The Epidemiological and Clinical Aspect of Pulmonary Tuberculosis in Elderly: A Comparison with None-elderly in Yazd

1. Department of Ageing Health, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2. Research Center of Prevention and Epidemiology of Non-Communicable Disease, Department of Statistics and Epidemiology, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
3. Department of infectious diseases, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4. Elderly Health Research Center, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
5. Department of Health Education, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

ARTICLE INFO		ABSTRACT
Original Article Received: 16 Apr 2018 Accepted: 6 May 2018		Introduction: The nature of life course, with aging, triggers changes in the respiratory and immune system of the elderly, which increases the susceptibility to Tubercle Bacilli (TB) in the elderly. Clinical characteristics and the natural course of TB in older adults are different. This study aimed to compare the epidemiological and clinical features of pulmonary TB in elderly and non-elderly patients over 16 years old in Yazd city in a five-year period. Methods: Within this historical cohort study, recorded of patient's data, including age, gender, clinical symptoms of the disease, history of treatment, drug resistance, and treatment results examined during 2012-2016. Results: From 177 patients with pulmonary TB, who admitted to this study, 107 were 65 years and older (60.5%), and 70 were aged 16-64 (39.5%). Elderly experienced fever significantly fewer (p = 0.02), nonetheless they are more complaining about dyspnea (p = 0.01) and anorexia (p = 0.04) than non-elderly people. The incidence of drug complications was significantly higher among the elderly. Drug side effects, especially dermal itching (p = 0.001), are higher for older people. The number of drug resistance associated with larger mortality and recurrence in the elderly, which is not significant. Mantel-Haenszel evaluation showed that irrespective of drug resistance, the elderly died more than non-elderly (OR = 1.37 ± 0.88) (p = 0.85). Conclusion: Clinical symptoms, diagnostic criteria and treatment outcome and complications of TB in the elderly are significantly different from others. Elderly people are considerably more likely to anorexia than non-elderly. Fever is not common among elderly people. The incidence of drug complications was significantly higher among the elderly. Considering these differences will help us to diagnose and treat them more effectively. Keywords: Epidemiology, Tuberculosis, Elderly, Treatment Outcome, Yazd
Corresponding Author: Seyedeh Mahdiah Namayandeh

Introduction‏
Tuberculosis (TB) is one of the oldest known human diseases. TB appears in both pulmonary and extra-pulmonary forms. People get infected by inhaling the TB bacillus. After entrance into the lung, TB germ makes the primary lesion and can spread to other parts of the body through bloodstream, lymphatic vessels, and bronchi.
The World Health Organization (WHO) considered it a global health emergency (1). Each case of TB with cavity can infect 20 people (2). According to WHO report, by the end of 2020, one billion people will develop a new infection with Mycobacterium tuberculosis, and 35 million TB patients will be died (3).In 2015, Iran according to the WHO report the incidence rate of tuberculosis was 16 cases per 100000 populations (4).
The population aged 60 or over is expected to go quickly double, however, growth in the number of older people is more rapidly in the least developed countries. Between 2015 and 2030, the projected 70 percent increase in the population aged 60 years or over is nearly identical with that projected in the other less developed countries. Thus, the challenges of age-related diseases are higher in these countries (5).
The results of general census of population and housing in 2011 in Iran shows that, about 2.8 percent (more than 6 million) of our population aged 60 years and over. Therefore, Iran is changing the demographic trend towards aging as other countries. It is expected that by 1406, the 60 years old or more of the population will reach 10 percent (6).
In general, non-behavioral risk factors of TB include age, homelessness, renal failure, diabetes, HIV infection, immunodeficiency, imprisonment, and behavioral risk factors, including malnutrition, alcohol, and smoking (7, 8). Risk factor is varying in societies with different climatic and economic conditions (9-14).
The nature of life course, with aging, triggers changes in the respiratory and immune system of the elderly, which increase the susceptibility to TB in the elderly. In the elderly, they are susceptible to increase to infectious diseases, especially respiratory diseases (15). Aging has a significant effect on Inherent immunity and acquired active immunity (16-18), which can increase the risk of TB in this group. Improving the life expectancy and the number of elderly people increases the use of immunosuppressive drugs that can increase the incidence of pulmonary tuberculosis in the elderly. (19). Cellular immunity against disease through phagocytic cells and T- cells against the bacterium (20).T-cell production lessened in the thymus gland in aging (21, 22). A large proportion of TB population occurs between the ages of 45 and 55, but in the West Pacific region, the eastern
and southeastern Mediterranean, ascents are increasingly occurring in people over the age of 65 (23). Recent studies show, there has been an increasing trend for the incidence of TB in people aged 65 and over in Asian countries. There are reports of upper incidence in the United States, especially in Central and South America (13) and North America (24). Two or more Co-morbidity and their treatment in advanced age are associated with an increased risk of TB. Several comorbidities were common in the aging may increase the risk of active TB. Overall, compared to younger ones, aging can lead to changes in simple symptoms, diagnosis, treatment and drug resistance.
TB Control Program integrated into the healthcare services in Iran and has been active. Treatment of patients and care based on the DOTS (Directly Observed Treatment Short Course) strategy, the complete treatment of patients with a goal of 70% detection and 85% recovery after treatment (25). This study aimed to compare the epidemiological and clinical characteristics of pulmonary TB in elderly and non-elderly in Yazd city during the years 2012-16.
Methods
The survey was a historical cohort type and had approved by the ethics committee of Yazd University of Medical Sciences (no.1395.159). Patients divided into 2 groups based on their age at diagnosis, as elderly (65 years and older) and non-elderly, including 2 subgroups of young and adults respectively 16-29 and 30-64 years old. The patients selected according to the WHO protocol, which included the hilar lymphadenopathy, the sputum cultures result, and clinical symptoms (18). Patient entered this study according to inclusion and exclusion criteria .inclusion was: residence In Yazd city confirmed as TB patient by a laboratory or clinical diagnosis (sputum smear results, sputum culture, and positive bronchial lavage). Patients lived in other provinces or those who referred to Yazd for diagnosis or periodic monitoring of treatment excluded. Patients with clinical diagnosis of TB without a positive test excluded from this study. According to immune system development during the puberty and complexity of infectious diseases in children, patient under the age of 16 years old excluded from this study‏.
 Based on the importance of TB and the implementations of the DOTS strategy, Nikpoor clinic selected as a referral center of TB in Yazd province.  Patients' data is collected contain; age, sex, clinical signs of the disease, including fever, sweating, cough and sputum, anorexia, hemoptysis, dyspnea, weight loss chest pain, blindness, bronchoscopy and sputum culture, chest radiography and comorbidity such as diabetes, renal failure, chronic obstructive pulmonary disease and immune deficiency, HIV, cancer, history of TB, history of treatment, drug resistance. TB patient monitored at least four times in two months and during maintenance four times in four months. The drug treatment response of pulmonary TB in a patient's case (including improved, died). This information collected and entered into SPSS 16 software. Chi-square and Mantel-Haenszel test analyzed the clinical signs and diagnosis and outcome.
Results
In this five-year period of study, we used census for including of TB patient. The studied population composed of 177 patients. The number of males was 95 (53.7%), and 82 (46.3%) were females. The mean age for the None-elderly 42.89 ± 12.20 (range from 18 to 63 years) and that of the elderly group was 76.99 ± 7.04 years (age range of 65-93 years).
The Nikpoor clinic is a referral center in Yazd province, the number of tuberculosis patients was censused and computed the incidence rate of positive-smear pulmonary TB, negative smear
TB and the annual incidence of TB in hundred thousand people in a five-year period. From including of TB patient, 107 people were 65 years and old (incidence rate =3.05 in 100,000) and 70 patients aged 16-64 years (incidence rate =59.42 in 100,000). The incidence rate of TB was more significant in the elderly (P < 0.0001). The incidence rate is shown in Figure 1.

 
Figure 1. Trends  in the incidence in each 100,000 persons of TB in elderly and non-elderly in Yazd province.
 

According to respiratory hospitalization before the diagnosis of TB, a higher percentage of elderly (72.9%) compared to the none-elderly group (47.1%) has been seen (P < 0.001).
The mean length of hospitalization in the elderly group (14.41 ± 8.88 days) was longer than the other group (10.32 ± 6.85 days) (P < 0.01).
Table 1 shows the history of TB treatment, although with increasing age the incidence of recurrence was higher than those groups, but was not statistically significant.
Clinical symptoms were evaluated in 2 groups, and we found that they had chief complain of dyspnea (p = 0.01) and anorexia (p = 0.04) than non-elderly people. As it can be seen, the elderly fever was seen significantly less than the non-elderly
(p = 0.02). (Table1).

P value	None-elderly		Elderly		Variables
	%	N	%	N
0.270	87.2	61	86	92	New case	History of TB treatment
	5.7	4	10	11	Relapse
	5.7	4	2	2	Cure after failure
	1.4	1	2	2	Resistant cases
0.026	37.14	26	21.50	23	Fever	Clinical symptoms
0.372	10	7	7.48	8	Sweating
0.483	74.29	52	75.70	81	Cough
0.426	31.43	22	28.97	31	Purulent sputum
0.089	8.57	6	2.80	3	Hemoptysis
0.011	28.57	20	46.73	50	Dyspnea
0.442	47.14	33	44.86	48	Recent weight loss
0.234	2.86	2	6.54	7	Chest pain
0.047	8.57	6	18.69	20	Anorexia
0.203	8.57	6	14.02	15	Weakness

Two main risk factors for pulmonary TB were smoking and opium addiction. These were significantly higher in none-elderly groups than another group (p <0.001) (P=0.03), respectively.
The patients' side effect of the drug analyzed. The elderly drug side effects is significant
(p = 0.01). The incidence of skin itching in the elderly is statistically significant (p = 0.001).
In 2 groups, there was no difference in the frequency of comorbidity, But In the none-elderly group, history of Corticosteroid use was significantly more than other (p = 0.02).
Furthermore, although the number of elderly people Who Non adherence with medication was slightly higher (p> 0.05).
At the end of the treatment, the rate of completed treatment in 2 groups was similar.
Mantel-Haenszel analysis showed that, regardless of drug resistance, older people died more than non-elderly (OR = 1.37 ± 0.88) (p = 0.85). At the same time, the rate of Completed treatment in both groups has reached a strategic goal of more than
85% (Table 3).

P value		None-elderly			elderly(%)     n			Drug side effect
		%	N		%	N
0.014		78.6	55		67.3	72	No one		Side effect
		7.1	5		1.9	2	Moderate
		14.3	10		30.8	33	Severe
0.540	10		7	9.3		10	Nausea
0.395	1.4		1	0		0	Burning feet
0.078	0		0	4.7		5	Skin spot
0.001	4.3		3	22.4		24	Itching
0.636	1.4		1	0.9		1	Hearing loss
0.320	2.9		2	5.6		6	Dizziness
0.610	5.7		4	5.6		6	Jaundice
0.161	7.1		5	2.8		3	Medicinal Hepatitis
0.605	0		0	0.9		1	Visual impairment
0.605	0		0	0.9		1	Renal failure

P value	None-elderly				Elderly		Outcome
	%			N	%	N
0.448		88.7	55		86	86		Remission
		8.1	5		10	10		TB related	Expired
		3.2	2		4	4		Other diseases

Discussion
The incidence of pulmonary tuberculosis in this study shows that tuberculosis occurs significantly among elderly. Clinical symptoms, diagnosis, and treatment of TB in the elderly are substantially different from others. Elderly people are significantly more likely to anorexia than non-elderly. Fever in the elderly isn't common. Other studies showed TB occurs in elderly people with nonspecific appearance (26). These differences can be explained through physiological changes that occur during aging. (27). The results of this study showed that young people have a significant fever and hemoptysis symptoms than older people. In similar studies, fever, hemoptysis(26, 28), and nighttime sweats (26), cough (26, 29) have been significantly observed in young adults. On the other hand, the elderly were less likely to have the fever and also had symptoms of dyspnea and anorexia  (28, 29) more than others. A study conducted in Iran by Talebi Taher et al. showed that in patients admitted to Rasool Akram Hospital was associated with lower incidence of fever, sweating, hemoptysis, anorexia and chest pain in older patients. (26, 27, 30)  however, comparing the results from the study confirmed their result except chest pain, and anorexia was more common in Yazd elderly. The cause of the prevalence of hemoptysis in young patients, the higher prevalence of cavity lesions in young people than in the elderly can be pointed out. Increasing the intensity of inflammatory reactions in the alveolar wall of young people leads to capillary laceration alveolar, thus bleeding is more than the elderly (31). Concerning the cause of decreasing the prevalence of fever and anorexia in elderly patients, it can be said that with age, the immune system's response decreases and inflammatory responses to microorganism's decrease and inflammatory mediators such as IL-6 and TNF-α Cause less fever and other inflammatory appearance (32). The results from this study and other studies indicated that the elderly significantly increased the prevalence of dyspnea (27) In relation to the risk factors associated with TB, a study done by Jeon, diabetes increased the risk of active TB by about three-fold (relative risk = 3.11, 95%) (CI :2.27-4.26) in all age groups. One reason for the high rate of TB in the elderly be increased the prevalence of diabetes (33). Furthermore, the study was similar to the underlying disease, such as diabetes mellitus, and renal failure (27, 30). Although these two diseases were more frequent in Yazd's elderly but not significant. The study by Van Den Brande. In Belgium also showed a significant increase in smoking in young people (29). In a study by Mauryra, there was a significant relationship between smoking and TB (16). The study by Brode on individuals with the rheumatoid disease has shown that the use of immunosuppressive drugs increases the risk of Mycobacterium infection (34). Among anti – TNF - mediated immunosuppressive therapies, increases particularly the risk of active TB (34-36). Corticosteroids (oral prednisolone> 7.5 mg/day) in other diseases are also an independent risk factor for active TB (37, 38). In another study, the use of suppressor drugs was more closely observed in the elderly group (29). The results from this study, similar to the study by Yee and Schaberg, showed that more side effects had been observed in the elderly (28, 39, 40). As seen in this study, the elderly is almost three times as likely to develop the Sid effect (41). In this study, the recovery rate (87%) has reached the goal of the strategy. However, as we can see in this study, the death rate from TB in the elderly is higher similar to other studies (1, 28, 42, 43). In another study, six times more deaths from TB in the elderly occurred, and postmortem morbidity was more than twenty times higher than that of young people (41).
Conclusion
TB presentation diagnostic criteria and treatment outcome and complications in the elderly are a significant difference with non-elderly.This study has shown the fundamental differences between the elderly and non-elderly. Knowing these differences will help us diagnose and treat them more effectively.
Acknowledgments
The authors acknowledge the ongoing friendly contributions from the Nikpoor clinic personnel especially Dr.Azam Mirshamsi and Mr. Mosayeb Rajabzade, staff of Shahid Sadoughi University of Medical Sciences.
Conflict of interest
The authors declare that they have no conflict of interests.

 
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