Availability and costs of medicines for the treatment of tuberculosis in Europe
Unreasonably priced drugs, lack of essential medicines and limited diagnostics impact the treatment of MDR-TB in a number of European countries.
Tuberculosis (TB) is the most common fatal bacterial infectious disease worldwide. The World Health Organization's (WHO) EndTB Strategy aims to eradicate TB by 2035. The reality, however, is different. Global TB report 2020 warned that indicators for TB incidence and TB mortality are not on track to reach the target reduction for 2015-2020. Over the past 10 years, TB incidence (the number of cases per 100,000 people in the population) worldwide has barely changed and deaths from tuberculosis is now on the rise for the first time in decades. Of particular concern is the increase in multidrug-resistant (MDR) cases of TB.
In some countries of Eastern Europe, the incidence of MDR-TB is particularly high. While in European Union countries the share of patients with MDR-TB is less than three percent of all TB patients, in countries bordering the European Union, i.e. the Russian Federation, Belarus, Republic of Moldova and Ukraine, more than 25 percent of patients are affected by MDR-TB. Currently, less than 60% of those affected by MDR-TB have a chance of being cured.
TBnet, our Europe-wide network of TB researchers, has analysed the current availability of drugs to treat TB patients, the cost of therapies, and the availability of diagnostics for antibiotic resistance testing in the WHO European Region. The study is published in the journal “Clinical Microbiology and Infection” and is available (open access) here: www.clinicalmicrobiologyandinfection.com/article/S1198-743X(22)00394-9/fulltext
The authors of the study are Gunar Günther, Lorenzo Guglielmetti, Claude Leu, Christoph Lange, and Frank van Leth.
The full list of colleagues who contributed to the study and their organizations can be found in the end of this text and in acknowledgement section of the paper (*). The results, of the study are alarming, please, share them with your colleagues for awareness.
The new anti-TB drugs - bedaquiline and delamanid - are only available in 36 (84%) and 24 (56%) of the 43 countries included in the survey of the WHO European Region, respectively. That is despite the fact these drugs are on the WHO list of essential medicines. Rifapentine, a drug that can reduce standard TB therapy from 6 months to 4 months and can reduce preventive therapy for TB from 3 months to 1 month, is available in only 6 of the 43 countries (14%). Combination therapy for patients with extensively drug-resistant TB (so-called XDR-TB) is available in only 17 of the 43 (40%) countries. At the same time, the cost of the medicines is exorbitantly high in some countries in Europe where the treatment of a patient can amount to several hundred thousand Euros.
Also of concern is the finding that while new drugs are available in some countries, antibiotic resistance testing to these drugs is frequently not available there. Without antibiotic resistance testing, patients simply receive standard therapies without knowing how many of the drugs in the cocktail are effective. This inevitably leads to the selection and spreading of resistant strains of Mycobacterium tuberculosis, bacteria that cause TB.
* Members of the TBnet study group:
Hasan Hafizi1, Naira Khachatryan 2, Harut Aroyan 2, Eduard Kabasakalyan 3, Michael Knappik 4, Alena Skrahina 5, Dzmitry Klimuk 5, Alena Nikolenka5, Inge Muylle 6, Vladimir Milanov 7, Desislava Velkovska 8, Neli Tarinska 8, Elizabeta Bachiyska 9, Mateja Jankovic10, Despo Pieridou 11, Tonia Adamide 12, Nicos Nicolaou 13, Martina Vasakova 14, Mariia Sukholytka 14, Emilia Kopeckà 14, Åse Bengård Andersen15, Dorte Bek Folkvardsen16, Erik Svensson16, Manfred Danilovits17, Tiina Kummik18, Tuula Vasankari19, 20, Mathilde Fréchet-Jachym21, Audrey Nahmiash 21, Tamar Togonidze 22, Zaza Avaliani22, Inga Kinkladze 22, Rusudan Aspindzelashvili 22, Teona Bichashvili 22, Gulnazi Losaberidze 22, Tsitsino Merabishvili 22, Barbara Kalsdorf 23,24,25,26, Katerina Manika 27, Karyofyllis Tsiakitzis 28, Agnes Bakos 29, Tinna Rán Ægisdóttir 30, Guðrún Svanhvít Michelsen 30, Kristín Karlsdóttir 30, Anne-Marie McLaughlin 31, Margaret Fitzgibbon 32, Daniel Chemtob 33, Luigi R. Codecasa 34, Maurizio Ferrarese 34, Stefania Torri 34, Majlinda Gjocaj 35, Liga Kuksa 36,37, Edita Davidaviciene 38, Gil Wirtz 39, Monique Perrin 40, Analita Pace Asciak 41, Dumitri Chesov 23,42, Wiel de Lange 43,44, Onno Akkerman 43,44, Biljana Ilievska Poposka 45, Ulrich Mack 46, Mogens Jensenius 47, Lajla Kvalvik 48, Anne Torunn Mengshoel 49, Katarzyna Kruczak 50, Raquel Duarte 51,52,53,54, Nadine Ribeiro 55, Elmira Ibraim 56, Anna Kaluzhenina 57, Olga Barkanova 57, Dragica Pesut 58,59, Ivan Solovic 60, Petra Svetina 61,62, Maria-Luiza de Souza-Galvão 63, Joan-Pau Millet 64,65,66, Xavi Casas 64, Montserrat Vives 64, Judith Bruchfeld 67,68, Paulina Dalemo 68, Jerker Jonsson 69, Katrin Aeschbacher 70, Peter Keller 71, Seref Özkara 72, Simon Tiberi 73,74, Christabelle Chen 75, Yana Terleeva 76, Andrii Dudnyk 77
1 Internal Medicine, University Hospital "Sh. Ndroqi", Tirana, Albania; 2 National Tuberculosis Control Program, Ministry of Health, Yerevan, Armenia; 3 National TB Reference Laboratory, National Center of Pulmonology, Abovyan, Armenia; 4 Klinik Penzing, Vienna, Austria; 5 RSPC for Pulmonology and TB, Minsk, Belarus; 6 Department of Respiratory Medicine, University Medical Center St Pieter, Brussels, Belgium; 7 Department of Pulmonary Diseases, Medical Faculty, Medical University of Sofia, University Hospital of Respiratory Diseases "St. Sofia", Sofia, Bulgaria; 8 Ministry of Health, Sofia, Bulgaria; 9 National Reference Laboratory of Tuberculosis, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria; 10 Clinic for Respiratory Diseases, University Hospital Center Zagreb, Zagreb, Croatia; 11 National Reference Laboratory for Mycobacteria, Microbiology Department, Nicosia General Hospital, Nicosia, Cyprus; 12 Pulmonary Clinic, Nicosia General Hospital, Nicosia, Cyprus; 13 Pharmacy Department, Nicosia General Hospital, Nicosia, Cyprus; 14 Department of Pneumology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic; 15 Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 16 Statens Serum Institut, International Reference Laboratory of Mycobacteriology, Copenhagen, Denmark; 17 Tartu University Hospital, Lung Clinic, Department of Tuberculosis, Tartu, Estonia; 18 Department of Mycobacteriology, University Hospital of Tartu, Tartu, Estonia; 19 Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Turku, Finland; 20 Finnish Lung Health Association (FILHA), Helsinki, Finland; 21 Centre Hospitalier de Bligny, Briis-sous-Forges, France; 22 National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia; 23 Research Center Borstel, Clinical Infectious Diseases, Borstel, Germany; 24 German Center for Infection Research (DZIF) Tuberculosis Unit, Borstel, Germany; 25 International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany; 26 Cluster Precision Medicine in Inflammation, University of Kiel, Kiel, Germany; 27 Pulmonary Department, Aristotle University of Thessaloniki, "G. Papanikolaou" Hospital, Thessaloniki, Greece; 28 Department of Hospital Pharmacy, "G. Papanikolaou" Hospital, Thessaloniki, Greece; 29 National TB Surveillance, Koranyi National Institute for Pulmonology, Budapest, Hungary; 30 Pharmaceutical Services, Landspitali University Hospital, Reykjavik, Iceland; 31 Respiratory Medicine Service, St James's Hospital, Dublin, Ireland; 32 Irish Mycobacterial Reference Laboratory, Dublin, Ireland; 33 Department of TB and AIDS, Ministry of Health, Jerusalem, Israel; 34 Regional TB Reference Centre and Laboratory, Villa Marelli Institute/Niguarda Hospital, Milano, Italy; 35 National TB Program, Ministry of Health, Pristina, Kosovo; 36 Tuberculosis and Lung Disease Clinic, Riga East University hospital, Riga, Latvia; 37 Riga Stradinš University, Riga, Latvia; 38 Vilnius University Hospital, Santaros Klinikos, Vilnius, Lithuania; 39 Centre Hospitalier du Luxembourg, City of Luxembourg, Luxembourg; 40 Laboratoire national de santé, Microbiology Department, Dudelange, Luxembourg; 41 Infectious Disease Prevention and Control Unit, Ministry of Health, Valetta, Malta; 42 Department of Pneumology and Allergology, State University of Medicine and Pharmacy ”Nicolae Testemitanu”, Chișinău, Republic of Moldova; 43 University of Groningen, University Medical Center Groningen, TB center Beatrixoord, Groningen, the Netherlands; 44 University of Groningen, University Medical Center Groningen, Department of Pulmonary diseases and Tuberculosis, Groningen, the Netherlands; 45 Focal point for Tuberculosis for Republic of North Macedonia, Institute for Lung Diseases and Tuberculosis, Skopje, Republic of North Macedonia; 46 Lovisenberg Diakonale Sykehus, Oslo, Norway; 47 Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway; 48 Hospital Pharmacy, Oslo University Hospital, Oslo, Norway; 49 National Reference Laboratory (NRL) for Mycobacteria, Department of Bacteriology, Norwegian Institute of Public Health, Oslo, Norway; 50 University Hospital, Krakow, Poland; 51 ICBAS. Instituto de Ciencias Biomédicas Abel Salazar. Universidade do Porto, Porto, Portugal; 52 ISPUP. Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal; 53 Serviço de Pneumologia. CHVNG/E. Centro Hospitalar de Vila Nova de Gaia/Espinho; 54 Unidade de Investigação Clínica. ARS Norte; 55 ARS Lisboa, Lisboa, Portugal; 56 Marius Nasta Institute of Pulmonology, Bucharest, Romania; 57 Tuberculosis Department, Volgograd State Medical University, Volgograd, Russia; 58 Faculty of Medicine, University of Belgrade; 59 University Clinical Center of Serbia, Teaching Hospital of Pulmonology, Belgrade, Serbia; 60 National Institute for TB, Lung Diseases and Thoracic Surgery, Vysne Hagy, Slovakia; 61 University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia; 62 National TB Program and TB Registry, Slovenia; 63 Servei de Pneumologia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; 64 Serveis Clínics, Barcelona, Spain; 65 Servei d'Epidemiologia, Agència de Salut Pública de Barcelona, Barcelona, Spain; 66 CIBER de Epidemiologia y Salud Pública (CIBERESP), Madrid, Spain; 67 Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; 68 Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; 69 Departement of public health analysis and data monitoring, The Public Health Agency of Sweden, Stockholm, Sweden; 70 Hospital Pharamcy, Inselspital, Bern University Hospital, Bern, Switzerland; 71 Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Switzerland; 72 Atatürk Sanatorium Education and Research Hospital, Ankara, Turkey; 73 Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; 74 Department of Infection, Royal London Hospital, Barts Health NHS Trust, London, United Kingdom; 75 Pharmacy Department, Barts Health NHS Trust, London, United Kingdom; 76 TB Management and Counteraction Department, Public Health Center of the Ministry of Health of Ukraine, Kyiv, Ukraine; 77 Department of Tuberculosis, Clinical Immunology & Allergy, National Pirogov Memorial Medical University, Vinnytsia, Ukraine.