Tuberculosis in China

There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and as DM increases the risk of TB and adversely affects TB treatment outcomes, there is a need for bidirectional screening of the two diseases. How this is best performed is not well determined. In this pilot project in China, we aimed to assess the feasibility and results of screening DM patients for TB within the routine healthcare setting of five DM clinics. Agreement on how to screen, monitor and record was reached in May 2011 at a national stakeholders meeting, and training was carried out for staff in the five clinics in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. DM patients were screened for TB at each clinic attendance using a symptom-based enquiry, and those positive to any symptom were referred for TB investigations. In the three quarters, 72% of 3174 patients, 79% of 7196 patients and 68% of 4972 patients were recorded as having been screened for TB, resulting in 7 patients found who were already known to have TB, 92 with a positive TB symptom screen and 48 of these newly diagnosed with TB as a result of referral and investigation. All patients except one were started on anti-TB treatment. TB case notification rates in screened DM patients were several times higher than those of the general population, were highest for the five sites combined in the final quarter (774/100 000) and were highest in one of the five clinics in the final quarter (804/100 000) where there was intensive in-house training, special assignment of staff for screening and colocation of services. This pilot project shows that it is feasible to carry out screening of DM patients for TB resulting in high detection rates of TB. This has major public health and patient-related implications.

To improve the effectiveness of case detection and treatment of multi-drug resistant tuberculosis (MDR-TB) by implementing a mechanism of cooperation between hospitals and centers for disease control (CDC). Since 1 March 2010, a new mechanism of cooperation between hospitals and CDCs had been established in 5 cities including Daqing, Quzhou, Puyang, Tianjin and Wanzhou in China. Data of MDR-TB case-detection, treatment and economic burdens before the intervention (January 1, 2006-June 30, 2009) and after the intervention (March 1, 2010-February 29, 2012) were collected. Then all data were analyzed by statistical method. After the intervention, samples from 68.4% (5 287/7 733) of smear-positive TB patients in the study regions underwent TB drug-resistant testing, and the number of the detected MDR-TB cases were 9.8 times that prior to the intervention. 93.1% (108/116) of the patients incorporated into the treatment of MDR-TB received the standardized initial chemotherapy program, and the number was 7 times that before the intervention. The referral rates after hospital discharge raised from 0% before the intervention to 92.8% after (90/97) the intervention; and 85.7% (83/97) of the patients received treatment and management by CDC. When the 6-month injection ended, MDR-TB patients still under treatment after the intervention were 84.5% (82/97), and those whose sputum culture became negative were 56.7% (55/97). The proportion of patients with self-paid and with catastrophic expenditures after the intervention were reduced to 18.0% (1 678/9 324) and 44.7% (17/38) respectively, as compared to 75.4% (7 659/10 158) and 76.7% (23/30) respectively before the intervention. To establish a well-performed Hospital-CDC cooperation mechanism could promote the performance of MDR-TB case detection and treatment.

After years of decline tuberculosis has re-emerged as a serious public health problem worldwide. In 1993 the World Health Organization (WHO) declared tuberculosis to be a global emergency and according to a recent WHO report there were 7.96 million new cases in 1997 with 2 million deaths. Factors contributing to the resurgence of tuberculosis include the HIV epidemic immigration of persons from countries with high incidence rates and political turmoil in some developing countries which hinder efforts to control the disease. The spread of the disease poses a public health concern especially with increased drug resistance among M. tuberculosis strains which have acquired varying degrees of resistance to firstline anti-tuberculous drugs. The underlying causes of single drug-resistant M. tuberculosis (SDR-TB) and/or multidrug-resistant M. tuberculosis (MDR-TB) have been suggested to be the result of incorrect treatment poor compliance shortage of anti-tuberculous drugs due to financial constraints in some developing countries and deficient or deteriorating TB control programs resulting in inadequate administration of effective chemotherapy. Previous reports indicate that single-drug resistance and multi-drug resistance to M. tuberculosis are on the increase in both developed and developing countries. The prevalence of SDR-TB or MDR-TB in the Kingdom of Saudi Arabia is largely unknown except for a few studies confined to large centers. The objective of this article is to review published materials from different regions of the Kingdom on the prevalence of SDR-TB and MDR-TB and to draw a conclusion of the actual status of drug-resistant tuberculosis in Saudi Arabia with a discussion of the findings. (excerpt)

Although the Republic of Angola is one of the 14 countries figuring in the three high tuberculosis (TB) burden country lists, the true multidrug-resistant TB (MDR-TB) situation is unknown. Patients aged 16 years with a diagnosis of pulmonary TB were prospectively enrolled from June 2014 to July 2015. Sputum samples were collected for culture and drug susceptibility testing in all patients, and for Xpert® MTB/RIF testing in all previously treated patients and in new patients whose sputum remained smear-positive after 2 months of treatment. A total of 422 patients were included; Mycobacterium tuberculosis was isolated in 308 sputum samples. The prevalence of MDR-TB was 8.0% (18/225) in new patients and 71.1% (59/83) in previously treated patients. Male sex (OR 2.95, 95%CI 1.35-6.44, P = 0.007), previous anti-tuberculosis treatment (OR 20.86, 95%CI 9.53-45.67, P < 0.001), presence of pleural thickening (OR 7.68, 95%CI 1.57-37.43, P = 0.012) and duration of illness >4 months (OR 3.34, 95%CI 1.45-7.69, P = 0.005) were independent risk factors for MDR-TB. The prevalence of MDR-TB in Cubal, Angola, was higher than estimated by the World Health Organization for Angola and one of the highest worldwide. Facilities to diagnose and treat MDR-TB are urgently needed in Angola.

World TB Day, March 24, 2000 – Forging new partnerships to stop TB

Objective: To analyse the epidemic features and programs of control on tuberculosis (TB) in China from 1990 to 2017 to provide references and evidence on prevention and control of the disease. Methods: We used data from the Global Burden of Disease Study 2017 to analyse the trends of incident and death cases of TB in China from 1990 to 2017. Results: In 2017, there were an estimated 831.0 thousand (age-standardized incidence: 54.18 per 100 000 population) incident cases and 39.3 thousand (age-standardised mortality: 2.17 per 100 000 population) deaths of TB in the country. The incident cases and deaths of TB decreased by 51.05% and 76.24% compared with the numbers in 1990, respectively. The average annual declining rates on incident cases and deaths of TB were 2.61% and 5.18%, respectively, from 1990 to 2017. The number of incident cases of TB decreased from 833.6 thousand in 2016 to 831.0 thousand in 2017 (decreased by 0.31%). The number of deaths of TB decreased from 40.7 thousand in 2016 to 39.3 thousand in 2017 (decreased by 3.44%). The number of incident cases and deaths of drug-sensitive TB showed a declining trend from 1990 to 2017. However, the number of incident cases and deaths showed first increased and then decreased trends for both multidrug-resistant TB (MDRTB) and extensively drug-resistant TB (XDRTB) in the same period. The number of incident cases of XDRTB increased from 2 979 in 2016 to 3 018 in 2017, with an increasing rate by 1.32%. The number of deaths of XDRTB increased from 819 in 2016 to 829 in 2017, with an increase rate by 1.22%. Conclusions: China made substantial progress in reducing both the TB incidence and mortality from 1990 to 2017 but the rate of decline became slow in the later years. We noticed that the increase of TB caused by XDR-TB had been increasing which called for special attention.

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.

Tuberculosis: A Global Problem at Our Doorstep

Optimising medication adherence is one of the essential factors in reversing the tide of a TB-HIV syndemic in sub-Saharan Africa, especially South Africa. Impairment in key neurocognitive domains may impair patients' ability to maintain adherence to treatment, but the level of cognition and its relationship to HIV status has not been examined in individuals with drug-resistant TB. We therefore investigated performance on several key neurocognitive domains in relationship to HIV status in a multidrug-resistant tuberculosis patients (MDR-TB) sample. We enrolled microbiologically confirmed MDR-TB inpatients at a TB-specialist referral hospital in KwaZulu-Natal province, South Africa. We collected cross-sectional data on sociodemographic, clinical and neurocognitive function (e.g. attention, memory, executive functioning, language fluency, visual-spatial, eye-hand coordination). For the primary analysis, we excluded participants with major depressive episode/substance use disorder (MDE/SUD). We fitted adjusted Poisson regression models to explore the association between HIV and neurocognitive function. We enrolled 200 people with MDR-TB; 33 had MDE/SUD, and data of 167 were analysed (151 HIV+, 16 HIV-). The mean age of participants was 34.2years; the majority were female (83%), and 53% had not completed secondary school. There was evidence of impaired neurocognitive functioning across all domains in both HIV+/- study participants. Based on the regression analyses, individuals with co-infection (MDR-TB/HIV+), as well as those who had longer duration of hospital stays experienced significantly lower cognitive performance in several domains. Poor cognitive performance was significantly related to older age and lower educational attainment. The presence of major depression or substance use disorders did not influence the significance of the findings. Adults with MDR-TB have significant neurocognitive impairment, especially if HIV positive. An integrated approach is necessary in the management of MDR-TB as cognitive health influences the ability to adhere to chronic treatment, clinical outcomes and functionality.

Nigeria is one of the countries with a high burden of tuberculosis (TB) in the world. TB associated inflammation is reported to be central to progression from latent TB to active TB or drug sensitive TB (DSTB) to drug resistant TB (DRTB). Inflammatory cytokines, especially interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), act synergistically in the control of TB infection. They activate macrophages to produce effector molecules such as inducible nitric oxide synthase (iNOS), nitric oxide, and ultimately 3-nitrotyrosines(3-NTs), which are involved in the control of TB. This study investigated the potential involvement of TNF-α, IFN-γ, iNOS, and 3-NT in differentiating DRTB and DSTB in Ibadan, Nigeria. One hundred participants above 18 years were recruited into this study and were grouped as follows: 32 DRTB, 34 DSTB, and 34 apparently healthy controls. Plasma from the patients was used for the analyses of inflammatory (TNF α and IFN-γ) and oxidative stress (iNOS and 3-NT) biomarkers using the ELISA. Mann-Whitney test was applied for the statistical test. Mean levels of plasma TNF-α, IFN-γ, iNOS, and 3-NT were higher in DRTB (19.74 ± 3.62 pg/mL, 4.41 ± 0.96 pg/mL, 1791.07 ± 419.42 pg/mL, and 20.27 ± 1.80 ng/mL, respectively) and DSTB (17.02 ± 1.84 pg/mL, 5.59 ± 1.40 pg/mL, 2823.42 ± 685.32 pg/mL, and 25.06 ± 2.15 ng/mL, respectively) compared with controls (12.18 ± 0.92 pg/mL, 1.58 ± 0.21 pg/mL, 1275.86 ± 166.12 pg/mL, and 19.98 ± 1.23 ng/mL, respectively). In addition, higher plasma levels of IFN-γ (P > 0.05), iNOS (P > 0.05), and 3-NT (P < 0.05) were observed in DSTB compared with DRTB patients. The 3-NT may be used as differentiating markers of DSTB from DRTB.

Population structure of multidrug-resistant Mycobacterium tuberculosis clinical isolates in Colombia

Emergence of additional drug resistance during treatment of multidrug-resistant tuberculosis in China: a prospective cohort study

Tuberculosis (TB) is an infective disease caused by Mycobacterium tuberculosis and it can affect any organs, usually the lungs. In the past two decades, global strategies for TB control have been recommended for acceptance and adaptation in all countries. The phenomenon of multidrug resistant-tuberculosis (MDR-TB) disease forms has led to the introduction of new measures in the treatment of TB, for example, the directly observed therapy short course (DOTS) strategy, by the World Health Organization. Because of the increase in the prevalence of TB and MDR-TB and its close association with AIDS, the most important aspect of treatment was the introduction and the routine use of new technologies for the quick detection of resistant strains and the development of special diagnostic algorithms. The new post-2015 Global TB Strategy, approved by the 67th World Health Assembly in May 2014, aims at “ending the global TB epidemic” by 2035. This implies a reduction of mortality for 95% by decreasing incidence for 90% and (<10 TB cases/100,000 population) to 2035 in comparison with 2015, and the decrease of any “catastrophic cost” for families affected with TB. Early discovery, patient motivation to comply with treatment, and the application of the DOTS strategy are crucial for preserving the efficacy of anti-TB therapy and disease control. Despite these all measures, however, TB is still one of the world’s biggest health problems.

Limited studies have been conducted to explore risk factors of developing multidrug-resistant tuberculosis (MDR-TB) in China. This study aimed to find the proportions and risk factors of developing MDR-TB in China among new patients and previously treated tuberculosis (TB) patients. A population-based case-control study was conducted from March 2010 to December 2013 in five cities in China. Proportions and risk factors of developing MDR-TB were calculated and analyzed separately for new patients and previously treated patients. The proportion of MDR-TB was 3.9% among new patients and 25.3% among previously treated patients in our study population. The proportion of extensively drug resistant TB was 0.1% among new patients and 1.4% among previously treated patients in our study population. Multivariate analysis found that being registered as migrants (odds ratio [OR] = 6.08; 95% confidence interval [CI]: 1.75-21.09), having more than three affected lung fields (OR = 2.18; 95% CI: 1.20-2.94), having more than 8 months of initial treatment (OR = 2.15; 95% CI: 1.09-4.28), having more than three prior episodes of anti-TB treatment (OR = 3.10; 95% CI: 1.48-6.48), and experiencing failure or continued worsening from the last treatment (OR = 3.82; 95% CI: 1.86-7.85) were associated with developing MDR-TB in previously treated patients with TB. Univariate analysis showed that less than 30 years of living in the same location (p = 0.034) was a risk factor for new patients with MDR-TB. The surveillance of multidrug resistance among patients with previously treated TB who also possess these risk factors and the management of patients with MDR-TB should be reinforced.

The Global Project on Anti-Tuberculosis Drug Resistance has been gathering data since 1994. This study provides the latest data on the extent of drug resistance worldwide.Data for drug susceptibility were gathered from 90 726 patients in 83 countries and territories between 2002 and 2007. Standardised collection of results enabled comparison both between and within countries. Where possible, data for HIV status and resistance to second-line drugs were also obtained. Laboratory data were quality assured by the Supranational Tuberculosis Reference Laboratory Network.The median prevalence of resistance to any drug in new cases of tuberculosis was 11·1% (IQR 7·0–22·3). The prevalence of multidrug resistance in new tuberculosis cases ranged from 0% in eight countries to 7% in two provinces in China, 11·1% in Northern Mariana Islands (although reporting only two cases), and between 6·8% and 22·3% in nine countries of the former Soviet Union, including 19·4% in Moldova and 22·3% in Baku, Azerbaijan (median for countries surveyed 1·6%, IQR 0·6–3·9). Trend analysis showed that between 1994 and 2007, the prevalence of multidrug-resistant (MDR) tuberculosis in new cases increased substantially in South Korea and in Tomsk Oblast and Orel Oblast, Russia, but was stable in Estonia and Latvia. The prevalence of MDR tuberculosis in all tuberculosis cases decreased in Hong Kong and the USA. 37 countries and territories reported representative data on extensively drug-resistant (XDR) tuberculosis. Five countries, all from the former Soviet Union, reported 25 cases or more of XDR tuberculosis each, with prevalence among MDR-tuberculosis cases ranging between 6·6% and 23·7%.MDR tuberculosis remains a threat to tuberculosis control in provinces in China and countries of the former Soviet Union. Data on drug resistance are unavailable in many countries, especially in Africa, emphasising the need to develop easier methods for surveillance of resistance in tuberculosis.Global Project: United States Agency for International Development and Eli Lilly and Company. Drug resistance surveys: national tuberculosis programmes, the Government of the Netherlands, the Global Fund to Fight AIDS, Tuberculosis and Malaria, Japan International Cooperation Agency, and Kreditanstalt für Wiederaufbau.