This retrospective cohort study collected 12661 primary TB case-patients in Shandong, the second largest province in China, from 2004 to 2019, to evaluate the epidemiological characteristics and trend among the elderly DR-TB. We have some findings in this study. Among the elderly, the proportions in these subgroups including MDR-TB, PDR-TB, RFP-resistance and cavitary DR-TB increased significantly. The pattern of DR-TB shifted into male,cavity and RFP, SM-resistant groups. Male,smoking,drinking, COPD and diabetes subgroups.subgroups should get more attention.
According to the WHO report, TB prevalence increased with age in Asia and some African countries (e.g. Ghana, Malawi,Rwanda, the United Republic of Tanzania and Zimbabwe), the peak of prevalence in some Africa countries (e.g. Ethiopia, Gambia, Namibia, Nigeria, Sudan, Uganda and Zambia) were among those people aged 35–54 years. And there is a estimated that the elderly population will come up to 400 million by 2030. The prevalence of tuberculosis in aged 65 years and older was more than twice as high than that in younger adults. Elderly patients have been repeatedly reported to have a lower treatment completion rate and are less health awaeness than younger patients .That means the diagnosis and treatment in elderly TB is very difficult for us.[17, 18] So the TB in the elderly should be appreciated. Meanwhile we found that the elderly (≥ 60 years) primary TB patients accounted for about one third(4368/12661, 34.50%)of the total new TB cases.
Besides, we found that the elderly with TB were more likely to be male, to have habits of smoking or drinking, and to develop complications such as COPD or diabetes than the non-elderly .We found that there was no statistical significance between elderly DR-TB cases and elderly susceptible TB cases in our statistical data. But we found that elderly DR-TB cases are more likely to be male and to like smoking than non elderly DR-TB cases. Some surveys showed a systematically higher burden of TB disease among men, with M:F (Male/Female) ratios ranging from 1.2 ( in Ethiopia) to 4.9 ( in Viet Nam). The M:F ratios were generally higher in Asia than in Africa, that was in the range 2–4.  In 2017 ,TB cases in all EU/EAA (European Union/East Asian Area) member States tended to be male. In Poland, men was the biggest in older age groups with TB. This phenomenon may be associated with Social behavior factors and biological sex-related factors, such as sex steroid hormones, the genetic makeup of the sex chromosomes, and sex-specific metabolic features. Risk factors are also very important in the control of tuberculosis. Diabetes, alcohol use, and smoking all accounted for about a quarter of tuberculosis deaths and DALYs (disability-adjusted life years )around the world in 2015.  These factors may increase the risk of TB by impairing the immune system of human.[21–23] Smoking made it easy to develop TB which is related to ciliary dysfunction, to a reduced immune response, and to defects in the immune response of macrophages, with or without a decrease in the CD4 count. Some evidence suggested that drinking was linked to tuberculosis treatment compliance and may lead to subsequent acquired drug resistance.besides it might be related to the sequelae of AUD (Alcohol Use Disorders), [21, 22, 23, 24, 25] Diabetes leaded the susceptibility to tuberculosis to increase by a few mechanisms, including hyperglycemia and cellular insulinopenia, which have indirect effects on macrophage and lymphocyte function. The study pointed out that factors impaired the innate defence mechanisms in the airways in COPD might increase the risk of TB infection or become activeTB. Besides the study suggested that immunity declined and susceptibility to chronic disease increased with aging . Taking some measures to prevent these risk factors may make cascade effect on the control of TB and DR-TB in the elderly.
The results of the National Prevalence Survey showed China has 5.7% of new and 25.6% of previously treated cases of MDR-TB  In addition, the DR-TB and MDR-TB were accounted for 18.10% and 2.89% respectively among the elderly with TB in our study. Meanwhile, we found that the annual drug resistant rate of MDR-TB, PDR-TB,RFP-resistance and cavitary DR-TB increased significantly in our study. The increment of MDR-TB were also be found in previous studies in Beijing(from 2005 to 2008), in Korea,in Taiwan et al. And in Zhejiang province the drug resistant rate of MDR-TB decreased  very slowly. China has the world’s largest number of patients with MDR -TB. Inadequate treatment in both the public health system and the hospital system may induced the MDR-TB.The treatment of MDR-TB/RR-TB is difficult, complicated and costly. [8, 34] All of these alarm us that the MDR-TB plays a key role in the burden of DR-TB disease. We found that the elderly had a higher resistantce rate only to INH or EMB and a lower resistance rate to any one of INH, RFP, EMB, and SM compared to that in non elderly. These could be found in TaiWan [35, 36, 37, 38], in United Kindom. And we also found that the drug resistant patterns changed into male, cavitary TB, RFP-resistant and SM-resistant among the elderly. Some previous studies suggested that the cavity of tuberculosis could lead to an increased possibility of DR-TB during treatment. the prevalence of DR-TB was significantly higher among males illuminated in some study.[41, 42, 43, 44] It had been noticed that cavities were more common in DR-TB cases than in susceptible TB cases, and this phenomenon may be caused by limited drug penetration into cavities, the suitable environment provided by cavities for bacili, patients’ immunity et. al.[45, 46, 47, 48]Elderly patients were more probably to get RR-TB than the younger patients which was stated in some surveis.[42, 44].These may be the reasons that DR-TB pattern changed The change of DR-TB pattern will bring us a huge challenge to control the DR-TB in the elderly.
There were several advantages in our study. Firstly, the study were conducted in Shandong province, the second largest province in China ,from 2004 to 2019. All DST data were involved in our study. The research time span is large and the scope is wide So that our findings are more likely to be generalized throughout the country. Secondly, we screened out the elderly with TB,and divided the elderly with TB and DR-TB into different subgroups according to sex, smoking history, drinking history, cavity, COPD, diabetes and so on.
Our study also had some limitations. Firstly, DST were not regularly executed among all TB patients, TB surveillance stations had differences in screen density and medical conditions, which might induce selection bias in our data. Secondly, there were some unavoidable bias induced by different technical levels and experimental conditions in TB surveillance. Lastly, the statistical data on smoking and drinking from 2004 to 2007 is missing in our study, thus we could not analyze the subgroups among the elderly with DR-TB including smoking, drinking et. al very well .