Tuberculosis 2019 - 2020

Tuberculosis - 2019-20 report on disease occurrence

Due to the COVID-19 pandemic, the 2019 report on tuberculosis has not previously been published. Thus, the present report covers 2019 and 2020.

2019 saw a total of 284 notified cases of tuberculosis (TB), 79 (28%) in persons of Danish origin and 205 (72%) in persons of non-Danish origin (immigrants or descendants to immigrants). The total incidence was 4.9 per 100,000.

2020 saw a total of 221 notified cases of tuberculosis, 62 (28%) in persons of Danish origin and 159 (72%) in persons of non-Danish origin (immigrants or descendants to immigrants). The total incidence was 3.8 per 100,000.

For persons of Danish origin, the median age was 50.5 years (range 0-84 years) in 2019 and 48.5 years (range 0-89 years) in 2020. Among persons of Danish origin, a total of 59 men and 20 women were notified in 2019, and 39 men and 23 women were notified in 2020. Until 2018, the median age followed an increasing trend from 49 years in 2008 to 57 years in 2018, but the two latest years have recorded a marginally lower median age.

For persons of non-Danish origin, the median age was 39 years (range 0-77 years) in 2019 and 40 years (range 1-83 years) in 2020. Among persons of non-Danish origin, a total of 122 men and 83 women were notified in 2019, and 88 men and 71 women were notified in 2020. The median age of persons who are not of Danish origin remains at the level observed in 2008.

The difference in median age is due to the fact that among persons of Danish origin, TB is observed mainly in middle-aged and elderly persons, whereas the condition is seen mainly in young and younger adults of non-Danish origin, Figure 1 and Figure 2.

Table 1 shows the 2019 distribution by area and origin. Table 2 shows the same data for 2020.

In 2019, the highest incidence (8.1 cases per 100,000, 64 cases) was seen in the City of Copenhagen, followed by Copenhagen subs. (6.2 per 100,000, 34 cases) and Funen (6.2 cases per 100,000, 31 cases). In 2019, the island of Bornholm recorded no tuberculosis notifications. The second lowest incidence was recorded in West and South Zealand (3.1 per 100,000, six cases) and South Jutland (3.2 cases per 100,000, 23 cases).

In 2020, the highest incidence (10.1 cases per 100,000, four cases) was seen on the island of Bornholm, followed by the City of Copenhagen (4.8 cases per 100,000, 38 cases), whereas the lowest incidence was observed in East Zealand (0.4 per 100,000, one case).

Figure 3 presents the development in TB incidence in persons of Danish origin, by region, in the 2011-2020 period.

All five regions recorded a declining incidence in the 2011-2017 period. Even so, a slight increase was observed in the Capital Region of Denmark in the 2015-2017 period and then a decline was observed from 2017 to 2020. In the Region of Southern Denmark, a decline in incidence was observed in the 2017-2018 period, whereas the 2018-2020 period recorded an increase, leaving the incidence in the Region of Southern Denmark on a par with the incidence in the Capital Region of Denmark in 2020. In the Region of Southern Denmark, TB was more prevalent among persons of non-Danish origin (71 cases from a total of 103 cases in the region) in 2019 and 2020. A total of 27 of the 71 cases of non-Danish origin were Greenlanders.

As from the 2017-2019 period, the incidence in Region Zealand, the Central Denmark Region and the North Denmark Region has followed an increasing trend, whereas the incidence declined in all three regions from 2019 to 2020.

Tables 3 and 4 show the distribution by localisation and origin for 2019 and 2020, respectively.

Overall, for 2019 and 2020, pulmonary TB was the most frequently observed presentation in patients of Danish and non-Danish origin alike. Persons of non-Danish origin more frequently presented with extra-pulmonary types of TB than people of Danish origin, particularly TB of the lymph nodes (glandular TB).

Overall, in 2019 and 2020, 35 (21 in 2019 (7%) and 14 in 2020 (6%)) patients were notified with TB relapse. Among the cases notified in 2019 and 2020 with TB relapse, 16 were Greenlanders, seven were Danes, four were Somalis, two were from Thailand and one was from Brazil, Eritrea, Ethiopia, China, the Philippines and Vietnam, respectively. For 14 of the 35 patients, the previous TB episode had occurred within the 2015-2018 period.

For a total of 99 (20%) patients, 42 Danes (28 in 2019, 14 in 2020) and 57 persons of non-Danish origin (32 in 2019, 25 in 2020), the notification included information about personal risk factors in the form of other chronic conditions, cancer, homelessness, alcoholism or other contact to a risk environment. As previously, it is estimated that risk factors are under-reported in the notifications.

Among the cases notified in 2019 and 2020, information was available about concurrent HIV infection and therefore AIDS for 11 (2.2%) patients; one of Danish origin and the remaining ten of non-Danish origin. In all, among the 505 TB cases notified in 2019 and 2020, 389 patients had tested HIV negative, whereas the HIV status of the remaining 105 patients was not provided on the notifications and therefore remained unknown. The Danish Health Authority (and international organisations including the WHO) still recommends that all TB patients undergo HIV testing, EPI-NEWS 46/09. This is so because TB outbreaks typically start among people who have become infected with tuberculosis when their immune system is weakened, as is the case for AIDS.

Country of infection and origin

Based on all notifications from 2019 and 2020, a total of 213 (42%) patients had presumably become infected in Denmark, including 117 of Danish origin. In all, 15 persons were born in Denmark, but were of non-Danish origin. A total of 96 (19%) persons of non-Danish origin were presumably infected in Denmark, including 46 from Greenland, nine from Somalia and eight from Pakistan; the remaining 33 cases were from 19 other countries.

Of the 292 (58%) patients who had presumably become infected abroad, 24 were of Danish origin. Hereof, two had presumably become infected in Africa, whereas one had presumably become infected in Greenland, Indonesia, Niger, Asia and Austria, respectively. The country of infection for the remaining four persons of Danish origin was unknown.

TB among persons of non-Danish origin

In 2019, a total of 58 TB cases were notified among Greenlanders, whereas 2020 recorded 42 TB cases in this group. This corresponds to a 28% decline from 2019 to 2020. However, it should be noted that a slight increase in the number of notified TB cases occurred among Greenlanders from 2018 to 2019, see Figure 3. Greenlanders residing in Denmark remain the largest group of TB cases, stated as number of cases, among persons of non-Danish origin. In 2019 and 2020, the majority of notified cases among persons of Greenlandic origin were notified from the City of Copenhagen (32 cases), followed by South Jutland (18 cases) and North Jutland (17 cases).

In 2019 and 2020, a total of 13 and nine TB cases were notified among persons from Eritrea. Overall, the number of TB cases from Eritrea followed a declining trend from 2015 through 2020, see Figure 4 presenting the TB incidence of selected countries of origin.

The highest incidences among persons of non-Danish origin were observed among patients from Greenland (351 cases per 100,000 in 2019 and 251 cases per 100,000 in 2020) and Eritrea (192 per 100,000 in 2019 and 125 per 100,000 in 2020).

2015 recorded an increasing incidence of TB among persons from Syria. One explanation of this increase may be the considerable flow of Syrian refugees into Denmark in 2015. However, as from 2016, declining incidences have been observed among persons of Syrian origin; and in 2020, no TB cases were notified in this group of origin. Additionally, from 2016 to 2020, declining incidences have been seen among persons whose country of origin is Afghanistan.

TB in children

Overall, 26 TB cases among children below 15 years were notified (16 cases in 2019 and 10 cases in 2020), whereas 2018 recorded a total of 11 notifications in the age group. Among the 26 cases, nine were children below five years of age (six cases in 2019 and three cases in 2020). Out of the nine children, eight were born in Denmark. The last child was born in Eritrea.

Eight of the nine children below five years of age had presumably become infected in Denmark, whereas one child had presumably become infected in Senegal. One child was of Danish origin, while the others were from Pakistan, Eritrea, Somalia, Senegal and Greenland, respectively.

Among the cases below five years of age, eight had pulmonary TB and one child had pleural TB. All nine children had probably become infected by a household member or a close family member.

Has COVID-19 had an impact on the number of notified TB cases in 2020?

Globally, a considerable decline has been observed in the number of persons diagnosed with TB and notified in 2020 compared with 2019. Following considerable increases in the 2017-2019 period, an 18% decline was observed between 2019 and 2020, from 7.1 mio. to 5.8 mio. In contrast, the global number of deaths caused by TB increased from 1.2 mio. in 2019 to 1.3 mio. in 2020 due to reduced access to diagnostics and treatment. The global effects of the COVID-19 pandemic on the TB situation are described in the WHO’s annual tuberculosis report, Global Tuberculosis Report 2021.

The marked decline in TB cases globally was reflected in Denmark from 2019 to 2020. In the past ten years, the number of notified TB cases has followed a declining trend, even though minor fluctuations have been observed between years. Whereas the incidence remained at roughly the same level from 2017 to 2019, a more pronounced and marked decline was recorded from 2019 to 2020, see Figure 5. The total reduction in the number of cases was 22.2% (284 in 2019 and 221 in 2020), with no difference between persons of Danish and non-Danish origin, see Table 5. The reduction covered most age groups but was greater for persons of Danish origin aged 35-44 years (53.8%) and was primarily seen among men. For persons of non-Danish origin, the largest reduction was observed in the age group 45-54 years (38.1%), see Table 5.

As was the case globally, it is assessed that the decline in the number of TB cases from 2019 to 2020 was likely due to COVID-19 lock-downs and/or poorer access to healthcare.

Occupational transmission

Occupational transmission among notified TB cases in 2019

In 2019, a total of six TB cases had possible occupational infection stated on the notification.

• One person had worked as a teacher at Haslev School where a major outbreak occurred in 2018. The outbreak was described in the 2018 annual report (Tuberculosis - report on disease occurrence 2018). The person’s PCR test was positive, but culture was negative. Therefore, genotyping was not possible. The affected person did not have any risk factors for TB infection, and occupational transmission is therefore considered likely.
• One persons stated possible transmission via a colleague at a builder’s merchant. However, no contact information was available for the colleague in question, and therefore the suspicion of occupational transmission could not be investigated further. Furthermore, the genotype belonged to the largest infectious chains observed in Denmark; M. tuberculosis complex type C2/1112-15 (also coined cluster 2).
• One patient stated possible transmission via his/her work with drug users. However, the place of work was not stated in detail, and therefore any occupational transmission could not be investigated further.
• One case stated possible occupational transmission via work at a housing service targeting mentally ill residents. The person was immunocompromised, and the genotype belonged to cluster 2. Occupational infection could not be substantiated; nor could they be disproved.
• One person stated having become infected via work in a social institution. The diagnosis was maintained based on histology results, and genotyping was therefore unavailable. Thus, occupational transmission could not be further substantiated.
• One case stated possible transmission via work at a refuge for battered women and women of non-Danish origin. In this case, the diagnosis was maintained exclusively on the basis of histology results, why occupational transmission could not be further substantiated.

The notifications of another two cases stated that it remained unknown if occupational transmission had occurred.

• In one case, possible occupational transmission through work at a bar was stated. The genotype belonged to cluster 2, why occupational transmission could neither be substantiated nor refuted.
• For one person, possible occupational transmission abroad was stated at a homeless shelter or in a refugee camp. The diagnosis was maintained based exclusively on clinical particulars and a positive quantiferon test. Occupational transmission abroad was therefore possible but could not be substantiated.

Occupational transmission among notified TB cases in 2020

In 2020, a total of three TB cases had possible occupational infection stated on the notification.

• One of these persons was employed as a secretary at a hospital ward where possible transmission was stated via two previously admitted patients in 2011 and 2016. Genotyping of the patient’s isolate showed the same genotype as the two cases in 2011 and 2016, respectively. Therefore, occupational transmission is considered probable, either in 2011 or in 2016.
• One case worked as a social and healthcare assistant and had provided home-based care to a citizen with active TB. Genotyping showed the same type as the citizen, why occupational transmission is considered probable.
• One case had worked many years previously as a nurse in a hospital ward where TB patients were admitted. Occupational infection was therefore considered possible, but this could not be further substantiated.

The notifications of another six cases stated that it remained unknown if occupational transmission had occurred.

• Among three of the unresolved cases, no specific place of work was stated, why occupational transmission could not be further substantiated.
• One case had worked as a physician in Saudi-Arabia and Pakistan where occupational transmission may have occurred. The genotype showed a type found in a very limited number of patients in the Capital Region of Denmark. Occupational transmission was therefore possible, but transmission may also have occurred in the Capital Region of Denmark where the patient resided. Therefore, potential occupational infection could not be substantiated any further.
• One case worked at a drug rehabilitation centre in the Capital region of Denmark. Furthermore, the person was of Turkish origin. The genotype of this person was seen in a limited number of patients from Turkey and Syria in the Capital Region of Denmark. Occupational infection is therefore possible, but this could not be further substantiated.

Outbreaks

No major outbreaks were recorded in 2019 or 2020.

Microbiological trends

In 2019, the TB diagnosis was confirmed by culture and subsequent determination of species in 229 of 284 cases (81%). This constituted an increase compared with 2018 when the corresponding share was 75%. Hereof, 62 of 79 (78%) were confirmed among Danes and 167 of 205 (81%) among immigrants. In one case, the disease was caused by Mycobacterium africanum; one by Mycobacterium orygis; the rest had classic Mycobacterium tuberculosis. In 2020, the TB diagnosis was confirmed by culture and subsequent determination of species in 180 of 221 cases (81%). This was the same share as recorded in 2019. Among the culture-positive cases, 47 of 62 (76%) were confirmed among Danes and 133 of 159 (84%) among immigrants. In two cases, the disease was caused by Mycobacterium africanum. Both of these cases were immigrants. The rest had classic Mycobacterium tuberculosis.

Among the 55 notified cases in 2019 that were not confirmed by culture, seven (13%) cases had a positive PCR performed at Statens Serum Institut (SSI). Among these seven PCR-positive cases, one was also positive by microscopy. Among the 41 cases notified in 2020 that were not confirmed by culture, seven (17%) cases had a positive PCR. All of these seven PCR-positive cases were negative by microscopy. Negative culture despite positive PCR and/or microscopy may be due to patients having been started on anti-tuberculosis treatment before the culture samples were taken.

According to the disease definition of the European Centre for Disease Prevention and Control (ECDC), 230 (81%) of the cases from 2019 were confirmed, six (2%) were probable cases and 48 (17%) were possible cases. For 2020, a total of 180 (81%) were confirmed cases, 14 (6%) probable cases and 37 (17%) were possible cases.

Among the 225 notified cases of pulmonary TB (± other localisation) in 2019, a total of 188 (84%) cases were verified by culture, including 57 of the 72 (79%) Danish cases and 131 of the 153 (86%) immigrant cases. By microscopy of expectorates from 57 Danes with culture-confirmed pulmonary TB (+/- other localisation), 24 (42%) tested positive and were thus regarded as infectious. This proportion was 53% in immigrants (70 of 131). Among all 188 cases of culture-verified pulmonary TB, 182 (97%) were tested by PCR at the SSI, of whom 119 (65%) tested positive.

For 2020, 134 (84%) of a total of 160 notified cases of pulmonary TB (± other localisation) cases were verified by culture, including 42 of the 53 (79%) Danish cases and 92 of the 107 (86%) immigrant cases. By microscopy of expectorates from the 42 Danes with culture-confirmed pulmonary TB (+/- other localisation), 26 (62%) tested positive and were thus, per definition, regarded as infectious. This proportion was 54% in immigrants (50 of 92). Among all 134 cases of culture-verified pulmonary TB, 132 (99%) were tested by PCR at the SSI, of whom 83 (63%) tested positive.

When comparing all notified TB cases in 2019 among Danes with the corresponding number for the previous year, 2019 witnessed a decline in the share of microscopy-positive pulmonary TB and thereby a decline from 48% to 42% in the share of infectious pulmonary TB cases. Among immigrants, an increase from 48% to 53% was observed. The decrease among Danes may reflect that TB patients are diagnosed earlier in their disease course, which may be associated with a more active screening effort in the risk groups, particularly in the Copenhagen area.

A comparison of all notified TB cases in 2020 with the corresponding number for 2019 shows that 2020 witnessed an increase in the share of microscopy-positive pulmonary TB and thereby an increase in the share of infectious pulmonary TB. The increase was primarily seen among Danes; from 42% to 62%. A more limited increase was observed among immigrants; from 53% to 54%. In connection with the SARS-CoV-2 and ensuing lock-down of countries, a considerable decline was observed all over Europe in the number of samples submitted for diagnostics. The same applied following the Danish lock-down on 11 March 2020, when a drop was observed in the number of samples submitted to the Department of Tuberculosis and Mycobacteria at the SSI. Simultaneously, TB screening among socially exposed individuals was discontinued in the Copenhagen area, among others. An increasing microscopy-positive percentage may reflect delayed diagnostics because the individual has had to be more self-reliant in terms of seeing a doctor in a situation in which a negative corona test was also required, which may have delayed diagnostics additionally. Thus, it remains unknown if the 22% decline in the number of notifications from 2019 to 2020 (from 284 in 2019 to 221 in 2020) may be explained in full by a real decline, i.e. owed to reduced immigration and a positive effect of restrictions on infection spreading, or if undiagnosed cases are occurring as may be indicated by the high microscopy-positive percentage, maybe in particular among socially exposed persons.

Typing of bacteria from 214 of the 230 (93%) culture-positive patients detected in 2019 shows that a single chain of infection, ”C2/1112-15” (also coined cluster 2), still dominates, accounting for 24% of all typed cases in Denmark, and that it follows an increasing trend compared with 18% in 2018 and 2017. The same applied in 2020 when typing of 155 mycobacteria isolates among a total of 180 (86%) showed that cluster 2 comprised 21% of all typed cases in Denmark. The number of ”C2/1112-15” followed a steadily increasing trend from subtyping of isolates was initiated in 1992 and until 2012, when the curve broke, which may be linked to the previously mentioned screening efforts made in the Copenhagen area. As from 2017, the number has started climbing again. Furthermore, it is clear that the share of patients of non-Danish origin in this chain of infection, which was previously all Danish, continues to rise, reaching 60% in 2019, the same level as in 2018 and an increase in comparison with previous years.

Resistance

For 2019, drug resistance results were available for 228 of the 230 culture-verified cases. In the final two cases, an overgrowth of other microorganisms was observed and therefore antimicrobial susceptibility testing was not possible. A total of 209 of these cases were notified with TB for the first time, including 60 Danes and 149 immigrants. Among those notified for the first time, isoniazid mono-resistance was detected in two (1%) patients, both of whom were immigrants from India and Eritrea, respectively. Poly-resistance was detected in a single patient (resistance to isoniazid and pyrazinamide). No rifampicin mono-resistance was detected. No resistance was detected among the 19 previously notified culture-positive TB patients, including three Danes and 16 immigrants.

Four cases of multi-drug resistance (MDR) were detected, corresponding to 2% of the culture-verified cases. No cases of extreme drug resistance (XDR) were detected in 2019. MDR is resistance to the two primary antibiotics; isoniazid and rifampicin and any other antibiotics. The term XDR resistance designates MDR resistance and additional resistance to a minimum of one of the important second-line drugs belonging to the group of fluoroquinolones and a minimum of one of the three injectable drugs amikacin, capreomycin or kanamycin. The definition of XDR was changed in January of 2021. Now, in addition to resistance to MDR, XDR also encompasses resistance to a minimum of one of the important second-line drugs belonging to the group of fluoroquinolones and to a minimum of one of the so-called group A antibiotics (levofloxacin, moxifloxacin, bedaquiline and linezolid).

One of the four MDR TB cases in 2019 was a Dane with pulmonary TB who belonged to the same MDR infectious chain observed in 2018 (EPI-NEWS 37/19). The three others were non-Danish cases from Somalia, Vietnam and the Ukraine, respectively. Two of the cases were Beijing strains, a strain associated with several MDR outbreaks globally.

For 2020, drug resistance results were available for 179 of the 180 culture-verified cases. In the final case, an overgrowth of other microorganisms was observed, and therefore antimicrobial susceptibility testing was not possible. A total of 168 of the cases for whom resistance could be determined were notified with TB for the first time, including 43 Danes and 125 immigrants. Among those notified for the first time, isoniazid mono-resistance was detected in nine (5%) patients. No rifampicin mono-resistance was detected.

In 2020, two cases of multiple resistance (MDR), corresponding to 1% of the culture-verified cases, were observed. One of these cases was a patient with a previous TB diagnosis from 2018 who was comprised by the first MDR-TB outbreak in Denmark, described in EPI-NEWS 37/19. No cases of extreme drug resistance (XDR) were detected in 2020.

This report is also described in EPI-NEWS 49-50/21.