Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China

Study population

The target population of the TB prevalence survey was residents of 15 years old or above who had lived in the selected clusters for more than 6 months. A population based, cross-sectional survey was conducted using multi-stage random cluster sampling method.

The survey employed the same sampling methods as the China national survey in 2010, which was similar to the sampling methods used in 2000 [6]. The design of the surveys was in accordance with WHO recommendations [7]. The design effect factor due to cluster sampling was estimated at 1.28 [8]. A sample size of 52500 adults (≧15 years old), in 35 clusters, was calculated based on detecting a change of 20% in prevalence rate of TB smear positive cases compared with the rate of the 2000 survey (95 per 100,000), with a probability greater than 95% and 95% power, accounting for 90% response rate of participants [9].

A stratified multi stage random sampling was used to select the 35 clusters within 17 prefectures in Shandong province. The number of clusters was randomly allocated in proportion to the provincial population at the prefectural, county/district and township levels. A cluster was defined as a community (a village in the rural area or a resident community in an urban area) with a population of 1250 to 1750 adults (i.e., those of 15 years or older). If the community contained less than 1250 adult residents, the neighboring community to the north was annexed. If the community or combined communities containing more than 1750 adults, we randomly selected households and then included all adults in the household for the survey until the total number of selected adults reached 1750. Military barracks and prisons located in the cluster were excluded [7].

Data collection

The survey was conducted from March to June 2010 by survey teams consisting of clinicians, public health doctors, radiologists, laboratory technicians and nurses. Local media was used to promote awareness of the survey. Community workers conducted a house-to-house census to update the database of residents, inform survey participants and obtain informed consent. The study did not involve children under 15 years old. Written informed consent was obtained from all participants of 16 years old or above. While from those of 15 years old, written informed consents were obtained from their parents or guardians. All documents were properly stored in the Shandong Chest Hospital. Ethical approvals for the study and consent procedures were obtained from the Institutional Review Board (IRB) of Shandong Chest Hospital (NIH register numberIRB00006010).

Those who agreed to participate in the survey were invited to the county TB dispensary, where they completed a consultation with a trained clinical TB doctor regarding any symptoms suggestive of TB, such as persistent cough (lasting two weeks or longer), haemoptysis, weight loss and fever. All participants had a chest X-ray (CXRAY) taken that then were reviewed by a panel of radiologists. Those with symptoms or CXRAY films suggestive of TB were classified as suspected TB cases. All suspected cases were asked to produce three sputum samples, one at the time of consultation, another at night and the third in the early morning of the following day. Identified suspects completed an additional questionnaire regarding their social-economic situation, smoking status, and the presence of TB related symptoms in the preceding six months (cough, fever, weight loss, chest pain and haemoptysis).

Classification and quality control

Sputum smears were conducted in local TB dispensaries. All sputum samples were cultured using the Löwenstein–Jensen medium in the provincial laboratory within 24 hours using cold chain transportation. Samples were excluded from TB when non-tuberculosis bacilli were identified from the culture. All sputum smear and culture were conducted strictly according the national TB laboratory external quality control measure, which is in consistent with the WHO TB prevalence survey guideline [7]. TB classification was made according to the China national TB guideline [10]. A positive smear had at least one acid fast bacillus identified during examination of at least 100 fields. Participants with positive sputum smear specimens were classified as sputum positive cases. Those with positive smear or culture sputum specimens were classified as sputum bacteriologically confirmed cases. Those being culture negative with abnormal CXRAY suggestive of TB and having been ruled out from other diseases by clinicians and radiologists were classified as CXRAY suggestive bacteriologically negative cases. Due to resource limitations the recommendation of broad-spectrum antimicrobial agents to confirm the diagnosis of negative TB cases was not applied in this survey [11]. Newly diagnosed cases were distinguished from previously diagnosed cases through checks during the interviews and against the TB registration system.

Initial diagnosis was made by a group of local clinicians and radiologists. Subsequently, samples and CXRAY films of all suspected and confirmed cases were re-assessed by a group of senior clinicians and radiologists at provincial and national levels. CXRAY films of 100% of those scored as abnormal and 10% random sampling of those scored as normal were transferred for independent reading. The provincial laboratory team randomly examined one slide from the three samples of sputum positive cases, all three samples of CXRAY suggestive TB cases, and randomly selected 10% of the non-TB cases.

Data analysis

Prevalence estimates of sputum positive, bacteriologically confirmed and all TB cases were calculated. In all analyses, population weightings were employed to adjust for the stratified multi-stage sampling design effect [8]. The survey results in 2010 and 2000 were standardized against the age structures of China’s census population in 2010. The 2000 TB prevalence survey included all age groups [12]. The WHO recommended method was used to enable comparison between the two surveys that prevalence rates of child TB were assumed to reduce to the same extent as adult TB from 2000 to 2010 [13]. Subgroup analysis in gender, age groups and urban/rural residence were conducted. Case identification rate was calculated as the number of cases identified by a screening method over all suspected cases found by the method. Yields of the symptom consultation and CXRAY were calculated as a proportion of the total number of bacteriologically confirmed cases.

Screening methods

All participants of the survey were first screened by symptoms and CXRAY. Those who had symptoms of consistent cough or haemoptysis, or CXRAY abnormalities were then screened by smear and culture. Case identification rates of new bacteriologically confirmed cases from the suspected cases were significantly higher with CXRAY as a primary tool (Figure 1, 3.8%, P = 0.012) and further increased by both symptom screen of persistent cough and CXRAY (10%, P < 0.001) compared with symptom screen alone (0.4%). The same pattern of case identification rate was observed in the sputum positive cases (7.5%, 1.9% and 0% respectively). The proportion reporting persistent cough was not significantly higher among bacteriologically confirmed cases compared with other suspects (P = 0.565). The symptom consultation alone identified 308 suspects, including 6 (1.9%) sputum smear positive TB and 9 (2.9%) bacteriologically confirmed TB. Among the 344 suspects with CXRAY abnormalities, 11 (3.2%) had sputum positive TB and 18 (5.2%) had bacteriologically confirmed TB. The yield of bacteriologically confirmed cases was 47.4% by screening consultation and 94.7% by CXRAY. In the population of over 65 years old, symptom consultation and the CXRAY identified 174 and 182 suspected cases respectively, yielding5 (2.9%) and 9 (4.9%) of bacteriologically confirmed cases. Yields of bacteriologically confirmed cases were 55.6% by symptom consultation and 100% by CXRAY among over 65’s.

Estimated prevalence

The crude prevalence rate in Shandong in 2010 of sputum positive cases was 22.1 (95% CI: 9.6-34.6), bacteriologically confirmed cases was 36.8 (95% CI: 17.8-55.8), and all cases were 337.1 (95% CI: 254.1-420.0) per 100,000 in adult population (Table 2). The adjusted prevalence rates of the whole population in Shandong were17.8 (95% CI: 8.3-17.5), 27.8 (95% CI: 14.8-28.0) and 239.4 (95% CI: 179.9-298.9) per 100,000 in 2010. A remarkable decline of 82.0%, 80.2% and 31.4% was observed in TB prevalence rates of sputum positive, bacteriologically confirmed, and all cases, respectively, compared to the adjusted rates in 2000 [12]. Large declines were observed in males between 40 and 65 years old, and in females over 60 years old (Figure 2).

	No. of participants	Rates of sputum positive cases (per 100000)	Rates of bacteriologically confirmed cases (per 100000)	Rates of all cases (per 100000)
Crude	54279	22.1 (9.6–34.6)	36.8 (17.8–55.8)	337.1 (254.1–420.0)
Adjusted for all populationa		17.8 (8.3–17.5)	27.8 (14.8–28.0)	239.4 (179.9–298.9)
Adjusted for adultsa		21.4 (10.0–32.8)	33.5 (17.8–49.2)	285.8 (215.2–356.4)
Sex: Malea	25406	29.5 (7.9–51.1)b	43.3 (15.9–70.7)b	388.0 (282.2–493.8)b
Femalea	28873	5.4 (0.9–9.9)	15.7 (3.9–27.5)	183.4 (128.1–238.7)
Age: 15-64a	46807	9.9 (1.4–18.3)	20.8 (5.0–36.6)	154.8 (113.9–195.6)
65 and oldera	7472	83.3 (17.2–149.4)c	118.3 (35.0–201.7)c	1429.9 (1011.4–1848.3)c
Area: Urbana	26101	9.0 (1.0–17.0)	9.0 (1.0–17.0)	139.1 (80.7–197.5)
Rurala	28178	24.2 (4.8–43.6)	43.1 (17.0–69.2)d	342.6 (242.4–442.8)d

^aAdjusted for sampling errors and against China’s census population in 2010.

^bSignificantly higher than female of prevalence rates of sputum positive cases (x² = 9.702, P = 0.002), bacteriologically confirmed cases (x ² = 11.722, P = 0.001), and all TB cases (x ² = 32.378, P<0.001).

^cSignificantly higher than year 15–64 of prevalence rates of sputum positive cases (x² = 20.083, P<0.001), bacteriologically confirmed cases (x² = 22.128, P<0.001), and all TB cases (x ² = 307.665, P<0.001).

^dSignificantly higher than urban area of prevalence rates of bacteriologically confirmed cases (x ² = 6.323, P = 0.012) and all TB cases (x ² = 26.904, P<0.001).

The adjusted prevalence rates in the adult population were 21.4 (95% CI: 10.0-32.8), 33.5 (95% CI: 17.8-49.2) and 285.8 (95% CI: 254.2-356.4) for sputum positive cases, bacteriologically confirmed cases and all cases, respectively. Significant differences regarding adjusted TB prevalence rates were observed between males and females, over 65’s and 15 to 64 years old, in rural and urban areas (Table 2, P < 0.001). The male to female ratios were 5.5 in sputum positive cases and 2.8 in bacteriologically confirmed cases, while the ratios climbed to 6.0 and 4.1, respectively, among those over 65 years. The majority of TB patients, 54.5% of sputum positive cases and 47.3% of bacteriologically confirmed cases, were from people 65 years or older. The ratio between over 65’s and 15 to 64 years old was 8.4 in sputum positive cases and 5.9 in bacteriologically confirmed cases. The ratio between rural and urban areas was 2.7 in sputum positive cases and 4.8 in bacteriologically confirmed cases.