Genome analysis confirms Europe-wide multidrug-resistant tuberculosis outbreak

The outbreak strain could be conclusively confirmed by genome analysis


The National Reference Center at the Research Center Borstel has confirmed a Europe-wide outbreak of a multidrug-resistant Mycobacterium tuberculosis strain in 29 refugees from the Horn of Africa. The Research Center Borstel as well as the European Centre for Disease Prevention and Control, the Robert Koch Institute and the University of Zurich’s National Reference Center for Mycobacteria were involved in the coordination of this Europe-wide investigation. The results have now been published in the renowned journal The Lancet Infectious Diseases.

In 2016, the National Reference Center for Mycobacteria (NRZ) in Borstel and in Switzerland (NZM) identified a previously unknown tuberculosis pathogen almost simultaneously. It was resistant to an unusual combination of four different types of antibiotic drugs. Based on this resistance pattern and genome analyses, the researchers identified 14 further German patients who were infected with this dangerous pathogen. All patients were refugees who had come to Europe from the Horn of Africa.

The cluster of patient cases with a migration background prompted the NRZ in Borstel to conduct further investigations in collaboration with participating health authorities, the Robert Koch Institute, the NZM, other European Reference Centres and the European Center for Disease Prevention and Control (ECDC).

Due to an “Early Warning and Response System” report from the ECDC, the outbreak strain could be confirmed in a total of 29 patients from seven European countries who had all come from the Horn of Africa or Sudan.

“The rapid report to the ECDC and the effective collaboration between the reference centres made a confirmation of this outbreak strain in different countries possible in the first place,” said Dr Katharina Kranzer, Head of the NRZ at the Research Center Borstel.

Molecular biology investigations paired with patient interviews enabled a partial reconstruction of the chain of infection. The data suggested that the infections had occurred prior to entry into Europe, in a Libyan refugee camp near Bani Waleed.

The outbreak strain is likely to have originated from a clone that is frequently found in the Horn of Africa and which developed the dangerous combination of multidrug-resistance. It is not possible to conclusively reconstruct how the pathogen was brought into the refugee camp.

“The outbreak strain could only be conclusively confirmed by genome analysis,” says Prof Stefan Niemann, last author of the study and Head of the Molecular and Experimental Mycobacteriology research group at the Research Center Borstel and Coordinator of the research field “Tuberculosis” at the German Center for Infection Research (DZIF). “This study has shown that genome sequencing can be employed for timely analysis of MDR-TB outbreaks across different countries. However, in order to comprehensively benefit from this technology, it should be integrated into routine outbreak investigations and TB surveillance.”

Genome sequencing for improved diagnostics, treatment and transmission analysis of MDR-TB strains constitute an important component of the Research Center Borstel’s work. It is currently also being conducted in different research projects at the DZIF.

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