Mycobacterium tuberculosis in HIV co-infection: a growing concern in Europe?

Context: The World Health Organization (WHO) European Region’s political attention shifted to the COVID-19 pandemic from the start of 2020 onwards. A consequence of this shift has been decreased political attention towards combating tuberculosis (TB) in the WHO European Region. As a result, decreasing TB data reporting, rising death rates, and increasing antimicrobial resistance (AMR) have prevented the WHO European Region from remaining on track to reach the United Nations Sustainable Development Goal 3 (SDG3) to eliminate TB epidemics by 2030. Furthermore, the WHO tuberculosis action plan for the WHO European Region 2016-2020 has missed opportunities to mitigate TB in this region, thus exacerbating the issue and preventing the achievement of SDG3. Policy Options: The WHO’s Roadmap to implement the tuberculosis action plan for the WHO European Region 2016-2020 provided guidance for TB management in the member states (MS), but did not sufficiently address AMR, lacking promotion of new TB vaccine rollout, nor describe national TB implementation strategies. The WHO 2016-2020 TB action plan is now overdue and WHO policymakers should consider the following recommendations when creating the new TB action plan. Recommendations: This policy brief addresses the urgent need for a new WHO TB action plan to integrate a national level implementation commitment, AMR programming, and WHO support in creating a vaccine strategy with aims for the WHO European Region to achieve SDG3 and eliminate TB epidemics by 2030.

Epidemiology News

Current Concepts in the Management of Tuberculosis

Setting: Tuberculosis (TB) morbidity in penitentiary sectors is one of the major barriers to ending TB in the World Health Organization (WHO) European Region. Objectives and design: a comparative analysis of TB notification rates during 2014–2018 and of treatment outcomes in the civilian and penitentiary sectors in the WHO European Region, with an assessment of risks of developing TB among people experience incarceration. Results: in the WHO European Region, incident TB rates in inmates were 4–24 times higher than in the civilian population. In 12 eastern Europe and central Asia (EECA) countries, inmates compared to civilians had higher relative risks of developing TB (RR = 25) than in the rest of the region (RR = 11), with the highest rates reported in inmates in Azerbaijan, Kazakhstan, Kyrgyzstan, Republic of Moldova, Russian Federation, and Ukraine. The average annual change in TB notification rates between 2014 and 2018 was −7.0% in the civilian sector and −10.9% in the penitentiary sector. A total of 15 countries achieved treatment success rates of over 85% for new penitentiary sector TB patients, the target for the WHO European Region. In 10 countries, there were no significant differences in treatment outcomes between civilian and penitentiary sectors. Conclusion: 42 out of 53 (79%) WHO European Region countries reported TB data for the selected time periods. Most countries in the region achieved a substantial decline in TB burden in prisons, which indicates the effectiveness of recent interventions in correctional institutions. Nevertheless, people who experience incarceration remain an at-risk population for acquiring infection, developing active disease and unfavourable treatment outcomes. Therefore, TB prevention and care practices in inmates need to be improved.

About one-third of the world's population has been infected with Mycobacterium tuberculosis (MTB). Active disease develops in eight to ten million people per year, and tuberculosis is responsible for three million deaths every year. This makes it the leading cause of death due to infections in the world. In 1996, 315,892 cases of tuberculosis were reported in 50 countries of the WHO European region. The notification rate was less than 20 per 100,000 in 21 countries, all of which are situated in the western part of Europe except the Czech Republic and Israel. The rate was 20 cases per 100,000 or more in 29 countries located in the eastern part of Europe except for Portugal and Spain. In addition to the rise of tuberculosis observed worldwide, the emergence of drug-resistant tuberculosis (TB) poses a major threat to TB control efforts. The prevalence of resistance is increasing dramatically, predominantly in eastern Europe. The aim of this article is to describe the situation of resistant TB in Europe, and to point out reasons for the increase of drug-resistant MTB strains.

Health-care provision for displaced populations arriving from Ukraine

Estimating antimicrobial resistance burden in Europe—what are the next steps?

The World Health Organization (WHO) European region estimates that more than 400,000 tuberculosis (TB) cases occur in Europe, a large proportion of them among migrants.A coordinated public health mechanism to guarantee TB prevention, diagnosis, treatment and care across borders is not in place. A consensus paper describing the minimum package of cross-border TB control and care was prepared by a task force following a literature review, and with input from the national TB control programme managers of the WHO European region and the Wolfheze 2011 conference. A literature review focused on the subject of TB in migrants was carried out, selecting documents published during the 11-yr period 2001–2011.Several issues were identified in cross-border TB control and care, varying from the limited access to early TB diagnosis, to the lack of continuity of care and information during migration, and the availability of, and access to, health services in the new country.The recommended minimum package addresses the current shortcomings and intends to improve the situation by covering several areas: political commitment (including the implementation of a legal framework for TB cross-border collaboration), financial mechanisms and adequate health service delivery (prevention, infection control, contact management, diagnosis and treatment, and psychosocial support).

Tuberculosis (TB) preventive treatment (TPT) is crucial for preventing infection with Mycobacterium tuberculosis from progressing to TB disease, especially among people in high-risk groups. The expansion of novel TPT regimens for drug-susceptible TB is a notable advancement in TB care. However, managing contacts of drug-resistant TB patients remains a major challenge, particularly in Eastern Europe and Central Asia. In 2020, the World Health Organization (WHO) recommended TPT for high-risk household contacts of multidrug-resistant (MDR) or rifampicin-resistant (RR) TB patients; this was further reinforced in 2024 with a recommendation of a 6-month levofloxacin (6-Lfx) regimen. This Perspective discusses the early adoption of 6-Lfx for MDR/RR-TPT in the WHO European Region. In 2023, 38 of 53 WHO European Region countries reported on 6-Lfx use, with only eight confirming its use for MDR-TB contact persons. Accelerating the adoption of the 6-Lfx regimen and other evidence-backed TPT regimens is crucial for achieving TB elimination in the WHO European Region. Addressing challenges such as slow uptake of the recommendations, low awareness in affected communities and resource shortages are essential for success.

Tuberculosis (TB) is considered to be a disease of poverty, since its incidence is exacerbated by socioeconomic factors, inconsistent or partial treatment practices, and immigration from endemic countries. A prospective country level study, using a comprehensive dataset of TB incidence and prevalence taken from countries within the World Health Organization (WHO) European region, was conducted. We employed quintile regression to investigate the prospective association between baseline (measured in 2000) and a nation's wealth, level of egalitarianism, migration rate, health-related lifestyle and social capital with TB incidence and prevalence over a 10-yr period (2000-2009). We found that ∼50% of TB variation is accounted for by a nation's wealth and level of egalitarianism. We observed a negative prospective association between logged gross domestic product and TB rates, and a positive prospective association between income inequality and TB. National income levels per capita and income inequality are important predictors for TB incidence and prevalence in the WHO European region. They account for 50% of country-level variation, indicating the importance of a combined absolute and relative socioeconomic disadvantage in the development of TB. These findings also provide a tool for forecasting potential fluctuations in the level of TB epidemics in the WHO European region, with respect to socioeconomic changes.

Due to a resurgence of tuberculosis (TB) globally, the world health organization (WHO) took an unprecedented step in 1993 and declared TB a global emergency [1]. New challenges, such as worsening of the HIV epidemic and rising TB/HIV co-infection, emergence of drug-resistant TB strains, and poor healthcare access of vulnerable populations proved that the efforts taken since 1995 did not suffice for effective TB control. Nowadays, TB remains a considerable health burden in the WHO European region [2]. Multidrug-resistant (MDR)-TB, a man-made phenomenon, is a major issue in this region, with increasing percentages of MDR-TB among all TB cases documented over the last 10 years [2]. Only one of ten MDR-TB patients receive appropriate treatment: poor healthcare access and poor implementation of fast, effective diagnostic methods for resistance detection hinder proper treatment of this condition [3]. The increasing incidence of MDR-TB has highlighted the insufficiency of histo-pathological diagnosis and pointed to the need for microbiological diagnosis associated with sensitivity evaluation of the causal strain. New improved culture media and identification methods reducing the time required for identification and sensitivity analyses might be extremely helpful [4]. In 2006, the WHO developed a new comprehensive strategy for TB control, the Stop TB Strategy, designed to address the spread of TB and HIV co-infection and MDR-TB. The aim of the Stop TB Strategy is to halt the epidemic and reverse it by 2015, with the ultimate goal of eliminating TB as a public health problem by 2050 [5]. Spinal tuberculosis, known as Pott’s disease, is reported together with other extra-pulmonary TB cases to the joint WHO/ECDC surveillance system and, therefore, the exact magnitude of this disease is unknown [2]. There remains a need to further analyze the related data by country, to document the extent of Pott’s disease, and to develop specific guidelines for timely diagnosis and treatment of this condition. Anti-TB drug therapy is the mainstay of treatment for spinal TB. However, with destruction of the anterior column of the spine by the infective process, kyphosis may result from progressive anterior collapse. After healing of the spinal infection, the post-TB kyphosis in adults is generally static, but in children kyphosis progresses dramatically in almost 40 % of cases [6]. The medical research council (MRC) Working Party on TB of the spine, which was formed in 1963, designed prospective multicenter clinical trials that ultimately proved that the Hong Kong operation (radical debridement and strut grafting) produces the best short-, medium-, and long-term results in aspects such as fusion rate, spinal deformity, and relapses of abscess and sinus [7]. We now know that progressive bone destruction with severe kyphosis can still develop in patients who have received successful non-surgical medical treatment. These late complications commonly present more than 15 years after the initial spinal infection and suggest that the 15-year follow-up study by the MRC may be insufficient to reach valid long-term conclusions [8]. There is still a high incidence of neurological involvement in Pott’s disease, with rates of 10 to 20 % of cases in highly developed nations and 20 to 40 % in underdeveloped countries. Most spinal cord injuries appear in the early, acute phase of the disease. However, patients treated with drugs alone or with simple debridement without fusion may experience disease reactivation, severe kyphosis, or late instability, which in turn may lead to late-onset Pott’s paraplegia, back pain, sagittal imbalance, and compromised pulmonary function, which can be difficult and risky to treat [8]. Correction of late deformity is only feasible with demanding three-column spinal osteotomies, and posterior vertebral column resection is probably the treatment of choice in extreme kyphosis [9]. Prevention of severe spinal deformity at an early stage should therefore be the modern standard of treatment especially for high-risk patients. The present ESJ supplement provides a unique, comprehensive overview of the current status of tuberculosis and Pott’s disease, considering many of the most relevant epidemiological, diagnostic, and therapeutic aspects. In-depth study of its content, delivered by worldwide experts in the field, should serve to improve our understanding of this condition and the care for affected patients. We wish you fruitful and enjoyable reading!

Prior to 2020, treatment options for multidrug-resistant tuberculosis (MDR-TB) were limited and typically involved long treatment durations and high financial burdens. In the eastern European and central Asian (EECA) region, traditional inpatient tuberculosis (TB) care models, alongside high MDR-TB rates, escalate nosocomial transmission risks and treatment costs. Modified, fully oral, shorter treatment regimens (mSTR) implemented in the WHO European Region under operational research conditions offered a potential reduction in the burden of MDR-TB treatment for both patients and health systems. We conducted the first regional evaluation of the cost-effectiveness of the novel mSTR treatment regimen compared with the standard of care (SOC) in Belarus, Georgia, Kazakhstan and Republic of Moldova. We used cohort data on mSTR efficacy and WHO data on SOC in patients with MDR-TB. We used a Markov model, with treatment costs calculated from the provider perspective. Outcomes were measured in quality-adjusted life years (QALYs), with incremental cost-effectiveness ratios (ICER) calculated per QALY gained in each country. An annual 3% discount rate was used for both costs and outcomes. We performed univariate and probabilistic sensitivity analysis (PSA) to assess the robustness of our cost-effectiveness calculations under varying assumptions. Finally, we estimated potential cost savings if mSTR was implemented nationally and we evaluated the incremental net monetary benefit (iNMB) and willingness-to-pay (WTP) thresholds based on Wood et al's country-level cost-effectiveness thresholds. All costs were reported in 2022 USD. We estimated that mSTR can reduce TB treatment costs by between 23% and 47% and drug costs by 39% to 74%, compared with SOC in the countries studied. mSTR resulted in cost savings of between $3596 and $8174 per patient and offered additional health gains of between 0.56 to 2.69 QALYs per patient. mSTR remained cost-effective (iNMB>0) compared with SOC in 78%, 85%, 91% and 92% of PSA simulations in Belarus, Georgia, Kazakhstan and Republic of Moldova, respectively, when compared with their country-level WTP threshold. Implementing mSTR in up to 80% of MDR/rifampicin-resistant TB patients may result in cost savings of $20.5, 2.5, 0.7 and 0.2 million in Kazakhstan, Belarus, Republic of Moldova and Georgia; equivalent to 17%, 3%, 4% and 1% of their national TB budgets, respectively. Compared with SOC, mSTR is a more cost-effective treatment option for MDR/RR-TB, which should be considered by policymakers in the EECA region. Using insights from current implementations to scale up, plan operational changes and reallocate savings from mSTR could greatly enhance TB services and patient care.

Universal health coverage is essential for the progress to end threats of the acquired immunodeficiency syndrome epidemic. The current review assesses the publication rate, strategies and barriers for antiretroviral therapy (ART) coverage, equity, quality of care, and financial protection. We searched Web of Science, PubMed, and Google Scholar. Of the available articles, 43.13% were on ART coverage, 40.28% were on financial protection, 10.43% were on quality of care, and 6.16% were on equity. A lack of ART, fear of unwanted disclosure, lack of transportation, unaffordable health care costs, long waiting time to receive care, and poverty were barriers to ART coverage. Catastrophic health care costs were higher among individuals who were living in rural settings, walked greater distances to reach health care institutions, had a lower socioeconomic status, and were immunocompromised. There were challenges to the provision of quality of care, including health care providers' inadequate salary, high workload and inadequate health workforce, inappropriate infrastructure, lack of training opportunities, unclear division of responsibility, and the presence of strict auditing. In conclusion, ART coverage was below the global average, and key populations were disproportionally less covered with ART in most countries. Huge catastrophic health expenditures were observed. UHC contexts of ART will be improved by reaching people with poor socioeconomic status, delivering appropriate services, establishing a proper health workforce and service stewardship.

PurposeTo provide an overview of the tuberculosis (TB) and multi-drug resistant tuberculosis (MDR-TB) in the WHO European Region and evolution of public health response with focus on extra-pulmonary tuberculosis and Pott’s disease.MethodsAuthors reviewed regional strategic documents related to TB. The epidemiologic data were reviewed and analyzed.ResultsIn the absence of associated pulmonary TB, Pott’s disease is reported as extra-pulmonary TB (up to 47 % of all TB cases in some settings). Due to limitations of the surveillance system, the epidemiology of Pott’s disease and its treatment success are unknown. The Stop TB Strategy and Consolidated Action Plan to Prevent and Combat M/XDR-TB provide comprehensive roadmaps to address all types of TB.ConclusionsThere is a need to further analyze country data to document the extent of Pott’s disease and develop specific guidelines for timely diagnosis and treatment of Pott’s disease.

Neurological disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2016. Unpacking how this burden varies regionally and nationally is important to inform public health policy and prevention strategies. The population in the EU is older than that of the WHO European region (western, central, and eastern Europe) and even older than the global population, suggesting that it might be particularly vulnerable to an increasing burden of age-related neurological disorders. We aimed to compare the burden of neurological disorders in the EU between 1990 and 2017 with those of the WHO European region and worldwide. The burden of neurological disorders was calculated for the year 2017 as incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability for the countries in the EU and the WHO European region, totally and, separately. Diseases analysed were Alzheimer's disease and other dementias, epilepsy, headache (migraine and tension-type headache), multiple sclerosis, Parkinson's disease, brain cancer, motor neuron diseases, neuroinfectious diseases, and stroke. Data are presented as totals and by sex, age, year, location and socio-demographic context, and shown as counts and rates. In 2017, the total number of DALYs attributable to neurological disorders was 21·0 million (95% uncertainty interval 18·5-23·9) in the EU and 41·1 million (36·7-45·9) in the WHO European region, and the total number of deaths was 1·1 million (1·09-1·14) in the EU and 1·97 million (1·95-2·01) in the WHO European region. In the EU, neurological disorders ranked third after cardiovascular diseases and cancers representing 13·3% (10·3-17·1) of total DALYs and 19·5% (18·0-21·3) of total deaths. Stroke, dementias, and headache were the three commonest causes of DALYs in the EU. Stroke was also the leading cause of DALYs in the WHO European region. During the study period we found a substantial increase in the all-age burden of neurodegenerative diseases, despite a substantial decrease in the rates of stroke and infections. The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80-84 years, and varied substantially with WHO European region and country. All-age DALYs, deaths, and prevalence of neurological disorders increased in all-age measures, but decreased when using age-standardised measures in all but three countries (Azerbaijan, Turkmenistan, and Uzbekistan). The decrease was mostly attributed to the reduction of premature mortality despite an overall increase in the number of DALYs. Neurological disorders are the third most common cause of disability and premature death in the EU and their prevalence and burden will likely increase with the progressive ageing of the European population. Greater attention to neurological diseases must be paid by health authorities for prevention and care. The data presented here suggest different priorities for health service development and resource allocation in different countries. European Academy of Neurology.