Advantages and disadvantages of maintaining the mandatory use of masks in health centers and nursing homes in Spain. How and when is it justified to maintain it?

We address the advantages and disadvantages of maintaining the mandatory use of masks in health centers and nursing homes in the current epidemiological situation in Spain and after the declaration of the World Health Organization on May 5, 2023 of the end of COVID-19 as public health emergency. We advocate for prudence and flexibility, respecting the individual decision to wear a mask and emphasizing the need for its use when symptoms suggestive of a respiratory infection appear, in situations of special vulnerability (such as immunosuppression), or when caring for patients with those infections. At present, given the observed low risk of severe COVID-19 and the low transmission of other respiratory infections, we believe that it is disproportionate to maintain the mandatory use of masks in a general way in health centers and nursing homes. However, this could change depending on the results of epidemiological surveillance and it would be necessary to reconsider returning to the obligation in periods with a high incidence of respiratory infections.

Tuberculosis in Spain: An opinion paper.

This document is the result of the deliberations of the Committee on Emerging Pathogens and COVID-19 of the Illustrious Official College of Physicians of Madrid (ICOMEM) regarding the current situation of tuberculosis, particularly in Spain. We have reviewed aspects such as the evolution of its incidence, the populations currently most exposed and the health care circuits for the care of these patients in Spain. We have also discussed latent tuberculosis, the reality of extrapulmonary disease in the XXI century and the means available in daily practice for the diagnosis of both latent and active forms. The contribution of molecular biology, which has changed the perspective of this disease, was another topic of discussion. The paper tries to put into perspective both the classical drugs and their resistance figures and the availability and indications of the new ones. In addition, the reality of direct observation in the administration of antituberculosis drugs has been discussed. All this revolution is making it possible to shorten the treatment time for tuberculosis, a subject that has also been reviewed. If everything is done well, the risk of relapse of tuberculosis is small but it exists. On the other hand, many special situations have been discussed in this paper, such as tuberculosis in pediatric age and tuberculosis as a cause for concern in surgery and intensive care. The status of the BCG vaccine and its present indications as well as the future of new vaccines to achieve the old dream of eradicating this disease have been discussed. Finally, the ethical and medicolegal implications of this disease are not a minor issue and our situation in this regard has been reviewed.

Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Linezolid: an effective, safe and cheap drug for patients failing multidrug-resistant tuberculosis treatment in India.

Linezolid is identified as an effective drug with which to treat patients failing multidrug-resistant (MDR)-tuberculosis (TB) treatment. However, cost and safety are the concerns. In India, the average price of a 600-mg pill of linezolid is less than one US dollar, much cheaper than most of the third-line drugs. A prospective study of 29 MDR-TB treatment failure patients (16 with laboratory-proven extensively drug-resistant (XDR)-TB and the remaining 13 with MDR-TB with resistance to any quinolone but sensitive to injectables) was carried out in Delhi, India. All patients received daily unsupervised therapy with linezolid, one injectable agent, one fluoroquinolone and two or more other drugs. Patients received a median of six anti-mycobacterial agents. Besides linezolid, capreomycin, moxifloxacin, levofloxacin and amoxycillin-clavulanic acid were used in 41.4%, 58.6%, 41.4%, and 79.3% of patients. Out of a total of 29 patients, 89.7% patients achieved sputum smear and culture conversion; 72.4% showed interim favourable outcome; 10.3% died, 6.8% failed and 10.3% patients defaulted. Linezolid had to be stopped in three (10.3%) patients due to adverse reactions. The outcome of treatment of 16 XDR-TB patients was comparable to the other 13 MDR-TB patients. Linezolid is an effective, cheap and relatively safe drug for patients failing MDR-TB treatment, including those with confirmed XDR-TB.

European union standards for tuberculosis care.

The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society (ERS) jointly developed European Union Standards for Tuberculosis Care (ESTC) aimed at providing European Union (EU)-tailored standards for the diagnosis, treatment and prevention of tuberculosis (TB). The International Standards for TB Care (ISTC) were developed in the global context and are not always adapted to the EU setting and practices. The majority of EU countries have the resources and capacity to implement higher standards to further secure quality TB diagnosis, treatment and prevention. On this basis, the ESTC were developed as standards specifically tailored to the EU setting. A panel of 30 international experts, led by a writing group and the ERS and ECDC, identified and developed the 21 ESTC in the areas of diagnosis, treatment, HIV and comorbid conditions, and public health and prevention. The ISTCs formed the basis for the 21 standards, upon which additional EU adaptations and supplements were developed. These patient-centred standards are targeted to clinicians and public health workers, providing an easy-to-use resource, guiding through all required activities to ensure optimal diagnosis, treatment and prevention of TB. These will support EU health programmes to identify and develop optimal procedures for TB care, control and elimination.

Clinical standards for drug-susceptible pulmonary TB.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

Spontaneous pneumothorax and tuberculosis: long-term follow-up.

Though spontaneous pneumothorax (SP) is a well-known complication of pulmonary tuberculosis (TB), there are very few reports addressing this topic. For this reason, we retrospectively analysed the experience of SP in patients diagnosed with TB in our hospital between 1989 and 2010. Out of 872 patients treated for SP during this period, 47 (5.4%) had TB antecedents, 21 with active TB (0.95% of the 2,089 TB cases diagnosed during this period) and 26 with residual inactive TB. 46 cases were treated with pleural drainage (PD): 40 (85%) with only one PD, two with two, and four with three. The mean ± SD length of PD treatment was 12.9 ± 11.3 days. In 11 (23%) cases, a relapse of SP occurred, with no statistical relationship between the different studied variables. In 13 (28%) cases, it became necessary to carry out a resection (atypical segmentectomy in all cases) for persistent air leaks with PD. Survival statistics were unfavourable only in elderly patients and those infected with HIV. We conclude that the treatment of SP secondary to TB with PD is usually a sound response, with a good general prognosis and a low percentage of cases that require another PD and surgical treatment.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Risk factors for early mortality in patients with pulmonary tuberculosis admitted to the emergency room.

BACKGROUND AND OBJECTIVES: Mortality of patients with pulmonary tuberculosis (TB) admitted to emergency departments is high. This study was aimed at analysing the risk factors associated with early mortality and designing a risk score based on simple parameters. METHODS: This prospective case-control study enrolled patients admitted to the emergency department of a referral TB hospital. Clinical, radiological, biochemical and microbiological risk factors associated with death were compared among patients dying within one week from admission (cases) and those surviving (controls). RESULTS: Forty-nine of 250 patients (19.6%) experienced early mortality. Multiple logistic regression analysis showed that oxygen saturation (SaO2) ≤90%, severe malnutrition, tachypnoea, tachycardia, hypotension, advanced disease at chest radiography, severe anaemia, hyponatremia, hypoproteinemia and hypercapnia were independently and significantly associated with early mortality. A clinical scoring system was further designed to stratify the risk of death by selecting five simple parameters (SpO2 ≤ 90%, tachypnoea, hypotension, advanced disease at chest radiography and tachycardia). This model predicted early mortality with a positive predictive value of 94.88% and a negative predictive value of 19.90%. CONCLUSIONS: The scoring system based on simple parameters may help to refer severely ill patients early to a higher level to reduce mortality, improve success rates, minimise the need for pulmonary rehabilitation and prevent post-treatment sequelae.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Evolution in the resistance of Mycobacterium tuberculosis to anti-tuberculosis drugs in Nicaragua.

SETTING: Nicaragua, a country where the DOTS strategy has been successfully implemented since 1984. OBJECTIVE: To estimate the prevalence and trends of Mycobacterium tuberculosis resistance to first-line anti-tuberculosis drugs. DESIGN: A prospective national survey carried out in 2004 according to the standardised model developed by the World Health Organisation and the International Union Against Tuberculosis and Lung Disease. RESULTS: A total of 423 M. tuberculosis strains were studied. Among the 320 strains evaluated for initial resistance, 13.1% displayed resistance to any drug, lower than the 1998 figure of 15.6%. Overall initial resistance to isoniazid (INH), rifampicin (RMP) and multidrug resistance (MDR) was respectively 6.6%, 0.9% and 0.6%. Initial resistance was higher in older age groups. Overall acquired resistance was 35.9% (n = 103); resistance to INH was 29.3% and to RMP 8.9%, while MDR was 7.9%. The acquired MDR rate was clearly higher in Category I failures (44.4%) than in relapses (3.8%) and retrieved defaulters (2.7%). All resistance rates found in this study were lower than those detected in 1998. CONCLUSION: This study shows low rates of resistance and MDR and a downward trend in all rates, undoubtedly related to the proper implementation of the National Tuberculosis Programme.

Isoniazid preventive therapy for people living with HIV: public health challenges and implementation issues.

Isoniazid preventive therapy (IPT) is recognised as an important component of collaborative tuberculosis (TB) and human immunodeficiency virus (HIV) activities to reduce the burden of TB in people living with HIV (PLHIV). However, there has been little in the way of IPT implementation at country level. This failure has resulted in a recent call to arms under the banner title of the 'Three I's' (infection control to prevent nosocomial transmission of TB in health care settings, intensified TB case finding and IPT). In this paper, we review the background of IPT. We then discuss the important challenges of IPT in PLHIV, namely responsibility and accountability for the implementation, identification of latent TB infection, exclusion of active TB and prevention of isoniazid resistance, length of treatment and duration of protective efficacy. We also highlight several research questions that currently remain unanswered. We finally offer practical suggestions about how to scale up IPT in the field, including the need to integrate IPT into a package of care for PLHIV, the setting up of operational projects with the philosophy of 'learning while doing', the development of flow charts for eligibility for IPT, the development and implementation of care prior to antiretroviral treatment, and finally issues around procurement, distribution, monitoring and evaluation. We support the implementation of IPT, but only if it is done in a safe and structured way. There is a definite risk that 'sloppy' IPT will be inefficient and, worse, could lead to the development of multidrug-resistant TB, and this must be avoided at all costs.

Curving Tuberculosis: Current Trends and Future Needs.

Tuberculosis (TB) presents new challenges as a global public health problem, especially at a time of increasing threats to some particular patients due to Human Immunodeficiency Virus (HIV) infection and multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. The World Health Assembly strives to reduce TB deaths by 95% and to decrease TB incidence by 95% by 2035. However, new approaches are necessary in order to attain these objectives. Such approaches include active ascertainment of cases in high risk populations, increasing the availability of accurate point-of-care testing, rapid detection of drug resistance, novel vaccines, and new prophylaxis and treatment regimens (particularly for MDR and XDR TB). The ultimate objective of those programs is to develop highly effective drug regimens that can achieve high cure rates regardless of strains' resistance patterns.

Likelihood of generating MDR-TB and XDR-TB under adequate National Tuberculosis Control Programme implementation.

The most frequent factors associated with selection of resistance at the community level and the generation of multidrug-resistant tuberculosis (MDR-TB) under epidemic conditions have been described in the last decades. These factors are multiple, and it is often a combination of these that has been implicated in the origin of MDR-TB epidemics in specific zones or countries. The analysis of and correct approach to the causes should be the first and most important step in the fight against this critical problem. However, it has never been investigated whether specific circumstances, even under adequate implementation of a National TB Control Programme (NTP), could lead to selection or amplification of resistance. The NTP should consider explanations for when there is no decline in MDR-TB rates even after appropriate control measures have been implemented. Under the special circumstances analysed in this article, the World Health Organization (WHO) Category I regimen can amplify resistance to rifampicin (in initial isoniazid-resistant cases) or ethambutol (EMB) + pyrazinamide (in initial MDR-TB cases). The WHO Category II regimen can also amplify resistance to EMB or streptomycin. The subsequent addition of the only second-line drugs available in many countries (fluoroquinolones and/or injectables) can worsen the situation and generate extensively drug-resistant TB. Strategies for minimising these risks of amplifying resistance are discussed in this article.

Tuberculosis drug resistance in Southern Mozambique: results of a population-level survey in the district of Manhiça.

SETTING: Mozambique, one of the world's high tuberculosis (TB) burden countries, has conducted only one national-level drug resistance survey, in 2007-2008. OBJECTIVE: To determine the drug resistance patterns of laboratory-confirmed TB cases. DESIGN: This was a population-level survey conducted over a 1-year period in the district of Manhiça. All laboratory-confirmed cases were evaluated for first-line anti-tuberculosis drug susceptibility testing using liquid culture. RESULTS: Resistance to at least one first-line drug was observed in 44 of 276 isolates (15.9%). Prevalence of drug resistance to each of the five anti-tuberculosis drugs tested was 4.0% for streptomycin, 10.1% for isoniazid (INH), 6.2% for rifampicin, 3.6% for ethambutol and 1.1% for pyrazinamide. The overall prevalence of multidrug-resistant TB (MDR-TB) was 5.1%: 3.8% (95%CI 2.0-7.0) in new and 13.2% (95%CI 5.8-27.3) in retreatment cases. Respectively 4.6% and 2.6% of new and retreatment cases were INH-monoresistant. Previous history of anti-tuberculosis treatment was associated with having MDR-TB (OR 4.3, 95%CI 1.3-14.1). CONCLUSION: The prevalence of drug resistance in the district of Manhiça is slightly higher than, but still compatible with, previous national estimates. INH monoresistance was high, posing the risk of hidden monotherapy in the continuation phase.

Treatment of multidrug-resistant tuberculosis: evidence and controversies.

In the last decade, multidrug-resistant tuberculosis (MDR-TB, defined as resistance to at least isoniazid and rifampicin) has become an epidemiological issue of first priority at the global level. Case management needs to be simplified and standardised, as in many countries MDR-TB cases cannot receive individualised attention from specialist physicians. However, before any decision can be made on standardisation, a careful analysis must first be made of the evidence and controversies behind the various published recommendations. Unfortunately, the controversies outweigh the evidence. The difficulties lie not only in the absence of controlled trials to validate specific recommendations, but also in the very different and even contradictory results found in the literature. It is therefore essential to analyse these discrepancies before developing rational, uniform recommendations. The analysis should encompass the most essential and controversial issues regarding the management of MDR-TB patients: 1) confirmation of diagnosis in a suspected MDR-TB patient, and determination of the value of drug susceptibility testing; 2) the number of anti-tuberculosis drugs required to treat MDR-TB; 3) the most rational use of effective drugs against tuberculosis; 4) the advisable length of parenteral drug administration or of the initial phase of treatment; 5) the contribution of surgery to the management of MDR-TB patients; and 6) the optimal regimen for treating MDR-TB: standardised vs. individualised regimens. The evidence and controversies regarding each of the above questions are analysed with the aim of facilitating decision making in the treatment of these complex patients.

[Controversies in the treatment of extrapulmonary tuberculosis]. / Controversias en el tratamiento de la tuberculosis extrapulmonar.

Tuberculosis (TB) can spread to any tissue or organ of the body by way of hematogenous or lymphatic dissemination or contiguity. However, pulmonary TB is the most common presentation and the only form of the disease of epidemiologic importance. Consequently, the literature on the various forms of extrapulmonary TB (EPTB) is scant, and most of the published authors are specialists in specific extrapulmonary forms. As a result, in most of the major areas of study of EPTB, recommendations similar to those for pulmonary TB or others based on little or no evidence have been accepted. This lack of evidence is of particular concern in the case of treatment guidelines. The present article reviews important work that has given rise to current treatment guidelines. While most of these guidelines reveal the lack of evidence available on this subject, it can, nevertheless, be concluded that a 6-month treatment regimen similar to that used in patients with pulmonary TB may be sufficient to treat all forms of EPTB, including meningeal disease. The role of steroids and surgery in the treatment of TB affecting different sites is also discussed. Other topics dealt with are the considerations that should be taken into account and the treatment modifications necessary in patients infected with the human immunodeficiency virus.

Detection of katG and inhA mutations to guide isoniazid and ethionamide use for drug-resistant tuberculosis.

BACKGROUND: Depending on the presence of mutations that determine isoniazid (INH) susceptibility (katG and inhA), Mycobacterium tuberculosis may be susceptible to high doses of INH or ethionamide (ETH). OBJECTIVE: To describe the INH resistance profile and association of katG mutation with previous INH treatment and level of drug resistance based on rapid molecular drug susceptibility testing (DST) in southern Brazil and central Mozambique. DESIGN: Descriptive study of 311 isolates from Ribeirão Preto, São Paulo, Brazil (2011-2014) and 155 isolates from Beira, Mozambique (2014-2015). Drug resistance patterns and specific gene mutations were determined using GenoType(®) MTBDRplus. RESULTS: katG gene mutations were detected in 12/22 (54.5%) Brazilian and 32/38 (84.2%) Mozambican isolates. inhA mutations were observed in 9/22 (40.9%) isolates in Brazil and in 4/38 (10.5%) in Mozambique. Both katG and inhA mutations were detected in respectively 1/22 (5%) and 2/38 (5.2%). The difference in the frequency of katG mutations in Brazil and Mozambique was statistically significant (P = 0.04). katG mutations were present in 68.8% (33/48) of patients previously treated with INH and 31.2% (15/48) of patients without previous INH. This difference was not statistically significant (P = 0.223). CONCLUSION: INH mutations varied geographically; molecular DST can be used to guide and accelerate decision making in the use of ETH or high doses of INH.

Factors Associated with Fatality during the Intensive Phase of Anti-Tuberculosis Treatment.

OBJECTIVE: To determine the case-fatality rate (CFR) at the end of the intensive phase of tuberculosis (TB) treatment, and factors associated with fatality. METHODS: TB patients diagnosed between 2006 and 2013 were followed-up during treatment. We computed the CFR at the end of the intensive phase of TB treatment, and the incidence of death per 100 person-days (pd) of follow-up. We performed survival analysis using the Kaplan-Meier method and Cox regression, and calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: A total of 5,182 patients were included, of whom 180 (3.5%) died; 87 of these deaths (48.3%) occurred during the intensive phase of treatment, with a CFR of 1.7%. The incidence of death was 0.028/100 pd. The following factors were associated with death during the intensive phase: being >50 years (HR = 36.9;CI:4.8-283.4); being retired (HR = 2.4;CI:1.1-5.1); having visited the emergency department (HR = 3.1;CI:1.2-7.7); HIV infection (HR = 3.4;CI:1.6-7.2); initial standard treatment with 3 drugs (HR = 2.0;CI:1.2-3.3) or non-standard treatments (HR = 2.68;CI:1.36-5.25); comprehension difficulties (HR = 2.8;CI:1.3-6.1); and smear-positive sputum (HR = 2.3-CI:1.0-4.8). CONCLUSION: There is a non-negligible CFR during the intensive phase of TB, whose reduction should be prioritised. The CFR could be a useful indicator for evaluating TB programs.

Results of a national study on anti-mycobacterial drug resistance in El Salvador.

SETTING: The DOTS strategy was introduced in El Salvador in 1997 and had become fully implemented countrywide by 2001. Previously, many deficiencies were identified in the management of patients with tuberculosis (TB). OBJECTIVE: To ascertain the prevalence of Mycobacterium tuberculosis resistant to first-line drugs. DESIGN: A national prospective survey was carried out in 2001 using the standardised World Health Organization/ International Union Against Tuberculosis and Lung Disease model. RESULTS: A total of 711 cultures were analysed (59% of total smear-positive cases); 611 were never treated and 100 were previously treated patients. The study showed resistance rates to isoniazid and rifampicin, either alone or combined (multidrug resistance, MDR), of 1.3%, 1.1% and 0.3%, respectively, in never treated patients, and 12%, 13% and 7%, respectively, in previously treated patients. CONCLUSION: The low rates of MDR-TB in El Salvador are puzzling, as out-patient DOTS was introduced only recently and fixed-dose combination tablets have not been used.