Influence of SARS-CoV-2 mRNA Vaccine Booster among Cancer Patients on Active Treatment Previously Immunized with Inactivated versus mRNA Vaccines: A Prospective Cohort Study.

Cancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8-12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% (p = 0.338), whereas NAb positivity reached 100% and 92% (p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates.

Avances en tuberculosis en el 54° Congreso Chileno de enfermedades respiratorias. 3a parte: Prevención de la tuberculosis activa mediante el tratamiento de la tuberculosis latente / Advances in tuberculosis at the 54th Chilean Congress of Respiratory Diseases. Part 3: prevention of active tuberculosis by treating latent tuberculosis

La infección tuberculosa latente (ITL) es un estado asintomático de la infección por Mycobacterium tuberculosis incapaz de transmitir la infección a otros, pero con el potencial de originar una tuberculosis (TBC) activa en el infectado, especialmente ante la presencia de factores de riesgo inmunológico. Es importante en personas de riesgo de desarrollar TBC reconocer la ITL utilizando test como la reacción a la tuberculina (PPD o TST) y los ensayos de liberación de Interferón-γ (IGRAs). Sin embargo, estos tests tienen limitaciones en su capacidad de predicción de riesgo de evolución de infección a enfermedad lo que conlleva a tener que tratar muchas personas para evitar algún caso de enfermedad. Nuevos tests se encuentran en desarrollo para mejorar la sensibilidad de reconocimiento de la ITL, distinguir infecciones recientes (que tienen el mayor riesgo de progresión a enfermedad) e incluso con la capacidad de detectar enfermedad subclínica o inicial. Para reducir la probabilidad de enfermar por TBC se utilizan tratamientos preventivos con fármacos, pero la cobertura mundial de esta terapia es reducida y la adherencia a terapias auto-administradas, como en el caso del uso de isoniazida diaria oral, es también baja. Otro problema de esta terapia son los riesgos de reacciones adversas (hepatitis, erupciones cutáneas) aunque no frecuentes. La recomendación de terapia actual de la ITL incluye el uso de rifamicinas y sus derivados. La asociación de isoniazida con rifapentina en una dosis semanal durante tres meses, administrada bajo supervisión, es la terapia de primera línea para mayores de 2 años, mostrando menos riesgo de hepatotoxicidad y mayor adherencia.

Latent Tuberculosis infection (LTBI) is the asymptomatic state of infection caused by Mycobacterium tuberculosis. Although untransmissible, LTBI can progress to active tuberculosis (TB), especially in people with immune risk factors. It is important to recognize LTBI in people at risk of developing TB; tuberculin skin test (PPD or TST) or interferon-γ release assays (IGRAs) are current diagnostic tests. However, these tests have limitations in their ability to predict subjects who will evolve from infection to disease; consequently, a large number of people with LTBI need treatment to avoid a reduced number of future TB disease cases. Newer tests are under development to improve the sensitivity in recognizing LTBI, distinguish recent infections with highest risk of progression to disease, and even be able to detect initial subclinical disease. Antimicrobial preventive treatment effectively reduces the probability of getting sick with TB, but worldwide availability of TB preventive therapy is limited, and adherence to self-administered therapies, as in the case of the use of daily oral isoniazid, is low. Adverse reactions risk (hepatitis, skin rash) although infrequent, is another problem with these therapies. Currently, LTBI management guidelines include regimens with use of rifamycins and their derivatives. The combination of isoniazid and rifapentine in a weekly dose for three months administered under supervision is the first line choice for LTBI therapy in those over 2 years of age, showing less hepatoxicity risk and greater adherence.

Reduced Immune Response to Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Cohort of Immunocompromised Patients in Chile.

BACKGROUND: Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. METHODS: This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined. RESULTS: NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (P<.01 or P = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon γ spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups. CONCLUSIONS: Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients. CLINICAL TRIALS REGISTRATION: NCT04888793.

Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Rathke's cleft cyst infections and pituitary abscesses: case series and review of the literature.

PURPOSE: Pituitary abscesses (PAs) are a rare clinical entity which may arise from normal pituitary tissue or underlying lesions within the gland. Rathke's cleft cysts (RCCs) are not commonly associated with the development of PA. METHODS: Retrospective chart review of three patients with PAs within RCCs at a single university center and review of the literature. RESULTS: Three cases are reported. The first case presented with fever and headache and a history of prior surgery due to RCC and a recent respiratory tract infection. The second case had a history of recent skin infections and presented with sudden onset headache and hypopituitarism. In the third case, chronic visual field impairment prompted an ophthalmologic evaluation resulting in a diagnosis of an adenoma and an infected RCC. In all three cases, an endoscopic endonasal approach was performed to drain infected tissue and allowed microbiological identification of gram-positive cocci, followed by treatment with antibiotics for at least three weeks. Cases in the literature are scarce and the diagnosis is usually made intraoperatively due to non-specific manifestations and imaging. PAs arising from underlying pituitary lesions are less common than primary PAs. Differential diagnosis should include pituitary apoplexy, hypophysitis and other cystic lesions. CONCLUSION: PAs occurring in RCCs are infrequent. Clinical manifestations are commonly subacute, without septic symptoms. Imaging is usually non-specific. Preoperative diagnosis is infrequent and a broad differential diagnosis should be considered. Empirical antimicrobial therapy should be initiated and adjusted after obtaining cultures to reduce the rate of recurrence and improve clinical outcomes.

Otomastoiditis por mycobacterium tuberculosis: un diagnóstico desafiante / Tuberculous otomastoiditis: a challenging diagnosis

RESUMEN La otomastoiditis tuberculosa es una presentación extremadamente rara de la forma extrapulmonar de la enfermedad y puede ser difícil llegar a su diagnóstico. Presentamos el caso de una paciente de 35 años con otomastoiditis tuberculosa bilateral acompañado de vértigo, hipoacusia mixta bilateral y paresia del nervio facial bilateral, como debut de una tuberculosis. Cultivos de Mycobacterium tuberculosis (MTB) y prueba de reacción en cadena de la polimerasa (PCR) de otorrea fueron inicialmente negativos. La tomografía computarizada de oídos y resonancia magnética mostraron cambios inflamatorios otomastoídeos bilaterales sin evidencia de erosión ósea ni extensión a partes blandas. Se realizó una mastoidotomía, las muestras del tejido obtenido evidenciaron osteomielitis crónica, bacterias ácido-alcohol resistentes y PCR positiva para MTB. La paciente recibió tratamiento con drogas antituberculosas durante 12 meses logrando una recuperación completa de la otalgia y vértigo, y mejoría parcial de audición y paresia facial. En resumen, los hallazgos clínicos e imagenológicos de la otomastoiditis tuberculosa son inespecíficos por lo cual se requiere de un alto índice de sospecha clínica para lograr el diagnóstico adecuado e iniciar el tratamiento de la infección subyacente.

ABSTRACT Tuberculous otomastoiditis is an extremely rare form of extrapulmonary disease that can be easily misdiagnosed. We hereby report the case of a previously healthy 35-yearold female with bilateral tuberculous otomastoiditis associated with vertigo, bilateral mixed hearing loss, and bilateral facial nerve palsy as the initial clinical presentation. Repeated Mycobacterium tuberculosis (MTB) culture and molecular testing of otorrhea aspirates were initially negative. High-resolution temporal bone computed tomography and magnetic resonance imaging showed partial opacification of the mastoid air cells without signs of bone erosion. A mastoidotomy was performed with mastoid tissue showing chronic osteomyelitis, positivity in acid-fast staining and MTB PCR. The patient was treated with a 12 month antituberculous treatment, with complete recovery of otalgia and vertigo, and improvement in hearing levels and facial nerve palsy. In summary, clinical and imaging findings for tuberculous otomastoiditis are non-specific, hence a high degree of suspicion is required in order to diagnose and promptly treat the underlying infection.

Evaluación de la técnica Xpert® MTB/RIF para la detección de Mycobacterium tuberculosis complex en muestras extra-pulmonares / Evaluation of Xpert® MTB/RIF technique for Mycobacterium tuberculosis complex detection in extra-respiratory specimens

Resumen La tuberculosis (TBC) extra-pulmonar alcanza al 26,2% de los casos totales de TBC en Chile. El cultivo es el método estándar de oro, pero es lento. La técnica Xpert® MTB/RIF permite detectar Mycobacterium tuberculosis complex (MTBc) por RPC en tiempo real en menos de 3 h, sin embargo, ha sido validada sólo para muestras respiratorias. El objetivo de este estudio fue determinar la utilidad de la prueba Xpert® MTB/RIF en la detección de MTBc en muestras extra-pulmonares en comparación con un estándar de oro combinado consistente en un cultivo de micobacterias positivo (medio sólido y líquido) y/o un método molecular validado positivo (q-RPC, Cobas® TaqMan-MTB). Se analizaron 50 muestras extra-pulmonares, de las cuales 25 fueron definidas positivas y 25 negativas para MTBc en base a estándar de oro combinado. Las 25 muestras definidas positivas tuvieron un resultado positivo por Xpert® MTB/RIF; de las 25 muestras definidas negativas, 24 tuvieron un resultado negativo y una de ellas un resultado positivo. Se obtuvo una concordancia global entre Xpert® MTB/RIF y el estándar de oro combinado de 98%. La prueba Xpert® MTB/RIF fue capaz de detectar 12 casos de TBC extra-pulmonar con baciloscopia negativa y 3 casos con cultivo negativo. El método Xpert® MTB/RIF ha demostrado tener una sensibilidad similar al q-RPC para detectar MTBc en muestras extra-pulmonares y permite reducir sustancialmente el tiempo de diagnóstico.

Extra-pulmonary tuberculosis (TB) represents the 26.2% of total TB cases in Chile. Culture is the gold standard method, but the process is extremely slow. Xpert®MTB/RIF technique detects Mycobacterium tuberculosis complex (MTBc) through real time PCR in less than 3 h. However, it has been validated only for respiratory specimens. We aimed to determine the performance of Xpert®MTB/RIF test in detecting MTBc in extra-respiratory specimens compared with a combined gold standard consisting in a positive (liquid and solid) mycobacterial culture and/or a positive validated molecular method (q-RPC, Cobas®TaqMan®-MTB). Fifty extra-respiratory specimens were analyzed, from which 25 were positive and 25 negative for MTBc based on the combined gold standard. The 25 positive specimens had a positive result by Xpert®MTB/RIF; from the 25 negative specimens, 24 had a negative result and one had a positive result. We obtained an overall concordance of 98% between Xpert®MTB/RIF and the combined gold standard. Xpert®MTB/RIF test was able to detect 12 smear-negative specimens and 3 culture-negative specimens, all of them corresponding to extra-pulmonary TB cases. Xpert®MTB/RIF showed similar sensitivity to q-RPC in detecting MTBc in extra-respiratory specimens. This procedure allowed a substantial reduction in the time of diagnosis.

Regional solar radiation is inversely correlated with incidence and severity of tuberculosis in Chile.

Vitamin D (VD) deficiency has been linked to increased incidence and morbidity of tuberculosis (TB). Chile has large variations in solar radiation (SR; a proxy of VD status) and high prevalence of VD deficiency in its southernmost regions with low SR. We investigated the correlation between regional SR and rates of TB incidence, admissions and deaths in Chile by reviewing national records on prospectively collected mandatory disease notifications, admissions and mortality between 2001 and 2011. Over the study period, 26 691 new TB notifications were registered. The TB incidence rate was 14·77 (95% confidence intervals (CIs) 14·60-14·95), admission rate was 12·12 (95% CI 11·96-12·28) and mortality rate was 1·61 (95% CI 1·55-1·67) per 100 000 population per year. Multivariable linear regressions adjusting for significant demographic TB risk factors in Chile (regional prevalence of HIV infection, rates of migration from TB-endemic countries and rates of imprisonment) revealed an independent and highly statistically significant inverse association between SR and TB incidence rate (ß -1·05, 95% CI -1·73 to -0·36, P = 0·007), admission rate (ß -1·58, 95% CI -2·23 to -0·93, P < 0·001), and mortality rate (ß -0·15, 95% CI -0·23 to -0·07, P = 0·002). These findings support a potential pathogenic role of VD deficiency in TB incidence and severity.

[Atypical mycobacterial infections in five adult patients without evidence of immunosuppression. Making an experience]. / Micobacterias atípicas en cinco pacientes adultos sin evidencias de inmunosupresión. Construyendo una experiencia.

We aim to communicate the experience gathered during the management of infections by atypical mycobacteria in immunocompetent patients in a general practice. Between 2008 and 2013, 5 patients with non-tuberculous mycobacterial infections were identified: 2 with cutaneous involvement and 3 with lung infection. None of them had evidence of immunosuppression. A patient with elbow bursitis by M. chelonae presented with a high mononuclear count in fluid analysis with mycobacterial growth at the fifth day of culture. He evolved satisfactorily with clarithromycin. A case with M. fortuitum skin infection had a delayed initial diagnosis with progression to local draining lymph nodes; the culture when requested was positive after 13 days of incubation. Patients with pulmonary infection presented with prolonged cough and sputum and had in common to be postmenopausal women displaying small nodules and bronchiectases at lung images, a classical pattern. Time elapsed between respiratory sampling and a definitive inform ranged from 40 to 89 days. Non-tuberculous mycobacterial infections in non-immunosuppresed patients can generate diagnostic and therapeutic challenges. Delay in identification contributes to this problem.

Micobacterias atípicas en cinco pacientes adultos sin evidencias de inmunosupresión: Construyendo una experiencia / Atypical mycobacterial infections in five adult patients without evidence of immunosuppression: Making an experience

We aim to communicate the experience gathered during the management of infections by atypical mycobacteria in immunocompetent patients in a general practice. Between 2008 and 2013, 5 patients with non-tuberculous mycobacterial infections were identified: 2 with cutaneous involvement and 3 with lung infection. None of them had evidence of immunosuppression. A patient with elbow bursitis by M. chelonae presented with a high mononuclear count in fluid analysis with mycobacterial growth at the fifth day of culture. He evolved satisfactorily with clarithromycin. A case with M. fortuitum skin infection had a delayed initial diagnosis with progression to local draining lymph nodes; the culture when requested was positive after 13 days of incubation. Patients with pulmonary infection presented with prolonged cough and sputum and had in common to be postmenopausal women displaying small nodules and bronchiectases at lung images, a classical pattern. Time elapsed between respiratory sampling and a definitive inform ranged from 40 to 89 days. Non-tuberculous mycobacterial infections in non-immunosuppresed patients can generate diagnostic and therapeutic challenges. Delay in identification contributes to this problem.

El objetivo de este trabajo es reportar la experiencia acumulada sobre infecciones por micobacterias atípicas en pacientes sin inmunosupresión. Entre el año 2008 y 2013 se observaron cinco pacientes con infección por micobacterias atípicas: dos con infección cutánea y tres con infección pulmonar. Ninguno de estos pacientes tenía evidencias de inmunosupresión. Un paciente con bursitis de codo por M. chelonae tuvo un estudio citoquímico con aumento de celularidad de predominio mononuclear y desarrollo de bacterias al quinto día; respondió favorablemente a claritromicina. Un caso con infección cutánea por M. fortuitum evolucionó en forma prolongada con supuración ganglionar antes del diagnóstico y el cultivo solicitado a los 13 días fue positivo. Los tres pacientes con aislados pulmonares presentaron tos y expectoración y tenían en común ser mujeres en edad post-menopáusica y presentar pequeños infiltrados nodulares asociados a bronquiectasias en el estudio de imágenes pulmonares, un patrón descrito en la literatura científica. En estos tres casos, la latencia entre la toma de muestra y el informe definitivo tuvo un rango de 40 a 89 días. El aislamiento de micobacterias atípicas en muestras de expectoración en pacientes sin inmunosupresión se da en un contexto típico pero plantea dificultades diagnósticas y terapéuticas. El lento crecimiento de estos microorganismos en el laboratorio contribuye a este problema.

Pesquisa de infección tuberculosa latente en personal de la salud en cuatro instituciones de salud en Santiago de Chile / Latent tuberculosis infection screening in healthcare workers in four large hospitals in Santiago, Chile

Background: It is currently unknown which is the prevalence of latent tuberculosis infection in healthcare workers in Chile, but this group has been described as at higher risk of developing active tuberculosis than general population. Objectives: To determine the prevalence of latent tuberculosis infection in a sample of healthcare workers from at risk areas. Methodology: A cross-sectional, descriptive study, conducted in health care workers from clinical laboratories or respiratory care areas in four hospitals in Santiago. Latent tuberculosis infection detection was determined by Quantiferon® TB Gold In Tube testing (QFT). Results: QFT resulted positive in 20 of 76 (26.3%) of the individuals tested. Test positivity reached 62.5% among the personnel that reported history of past TB contact in the community, 50% among the personnel who belonged to the national tuberculosis control program and 38% among those doing induced sputum, acid fast smear or mycobacterial cultures. The proportion of individuals with positive QFT was significantly lower in those personnel who had no such risk factors (15.7%, p = 0.03). The proportion of latent tuberculosis infection also increased in direct relation to the age of the subject. Conclusion: Latent tuberculosis infection as detected by QFT testing was highly prevalent in healthcare workers included in the present study. Further exploring the limitations and possible scenarios for this new diagnostic tool is needed, with emphasis on health personnel at higher-risk and younger individuals.

Introducción: Se desconoce en la actualidad cuál es la real prevalencia de infección tuberculosa latente en el personal de salud en Chile; sin embargo, este grupo ha sido descrito como con mayor riesgo de desarrollar tuberculosis activa que la población general. Objetivo: Determinar la prevalencia de infección tuberculosa latente en funcionarios de la salud en diferentes áreas laborales de riesgo. Metodología: Estudio de corte transversal, descriptivo, realizado en funcionarios pertenecientes a laboratorios clínicos o áreas de atención broncopulmonar de cuatro hospitales de la Región Metropolitana en quienes se hizo test de Quantiferon TB Gold®In tube(QFT). Resultados: Se evidenció infección tuberculosa latente en 20 de las 76 (26,3%) personas estudiadas. En aquellos funcionarios que referían antecedente de contacto en el pasado en la comunidad con enfermos de tuberculosis, la positividad del test llegó a 62,5%; en aquellos que pertenecían al Programa Nacional de Control de la Tuberculosis, a 50% y en los que realizaban toma de esputo inducido, baciloscopias o cultivo de micobacterias, a 38%. La proporción de individuos con QFT positivo fue significativamente menor en aquellos funcionarios que no tenían estos antecedentes (15,7%, p = 0,03). Se encontró además una mayor proporción de infección tuberculosa latente a mayor edad del individuo estudiado. Conclusión: La infección tuberculosa latente medida por QFT resultó altamente prevalente en el personal de la salud incluido en el presente estudio. Es necesario seguir profundizando en los posibles escenarios de implementación y limitaciones del uso de esta nueva herramienta diagnóstica, haciendo énfasis en el personal de la salud de mayor riesgo y menor edad.

Presencia del genotipo Beijing entre cepas del complejo Mycobacterium tuberculosis en dos centros de salud de la Región Metropolitana-Chile / Presence of Bejing genotype among Mycobacterium tuberculosis strains in two centres of the Region Metropolitana of Chile

Background: Genotyping of Mycobacterium tuberculosis complex (cMtb) allows us to know geographically predominant lineages. Some lineages spread more rapidly and are associated with multidrug resistance, particularly Beijing, which has been reported in Latin America (Peru). There is little information about this topic in Chile and there are no reports of the presence of the Beijing genotype. Aim: To determine the most prevalent lineages in the Metropolitan Region of Chile with emphasis on the search for Beijing in two health centers. Methods: Two complementary molecular methods were used: spoligotyping, based on the variations of the direct repeat regions in the genome of cMtb and MIRU-VNTR, based in the variable number of tandem repeats of mycobacterial interspersed repetitive units, and subsequent analysis in international databases. A designed lineage was assigned to 37 of the 43 strains studied (86%); 6 isolates could not be assigned to any genotype. LAM and T genotype were the most frequent (39.5 and 32.5%, respectively) followed by Haarlem (7.0%), Beijing (4.7%) and X (2.3%). Conclusion: We describe for the first time the presence of the Beijing genotype in Chile. cMtb molecular surveillance should be implemented in our country in order to know the dynamics of its transmission.

Introducción: La genotipificación del complejo Mycobacterium tuberculosis (cMtbc) permite conocer los genotipos geográficamente predominantes. Algunos genotipos se diseminan con mayor rapidez y se asocian a multi-resistencia, tal como Beijing, reportado en América Latina en Perú. Existe poca información al respecto en Chile, sin reportes de la presencia de Beijing. Objetivo: Conocer los genotipos prevalentes en dos centros de salud de la Región Metropolitana de Chile con énfasis en la búsqueda de Beijing. Métodos: Se utilizaron dos métodos moleculares complementarios basados en la variación de las regiones de repeticiones directa en el genoma de M. tuberculosis (espoligotipificación) y número variable de repeticiones en tandem de las unidades repetitivas de interespaciadores micobacterianos (MIRU-VNTRs) y posterior análisis en bases de datos internacionales. Resultados: Se asignó un genotipo conocido a 37 de las 43 cepas estudiadas (86%), mientras que en 14% no se asignó alguno. Los genotipos LAM y T fueron los más frecuentes (39,5 y 32,5%, respectivamente), seguidos por Haarlem (7,0%), Beijing (4,7%) y X (2,3%). Conclusión: Se describe por primera vez en Chile la presencia del genotipo Beijing en cepas de cMtb. Es necesario realizar una vigilancia epidemiológica molecular en el cMtb para conocer la dinámica de la transmisión en nuestro país.

Comparación de adenosina deaminasa y detección de anticuerpos anti-antígeno A60 para el diagnóstico de meningitis tuberculosa / A comparative study for adenosine deaminase and anti-antigen A-60 antibodies detection for the diagnosis of tuberculous meningitis

Background: Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of rapid and accurate diagnostic tools. We evaluated the immunological response to Mycobacterium tuberculosis anti-A60 antibodies in cerebrospinal fluid (CSF) in comparison to adenosine deaminase (ADA) determination, for the diagnosis of TBM. Methods: A total of 63 CSF samples were analyzed by indirect ELISA for the detection of anti- A60 IgG, IgM and IgA. These include samples from 17 patients with confirmed TBM and 46 control patients with other infections. Results: The mean individual anti-A60 IgM, IgG and IgA CSF antibody titers were significantly higher in TBM in comparison with control groups (p < 0.01). The best discriminatory CSF antibody for confirming TBM diagnosis was IgM, with an area under the receiver operating characteristic curve of 0.928 (95%CI 0.834-0.978), compared to 0.863 (95% CI: 0.752-0.936) for ADA testing (p = NS). The sensitivity of anti- A60 IgM CSF antibody titers (cutoff > 0.06 U/ml) was 94.1% compared to 88.2% for ADA (cutoff > 6.2 U/ml), p = NS. Both anti A60 IgM and ADA showed the same moderate specificity (80.4%). Two cases of TBM were correctly identified by anti-A60 IgM but missed by ADA. Conclusion: The ELISA test for anti-antigen A60 antibodies (IgM) is a rapid and sensitive tool for the rapid diagnosis of TBM that can be a complement to ALDA determination. The specificity of both tests is still a limitation in TBM diagnosis.

Antecedentes: El diagnóstico de meningitis tuberculosa (MTBC) se ve limitado por la ausencia de técnicas diagnósticas rápidas y precisas en líquido cefalorraquídeo (LCR). En este estudio evaluamos la respuesta inmunoló-gica de anticuerpos anti-antígeno A60 de Mycobacterium tuberculosis en LCR en comparación a la determinación de adenosina deaminasa (ADA). Métodos: Un total de 63 muestras de LCR fueron estudiadas mediante ELISA indirecto para detección de IgG, IgM e IgA anti-A60. Estas muestras incluyeron 17 casos de MTBC confirmada y 46 controles con otras infecciones. Resultados: Los títulos de IgG, IgM e IgA anti A-60 resultaron significativamente superiores en casos de MTBC versus controles (p > 0,01). El anticuerpo con mej or poder discriminatorio resultó IgM, con un área bajo la curva ROC de 0,928 (95%IC 0,8340,978), comparado a 0,863 (95% IC: 0,752-0,936) para ADA (p = NS). La sensibilidad de IgM anti-A60 (nivel de corte > 0,06 U/ml) fue de 94,1% versus 88,2% para ADA (nivel de corte > 6,2 U/ml), p = NS. Ambos IgM anti-A60 y ADA presentaron la misma especificidad baja-moderada (80,4%). Dos casos de MMTBC fueron correctamente identificados por IgM anti-A60 pero no por ALDA. Conclusión: La detección de anticuerpos anti-A60 (IgM) puede ser de ayuda en el diagnostico de MTBC en forma complementaria a la determinación de ALDA. La baja especificidad de ambos tests constituye su principal limitante.

Rapid molecular detection of pulmonary tuberculosis in HIV-infected patients in Santiago, Chile.

SETTING: Santiago, Chile, has a mean annual tuberculosis (TB) rate of 13 per 100 000 population; however, TB incidence in human immunodeficiency virus (HIV) infected individuals is at least 20 times higher. OBJECTIVE: To assess the accuracy of rapid molecular testing for pulmonary TB (PTB) detection in routine care in HIV-infected patients. DESIGN: Cross-sectional study, conducted prospectively in five hospitals between March 2010 and June 2011. HIV-positive subjects with suspected PTB provided sputum or mouth wash samples that were directly processed for acid-fast smear, mycobacterial cultures and Xpert® MTB/RIF. Positive test results were reported on the same day. RESULTS: We enrolled 166 subjects into the study; 50.6% provided two sputum samples, 33.1% only one sputum sample and 16.3% a mouth wash sample. The prevalence of TB was 8.1% (13/160). Diagnostic sensitivity increased from 66.7% (95%CI 39.1-86.2) for acid-fast smear to 91.7% (95%CI 64.6-98.5) for Xpert MTB/RIF, with comparable specificity at 98.6% (146/148, 95%CI 95.2-99.6) and 99.3% (147/148, 95%CI 96.3-99.9). Xpert MTB/RIF allowed early detection of rifampicin resistance in 16.6% of cases, with rapid adjustment to multidrug-resistant treatment. CONCLUSION: Xpert MTB/RIF provided earlier TB diagnosis in 25% more cases than acid-fast smear alone. Its implementation should be considered for TB diagnosis in HIV-positive patients even outside TB-endemic areas.

Perfil clínico y epidemiológico de los casos de tuberculosis atendidos en una red de salud universitaria en Santiago de Chile entre los años 2000-2010 / Clinical and epidemiological profile of tuberculosis in a university hospital in Santiago, Chile

Background:The incidence and epidemiological profile of tuberculosis (TB) has changed significantly in the recent years in Chile. Aim: To evaluate the clinical and epidemiological characteristics of TB cases diagnosed in the last decade at a university hospital in Santiago. Material and Methods: The Mycobacterium tuberculosis culture registry of the microbiology laboratory was reviewed. Medical records of patients with a positive culture registered between 2000 and 2010 were retrieved and analyzed. Results: Two hundred forty positive Mycobacterium tuberculosis cultures were identified and the medical records of 158 of these patients were accessed for analysis. The median age was 53 years (range: 3 to 89), 55.1% were female and nearly 42% had extra-pulmonary TB. Among known risk factors, 32.9% of patients were older than 65 years, 4.4% were health care workers and 3.9% immigrants. Twenty eight percent (41/145) had some type of immunosuppression at diagnosis: 11.7% HIV infection and 16.6% were using immunosuppressive drugs. In this group, a previous tuberculin skin test was done in only 5 cases (12.2%). Adverse events related to TB treatment were reported in 21.3% of cases (17/80). No cases of fulminant hepatitis or death from this cause were identified. Four of 92 patients that had a complete follow up during treatment, died. Two of these patients were receiving steroids. Conclusions:Almost one third of TB cases occurred among immunosuppressed patients and 42% were extra-pulmonary forms. The prevention of TB reactivation in this group should be strengthened.

Angiomatosis bacilar por Bartonella quintana como primera manifestación de infección por VIH: Report of one case / Bacillary angiomatosis

Background: Bacillary angiomatosis is an unusual infectious disease, with angioproliferative lesions, typical of immunocompromised patients. It is caused by Bartonella quintana and Bartonella henselae, two infectious agents of the genus Bartonella, which trigger variable clinical manifestations, including cutaneous vascular and purpuric lesions, and regional lymphadenopathy, and even a systemic disease with visceral involvement. We report a 38-year-old HIV positive male presenting with a history of six months of cutaneous growing purple angiomatous lesions, located also in nasal fossae, rhi-nopharynx and larynx. The skin biopsy was compatible with bacillary angiomatosis. Polymerase chain reaction of a tissue sample showed homology with B. quintana strain Toulouse. The patient was treated with azithromycin and ciprofloxacin with a favorable evolution.

[A comparative study for adenosine deaminase and anti-antigen A-60 antibodies detection for the diagnosis of tuberculous meningitis]. / Comparación de adenosina deaminasa y detección de anticuerpos anti-antígeno A60 para el diagnóstico de meningitis tuberculosa.

BACKGROUND: Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of rapid and accurate diagnostic tools. We evaluated the immunological response to Mycobacterium tuberculosis anti-A60 antibodies in cerebrospinal fluid (CSF) in comparison to adenosine deaminase (ADA) determination, for the diagnosis of TBM. METHODS: A total of 63 CSF samples were analyzed by indirect ELISA for the detection of anti- A60 IgG, IgM and IgA. These include samples from 17 patients with confirmed TBM and 46 control patients with other infections. RESULTS: The mean individual anti-A60 IgM, IgG and IgA CSF antibody titers were significantly higher in TBM in comparison with control groups (p < 0.01). The best discriminatory CSF antibody for confirming TBM diagnosis was IgM, with an area under the receiver operating characteristic curve of 0.928 (95%CI 0.834-0.978), compared to 0.863 (95% CI: 0.752-0.936) for ADA testing (p = NS). The sensitivity of anti- A60 IgM CSF antibody titers (cutoff > 0.06 U/ml) was 94.1% compared to 88.2% for ADA (cutoff > 6.2 U/ml), p = NS. Both anti A60 IgM and ADA showed the same moderate specificity (80.4%). Two cases of TBM were correctly identified by anti-A60 IgM but missed by ADA. CONCLUSION: The ELISA test for anti-antigen A60 antibodies (IgM) is a rapid and sensitive tool for the rapid diagnosis of TBM that can be a complement to ALDA determination. The specificity of both tests is still a limitation in TBM diagnosis.

[Bacillary angiomatosis]. / Angiomatosis bacilar por Bartonella quintana como primera manifestación de infección por VIH: Report of one case.

Bacillary angiomatosis is an unusual infectious disease, with angioproliferative lesions, typical of immunocompromised patients. It is caused by Bartonella quintana and Bartonella henselae, two infectious agents of the genus Bartonella, which trigger variable clinical manifestations, including cutaneous vascular and purpuric lesions, and regional lymphadenopathy, and even a systemic disease with visceral involvement. We report a 38-year-old HIV positive male presenting with a history of six months of cutaneous growing purple angiomatous lesions, located also in nasal fossae, rhi-nopharynx and larynx. The skin biopsy was compatible with bacillary angiomatosis. Polymerase chain reaction of a tissue sample showed homology with B. quintana strain Toulouse. The patient was treated with azithromycin and ciprofloxacin with a favorable evolution.

Metodología de adaptación de una guía clínica para el manejo de pacientes adultos con neumonía adquirida en la comunidad en una red de salud privada / The adaptation methodology of a guideline for the management of adults with community-acquired pneumonia

Background: Clinical practice guidelines (CPG) are widely used as tools for improving quality of health care. Guidelines developed elsewhere, can be adapted using a valid and systematic process. Aim: To describe the methodology used in the process of adaptation of a guideline for the management of adults with community-acquired pneumonia (CAP) in a private health care organization. Material and Methods: We used the ADAPTE framework involving three main phases. At the set-up phase a guideline adaptation group integrated by medical specialists from different disciplines, a methodologist and a nurse coordinator was formed. At the adaptation phase, the specific clinical questions to be addressed by the guidelines were identified. Results: Twenty five guidelines were initially retrieved. After their assessment, the number was reduced to only three. Recommendations from these guidelines were 'mapped' and focused searches were carried out where 'evidence gaps' were identified. An initial draft was written and revised by the adaptation group. At the finalization phase, the external review of the guideline was carried out and a process for the regular review and update of the adapted guideline was defined. Conclusions: We developed a guideline for the management of adults with CAP, adapted to the local context of our health care system, using guidelines developed elsewhere. This guideline creation method can be an efficient means of saving professional resources.

Endemic scrub typhus-like illness, Chile.

We report a case of scrub typhus in a 54-year-old man who was bitten by several terrestrial leeches during a trip to Chiloé Island in southern Chile in 2006. A molecular sample, identified as related to Orientia tsutsugamushi based on the sequence of the16S rRNA gene, was obtained from a biopsy specimen of the eschar on the patient's leg. Serologic analysis showed immunoglobulin G conversion against O. tsutsugamushi whole cell antigen. This case and its associated molecular analyses suggest that an Orientia-like agent is present in the Western Hemisphere that can produce scrub typhus-like illness. The molecular analysis suggests that the infectious agent is closely related, although not identical, to members of the Orientia sp. from Asia.