Comparison between the persistence of post COVID-19 symptoms on critical patients requiring invasive mechanical ventilation and non-critical patients.

BACKGROUND: During follow-up, patients severely affected by coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation (IMV), show symptoms of Post-Intensive Care Syndrome (PICS) such as cognitive impairment, psychological disability, and neuromuscular deconditioning. In COVID-19 pandemic, it is a priority to develop multidisciplinary post-acute care services to address the long-term multisystemic impact of COVID-19. RESEARCH QUESTION: Which are the most relevant multisystemic sequelae in severe post-COVID-19 patients? STUDY DESIGN AND METHODS: Observational chart review study that included adult patients discharged from a referral hospital for respiratory diseases in Mexico after recovering from severe COVID-19 disease from December 23, 2020, to April 24, 2021. Data were collected from 280 of 612 potentially eligible patients to evaluate persistent symptoms and compare sequelae in patients who required intubation, using a standardized questionnaire of symptoms, in addition to findings reported during the face-to-face health assessment. Univariable and multivariate analyses were performed for the association among the requirement of IMV and the long-term persistence of symptoms. RESULTS: 280 patients were included. The median age was 55 (range, 19 to 86) years, and 152 (54.3%) were men. The mean length of hospital stay was 19 (SD, 14.1) days. During hospitalization 168 (60%) participants received IMV. A large proportion of these patients reported fatigue (38.7%), paresthesia (35.1%), dyspnea (32.7%) and headache (28%); meanwhile only 3 (1.8%) of them were asymptomatic. Patients who required intubation were more likely to have neuropsychiatric (67.3% vs 55.4%; OR, 1.79 [95% CI, 1.08 to 2.97]) and musculoskeletal involvement (38.7% vs. 25.9%; OR, 1.92 [95% CI, 1.12 to 3.27]), adjusted for age,sex and hospitalization time. INTERPRETATION: The proportion of patients requiring intubation was 60%, reporting persistent symptoms in 98% of them. Neuropsychiatric and musculoskeletal symptoms were the most predominant symptoms in these patients, with a significant difference. Post-COVID-19 syndrome is a frequent problem in patients who required IVM. Physicians in ICU and in care of COVID-19 patients should be aware of this syndrome in order to avoid more complications.

A bioinformatics pipeline for Mycobacterium tuberculosis sequencing that cleans contaminant reads from sputum samples.

Next-Generation Sequencing (NGS) is widely used to investigate genomic variation. In several studies, the genetic variation of Mycobacterium tuberculosis has been analyzed in sputum samples without previous culture, using target enrichment methodologies for NGS. Alignments obtained by different programs generally map the sequences under default parameters, and from these results, it is assumed that only Mycobacterium reads will be obtained. However, variants of interest microorganism in clinical samples can be confused with a vast collection of reads from other bacteria, viruses, and human DNA. Currently, there are no standardized pipelines, and the cleaning success is never verified since there is a lack of rigorous controls to identify and remove reads from other sputum-microorganisms genetically similar to M. tuberculosis. Therefore, we designed a bioinformatic pipeline to process NGS data from sputum samples, including several filters and quality control points to identify and eliminate non-M. tuberculosis reads to obtain a reliable genetic variant report. Our proposal uses the SURPI software as a taxonomic classifier to filter input sequences and perform a mapping that provides the highest percentage of Mycobacterium reads, minimizing the reads from other microorganisms. We then use the filtered sequences to perform variant calling with the GATK software, ensuring the mapping quality, realignment, recalibration, hard-filtering, and post-filter to increase the reliability of the reported variants. Using default mapping parameters, we identified reads of contaminant bacteria, such as Streptococcus, Rhotia, Actinomyces, and Veillonella. Our final mapping strategy allowed a sequence identity of 97.8% between the input reads and the whole M. tuberculosis reference genome H37Rv using a genomic edit distance of three, thus removing 98.8% of the off-target sequences with a Mycobacterium reads loss of 1.7%. Finally, more than 200 unreliable genetic variants were removed during the variant calling, increasing the report's reliability.

Interleukin-17 limits hypoxia-inducible factor 1α and development of hypoxic granulomas during tuberculosis.

Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 production negatively regulates the development of hypoxic TB granulomas by limiting the expression of the transcription factor hypoxia-inducible factor 1α (HIF1α). In human TB patients, HIF1α mRNA expression is increased. Through genotyping and association analyses in human samples, we identified a link between the single nucleotide polymorphism rs2275913 in the IL-17 promoter (-197G/G), which is associated with decreased IL-17 production upon stimulation with Mtb cell wall. Together, our data highlight a potentially novel role for IL-17 in limiting the development of hypoxic necrotic granulomas and reducing disease severity in TB.

La diabetes se asocia con reacciones adversas graves en la tuberculosis multirresistente / Diabetes is Associated with Severe Adverse Events in Multidrug-Resistant Tuberculosis

Introducción: La diabetes mellitus (DM), una enfermedad muy frecuente en México, es un factor de riesgo bien conocido para el desarrollo de tuberculosis (TB). Sin embargo, se desconoce en qué medida la DM predispone al desarrollo de reacciones adversas (RA) a los fármacos anti-tuberculosis y/o si predispone a un peor resultado en pacientes con pacientes con TB multirresistente (TB-MR) y TB extremadamente resistente (TB-XR). El objetivo principal de este estudio fue describir los resultados del tratamiento anti-tuberculosis, el impacto de la DM y la prevalencia de RA en una cohorte de pacientes con TB pulmonar MR/XR tratados en el centro de referencia nacional para TB, en la Ciudad de México. Resultados: Entre 2010 y 2015 se incluyeron 90 pacientes -73 con TB-MR (81,1%), 11 con TB pre-XR (12,2%) y 6 (6,7%) con TB-XR-, 49 (54,4%) de los cuales tenían DM y 3 con co-infección por el virus de la inmunodeficiencia humana (VIH) (3,3%). El diagnóstico se realizó mediante cultivo y pruebas de fármaco-sensibilidad (PFS) en el 98% de los pacientes y mediante prueba molecular en un caso. La presencia de DM se asoció con un mayor riesgo de RA graves, tales como nefrotoxicidad (odds ratio [OR] = 6,5; intervalo de confianza del 95% [IC 95%]: 1,9-21,8) e hipotiroidismo (OR = 8,8; IC 95%: 1,8-54,2), aunque no con peor resultado del tratamiento. onclusiones: Nuestros datos sugieren que la DM no tiene un impacto sobre los resultados del tratamiento anti-tuberculosis de segunda línea, pero los pacientes con DM tienen mayor riesgo de presentar RA graves secundarias al tratamiento, tales como nefrotoxicidad e hipotiroidismo

Introduction: Diabetes mellitus (DM), a very common disease in Mexico, is a well-known risk factor for tuberculosis (TB). However, it is not known by which extent DM predisposes to adverse events (AE) to anti-TB drugs and/or to worse outcomes in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). The main objective of this study was to describe the outcomes of TB treatment, the impact of DM and the prevalence of AE in a cohort of patients with MDR-/XDR pulmonary TB treated at the national TB referral centre in Mexico City. Results: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (12.2%) and 6 (6.7%) with XDR-TB, including 49 (54.4%) with DM, and 3 with Human Immunodeficiency Virus (HIV) co-infection (3.3%). In 98% of patients, diagnosis was made by culture and drug susceptibility testing, while in a single case the diagnosis was made by a molecular test. The presence of DM was associated with an increased risk of serious drug-related AEs, such as nephrotoxicity (Odds Ratio [OR] = 6.5; 95% Confidence Interval [95% CI]: 1.9-21.8) and hypothyroidism (OR = 8.8; 95% CI: 1.8-54.2), but not for a worse outcome. Conclusions: Our data suggest that DM does not impact second-line TB treatment outcomes, but patients with DM have a higher risk of developing serious AEs to drug-resistant TB treatment, such as nephrotoxicity and hypothyroidism

Diabetes is Associated with Severe Adverse Events in Multidrug-Resistant Tuberculosis. / La diabetes se asocia con reacciones adversas graves en la tuberculosis multirresistente.

INTRODUCTION: Diabetes mellitus (DM), a very common disease in Mexico, is a well-known risk factor for tuberculosis (TB). However, it is not known by which extent DM predisposes to adverse events (AE) to anti-TB drugs and/or to worse outcomes in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). The main objective of this study was to describe the outcomes of TB treatment, the impact of DM and the prevalence of AE in a cohort of patients with MDR-/XDR pulmonary TB treated at the national TB referral centre in Mexico City. RESULTS: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (12.2%) and 6 (6.7%) with XDR-TB, including 49 (54.4%) with DM, and 3 with Human Immunodeficiency Virus (HIV) co-infection (3.3%). In 98% of patients, diagnosis was made by culture and drug susceptibility testing, while in a single case the diagnosis was made by a molecular test. The presence of DM was associated with an increased risk of serious drug-related AEs, such as nephrotoxicity (Odds Ratio [OR]=6.5; 95% Confidence Interval [95% CI]: 1.9-21.8) and hypothyroidism (OR=8.8; 95% CI: 1.8-54.2), but not for a worse outcome. CONCLUSIONS: Our data suggest that DM does not impact second-line TB treatment outcomes, but patients with DM have a higher risk of developing serious AEs to drug-resistant TB treatment, such as nephrotoxicity and hypothyroidism.

Classifying new anti-tuberculosis drugs: rationale and future perspectives.

The classification of anti-tuberculosis (TB) drugs is important as it helps the clinician to build an appropriate anti-TB regimen for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases that do not fulfil the criteria for the shorter MDR-TB regimen. The World Health Organization (WHO) has recently approved a revision of the classification of new anti-TB drugs based on current evidence on each drug. In the previous WHO guidelines, the choice of drugs was based on efficacy and toxicity in a step-down manner, from group 1 first-line drugs and groups 2-5 second-line drugs, to group 5 drugs with potentially limited efficacy or limited clinical evidence. In the revised WHO classification, exclusively aimed at managing drug-resistant cases, medicines are again listed in hierarchical order from group A to group D. In parallel, a possible future classification is independently proposed. The aim of this viewpoint article is to describe the evolution in WHO TB classification (taking into account an independently proposed new classification) and recent changes in WHO guidance, while commenting on the differences between them. The latest evidence on the ex-group 5 drugs is also discussed.

CD161 Expression Defines a Th1/Th17 Polyfunctional Subset of Resident Memory T Lymphocytes in Bronchoalveolar Cells.

Alveolar resident memory T cells (T(RM)) comprise a currently uncharacterized mixture of cell subpopulations. The CD3(+)CD161(+) T cell subpopulation resides in the liver, intestine and skin, but it has the capacity for tissue migration; however, the presence of resident CD3(+)CD161(+) T cells in the bronchoalveolar space under normal conditions has not been reported. Bronchoalveolar cells (BACs) from healthy volunteers were evaluated and found that 8.6% (range 2.5%-21%) of these cells were CD3(+) T lymphocytes. Within the CD3(+) population, 4.6% of the cells (2.1-11.3) expressed CD161 on the cell surface, and 74.2% of the CD161(+)CD3(+) T cells expressed CD45RO. The number of CD3(+)CD161(+) T cells was significantly lower in the bronchoalveolar space than in the blood (4.6% of BACs vs 8.4% of peripheral blood mononuclear cells (PBMCs); P<0.05). We also found that 2.17% of CD4(+) T lymphocytes and 1.52% of CD8(+) T lymphocytes expressed CD161. Twenty-two percent of the alveolar CD3(+)CD161(+) T lymphocytes produced cytokines upon stimulation by PMA plus ionomycin, and significantly more interferon gamma (IFN-γ) was produced compared with other cytokines (P = 0.05). Most alveolar CD3(+)CD161(+) T cells produced interleukin-17 (IL-17) and IFN-γ simultaneously, and the percentage of these cells was significantly higher than the percentage of CD3(+)CD161- T cells. Moreover, the percentage of alveolar CD3(+)CD161(+) T lymphocytes that produced IFN-γ/IL-17 was significantly higher than those in the peripheral blood (p<0.05). In conclusion, Th1/Th17-CD3(+)CD161(+) TRM could contribute to compartment-specific immune responses in the lung.

Diabetes and Other Risk Factors for Multi-drug Resistant Tuberculosis in a Mexican Population with Pulmonary Tuberculosis: Case Control Study.

BACKGROUND AND AIMS: Multidrug resistant tuberculosis (MDR-TB) poses problems in treatment, costs and treatment outcomes. It is not known if classically described risk factors for MDR-TB in other countries are the same in Mexico and the frequency of the association between diabetes mellitus (DM) and MDR-TB in our country is not clear. We undertook this study to analyze risk factors associated with the development of MDR-TB, with emphasis on DM. METHODS: A case-control study in the state of San Luis Potosi (SLP), Mexico was carried out. All pulmonary MDR-TB patients diagnosed in the state of SLP between 1998 and 2013 (36 cases) evaluated at a state pharmacoresistant tuberculosis (TB) clinic and committee; 139 controls were randomly selected from all pulmonary non-multidrug-resistant tuberculosis (non-MDR-TB) cases identified between 2003 and 2008. Cases and controls were diagnosed and treated under programmatic conditions. RESULTS: Age, gender, malnutrition, being a health-care worker, HIV/AIDS status, and drug abuse were not significantly different between MDR-TB and non-MDR-TB patients. Significant differences between MDR-TB and non-MDR-TB patients were DM (47.2 vs. 28.1%; p = 0.028); previous anti-TB treatments (3 vs. 0, respectively; p <0.001), and duration of first anti-TB treatment (8 vs. 6 months, respectively; p <0.001). CONCLUSIONS: MDR-TB and DM are associated in 47.2% of MDR TB cases (17/36) in this study. Other recognized factors were not found to be significantly different in MDR-TB compared to non-MDR-TB in this study. Cost-feasible strategies must be implemented in the treatment of DM-TB in order to prevent the selection of MDR-TB.

The Tim3-galectin 9 pathway induces antibacterial activity in human macrophages infected with Mycobacterium tuberculosis.

T cell Ig and mucin domain 3 (Tim3) is an inhibitory molecule involved in immune tolerance, autoimmune responses, and antiviral immune evasion. However, we recently demonstrated that Tim3 and Galectin-9 (Gal9) interaction induces a program of macrophage activation that results in killing of Mycobacterium tuberculosis in the mouse model of infection. In this study, we sought to determine whether the Tim3-Gal9 pathway plays a similar role in human pulmonary TB. We identified that pulmonary TB patients have reduced expression of Tim3 on CD14(+) monocytes in vivo. By blocking Tim3 and Gal9 interaction in vitro, we show that these molecules contribute to the control of intracellular bacterial replication in human macrophages. The antimicrobial effect was partially dependent on the production of IL-1ß. Our results establish that Tim3-Gal9 interaction activates human M. tuberculosis -infected macrophages and leads to the control of bacterial growth through the production of the proinflammatory cytokine IL-1ß. Data presented in this study suggest that one of the potential pathways activated by Tim3/Gal9 is the secretion of IL-1ß, which plays a crucial role in antimicrobial immunity by modulating innate inflammatory networks.

Respuesta al tratamiento antituberculosis en pacientes con historia de tratamientos previos en el Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas / Response to antituberculous therapy in patients previously treated for TB at the National Institue for Respiratory Diseases Ismael Cosío Villegas

Antecedentes y objetivos: El Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER), como centro de referencia nacional de enfermedades respiratorias, recibe pacientes con tuberculosis pulmonar (TBp) que ya han recibido múltiples tratamientos. El objetivo de este estudio fue evaluar los resultados del tratamiento antituberculosis en pacientes previamente tratados que fueron supervisados por el INER durante un nuevo retratamiento. Métodos: Estudio retrospectivo con análisis de los expedientes clínicos mediante un cuestionario estandarizado de los pacientes con TBp con antecedente de tratamiento previo, y cuyo nuevo tratamiento fue supervisado en el INER de 1994-2001. La respuesta al tratamiento fue analizada de acuerdo al número de tratamientos previos, al antecedente de fracaso al tratamiento antes de ingresar al INER, y de acuerdo a la presencia o no de tuberculosis multifarma-corresistente (TB-MFR). Resultados: Se incluyeron a 147 pacientes diagnosticados con TBp que habían recibido tratamiento previo. Las tasas de curación en el INER para los pacientes con uno, dos y tres o más tratamientos previos fueron 68.2%, 40.4%, 8.8% (p = 0.009); de abandono 6.8%, 4.3%, 3.1% (p = 0.7) y de fracaso 18.2%, 27.7%, 25.0% (p = 0.6) para cada uno de los grupos, respectivamente. La proporción de TB-MFR fue de 64.4% 86.3% y 94.4% en cada grupo (x² de tendencia, p = 0.0004). El fracaso previo fue predictor independiente de fracaso actual [RM = 2.4 (IC95% 0.9-6.4) p = 0.04]. Las tasas de curación de acuerdo al patrón de resistencia fueron: monorresistencia 71.4%; multifarmaco-rresistencia 44.9% y polirresistencia 30.8%, (x² de tendencia, p = -03). Conclusiones: En pacientes con TBp con múltiples tratamientos previos y que recibieron un retratamiento supervisado por el INER, hubo bajas tasas de curación, una proporción persistente de fracasos al tratamiento y una alta tasa de TB-MFR.

Background: The National Institute of Respiratory Diseases Ismael Cosío Villegas (INER) is a national third level referral center for all respiratory diseases, including multitreaded pulmonary tuberculosis patients (PTb). The purpose of this study was to evaluate the results of supervised PTb retreatment at the INER in patients previously treated for PTb. Methods: Retrospective review of clinical charts by a standardized questionary of previous treated PTb patients and whose new treatment was given and supervised al the INER from 1994 to 2001. The response was analyzed according to the number of previous treatments, history of failure to previous treatments and presence or absence of MDR PTb. Results: One hundred and forty seven patients had previously received treatment for PTb. The cure rates for patients with one, two, three or more previous PTb treatments were 68.2%, 40.4%, and 8.8% (p = 0.009); desertion 6.8%, 4.3%, and 3.1% (p = 0.7); failure 18.2%, 27.7%, and 25 % (p = 0.6) for each one of the groups, respectively. The proportion of MDR- PTb was 64.4%, 86.3%, and 94.4% in each group (X² trend, p = 0.0004). A previous treatment failure was a predictor of failure of treatment at the INER [OR = 2.4 (CI95% 0.9-9.64), p = 0.04]. According to resistance, cure rates were 71.4% for one drug resistance, MDR 44.9% and poly resistance 30.8% (X² trend, p= -03). Conclusions: For patients with one or more failed previous treatments for PTb, receiving a new supervised treatment regime at the INER, there were low cure rates, a high proportion of treatment failures and a high rate of MDR-PTb.

Motivos de hospitalización en pacientes con tuberculosis pulmonar en un hospital de referencia / Reasons for medical admission in patients with pulmonary tuberculosis in a referral institute

Objetivo: Determinar la prevaíencia de complicaciones torácicas en pacientes con tuberculosis pulmonar hospitalizados en el Instituto Nacional de Enfermedades Respiratorias (INER). Lugar del estudio: INER, centro de tercer nivel y referencia dedicado a la atención médica especializada, docencia e investigación de enfermedades respiratorias. Material y métodos: Se realizó un estudio retrospectivo con la revisión de los expedientes clínicos de pacientes con tuberculosis pulmonar ingresados al INER, en un período que comprendió del 1 de julio al 31 de diciembre de 2003. Resultados: De los 124 pacientes con tuberculosis pulmonar que acudieron al INER durante el período de estudio, 62.9% (78/124) fueron hospitalizados; 44.9% (35/78) del sexo masculino; mediana de edad, 44.5 años (rango 16-78); el diagnóstico bacteriológico se hizo por baciloscopía en 51.3% (40/78); sólo por cultivo, 5.1% (4/78) y por baciloscopía y cultivo, 43.6% (34/78). Del total de pacientes, 66.6% (52/78) se clasificaron en la categoría I de la Organización Mundial de la Salud. La prevaíencia de diabetes mellitus fue 43.7% (31/78). Los motivos de hospitalización fueron: 46.2% (36/78) para diagnóstico; hemoptisis, 34.6% (27/78); infecciones, 5.2% (4/78) y otros motivos, 14.0% (11/78). Presentaron bronquiectasias, 85.7% (66/78); neumonía, 6.4% (5/78); neumonía por Mycobacterium tuberculosis, 5.1% (4/78); empierna, 5.1% (4/78); fístula broncopleural, 3.9% (3/78); aspergiloma, 2.6% (2/78); compresión tráqueo-bronquial, 1.3% (l/78) y fibrotórax, 12.8% (10/78). Conclusiones: Los pacientes hospitalizados en el INER por tuberculosis pulmonar manifestaron una elevada frecuencia de complicaciones, especialmente de bronquiectasias y hemoptisis. Casi 44% de los pacientes presentó diabetes mellitus; uno de cada dos fue hospitalizado para diagnóstico.

Purpose: To determine the prevalence of thoracic complications in hospitalized patients with pulmonary tuberculosis. Setting: National referral hospital for the care, teaching and investigation of respiratory diseases. Material and methods: This study is based on the retrospective analysis of pulmonary tuberculosis patients admitted from July 1 to December 31, 2003 and was conducted at The National Institute of Respiratory Diseases (INER), Mexico. Results: Seventy eight patients with pulmonary tuberculosis were included in the six month period; 35 (44.9%) were male; the bacteriological diagnosis was done by sputum smear in 51.3% (40/78), culture in 5.1% (4/78) and sputum smear and culture in 43.6% (34/78). Patients were classified as WHO category I in 66.7% (52/78); 43.7% had diabetes mellitus (31/78). Admission causes: for diagnosis in 46.2% (36/78); hemoptysis in 34.6% (27/78); infection in 5.2% (4/78); other causes in 14.0% (11/78); bronchiectasis were present in 85.7% (66/ 77); pneumonia in 6.4% (5/78); Mycobacterium tuberculosis pneumonia in 5.1% (4/78); empyema in 5.1% (4/78); bronchopleural fistula in 3.9% (3/ 78); aspergilloma in 2.6% (2/78); tracheobronchial obstruction in 1.3% (1/78); fibrothorax in 12.8% (10/78). Conclusions: Hospitalized pulmonary tuberculosis patients show an elevated rate of pulmonary complications. Almost half had diabetes mellitus; almost half were hospitalized for diagnosis.

Resultados de taatamiento de tuberculosis resisente en 91 pacientes del instittuto nacional de enfermedades respiratorias: 2001-2003

Introducción: La tuberculosis persiste como un problema mundial de salud pública. Aliviar la enfermedad, el sufrimiento y la muerte de los individuos causados por la tuberculosis es la principal inquietud humanitaria y requiere un enfoque de responsabilidad política social y económica centrado en el paciente para el control de esta enfermedad. Material y métodos: Se revisaron los expedientes de 91 pacientes con diagnóstico de tuberculosis farmacorresistente que fueron referidos al Instituto Nacional de Enfermedades Respiratorias por los servicios de salud de los distintos estados del país y del Distrito Federal. Los casos fueron clasificados al final, acorde con los criterios establecidos por la Organización Mundial de la Salud. Resultados: En el Grupo 1 el éxito fue del 63%, en el Grupo 2 del 100% y en el Grupo 3 del 41.8%. En el total de los tres grupos la tasa de éxito fue del 49%. Al hacer el análisis de estado por estado, los resultados menos favorables fueron Morelos con 0%, Puebla 25%, México 38%, y Distrito Federal 58% (7 de 12). Los mejores resultados obtenidos fueron en Veracruz con 77%, Guerrero con 75%, y Chiapas con 71%. Lo que hace evidente que la distancia no fue un factor de riesgo para el fracaso del tratamiento. Conclusiones: Los bajos resultados del estudio obligan a pensar que la prioridad es prevenir la aparición de casos multifarmacorresistentes al asegurar mejores tasas de curación, y reducir la diseminación de la enfermedad al tratar en forma eficiente a todos los casos nuevos.

Background: Tuberculosis (TB) persists as a public health world-wide problem. The principal human concern is to cure, relieve the suffering and reduce the mortality caused by this disease. A serious problem is the increasing prevalence of multidrug-resistant tuberculosis which contributes to the failure to erradicate TB. This requires an approach based on political, social and economic responsibility focused on the patient for TB control. Methods: We analyzed ninety-one files of patients with multidrug-resistant tuberculosis that were referred to the Institute by health services of different states and Mexico City. The cases were classified according to the criteria established by the World Health Organization (WHO). Results: In Group 1, the success rate was 63%, in Group 2 was 100% and in Group 3 was 41.8%. In the three groups the rate of success was 49%. After analyzing data by state, the worst results were from Morelos with 0%, Puebla 25%, Mexico state 38% and Mexico City with 58% (7 of 12). The best results were from Veracruz with 77%, Guerrero 75% and Chiapas 71%. This makes evident that the distance from the reference center is not a risk factor for treatment failure. Conclusions: It is imperative to prevent new cases of multidrug-resistant tuberculosis by increasing the rate of cure and to reduce the dissemination of the disease by efficiently treating all new cases.

[Tuberculosis: a current problem]. / Tuberculosis: un problema de actualidad.

Tuberculosis is a public health problem. If the current trends continue, is expected to arrive to 10.2 million of new cases in 2005. There are three studies accomplished in 1995 in Mexican patients. The results show important difficulty in the application and the follow-up of the program of control of the tuberculosis, what has caused accumulation of chronic cases, moderate rate of primary resistance and alarming levels of primary and secondary multiresistance (23%). Mechanism of protective immunity against mycobacterium tuberculosis (MTB) in humans have not been clarified. Different subpopulations of lymphocytes CD4, CD8 and other populations as well as macrophages, and monocytes, have an important role. In industrialized countries, the managing of the MDRTB is based on the use of individualized treatments with second line drugs according to susceptibility test, however the foregoing has not been possible to apply it middle or low income countries. WHO has launches the initiative "DOTS plus" that consist in the administration of a standarized regimen on the basis of epidemiology of resistance in the country or region.

[Epidemiology of Tuberculosis in Mexico, 1981-1998. Inconsistencies between reports of the WHO and the Ministry of health]. / Discrepancias entre los datos ofrecidos por la Secretaría de Salud y la Organización Mundial de la Salud sobre tuberculosis en México, 1981-1998.

OBJECTIVE: To describe the tuberculosis morbidity and mortality trends in Mexico, by comparing the data reported by the Ministry of Health (MH) and the World Health Organization (WHO) between 1981 and 1998. MATERIAL AND METHODS: The number of cases notified in the past few years, their rates, and the trends of the disease in Mexico were analyzed. The incidence of smear-positive pulmonary tuberculosis was estimated for 1997 and 1998 with the annual tuberculosis infection risk (ATIR), to estimate the percentage of bacilliferous cases in 1997-1998. RESULTS: WHO reported more tuberculosis cases for Mexico than the MH. However, this difference has decreased throughout the years. The notification of smear-positive cases remained stable during 1993-1998. The estimated percentages of detection were 66% for 1997 and 26% for 1998 (based on ATIR of 0.5%). Tuberculosis mortality decreased gradually (6.7% per year) between 1990 and 1998, whereas the number of new cases increased, suggesting the persistence of disease transmission in the population. CONCLUSIONS: Inconsistencies between case notifications from national data and WHO were considerable, but decreased progressively during the study period. According to ATIR estimations, a considerable number of infectious tuberculosis cases are not detected. The English version of this paper is available at: http://www.insp.mx/salud/index.html.

Discrepancias entre los datos ofrecidos por la Secretaría de Salud y la Organización Mundial de la Salud sobre tuberculosis en México, 1981-1998 / Inconsistencies between reports from the World Health Organization and the Ministry of Health

OBJETIVO: Describir las tendencias de la morbilidad y mortalidad de la tuberculosis en México, entre 1981 y 1998, comparando datos de la Secretaría de Salud y de la Organización Mundial de la Salud. MATERIAL Y MÉTODOS: Se analizó el número de casos y tasas notificados y la tendencia de la enfermedad en los últimos años. Se calculó la incidencia de casos nuevos de tuberculosis bacilíferos mediante el riesgo anual de infección tuberculosa, con lo que se estimó el porcentaje de detección de casos bacilíferos en 1997-1998. RESULTADOS: El número de casos de tuberculosis emitido por la Organización Mundial de la Salud supera al notificado por la Secretaría de Salud, discrepancia que se ha reducido. Los casos bacilíferos se han mantenido entre 1993-1998 y se estimó una detección de 66 y de 26 por ciento en 1997 y 1998, respectivamente (para un Riesgo Anual de Infección Tuberculosa de 0.5 por ciento). La mortalidad se redujo 6.7 por ciento cada año entre 1990 y 1998 mientras que se observó un aumento de casos nuevos, lo que implica la persistencia de la transmisión de la infección entre la población. CONCLUSIONES: Hay discrepancia entre el número de casos de tuberculosis ofrecido por la Secretaría de Salud y la Organización Mundial de la Salud. De acuerdo con las estimaciones por el Riesgo Anual de Infección Tuberculosa se deja de detectar un número considerable de casos bacilíferos

Empiema tuberculoso / Tuberculous empyema

El empiema tuberculoso es considerado como una entidad poco frecuente y habitualmente es la complicación de una tuberculosis pleural, sin embargo hay condiciones clínicas que pueden favorecer su desarrollo como son el plombage, oleotórax y neumotórax terapéutico, también se puede desarrollar a partir de una cicatriz fibrosa, por una neumonectomía o por una toracoplastia. Su fisiopatogenia es poco conocida, pero a diferencia de la tuberculosis pleural, el empiema de tipo tuberculoso es ocasionado por una infección de la cavidad pleural por el Mycobacterium tuberculosis. Sus cuadros clínico y radiológico no son muy diferentes al derrame pleural tuberculoso, pero la presencia de fístula broncopleural puede complicar su cuadro clínico. El tratamiento requiere de un manejo con medicamentos antituberculosos, conjuntamente con manejo quirúrgico. El manejo quirúrgico se basa en el drenaje del material purulento, y puede ser tan sencillo como el colocar una sonda endopleural, pero en algunos casos será necesario un manejo más agresivo como la pleurotomía abierta o bien, la toracotomía.

Etiología del derrame pleural en el Instituto Nacional de Enfermedades Respiratorias / Pleural effusion etiology at the National Institute of Respiratory Diseases

Objetivo. Establecer la distribución etiológica del derrame pleural en una región geográfica determinada, así como la edad de los pacientes, avances en el diagnóstico y tratamiento de las enfermedades subyacentes y optimizar las actitudes diagnósticas y terapéuticas. Sitio. El Instituto Nacional de Enfermedades Respiratorias en la Ciudad de México. Material y métodos. Estudio retrospectivo de 314 expedientes de pacientes que ingresaron al Instituto Nacional de Enfermedades Respiratorias durante el periodo comprendido de enero de 1991 a diciembre de 1996. Resultados. La edad de todos los pacientes estudiados fue de 49.9 ñ 18.4. La causa más frecuente del derrame pleural fue tuberculosis en 133 pacientes (42 por ciento), con un promedio de edad de 42.8 ñ 17.9; seguido de neoplasias en 89 (28 por ciento), edad 61.5 ñ 13.3; la tercera causa fue derrame pleural paraneumónico complicado con 54 casos (17 por ciento) con edad promedio de 42 ñ 18.2. Encontramos 30 trasudados que significaron el 9 por ciento en frecuencia, de los cuales 20 eran secundarios a insuficiencia cardiaca (edad 59.2 ñ 11.9). Otras causas de derrame pleural incluyeron trauma, enfermedades colágeno-vasculares y embolismo pulmonar. En cuatro sujetos no fue posible establecer la causa del derrame. Conclusiones. El 42 por ciento de los casos fueron secundarios a TB, el 28 por ciento a neoplasia,el 17 por ciento infección no tuberculosa y el 9 por ciento a trasudados. La causa más común de derrame pleural fue la tuberculosis que, aunque de esperarse dada la alta incidencia de la enfermedad en nuestra región, también pueden encontrarse diversas etiologías en los mismos grupos de edad