Transmission Dynamics of a Mycobacterium tuberculosis Complex Outbreak in an Indigenous Population in the Colombian Amazon Region.

Whole genome sequencing (WGS) has become the main tool for studying the transmission of Mycobacterium tuberculosis complex (MTBC) strains; however, the clonal expansion of one strain often limits its application in local MTBC outbreaks. The use of an alternative reference genome and the inclusion of repetitive regions in the analysis could potentially increase the resolution, but the added value has not yet been defined. Here, we leveraged short and long WGS read data of a previously reported MTBC outbreak in the Colombian Amazon Region to analyze possible transmission chains among 74 patients in the indigenous setting of Puerto Nariño (March to October 2016). In total, 90.5% (67/74) of the patients were infected with one distinct MTBC strain belonging to lineage 4.3.3. Employing a reference genome from an outbreak strain and highly confident single nucleotide polymorphisms (SNPs) in repetitive genomic regions, e.g., the proline-glutamic acid/proline-proline-glutamic-acid (PE/PPE) gene family, increased the phylogenetic resolution compared to a classical H37Rv reference mapping approach. Specifically, the number of differentiating SNPs increased from 890 to 1,094, which resulted in a more granular transmission network as judged by an increasing number of individual nodes in a maximum parsimony tree, i.e., 5 versus 9 nodes. We also found in 29.9% (20/67) of the outbreak isolates, heterogenous alleles at phylogenetically informative sites, suggesting that these patients are infected with more than one clone. In conclusion, customized SNP calling thresholds and employment of a local reference genome for a mapping approach can improve the phylogenetic resolution in highly clonal MTBC populations and help elucidate within-host MTBC diversity. IMPORTANCE The Colombian Amazon around Puerto Nariño has a high tuberculosis burden with a prevalence of 1,267/100,000 people in 2016. Recently, an outbreak of Mycobacterium tuberculosis complex (MTBC) bacteria among the indigenous populations was identified with classical MTBC genotyping methods. Here, we employed a whole-genome sequencing-based outbreak investigation in order to improve the phylogenetic resolution and gain new insights into the transmission dynamics in this remote Colombian Amazon Region. The inclusion of well-supported single nucleotide polymorphisms in repetitive regions and a de novo-assembled local reference genome provided a more granular picture of the circulating outbreak strain and revealed new transmission chains. Multiple patients from different settlements were possibly infected with at least two different clones in this high-incidence setting. Thus, our results have the potential to improve molecular surveillance studies in other high-burden settings, especially regions with few clonal multidrug-resistant (MDR) MTBC lineages/clades.

Close Related Drug-Resistance Beijing Isolates of Mycobacterium tuberculosis Reveal a Different Transcriptomic Signature in a Murine Disease Progression Model.

Mycobacterium tuberculosis (MTB) lineage 2/Beijing is associated with high virulence and drug resistance worldwide. In Colombia, the Beijing genotype has circulated since 1997, predominantly on the pacific coast, with the Beijing-Like SIT-190 being more prevalent. This genotype conforms to a drug-resistant cluster and shows a fatal outcome in patients. To better understand virulence determinants, we performed a transcriptomic analysis with a Beijing-Like SIT-190 isolate (BL-323), and Beijing-Classic SIT-1 isolate (BC-391) in progressive tuberculosis (TB) murine model. Bacterial RNA was extracted from mice lungs on days 3, 14, 28, and 60. On average, 0.6% of the total reads mapped against MTB genomes and of those, 90% against coding genes. The strains were independently associated as determined by hierarchical cluster and multidimensional scaling analysis. Gene ontology showed that in strain BL-323 enriched functions were related to host immune response and hypoxia, while proteolysis and protein folding were enriched in the BC-391 strain. Altogether, our results suggested a differential bacterial transcriptional program when evaluating these two closely related strains. The data presented here could potentially impact the control of this emerging, highly virulent, and drug-resistant genotype.

Heterogeneous fitness landscape cues, pknG low expression, and phthiocerol dimycocerosate low production of Mycobacterium tuberculosis ATCC25618 rpoB S450L in enriched broth.

Multidrug-resistant tuberculosis (isoniazid/rifampin[RIF]-resistant TB) ravages developing countries. Fitness is critical in clinical outcomes. Previous studies on RIF-resistant TB (RR-TB) showed competitive fitness gains and losses, with rpoB-S450L as the most isolated/fit mutation. This study measured virulence/resistance genes, phthiocerol dimycocerosate (PDIM) levels and their relationship with rpoB S450L ATCC25618 RR-TB strain fitness. After obtaining 10 different RR-TB GenoType MTBDRplus 2.0-genotyped isolates (with nontyped, S441, H445 and S450 positions), only one S450L isolate (R9, rpoB-S450L ATCC 25618, RR 1 µg/mL) was observed, with H445Y being the most common. A competitive fitness in vitro assay with wild-type (wt) ATCC 25618: R9 1:1 in 50 mL Middlebrook 7H9/OADC was performed, and generation time (G) in vitro and relative fitness were obtained. mRNA and PDIM were extracted on log and stationary phases. Fitness decreased in rpoB S450L and H445Y strains, with heterogeneous fitness cues in three biological replicas of rpoB-S450L: one high and two low fitness replicas. S450L strain had significant pknG increase. Compared with S450L, wt-rpoB showed increased polyketide synthase ppsA expression and high PDIM peak measured by HPLC-MS in log phase compared to S450L. This contrasts with previously increased PDIM in other RR-TB isolates.

First approach to the population structure of Mycobacterium tuberculosis complex in the indigenous population in Puerto Nariño-Amazonas, Colombia.

INTRODUCTION: Tuberculosis affects vulnerable groups to a greater degree, indigenous population among them. OBJECTIVE: To determine molecular epidemiology of clinical isolates of Mycobacterium tuberculosis circulating in an indigenous population through Spoligotyping and 24-loci MIRU-VNTR. METHODOLOGY: A descriptive cross-sectional study was conducted in 23 indigenous communities of Puerto Nariño-Amazonas, Colombia. Recovered clinical isolates were genotyped. For genotyping analyzes global SITVIT2 database and the MIRU-VNTRplus web portal were used. RESULTS: 74 clinical isolates were recovered. Genotyping of clinical isolates by spoligotyping determined 5 different genotypes, all of them belonged to Euro-American lineage. By MIRU-VNTR typing, a total of 14 different genotypes were recorded. Furthermore, polyclonal infection was found in two patients from the same community. The combination of the two methodologies determined the presence of 19 genotypes, 8 formed clusters with 63 clinical isolates in total. Based on epidemiological information, it was possible to establish a potential chain of active transmission in 10/63 (15.9%) patients. CONCLUSIONS: High genomic homogeneity was determined in the indigenous population suggesting possible chains of active transmission. The results obtained showed that specific genotypes circulating among the indigenous population of Colombia are significantly different from those found in the general population.

Population structure of multidrug-resistant Mycobacterium tuberculosis clinical isolates in Colombia.

Emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) isolates is a major public health problem that threatens progress made in tuberculosis (TB) care and control worldwide. In Colombia, the prevalence of MDR tuberculosis (MDR-TB) has increased slowly but steadily since 2001. However, the population structure of the MDR-TB strains circulating in Colombia is sparsely known. In this work, 203 MDR isolates isolated in 2012-2013 were collected, and characterized by spoligotyping, followed by 24-loci MIRU-VNTR (data available for 190 isolates). The most prevalent genotypes corresponded to SIT42/LAM9 (12.81%), SIT62/H1 (10.34%), and SIT190/Beijing (10.34%). A fine analysis showed that although the MDR strains came from 29 of the 33 departments of Colombia, the distribution of these main lineages was not at random and depended on the city of isolation (p-value <0.000001). Both LAM and Beijing lineage strains were significantly associated with MDR-TB (p-value <0.0001): LAM lineage was associated with 2 patterns of MDR, namely combined resistance to INH + Rifampin (HR), and to SHRE (Streptomycin + INH + Rifampin + Ethambutol), while the Beijing lineage strains were essentially associated with MDR (SHRE). Interestingly, distribution of genotypic lineages in function of drug resistance information (e.g. pansusceptible vs. MDR) was different in our setting as compared to other countries in Latin America. However, MIRU-VNTR patterns were unique for all strains, an observation that did not support active transmission of circulating MDR clones.

Genetic diversity of Mycobacterium tuberculosis clinical isolates from HIV-TB patients from two public hospitals at Bogotá, Colombia.

The co-infection of TB/HIV is an increasing problem for public health worldwide. In Colombia, of 13.871 confirmed cases of TB in 2016 (prevalence of 0,028%) 14% correspond to HIV co-infection. However, we have scarce information regarding genetic diversity of strains infecting HIV patients. In this study, we carried-out an active search of cases of TB in 356 HIV-infected individuals, who were enrolled in two Public Hospitals at Bogotá-Colombia, between 2014 and 2015. We found 49 patients with HIV-TB co-infection. Genetic characterization of Mycobacterium tuberculosis (Mtb) isolates from these patients showed a predominance of three major sub-lineages: Haarlem (n = 26), LAM (n = 12) and T (n = 11). Remarkably, the most predominant pattern in the present study (SIT62/H1, n = 11) is very specific to this country. Indeed, taking in account distribution in countries with at least 3% of SIT62/H1, 36% of all such patterns collected worldwide were from Colombia. Furthermore, Colombia alone is responsible for almost all the SIT62/H1 strains in South America, suggesting a successful transmission of this genotype inside TB/HIV population from Colombia.

Characterization of clinical isolates of Mycobacterium tuberculosis from indigenous peoples of Colombia / Caracterización de aislamientos clínicos de Mycobacterium tuberculosis de pueblos indígenas de Colombia

INTRODUCTION: Tuberculosis continues to be a public health priority. Indigenous peoples are vulnerable groups with cultural determinants that increase the risk of the disease. OBJECTIVE: To determine molecular epidemiology and phenotypical features and of Mycobacterium tuberculosis isolates from indigenous people in Colombia during the period from 2009 to 2014. MATERIALS AND METHODS: We conducted an analytical observational study; we analyzed 234 isolates to determine their patterns of sensitivity to antituberculosis drugs and their molecular structures by spoligotyping. RESULTS: The isolates came from 41 indigenous groups, predominantly the Wayúu (13.10%) and Emberá Chamí (11.35%). We found 102 spoligotypes distributed among seven genetic families (37.2% LAM, 15.8% Haarlem, 8.1% T, 3.4% U, 2.6% S, 2.1% X, and 0.9%, Beijing). The association analysis showed that the non-clustered isolates were related to prior treatment, relapse, orphan spoligotypes, and the Beijing family. The H family presented an association with the Arhuaco and Camëntsá indigenous groups, the U family was associated with the Wounaan group, and the T family was associated with the Motilón Barí group. CONCLUSIONS: This is the first national study on M. tuberculosis characterization in indigenous groups. The study evidenced that diagnosis in indigenous people is late. We described 53% of orphan patterns that could be typical of the Colombian indigenous population. The high percentage of grouping by spoligotyping (62%) could indicate cases of active transmission, a situation that should be corroborated using a second genotyping marker. A new Beijing spoligotype (Beijing-like SIT 406) was identified in Colombia.

Introducción. La tuberculosis es prioridad de salud pública. Los pueblos indígenas son vulnerables debido a los factores culturales determinantes que aumentan el riesgo de tuberculosis. Objetivo. Determinar la epidemiologia molecular y las características fenotípicas de los aislamientos de Mycobacterium tuberculosis de pueblos indígenas de Colombia entre 2009 y 2014. Materiales y métodos. Se hizo un estudio observacional analítico; se analizaron 234 aislamientos para determinar la sensibilidad a los fármacos antituberculosos y la estructura molecular usando spoligotyping. La información epidemiológica se recolectó utilizando el formato único de vigilancia de micobacterias. Resultados. Los aislamientos provenían de 41 grupos indígenas, principalmente los wayúu (13,10 %) y emberá chamí (11,35 %). Se encontraron 102 genotipos distribuidos en siete familias genéticas (37,2 %, LAM; 15,8 %, Haarlem; 8,1 %, T; 3,4 %, U; 2,6 %, S; 2,1 %, X, y 0,9%, Beijing). El análisis de asociación mostró que los aislamientos no agrupados se asociaron con el tratamiento previo, las recaídas, los genotipos huérfanos y la familia Beijing. La familia H presentó una asociación con los grupos indígenas arhuaco y camëntsá, la familia U se asoció con el grupo wounaan y la familia T con el grupo motilón barí. Conclusiones. Este es el primer estudio nacional de caracterización de M. tuberculosis en grupos indígenas. Se evidenció que el diagnóstico en indígenas es tardío, y que 53 % de los patrones huérfanos podrían ser típicos de la población indígena colombiana. El alto porcentaje de agrupamiento por spoligotyping (62%) podría indicar casos de transmisión activa, una situación que debe ser corroborada usando un segundo marcador de genotipificación. Se identificó un nuevo genotipo (Beijing-like SIT 406) en Colombia.

Active and latent tuberculosis among inmates in La Esperanza prison in Guaduas, Colombia.

INTRODUCTION: Active tuberculosis (TB) and latent tuberculosis infection (LTBI) are a public health threat in prisons around the world. The objectives of the study were to estimate the prevalence of LTBI and TB as well as to investigate TB transmission inside one prison, in Colombia. METHODS: A Cross-sectional study was conducted in inmates who agreed to participate. Inmates with respiratory symptoms (RS) of any duration underwent to medical evaluation and three sputum samples were taken for smear microscopy and culture for TB diagnosis. Drug susceptibility was analyzed using BACTEC MGIT 960 and GenoType MTBDRplus. Molecular genotyping of Mycobacterium tuberculosis isolates was performed by 24-Locus MIRU-VNTR and spoligotyping. LTBI was evaluated according to the result of the tuberculin skin test (TST). Close contact investigation was conducted inside the prison for inmates that shared the cell with the index TB case. RESULTS: Among 301/2,020 (15%) inmates with RS of any duration, 8% were diagnosed with active TB. The prevalence of active TB was 1,026 cases/100,000 inmates. We isolated M. tuberculosis in 19/24 (79%) TB cases, 94.7% were susceptible to first line drugs and only one was monoresistant to isoniazid. The most prevalent sub-lineage was Haarlem (68.4%), followed by LAM (26.3%) and T superfamily (5.3%). 24-Locus MIRU-VNTR typing results alone or in combination with spoligotyping identified three clusters containing two isolates each. Two clusters corresponded to inmates that shared the same cell, but each one was located in different blocks of the prison. Inmates from the last cluster were in the same block in nearby cells. TST reading was performed in 95.6% inmates, and 67.6% had a positive reaction. CONCLUSIONS: The prevalence of LTBI and TB was higher in prison than in the general population. Molecular genotyping suggests that TB in this prison is mainly caused by strains imported by inmates or endogenous reactivation.

Tuberculosis associated with tumor necrosis factor-α antagonists, case description and analysis of reported cases in Colombia.

Tumor necrosis factor-α (TNF-α) is an important fundamental cytokine during the immune response against cancer and infections such as tuberculosis. This molecule also plays a key pathogenic role in complex and difficult-to-treat diseases such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriasis and ulcerative colitis. The treatment of these diseases frequently needs TNF-α antagonists, which has been related to an increased risk of developing tuberculosis, mycoses, and other severe infections.We report the case of a 68-year-old man with Crohn's disease, who developed  disseminated tuberculosis due to anti-TNF-α immunosuppressive therapy. The diagnosis was based on the histopathological findings and molecular biology assays.We discuss the clinical presentation and workup of this case, and we present a comparative analysis of tuberculosis cases associated with anti-TNF-α reported in Colombia during the last 10 years emphasizing on the diagnosis and treatment of latent tuberculosis.

[Prevalence and risk factors associated to tuberculosis and non-tuberculous mycobacterial infections in HIV-positive patients in Bogotá].

INTRODUCTION: Tuberculosis is one of the most widely distributed infectious diseases worldwide. It is the most common cause of mortality among AIDS patients. In Colombia, 12,918 tuberculosis cases were notified, and 926 deaths were reported in 2015. OBJECTIVE: To determine the prevalence and risk factors associated to mycobacterial infections in HIVpositive patients in two public hospitals from Bogotá. MATERIALS AND METHODS: A prospective and descriptive study was carried out by an active search for tuberculosis cases and non-tuberculous mycobacterial infections in HIV-positive patients. We considered demographic, social, clinical, and personal habits as variables. Statistical analyses were done using Stata 13™ software. RESULTS: Three hundred and fifty six patients were included, 81.2% were men and 18.8% were women; the mean age was 36.5 years. Tuberculosis infection had a frequency of 19.9% (95% CI: 15.9-24.5%) and non-tuberculous mycobacterial infection had a 3.9% frequency (95% CI: 2.16-6.5%). Bivariate analysis showed a statistically significant association between tuberculosis infection and CD4+ T cell counts (p=0.003), viral load (p=0.008), antiretroviral therapy (p=0.014), and body mass index (BMI) <18 kg/m2 (p=0.000). In non-tuberculous mycobacterial infections there was a statistically significantassociation with BMI (p=0.027) and CD4+ T cell counts (p=0.045). CONCLUSION: Factors associated with an impaired immune system caused by HIV infection are an important risk factor for developing tuberculosis. The lack of antiretroviral therapy and the BMI were also important risk factors for tuberculosis.

Tuberculosis asociada a antagonistas del factor de necrosis tumoral alfa, presentación de un caso y análisis de los casos reportados en Colombia / Tuberculosis associated with tumor necrosis factor-α antagonists, case description and analysis of reported cases in Colombia

Resumen El factor de necrosis tumoral alfa (FNTα) es una citocina fundamental en la reacción inmunitaria frente al cáncer y a infecciones tales como la tuberculosis. Esta molécula también desempeña un papel fundamental en la patogenia de enfermedades complejas y de difícil tratamiento, como la artritis reumatoidea, la espondilitis anquilosante, la enfermedad de Crohn, la psoriasis y la colitis ulcerativa, condiciones que suelen requerir el uso de medicamentos que antagonizan la función del factor de necrosis tumoral alfa, el cual se ha relacionado con un incremento del riesgo de desarrollar tuberculosis, micosis y otras infecciones graves. Se reporta el caso de un hombre de 68 años de edad con diagnóstico de enfermedad de Crohn, a quien se le administró tratamiento con antagonistas del FNTα, debido a lo cual desarrolló tuberculosis diseminada. El diagnóstico se hizo con base en los hallazgos histológicos y mediante pruebas de biología molecular. Se discuten la presentación clínica y el manejo del caso, y se hace un análisis comparativo de los casos de tuberculosis asociados al tratamiento con antagonistas del FNTα reportados en Colombia durante los últimos diez años, con especial énfasisen la detección y el tratamiento de la tuberculosis latente.

Abstract Tumor necrosis factor-α (TNF-α) is an important fundamental cytokine during the immune response against cancer and infections such as tuberculosis. This molecule also plays a key pathogenic role in complex and difficult-to-treat diseases such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriasis and ulcerative colitis. The treatment of these diseases frequently needs TNF-αantagonists, which has been related to an increased risk of developing tuberculosis, mycoses, and other severe infections. We report the case of a 68-year-old man with Crohn's disease, who developed disseminated tuberculosis due to anti-TNF-α immunosuppressive therapy. The diagnosis was based on the histopathological findings and molecular biology assays. We discuss the clinical presentation and workup of this case, and we present a comparative analysis of tuberculosis cases associated with anti-TNF-α reported in Colombia during the last 10 years emphasizing on the diagnosis and treatment of latent tuberculosis.

Prevalencia y factores asociados a la tuberculosis y las micobacteriosis en pacientes positivos para HIV en Bogotá / Prevalence and risk factors associated to tuberculosis and non-tuberculous mycobacterial infections in HIV-positive patients in Bogotá

Resumen Introducción. La tuberculosis es una de las enfermedades infecciosas de más amplia distribución en el mundo y constituye una de las primeras causas de muerte en pacientes con sida. En Colombia, en el 2015, se notificaron 12.918 casos de tuberculosis y 926 muertes. Objetivo. Determinar la prevalencia y los factores asociados a infecciones micobacterianas en pacientes infectados con el virus de inmunodeficiencia humana (HIV) en dos hospitales públicos de Bogotá. Materiales y métodos. Se hizo un estudio descriptivo de corte transversal con búsqueda activa de casos de tuberculosis y micobacteriosis en pacientes positivos para HIV. Se estudiaron variables demográficas, sociales, clínicas y de hábitos personales. Los análisis estadísticos se hicieron con el programa Stata 13TM. Resultados. Se incluyeron en el estudio 356 pacientes: 81,2 % hombres y 18,8 %, mujeres, con una media de edad de 36,5 años. La frecuencia de la tuberculosis fue de 19,9 % (IC95% 15,9-24,5 %) y la de infecciones por micobacterias no tuberculosas, de 3,9 % (IC95% 2,16-6,5 %). El análisis bivariado evidenció una asociación estadísticamente significativa entre la tuberculosis y el conteo de linfocitos TCD4+ (p=0,003), la carga viral (p=0,0008), el tratamiento antirretroviral (p=0,017) y un índice de masa corporal (IMC) menor de 18 kg/m2 (p=0,000). En las micobacteriosis solamente se presentó asociación estadísticamente significativa con el IMC (p=0,017) y con el conteo de linfocitos TCD4+ (p=0,045). Conclusión. Los factores asociados al deterioro del sistema inmunitario causados por el HIV, así como el no administrar el tratamiento antirretroviral de gran actividad y el IMC, constituyeron factores de riesgo para desarrollar la tuberculosis.

Abstract Introduction. Tuberculosis is one of the most widely distributed infectious diseases worldwide. It is the most common cause of mortality among AIDS patients. In Colombia, 12,918 tuberculosis cases were notified, and 926 deaths were reported in 2015. Objective. To determine the prevalence and risk factors associated to mycobacterial infections in HIV-positive patients in two public hospitals from Bogotá. Materials and methods. A prospective and descriptive study was carried out by an active search for tuberculosis cases and non-tuberculous mycobacterial infections in HIV-positive patients. We considered demographic, social, clinical, and personal habits as variables. Statistical analyses were done using Stata 13TM software. Results. Three hundred and fifty six patients were included, 81.2% were men and 18.8% were women; the mean age was 36.5 years. Tuberculosis infection had a frequency of 19.9% (95% CI: 15.9-24.5%) and non-tuberculous mycobacterial infection had a 3.9% frequency (95% CI: 2.16-6.5%). Bivariate analysis showed a statistically significant association between tuberculosis infection and CD4+ T cell counts (p=0.003), viral load (p=0.008), antiretroviral therapy (p=0.014), and body mass index (BMI) <18 kg/m2 (p=0.000). In non-tuberculous mycobacterial infections there was a statistically significant association with BMI (p=0.027) and CD4+ T cell counts (p=0.045). Conclusion. Factors associated with an impaired immune system caused by HIV infection are an important risk factor for developing tuberculosis. The lack of antiretroviral therapy and the BMI were also important risk factors for tuberculosis.

[Prevalence of Mycobacterium tuberculosis resistance to quinolones and injectables in Colombia, 2012-2013].

INTRODUCTION: Tuberculosis is a health problem worldwide. The World Health Organization estimated 9.6 million new cases and 480,000 multirresistant cases for 2014. The assessment of resistance to quinolones and injectables was implemented only a few years ago, so its prevalence is not known. OBJECTIVE: To determine the prevalence of resistance to amikacin, capreomycin and ofloxacin in cases of tuberculosis resistant to isoniazid and/or rifampin during 2012-2013. MATERIALS AND METHODS: This was a cross-sectional study of 489 isolates resistant to isoniazid and/or rifampin. We used the Bactec MGITTM technique for susceptibility tests. For analyzing the rate of resistance, we grouped cases according to the history of treatment with second line drugs. RESULTS: In the 438 new cases, the drug that showed greater overall resistance was kanamycin with 7.1 % (95% CI: 4.6 to 9.6). In 51 previously treated cases, this highest resistance was 27.5 % (95% CI:14.2 to 40.7). The overall resistance was higher in cases with a history of treatment with quinolones and injectables. We found seven cases of extremely resistant tuberculosis. CONCLUSION: This study demonstrates the presence of resistance to second line drugs in people with drug-resistant tuberculosis with and without previous treatment with quinolones and/or injectables, these latter having a higher percentage of resistance. For that reason, it is essential to perform susceptibility testing and analyze this information routinely.

Prevalencia de la resistencia de Mycobacterium tuberculosis a quinolonas y fármacos inyectables en Colombia, 2012-2013 / Prevalence of Mycobacterium tuberculosis resistance to quinolones and injectables in Colombia, 2012-2013

Resumen Introducción: La tuberculosis es un problema de salud pública a nivel mundial. En 2014, la Organización Mundial de la Salud estimó que se habían presentado 9,6 millones de casos nuevos y 480.000 multirresistentes. La evaluación de la resistencia a fármacos inyectables y a quinolonas se introdujo hace pocos años, por lo cual no se conoce su prevalencia. Objetivo: Determinar la prevalencia de la resistencia a amicacina, kanamicina, capreomicina y ofloxacina en casos de tuberculosis resistente a isoniacida, rifampicina o a ambas, entre 2012 y 2013. Materiales y métodos: Se hizo un estudio de corte transversal con 489 aislamientos resistentes a isoniacida o rifampicina. Las pruebas de sensibilidad se hicieron con la técnica Bactec MGITTM. Para el análisis de la proporción de la resistencia, los casos se agruparon según el antecedente de tratamiento con medicamentos de segunda línea. Resultados: En los 438 casos nuevos, la resistencia global a la kanamicina fue mayor (7,1 %; IC95% 4,6-9,6); en los 51 casos previamente tratados, dicha resistencia fue de 27,5 % (IC95% 14,2-40,7). La resistencia global fue mayor en casos con antecedentes de tratamiento con quinolonas y fármacos inyectables. Se encontraron siete casos de tuberculosis extremadamente resistente. Conclusión: El estudio evidenció la presencia de resistencia a fármacos de segunda línea en personas con tuberculosis farmacorresistente sin tratamiento previo o tratadas previamente con quinolonas o fármacos inyectables, estos últimos con mayor porcentaje de resistencia. En consecuencia, es esencial practicar rutinariamente las pruebas de sensibilidad y el análisis de esta información.

Abstract Introduction: Tuberculosis is a health problem worldwide. The World Health Organization estimated 9.6 million new cases and 480,000 multirresistant cases for 2014. The assessment of resistance to quinolones and injectables was implemented only a few years ago, so its prevalence is not known. Objective: To determine the prevalence of resistance to amikacin, capreomycin and ofloxacin in cases of tuberculosis resistant to isoniazid and/or rifampin during 2012-2013. Materials and methods: This was a cross-sectional study of 489 isolates resistant to isoniazid and/or rifampin. We used the Bactec MGITTM technique for susceptibility tests. For analyzing the rate of resistance, we grouped cases according to the history of treatment with second line drugs. Results: In the 438 new cases, the drug that showed greater overall resistance was kanamycin with 7.1 % (95% CI: 4.6 to 9.6). In 51 previously treated cases, this highest resistance was 27.5 % (95% CI: 14.2 to 40.7). The overall resistance was higher in cases with a history of treatment with quinolones and injectables. We found seven cases of extremely resistant tuberculosis. Conclusion: This study demonstrates the presence of resistance to second line drugs in people with drug-resistant tuberculosis with and without previous treatment with quinolones and/or injectables, these latter having a higher percentage of resistance. For that reason, it is essential to perform susceptibility testing and analyze this information routinely.

Cerebral microcalcifications in a newborn with congenital tuberculosis.

Tuberculosis is a serious public health problem worldwide. In 2012, the World Health Organization estimated 8.6 million new cases and 1.3 million deaths due to the disease. In 2011, the incidence in Colombia was 24 cases per 100,000 inhabitants. There is little information about tuberculosis in pregnant women, and congenital infection is considered a rare disease that is difficult to diagnose, leads to high mortality, and may be confused with tuberculosis acquired after birth. In addition, it has been associated with HIV infection in mothers and infants. Moreover, there is increasing incidence of congenital syphilis in the world. In Colombia, the prevalence is 2.5 cases per 1,000 births and its frequency in the Instituto Materno Infantil-Hospital La Victoria is one case per 57 births. We report the case of a newborn under treatment for congenital syphilis and in whom microcalcifications were found in a transfontanelar ultrasound. This finding warned about the existence of another infectious agent. PCR was negative for cytomegalovirus, and IgM titers for toxoplasma, rubella and herpes I and II were also negative. After learning about a history of incomplete treatment for tuberculosis in the mother, we suspected the presence of an infection by the tubercle bacillus in the newborn. No acid-fast bacilli were demonstrated in three gastric juice samples. The IS6110 PCR assay was found positive in cerebrospinal fluid and urine, but not in blood. The newborn was treated with crystalline penicillin for 10 days along with isoniazid, rifampicin, pyrazinamide and streptomycin. The patient is currently under clinical monitoring.

Microcalcificaciones cerebrales en un recién nacido con tuberculosis congénita / Cerebral microcalcifications in a newborn with congenital tuberculosis

La tuberculosis es un problema grave de salud pública a nivel mundial. La Organización Mundial de la Salud estimaba que en el 2012 se habían presentado 8,6 millones de casos nuevos y 1,3 millones de muertes a causa de la enfermedad. En Colombia, la incidencia en 2011 fue de 24 casos por 100.000 habitantes. No hay información sobre la tuberculosis en las mujeres gestantes y la infección congénita se considera una enfermedad rara, de difícil diagnóstico, que genera alta mortalidad y puede confundirse con la adquirida después del nacimiento. La tuberculosis se ha relacionado con la infección por el virus de la inmunodeficiencia humana en madres y neonatos. Por otra parte, los casos de sífilis congénita han aumentado en el mundo y, en Colombia, la prevalencia es de 2,5 casos por 1.000 nacimientos, en tanto que, en el Instituto Materno Infantil-Hospital La Victoria, la frecuencia es de un caso por 57 nacimientos. Se presenta el caso de un recién nacido en tratamiento para sífilis congénita que presentó microcalcificaciones detectadas en una ecografía transfontanelar, lo que alertó sobre la existencia de otro agente infeccioso. La prueba de PCR fue negativa para citomegalovirus, así como los títulos de IgM para toxoplasma, rubéola y herpes I y II. Dado el antecedente de un tratamiento incompleto para tuberculosis en la mujer gestante, se sospechó la presencia de infección por el bacilo de la tuberculosis. No se encontraron bacilos ácido-alcohol resistentes en tres muestras de jugo gástrico, y la prueba de PCR-IS 6110 fue positiva en líquido cefalorraquídeo y en orina, pero no en sangre. El recién nacido recibió tratamiento con penicilina cristalina durante 10 días, así como con isoniacida, rifampicina, pirazinamida y estreptomicina. Actualmente se le hace seguimiento clínico.

Tuberculosis is a serious public health problem worldwide. In 2012, the World Health Organization estimated 8.6 million new cases and 1.3 million deaths due to the disease. In 2011, the incidence in Colombia was 24 cases per 100,000 inhabitants. There is little information about tuberculosis in pregnant women, and congenital infection is considered a rare disease that is difficult to diagnose, leads to high mortality, and may be confused with tuberculosis acquired after birth. In addition, it has been associated with HIV infection in mothers and infants. Moreover, there is increasing incidence of congenital syphilis in the world. In Colombia, the prevalence is 2.5 cases per 1,000 births and its frequency in the Instituto Materno Infantil-Hospital La Victoria is one case per 57 births. We report the case of a newborn under treatment for congenital syphilis and in whom microcalcifications were found in a transfontanelar ultrasound. This finding warned about the existence of another infectious agent. PCR was negative for cytomegalovirus, and IgM titers for toxoplasma, rubella and herpes I and II were also negative. After learning about a history of incomplete treatment for tuberculosis in the mother, we suspected the presence of an infection by the tubercle bacillus in the newborn. No acid-fast bacilli were demonstrated in three gastric juice samples. The IS 6110 PCR assay was found positive in cerebrospinal fluid and urine, but not in blood. The newborn was treated with crystalline penicillin for 10 days along with isoniazid, rifampicin, pyrazinamide and streptomycin. The patient is currently under clinical monitoring.

Mal de Pott en un indígena colombiano / Pott´s disease in a Colombian indigenous man

Cada año mueren alrededor de dos millones de personas a causa de la tuberculosis y se estima que un tercio de la población mundial está infectada con el bacilo que la causa, pero solo entre 5 y 10 % desarrolla la enfermedad. El riesgo de que la enfermedad progrese al estado activo depende de factores endógenos y exógenos. Las comunidades indígenas son un grupo con un alto riesgo de infectarse y enfermar de tuberculosis; además de factores como el aislamiento geográfico, el abandono social y cultural y la desnutrición, se han identificado en ellos polimorfismos genéticos que los hacen más propensos a la infección. La tuberculosis vertebral es la forma más destructiva de la enfermedad y representa cerca de la mitad de los casos de tuberculosis esquelética. Se presenta el caso de un paciente indígena colombiano con tuberculosis vertebral y resultado negativo para HIV. El diagnóstico se basó en los hallazgos clínicos y en los estudios de imaginología, y se confirmó mediante la prueba molecular rápida Genotype MTBDR plus ® y de la reacción en cadena de la polimerasa PCR IS6110; el cultivo fue negativo a las 16 semanas de incubación. Se discuten brevemente la patogénesis, el diagnóstico y el tratamiento, y se comentan algunos aspectos relacionados con la situación de la tuberculosis en las comunidades indígenas colombianas.

Approximately 2 million people die each year from tuberculosis. One third of the world´s population is estimated to be infected with the tuberculosis bacillus, although only 5-10% will develop the disease in their lifetime. The disease progression risk depends on endogenous and exogenous factors. Indigenous communities are a high-risk group for infection and development of tuberculosis. In addition to factors such as geographical isolation, social and cultural neglect and malnutrition, susceptibility to genetic polymorphisms has been identified in them. Spinal tuberculosis is the most destructive form of the disease, which represents approximately half of all cases of skeletal tuberculosis. The case of an HIV negative, indigenous Colombian man is presented. His diagnosis was done based on clinical and image findings, and it was confirmed with the rapid molecular assay Genotype MTBDRplus ® and IS6110 PCR.The culture in solid media was negative after 16 weeks. We briefly discuss the pathogenesis, diagnosis and treatment. Finally, we comment on some aspects of the situation of tuberculosis among indigenous Colombian communities.

[Phenotypic and genotypic diagnosis of bone and miliary tuberculosis in an HIV+ patient in Bogotá, Colombia]. / Diagnóstico genotípico y fenotípico de tuberculosis ósea y miliar en un paciente positivo para HIV en Bogotá, Colombia.

Tuberculosis is the single most frequent cause of death by an infectious agent worldwide. Diagnosis of extra-pulmonary tuberculosis is not always possible through conventional methods, due to the long time required for cultures and the paucibacillary nature of samples; hence the need of rapid molecular methods. HIV infection increases the risk of tuberculosis, and HIV/tuberculosis coinfection is associated with higher mortality. We describe the case of a 56-year old mestizo male patient suspected of having tuberculosis who consulted the San Ignacio Hospital in Bogotá with a two-month history of a painful ulcerated lesion over the distal third area of the right forearm and in whom HIV coinfection was confirmed. Bone and pulmonary histological examination evidenced multiple granulomas, giant cells and fibrosis. Cultures and IS6110-PCR from lung and bone tissues were positive for Mycobacterium tuberculosis complex. Mycobacterium tuberculosis isolates were sensitive to first line drugs.