Evaluation of Microsphere-based xMAP Test for gyrA Mutation Identification in Mycobacterium Tuberculosis

Drug-resistant(DR) tuberculosis(TB) is a growing threat to public health[1]. Fluoroquinolone(FQ) antibiotics have long been used as anti-tuberculosis drugs, and their widespread application has led to the development of resistance in clinical isolates of Mycobacterium tuberculosis complex(MTBC).

The Current Status and Challenges Regarding Tuberculosis Infection Control in Health Care Facilities in China

Health care facilities are a high-risk environment for generating and spreading respiratory infectious diseases such as tuberculosis （TB）. The TB prevention and treatment staff in health care facilities are responsible for the identification, diagnosis, treatment, supervision, and management of TB patients .

Comparison of Xpert MTB/RIF, Real Amp, and CPA Tests in Detecting Mycobacterium tuberculosis

Today, tuberculosis (TB) remains a global public health threat associated with significantly high rates of morbidity and mortality. The World Health Organization's (WHO) Global Tuberculosis Report 2018[1] has reported that in 2017, 10.0 million people across the world had developed TB diseases that resulted in an estimated 1.6 million deaths, and 889, 000 people developed TB in China that led to 39, 000 TB-related deaths. Therefore, rapid and accurate detection of Mycobacterium tuberculosis (MTB) is important for initiating early treatment and reducing mortality. Traditional diagnostic methods for pulmonary TB incorporate chest radiography and sputum smear microscopy;however, several cases of tuberculosis go undiagnosed because of the low sensitivity of smear microscopy[2].

Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China

Objective To investigate the prevalence of primary drug-resistant tuberculosis（TB） and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis（MDR-TB）. Methods A total of 2794 representative, Mycobacterium tuberculosis isolates from treatment-naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains. Results Among 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR-TB isolates were classified into six sublineages, of which, 75（80.6%） isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65（69.9%） isolates with concurrent deletions of RD105, RD207, and RD181. Twenty-nine（31.2%） primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531 L rpoB mutation. Conclusion This study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB.

Evaluation of Multidrug Resistant Loop-mediated Isothermal Amplification Assay for Detecting the Drug Resistance of Mycobacterium tuberculosis

Objective To evaluate multidrug resistant loop-mediated isothermal amplification(MDR-LAMP)assay for the early diagnosis of multidrug-resistant tuberculosis and to compare the mutation patterns associated with the rpoB,katG,and inhA genes at the Chinese Center for Disease Control and Prevention.Methods MDR-LAMP assay was evaluated using 100 Mycobacterium tuberculosis(Mtb)isolates obtained from the National Reference Laboratory for Tuberculosis in China.Phenotypic resistance to isoniazid and rifampicin and whole-genome sequencing served as reference standards.Results The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of MDR-LAMP were 85.5%,93.6%,96.7%,and 74.4%for the detection of resistance to isoniazid and rifampicin,respectively,and 80.5%,92.3%,98.6%,and 41.4%for the detection of Mtb cultured from smear-positive sputum samples,respectively.When DNA sequencing was used as the reference standard,the sensitivity,specificity,PPV,and NPV of MDR-LAMP were 93.1%,92.3%,97.2%,and 82.8%for the detection of katG and inhA gene mutations,respectively,and 89.1%,88.9%,93.4%,and 81.1%for the detection of rpoB gene mutation,respectively.Conclusion MDR-LAMP is a rapid and accessible assay for the laboratory identification of rifampicin and isoniazid resistance of Mtb isolates.

Mutual Impact of Diabetes Mellitus and Tuberculosis in China

China has a double burden of diabetes mellitus and tuberculosis, and many studies have been carried out on the mutual impact of these two diseases. This paper systematically reviewed studies conducted in China covering the mutual impact of epidemics of diabetes and tuberculosis, the impact of diabetes on multi-drug resistant tuberculosis and on the tuberculosis clinical manifestation and treatment outcome, the yields of bi-directional screening, and economic evaluation for tuberculosis screening among diabetes patients.

Evaluation of the New Automatic Mycob.T Stainer andScanner for Detecting Acid-fast Bacilli in China

Objective To validate the performance of Mycob. T Stainer and Scanner(MTSS) for detecting acid-fast bacilli(AFB). Methods A total of 3,816 sputum samples from 1,515 tuberculosis(TB) suspects were tested at the Anhui Provincial Chest Hospital and the Linyi People’s Hospital from April-August, 2016. Each specimen was placed on two smear slides. One slide was stained by the ziehl-neelsen(ZN) method to be read by conventional microscopy(CM). The other slide was stained and scanned by MTSS. All specimens were decontaminated with 4% NaO H, and then inoculated into solid culture. The performance of MTSS was assessed. Results MTSS produced higher average positivity rate(27.96%) as compared with the CM(26.83%). The overall sensitivity and specificity of MTSS were 78.9% and 93.9%, respectively. The sensitivity and specificity of CM was 77.4% and 95.0%, respectively. Conclusion MTSS exhibited a favorable performance in the detection of AFB. It may be an alternative to CM for screening TB.

Now-and Fore-casting the Secular Epidemiological Trends and Seasonality of the Comeback of Scarlet Fever in China:A 16-year Time Series Analysis

Scarlet fever(SF)is a common communicable disease that results from group A Streptococcus(GAS)infections[1].SF accounted for the global loss of life among children 5–15 years of age in the 18th and 19th centuries[2].A rapid reduction in SF morbidity and mortality occurred due to the scale-up of effective antibiotics and improvements in sanitation and nutrition[3].The unexpected increase in the incidence of SF has attracted a renewed interest in infectious diseases[3].Because the triggers that cause SF outbreaks are not fully understood and there is a scarcity of available vaccines protecting susceptible populations from GAS infections,effective prevention and control plans are required to stop the continued spread of SF.

Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in China

Objective This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline(BR)and the conventional treatment regimen(CR,not containing Bedaquiline)for the treatment of adults with multidrug-resistant tuberculosis(MDR-TB)in China.Methods A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years.The model parameter data were synthesized from the literature,the national TB surveillance information system,and consultation with experts.The incremental cost-effectiveness ratio(ICER)of BR vs.CR was determined.Results BR(vs.CR)had a higher sputum culture conversion rate and cure rate and prevented many premature deaths(decreased by 12.8%),thereby obtaining more quality-adjusted life years(QALYs)(increased by 2.31 years).The per capita cost in BR was as high as 138,000 yuan,roughly double that of CR.The ICER for BR was 33,700 yuan/QALY,which was lower than China's 1×per capita Gross Domestic Product(GDP)in 2020(72,400 yuan).Conclusion BR is shown to be cost effective.When the unit price of Bedaquiline reaches or falls below57.21 yuan per unit,BR is expected to be the dominant strategy in China over CR.

Guidelines for the Prevention and Control of Tuberculosis in Schools:Recommendations from China CDC

China is still a high tuberculosis(TB)burden country,and the number of new cases of TB was 833,000 in 2019(1).School campuses are highlycrowded places with potential for close contact,which suggests that a few cases of TB may lead to a large outbreak.Thus,TB prevention and control in schools is an important disease control challenge for educational and health departments at all levels.

Patient,Diagnosis,and Treatment Delays Among Tuberculosis Patients Before and During COVID-19 Epidemic—China,2018-2022

Summary What is already known about this topic?The coronavirus disease(COVID-19)pandemic could have a damaging impact on access to tuberculosis(TB)diagnosis and treatment.What is added by this report?The overall delay experienced by TB patients during the COVID-19 pandemic has shown a modest decrease in comparison to the period before the pandemic.Notably,higher patient delays were observed among agricultural workers and those identified through passive case-finding methods.Furthermore,the patient delay in eastern regions was shorter compared to western and central regions.

Impacts of a comprehensive tuberculosis control model on the quality of clinical services and the financial burden of treatment for patients with drug-resistant tuberculosis in China:a mixed-methods evaluation

Background:The China National Health Commission-GatesTB Project Phase III implemented a comprehensive TB control model including multiple interventions to address the burden of drug-resistant TB(DRTB).This study aims to evaluate the quality of DRTB clinical services and assess the financial burden of DRTB patients during the intervention period.

Role of Diabetes Mellitus on Treatment Effects in Drug-susceptible Initial Pulmonary Tuberculosis Patients in China

We assessed the role of diabetes mellitus（DM） on treatment effects in drug‐susceptible initial pulmonary tuberculosis（PTB） patients. A prospective study was conducted in eight provinces of China from October 2008 to December 2010. We enrolled 1,313 confirmed drug‐susceptible initial PTB patients, and all subjects received the treatment regimen（2 H3 R3 E3 Z3/4 H3 R3） as recommended by the national guidelines. Of the 1,313 PTB patients, 157（11.9%） had DM; these patients had more sputum smear‐positive rates at the end of the second month [adjusted odds ratios（aO R） 2.829, 95% confidence intervals（CI） 1.783‐4.490], and higher treatment failure（aO R 2.120, 95% CI 1.565‐3.477） and death rates（aO R 1.536, 95% CI 1.011‐2.628）. DM was a contributing factor for culture‐positive rates at the end of the second month and treatment failure and death of PTB patients, thus playing an unfavorable role in treatment effects of PTB.

Interleukin 8 Gene Polymorphisms Are Not Associated with Tuberculosis Susceptibility in the Chinese Population

Interleukin 8 （IL8） is an important chemokine that elicits host immune response against tuberculosis （TB）. However, whether there is an association between IL8 gene polymorphism and TB susceptibility in the Chinese population is unknown. IL8 gene was amplified and sequenced to search for nucleotide polymorphisms among the Chinese population. Four single nucleotide polymorphisms （SNPs） were identified, selected, and analyzed in a cohort of 438 patients with TB and 536 healthy controls. Allelic, genotypic, and haplotypic analysis demonstrated that the distribution of the four IL8 SNPs between patients with TB and healthy controls was not significantly different （P〉0.05）. The four IL8 SNPs detected in this study were not associated with TB susceptibility in the Chinese population. Secretion of IL8 by peripheral blood cells was greatly stimulated upon exposure to Mycobacterium tuberculosis whole cell extract, but such enhanced secretion was not associated with the IL8 rs4073 alleles.

Risk of Treatment Failure in Patients with Drug-susceptible Pulmonary Tuberculosis in China

The objective of this prospective study of the risks of treatment failure in patients with drug-susceptible pulmonary tuberculosis （PTB） was to provide reference data to help develop a disease control strategy. Participants were recruited in eight provinces of China from October 2008 to December 2010. A total of 1447 patients with drug-susceptible PTB and older than 15 years of age were enrolled.

Human Immunodeficiency Virus Infection-Associated Mortality during Pulmonary Tuberculosis Treatment in Six Provinces of China

Objective To investigate the risk factors attributable to tuberculosis-related deaths in areas with human immunodeficiency virus（HIV） infection epidemics. Methods A prospective cohort study of newly registered patients in tuberculosis（TB） dispensaries in six representative Chinese provinces was conducted from September 1, 2009 to August 31, 2011. Risk factors for TB-associated death were identified through logistic regression analysis. Results Of 19,103 newly registered pulmonary TB patients, 925（4.8%） were found to be HIV-positive. Miliary TB and acid-fast bacillus smear-negative TB were more common among these patients. Out of a total of 322（1.7%） deaths that occurred during TB treatment, 85（26%） of the patients were co-infected with HIV. Multivariate analysis revealed that HIV infection was the strongest predictor of death [adjusted odds ratio（aO R） 7.86]. Other significant mortality risk factors included presentation with miliary TB（aO R 4.10; 95% confidence interval： 2.14-7.88）, ≥35 years of age（aO R 3.04）, non-Han ethnicity（aO R 1.67）, and farming as an occupation（aO R 1.59）. For patients with TB/HIV co-infection, miliary TB was the strongest risk factor for death（aO R 5.48）. A low CD4 count（≤ 200 cells/μL）（aO R 3.27） at the time of TB treatment initiation and a lack of antiretroviral therapy（ART） administration（aO R 3.78） were also correlated with an increased risk of death. Conclusion Infection with HIV was independently associated with increased mortality during TB treatment. Offering HIV testing at the time of diagnosis with TB, early TB diagnosis among HIV/acquired immunodeficiency syndrome patients, and the timely provision of ART were identified as the key approaches that could reduce the number of HIV-associated TB deaths.

Molecular characterization of the rpoB gene mutations of Mycobacterium tuberculosis isolated from China

Objective: To analyze characterization of the rpoBgene mutations of Mycobacterium tuber- culosis isolated from China and to explore the association of specific mutations conferring rifampicin (RIF) resistance with Beijing genotype strains. Methods: Genotypic analysis of 3479M. tuberculosis isolatesincluding 402 RIF-resistantand 3077 RIF-susceptible isolated from the na- tional drug-resistant tuberculosis baseline survey was performed. Results: DNA sequencing analysis of the 81-bp RIF resistance determining region (RRDR) of the ropB gene revealed that 98.01% of RIF-resistant strains showedrpoBgene mutation, isolates with mutations at codon rpoB531, rpoB 526 and rpoB 516 were the most frequently. Analysis of the rpoB gene of 3077 RIF-susceptible strains revealed that 98.96% of the strains had no mutation. The distribution of mutation frequency at differentcritical codons in different regions of China was statistically significant (p = 0.001). There was no significant difference in the occurrence of mutations at critical codons between the rifampicin-resistant Bei-jing and non-Beijing isolates.Conclusion: About 98% of RIF-resistant strains isolated from China carry mutations in RRDR ofrpoB gene.Mutation profiles in RIF-resistantM. tuberculosis clinical isolates are variable depending on the different geographical regionsof China. The results provide valuable information in adopting new molecular methods for diagnosis of TB in China.

Interpretation of the Protocol for Prevention and Control of COVID-19 in China(Edition 8)

BACKGROUND Since the release of Protocol for Prevention and Control of COVID-19(Edition 7),coronavirus disease 2019(COVID-19)control and prevention has been facing new challenges in China with evolving domestic and global epidemiological situations.Since September 2020,China has experienced more than 20 local outbreak waves,all of which were able to be contained within a few weeks.

Interpretation of the Protocol for Prevention and Control of COVID-19 in China (Edition 7)

After coronavirus disease 2019(COVID-19),previously known as pneumonia of unknown etiology(PUE)and 2019 novel coronavirus(2019-nCoV),was first discovered in Wuhan City,Hubei Province,the Chinese government took measures to stop the spread of the epidemic nationwide and interrupted local transmission in China(1–2).Although there have been several localized outbreaks that were caused by overseas importation of the virus—including Heilongjiang,Jilin,Beijing,Liaoning,and other provincial-level administrative divisions(PLADs)—these outbreaks have been stopped within two to four weeks and were limited in scope to less than ten cases or a few hundred cases for each event.With the COVID-19 pandemic still uncontrolled globally,the threat of importing the virus continues unabated and still threatens China’s population,virtually all of which is susceptible.

Factors Associated with Diagnostic Delay of Pulmonary Tuberculosis in China

Tuberculosis(TB)remains a major public health threat;approximately 10 million new TB cases are recorded worldwide,and more than 1.2 million deaths were caused by TB in 2019[1].The diagnostic delay presents a major obstacle to the control of the TB epidemic.