Challenges and opportunities to prevent tuberculosis in people living with HIV in low-income countries.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

Team approach to manage difficult-to-treat TB cases: Experiences in Europe and beyond.

As recommended by the World Health Organization (WHO), optimal management of MDR-TB cases can be ensured by a multi-speciality consultation body known as 'TB Consilium'. This body usually includes different medical specialities, competences and perspectives (e.g., clinical expertise both for adults and children; surgical, radiological and public health expertise; psychological background and nursing experience, among others), thus lowering the risk of making mistakes - or managing the patients inappropriately, in order to improve their clinical outcomes. At present, several high MDR-TB burden countries in the different WHO regions (and beyond) have introduced TB Consilium-like bodies at the national or subnational level to reach consensus on the best treatment approach for their patients affected by TB. In addition, in countries/settings where a formal system of consultation does not exist, specialized staff from MDR-TB reference centres or international organizations usually spend a considerable amount of their working time responding to phone or e-mail clinical queries on how to manage M/XDR-TB cases. The aim of this manuscript is to describe the different experiences with the TB Consilia both at the international level (European Respiratory Society - ERS/WHO TB Consilium) and in some of the countries where this experience operates successfully in Europe and beyond. The Consilium experiences are described around the following topics: (1) history, aims and focus; (2) management and funding; (3) technical functioning and structure; (4) results achieved. In addition a comparative analysis of the TB Consilia in the different countries has been performed.

Comparison of bacteriological conversion and treatment outcomes among MDR-TB patients with and without diabetes in Mexico: Preliminary data.

Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). However, it is not known to what extent DM affects the outcome in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) treated with second-line anti-TB drugs. The objective of this study was to compare the microbiological evolution (sputum smear and culture conversion) and final outcomes of MDR/XDR-TB patients with and without DM, managed at the national TB reference centre in Mexico City. RESULTS: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (e.g. MDR-TB with additional resistance to one injectable drug or a fluoroquinolone, 12.2%) and 6 (6.7%) with XDR-TB. Out of these, 49 (54.4%) had DM and 42 (86%) were undergoing insulin treatment. No statistically significant differences were found in treatment outcomes comparing DM vs. non-DM MDR-TB cases: 18/32 (56.3%) of DM cases and 19/24 (79.2%) non DM patients achieved treatment success (p=0.07). The time to sputum smear and culture conversion was longer (although not statistically) in patients without DM, as follows: the mean (±SD) time to sputum smear conversion was 53.9 (±31.4) days in DM patients and 65.2 (±34.8) days in non-DM ones (p=0.15), while the time to culture conversion was 66.2 (±27.6) days for DM and 81.4 (±37.7) days for non-DM MDR-TB cases (p=0.06). CONCLUSIONS: The study results support the Mexican National TB programme to strengthen its collaboration with the DM programme, as an entry point for TB (and latent TB infection) screening and management.

Update on the diagnosis and treatment of pulmonary tuberculosis.

Tuberculosis (TB) remains the most important human infectious disease. Currently, the TB diagnosis is still based on the clinical presentation, radiographic findings and microbiological results; all of which have sensitivity or specificity issues. For that reason, the immediate future involves rapid molecular microbiological techniques, in particular GeneXpert (which is more sensitive than bacilloscopy and is able to detect rifampicin resistance) and GenoType. The current six-month treatment for TB has remained unchanged for decades. Attempts to shorten this treatment have failed. In recent years, new drugs have been reported that could contribute to TB treatment in the near future, and are already being used in multi-drug-resistance TB.

Actualización en el tratamiento de la tuberculosis / Update in the Treatment of Tuberculosis

La tuberculosis (TB) acabó convirtiéndose en una enfermedad curable hace ya casi 60 años, con el descubrimiento de diversos fármacos con acción frente a Mycobacterium tuberculosis. Los estudios realizados entonces llegaron a la conclusión de que todo tratamiento de la TB debe fundamentarse en 2 grandes bases bacteriológicas, la asociación de fármacos para evitar la selección de resistencias y la necesidad de tratamientos prolongados para poder matar a todos los bacilos en sus diferentes fases de crecimiento metabólico. Razonamientos microbiológicos efectuados en las décadas de 1950a 1970 llevaron a la conclusión de que el mejor tratamiento que se puede administrar a una TB sensible es 2HRZ/4HR, aunque, cómo en extensas zonas del mundo se han utilizado los fármacos indiscriminadamente, a no ser que se demuestre que la resistencia inicial a isoniacida (H) es menor del 4% (en escasas zonas del mundo), siempre se debe asociar el etambutol (E) durante los 2 primeros meses. También ha sido probado que si no se realiza una supervisión estricta de la medicación durante todo el tratamiento, se corre un elevado riesgo de selección de resistencia a (rifampicina) R. Es por ello que, al menos en aquellos enfermos que pertenecen a grupos de riesgo de poder abandonar el tratamiento, este se debe dar en supervisión directa por el personal de salud. No obstante, este tratamiento farmacológico de la TB, altamente efectivo, ha pasado por múltiples retos a lo largo de las últimas 2-3décadas, sobre todo por la aparición de las resistencias a los diferentes fármacos que se han ido utilizando. Sin embargo, incluso los enfermos con diferentes patrones de resistencia tienen una importante(..) (AU)

Tuberculosis (TB) became a curable disease about 60 years ago with the discovery of a variety of medications that could act against mycobacterium tuberculosis. The studies carried out at the time reached the conclusion that all treatment of TB should be based on two large bacteriological bases, the association of drugs to avoid the selection of resistances and the necessity of prolonged treatments, to be able to kill to all the bacilli in their different phases of metabolic growth. Microbiological reasoning between 1950 and 1970 led to the conclusion that the best treatment that can be administered to a sensitive TB is 2HRZ/4HR. However, being that in extensive areas of the world the drugs have been used indiscriminately, unless it can be proven that the initial resistance to isoniacid (H) is less than 4%(in few areas of the world), it must always be associated with etambutol (E) during the first 2 months. It has also been proven that ifa strict supervision of the medication during the whole treatment is not carried out, there is a high selection risk of resistance torifampicine (R). This is why, at least in those patients who belong to groups at risk of abandoning the treatment this must be give nunder direct supervision by the health care personnel. Nevertheless, this highly effective pharmacological treatment of TB has faced multiple challenges throughout the last two or three decades, above all due to the appearance of resistances to the various drugs that have been used. However, even the patients with different resistance patterns have a major possibility of being cured if the available health resources are used appropriately and suitable associations of drugs are designed, as is argued in this article. It is obvious that the best prognosis is for those patients who are susceptible to all the drugs, when you (..) (AU)

Comentarios a la reciente normativa de tratamiento de la tuberculosis de la ATS/CDC/IDS / Comments on recent guidelines for the treatment of tuberculosis by the American Thoracic Society, the Centers for Disease Control and Prevention, and the Infectious Diseases Society of America

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Factores de riesgo en asma / Risk factors in asthma

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Origen, presente y futuro de las resistencias en tuberculosis / Origin, present and future of resistance in tuberculosis

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[Complications of endovesical treatment with BCG in a series of 200 patients]. / Complicaciones del tratamiento endovesical con BCG en una serie de doscientos pacientes.

OBJECTIVE: To describe and quantify the side effects of intravesical BCG therapy (Connaught strain) in different therapeutic protocols. METHODS: 200 patients were studied; 126 treated according to the standard protocol of our hospital (modality 1 and modality 2: twelve and nine 81 mg instillations, respectively) and 74 patients in the CUETO protocols (90008, 93009, 95011, 95012). Classification of BCG toxicity was based on the criteria utilized by Lamm which divides it into side effects and complications. We have distinguished side effects further as local irritative symptoms (LIS) and cystitis. RESULTS: The most common side effects were LIS (80%) and cystitis (21.5%). The incidence of cystitis (44.4%) and general malaise (44.4%) was higher for modality 1 than for modality 2 (24.1% and 20.3%, respectively). The CUETO 93009 protocol (mitomycin + BCG) showed the highest incidence of side effects (LIS 100%, cystitis 57.1% and fever < 39 degrees C 71.4%). The most frequent complication was fever > 39 degrees C (4%), followed by hepatitis (3%). The rate of bladder retraction was notably high (1.5%), requiring cystectomy with neobladder substitution in two cases. The overall complication rate for modality 1 (16.6%) was reduced when modality 2 was utilized (8.3%). In the CUETO 90008 protocol, dose reduction did not reduce the complication rate (81 mg: 7.1%; 21 mg: 19.2%). BCG therapy was discontinued in 14%. CONCLUSIONS: Toxicity due to intravesical BCG therapy did not decrease when the dose was reduced, but diminished in number and intensity when the number of consecutive instillations was reduced.