Tuberculosis Experts Research Articles

A Collaborative Approach for “ReSeq-ing” Mycobacterium tuberculosis Drug Resistance: Convergence for Drug and Diagnostic Developers

A Collaborative Approach for “ReSeq-ing” Mycobacterium tuberculosis Drug Resistance: Convergence for Drug and Diagnostic Developers

Tuberculosis among migrant populations in the European Union and the European Economic Area.

Background: Although tuberculosis (TB) incidence has been decreasing in the European Union/European Economic Area (EU/EEA) in the last decades, specific subgroups of the population, such as migrants, remain at high risk of TB. This study is based on the report ‘Key Infectious Diseases in Migrant Populations in the EU/EEA’ commissioned by The European Centre for Disease Prevention and Control. Methods: We collected, critically appraised and summarized the available evidence on the TB burden in migrants in the EU/EEA. Data were collected through: (i) a comprehensive literature review; (ii) analysis of data from The European Surveillance System (TESSy) and (iii) evidence provided by TB experts during an infectious disease workshop in 2012. Results: In 2010, of the 73 996 TB cases notified in the EU/EEA, 25% were of foreign origin. The overall decrease of TB cases observed in recent years has not been reflected in migrant populations. Foreign-born people with TB exhibit different socioeconomic and clinical characteristics than native sufferers. Conclusion: This is one of the first studies to use multiple data sources, including the largest available European database on infectious disease notifications, to assess the burden and provide a comprehensive description and analysis of specific TB features in migrants in the EU/EEA. Strengthened information about health determinants and factors for migrants’ vulnerability is needed to plan, implement and evaluate targeted TB care and control interventions for migrants in the EU/EEA.

Current Treatment Options in Tuberculosis

Tuberculosis (TB) is a leading cause of morbidity and ranks among the ten most common causes of death worldwide. Due to the wide range of clinical pictures TB can cause, diagnosis is often difficult and, especially in low-incidence countries, is sometimes underestimated. Therefore, it is important to consider the diagnosis of TB, especially in immunocompromised patients, and contact TB experts if diagnosis is unclear. Since the emergence of resistant strains is increasing, it is important to test resistance once TB is diagnosed. A drug-susceptible TB is treated with a standard 6-month chemotherapy regimen using a combination of four drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months followed by rifampicin and isoniazid for 4 months) according to the current guidelines. With this treatment, cure rates of approximately 90 % can be achieved. Because of adverse effects, drug–drug interactions, and sometimes reduced compliance towards treatment, regular clinical and laboratory monitoring of patients under TB treatment is required. Drug-resistant TB should only be treated by experienced infectious disease specialists. In patients with a positive interferon-γ release assay or tuberculin skin test without clinical signs of active disease, latent TB should be considered and the need for chemoprevention has to be evaluated. Fortunately, promising new drugs are currently in the development pipeline that, after careful evaluation in clinical studies, may lead to shortened treatment regimens in the future. BCG (Bacillus Calmette–Guerin) vaccine is still the only available vaccine with a >50 % efficacy for protection against progression from infection to active disease. New vaccines are currently under investigation.

Facing multi-drug resistant tuberculosis

Multi-drug resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis strains resistant to at least two of the most effective anti-tuberculosis drugs (i.e., isoniazid and rifampicin). Therapeutic regimens based on second- and third-line anti-tuberculosis medicines showed poor efficacy, safety, and tolerability profiles. It was estimated that in 2012 the multi-drug resistant tuberculosis incidence ranged from 300,000 to 600,000 cases, mainly diagnosed in the Eastern European and Central Asian countries. The highest proportion of cases is among individuals previously exposed to anti-tuberculosis drugs. Three main conditions can favour the emergence and spread of multi-drug resistant tuberculosis: the poor implementation of the DOTS strategy, the shortage or the poor quality of the anti-tuberculosis drugs, and the poor therapeutic adherence of the patients to the prescribed regimens.Consultation with tuberculosis experts (e.g., consilium) is crucial to tailor the best anti-tuberculosis therapy.New therapeutic options are necessary: bedaquiline and delamanid seem promising drugs; in particular, during the development phase they demonstrated a protective effect against the emergence of further resistances towards the backbone drugs. In the recent past, other antibiotics have been administered off-label: the most relevant efficacy, safety, and tolerability profile was proved in linezolid-, meropenem/clavulanate-, cotrimoxazole-containing regimens.New research and development activities are needed in the diagnostic, therapeutic, preventive fields.

Diagnosis and Management of Tuberculosis in Candidates for Tumor Necrosis Factor Alpha Antagonists: An Experts Survey

Background: There are some controversies regarding the management of latent tuberculosis infection and tuberculosis in patients with rheumatologic indications for biologic therapy. Objectives: To describe current expert opinions and preferences regarding the evaluation and management of latent tuberculosis infection and tuberculosis in candidates and recipients of tumor-necrosis factor-alpha blocking therapy. Methods: A questionnaire addressing preferences related to management and treatment of latent tuberculosis infection and active tuberculosis in tumor-necrosis factor-alpha blocking candidates was distributed to tuberculosis and rheumatology experts across the United States between August 18, 2009, and June 21, 2010. Survey responses were formulated as a 5-point Likert scale (strongly disagree to strongly agree), or as a priority rank order list (1 to 6 or 7), and data were analyzed for percent agreement and median rankings. Measurements and main results: The tuberculin skin test and interferon-gamma release assays for latent tuberculosis infection screening were highly accepted among tuberculosis and rheumatology experts. Most participants supported the use of daily isoniazid for 9 months for latent tuberculosis infection therapy, but responses were mixed regarding timing to initiation of tumor-necrosis factor-alpha blocking therapy. Most tuberculosis experts supported standard anti-tuberculosis therapy for treatment of tuberculosis, but preferences varied among rheumatologists. In contrast, most rheumatologists believed tumor-necrosis factor-alpha blocking therapy should be stopped in individuals with active tuberculosis, while opinions varied among tuberculosis experts. Conclusions: Agreement among experts was common regarding preferences for diagnosis and management of latent tuberculosis infection and tuberculosis under hypothetical but likely common clinical scenarios, but some differences exist.

Development and Initial Testing of Messages to Encourage Tuberculosis Testing and Treatment Among Bacille Calmette-Guerin (BCG) Vaccinated Persons

Misperceptions surrounding the Bacille Calmette-Guerin (BCG) vaccine can lead some vaccinated individuals to resist being tested and treated for tuberculosis (TB). Educational messages to best explain the risk of TB to BCG-vaccinated, Hispanic persons were systematically developed and tested. First, TB program staff provided messages they considered effective. These were analyzed and validated by TB experts, and then presented in group interviews initially to foreign-born Hispanic persons with a TB diagnosis, and then persons without a prior TB diagnosis. Based on interviewees' feedback, preferred statements were used to develop one long and three short comprehensive messages. One-on-one interviews were conducted with Hispanic persons to assess the saliency of the comprehensive educational messages. Participants preferred messages that were gain or positively-framed and explained that BCG does not confer lifelong protection against TB. Participants confirmed the messages would likely have a positive impact on patient decisions to undergo TB testing and treatment.

The National Tuberculosis Surveillance System Training Program to Ensure Accuracy of Tuberculosis Data

The Centers for Disease Control and Prevention implemented a national training program for health care workers and surveillance staff to ensure accuracy of data reported to the Centers for Disease Control and Prevention's National Tuberculosis Surveillance System and increase training capacity in tuberculosis surveillance. To address the changing epidemiology of tuberculosis and related reporting requirements, a working group of tuberculosis experts revised the Report of Verified Case of Tuberculosis (RVCT), the National Tuberculosis Surveillance System data collection form. The revision prompted a need for training in accurately completing the form. A Centers for Disease Control and Prevention interdisciplinary training team collaborated with key partners in assessing health care worker training needs regarding the RVCT. The team conducted 5 field tests to ensure instructional effectiveness of the training materials. Participants worked through materials, shared experiences, asked questions, and stated concerns about the RVCT. On the basis of these inputs, the team developed an innovative and comprehensive training program. The training materials included instructions for completing each item on the RVCT form, case studies to enable participants to apply the instructions to real-life situations, and visual aids to enhance learning. In both quantitative and qualitative responses, participants indicated that the RVCT training course and self-study materials helped them gain the knowledge needed to accurately complete the RVCT. The team conducted 14 facilitator-led courses and trained 343 health care workers and surveillance staff; 82 of these were training-of-trainers participants. Collaboration and innovation are essential in implementing an effective national surveillance-training program to ensure the accurate collection and reporting of tuberculosis surveillance data.

British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children

SUMMARY AND KEY RECOMMENDATIONS: The aim of these guidelines is to describe a practical but evidence-based approach to the diagnosis and treatment of central nervous system tuberculosis in children and adults. We have presented guidance on tuberculous meningitis (TBM), intra-cerebral tuberculoma without meningitis, and tuberculosis affecting the spinal cord. Our key recommendations are as follows: 1. TBM is a medical emergency. Treatment delay is strongly associated with death and empirical anti-tuberculosis therapy should be started promptly in all patients in whom the diagnosis of TBM is suspected. Do not wait for microbiological or molecular diagnostic confirmation. 2. The diagnosis of TBM is best made with lumbar puncture and examination of the cerebrospinal fluid (CSF). Suspect TBM if there is a CSF leucocytosis (predominantly lymphocytes), the CSF protein is raised, and the CSF:plasma glucose is <50%. The diagnostic yield of CSF microscopy and culture for Mycobacterium tuberculosis increases with the volume of CSF submitted; repeat the lumbar puncture if the diagnosis remains uncertain. 3. Imaging is essential for the diagnosis of cerebral tuberculoma and tuberculosis involving the spinal cord, although the radiological appearances do not confirm the diagnosis. A tissue diagnosis (by histopathology and mycobacterial culture) should be attempted whenever possible, either by biopsy of the lesion itself, or through diagnostic sampling from extra-neural sites of disease e.g. lung, gastric fluid, lymph nodes, liver, bone marrow. 4. Treatment for all forms of CNS tuberculosis should consist of 4 drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months followed by 2 drugs (isoniazid, rifampicin) for at least 10 months. Adjunctive corticosteroids (either dexamethasone or prednisolone) should be given to all patients with TBM, regardless of disease severity. 5. Children with CNS tuberculosis should ideally be managed by a paediatrician with familiarity and expertise in paediatric tuberculosis or otherwise with input from a paediatric infectious diseases unit. The Children's HIV Association of UK and Ireland (CHIVA) provide further guidance on the management of HIV-infected children (www.chiva.org.uk). 6. All patients with suspected or proven tuberculosis should be offered testing for HIV infection. The principles of CNS tuberculosis diagnosis and treatment are the same for HIV infected and uninfected individuals, although HIV infection broadens the differential diagnosis and anti-retroviral treatment complicates management. Tuberculosis in HIV infected patients should be managed either within specialist units by physicians with expertise in both HIV and tuberculosis, or in a combined approach between HIV and tuberculosis experts. The co-administration of anti-retroviral and anti-tuberculosis drugs should follow guidance issued by the British HIV association (www.bhiva.org).

Development of a tuberculosis education booklet for Latino immigrant patients

The incidence and prevalence of tuberculosis are far more common among third world populations immigrating to the United States than among US-born citizens. Immigrants’ failure to comply with an anti-tuberculosis treatment can impede completion of care and further confound this public health problem. Barriers to patient–provider communication can negatively influence adherence to a medical regimen. Patients who are unable to comprehend medical advice and do not see it as personally salient are less likely to follow their provider’s medical advice. In this paper, the authors focus on efforts to develop a patient education tool targeting Spanish-speaking Latino immigrant patients to facilitate communication with tuberculosis clinicians. A description of the multi-stage developmental processes is presented including conducting a needs assessment, development of visual and written messages, review/critique by tuberculosis experts, field-testing, revisions, and distribution. Formative evaluation and field testing indicates promise for improving communication using this tool.

Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project.

To estimate the risk and prevalence of Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB) incidence, prevalence, and mortality, including disease attributable to human immunodeficiency virus (HIV), for 212 countries in 1997. A panel of 86 TB experts and epidemiologists from more than 40 countries was chosen by the World Health Organization (WHO), with final agreement being reached between country experts and WHO staff. Incidence of TB and mortality in each country was determined by (1) case notification to the WHO, (2) annual risk of infection data from tuberculin surveys, and (3) data on prevalence of smear-positive pulmonary disease from prevalence surveys. Estimates derived from relatively poor data were strongly influenced by panel member opinion. Objective estimates were derived from high-quality data collected recently by approved procedures. Agreement was reached by (1) participants reviewing methods and data and making provisional estimates in closed workshops held at WHO's 6 regional offices, (2) principal authors refining estimates using standard methods and all available data, and (3) country experts reviewing and adjusting these estimates and reaching final agreement with WHO staff. In 1997, new cases of TB totaled an estimated 7.96 million (range, 6.3 million-11.1 million), including 3.52 million (2.8 million-4.9 million) cases (44%) of infectious pulmonary disease (smear-positive), and there were 16.2 million (12.1 million-22.5 million) existing cases of disease. An estimated 1.87 million (1.4 million-2.8 million) people died of TB and the global case fatality rate was 23% but exceeded 50% in some African countries with high HIV rates. Global prevalence of MTB infection was 32% (1.86 billion people). Eighty percent of all incident TB cases were found in 22 countries, with more than half the cases occurring in 5 Southeast Asian countries. Nine of 10 countries with the highest incidence rates per capita were in Africa. Prevalence of MTB/HIV coinfection worldwide was 0.18% and 640000 incident TB cases (8%) had HIV infection. The global burden of tuberculosis remains enormous, mainly because of poor control in Southeast Asia, sub-Saharan Africa, and eastern Europe, and because of high rates of M tuberculosis and HIV coinfection in some African countries.

Compliance with tuberculosis drug regimens: incentives and enablers offered by public health departments.

This research examined incentives implemented by public health departments to encourage tuberculosis patients to comply with tuberculosis drug regimens. A questionnaire addressing incentives was mailed to the directors of each state's health department during May 1995. All 50 states and the District of Columbia returned questionnaires. The survey results indicate that public health departments in almost all states are implementing the incentives advocated by tuberculosis experts. The implementation of these incentives may help to explain why the incidence of tuberculosis resumed its long-term decline in the United States during 1993 after a decade of resurgence.

Tuberculosis in sub-Saharan Africa: A regional assessment of the impact of the human immunodeficiency virus and National Tuberculosis Control Program quality

Background: The effect of the human immunodeficiency virus (HIV) epidemic on tuberculosis (TB) has been evaluated for certain countries in sub-Saharan Africa. However, no multi-country comparisons have been performed of the magnitude of the changes in TB case rates and the roles of the HIV epidemic and national TB control program (NTP) quality in these changes. Methods: We examined trends in TB case rates after 1985 for 20 sub-Saharan African countries, and also from 1975–1984 for 10 of these countries (core countries). Average annual changes in TB case rates after 1985 were stratified by 1992 urban low-risk HIV seroprevalence and by NTP quality, as determined by a survey of international TB experts. Results: Case rates in the core countries decreased by an average of −1.6% per year prior to 1985, but increased by an average of +7.0% per year after 1985 (+7.7% per year after 1985 in all 20 countries). Average annual case rates after 1985 increased approximately twice as fast in countries with high vs low or intermediate HIV seroprevalence ratings. In both the core countries and all 20 countries, the average annual rate of rise in case rates after 1985 decreased as NTP quality rating increased. This relationship persisted even after stratification by HIV seroprevalence rating. Conclusions: TB case rates have increased in sub-Saharan Africa since 1985. These increases were relatively greater as HIV seroprevalence increased, and relatively lower as NTP quality increased. Improving NTP quality is essential to mitigate the resurgence of TB in the HIV era.