006 (P = 0.99). The percentage of MDR-TB cases significantly increased significantly from 2000 to 2003 (P < 0.01), and decreased non-significantly from 2004 to 2006 (P = 0.32).
Risk factors for resistance to any first-line anti-tuberculosis drug and MDR
By univariate analysis (Table 2), the following characteristics were significantly associated with resistance to any first-line drug and MDR-TB: diagnosis during 2004–2006, age 30–44 years, age 45–59 years, previous treatment for TB, being a migrant and residence in an urban area of Shanghai. Sex, presence of a cavity on initial chest radiograph, sputum smear positivity and diabetes at time of TB diagnosis were not significantly associated with resistance to any first-line drug or MDR-TB.
Table 2.
Results of the univariate analysis of the characteristics of tuberculosis patients associated with resistance to any first-line anti-tuberculosis drug and multidrug resistance in Shanghai, 2000–2006
| Characteristics of TB patients | Drug susceptibility* |
Any resistance† | Multidrug Resistance‡ | ||||||
|---|---|---|---|---|---|---|---|---|---|
| n (%) | n (%) | OR | (95% CI) | P value | n (%) | OR | (95% CI) | P value | |
| Year | |||||||||
| 2000–2003 (n = 4048) | 3413 (84.3) | 635 (15.7) | Referent | 135 (3.3) | Referent | ||||
| 2004–2006 (n = 4371) | 3605 (82.5) | 766 (17.5) | 1.1 | (1.0–1.3) | 0.02 | 198 (4.5) | 1.4 | (1.1–1.8) | <0.01 |
| Age, years | |||||||||
| 15–14 (n = 23) | 18 (78.3) | 5 (21.7) | 1.9 | (0.5–5.3) | 0.21 | 2 (8.7) | 3.4 | (0.4–14.5) | 0.09 |
| 15–29 (n = 1679) | 1397 (83.2) | 282 (16.8) | 1.4 | (1.1.–1.6) | <0.01 | 50 (3.0) | 1.1 | (0.7–1.6) | 0.65 |
| 30–44 (n = 1981) | 1583 (79.9) | 398 (20.1) | 1.7 | (1.4–2.0) | <0.01 | 101 (5.1) | 1.9 | (1.4–2.6) | <0.01 |
| 45–59 (n = 1908) | 1557 (81.6) | 351 (18.4) | 154 | (1.3–1.8) | <0.01 | 99 (5.2) | 1.9 | (1.4–2.6) | <0.01 |
| ≥60 (n = 2827) | 2462 (87.1) | 365 (12.9) | Referent | 81 (2.9) | Referent | ||||
| Sex | |||||||||
| Female (n = 2112) | 1757 (83.2) | 355 (16.8) | Referent | 80 (3.8) | Referent | ||||
| Male (n = 6307) | 5261 (83.4) | 1046 (16.6) | 1.0 | (0.9–1.1) | 0.91 | 253 (4.0) | 1.1 | (0.8–1.4) | 0.68 |
| Previous TB Treatment§ | |||||||||
| Yes (n = 1380) | 995 (72.1) | 385 (27.9) | 2.3 | (2.0–2.6) | <0.01 | 134 (9.7) | 4.1 | (3.2–5.2) | <0.01 |
| No (n = 7035) | 6019 (85.6) | 1016 (14.4) | Referent | 199 (2.8) | Referent | ||||
| Cavity on initial chest radiograph¶ | |||||||||
| Present (n = 2714) | 2235 (82.4) | 479 (17.6) | 1.1 | (1.0–1.3) | 0.09 | 99 (3.6) | 0.9 | (0.7–1.2) | 0.49 |
| Absent (n = 5410) | 4535 (83.8) | 875 (16.2) | Referent | 219 (4.0) | Referent | ||||
| Sputum smear result# | |||||||||
| Positive (n = 6990) | 5803 (83.0) | 1187 (17.0) | 1.2 | (1.0–1.4) | 0.06 | 284 (4.1) | 1.3 | (0.9–1.7) | 0.17 |
| Negative (n = 1378) | 1172 (85.1) | 206 (14.9) | Referent | 46 (3.3) | Referent | ||||
| Diabetes at time of TB diagnosis | |||||||||
| Present (n = 916) | 771 (84.2) | 145 (15.8) | 0.9 | (0.8–1.1) | 0.49 | 32 (3.5) | 0.9 | (0.6–1.3) | 0.43 |
| Uncertain (n = 7503) | 6247 (83.3) | 1256 (16.7) | Referent | 301 (4.0) | Referent | ||||
| Residents versus. Migrants | |||||||||
| Residents (n = 6651) | 5608 (84.3) | 1043 (15.7) | Referent | 247 (3.7) | Referent | ||||
| Migrants (n = 1768) | 1410 (79.8) | 358 (20.2) | 1.4 | (1.2–1.6) | <0.01 | 86 (4.9) | 1.4 | (1.1–1.8) | 0.01 |
| Residential Area | |||||||||
| Rural and Suburban (n = 5554) | 4726 (85.1) | 828 (14.9) | Referent | 179 (3.2) | Referent | ||||
| Urban (n=2,865) | 2292 (80.0) | 573 (20.0) | 1.4 | (1.3–1.6) | <0.01 | 154 (5.4) | 1.8 | (1.4–2.2) | <0.01 |
Mycobacterium tuberculosis strains susceptible to four first-line anti-tuberculosis drugs (INH, RMP, EMB and SM).
Defined as resistance to at least one of four first-line anti-tuberculosis drugs (INH, RMP, EMB and SM).
Defined as resistance to at least INH and RMP.
Unknown for four patients.
295 patients had a chest radiograph in which the presence of a cavity was uncertain.
Unknown for 51 patients.
OR = odds ratio; CI = confidence interval; TB – tuberculosis; INH = isoniazid; RMP = rifampicin; EMB = ethambutol; SM = streptomycin.
In the multivariate analysis (Table 3), we separately determined the characteristics that were independently associated with resistance to any first-line drug and MDR-TB in new and previously treated cases. For new cases, those who were aged 30–59 years, migrants and residents in an urban area of Shanghai were more likely to have resistance to any first-line drug and MDR-TB. Moreover, the interaction between migrants and age 30–59 years was also significant for resistance to any first-line drug. In previously treated cases, those aged 30–59 years and migrants were more likely to have resistance to any first-line drug and MDR-TB.
Table 3.
Results of the multivariate analyses of the characteristics of tuberculosis patients that were independently associated with resistance to any first-line anti-tuberculosis drug and multidrug resistance in Shanghai, 2000–2006
| Any Resistance* | Multidrug Resistance† | |||||
|---|---|---|---|---|---|---|
| Variables | aOR | (95%CI) | P value | aOR | (95%CI) | P value |
| New cases | ||||||
| Age 30–59 years | 1.4 | (1.2–1.6) | <0.01 | 1.5 | (1.1–2.0) | <0.01 |
| Migrants | 1.7 | (1.4–2.2) | <0.01 | 1.5 | (1.1–2.0) | 0.02 |
| Residence in an urban area | 1.5 | (1.3–1.8) | <0.01 | 2.0 | (1.5–2.7) | <0.01 |
| Interaction‡ | ||||||
| Migrants and age 30–59 years | 0.7 | (0.5–0.9) | 0.02 | NS | ||
| Previously treated cases | ||||||
| Age 30–59 years | 2.1 | (1.6–2.6) | <0.01 | 2.8 | (1.9–4.1) | <0.01 |
| Migrants | 1.9 | (1.4–2.7) | <0.01 | 2.1 | (1.4–3.4) | <0.01 |
Defined as resistance to at least one of four first-line anti-tuberculosis drugs (INH, RMP, EMB and SM).
Defined as resistance to at least INH and RMP.
The product of two listed variables, where “residents vs. migrants”=1 for migrants, “age” = 1 for age 30–59 years. Therefore, the interaction terms referred to migrants with age 30–59 years.
aOR = adjusted odds ratio; CI = confidence interval; NS = not significant; INH = isoniazid; RMP = rifampicin.
DISCUSSION
In Shanghai, resistance to any of the four first-line anti-tuberculosis drugs and MDR-TB significantly increased among pulmonary TB patients between 2000 and 2003. However, after improvements in the TB control programme were implemented in 2004, such as free diagnosis and treatment for all patients and DOTS for migrants as well as residents, the increasing trend in drug resistance was contained, suggesting that the improved TB programme activities had helped prevent further increases in drug resistance in this setting, a metropolitan area in China with a large number of migrants. Furthermore, a number of patient characteristics, including migrant status, age 30–59 years and residence in an urban area were independently associated with drug-resistant TB in Shanghai.
Compared to other areas in China, Shanghai had a lower prevalence of drug-resistant TB and MDR-TB among both new patients and previously treated cases.1–3 Shanghai’s relatively low prevalence of drug resistant TB and MDR-TB might be attributed to the easy access and high quality of health care and DOTS. Since 1990, there have been high cure rates (>85%) among the residents of Shanghai.15 However, the prevalence of drug-resistant TB and MDR-TB in Shanghai was still higher than the median prevalence worldwide.1–3
Drug-resistant TB in Shanghai may have appeared for several factors. First, recent or ongoing transmission of drug resistant M. tuberculosis is occurring. The majority of TB patients with resistance to at least one first-line drug (72.5%) and MDR-TB (59.8%) did not report any history of previous TB treatment, and it is thus likely that these patients were infected with a drug resistant strain of M. tuberculosis. A recent molecular epidemiological study in Shanghai showed that among previously treated patients, the percentage of TB cases that were attributed to recent transmission in Shanghai was high.16,17 Previous studies, mainly from similar settings in low-incidence countries, showed that residence in an urban area18–21 was independently associated with recent TB transmission. In the present study, new patients residing in an urban area were more likely to have drug-resistant TB, further suggesting recent transmission.
Second, inadequate case management or poor treatment could result in the emergence or amplification of drug resistance. We found that the percentage of cases with resistance to any first-line anti-tuberculosis drug and MDR was much higher among previously treated cases than among new cases. A history of previous treatment for TB has been well documented as a strong predictor of drug resistance and, in particular, of MDR-TB.8–10,22 In the present study, 58.1% of the previously treated cases reported among residents from 2004 to 2006 were treated for their first episode of TB before 1990 and prior to the initiation of DOTS in Shanghai, an era with poor adherence to treatment and low rates of treatment success.
Previous studies in other countries showed that DOTS could reduce TB transmission,23,24 reduce the incidence of drug-resistance24 and prevent acquired drug resistance.22,25 A study during 1978–1996 in Beijing, another metropolitan area in China, showed that DOTS could effectively reduce the prevalence of initial drug resistance when the number of migrants with TB was not high.26 The efficacy of DOTS in migrants, however, remained unknown. Family-member DOTS is used in Shanghai, and a recent review of 11 randomized controlled trials conducted in low-, middle- and high-income countries with 3985 participants showed that there is no assurance that DOTS administered at a clinic vs. by a family member or community health worker has a quantitatively important effect on cure or completion of therapy in TB patients.27 Our study showed a decreasing trend in drug resistance from 2004 to 2006, suggesting that the DOTS strategy can prevent increases in drug resistance in settings with large numbers of urban migrants in China. The lack of increase in drug resistance might be due to the intensified detection of migrant TB patients and rendering them non-infectious by treatment under DOTS. From 2004 to 2006, both the percentage of TB suspects examined by sputum microscopy and the percentage of TB patients treated under DOTS among migrant TB patient increased (data not shown).
There are several limitations to our study. First, the low proportion (32.4 %) of patients with an available DST result may have introduced a bias. Patients were more likely to have a DST result available if they were detected during 2004–2006 and were male, previously treated for TB, had a cavity on the initial chest radiograph, had a positive sputum smear result, and were a resident of Shanghai (data not shown). Second, treatment history is difficult to determine precisely. Although we interviewed the patients, reviewed the medical records and screened the mandatory notification system to check for previous episodes of TB, we cannot exclude the possibility that misclassification occurred and that some of the new TB patients were in fact previously treated cases, particularly among the migrants. Third, we were not able to perform DST for second-line anti-tuberculosis drugs in this study. However, given that the prevalence of MDR-TB in Shanghai is high and second-line anti-tuberculosis drugs (such as capreomycin, amikacin, and kanamycin) and fluoroquinolones are widely used for other bacterial infections and are used to treat TB more frequently now than before, we cannot exclude the possibility that XDR-TB is prevalent in Shanghai.
CONCLUSION
This study has shown that drug-resistant TB and MDR-TB pose a great challenge for TB control in Shanghai. Improvements in the TB control programme have helped prevent further increases in drug-resistant TB in this metropolitan setting with large numbers of migrants. Recent or ongoing transmission of drug-resistant M. tuberculosis may be a major cause of drug-resistant TB and MDR-TB. Improved case management, including DOTS and appropriate treatment regimens for drug-resistant TB and MDR-TB, should be sustained to prevent further transmission of M. tuberculosis and acquired drug resistance.
Acknowledgements
The authors wish to thank the TB controllers, programme field staff and laboratory staff in Shanghai who reported the data used in this study and R Fang for data cleaning. This study was supported by the Key Project of Chinese National Programmes for Fundamental Research and Development (973 programme 2005CB523102 and 2002CB512804), the Chinese National Programmes 863 (2006AA02Z423), the Shanghai CDC Research and Education Development Foundation (2006-02), and the National Institutes of Health, USA (grants TW01409 and D43TW007887).
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