Tuberculosis in elderly patients in the city of Cali, Colombia: a hospital-based cohort study

TO THE EDITOR:

Elderly patients are at an increased risk of tuberculosis because of immune system alterations affecting cell-mediated responses.¹ Several studies have shown that tuberculosis incidence and mortality rates are significantly higher in patients over 80 years of age than in those in any other age group.² Elderly patients are also at an increased risk of developing age-related diseases such as cancer and cardiovascular disease.³ In Colombia, tuberculosis remains a public health problem, and, with the increase in life expectancy, it has become an issue in the elderly population. In addition, data on tuberculosis treatment outcomes and adverse reactions in patients over 65 years of age are limited.

Here, we report 108 cases of tuberculosis in elderly patients treated at Fundación Valle del Lili, a university hospital located in the city of Cali, Colombia, where the tuberculosis notification rate in 2015 was 40 cases per 100,000 population. All cases were recorded in the institutional tuberculosis database between January 1st, 2011 and December 31st, 2016. The inclusion criteria were as follows: being 65 years of age or older and having been diagnosed with tuberculosis on the basis of an AFB-positive sputum smear, a positive culture for Mycobacterium tuberculosis, or a positive GeneXpert result. Cases of nontuberculous mycobacterial infection were excluded, as were suspected but unconfirmed cases of tuberculosis.

Descriptive statistics were calculated for all variables. The chi-square test or Fisher’s exact test was used in order to compare categorical variables, and a t-test was used in order to compare continuous variables. A subanalysis was performed on patients in the 65- to 79-year age bracket (the non-octogenarian group) and on those ≥ 80 years of age (the octogenarian group). Patients for whom there was information regarding treatment outcomes were evaluated and divided into two groups, namely, treatment success and treatment failure. Survival analysis was performed with the Kaplan-Meier method. Differences in survival between the two age groups were assessed by the log-rank test. A value of p < 0.05 was considered significant for all statistical analyses. All analyses were performed with the Stata statistical software package, version 14.0 (StataCorp LP, College Station, TX, USA).

Patient clinical and sociodemographic characteristics, as well as comorbidities, risk factors for tuberculosis, and treatment outcomes, are summarized in Table 1. The most common comorbidities in the non-octogenarian group were diabetes, in 36%; COPD, in 23%; and malignancy, in 21%. In the octogenarian group, the most common comorbidities were COPD, in 46%; malignancy, in 14%; and diabetes, in 7%. Diabetes was less common in the octogenarian group than in the non-octogenarian group, whereas COPD was more common in the former than in the latter. There was a significant difference between the two groups regarding diabetes (p = 0.004) and COPD (p = 0.017). With regard to tuberculosis presentation, there were no differences between the two groups.

Table 1
Descriptive statistics and univariate analysis results in tuberculosis patients in the 65- to 79-year age bracket (the non-octogenarian group) and in those ≥ 80 years of age (the octogenarian group).^a

Variable	Total sample		Non-octogenarian patients		Octogenarian patients		p
	(N = 108)		(n = 80)		(n = 28)
	n	%	n	%	n	%
Age, yearsb	74.0 (65.0-91.0)		72.0 (67.5-76.0)		84.0 (81.0-86.0)
Male sex	64	59	50	63	14	50	0.247
Ethnic groupc Hispanic American Afro-Colombian European ancestry Native South American	71 7 6 3	66 6 6 3	58 6 3 3	68 8 3 3	17 1 3 -	61 3 11 -	1
Comorbidities Diabetes COPD Malignancy End-stage renal disease HIV infection Chronic hepatitis C Bariatric surgery Solid organ transplantation	31 31 19 5 4 2 1 1	29 29 18 5 4 2 1 1	29 18 17 4 4 2 1 1	36 23 21 5 5 3 1 1	2 13 4 1 - - - -	7 46 14 3 - - - -	0.004 0.017 0.451 1 0.571 1 1
Risk factors for TB Cigarette smoking Previous TB treatment Household contact Positive tuberculin skin test Drug abuse	36 14 8 2 2	33 13 7 2 2	30 10 6 2 2	38 13 8 3 3	9 4 2 - -	32 14 7 - -	0.648 0.811 1 0.487 1
Duration of symptoms prior to TB diagnosis, daysd ≤ 30 31-90 ≥ 91	38 25 39	35 23 36	18 32 27	23 42 35	7 6 12	28 24 48	0.302
TB presentation Pulmonary Extrapulmonary Pleural Central nervous system Osteoarticular Genitourinary Disseminated Spinal Gastrointestinal Lymph node Cutaneous	87 21 4 3 3 3 3 2 1 1 1	81 19 4 3 3 3 3 2 1 1 1	64 16 4 3 2 2 3 1 - 1 -	80 20 5 4 3 3 4 1 - 1 -	23 5 - - 1 1 - 1 1 - 1	82 18 - - 4 4 - 4 4 - 4	0.805 0.571 0.567 1 1 0.567 0.453 0.259 1 0.259
Treatment outcomes Treatment success Loss to follow-up Death Transfer Treatment failure	45 37 20 4 2	42 34 18 4 2	33 25 15 4 3	41 31 19 5 4	12 9 5 - 2	43 32 18 - 7	0.618

• TB: tuberculosis. ^aData expressed as n (%), except where otherwise indicated. ^bData expressed as median (interquartile range). ^cMissing data for 21 patients. ^dMissing data for 6 patients.

Of the sample as a whole, 25 (23%) had a diagnostic delay of 31-90 days and 39 (36%) had a diagnostic delay of more than 90 days. In the treatment success and treatment failure groups, respectively, 10 (22%) and 7 (32%) had a diagnostic delay of 31-90 days, whereas 15 (33%) and 4 (18%) had a diagnostic delay of more than 90 days.

Of the 108 patients included in the study, 106 were started on antituberculosis therapy and 2 died before receiving treatment. Thirty-six patients (34%) were lost to follow-up, and 20 (18%) died after treatment initiation. Forty-one patients were excluded from our analysis because they did not complete tuberculosis treatment at our institution or because they were lost to follow-up. There were no significant differences between the treatment success and treatment failure groups regarding risk factors for tuberculosis, the exception being malignancy (p = 0.013).

At five years of follow-up, 24 (21.77%) had died, the remaining 84 being censored at follow-up. Five-year overall survival for tuberculosis was 78.23%. There were no differences in survival between the non-octogenarian and octogenarian groups (p = 0.5936).

Twenty patients (18%) died after tuberculosis treatment initiation. Of those 20 patients, 10 (50%) died of tuberculosis. Of those, 1 died of central nervous system tuberculosis. Other causes of death included lung cancer, in 10%; hepatocellular carcinoma, in 5%; gastrointestinal bleeding, in 15%; intra-abdominal bacterial infection, in 10%; cryptococcosis/HIV coinfection, in 5%; and stroke, in 5%. Case-fatality rates were similar between the non-octogenarian and octogenarian groups (19% vs. 18%).

Tuberculosis carries a high disease burden and a high morbidity in Colombia and across Latin America, where elderly individuals, who constitute approximately 3% of the Colombian population, are at risk of acquiring the disease. This is due to the epidemiological transition and several other factors, including immunosenescence, malnutrition, comorbidities, polypharmacy, and concurrent socioeconomic disparities.¹

The clinical presentation of tuberculosis in elderly patients can be atypical, meaning that the classic symptoms (fever, sweating, weight loss, and cough) are either not present or, if present, due to decompensated comorbidities.⁴ A high index of suspicion should therefore be maintained. In elderly patients, the most common presentation of tuberculosis is pulmonary tuberculosis, and there is a low prevalence of cavitary disease.⁵ Although there is no difference in the recommended tuberculosis treatment regimen between elderly patients (over 65 years of age) and younger patients, there is a higher risk of drug-drug interactions in the former, especially between rifampin and antihypertensive or hypoglycemic agents.⁶ These drug-drug interactions can reduce tuberculosis treatment success rates.

In a meta-analysis published in 2018, moderate-quality evidence showed an association of pulmonary tuberculosis with comorbid malignancy and an increased risk of in-hospital mortality (OR = 1.85; 95% CI, 1.01-3.40).⁷ These results are consistent with our findings that there were more cases of malignancy in the treatment failure group.

Most of the elderly patients in the present study had pulmonary tuberculosis and experienced a diagnostic delay. They had unfavorable treatment outcomes, with high case-fatality rates, and some were lost to follow-up.^8-10 These losses could be attributable to limitations of program coordination, with patients being transferred to and treated in different hospitals and health care centers, which is a constant problem in Latin America.

Tuberculosis control programs should evaluate care models to improve tuberculosis treatment success rates and health care coordination. The results of the present study can form the basis for future studies and contribute to changes in health policies related to tuberculosis control programs, including cost-effectiveness studies and more frequent follow-up of this population.

REFERENCES

• ¹
  Rajagopalan S. Tuberculosis in Older Adults. Clin Geriatr Med. 2016;32(3):479-491. https://doi.org/10.1016/j.cger.2016.02.006
  » https://doi.org/10.1016/j.cger.2016.02.006
• ²
  World Health Organization [homepage on the Internet]. Geneva: World Health Organization [cited 2019 Mar 10]. Global tuberculosis report 2017. Available from: https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1
  » https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1
• ³
  Min J, Mi Shin Y, Lee WJ, Truong TT, Kang ES, An JY, et al. Clinical features of octogenarian patients with tuberculosis at a tertiary hospital in South Korea. J Int Med Res. 2019;47(1):271-280. https://doi.org/10.1177/0300060518800597
  » https://doi.org/10.1177/0300060518800597
• ⁴
  Meira L, Boaventura R, Araújo D, Almeida LM, Bastos HN. Clinical presentation and mortality of tuberculosis in the elderly. Eur Respir J. 2016;48:PA2653. https://doi.org/10.1183/13993003.congress-2016.PA2653
  » https://doi.org/10.1183/13993003.congress-2016.PA2653
• ⁵
  Morris CD. Pulmonary tuberculosis in the elderly: a different disease?. Thorax. 1990;45(12):912-3. https://doi.org/10.1136/thx.45.12.912
  » https://doi.org/10.1136/thx.45.12.912
• ⁶
  Arbex MA, Varella Mde C, Siqueira HR, Mello FA. Antituberculosis drugs: drug interactions, adverse effects, and use in special situations. Part 1: first-line drugs. J Bras Pneumol. 2010;36(5):626-640. https://doi.org/10.1590/S1806-37132010000500016
  » https://doi.org/10.1590/S1806-37132010000500016
• ⁷
  de Almeida CPB, Ziegelmann PK, Couban R, Wang L, Busse JW, Silva DR. Predictors of In-Hospital Mortality among Patients with Pulmonary Tuberculosis: A Systematic Review and Meta-analysis. Sci Rep. 2018;8(1):7230. https://doi.org/10.1038/s41598-018-25409-5
  » https://doi.org/10.1038/s41598-018-25409-5
• ⁸
  Lee CH, Wang JY, Lin HC, Lin PY, Chang JH, Suk CW, et al. Treatment delay and fatal outcomes of pulmonary tuberculosis in advanced age: a retrospective nationwide cohort study. BMC Infect Dis. 2017;17(1):449. https://doi.org/10.1186/s12879-017-2554-y
  » https://doi.org/10.1186/s12879-017-2554-y
• ⁹
  Cavalcanti Zdo R, de Albuquerque Mde F, Campello AR, Ximenes R, Montarroyos U, Verçosa MK. Characteristics of elderly tuberculosis patients in Recife, Brazil: a contribution to the tuberculosis control program. J Bras Pneumol. 2006;32(6):535-543. https://doi.org/10.1590/S1806-37132006000600011
  » https://doi.org/10.1590/S1806-37132006000600011
• ¹⁰
  Yen YF, Feng JY, Pan SW, Chuang PH, Su VY, Su WJ. Determinants of mortality in elderly patients with tuberculosis: a population-based follow-up study. Epidemiol Infect. 2017;145(7):1374-1381. https://doi.org/10.1017/S0950268817000152
  » https://doi.org/10.1017/S0950268817000152

Publication Dates

• Publication in this collection
  23 Sept 2020
• Date of issue
  2020