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Original articles

Changes in the epidemiological situation of multidrug-resistant tuberculosis in Poland in the years 2018–2022

Monika Kozińska1, Dorota Filipczak1, Magdalena Klatt1, Jarosław Dziadek2, Alina Minias2, Daria Zygała-Pytlos2, Tatiana Makarevich3, Ewa Augustynowicz-Kopeć1
1 Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warszawa, Poland
2 Laboratory of Genetics and Physiology of Mycobacterium, Institute of Medical Biology, Polish Academy of Sciences, Łódź, Poland
3 World Health Organization Country Office in Poland, Warszawa, Poland
DOI: 10.20452/pamw.16904
Published online: January 2, 2025.
Key words: Beijing genotype, immigrants, multidrug-resistant tuberculosis, Mycobacterium tuberculosis, Ukraine
CCBYCC BY 4.0

In this article
Abstract

Introduction: The presented analysis was conducted against the backdrop of the global pandemic and the Russian–Ukrainian war. The conflict on Poland’s eastern border raised concerns about potential deterioration of the epidemiological situation in Poland due to the influx of immigrants from countries with a high incidence of multidrug‑resistant (MDR) tuberculosis (TB) and the Beijing genotype.

Objectives: We aimed to assess the epidemiological situation of MDR‑TB in Poland from 2018 to 2022 and to analyze the prevalence of the Beijing genotype in both the Polish and immigrant populations.

Patients and methods: The study group comprised 250 patients with bacteriologically confirmed MDR‑TB, diagnosed between 2018 and 2022. Microbiological, phenotypic, and molecular analyses were performed.

Results: Significant changes were observed in the number of MDR‑TB cases, with a notable increase in registered cases after the outbreak of the war. One in 3 patients was infected with pre‑XDR strains, and 1 in 4 with XDR strains. A total of 40% of cases were resistant to fluoroquinolones, with higher resistance rates observed among Polish patients than the immigrants. MDR as well as MDR with resistance to second‑line injectable drugs were identified more often among the immigrants than the Polish population. The Beijing genotype dominated with 179 isolates (71.6%), identified with a similarly high frequency in both the immigrant and Polish populations.

Conclusions: The war in Ukraine caused a massive influx of immigrants to Poland, many of whom were infected with MDR and Beijing strains of TB. There is a significant risk of an increase in the incidence of MDR‑TB in Poland in the future, as well as a potential for TB transmission between the immigrants and the native population.

What's new?

The presented work is the first epidemiological and molecular analysis of multidrug‑resistant (MDR) tuberculosis (TB) in Poland since the outbreak of the war in Ukraine. During the study period (2018–2022), significant changes were observed in the population of patients with drug‑resistant TB. The COVID‑19 pandemic seems to have reduced the incidence rates of this form of TB, while the war, through the influx of immigrants from beyond Poland’s eastern border, resulted in a dramatic increase in the number of registered cases. Our findings show that before 2022, a majority of MDR‑TB patients were Polish. However, the current population predominantly consists of immigrants, mainly men aged 35 to 44 years from Ukraine. These results emphasize the need for enhanced epidemiological surveillance of patients of Ukrainian origin.

Introduction

The recent COVID‑19 pandemic contributed to a global decline in TB detection. In Poland, TB registration rates also shifted, dropping from 14.3 and 13.9 per 100 000 population in 2018 and 2019, respectively, to 8.8 and 9.7 per 100 000 population, respectively, during the 2020 and 2021 pandemic period.1-5 These changes were likely influenced by sanitary restrictions, limited access to medical care, and reduced disease detection. Furthermore, mandatory lifestyle changes may have reduced the risk of TB transmission in the community.

In 2022, the TB reporting rate in Poland increased as compared with the pandemic years, reaching 11.4 per 100 000 population.6

Similar values were observed in 2023. That year, a total of 4436 TB cases were reported (reporting rate of 11.8 per 100 000), of which 3920 had no history of anti‑TB treatment and 516 were relapses. Pediatric TB cases (n = 51) accounted for 1.1% of all reported cases. In 2023, TB was culture‑confirmed in 3554 patients, representing 80% of registered cases.6

Since 2022, Poland has faced epidemiological challenges due to the influx of war refugees from Ukraine. Data on TB incidence rates among foreigners in Poland are imprecise and difficult to interpret. The National Tuberculosis Incidence Register, established in 1957 and maintained by the Institute of Tuberculosis and Lung Diseases, historically provided basic data on TB incidence in the general population but lacked epidemiological and demographic data on immigrants. Since 2004, however, data on TB cases among immigrants have been recorded in detail. Based on these records, between 2011 and 2021, immigrants with TB accounted for 0.4% to 3.6% of all detected TB cases annually.2-5 In 2023, this percentage rose with 352 immigrants constituting 7.9% of all registered TB cases.6

In Poland, as in other Western European countries, the proportion of newly diagnosed patients with culture‑confirmed excretion of multidrug‑resistant (MDR) bacilli remains low and does not exceed 3% of all TB cases.2,4-7 In 2023, 99 patients were diagnosed with MDR‑TB in Poland (2.8% of all culture‑confirmed cases), 71 of whom were immigrants (2% of culture‑confirmed TB cases).6

In contrast, approximately 15‑fold higher rates than those noted in Poland are reported beyond Poland’s eastern border, in the countries of the former Union of Soviet Socialist Republics (USSR). In the Russian Federation, Belarus, Moldova, and Ukraine, over 25% of newly diagnosed patients are affected by MDR‑TB.2-7

Drug‑resistant (DR) TB is a serious global health challenge, undermining efforts to control TB effectively. The World Health Organization (WHO) estimates that approximately 450 000 cases of DR‑TB were reported in 2021, an increase by 3.1% as compared with the previous year. MDR‑TB and particularly extensively drug‑resistant (XDR) TB require complex and expensive treatment regimens that last longer and are associated with more adverse effects than standard therapies.8 New treatment regimens, such as BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin), shorten treatment duration to 6 months. However, their high cost and limited availability are significant barriers, especially in low‑income countries.9

The Mycobacterium tuberculosis complex (MTBC) strain family known as Beijing (Beijing‑TB) is strongly linked to MDR‑TB, and it is estimated to account for approximately 50% of all TB strains in East‑Asian countries.10-12 Since its identification nearly 30 years ago, Beijing‑TB has spread globally through migration of the population to all continents and is currently found in most countries, particularly in the countries of the former USSR.12,13 Consequently, it is likely that many migrants with TB arriving in Poland from the former USSR countries are infected with the Beijing genotype.

The study aimed to conduct an epidemiological, microbiological, and molecular analysis of MDR MTBC strains isolated from patients in Poland between 2018 and 2022. The analysis was conducted within the context of social changes in Poland and Europe resulting from the COVID‑19 pandemic and the ongoing military conflict in Ukraine, with particular focus on TB in immigrants from beyond Poland’s eastern border, where higher incidence rates of MDR‑TB are reported.

Patients and methods

Patients and bacterial isolates

The study group consisted of 250 patients with culture‑confirmed MDR‑TB diagnosed between 2018 and 2022, including 196 men (78.4%) and 54 women (21.6%) (Table 1). The sample selected for the study represented 1.5% of all patients with culture‑confrmed TB in Poland during this period (n = 16 892) and 90% of patients with MDR‑TB (n = 278). Of the 16 892 cases, 514 (3%) were detected in the Department of Microbiology of the National Reference Laboratory for Mycobacteria (NRLM) in Warsaw, among whom 15 cases of MDR‑TB were identified. The remaining 16 378 patients, 235 of whom had confirmed MDR‑TB, were diagnosed in Polish provincial laboratories for the diagnosis of TB and sent to the NRLM for mandatory drug susceptibility testing.

Table 1. Structure of origin, sex, and age of the study population (n = 250)
Parameter
Country of origin
Total
Poland
Other (immigrants)
Data are presented as number (percentage).
a No data on origin
Patients
133 (53.2)
Overall
117 (46.8)
250 (100)
Ukraine
86 (73.5)
Georgia
4 (3.3)
Moldova
4 (3.3)
Vietnam
2 (1.7)
Romania
1 (0.9)
Indonesia
1 (0.9)
Armenia
1 (0.9)
Uzbekistan
1 (0.9)
Turkey
1 (0.9)
Russia
1 (0.9)
Othera
15 (12.8)
Sex
Men
107 (80.4)
89 (76)
196 (78.4)
Women
26 (19.6)
28 (24)
54 (21.6)
Age, y
0–14
1 (0.8)
1 (0.9)
2 (0.8)
15–24
4 (3)
8 (6.8)
12 (4.8)
25–34
8 (6)
27 (23)
35 (14)
35–44
35 (26.3)
47 (40.2)
82 (32.8)
45–54
30 (22.6)
26 (22.2)
56 (22.4)
55–64
31 (23.3)
7 (6)
38 (15.2)
65+
24 (18)
1 (0.9)
25 (10)

The analysis covered 90% of MDR isolates. The missing 10% (n = 28) were strains that regional laboratories did not provide to the NRLM, or the NRLM was not able to reproduce or analyze molecularly. Most of the strains excluded from the analysis for these reasons were isolated from patients in 2019. Demographic, clinical, and microbiological data were collected from the National Tuberculosis Registry and the NRLM.

Based on the verification of the drug resistance profile of the strains carried out at the NRLM, the isolates were classified as MDR, pre‑XDR, and XDR. Using the WHO classification valid until 2021, the MDR resistance was identified as resistance to isoniazid (INH) and rifampicin (RIF); pre‑XDR as MDR with resistance to either fluoroquinolone (FLQ) or any of the second‑line injectable drugs (SLIDs), such as amikacin (AMK), kanamycin (KAN), or capreomycin (CAP); and XDR as MDR with additional resistance to both FLQ and one of the SLIDs.14

A total of 133 (53.2%) of the study patients were Poles (107 men and 26 women) and 117 (46.8%) were immigrants (89 men and 28 women). The population of immigrants consisted mainly of Ukrainians (n = 86; 73.5%), while the remainder (n = 31; 16.5%) were citizens of Georgia (n = 4), Moldova (n = 4), Vietnam (n = 2), Romania (n = 1), Indonesia (n = 1), Armenia (n = 1), Uzbekistan (n = 1), Turkey (n = 1), and Russia (n = 1), or of unknown nationality (n = 15). The age of the patients ranged from 1 to 88 years (median, 45 years), including 2 children younger than 15 years of age.

Phenotypic drug resistance

The initial identification and determination of phenotype for resistance to basic antimycobacterial drugs (INH, RIF, streptomycin [STR], and ethambutol [EMB]) were conducted in regional mycobacterium laboratories. Then, the strains were sent to the NRLM, where phenotypic and genotypic resistance to primary (INH, RIF, STR, EMB) and secondary (KAN, AMK, CAP, ofloxacin [OFX]) drugs was verified, and molecular families were identified.

Conventional drug susceptibility testing was performed using the standard 1% proportion method on the Löwenstein–Jensen (LJ) medium and a liquid medium using the Bactec MGIT 960 system (Becton Dickinson Diagnostic Systems, Sparks, Maryland, United States), following the WHO recommendations.15 The M. tuberculosis H37Rv reference strain was used for quality control.

Critical drug concentrations were as follows: on the LJ medium, 0.2 μg/ml INH, 40 μg/ml RIF, 2 μg/ml EMB, 4 μg/ml STR, 30 mg/l KAN, 30 mg/l AMK, 40 mg/l CAP, and 4 mg/l OFX; on the liquid medium, 0.1 μg/ml INH, 1 μg/ml RIF, 5 μg/ml EMB, 100 μg/ml STR, 2.5 μg/ml KAN, 1 μg/ml AMK, and 2.5 μg/ml CAP.15

Genotyping

MTBC genomic DNA was isolated using a previously described protocol.16 Strain genotyping was performed via spoligotyping (Ocimum Biosolutions, Hyderabad, India) with commercially available membranes, following the standard protocol described previously.17 The M. tuberculosis H37Rv and M. bovis bacillus Calmette–Guérin reference strains were used for quality control in each run. Spoligotype shared types and phylogenetic clades (sublineages and families) were assigned according to the SITVIT2 database.18,19

Results

During the study, the epidemiological situation of MDR‑TB in Poland evolved in response to shifting social dynamics (Table 2). In 2018 to 2019, before the COVID‑19 pandemic, approximately 70% of culture‑confirmed MDR‑TB cases involved Poles, 24% concerned Ukrainians, and the remaining 6% involved patients of other or unknown nationality.

Table 2. Changes in the population of patients with culture‑confirmed drug‑resistant tuberculosis in Poland in the context of social problems in the years 2018–2022
Historical context
Year of isolation
Isolate origin
Polish citizens
Immigrants
Total
Ukrainian
Others
Data are presented as number (percentage).
Before the COVID‑19 pandemic
2018
39 (72.2)
12 (22.2)
3 (5.6)
54 (21.6)
2019
20 (64.5)
8 (25.8)
3 (9.7)
31 (12.4)
COVID‑19 pandemic
2020
22 (61.1)
10 (27.8)
4 (11.1)
36 (14.4)
2021
24 (47)
18 (35.3)
9 (17.7)
51 (20.4)
February – Russian invasion of Ukraine; April – end of the COVID‑19 pandemic
2022
28 (35.9)
38 (48.7)
12 (15.4)
78 (31.2)
Total
133 (53.2)
86 (34.4)
31 (12.4)
250 (100)

During the pandemic years 2020 and 2021, the distribution shifted, with Poles comprising approximately 54%, Ukrainians 32%, and individuals of other nationalities 14% of all registered MDR‑TB cases. The year 2022, marked by the outbreak of war in Ukraine and subsequent population migration to Poland, further altered these proportions. In that year, about 36% of patients with MDR‑TB were Poles, 49% were immigrants from Ukraine, and 15% were of other nationalities. Notably, 2022 also saw a rise in the total number of culture‑confirmed cases of MDR‑TB in Poland (78 patients), nearly matching the combined total of cases reported in 2020 and 2021.

Drug resistance profile analysis

Among the 250 patients with MDR‑TB included in the study, pre‑XDR‑TB was identified in 78 individuals (31.2%) and XDR‑TB in 63 patients (25.2%) (Table 3). MDR‑TB without additional resistance was more frequently registered in the immigrants than in the Polish population (immigrants, 64 [25.6% of the study population]; Poles, 45 [18%]). Pre‑XDR‑TB was more frequently reported in Poles (immigrants, 36 [14.4%]; Poles, 42 [16.8%]), as was the case for XDR‑TB (immigrants, 17 [6.8%]; Poles, 46 [18.4%]).

Table 3. Drug resistance profile of the tested strains isolated from the Polish and immigrant populations
Drugs
Isolate origin
Overall
Polish citizens
Immigrants
Data are presented as number (percentage).
Abbreviations: FLQ, fluoroquinolone; MDR, multidrug‑resistant; PRE‑XDR, pre‑extensively drug‑resistant; SLID, second‑line injectable drug; XDR, extensively drug‑resistant
MDR: first‑line
109 (43.6)
45 (33.8)
64 (54.7)
PRE‑XDR
First‑line + FLQ
37 (14.8)
28 (21.1)
9 (7.7)
First‑line + at least 1 SLID
41 (16.4)
14 (10.5)
27 (23.1)
XDR: First line + FLQ + at least 1 SLID
63 (25.2)
46 (34.6)
17 (14.5)
Total
250 (100)
133 (53.2)
117 (46.8)

Among pre‑XDR strains, resistance to first‑line drugs in combination with resistance to one of SLIDs was observed more often (41 strains, 16.4% of the study population) than resistance to first‑line drugs in combination with resistance to FLQ (37 strains, 14.8% of the study population).

Of all the strains tested, 100 isolates (40% of the tested pool of strains) were resistant to first‑line drugs in combination with FLQ. Resistance to FLQ was observed more often in Polish patients than the immigrants (immigrants, 26 [22.2% of the immigrant population]; Poles, 74 [55.6% of the Polish population]).

Resistance to first‑line drugs in combination with SLIDs was also more frequently observed in the Polish patients (immigrants, 44 cases [37.6% of the immigrant population]; Poles, 60 [45.1% of the Polish population]).

Patients with XDR‑TB constituted 34.6% of the Polish population (46 cases) and 14.5% of the studied immigrant population (17 cases).

Overall, resistance to first‑line drugs combined with resistance to additional drugs was observed more frequently in the Polish population (immigrants, 53 [21.2% of the study population]; Poles, 88 [35.2% of the study population]).

Strain genotyping

Molecular analysis using the spoligotyping method classified the strains into 3 phylogenetic lines: lineage 1 (L1, Indo‑Oceanic), lineage 2 (L2, East‑Asian), and lineage 4 (L4, Euro‑American). These lineages encompassed 8 clades: EAI, MANU, BEIJING, X, T, Haarlem, LAM, and Ural, along with some unclassified clades, resulting in 12 genetic families (Table 4). A total of 44 spoligotypes were identified, of which 35 were recorded in the international spoligotype database SITVIT2.19 The Beijing genotype was the most prevalent (179 strains, 71.6% of isolates), with similar frequencies in the Polish (89 cases, 35.6% of the study population) and immigrant (90 cases, 36% of the study population) populations.

Table 4. Diversity of spoligotypes of strains included in the study
Spoligotyping
Isolates, n (%)
Lineage
Clade
Family
SIT
Octal code
Abbreviations: EAI, East‑African Indian; LAM, Latin American and Mediterranean; SIT, spoligotype international type
Lineage 1: Indo‑Oceanic
EAI
EAI1_SOM
48
777777777413731
1
1 (0.4)
MANU
MANU2
226
777777777413731
1
7 (2.8)
567
777760007763771
1
1247
777760007763771
3
1291
777760007763771
1
1481
774777777423771
1
Lineage 2: East‑Asian
BEIJING
BEIJING
1
000000000003771
113
179 (71.6)
265
000000000003371
64
541
000000000003711
1
250
000000000000371
1
Lineage 4: Euro‑American
X
X1
119
777776777760771
1
1 (0.4)
T
T1
53
777776777760771
8
20 (8)
118
777767777760771
1
251
774000000760771
1
253
777777663760771
2
801
774777777760771
1
1558
777777775660771
4
Orphan A
770003777760771
1
Orphan B
716000003760771
1
Orphan C
777177377760731
1
Haarlem
H1
382
757777774020771
1
9 (3.6)
531
737777774020771
2
1557
777677774020771
1
H3
50
777777777720771
2
390
777777777620771
1
746
777777777520771
1
Orphan A
777767374020771
1
LAM
LAM1
20
677777607760771
1
18 (7.2)
LAM9
42
777777607760771
2
161
777777607740771
2
766
777761007760771
2
891
777777607660771
5
2263
767777607760771
1
LAM‑RUS
254
777760007760771
5
Ural
Ural‑1
262
774777777420771
5
8 (3.2)
1134
777737777420731
1
New type
770337777420771
2
Unknown
237
777777777700000
1
7 (2.8)
267
777700003760771
1
560
777000000000371
1
Orphan A
000000007723771
1
Orphan B
376760001770371
1
Orphan C
777777700002071
1
Orphan D
477777677720771
1
Total
250 (100)

Within the Beijing genotype, 2 spoligotypes predominated: Beijing 1 (113 strains, 63%) and Beijing 265 (64 strains, 35.8%). Beijing 1 was identified mainly in the patients from Ukraine (52 cases, 44.4% of the immigrant population) and less often in the Polish patients (43 cases, 32.3% of the Polish population) (Table 5). Additional Beijing 1 strains were isolated from the individuals from other countries (Moldova, Vietnam, Armenia, Georgia, Indonesia, Russia, Turkey, Uzbekistan). The Beijing 265 genotype was more common among Poles (45 cases, 33.8% of the Polish population) but less frequent in the Ukrainian immigrants (13 cases, 11.1% of the immigrant population) and the individuals from other countries (6 cases, 5.2% of the immigrant population).

Table 5. Proportion of identified spoligotypes in the Polish and immigrant populations
Spoligotyping
Isolates, n
Country of origin
Isolates, n (%)
Clade
Family
SIT
a No data on origin
Abbreviations: see Tables 3 and 4
EAI
EAI1_SOM
48
1
Poland
1 (100)
MANU
MANU2
226
1
Ukraine
1 (100)
567
1
Ukraine
1 (100)
1247
3
Ukraine
3 (100)
1291
1
Moldova
1 (100)
1481
1
Poland
1 (100)
BEIJING
BEIJING
1
113
Ukraine
52 (46)
Poland
43 (38)
Othera
8 (7)
Moldova
2 (1.8)
Vietnam
2 (1.8)
Armenia
1 (0.9)
Georgia
1 (0.9)
Indonesia
1 (0.9)
Russia
1 (0.9)
Turkey
1 (0.9)
Uzbekistan
1 (0.9)
265
64
Poland
45 (70.3)
Ukraine
13 (20.3)
Othera
4 (6.3)
Georgia
2 (3.1)
541
1
Ukraine
1 (100)
250
1
Poland
1 (100)
X
X1
119
1
Poland
1 (100)
T
T1
53
8
Poland
8 (100)
118
1
Poland
1 (100)
251
1
Ukraine
1 (100)
253
2
Poland
2 (100)
801
1
Poland
1 (100)
1558
4
Poland
4 (100)
Orphan A
1
Poland
1 (100)
Orphan B
1
Poland
1 (100)
Orphan C
1
Romania
1 (100)
Haarlem
H1
382
1
Poland
1 (100)
531
2
Poland
2 (100)
1557
1
Poland
1 (100)
H3
50
2
Poland
1 (50)
Ukraine
1 (50)
390
1
Poland
1 (100)
746
1
Poland
1 (100)
Orphan A
1
Poland
1 (100)
LAM
LAM1
20
1
Othera
1 (100)
LAM9
42
2
Poland
1 (50)
Ukraine
1 (50)
161
2
Ukraine
2 (100)
766
2
Georgia
1 (50)
Ukraine
1 (50)
891
5
Poland
5 (100)
2263
1
Ukraine
1 (100)
LAM‑RUS
254
5
Poland
1 (20)
Ural
Ural1
262
5
Poland
3 (60)
Moldova
1 (20)
Ukraine
1 (20)
1134
1
Ukraine
1 (100)
New Type
2
Ukraine
2 (100)
Unknown
Unknown
237
1
Poland
1 (100)
267
1
Poland
1 (100)
560
1
Ukraine
1 (100)
Orphan A
1
Poland
1 (100)
Orphan B
1
Othera
1 (100)
Orphan C
1
Poland
1 (100)
Orphan D
1
Poland
1 (100)

Spoligotypes from the T and Haarlem clades were more frequently identified in Polish patients (24 cases, 9.6% of the study population) than immigrants (3 cases, 1.2% of the study population), especially T1 53, T1 1558, T1 253, and H1 531, which were exclusive to Poles. On the other hand, the MANU, LAM, and Ural clades were more commonly detected in the immigrants (22 cases, 8.8% of the study population) than in Poles (9 cases, 3.6% of the study population), except for LAM9 891 and LAM‑RUS 254, which were detected only in Polish patients.

Drug resistance profile, molecular family, and nationality of patients

Among the Beijing spoligotype strains, MDR was the most frequently identified resistance profile (71 isolates, 39.7% of the Beijing isolates), followed by XDR (56 isolates, 31.3% of the Beijing isolates) and pre‑XDR (52 isolates, 29% of the Beijing isolates) (Table 6). Outside the Beijing spoligotype, MDR was predominantly detected in strains belonging to the MANU, T, and LAM clades, as well as those from unclassified families (32 isolates, 61.5% of the isolates of these clades). Pre‑XDR was most characteristic of the strains from the Haarlem and Ural clades (10 isolates, 66.7% of the isolates of these clades). Among the isolates exhibiting XDR resistance, the Beijing genotype was predominant (56 isolates, 88.9% of the XDR isolates).

Table 6. Distribution of multidrug‑resistant, pre‑extensively drug‑resistant, and extensively drug‑resistant isolates in the Polish and immigrant populations by the molecular family
Clade
Isolate origin, n (%)
Overall
Polish citizens
Immigrants
MDR
PRE‑XDR
XDR
MDR
PRE‑XDR
XDR
MDR
PRE‑XDR
XDR
Abbreviations: see Tables 3 and 4
Beijing
71 (39.7)
52 (29)
56 (31.3)
21 (23.6)
27(30.3)
41 (46.1)
50 (55.6)
25 (27.8)
15 (16.6)
EAI
1 (100)
1 (100)
MANU
4 (57.1)
3 (42.9)
1 (100)
4 (66.7)
2 (33.3)
T
11 (55)
7 (35)
2 (10)
10 (55.6)
6 (33.3)
2 (11.1)
1 (50)
1 (50)
Haarlem
4 (44.4)
5 (55.6)
4 (50)
4 (50)
1 (100)
LAM
13 (72.2)
3 (16.7)
2 (11.1)
6 (85.7)
1 (14.3)
7 (63.7)
3 (27.2)
1 (9.1)
Ural
1 (12.5)
5 (62.5)
2 (25)
2 (66.7)
1 (33.3)
1 (20)
3 (60)
1 (20)
X
1 (100)
1 (100)
Unknown
4 (57.1)
2 (28.6)
1 (14.3)
3 (60)
1 (20)
1 (20)
1 (50)
1 (50)
Total
109 (43.6)
78 (31.2)
63 (25.2)
45 (33.8)
42 (31.6)
46 (34.6)
64 (54.7)
36 (30.8)
17 (14.5)
250 (100)
133 (53.2)
117 (46.8)

Discussion

Our study provides the first epidemiological analysis of MDR‑TB in Poland involving such a large population of Poles and immigrants. The findings highlight an important problem for Poland: the substantial migration of war‑affected populations from Ukraine, a country with a much more difficult epidemiological landscape of TB than Poland.

As demonstrated in previous sections, a considerable proportion of the immigrants are infected with the pre‑XDR and XDR strains of TB as well as the Beijing genotype.

Historically, until 2015, the highest TB incidence rates in Poland were observed among individuals older than 65 years of age. More recently, according to the National Tuberculosis Registry, the largest proportion of patients with TB are now younger, professionally active people aged 45 to 65 years (45.5%).20 Our analysis of the immigrant population with MDR‑TB between 2018 and 2022 shows that a majority of cases involved men aged 35 to 44 years, a generally socially and professionally active and mobile group. This trend was evident both before and during the COVID‑19 pandemic, as well as just before the outbreak of the war.

The armed conflict has changed the reasons for migration to Poland. Since the war began, 75% of Ukrainian citizens who crossed the Ukrainian–Polish border have been adults, with 96% being women with children and 3% men.21 It is anticipated that, in the coming years, the number of TB cases in this population will rise due to the transmission of TB and the progression from latent TB infection to active disease. The risk of TB among immigrants is highest within the first 2 to 5 years after migration and remains elevated for over a decade. War migrants are particularly vulnerable, as they often face conditions that increase the risk of TB transmission, such as overcrowded camps, inadequate nutrition, and elevated stress levels. Additionally, after resettling, these individuals may encounter significant barriers to accessing health care services in the host country, which can further hinder timely diagnosis and treatment.22

Among children, we documented only a single case of TB, involving a Ukrainian child infected with MDR‑TB transmitted by the parent. Data on childhood TB in Ukraine remain sparse and likely underestimated, primarily due to insufficient TB registration in both adult and pediatric populations. According to the WHO, only one‑third of patients with TB are registered in the Ukrainian National TB Program, and of these, only 1.8% are pediatric cases.23 This Figure likely underrepresents the actual prevalence of MDR‑TB among children, which is estimated to account for 27% of all MDR‑TB cases.21,24 The challenge of addressing pediatric MDR‑TB in Ukraine is further complicated by the high incidence of HIV infections, which affect approximately 2% of the population of Ukrainian children younger than 15 years.25

Using the definition of pre‑XDR and XDR‑TB, recommended by the WHO until 2021, this analysis of 250 patients identified 109 cases (43.6%) of MDR‑TB, 78 (31.2%) of pre‑XDR‑TB, and 63 (25.2%) of XDR‑TB. Among the Polish patients, pre‑XDR and XDR resistance was more common, whereas MDR resistance combined with sensitivity to additional drugs prevailed among the immigrants. One potential explanation for this discrepancy is the predominance of Beijing 265 strains in the Polish population and Beijing 1 strains among the immigrants. The Beijing strains are known to be associated with drug resistance and are more likely to acquire resistance than other molecular types. However, they are not a genetically and phenotypically homogeneous group, as they can also occur in a drug‑sensitive form.26 Previous studies conducted in Poland have identified both drug‑resistant and drug‑sensitive patients with TB infected with the Beijing 1 spoligotype. Additionally, drug‑resistant cases have been linked to Beijing 265 and Beijing 541 strains.27,28

In comparison with our previous studies, this analysis highlights a significant increase in the number of patients with MDR‑TB resistant to additional drugs in Poland in recent years.29 Between 2000 and 2009, approximately 14% of MDR strains were resistant to FLQs, and 11% were resistant to SLIDs. Currently, as many as 40% of MDR strains exhibit resistance to FLQ—an essential drug in the treatment of MDR‑TB, particularly when first‑line drugs are not tolerated. The primary cause of MTBC drug resistance to FLQs is the excessive and uncontrolled use of these drugs in the treatment of bacterial infections other than TB. High rates of FLQ‑resistant TB have been reported in the Philippines, India, and the United States.30-33 However, the extent of MTBC resistance to FLQs has not been sufficiently investigated, with existing data remaining limited and underreported.

Ukraine is one of the countries where more than one‑third of patients with TB in the general population are infected with the pre‑XDR or XDR form of the disease.30 These forms are particularly prevalent in the south‑eastern regions of the country.34

In 2018, the results of the first national study on anti‑TB drug resistance in Ukraine were published, revealing that nearly a quarter of new cases and 60% of previously treated cases were those of MDR‑TB. The highest incidence of MDR‑TB is observed in the south‑eastern regions, where it accounts for more than 30% of newly detected cases in areas such as Dnipropetrovsk, Kherson, Luhansk, and Autonomous Republic of Crimea. In the central regions, 10% to 20% of newly diagnosed patients have MDR‑TB, while in several western regions (Zakarpattia, Ivano‑Frankivsk, and Kyiv) the prevalence is below 10%.35

However, there is a lack of complete epidemiological data and up‑to‑date national reports on TB in Ukraine. The current geopolitical situation further hampers effective surveillance of the epidemiological situation regarding TB in the country.

Our study identified 179 patients (71.6%) infected with Beijing‑TB. This result represents an almost 10‑fold increase, as compared with the prevalence of Beijing‑TB strains detected among patients with MDR‑TB in Poland in 2000.36 It is important to note that between 2000 and 2009, Beijing‑TB was less often reported in Poland among immigrants (40.8%), primarily from Chechnya (38%) and Vietnam (24%), and more commonly among Poles (59.2%).27 Currently, according to our study, there has been nearly a 10% increase in the incidence of Beijing‑TB among immigrants (50.2%). This shift is probably due to the influx of immigrants across the Polish–Ukrainian border, which significantly increased after 2014 as a result of the armed conflict in the eastern part of Ukraine.

We observed that Beijing‑TB was the dominant form in both the immigrant population (90 cases, 76.9% of the immigrant population) and the Polish population (89 cases, 66.9% of the Polish population). This finding is not in line with research conducted by Bakuła et al,37 who reported that MDR Beijing‑TB was present in 66.7% of the Poles and 33.3% of immigrants. This discrepancy is likely due to the nature of Bakuła’s study sample, which was limited to only 2 regions of Poland and included just 39 patients (30 Poles and 9 immigrants), making it less representative of the general population.

Molecular studies on the epidemiology of MTBC strains circulating among patients in Ukraine are limited to selected areas of the country. In the southern and eastern regions, there has been a noticeable increase in the incidence of the Beijing molecular family. In 2007, the Beijing family accounted for 30.5% of TB cases in new patients and 54.8% in previously registered patients in the Odessa and Mykolaiv regions, while in 2018, 81% of cases in Kharkiv were attributed to this strain.38,39 These regions are located along transport routes connecting Asia with Europe, which may partly explain the high prevalence of the Asian Beijing strain. However, the molecular epidemiology of TB in the central and western Ukraine remains unclear due to the limited research conducted in these regions.

It is also worth noting that our analysis identified Beijing‑TB in patients of other nationalities, including individuals from Moldova, Vietnam, Armenia, Georgia, Indonesia, Russia, Turkey, and Uzbekistan. This finding further supports the global spread of Beijing‑TB.12,18

Conclusions

Our study was conducted against the backdrop of the difficult global context, including the COVID‑19 pandemic and the Russian invasion of Ukraine. We observed an increase in the number of registered cases of MDR‑TB among immigrants, particularly among men aged 35 to 44 years. Notably, resistance to additional drugs, and most worryingly, to FLQs, was more prevalent among Poles than immigrants. The overuse of FLQs by Polish health care providers may present significant challenges in the treatment of MDR‑TB and possibly other diseases for which FLQs are prescribed.

Our analysis opens the way to further epidemiological and genetic studies. Given that 2022 marked the beginning of the war, it is crucial to continue these studies and observations in the coming years. Additionally, investigating immigrants with drug‑sensitive TB and detecting latent infections may provide valuable insights for future public health interventions.

Acknowledgments: The authors are grateful to the teams working at the Regional Mycobacteria Laboratories for sending the strains and providing microbiological and demographic data on the patients.
Funding: This research was funded by the National Science Centre, grant number 2019/35/B/NZ7/00942; to EA‑K.
Contribution statement: MKozińska designed the study and prepared the manuscript. MKlatt helped to prepare the methods. DF and TM helped to prepare the results section. JD helped to interpret the findings. AM drafted the introduction. DZ‑P conducted the literature review and helped to prepare the tables. EA‑K supervised the study. All authors edited and approved the final version of the manuscript.
Conflict of interest: None declared.
References
  1. Borkowska‑Tatar D, Zabost A, Kozińska M, Augustynowicz‑Kopeć E. Tuberculosis in Poland: epidemiological and molecular analysis during the COVID‑19 pandemic. Diagnostics (Basel). 2022; 12: 1883. | Crossref
  2. Korzeniewska‑Koseła M. Tuberculosis and respiratory tract diseases in Poland in 2021 [in Polish]. Institute of Tuberculosis and Lung Diseases, Warsaw, Poland. 2022.
  3. Korzeniewska‑Koseła M. Tuberculosis and respiratory tract diseases in Poland in 2020 [in Polish]. Institute of Tuberculosis and Lung Diseases, Warsaw, Poland. 2021.
  4. Korzeniewska‑Koseła M. Tuberculosis and respiratory tract diseases in Poland in 2019 [in Polish]. Institute of Tuberculosis and Lung Diseases, Warsaw, Poland. 2020.
  5. Korzeniewska‑Koseła M. Tuberculosis and respiratory tract diseases in Poland in 2018 [in Polish]. Institute of Tuberculosis and Lung Diseases, Warsaw, Poland. 2019.