Screening for pulmonary tuberculosis in type 2 diabetes elderly: a cross-sectional study in a community hospital

Tuberculosis (TB) and diabetes mellitus (DM) are both the major global health problems. According to the World Health Organization (WHO), there were an estimated 8.7 million incident cases of TB and 1.4 million deaths from TB in 2011 [1]. On the other hand, the International Diabetes Federation (IDF) reported that more than 371 million people all over the world had DM and 471 billion USD were spent treating diabetes in 2012 [2]. Many risk factors have been associated with TB, such as male gender [1], cigarette smoking [3, 4], alcohol consumption [5], underweight [6], renal disease [7], household contact [8], socioeconomic status [9], and diabetes mellitus [10]. As diabetes patients increased year by year, more and more studies focused on TB prevention in diabetic group in these years [10‐17].

In Taiwan, a total of 12,220 new tuberculosis cases were recorded in 2012, including 8,546 males and 3,674 females [18]. Among these cases, about 52% were aged over 65 years, with the disease possibly induced from impaired immunity with aging. Furthermore, the ratio of extra-pulmonary tuberculosis in Taiwan is decreasing year by year, claiming only about 4% of all incidence tuberculosis in 2010 [19]. Hence, given that they are at high risk for tuberculosis infection, especially pulmonary tuberculosis, it is important for the elderly to be screened. As an aging country composed of more than 11% of the population over 65 years, Taiwan has a high prevalence of diabetes. According to the Nutrition and Health Survey in Taiwan (NAHSIT) 2004–2008 [20], the prevalence of diabetes in Taiwan was 8.8%, higher than the global data of 8.3% [2]. The prevalence was especially high in old people over 65 years, accounting for 27.7% in males and 24% in females, which further increases the risk of tuberculosis infection.

For tuberculosis prevention, many studies focus on the effects of diabetes on tuberculosis infection. The risk of tuberculosis infection not only rises in diabetes patients, but is also associated with a higher risk of an increased number of diabetes complications [10]. Diabetes patients also require longer treatment and are more likely to develop multi-drug resistant tuberculosis [21]. Additionally, joint management of both diseases appears to improve clinical outcomes [17]. However, most studies to date have employed case control or cohort design. In this study, we focus on the active screening of tuberculosis in elderly diabetes patients and assess other possible risk factors among this group of patients.

Although diabetes as an important risk factor of tuberculosis infection is well documented [10‐13], most of the relevant literature is retrospective. A systemic review in 2010 included only 12 studies about active screening for TB in diabetic patients and some of them used non-specific methods (such as chest X-ray) to diagnose TB [15]. However, screening rate increased with the prevalence of TB in the study region and with the severity of diabetes. One pilot large scale intensive screening project, reported in China [14], enrolled 15,342 diabetes patients over 14 years of age in 5 medical centers without documented HbA1c. Only symptom screening positive patients went on for further studies for TB. From September 2011 to March 2012, the TB notification rate rose from 0.31-1.11‰ (each medical center) to 3.52-7.74‰ (average of 5 centers for each quarter). In a similar symptom screening project in a tertiary care hospital in south India, 38 of 7,083 diabetic patient already had TB and 12 of 125 underwent TB investigation were newly diagnosed TB. The incidence rate increases with HbA1c level and diabetes duration, especially in patients with HbA1c over 9.0% and with diabetes duration over 10 years [16]. Another symptom screening research in Mexico detected 38 TB cases in 7,763 diabetes patients and 11 of them were unaware of their TB [17]. These studies pointed out that active screening and better glucose control might be important in TB prevention.

In Taiwan, there were 12,220 TB notifications in 2012 and 6,328 (52%) of them were over 65 years of age [18]. The prevalence of TB in the general population and in the elderly over 65 years was 0.52‰ and 2.43‰ respectively. In our main study area of Chiayi County, the data was similar, 0.62‰ and 2.54‰, indicating an increased risk of TB infection in the elderly. Similarly, Baker MA et al. reported that diabetes and treated diabetes patients had an increased risk for TB (Hazard Ratio: 3.60 & 4.37, respectively) [10]. According to our findings, the prevalence rate of TB (3.89‰) was further increased 6- to 7-fold in advanced aged diabetes patients, suggesting the worth of wide-spread screening.

Two comorbidities reached statistical significance in our study: higher liver cirrhosis prevalence in the new TB group and lower hypertension prevalence rate in all TB groups. Based on previous research in Taiwan, liver cirrhosis was not found to be a risk factor of pulmonary TB with pulmonary infection [27], but this finding may be due to an insufficient number of active TB cases. Further subgroup studies on the etiologies of liver cirrhosis are also needed to clarify the relation between liver cirrhosis and active tuberculosis in diabetic older patients. Furthermore, BMI was documented to have a positive relationship with blood pressure [28], and being overweight was also associated with high risk of hypertension and cardiovascular events [29]; for these reasons, the lower BMI in all TB groups likely resulted in a lower hypertension prevalence rate. Other risk factors, such as male gender, lower BMI, smoking, alcohol drinking, and TB family history are comparable with previous findings [1, 3‐6, 8, 16].

Accumulating literatures have described the difference in lipid profiles between TB and health controls, showing lower levels of total cholesterol, LDL, and high-density lipoprotein (HDL) level in TB cases [30, 31]. Some authors speculated that it might be the result of increased lipid metabolism during inflammatory or infection status for immune response [32]. In our study, however, the levels of LDL and HDL tended to be lower in the new TB group without statistical significance. The reasons for this discrepancy are not clear and may be attributed to the insufficient numbers of TB cases and different patient population in this study.

Based on a survey of symptoms in 313 adult tuberculosis patients, the percentage of cough ≥ 2 weeks, chest pain, anorexia, and body weight loss was reported as only 48.2%, 41.0%, 40.6%, and 44.5%, respectively [33]. In the elderly, one meta-analysis review reported no differences between old and young TB patients with respect to cough, sputum production, weight loss, and fatigue, but older patients had a lower prevalence of fever, sweating, and hemoptysis [34]. In this study, we found that neither a symptom score of greater than 5 points nor any symptom could clearly distinguish TB cases, with the exception of subjective body weight loss. Similarly, the weakness of symptom screening was also demonstrated in a Vietnam study [35]. In fact, we showed that subjective body weight loss is an independent factor associated with pulmonary TB. In this regard, underweight has been shown to be an independent factor associated with tuberculosis [6]. Taken together, elderly diabetic patients with complaints of body weight loss should prompt active TB screening in practice.

This study has several limitations. The first limitation is about the short duration. In an observational study in the U.S., TB was observed to be a seasonal disease, with a peak in spring and trough in late fall [36]. Our study period that covered September to November, the results may thus underestimate of the effect of intensive screening due to relatively lower incidence rate. Secondly, we examined acid fast stain and mycobacterial culture only in suspicious cases. It is likely that we underestimated the occurrence of pulmonary TB in this population. This underestimation may constitute an under-reporting bias and negatively impact the accuracy of the risk factors for TB in this analysis. Further studies are needed to clarify this issue.

Subjective body weight loss, smoking and liver cirrhosis are independent factors associated with pulmonary tuberculosis in elderly diabetic patients. In these subgroups of patients, active surveillance should be prompted to identify patients who are in need of treatment. Considering the potential benefit of joint management of TB and DM, further investigations are needed to study the impact of active screening program on the treatment outcomes in elderly diabetic patients with TB.