Pulmonologists Advise Screening Ukrainian Refugees for TB

The German Respiratory Society (DGP) is expecting patients with tuberculosis (TB) to be among the war refugees from Ukraine. "Therefore, it must be ensured that these people continue to be medically treated without any breaks, so that their treatment is successful," said Torsten Bauer, MD, in a press release from the DGP and the German Central Committee Against Tuberculosis (DZK). Bauer is president of the DGP and DZK, as well as chief physician of the Heckeshorn Pulmonary Clinic in Berlin.

The current challenge is to identify those war refugees who are infected with TB so that they may be treated further. This is not so simple, but it is feasible, said Bauer.

"Not all refugees are routinely screened for TB. There have always been efforts to examine individuals such as au pairs from Ukraine or countries with a similarly high incidence of TB. But to date, there is no legal basis for this," he said. "The Infection Protection Law is only effective if these people are housed in shared accommodations. Screening for TB takes place there."

For adults, an X-ray image is usually taken as well. For children, an interferon gamma release assay (IGRA) ideally should be performed for further clarification. In contrast to the century-old Mantoux tuberculin skin test, there are no cross-reactions with BCG strains after the BCG vaccine for the IGRA. "That is relevant because the BCG vaccine is one of the precautions for children in Ukraine," says Bauer.

For World Tuberculosis Day on March 24, the World Health Organization (WHO) updated its guidelines for treating children and adolescents (see box below).

Prompt Care Recommended

War refugees who are housed with host families are falling through the cracks in this system. "We want to raise awareness of the fact that war refugees in host families must be given general medical care as promptly as possible in the form of an entrance examination. In the context of medical duty of care, it is particularly important here to also think about TB," Bauer emphasized. If there are any symptoms, or indications in the medical history of TB, then corresponding diagnostic measures should be initiated swiftly.

Two factors differentiate the current situation from the refugee crisis in 2015. First, refugees from Ukraine do not need to apply for asylum; they can stay in the Schengen area for up to 90 days without a visa. According to Federal Minister of the Interior Nancy Faeser, the plan is for Ukrainian refugees to receive protected status for up to 3 years. It is also likely that they will very quickly have access to health insurance. "That's enough for right now to screen for TB," said Bauer.

In Germany, an average of 5 in 100,000 citizens are affected by TB annually. In Ukraine, the number is 73 cases in 100,000 citizens.

Multidrug-Resistant TB

The proportion of multidrug-resistant TB (MDR-TB) in refugees with documented TB from Ukraine is very high (29%), and treatment success for MDR-TB is only approximately 51% in Ukraine. By way of comparison, in 2020 in Germany, the proportion was 2.7%, according to the Robert Koch Institute (RKI).

The therapy is expensive. "MDR-TB must be treated with at least four, better with five to six, antibiotics, and these must be taken for at least 18 months," said Bauer.

The continuity of the therapy is important. "If there is an interruption of just 8 weeks, the treatment must be started again from scratch," said Tom Schaberg, MD, PhD, lead author of the German TB guidelines.

Co-infections may complicate TB treatment significantly. In around 22% of Ukrainian patients with TB, there is an HIV infection, often accompanied by a hepatitis C infection. COVID-19 does not play a role in the issue of co-infections with TB.

In overfilled train stations and on trains, distancing rules cannot be followed, and with a highly infectious disease such as this, such conditions lead to a coronavirus infestation within a few days. If these people then arrive in Germany, they must be vaccinated again against COVID-19. However, is not known whether a COVID-19 infection is associated with an elevated risk of catching TB.

The chances of recovery from MDR-TB are significantly worse than for sensitive TB. In Ukraine, treatment success for MDR-TB is approximately 51%. But there is experience with this too. The Heckeshorn Pulmonary Clinic, one of the largest TB clinics in Germany, has been treating patients with TB from Ukraine for several years now. However, the treatment costs are very high. "The day therapy costs are then significantly over €400 (400 euros), and that must of course be refinanced somehow."

Staffing and Funding Requested

The DGP is asking health officials to boost the staffing of structures for the outpatient and inpatient care of refugees as quickly as possible and, at the same time, nonbureaucratically guarantee the absorption of costs. Specifically, it has made the following requests:

The public health service must receive more staffing and a higher budget in the short term to guarantee TB screening as quickly as possible.
The costs for inpatient and outpatient treatment of MDR-TB must be completely absorbed.
The cost absorption for the longer-term care of patients with co-infections such as HIV or an additional dependency on intravenous drugs must be guaranteed by the legislators.
Information must be disseminated to physicians who are in first contact with the refugees to raise awareness of TB as a differential diagnosis. In the medium term, the continuing education of the medical profession in infection-relevant questions should be encouraged so that crisis situations can be handled quickly in the future.

DGP and DZK expressly indicate in their press release that the absorption of costs must be guaranteed.

"We opened an additional TB ward at our clinic during the 2015 refugee crisis and conducted the therapy and isolation there," said Bauer. "Up to 3 years later, the medical service of the health insurers tried to dispute these cases with us. The justification for the dispute was frequently that the cases could have been treated on an outpatient basis, or that the hospital was not responsible for the isolation."

This meant that the clinic was threatened with millions of euros in financial recovery claims. It was not until fall 2021, after intensive preliminary work, that a mutual solution was found with the State Office for Refugees. Bauer is afraid that something similar will happen now. "This means, treat first and then we'll see." Bauer believes that in this situation, people do not want to guess anymore.

Seeking a TB Vaccine

"We expect that the rate of MDR-TB has doubled or tripled through the war refugees," said Bauer. "This sounds dramatic, but ultimately it should not be a problem for the German health system."

He demonstrated his position with an example. "Should a million refugees be accepted in Germany, at least 500 to 1000 new TB cases could come with them. It can be assumed that approximately 25% to 30% of them will be MDR-TB. That is definitely a manageable problem, if the framework conditions are established," said Bauer.

TB bacteria are less infectious than the coronavirus. Even if the number of TB cases now increases, it will not prompt a re-evaluation of the BCG vaccination, which has not been recommended by the RKI since 1998, says Bauer. "Currently, the BCG vaccination is only performed for children in high-risk incidence countries. In these countries, the infants are vaccinated because it has been shown that they then become less seriously ill. But we are still a long way away from this."

New vaccines against TB are currently undergoing phase 3 studies, said Bauer. "We have been searching for a vaccine against TB for 100 years, and we hope that the COVID-19 crisis might bring an innovation drive, including for the TB vaccine."

WHO Updates Guidelines

For World Tuberculosis Day on March 24, the World Health Organization (WHO) updated its guidelines for TB therapy for children and adolescents and also called for urgent investment in the fight against TB. For the first time in over a decade, the number of TB fatalities rose in 2020. Persistent conflicts in Eastern Europe, Africa, and the Middle East have further exacerbated the situation for endangered groups of people.

In 2018 and 2020, around 20 million people received TB therapy. This number is only 50% of the 5-year target of 40 million people who should receive TB treatment in the period from 2018 through 2022. For children and adolescents, the situation is even worse: in 2020, an estimated 63% of children and adolescents under the age of 15 with TB did not receive, or could not access, any diagnosis or therapy. For children under 5 years old, the proportion was even higher (72%).

"Children and adolescents sick with TB lag behind adults with regard to access to TB prevention and treatment," said Tereza Kasaeva, MD, PhD, director of the WHO global TB program, at a press briefing. "The WHO guidelines published today are of vital importance to children and adolescents because they help them to be diagnosed earlier and to have access to treatment. This leads to better results and reduces transmission." Now the idea is to quickly promote the implementation of the guidelines in all countries to save younger people and prevent harm, said Kasaeva.

The most recent guidelines recommend the molecular rapid diagnosis as the first test for TB diagnosis in children and adolescents. For children and adolescents who exhibit a drug-sensitive, nonserious form of TB, the treatment duration has been shortened from 6 to 4 months. For children and adolescents with TB meningitis, the treatment duration has been shortened from 12 to 6 months. Two of the most recent medications for the therapy of drug-resistant TB (bedaquiline and delamanid) are now recommended for children of all age groups. This means that children with drug-resistant TB can receive a purely oral treatment, regardless of their age.

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