Clinical and epidemiological features of the detection and course of the infectious disease tuberculosis depending on the presence of concomitant pathology

Nina V. Davletbaeva, Raul A. Sharipov, Daminov E.A., Davlet-baev R.N., Daria M. Kutuzova, Nelli F. Khabibullina, Tatiana E. Tyulkova. Clinical and epidemiological features of the detection and course of the infectious disease tuberculosis depending on the presence of concomitant pathology. Cardiometry; Issue No. 29; November 2023; p. 74-79; DOI: 10.18137/cardiome-try.2023.29.7479; Available from: issues/no29-november-2023/clinical-and-epidemiological-fea-tures-detection-and-course

Tuberculosis, a widespread infectious disease in the world , increasingly affects people with concomitant pathology, which is accompanied by dysfunction of the immune system. Such pathologies include oncological diseases, diseases of the endocrine system of the respiratory system (chronic bronchitis, pneumoconiosis), gastric ulcer, pathology of the urinary system, malnutrition, smoking [18]. One of the biggest medical advances of the last century has been the use of biological therapy, which also changes the patient’s immune status. Using genetically engineered biological drugs (GEBPs) in practice reduces the activity of inflammatory phenomena due to suppression of the immune response, but increases the risk of developing infectious diseases, primarily tuberculosis [1, 7]. Immunosuppressive therapy in organ transplant patients is also associated with a risk of developing tuberculosis [1]. A special nature of immune disorders develops during HIV infection, a comorbid disease in patients with tuberculosis. The diseases listed above create a medical risk group in patients with immunocompromise, which is the basis for the development of tuberculosis. According to the previous research, diabetes mellitus increases the risk of developing tuberculosis by 8.4% [4], chronic obstructive pulmonary disease (COPD) – by 1.8–8.9 times [19], and GEBD therapy – by 5–10 times [15]. Therefore, among patients with concomitant pathology, it is necessary to perform measures for the active detection of tuberculosis [3]. In addition to the risk of developing infection, patients with concomitant diseases have unfavorable results from treatment of tuberculosis [2], which does not allow achieving abacillation in a short time, thereby maintaining a reservoir of infection in the community. Based on the above, the purpose of our research was to study the clinical and epidemiological features of the detection and course of tuberculosis in patients depending on the presence of concomitant pathology.

Materials and methods

A study was conducted using a continuous sampling method for the period from December 2020 to August 2021. 67 medical records of an inpatient at the state budgetary healthcare institution Republican Clinical Tuberculosis Dispensary (Ufa) were analyzed. The groups were formed based on the detection of concomitant pathology (main, n=33) and its absence (control, n=34).

In the main group, patients had HIV infection (n=24), viral hepatitis (n=19), diabetes mellitus (n=4), rheumatoid arthritis (n=2), allergic dermatitis (n=3), stomach diseases (n = 4) and kidneys (n=2), chronic obstructive pulmonary disease (n=2). More than 1 nosology occurred in 33 patients. The most common combina- tion (HIV + hepatitis) was registered in 19 people, and a combination of other pathologies – in 14 people.

To achieve the goal of the study, a comparative analysis of methods for detecting tuberculosis and clinical manifestations of tuberculosis was performed; prevalence of the process, detection of the fact of bacterial excretion and drug sensitivity of Mycobacterium tuberculosis (MBT) in patients of the studied groups.

To assess the clinical signs of immune deficiency, a questionnaire from V.Yu. Mishlanov et al. was used, where the fact of immune deficiency was established if there were 5 or more positive answers to the questionnaire [12].

Statistical data processing was performed using licensed software Statistica 6.0 when calculating two types of data: discrete and interval. To assess the chances of detecting the studied factor in both groups, the indicator (OR) was used to calculate the 95% confidence interval (CI). Interval indicators were studied using the t-test for independent samples, with Livigne’s correction [5].

Results

The study revealed that in both groups men predominated (79.4% and 75.8%, respectively), the average age of patients in the main group was 43.0 ± 11.6 years, in the control group - 40.2 ± 8.96 (p> 0.05). That is, all patients were of working age, and the groups were comparable by gender and age.

According to the table, the authors revealed that the use of psychoactive substances was recorded only in the main group. It is noteworthy that observation by a narcologist also occurred only in patients of the main group, but much less frequently (see Table 1). People who use psychoactive substances are more often stigmatized [16] and have an increased level of anxiety [7]. Similar negative effects have been described when drinking alcohol. According to the previous research, the incidence of tuberculosis among patients suffering from alcohol dependence is 18 times higher compared to healthy individuals [12]. We recorded equal chances of identifying smoking patients in both groups (4241%). At the same time, chronic obstructive pulmonary disease was diagnosed only in the main group. According to the previous research, there is a delay in the diagnosis of tuberculosis and smear conversion in smoking patients [14]. These factors contribute to the formation of a chronic course of specific inflammation, which was confirmed during the study (see Tables 2, 3). Considering that patients in the main group have two or more

Table 1

Patient’s social status and bad habits

Parameter	Group 1 n=33		Group 2 n=34		OR	95% CI
	abs	%	abs	%
is registered with a narcologist	5	15	0	0	-	-
smoking	14	42	14	41	1.053	0.399-2.780
bad habits alcohol	7	21	7	21	1.038	0.320-3.373
other psychoactive substances	10	30	0	0	-	-
working	9	27	15	44	0.475	0.171-1.320
Not working, of working age	24	73	19	56	2.195	0.757-5.852

Table 2

Clinical forms of tuberculosis

Clinical forms of tuberculosis	1 group n= 33		2nd group n= 34		OR	95% CI
	abs	%	abs	%
Infiltrative pulmonary tuberculosis	22	66.7	25	73.6	0.640	0.218-1.877
Disseminated pulmonary tuberculosis	4	12.1	3	8.8	1.425	0.293-6.922
Focal tuberculosis lungs	1	3.0	3	8.8	0.323	0.032-3.274
Fibrous-cavernous/ cirrhotic pulmonary tuberculosis	5/1	18.2	2	5.9	3.556	0.662-19.083
Exudative pleurisy of tuberculous etiology	0	0	1	2.9	-	-
total	33	100	34	100	-	-

Table 3

Characteristics of the tuberculosis process.

Parameter	1 group n= 33		2nd group n= 34		OR	95% CI
	abs	%	abs	%
Presence of destruction of lung tissue	13	39.4	12	35.3	1,192	0.442-3.211
The fact of detection of bacterial excretion	21	63.6	19	55.9	1,382	0.518-3.683
Drug sensitivity to MBT	7	21.2	9	26.5	0.748	0.242-2.315
Drug resistance to MBT to any 1 drug except isoniazid and rifampicin	1	3.0	1	2.9	1.031	0.062-17.201
Multidrug resistance to MBT	5	15.2	5	14.7	1.036	0.270-3.971
Extensive drug resistance to MBT	8	24.2	4	11.8	2,400	0.646-8.916

factors, we can think about their cumulative effect. For example, tobacco smoking was an aggravating factor in patients of the main group. According to the previous research, smoking along with concomitant pathology increases the risk of developing a specific process by more than 15 times [8] . Unemployed patients of working age in the main group are 2.2 times more common 76 | Cardiometry | Issue 29. November 2023

(95% CI 0.896-2.23) than in the control group. Deviant behavior, playing a leading role in the disruption of socialization, leads and/or accompanies concomitant pathology. Patients in the main group prefer a parasitic lifestyle and unemployment (as an indicator of marginalization and lower socio-economic status), which increases the risk of developing tuberculosis (see Table 1).

In the clinical picture, as in the general population, infiltrative forms of tuberculosis predominate in both groups [6]. Clinical forms of tuberculosis did not have significant differences in the studied groups. The infiltrative form was predominant (in 66.7 and 73.6% of cases) (see Table 2).

According to Table 2, an increase of 3.6 times (95% CI 0.662-19.083) was established in the main group of patients with fibro-cavernous and cirrhotic tuberculosis in comparison with the control group. These forms are characteristic of the chronic course of infection, which may be due to the use of psychoactive substances, which, according to the previous research [10], increase the incidence of tuberculosis by 3.5 times.

The characteristics of specific inflammation are no different (see Table 3).

According to Table 3, destruction of lung tissue (95% CI 0.442-3.211) and the detection of bacterial excretion (95% CI 0.518-3.683) are observed equally often in both study groups. There are no differences in drug sensitivity and resistance to Mycobacteriae tuberculosis (MBT), although extensive drug resistance to isoniazid, rifampicin, aminoglycosides and fluoroquinolones is recorded somewhat more often (2.4 times) in patients of the main group (95% CI 0.646-8.916). According to the previous research, people with deviant behavior and concomitant pathology have a high bacterial load and the likelihood of developing drug resistance [13], which leads to an increase in treatment regimens and the formation of chronic forms of tuberculosis, the risk of relapse [17]. During our research, newly diagnosed patients were significantly less likely to be registered in the main group (see Table 4), but relapses and chronic course were somewhat more common (p>0.05) (see Table 4).

The increase in the incidence of relapses and chronic course of tuberculosis is explained by the mutual influence of pathogens that cause tuberculosis and other diseases [21], as well as the intestinal microbiota [20]. In people with concomitant pathology, its changes are facilitated by nutritional disorders and medication [20]. Altered microbiota can influence the immune response, contributing to the development and progression of diseases.

The chronic course of the disease is often facilitated by late detection. In this regard, we made an attempt to analyze the methods for detecting tuberculosis (see Table 5).

When analyzing Table 5, it was found that in the main group the chances of detecting tuberculosis during a preventive examination are 2.3 times higher (95% CI 0.845-6.262). This fact should be considered as favorable, because the concomitant pathology in patients included in the study suggests that patients

Table 4

Patient populations.

Patient populations	1 group n= 33		2nd group n= 34		OR	95% CI
	abs	%	abs	%
Newly identified patients	19	57.6	28	82.4	0.291	0.0950.891
Relapse of tuberculosis	8	24.2	4	11.7	2,400	0.6468.916
Chronic course of tuberculosis	6	18.2	2	5.9	3.556	0.662 19.083

Table 5

Methods for detecting tuberculosis

Sign		1 group n= 33		2nd group n= 34		OR	95% CI
		abs	%	abs	%
Methods for detecting tuberculosis	when filing complaints	10	30.3	17	50.0	0.435	0.160-1.184
	during a preventive examination in a general medical network	23	69.7	17	50.0	2.300	0.845-6.262

are in a medical risk group, in which examinations are performed twice a year for the timely detection of limited forms of tuberculosis [11]. Unfortunately, among those examined in the main group, focal tuberculosis is registered in a single case (see Table 2), which requires analysis of the regularity of medical examinations. In our study, 11-16 months have elapsed since the last screening examination was (median - 14 months). The fact of established contact when questioned was indicated by the same number of patients in both groups (9 out of 33 and 6 out of 34, OR-1.750 95% CI 0.544-5.628). This requires double attention to patients of the main group from the general medical network, as a medical risk group, and from TB specialists, as those in contact with the source of infection. The high frequency of contacts with a patient with tuberculosis aggravates the course of tuberculosis and, along with other factors (smoking, alcohol, use of psychoactive substances), does not contribute to a favorable outcome of tuberculosis and, possibly, is the cause of the chronic and recurrent course of tuberculosis.

When analyzing questionnaires [9], patients noted complaints indicating immune deficiency in 11 cases out of 33 and 5 out of 34 OR = 3.400 95% CI 1.03911.125). That is, among patients with concomitant pathologies there are more of them than in the control group. Among the described symptoms, patients in the main group are 4.1 times more likely to experience repeated pain in the right hypochondrium, accompanied by nausea, belching with increased body temperature over the past year (12 out of 33 versus 4 out of 34, 95%CI 1.171-14.654); 3.9 times - to experience long-term digestive disorders for more than 1 month (15 out of 33 versus 6 out of 34, 95%CI 1.273-11.879); and 9.1 times - to experience dysuric phenomena (12 out of 33 and 2 out of 34, 95%CI 1.855-45.057). Considering the nature of the listed indicators from the questionnaire, they can be considered as manifestations of concomitant pathology, which proves the informativeness of the parameters proposed in the questionnaire.

Conclusion

Detection of tuberculosis in patients with concomitant pathology in a third of cases (30.3%) is performed when reporting complaints, and in 69.7% - during a preventive examination. At the same time, a focal process was registered in a single case in this cohort of patients. This fact indicates the pathomor- 78 | Cardiometry | Issue 29. November 2023

phosis of tuberculosis in persons with immunocompromise, which consists in the development and intensive spread of specific inflammation in the lung tissue during a short period of time between medical examinations (less than 6 months). In this regard, it is necessary to strictly act within the framework of regulatory documents [14] and comply with the terms of clinical examination. The fact of established contact occurs equally often in patients of both groups, which, in case of concomitant pathology, requires close attention from the general medical network and TB specialist with the coordination of routine examinations for tuberculosis. Moreover, it should include not only visualization of the chest organs, but also etiological diagnostic methods. This was formulated based on the fact that drug resistance to isoniazid, rifampicin, aminoglycosides and fluoroquinolones was registered in patients of the main group somewhat more often (OR 2.400; 95% CI 0.646-8.916) than in the control group, with a comparable frequency of bacterial excretion (63.6% and 55. 9%) in the studied groups. That is, the determination of the causative agent of tuberculosis and its resistance to anti-tuberculosis drugs by different methods in patients with concomitant pathology must be performed using different respiratory material. Clinical signs of immune deficiency in patients with concomitant pathologies are revealed during the survey 3.4 times more often (95% CI 1.039-11.125) than in the control group. This creates the prerequisites for a targeted search for it by including questionnaires [12] in the initial examination of the patient for timely diagnosis of concomitant pathology, early detection of tuberculosis and prevention of the pathogen resistance development, chronicization of the process, which is found more often in patients of the main group (18.2 % vs. 5.9% with 95%CI 0.662-19.083).