Lucelly López

IFNγ Response to Mycobacterium tuberculosis, Risk of Infection and Disease in Household Contacts of Tuberculosis Patients in Colombia

Objectives Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNγ produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNγ levels in HHCs correlate with tuberculosis development. Methods A cohort of 2060 HHCs was followed for 2–3 years after exposure to a tuberculosis case. Besides TST, IFNγ responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. Results Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNγ response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNγ responders to CFP-10 (HR 1.82 95% CI 0.79–4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNγ producers was observed (trend Log rank p = 0.007). Discussion CFP-10-induced IFNγ production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprohylaxis to child contacts regardless of BCG vaccination.

High Incidence of Tuberculosis, Low Sensitivity of Current Diagnostic Scheme and Prolonged Culture Positivity in Four Colombian Prisons. A Cohort Study

Objective To determine the incidence of pulmonary tuberculosis (TB) in inmates, factors associated with TB, and the time to sputum smear and culture conversion during TB treatment. Methods Prospective cohort study. All prisoners with respiratory symptoms (RS) of any duration were evaluated. After participants signed consent forms, we collected three spontaneous sputum samples on consecutive days. We performed auramine-rhodamine staining, culturing with the thin-layer agar method, Löwestein-Jensen medium and MGIT, susceptibility testing for first-line drugs; and HIV testing. TB cases were followed, and the times to smear and culture conversion to negative were evaluated. Results Of 9,507 prisoners held in four prisons between April/30/2010 and April/30/2012, among them 4,463 were screened, 1,305 were evaluated for TB because of the lower RS of any duration, and 72 were diagnosed with TB. The annual incidence was 505 cases/100,000 prisoners. Among TB cases, the median age was 30 years, 25% had <15 days of cough, 12.5% had a history of prior TB, and 40.3% had prior contact with a TB case. TB-HIV coinfection was diagnosed in three cases. History of prior TB, contact with a TB case, and being underweight were risk factors associated with TB. Overweight was a protective factor. Almost a quarter of TB cases were detected only by culture; three cases were isoniazid resistant, and two resistant to streptomycin. The median times to culture conversion was 59 days, and smear conversion was 33. Conclusions The TB incidence in prisons is 20 times higher than in the general Colombian population. TB should be considered in inmates with lower RS of any duration. Our data demonstrate that patients receiving adequate anti-TB treatment remain infectious for prolonged periods. These findings suggest that current recommendations regarding isolation of prisoners with TB should be reconsidered, and suggest the need for mycobacterial cultures during follow-up.

IS-seq: A novel high throughput survey of in vivo IS6110 transposition in multiple Mycobacterium tuberculosis genomes

BackgroundThe insertion element IS6110 is one of the main sources of genomic variability in Mycobacterium tuberculosis, the etiological agent of human tuberculosis. Although IS 6110 has been used extensively as an epidemiological marker, the identification of the precise chromosomal insertion sites has been limited by technical challenges. Here, we present IS-seq, a novel method that combines high-throughput sequencing using Illumina technology with efficient combinatorial sample multiplexing to simultaneously probe 519 clinical isolates, identifying almost all the flanking regions of the element in a single experiment.ResultsWe identified a total of 6,976 IS6110 flanking regions on the different isolates. When validated using reference strains, the method had 100% specificity and 98% positive predictive value. The insertions mapped to both coding and non-coding regions, and in some cases interrupted genes thought to be essential for virulence or in vitro growth. Strains were classified into families using insertion sites, and high agreement with previous studies was observed.ConclusionsThis high-throughput IS-seq method, which can also be used to map insertions in other organisms, extends previous surveys of in vivo interrupted loci and provides a baseline for probing the consequences of disruptions in M. tuberculosis strains.

Similar Frequencies of Pseudomonas aeruginosa Isolates Producing KPC and VIM Carbapenemases in Diverse Genetic Clones at Tertiary-Care Hospitals in Medellín, Colombia

ABSTRACT Carbapenem-resistant Pseudomonas aeruginosa has become a serious health threat worldwide due to the limited options available for its treatment. Understanding its epidemiology contributes to the control of antibiotic resistance. The aim of this study was to describe the clinical and molecular characteristics of infections caused by carbapenem-resistant P. aeruginosa isolates in five tertiary-care hospitals in Medellín, Colombia. A cross-sectional study was conducted in five tertiary-care hospitals from June 2012 to March 2014. All hospitalized patients infected by carbapenem-resistant P. aeruginosa were included. Clinical information was obtained from medical records. Molecular analyses included PCR for detection of bla VIM, bla IMP, bla NDM, bla OXA-48, and bla KPC genes plus pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) for molecular typing. A total of 235 patients were enrolled: 91.1% of them were adults (n = 214), 88.1% (n = 207) had prior antibiotic use, and 14.9% (n = 35) had urinary tract infections. The bla VIM-2 and bla KPC-2 genes were detected in 13.6% (n = 32) and 11.5% (n = 27), respectively, of all isolates. Two isolates harbored both genes simultaneously. For KPC-producing isolates, PFGE revealed closely related strains within each hospital, and sequence types (STs) ST362 and ST235 and two new STs were found by MLST. With PFGE, VIM-producing isolates appeared highly diverse, and MLST revealed ST111 in four hospitals and five new STs. These results show that KPC-producing P. aeruginosa is currently disseminating rapidly and occurring at a frequency similar to that of VIM-producing P. aeruginosa isolates (approximately 1:1 ratio) in Medellín, Colombia. Diverse genetic backgrounds among resistant strains suggest an excessive antibiotic pressure resulting in the selection of resistant strains.

High prevalence and risk factors associated with latent tuberculous infection in two Colombian prisons.

SETTING Two prisons in Medellín and Itagüí, Colombia. OBJECTIVE To determine the prevalence of tuberculin skin test (TST) positivity in prisoners and the annual risk of tuberculous infection (ARTI), to identify risk factors associated with a positive result, and to describe progression to active disease. DESIGN Cross-sectional study. Inmates were included if time of incarceration was ⩾1 year and excluded if subjects had had previous or active tuberculosis (TB), or conditions that could hamper TST administration or interpretation. RESULTS We screened 1014 inmates. The overall prevalence of TST positivity was 77.6%. The first TST administration resulted in 66% positivity, and the second TST an additional 11.6%. In Prison One, the ARTI was 5.09% in high TB incidence cell blocks and 2.72% in low TB incidence blocks. In Prison Two, the ARTI was 2.77%. Risk factors associated with TST positivity were history of previous incarceration and length of incarceration. Among all those included in the study, four individuals developed active pulmonary TB. CONCLUSION Prevalence of TST positivity in prisoners and the ARTI were higher than in the general population, but differed between prisons; it is important to apply a second TST to avoid an overestimation of converters during follow-up.

Costo-efectividad de un tratamiento antituberculoso alternativo: seguimiento a convivientes residenciales de los pacientes

Objetivo. Estimar la relacion de costo-efectividad del tratamiento de corta duracion bajoobservacion directa (DOTS), comparandolo con una variacion de dicho tratamiento, que incluyeun mayor seguimiento a los convivientes residenciales de los pacientes (DOTS-R) parael tratamiento de tuberculosis (TB).Metodos. Tomando una perspectiva social que incluye los costos para las institucionesde salud, para los pacientes y sus familiares, y para otras entidades que contribuyen a hacerefectiva la operacion del programa, se evaluaron los costos incurridos con cada una de las dosestrategias y se estimaron razones costo-efectividad adoptando las medidas de efecto usadas porlos programas de control. La estimacion de los costos de cada una de las dos estrategias incluyelos correspondientes a las instituciones de salud que administran el tratamiento, los pacientesy sus familiares, y los de la secretaria de salud que gestiona los programas de salud publica anivel municipal. Con base en estos costos y el numero de casos curados y tratamientos terminadoscomo medidas de resultado de cada una de las estrategias evaluadas, se calcularon lasrazones costo-efectividad y costo incremental.Resultados. El DOTS-R se hallo mas costo-efectivo para lograr tratamientos exitosos queel DOTS. El DOTS-R registro costos de entre US

Negative latent tuberculosis at time of incarceration: identifying a very high-risk group for infection

1 122,4 y US

PPD-induced monocyte mitochondrial damage is associated with a protective effect to develop tuberculosis in BCG vaccinated individuals: A cohort study

1 152,7 por caso curado,comparados con valores de entre US

Strongyloidiasis in humans: diagnostic efficacy of four conventional methods and real-time polymerase chain reaction

1 137,0 y US

Guards in Prisons: A Risk Group for Latent Tuberculosis Infection

1 494,3 correspondientes al DOTS. Laproporcion de casos tratados con exito fue mayor con DOTS-R que con DOTS.Conclusiones. El DOTS-R es una alternativa costo-efectiva promisoria para mejorar elcontrol de la TB en sitios endemicos. Se recomienda a las autoridades del sector salud incorporaren su gestion institucional del programa contra la TB, acciones de seguimiento de losconvivientes de pacientes, con la participacion del personal de salud y los recursos fisicos yfinancieros que apoyan actualmente dicho programa.(AU)