Genetic Diversity and Drug Susceptibility of Mycobacterium tuberculosis Isolates in a Remote Mountain Area of China

Objective We determined the genetic diversity of Mycobacterium tuberculosis（MTB） in a remote mountainous area of southwest China and evaluated the resolving ability of single nucleotide polymorphism（SNP） genotyping combined with variable number tandem repeat（VNTR） genotyping for Beijing family strains in association with drug resistance status.Methods Three hundred thirty-one MTB strains were isolated from patients living in mountainous regions of southwest China,and 8-loci SNP,VNTR-15 genotyping assays,and drug susceptibility testing of 9 drugs were performed.Results A total of 183 [55.29%（183/331）] strains were classified into the Beijing family.Of the 183 strains,111（60.66%） were defined as modern Beijing strains.The most predominant modern Beijing sub-lineage and ancient Beijing sub-lineage were Bmyc10 [39.34%（72/183）] and Bmyc25 [20.77%（38/183）],respectively.Of the isolates,19.64%（65/331） were resistant to at least 1 of the 9 anti-TB drugs and 17 [4.98%（17/331）] MTB isolates were multi-drug resistant tuberculosis（MDR-TB）.Two hundred sixty-one isolates showed a clustering rate of 14.18%（37/261） and a discriminatory index of 0.9990.The Beijing lineage exhibited a significantly higher prevalence of MDR-TB,as well as resistance to isoniazid（INH）,rifampin（RIF）,and para-aminosalicylic acid（PAS） when analyzed independently（P = 0.005,P = 0.017,P = 0.014,and P = 0.006 respectively）.The Beijing lineage was not associated with genetic clustering or resistance to any drug.In addition,genetic clustering was not associated with drug resistance.Conclusion MTB strains demonstrate high genetic diversity in remote mountainous areas of southwest China.Beijing strains,especially modern Beijing strains,are predominant in remote mountainous area of China.The combination of 8-loci SNPs and VNTR-15 genotyping is a useful tool to study the molecular epidemiology of MTB strains in this area.

Access to and affordability of healthcare for TB patients in China: issues and challenges

This paper introduces the background,aim and objectives of the project entitled“China—the Gates Foundation Collaboration on TB Control in China”that has been underway for many years.It also summarizes the key findings of the nine papers included in this special issue,which used data from the baseline survey of Phase II of the project.Data were collected from the survey of TB and MDR-TB patients,from designated hospitals,health insurance agencies and the routine health information systems,as well as key informant interviews and focus group discussions with relevant key stakeholders.Key issues discussed in this series of papers include the uses of TB services and anti-TB medicines and their determining factors related to socio-economic and health systems development;expenditures on TB care and the financial burden incurred on TB patients;and the impact of health insurance schemes implemented in China on financial protection.

Prevalence of Tuberculosis among Close Contacts of Index Cases in 27 Universities in Beijing,China,2017-2018

The World Health Organization(WHO)launched the‘End TB Strategy’,which aims to reduce the mortality and incidence rate of tuberculosis(TB)by 95% and 90% by 2035,respectively,compared with the levels in 2015.To achieve these targets and milestones,the strategy set three pillars and 10 indicators,one of which is systematic screening of contacts and high-risk groups[1].

Erratum to“Tuberculosis in areas and countries along the China-Proposed Belt and Road Initiative”[Biosafety Health 3(2021)319–324]

The authors regret that the zip code of the affiliation“Chinese Journal of Antituberculosis”was misspelt.It should be corrected as“100035”.The managing editors regret that the article“Tuberculosis in areas and countries along the China-Proposed Belt and Road Initiative”was misclassified under the“Review article”section.It should be placed under the section“Short Report”.The authors and editorial office would like to apologize for any inconvenience caused.

Improving tuberculosis case detection in underdeveloped multi-ethnic regions with high disease burden:a case study of integrated control program in China

Background:In the underdeveloped multi-ethnic regions of China,high tuberculosis(TB)burden and regional inequity in access to healthcare service increase the challenge of achieving the End TB goals.Among all the provinces,the highest TB burden is reported in Xinjiang,where ethnic minorities and older people have suffered most.However,current case-finding strategy is inadequate given the complex social determinants and suboptimal case detection rates.Thus,we developed an integrated TB control program to improve case detection and conducted a pilot in Xinjiang from 2014 to 2015.In this case study,we summarized the activities and key findings.We also shared the experiences and challenges of implementing interventions and provided recommendations to inform the TB control program in the future.Case presentation:The pilot interventions were implemented in one selected town in Yining based on local TB control programs.By applying tailor-made educational materials,outreach TB educational activities were conducted in diverse ways.In 22 Masjids,the trained imams promoted TB education to the Muslims,covering 20,440 persontimes in 88 delivered preaching sessions.In seven schools,1944 students were educated by the teachers and contributed to educating 6929 family members.In the village communities,13,073 residents participated in household education and screening.Among them,12,292 people aged under 65 years were investigated for suspicious pulmonary TB symptoms,where six TB patients were diagnosed out of 89 TB suspects;781 older people were mobilized for screening directly by chest X-ray,where 10 patients were diagnosed out of 692 participants.Supportive healthcare system,multi-sectoral cooperation and multi-channel financing mechanism were the successful experiences of implementation.The interventions were proved to be more effective than the previous performance:the number of TB suspects consulting doctors and patients detected increased by 50%and 26%,respectively.The potential challenges,implications and recommendations should been taken into account for further program improvement.Conclusions:In underdeveloped multi-ethnic regions with high TB burden,improving case detection is necessary and the interventions can be feasible and effective within a supportive system.More intensive educational and training approaches,a high index of TB suspicion and prioritization of older people in screening are recommended.To sustain and scale up the program,the impacts,cost-effectiveness,feasibility and acceptability of interventions warrant further research and evaluation in each specific context.

Characteristics and Morbidity of the Tuberculosis Epidemic--China,2019

Introduction:The year 2019 was crucial for the implementation of China’s National“13th 5-Year”Tuberculosis(TB)Control Plan.We conducted this study to evaluate the characteristics and progress towards controlling TB in China.Methods:We collected and analyzed the pulmonary tuberculosis(PTB)data of China between January 1,2015 and December 31,2019 from the National Notifiable Disease Reporting System(NNDRS).Results:In 2019,there were 775,764 PTB cases reported in NNDRS,of which 349,307 were bacteriologically-confirmed(Bac+)cases.The PTB case notification rate(CNR)was 55.55 per 100,000,and the Bac+CNR was 25.01 per 100,000.From 2018 to 2019,the number of PTB cases fell by 6.3%,but the number of Bac+cases increased by 25.9%.The annual decrease in the rate of reported PTB was 3.4% from 2015 to 2019.The 5 provincial-level administrative divisions(PLADs)with the highest PTB CNR were as follows:Tibet(182.38 per 100,000),Xinjiang(169.05 per 100,000),Qinghai(134.53 per 100,000),Guizhou(102.51 per 100,000),and Hainan(90.22 per 100,000).The rate of reported PTB was 74.84 per 100,000 for males and 35.40 per 100,000 for females.There were 8,116 cases(1.0%)among children aged 0–14 years,and 197,730 cases(25.5%)among adults aged 65 years and over.Of the reported cases,470,932 were farmers,which was the most common occupation at 60.7%.Conclusions and Implications for Public Health Practice:The TB epidemic has decreased dramatically year by year.Most PTB cases were in the central and western regions of China,and the high-risk groups were farmers and elderly people aged 65 years and over.

Factors that determine catastrophic expenditure for tuberculosis care: a patient survey in China

Background:Tuberculosis(TB)often causes catastrophic economic effects on both the individual suffering the disease and their households.A number of studies have analyzed patient and household expenditure on TB care,but there does not appear to be any that have assessed the incidence,intensity and determinants of catastrophic health expenditure(CHE)relating to TB care in China.That will be the objective of this paper.Methods:The data used for this study were derived from the baseline survey of the China Government–Gates Foundation TB Phase Ⅱ program.Our analysis included 747 TB cases.Catastrophic health expenditure for TB care was estimated using two approaches,with households defined as experiencing CHE if their annual expenditure on TB care:(a)exceeded 10%of total household income;and(b)exceeded 40%of their non-food expenditure(capacity to pay).Chi-square tests were used to identify associated factors and logistic regression analysis to identify the determinants of CHE.Results:The incidence of CHE was 66.8%using the household income measure and 54.7%using non-food expenditure(capacity to pay).An inverse association was observed between CHE rates and household income level.Significant determinants of CHE were:age,household size,employment status,health insurance status,patient income as a percentage of total household income,hospitalization and status as a minimum living security household.Factors including gender,marital status and type of TB case had no significant associations with CHE.Conclusions:Catastrophic health expenditure incidence from TB care is high in China.An integrated policy expanding the free treatment package and ensuring universal coverage,especially the height of UHC for TB patients,is needed.Financial and social protection interventions are essential for identified at-risk groups.

Study on factors affecting TB/HIV co-infection in four counties of China

The factors affecting case detection of tuber-culosis(TB)/human immunodeficiency virus(HIV)co-infection cases were explored in order to provide evidence-based formulation of a TB/HIV co-infection control strategy in China.Four counties with different modes of HIV transmission and varying cooperation mechanisms between TB and HIV institutions were selected.HIV test among TB patients and TB examination among people living with HIV/acquired immunodeficiency syndrome(AIDS)were conducted.Patients also completed ques-tionnaires on potential factors affecting TB/HIV co-infection.The results showed that 19(1.7%)were HIV-positive among 1089 cases of people living with active TB who received HIV testing.Conversely,there were 126(10%)cases of active TB among 1255 cases of people living with HIV/AIDS.Among the newly discovered 145 cases of TB/HIV co-infection,AIDS institutions found 86.9%of these co-infections and 14.1%came from TB institutes.In different registration categories,there were 31(21.4%)cases of smear positive TB,104(71.7%)cases of smear negative TB,and extrapulmonary cases accounted for 10(6.9%).Gender,occupation,marital status,ethnic group,education,HIV transmission route,CD4 level,and type of TB susceptible symptoms had significant effects on whether HIV/AIDS patients were co-infected with TB disease(P<0.01).Sex,age,ethnic group,occupation,and type of tuberculosis had no significant influence on whether TB patients had HIV infection.AIDS institutions couldfind more TB/HIV co-infection patients in compar-ison with TB institutions,particularly in patients with smear negative pulmonary tuberculosis and extrapulmon-ary tuberculosis.Therefore,a cooperation mechanism should be built up between TB and HIV control systems,and routine TB checks should be conducted for HIV/AIDS patients.In areas where sex or drug use is the major transmission mode of HIV infection,antiretroviral therapy should be expanded,treatment adherence should be improved and patients’immunity level should be increased in order to decrease TB incidence.Cough and expectora-tion of more than two weeks,bloody sputum,and recurrent fevers could be revealing symptoms in TB screening of HIV/AIDS patients.

Tuberculosis in areas and countries along the China–Proposed Belt and Road Initiative

To assess the tuberculosis(TB)epidemic and incidence trends in areas and countries along the Belt and Road Initiative,we analyzed the prevalence,diagnosis,and treatment of tuberculosis through consulting the data of the World Health Organization’s Global Tuberculosis Report.We estimated the tuberculosis incidence trends in these countries using joinpoint regression.Among the 65 countries along the route,in addition to Palestine with no relevant data,the incidence rate was 181.5 per 100,000,and the mortality rate was 23.1 per 100,000 in 2018.Both the incidence rates in 26 countries and the mortalities in 32 countries were higher than in China.Among the regions,the incidence and mortality of tuberculosis were the highest in South Asia,East Asia,and The Association of Southeast Asia Nations(ASEAN)countries,while the tuberculosis detection rate and positive bacteriological rate were the lowest in East Asia and ASEAN countries.Average yearly incidence decreased from 235.7 per 100,000 in 2004 to 181.5 per 100,000 in 2018(average annual percentage change 1.9%)in these countries.Although TB incidence of most countries along the Belt and Road Initiative was declining,the rate of decrease was not yet fast enough.Therefore,it is essential to establish the exchange and cooperation mechanism of TB prevention and control experience among different countries,strengthen information communication and sharing,and explore a cross-border notification system.In addition,TB detection of international travelers should be carried out and improved.

Are free anti-tuberculosis drugs enough? An empirical study from three cities in China

Background:Tuberculosis(TB)patients in China still face a number of barriers in seeking diagnosis and treatment.There is evidence that the economic burden on TB patients and their households discourages treatment compliance.Methods:A cross-sectional study was conducted in three cities of China.Patients were selected using probability proportional to size(PPS)cluster sampling of rural townships or urban streets,followed by list sampling from a patient register.Data were collected using a questionnaire survey,key informant interviews and focus group discussions with TB patients to gain an understanding of the economic burden of TB and implications of this burden for treatment compliance.Results:A total of 797 TB patients were surveyed,of which 60 were interviewed in-depth following the survey.More than half had catastrophic health expenditure.TB patients with higher household incomes were less likely to report non-compliance(OR 0.355,95%CI 0.140–0.830)and patients who felt that the economic burden relating to TB treatment was high more likely to report non-compliance(OR 3.650,95%CI 1.278–12.346).Those who had high costs for transportation,lodging and food were also more likely to report non-compliance(OR 4.150,95%CI 1.804–21.999).The findings from the qualitative studies supported those from the survey.Conclusion:The economic burden associated with seeking diagnosis and treatment remains a barrier for TB patients in China.Reducing the cost of treatment and giving patients subsidies for transportation,lodging and food is likely to improve treatment compliance.Improving doctors’salary system to cut off the revenue-oriented incentive,and expanding current insurance’s coverage can be helpful to reduce patients’actual burden or anticipated burden.Future research on this issue is needed.

Use of anti-tuberculosis drugs among newly diagnosed pulmonary tuberculosis inpatients in China: a retrospective study

Background:China’s national tuberculosis control program(NTP)provides free,first-line anti-tuberculosis(TB)drugs to pulmonary TB patients.This treatment regimen follows the World Health Organization’s(WHO)guideline.The objective of this paper is to evaluate the current status of anti-TB drug use for newly diagnosed pulmonary TB inpatients treated in prefecture-and county-level designated hospitals.Methods:Three prefecture-level hospitals and nine county-level hospitals were selected for the study.All newly diagnosed pulmonary TB inpatient medical records from 2012 were reviewed and doubly examined by two national senior physicians.The rational use of anti-TB drugs was evaluated based on criteria in line with WHO’s guideline.Results:Of the 2,060 total treatment regimens for TB,53.1%were found to be rational(1093/2060).The percentages in prefecture-level and county-level hospitals were 50.3%(761/1513)and 60.7%(332/547),respectively.The difference between the two levels of hospitals was statistically significant(Chi-square value=17.44,P<0.01).The percentages of rational treatment regimens for first-time hospitalizations and for two or more hospitalizations were 59.5%(983/1653)and 27.0%(110/407),respectively,with a statistically significant difference(Chi-square value=138.00,P<0.01).The overall use of second-line drugs(SLD)was 54.9%(1131/2060).The percentages for prefecture-level and county-level hospitals were 50.6%(766/1513)and 66.7%(365/547),respectively.A statistically significant difference was found(Chi-square value=42.06,P<0.01).The use of SLD for inpatients hospitalized once and inpatients hospitalized twice or more was 58.4%(966/1653)and 40.5%(165/407),respectively,with a statistically significant difference(Chi-square value=42.26,P<0.01).Conclusions:Half of inpatients might be treated with irrational regimens,and the use of SLD was more appropriately dispensed in city-level hospitals than in county-level hospitals.Trainings and guidelines for health personnel,supervision led by health authorities and increased investment to designated hospitals may help to improve the rational use of anti-TB drugs.