Tuberculosis prevalence

Articles
Tuberculosis prevalence in China, 1990–2010;
a longitudinal analysis of national survey data
Lixia Wang*, Hui Zhang*, Yunzhou Ruan*, Daniel P Chin*, Yinyin Xia, Shiming Cheng, Mingting Chen, Yanlin Zhao, Shiwen Jiang, Xin Du,
Guangxue He, Jun Li, Shengfen Wang, Wei Chen, Caihong Xu, Fei Huang, Xiaoqiu Liu, Yu Wang
Summary
Background China scaled up a tuberculosis control programme (based on the directly observed treatment, short-course
[DOTS] strategy) to cover half the population during the 1990s, and to the entire population after 2000. We assessed
the effect of the programme.
Methods In this longitudinal analysis, we compared data from three national tuberculosis prevalence surveys done in
1990, 2000, and 2010. The 2010 survey screened 252 940 eligible individuals aged 15 years and older at 176 investigation
points, chosen by stratified random sampling from all 31 mainland provinces. All individuals had chest radiographs
taken. Those with abnormal radiographs, persistent cough, or both, were classified as having suspected tuberculosis.
Tuberculosis was diagnosed by chest radiograph, sputum-smear microscopy, and culture. Trained staff interviewed
each patient with tuberculosis. The 1990 and 2000 surveys were reanalysed and compared with the 2010 survey.
Findings From 1990 to 2010, the prevalence of smear-positive tuberculosis decreased from 170 cases (95% CI 166–174)
to 59 cases (49–72) per 100 000 population. During the 1990s, smear-positive prevalence fell only in the provinces with
the DOTS programme; after 2000, prevalence decreased in all provinces. The percentage reduction in smear-positive
prevalence was greater for the decade after 2000 than the decade before (57% vs 19%; p<0·0001). 70% of the total
reduction in smear-positive prevalence (78 of 111 cases per 100 000 population) occurred after 2000. Of these cases,
68 (87%) were in known cases—ie, cases diagnosed with tuberculosis before the survey. Of the known cases, the
proportion treated by the public health system (using the DOTS strategy) increased from 59 (15%) of 370 cases in 2000
to 79 (66%) of 123 cases in 2010, contributing to reduced proportions of treatment default (from 163 [43%] of 370 cases
to 35 [22%] of 123 cases) and retreatment cases (from 312 [84%] of 374 cases to 48 [31%] of 137 cases; both p<0·0001).
Interpretation In 20 years, China more than halved its tuberculosis prevalence. Marked improvement in tuberculosis
treatment, driven by a major shift in treatment from hospitals to the public health centres (that implemented the
DOTS strategy) was largely responsible for this epidemiological effect.
Lancet 2014; 383: 2057–64
Published Online
March 18, 2014
http://dx.doi.org/10.1016/
S0140-6736(13)62639-2
See Comment page 2026
*Authors contributed equally
Chinese Center for Disease
Control and Prevention,
Beijing, China
(L Wang MS, H Zhang PhD,
Y Ruan PhD, Y Xia PhD,
S Cheng BS, M Chen MS,
Y Zhao PhD, S Jiang BS, X Du BS,
G He PhD, J Li MS, S Wang PhD,
W Chen PhD, C Xu MS,
F Huang MS, X Liu MS,
Y Wang MD); and China Office,
The Bill & Melinda Gates
Foundation, Beijing, China
(D P Chin MD)
Correspondence to:
Dr Yu Wang, Chinese Center for
Disease Control and Prevention,
Beijing, 102206, China
wangyu@chinacdc.cn
Funding Chinese Ministry of Health.
Introduction
In 2010, China had an estimated 1 million new
tuberculosis cases, accounting for 11% of global
tuberculosis incidence.1 The country began to address its
tuberculosis problem on a large scale in the 1990s when
a tuberculosis control project, containing key elements
of the internationally recommended directly observed
treatment, short-course (DOTS) strategy (hereafter
called the DOTS programme), was implemented in
13 provinces containing half the country’s population.2
Two national surveys of the prevalence of tuberculosis—
done in 1990 and 2000—showed a 30% increased
reduction in tuberculosis prevalence in areas that
implemented this project.3 However, the national
tuberculosis prevalence fell by less than 20% in 10 years;3
this slight reduction could be because, at its peak, the
project treated only 30% of the estimated new smearpositive tuberculosis cases in the country.4
To accelerate the national tuberculosis control effort, the
State Council of China issued a new 10-year tuberculosis
control plan in 2001, which expanded the DOTS
programme to the entire country by 2005. A previous
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report detailed the measures developed and implemented
by the government to increase the number of tuberculosis
patients treated in the DOTS programme.5 Through these
efforts, China achieved the 2005 global tuberculosis
control targets of detecting at least 70% of all estimated
new smear-positive tuberculosis cases and successfully
treating more than 85% of these patients—the only
country with a high tuberculosis burden to achieve this.1,6
To re-evaluate China’s tuberculosis burden, a national
tuberculosis prevalence survey was done in 2010. We
report the main findings of the latest survey and compare
the results with those from the 1990 and 2000 surveys;7,8
this analysis allowed us to assess the effects of 20 years of
tuberculosis control.
Methods
Survey design
We undertook a longitudinal analysis of data from 1990,
2000, and 2010 national tuberculosis prevalence surveys in
China. For the 2010 survey, we used multistage, stratified
sampling to randomly select 176 investigation points from
within the 31 mainland provinces, municipalities, and
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autonomous regions (hereafter termed provinces). We
sampled urban and rural sites separately to ensure the
survey had 77 urban and 99 rural investigation points, in
line with the urban:rural ratio of the national population.
All people aged 15 years or older and a local resident
(defined as residing in the survey area for at least 6 months)
were eligible for the survey. Each investigation point
averaged 1503 people. The survey was done from April,
2010, to July, 2010. The survey design is consistent with
global guidelines.9 The study was reviewed and approved
by the Tuberculosis Operational Research Ethics Review
Committee of Chinese Ministry of Health; the need for
individual informed consent was waived by the committee.
Patients and procedures
All participants had chest radiographs taken. Those with
cough for greater than 2 weeks or haemoptysis were
classified as having symptoms of tuberculosis (figure 1).
We collected sputum from individuals with any of the
four following characteristics: tuberculosis symptoms,
an abnormal chest radiograph, a diagnosis of tuberculosis
before the survey, and a pregnant woman or person with
restricted mobility who were not examined by chest
radiography. Three sputum specimens (spot, night, and
morning) were collected for smear microscopy and two
specimens were cultured on Löwenstein–Jensen
medium. The selection of specimens for culture was
based on the level of smear positivity and appearance.
Individuals 15 years or older,
resident at investigation point
Clinical history/chest x-ray
Abnormal chest
radiograph or
tuberculosis symptoms
Known tuberculosis
patient
Pregnant women or
individuals with
restricted mobility
(no chest radiograph)
Normal chest
radiograph and no
tuberculosis symptoms
Sputum smear and culture
Positive smear and
negative culture
Mycobacterium
tuberculosis
Positive culture ±
positive smear
Non-tuberculous
mycobacteria
Negative smear
and culture
Expert panel re-read
chest radiograph
A positive smear had at least one acid-fast bacillus
identified during examination of 100 fields. Slides were
reviewed by a central team of experts, and only those
identified as positive on both initial and repeat
examinations were classified as positive. A positive
culture had at least one colony of Mycobacterium
tuberculosis complex isolated. Bacteriologically positive
cases were those with at least one positive smear or
culture. Smear and culture were done at a tuberculosis
laboratory in either the city or county closest to the
investigation site. These laboratories had technicians
trained to undertake tuberculosis testing according to
national guidelines and participated in internal and
external quality assurance programmes for smear
microscopy. During the survey period, a provincial
tuberculosis reference laboratory closely monitored the
quality of the sputum culture and provided assistance to
laboratories whenever culture contamination exceeded
5% or the percentage of negative culture in the smearpositive specimens exceeded 10%. Cultures with growing
colonies were sent to the National Tuberculosis Reference
Laboratory for identification.
Patients with active tuberculosis included those with
bacteriologically-positive sputum and those diagnosed
only by changes on their chest radiographs. Therefore,
individuals with active tuberculosis included patients
with smear-positive and culture-negative sputum, smearnegative but culture-positive sputum, and smear-negative
and culture-negative sputum. Survey staff were trained to
diagnose active tuberculosis cases on the basis of patient
symptoms and clinical history, radiographic findings,
bacteriological results, and response to antibiotics, in
accordance with national guidelines. A national expert
group reviewed the data from each patient to confirm the
diagnosis.
Newly identified cases were separated from known, or
previously diagnosed, cases that were still active at the
time of the survey. The sampling approach and the
clinical and laboratory methods for diagnosis of
tuberculosis in the 2010 survey were the same as those
used in the 1990 and 2000 surveys, but were done at
different investigation sites and by different survey teams
than those in 2010.
Trained staff administered a standard questionnaire to
every person with tuberculosis. People with a previous
diagnosis of tuberculosis, were classified as known cases
and were asked questions about their past and present
diagnosis and treatment. For the known cases, we
checked the tuberculosis registry of the public health
system to establish whether the patient had been reported
to, and registered in, the Chinese Center for Disease
Control and Prevention (CDC) system.
Previous surveys
Tuberculosis
Figure 1: Diagnostic algorithm used during the 2010 prevalence survey
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Not tuberculosis
Although the 1990 and 2000 surveys had similar designs,
they differed in some areas.7,8 First, both the 1990 and
2000 surveys included testing for individuals aged
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Articles
Prevalence per 100 000 population
Change (%)*
1990
2000†
2010†
1990–2000
2000–2010
1990–2010
All pulmonary
611 (603 to 619)
414 (390 to 439)
442 (417 to 469)
–32% (–36 to –28)
7% (–2 to 16)
–28% (–32 to –23)
Bacteriologically positive
221 (216 to 226)
178 (163 to 195)
116 (101 to 132)
–19% (–27 to –12)
–35% (–45 to –23)
–48% (–55 to –40)
Smear positive
170 (166 to 174)
137 (123 to 153)
59 (49 to 72)
–19% (–28 to –10)
–57% (–66 to –46)
–65% (–72 to –58)
All provinces
Provinces that implemented DOTS in 1990s‡
All pulmonary
665 (653 to 677)
364 (335 to 395)
462 (423 to 505)
–45% (–50 to –40)
27% (12 to 44)
–31% (–37 to –24)
Bacteriologically positive
239 (232 to 246)
154 (135 to 174)
110 (93 to 130)
–36% (–44 to –27)
–29% (–43 to –12)
–54% (–62 to –46)
Smear positive
176 (170 to 182)
113 (96 to 133)
63 (50 to 80)
–36% (–46 to –24)
–44% (–59 to –26)
–64% (–72 to –55)
Provinces that implemented DOTS after 2000‡
All pulmonary
663 (652 to 674)
499 (459 to 542)
443 (411 to 478)
–25% (–31 to –18)
–11% (–21 to 0)
–33% (–38 to –28)
Bacteriologically positive
225 (219 to 231)
219 (194 to 248)
124 (101 to 152)
–3% (–15 to 10)
–43% (–56 to –28)
–45% (–56 to –33)
Smear positive
180 (174 to 186)
174 (151 to 201)
59 (43 to 79)
–3% (–17 to 12)
–66% (–76 to –53)
–67% (–77 to –56)
Data are mean (95% CI) for individuals aged 15 years and older. DOTS=direct observed treatment, short-course. *Negative values show decrease in prevalence. †Data analysed
with 1990 diagnostic protocol, except chest radiograph used in initial screening instead of fluoroscopy in 2010; results unstandardised for age or other variables. ‡Provinces
that implemented DOTS in 1990s include Chongqing, Gansu, Guangdong, Hainan, Hebei, Heilongjiang, Hubei, Hunan, Liaoning, Ningxia, Shandong, Sichuan, and Xinjiang;
provinces that implemented DOTS after 2000 include Anhui, Fujian, Guangxi, Guizhou, Henan, Jiangsu, Jiangxi, Jilin, Neimeng, Qinghai, Shaanxi, Shanxi, Tibet, Yunnan, and
Zhejiang. The three municipalities of Beijing, Shanghai, and Tianjin are excluded from this analysis because, for more than 30 years, they have had high economic development,
substantial expertise in tuberculosis control, and organised tuberculosis control programmes similar to the DOTS programme.
Table 1: Comparison of tuberculosis prevalence over time in provinces that implemented DOTS in 1990s and after 2000
younger than 15 years; the 2010 survey did not do this. In
this study, we reanalysed the 1990 and 2000 surveys with
only results from individuals aged 15 years or older.
Second, chest fluoroscopy was used to screen individuals
in 1990 and 2000; chest radiographs were used in 2010.
Third, in 1990, only symptomatic individuals were
examined by chest fluoroscopy and asked to provide
sputum if the fluoroscopic examination was abnormal.
In 2000 and 2010, individuals with tuberculosis
symptoms but normal fluoroscopic examinations (or
normal chest radiographs) were also asked to provide
sputum. Finally, in 1990, two sputum smears were used
instead of three, and in both 1990 and 2000 only one
specimen was cultured.
The diagnostic protocol used in 2000 was therefore
more sensitive than that used in 1990, and the protocol
used in 2010 was more sensitive than that used in 2000.
For comparisons involving all three surveys, we
calculated prevalences according to the 1990 diagnostic
protocol. With this protocol, only individuals with
tuberculosis symptoms were further assessed. In
symptomatic patients with abnormal radiographic
examination, we used the results of two sputum smears
and one culture to establish each patient’s bacteriological
status. For comparisons involving only the 2000 and 2010
surveys, we used the 2000 diagnostic protocol. This
protocol differed from the 1990 protocol in only one
aspect: three sputum smears were used instead of two.
Statistical analysis
The survey was designed to detect an annual decline
of 3·2% in national prevalence of smear-positive
tuberculosis between 2000 and 2010 with a probability of
www.thelancet.com Vol 383 June 14, 2014
greater than 95% and power of 95%. This rate of decline
was observed in areas implementing the DOTS strategy
from 1990 to 2000.3 We calculated the sample size to be
264 630 with simple random sampling, a design effect of
1·8 from the 2000 survey, and 90% participation rate.
Although the survey was not designed a priori to
compare subpopulations within China, we stratified the
data in several ways: sex, age, urbanisation (urban and
rural), region (western, central, and eastern parts of the
country), and provinces that implemented the DOTS
programme in the 1990s and after 2000.
We calculated the overall prevalence rates and the
stratum-specific rates for various subpopulations and
analysed patient information using the complex survey
module in SPSS Statistics 17.0. This module takes into
account the clustered sampling design of the survey. CIs
were adjusted for the cluster design by the Taylor series
linearisation. When comparing prevalences in different
subpopulations and over time, we adjusted p values using
the second-order correction of Rao–Scott for the χ² test.
The difference or change in prevalence was assumed to
follow a beta distribution. Two shape parameters needed to
define the β distribution were computed using the method
of moments. The upper and lower 2·5% of the resulting
distribution were used to determine the 95% CI. We did
these computations using R statistical package (2.15.1).
Role of the funding source
The sponsor of the study had no role in study design,
data collection, data analysis, data interpretation, or
writing of the report. The Chinese CDC operates under
the general guidance of the Ministry and was responsible
for the design, implementation, and analysis of the 2010
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survey. LW, HZ, YR, YX, and DPC had complete access to
the data and were responsible for submitting the Article
for publication.
Results
Of 263 281 individuals eligible in 2010, 252 940 (96%)
participated in the survey, 4541 (2%) refused to participate,
3709 (1%) were not at the investigation site during the
survey, and 2091 (1%) did not participate for other
reasons. Of 9825 people eligible for sputum examination,
9716 (99%) had examination results, and 109 (1%) did not
submit sputum samples. With the 2010 diagnostic
protocol, 1310 cases of active pulmonary tuberculosis
were detected, of which 347 were bacteriologically
positive (119 per 100 000 population; 95% CI 103–135)
and 188 were sputum smear-positive (66 per 100 000
population; 95% CI 53–79).
From 1990 to 2010, smear-positive prevalence fell
by 65%, bacteriologically positive prevalence declined by
48%, and prevalence of all pulmonary cases
declined by 28% (table 1). 70% of the reduction in smearpositive prevalence and 59% of the reduction in
bacteriologically-positive prevalence occurred after 2000.
Smear-positive prevalence
(per 100 000 population)
250
New cases
Known cases
From 1990 to 2000, provinces that implemented the
DOTS programme had a significant reduction in the
prevalence of smear-positive and bacteriologically
positive tuberculosis cases; other provinces did not have
this reduction (table 1). From 2000 to 2010, these
prevalences decreased in both groups of provinces,
reaching roughly the same level by 2010; this resulted
from a greater (although not statistically significant)
reduction in provinces that implemented DOTS after
2000.
The reduction in prevalence of smear-positive and
bacteriologically positive tuberculosis cases was largely
due to a reduction in the prevalence of known cases
(figure 2). From 2000 to 2010, the prevalence of smearpositive tuberculosis among known cases decreased by
88% (from 77 to 9 per 100 000 population). This decrease
accounted for 87% of the total reduction in smear-positive
prevalence (68 of 78 per 100 000 population).
From 2000 to 2010, the prevalence of bacteriologically
positive tuberculosis decreased significantly in all
subpopulations examined, including men, women, all
age groups, urban and rural areas, and all regions except
western China (table 2). The reduction in prevalence was
significantly less in western than in eastern China
(p=0·0026), but not significantly different between strata
in other subpopulations.
200
Prevalence per
100 000 population*
150
100
Change,
2000–2010 (%)†
2000
2010
Male
304 (275 to 337)
183 (157 to 215)
–40% (–51 to –27)
Female
115 (96 to 139)
64 (52 to 79)
–44% (–58 to –26)
Sex
50
Age group (years)
0
Bacteriologically positive prevalence
(per 100 000 population)
250
200
92 (72 to 116)
59 (40 to 86)
–36% (–61 to 0)
30–44
119 (96 to 146)
73 (54 to 99)
–39% (–59 to –11)
45–59
213 (174 to 260)
133 (106 to 168)
–38% (–55 to –15)
≥60
596 (510 to 698) 346 (294 to 407)
–42% (–54 to –27)
Urbanisation
150
Urban
152 (115 to 202)
Rural
225 (206 to 246) 163 (143 to 185)
73 (51 to 105)
–52% (–71 to –23)
–28% (–38 to –15)
Region‡
100
50
0
1990
2000
Year
2010
Figure 2: Prevalence of smear-positive and bacteriologically positive
tuberculosis stratified by new and known cases, 1990–2010
Analysed by use of 1990 diagnostic protocol and unstandardised for age or
other variables. Error bars show the 95% CI. Prevalence of smear-positive or
bacteriologically positive tuberculosis in known cases was significantly lower in
2010 than in 1990 or 2000. Prevalence of smear-positive tuberculosis in new
cases was significantly lower in 2010 than in 1990; this difference is not seen in
bacteriologically positive new cases.
2060
15–29
Eastern
158 (137 to 183)
66 (52 to 84)
–58% (–69 to –45)
Central
241 (203 to 285)
124 (92 to 166)
–49% (–64 to –28)
Western
262 (228 to 302)
212 (180 to 249)
–19% (–35 to 1)
Data are mean (95% CI) for individuals aged 15 years and older. *Data analysed
with 2000 diagnostic protocol, except chest radiograph used in initial screening
instead of fluoroscopy in 2010, and unstandardised for age or other variables.
†Negative values show decrease in prevalence. ‡Eastern provinces include
Beijing, Fujian, Guangdong, Hainan, Heibei, Jiangsu, Liaoning, Shandong,
Shanghai, Tianjin, and Zhejiang; central provinces include Anhui, Heilongjiang,
Henan, Hunan, Hubei, Jiangxi, Jilin, and Shanxi; western provinces include
Chongqing, Gansu, Guangxi, Guizhou, Neimeng, Ningxia, Qinghai, Shaanxi,
Sichuan, Tibet, Xinjiang, and Yunnan.
Table 2: Change in the prevalence of bacteriologically positive
tuberculosis in subpopulations, 2000 and 2010
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Hospitals
Cases classified by where they were diagnosed
Reported and registered in CDC system
CDC
2000
2010
329
77
50 (15%)
34 (50%)
p value
··
<0·0001
All institutions
2000
2010
45
60
43 (95%)
56 (95%
p value
··
0·6948
2000
2010
374
137
93 (23%)
90 (69%)
p value
··
<0·0001
Classified as retreatment case during most recent diagnosis
281 (86%
30 (33%)
<0·0001
31 (67%)
18 (28%)
<0·0001
312 (84%)
48 (31%)
<0·0001
Started tuberculosis treatment after recent diagnosis
325 (99%)
66 (87%)
<0·0001
45 (100%)
57 (96%)
<0·0001
370 (99%)
123 (91%)
<0·0001
311
44
59
79
370
123
Cases started on treatment classified by where they were treated*
Regularity of drug intake‡
··
<0·0001
··
<0·0001
··
<0·0001
Regular
62 (21%)
14 (41%)
··
36 (57%)
59 (82%)
··
98 (26%)
73 (68%)
··
Intermittent (on and off)
99 (34%)
9 (17%)
··
10 (17%)
6 (7%)
··
109 (31%)
15 (10%)
··
Defaulted from treatment
150 (46%)
21 (42%)
··
13 (26%)
14 (12%)
··
163 (43%)
35 (22%)
Reasons for defaulting from treatment‡
0·0335
0·0002
··
<0·0001
Felt better, self discontinued
69 (45%)
13 (60%)
··
3 (20%)
3 (22%)
··
72 (42%)
16 (47%)
··
Financial difficulties
65 (45%)
3 (17%)
··
6 (46%)
1 (11%)
··
71 (45%)
4 (15%)
··
6 (5%)
2 (8%)
··
0 (0%)
8 (57%)
··
6 (4%)
10 (25%)
··
10 (6%)
3 (14%)
··
4 (33%)
2 (9%)
··
14 (8%)
5 (13%)
··
Side-effects
Others
Data are N or n (%). CDC=Centers for Disease Control. Calculation of percentages takes into account the multistage, stratified sampling design, therefore the percentages presented in the table might not be
reproducible simply from data in the table. *Few patients were not treated in the type of institution where they were diagnosed. ‡Denominator for regularity of drug intake is the number of patients started on
treatment; denominator for reasons for defaulting is the number of patients defaulted from treatment.
Table 3: Reporting and treatment of previously diagnosed tuberculosis cases by where patients were diagnosed and treated, 2000 and 2010
From 2000 to 2010, substantial programmatic improvements occurred. More patients were reported to, and
registered with, the CDC system. The percentage of
patients defaulting from treatment decreased from 43%
(163 of 370) to 22% (35 of 123), and the percentage of
retreatment cases decreased from 84% (312 of 374) to 31%
(48 of 137; both p<0·0001). This resulted from an increase
in the proportion of patients treated by the CDC system
and, to a lesser extent, from treatment improvement in
both the CDC and the hospital systems (table 3). Among
known cases, the proportion treated by the CDC system
(using the DOTS strategy) increased from 59 (15%) of 370
in 2000 to 79 (66%) of 123 in 2010. However, in 2010, half
of the patients diagnosed in the hospital system still had
not been reported to the CDC and nearly half of those
treated by hospitals had defaulted from treatment.
The programmatic improvements from 1990 to 2000
were fairly minor. The proportion of tuberculosis cases
reported to the CDC system increased from 460 (19%) of
2453 to 93 (23%) of 374 (p=0·0055); the proportion of
patients who received tuberculosis treatment increased
from 2313 (94%) of 2453 to 370 (99%) of 374 (p=0·00014),
and the proportion of patients who defaulted from
treatment decreased from 1118 (51%) of 2202 to 163 (43%)
of 370 (p=0·0168). Calculation of the above percentages
took into account the sampling design and therefore might
not be reproducible simply from the numbers presented.
Discussion
From 1990 to 2010, for individuals aged 15 years and
older in China, the prevalence of smear-positive
tuberculosis fell by 65% and the prevalence of
bacteriologically positive tuberculosis fell by 48% (panel).
By 2010, China had thus achieved one of the key global
www.thelancet.com Vol 383 June 14, 2014
tuberculosis targets set by the Stop TB Partnership: to
reduce the prevalence of smear-positive tuberculosis by
50%.6 This reduction was achieved 5 years before the
target date of 2015. This analysis did not include data
from individuals younger than 15 years; however, the
absence of such data is unlikely to change the major
findings because less than 2% of laboratory confirmed
tuberculosis cases come from this age group.7,8
The reduction in tuberculosis prevalence occurred
concurrently with the scale-up of the DOTS programme
in China. This scale-up, which was implemented by the
CDC system through its local public health clinics,
occurred in two distinct phases. During the 1990s, the
country expanded the DOTS programme to cover half of
its population, and increased the tuberculosis case
detection rate—the percentage of all estimated new
smear-positive tuberculosis patients detected—to roughly
30%.1,5 Concurrently, the prevalence of smear-positive
tuberculosis fell by 19%. From 2001 to 2005, China scaled
up the DOTS programme nationwide and used a series of
public health interventions to increase the tuberculosis
case detection rate to nearly 80%.5 The prevalence of
smear-positive tuberculosis fell by 57% for the decade
after 2000—tripling the reduction of the previous decade.
70% of the absolute reduction in smear-positive
prevalence in two decades occurred during the second
decade when tuberculosis control efforts intensified.
Even though the prevalence of smear-positive tuberculosis decreased significantly during the 1990s, the
change was only seen in areas of China where the DOTS
programme was implemented. After adjustments for
changing age structure and other factors, a previous
analysis attributed a 30% reduction in tuberculosis
prevalence to the DOTS programme,3 supporting a
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Panel: Research in context
Systematic review
We searched PubMed from Jan 1, 1995, to Aug 31, 2013, for English publications that
measured tuberculosis prevalence at a national level. We used the search terms
“tuberculosis” and “prevalence”. We included studies with serial national tuberculosis
prevalence surveys, which allowed an assessment of changes in tuberculosis prevalence
with time. Studies with subnational data that were not representative of the entire
country were not included. We identified only two studies—from China and the
Philippines—that contained data from serial national tuberculosis prevalence surveys
during the period when the directly observed treatment, short-course (DOTS) strategy
was being implemented.3,10
Interpretation
Aside from China, no other country with high burden of tuberculosis has done more than
two tuberculosis prevalence surveys during the period when the DOTS strategy was being
implemented. The Philippines is the only other high tuberculosis-burden country with more
than one survey. After 10 years of DOTS implementation, the second Philippines survey
showed a 31% reduction in prevalence of bacteriologically positive tuberculosis and a
27% reduction in prevalence of smear-positive tuberculosis.9 However, the decrease in
smear-positive prevalence was not significant. One of the key global tuberculosis targets
aims to reduce tuberculosis prevalence by 50% between 1990 and 2015. This study in China
is the first to show the feasibility of achieving such a target, and China achieved this 5 years
earlier than the target date. In fact, China achieved a 57% reduction in prevalence of
smear-positive tuberculosis from 2000 to 2010—a mere 10 years, coincident with a massive
scale up of the DOTS programme. Additionally, the study linked the epidemiological effect to
huge improvements in tuberculosis treatment at a population level, showing the
importance of addressing of poor tuberculosis treatment in the hospital system.
causal llinkage between DOTS implementation and
reduced tuberculosis prevalence; however, information
from the two most recent surveys provides even stronger
support for this link.
A national tuberculosis prevalence survey can identify
an unbiased, cross-sectional sample of existing
tuberculosis patients in a country, including those with a
previous diagnosis of tuberculosis—ie, known cases at
time of survey. By collecting information on the status of
their tuberculosis treatment, we can learn about the
quality of treatment at a population level.
More than 40% of all patients known to have
tuberculosis in the 2000 survey had defaulted from their
treatment. More than 80% of these known patients were
treated by the hospital system and, of those, half had
defaulted from their treatment. The 2010 survey
identified substantial improvements in tuberculosis
treatment. Compared with the 2000 survey, an increased
percentage of known patients were taking their drugs
regularly and a reduced percentage of patients had
defaulted from treatment. Notably, the percentage of
known patients with one or more previous courses of
treatment for tuberculosis—an indicator of poor
treatment quality—decreased from more than 80% to
around 30%.
After 2000, two major changes played an important part
in improving tuberculosis treatment. First, the government
2062
expanded the DOTS programme nationwide, providing
standard short-course chemotherapy throughout the
country’s network of local CDC.5 Second, the DOTS
programme expanded its free treatment policy to all
patients with active pulmonary tuberculosis.5 Before 2000,
when the free treatment policy applied only to smearpositive cases, an estimated 30% of new smear-positive
cases were treated in the DOTS programme. These
patients corresponded roughly to 15% of all patients with
tuberculosis—the percentage identified in the 2000 survey.
The expansion of free treatment allowed many more
patients to access the CDC for treatment.
With these two changes, the percentage of patients
treated by the CDC system increased from 15% in 2000
to 66% in 2010. Without these changes, most patients
would have continued to access the hospital system for
treatment, but only a small proportion of those treated
would have continued their treatment. This shift in
where patients were treated—from hospitals to the
CDCs—accounted for most of the treatment improvement for the entire patient population. Improved
tuberculosis reporting and referral by hospitals to the
CDC system, coupled with active follow-up by the CDC
system, helped with this shift.11,12
The population-based improvements in tuberculosis
treatment can be directly linked to the reduction in
tuberculosis prevalence. Nearly all the decrease in
tuberculosis prevalence was due to a reduction in the
prevalence of tuberculosis among known cases—ie,
cases already diagnosed before the survey. A decrease in
disease prevalence can result from a reduced disease
incidence, or duration of illness, or both. If the 90%
reduction in prevalence in known cases was primarily
due to decreased tuberculosis incidence, then one would
expect to see a similar reduction in prevalence among
new cases; but this reduction did not happen. Therefore,
a substantial shortening in the duration of illness after
tuberculosis diagnosis—a result of more effective
tuberculosis treatment—must have played an important
part in reducing the prevalence among known cases.
This study provides insights into how the country can
further reduce its tuberculosis burden. First, increased
focus should be placed on western China because this
region has the highest prevalence of tuberculosis and is
lagging behind in reducing its tuberculosis burden.3,7,8
Our study showed that, between 2000 and 2010, the
decrease in prevalence of bacteriologically positive
tuberculosis—measured in both absolute and percentage
changes—was greater in the eastern-central region than
in the western region. As a result, the gap between nonwestern and western areas in tuberculosis prevalence has
widened. Rural areas have consistently higher
tuberculosis prevalence than urban areas,3,7,8 and we see a
similar trend toward a widening urban–rural gap in
tuberculosis prevalence although this finding is not
significant. With slower economic development, these
lagging areas have less financial resources, fewer well
www.thelancet.com Vol 383 June 14, 2014
Articles
trained health-care workers, and weaker public health
infrastructure to address a problem such as tuberculosis.
Increased governmental inputs are needed to improve
tuberculosis control efforts in these areas.
Second, the reporting and treatment of patients with
tuberculosis in the hospital system should be improved.
In 2010, fewer than half of the cases diagnosed in
hospitals were reported to, and registered in, the CDC
system, and only 41% of patients started on treatment in
hospitals were taking their drugs regularly when in the
community. Furthermore, use of improper treatment
regimens in hospitals is widespread.13
Third, the DOTS programme has been much more
effective in reducing the prevalence of tuberculosis in
known cases than in new cases. Because the prevalence
in known cases is already very low, future reduction in
tuberculosis prevalence is likely to slow substantially
unless control efforts in addition to the DOTS strategy
are implemented, especially in earlier case detection and
treatment and use of new instruments.14,15 Future studies
can help to identify populations at high risk of
tuberculosis and assess the feasibility and effectiveness
of active case-finding or preventive treatment. China
already has a policy to screen individuals with HIV for
tuberculosis, and the use of preventive treatment is being
evaluated. Although more should be done to prevent
HIV-associated tuberculosis, such efforts will not have a
major effect on the overall reduction in tuberculosis
prevalence given the fairly small and concentrated HIV
epidemic in the country.16,17
An intriguing finding is the absence of reduction in the
prevalence of all pulmonary cases between 2000 and
2010. We believe this absence is due to the use of chest
radiography as the initial screening instrument in 2010
instead of chest fluoroscopy in the earlier surveys. This
change in instrument probably increased the sensitivity
of case detection in 2010, thus masking any real decrease
in the prevalence of pulmonary cases.
There are several limitations to our study. First, chest
radiographs were used to screen the survey population in
2010, whereas fluoroscopy was used in earlier surveys.
The 2010 survey was therefore more sensitive in
identifying patients with tuberculosis. However, the
reductions in this study would have been greater if
fluoroscopy had been used in 2010 instead of chest
radiographs. Second, we excluded individuals younger
than 15 years from this analysis. Because the proportion
of the Chinese population in this age group has been
decreasing, to include them in our analysis would have
reduced (albeit by a very small amount) the decrease of
tuberculosis prevalence in the entire population. Third,
socioeconomic development probably contributed to the
reduction in tuberculosis prevalence, but its effects
cannot be distinguished from tuberculosis control
efforts. However, its contribution was unlikely to have
varied greatly with time because the annual growth in
gross domestic product per head adjusted for purchasing
www.thelancet.com Vol 383 June 14, 2014
power parity was 10% between 1990 and 2000 and 11%
between 2000 and 2010. During this 20 years of steady
economic growth, the observed correlation between
intensity of tuberculosis control efforts and greater
reduction in tuberculosis prevalence supports a causal
linkage between the two.
Finally, our results have implications for the present
discussion about a new agenda for global tuberculosis
control and elimination after the UN Millennium
Development Goals expire in 2015.18–22 Of the new
tuberculosis targets that will probably be considered by
the World Health Assembly is a 50% reduction in
tuberculosis incidence between 2015 and 2025.
Achievement of such a target would be an important
milestone toward tuberculosis elimination. Our results
show the feasibility of such a target when a programme
is put into place to substantially improve the quality of
tuberculosis treatment. Countries can achieve this
improvement with an aggressive scale-up of the DOTS
programme if they have not done so already, but
improvement of the treatment of patients diagnosed
outside the DOTS programme, which is usually
implemented only in the public sector, is essential.
However, because many developing countries—
including those with the highest tuberculosis burden—
have already improved tuberculosis treatment in the past
10–15 years using the DOTS strategy, long-term, rapid
reduction in the tuberculosis burden will need additional
control efforts. These efforts include earlier detection
and treatment of active tuberculosis and ultimately
interventions and new instruments to reduce the risk of
tuberculosis in the large global population with latent
tuberculosis infection.
For more on World Bank GDP
per capita see http://data.
worldbank.org/indicator/NY.
GDP.PCAP.CD
Contributors
YW, LW, HZ, YR, SC, MC, YZ, SJ, XD, GH, and DPC participated in the
design and planning of the study. JL, SW, WC, CX, FH, and XL collected
the data. LW, HZ, YR, YX, DPC, and YW did the data analysis and
prepared the report for publication.
Declaration of interests
We declare that we have no competing interests.
Acknowledgments
We thank members of the National Tuberculosis Epidemiological
Investigation Steering Group (especially Yude Chen, Xiexiu Wang,
Shuigao Jin, and Liya Wan), Ikushi Onozaki of the World Health
Organization, and Zhongwei Jia of the Peking University Health Science
Center for their valuable advice and assistance during the design or
analysis of the 2010 National Tuberculosis Prevalence Survey. We also
thank the tireless contributions of staff in the Ministry of Health,
provincial health bureaus, provincial CDCs, and local CDCs in
undertaking the tuberculosis prevalence surveys.
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