Risk of infection and disease progression in children exposed to tuberculosis at home, Colombia / Riesgo de infección y progresión de la enfermedad en niños expuestos a tuberculosis en el hogar, Colombia

Abstract Aim: To assess the risk of tuberculosis (infection and disease) in children less than 15 years' old who are household contacts of pulmonary tuberculosis patients in three Colombian cities (Medellín, Cali, and Popayán). Methods: A cohort of 1,040 children household contacts of 380 adults with smear-positive pulmonary tuberculosis was followed up for 24 months. Study period 2005-2009. Results: Tuberculin skin test was positive (≥10 mm) in 43.7% (95% CI: 39.2-48.2). Tuberculin skin test positivity was associated with age 10-14 years (Prevalence Ratio -PR= 1.43, 95% CI: 1.1-1.9), having a BCG vaccine scar (PR= 1.52, 95% CI: 1.1-2.1), underweight, closer proximity to the index case and exposure time >3 months. The annual risk of infection (tuberculin skin test induration increase of 6 mm or more per year) was 17% (95% CI: 11.8-22.2) and was associated with a bacillary load of the adult index case (Relative Risk -RR= 2.12, 95% CI: 1.0-4.3). The incidence rate of active tuberculosis was 12.4 cases per 1,000 persons-year. Children <5 years without BCG vaccine scar had a greater risk of developing active disease (Hazard Ratio -HR= 6.00, 95% CI: 1.3-28.3) than those with scar (HR= 1.33, 95% CI: 0.5-3.4). The risk of developing active tuberculosis augmented along with the increase from initial tuberculin skin test (tuberculin skin test 5-9 mm HR= 8.55, 95% CI: 2.5-29.2; tuberculin skin test ≥10 mm HR= 8.16, 95% CI: 2.0-32.9). Conclusions: There is a need for prompt interruption of adult-to-children tuberculosis transmission within households. Conducting proper contact investigation and offering chemoprophylaxis to infected children could reduce tuberculosis transmission.

Resumen Objetivo: Evaluar el riesgo de tuberculosis (infección y enfermedad) en niños menores de 15 años de edad convivientes de pacientes con tuberculosis pulmonar en tres ciudades colombianas (Medellín, Cali y Popayán). Métodos: Se siguió durante 24 meses una cohorte de 1,040 niños convivientes de 380 adultos con tuberculosis pulmonar bacilífera. Periodo de estudio 2005-2009. Resultados: La prueba de tuberculina fue positiva (≥10 mm) en el 43.7% (IC 95%: 39.2-48.2), y estuvo asociada con la edad de 10-14 años (Razón de Prevalencia-RP= 1.43, IC 95%: 1.1-1.9), tener cicatriz de la vacuna BCG (RP= 1.52, IC 95%: 1.1-2.1). El riesgo anual de infección (aumento de la induración en la prueba de tuberculina de 6 mm o más al año) fue 17% (IC 95%: 11.8-22.2), y estuvo asociado con mayor carga bacilar en el adulto con tuberculosis pulmonar (Riesgo Relativo-RR= 2.12, IC 95%: 1.0-4.3). La tasa de incidencia de tuberculosis activa fue de 12.4 casos por 1,000 años-persona de seguimiento. Los niños menores de 5 años sin cicatriz de vacuna BCG tuvieron un mayor riesgo de desarrollar tuberculosis activa (Razón de Peligro -HR= 6.00, IC 95%: 1.3-28.3), que quienes tenían cicatriz (HR= 1.33, IC 95%: 0.5-3.4). El riesgo de desarrollar tuberculosis activa aumentó conforme el aumento de la prueba de tuberculina inicial (prueba de tuberculina 5-9 mm HR= 8.55, IC 95%: 2.5-29.2; prueba de tuberculina ≥10 mm HR= 8.16, IC 95%: 2.0-32.9). Conclusión: Es necesario interrumpir rápidamente la transmisión de tuberculosis de adultos a niños en los hogares. Realizar investigaciones de contacto apropiadas y ofrecer quimioprofilaxis a los niños infectados podría reducir la transmisión de la tuberculosis.

Risk of infection and disease progression in children exposed to tuberculosis at home, Colombia.

AIM: To assess the risk of tuberculosis (infection and disease) in children less than 15 years' old who are household contacts of pulmonary tuberculosis patients in three Colombian cities (Medellín, Cali, and Popayán). METHODS: A cohort of 1,040 children household contacts of 380 adults with smear-positive pulmonary tuberculosis was followed up for 24 months. Study period 2005-2009. RESULTS: Tuberculin skin test was positive (≥10 mm) in 43.7% (95% CI: 39.2-48.2). Tuberculin skin test positivity was associated with age 10-14 years (Prevalence Ratio -PR= 1.43, 95% CI: 1.1-1.9), having a BCG vaccine scar (PR= 1.52, 95% CI: 1.1-2.1), underweight, closer proximity to the index case and exposure time >3 months. The annual risk of infection (tuberculin skin test induration increase of 6 mm or more per year) was 17% (95% CI: 11.8-22.2) and was associated with a bacillary load of the adult index case (Relative Risk -RR= 2.12, 95% CI: 1.0-4.3). The incidence rate of active tuberculosis was 12.4 cases per 1,000 persons-year. Children <5 years without BCG vaccine scar had a greater risk of developing active disease (Hazard Ratio -HR= 6.00, 95% CI: 1.3-28.3) than those with scar (HR= 1.33, 95% CI: 0.5-3.4). The risk of developing active tuberculosis augmented along with the increase from initial tuberculin skin test (tuberculin skin test 5-9 mm HR= 8.55, 95% CI: 2.5-29.2; tuberculin skin test ≥10 mm HR= 8.16, 95% CI: 2.0-32.9). CONCLUSIONS: There is a need for prompt interruption of adult-to-children tuberculosis transmission within households. Conducting proper contact investigation and offering chemoprophylaxis to infected children could reduce tuberculosis transmission.

OBJETIVO: Evaluar el riesgo de tuberculosis (infección y enfermedad) en niños menores de 15 años de edad convivientes de pacientes con tuberculosis pulmonar en tres ciudades colombianas (Medellín, Cali y Popayán). MÉTODOS: Se siguió durante 24 meses una cohorte de 1,040 niños convivientes de 380 adultos con tuberculosis pulmonar bacilífera. Periodo de estudio 2005-2009. Resultados: La prueba de tuberculina fue positiva (≥10 mm) en el 43.7% (IC 95%: 39.2-48.2), y estuvo asociada con la edad de 10-14 años (Razón de Prevalencia-RP= 1.43, IC 95%: 1.1-1.9), tener cicatriz de la vacuna BCG (RP= 1.52, IC 95%: 1.1-2.1). El riesgo anual de infección (aumento de la induración en la prueba de tuberculina de 6 mm o más al año) fue 17% (IC 95%: 11.8-22.2), y estuvo asociado con mayor carga bacilar en el adulto con tuberculosis pulmonar (Riesgo Relativo-RR= 2.12, IC 95%: 1.0-4.3). La tasa de incidencia de tuberculosis activa fue de 12.4 casos por 1,000 años-persona de seguimiento. Los niños menores de 5 años sin cicatriz de vacuna BCG tuvieron un mayor riesgo de desarrollar tuberculosis activa (Razón de Peligro -HR= 6.00, IC 95%: 1.3-28.3), que quienes tenían cicatriz (HR= 1.33, IC 95%: 0.5-3.4). El riesgo de desarrollar tuberculosis activa aumentó conforme el aumento de la prueba de tuberculina inicial (prueba de tuberculina 5-9 mm HR= 8.55, IC 95%: 2.5-29.2; prueba de tuberculina ≥10 mm HR= 8.16, IC 95%: 2.0-32.9). CONCLUSIÓN: Es necesario interrumpir rápidamente la transmisión de tuberculosis de adultos a niños en los hogares. Realizar investigaciones de contacto apropiadas y ofrecer quimioprofilaxis a los niños infectados podría reducir la transmisión de la tuberculosis.

Increased percentage of IFN-γ producing CD56+CD3+ cells in active tuberculosis patients upon CFP-10 stimulation of peripheral mononuclear cells.

Aiming to identify a possible biomarker that distinguishes immune cellular response of active tuberculosis from latent infection. Peripheral blood mononuclear cells (PBMCs) of pulmonary tuberculosis patients (PTB), tuberculin positive household contacts (TST(+) HHC), and tuberculin negative non-household contacts (TST− Non HHC) were stimulated with PPD or CFP-10 and the percentage of CD69(+) cells, proliferating precursor and IFN-γ producing CD4(+), CD8(+), CD56(+)CD3(−) and CD56(+)CD3(+) cells were compared. IL-2, IL-12p70, IL-15, IL-18 and IL-10 were measured in culture supernatants. PTB and TST+ HHC presented higher percentages of CD69(+) cells, IFN-γ(+) and proliferating precursors in all subpopulations studied and higher IL-12p70 levels than TST- Non HHC. The increased percentage of IFN-γ producing CD56(+)CD3(+) cells in response to CFP-10 in PTB, compared with TST− Non HHC and the ratios between the percentage of CD56(+)CD3(+) cells/CD56(+)CD3(−) and CD8(+) cells producing IFN-γ suggest that these parameters may distinguish active TB from latently infected individuals.

Population structure among mycobacterium tuberculosis isolates from pulmonary tuberculosis patients in Colombia.

BACKGROUND: Phylogeographic composition of M. tuberculosis populations reveals associations between lineages and human populations that might have implications for the development of strategies to control the disease. In Latin America, lineage 4 or the Euro-American, is predominant with considerable variations among and within countries. In Colombia, although few studies from specific localities have revealed differences in M. tuberculosis populations, there are still areas of the country where this information is lacking, as is a comparison of Colombian isolates with those from the rest of the world. PRINCIPAL FINDINGS: A total of 414 M. tuberculosis isolates from adult pulmonary tuberculosis cases from three Colombian states were studied. Isolates were genotyped using IS6110-restriction fragment length polymorphism (RFLP), spoligotyping, and 24-locus Mycobacterial interspersed repetitive units variable number tandem repeats (MIRU-VNTRs). SIT42 (LAM9) and SIT62 (H1) represented 53.3% of isolates, followed by 8.21% SIT50 (H3), 5.07% SIT53 (T1), and 3.14% SIT727 (H1). Composite spoligotyping and 24-locus MIRU- VNTR minimum spanning tree analysis suggest a recent expansion of SIT42 and SIT62 evolved originally from SIT53 (T1). The proportion of Haarlem sublineage (44.3%) was significantly higher than that in neighboring countries. Associations were found between M. tuberculosis MDR and SIT45 (H1), as well as HIV-positive serology with SIT727 (H1) and SIT53 (T1). CONCLUSIONS: This study showed the population structure of M. tuberculosis in several regions from Colombia with a dominance of the LAM and Haarlem sublineages, particularly in two major urban settings (Medellín and Cali). Dominant spoligotypes were LAM9 (SIT 42) and Haarlem (SIT62). The proportion of the Haarlem sublineage was higher in Colombia compared to that in neighboring countries, suggesting particular conditions of co-evolution with the corresponding human population that favor the success of this sublineage.

[Tuberculosis in the San José University Hospital in Popayán, Colombia, 1998-2000]. / Tuberculosis en el Hospital Universitario San José, Popayán, 1998-2000.

TB is a public health problem in the world. In Colombia the Health 100 Law caused changes in prevention programs. The TB control program was compromised too. The actions in relation with active looking and examination of respiratory symptomatic people has been lowering. This retrospective study describes the clinical, epidemiological and medical care characteristics of tuberculosis patients attended in the Hospital Universitario San José de-Popayán. The clinical expedients and laboratory registers were investigated. 120 cases of 187 registered patients were included; finally only 89 were tuberculosis cases: 39 pulmonary (43.8%) and 50 extrapulmonary (56.2%). The extrapulmonary forms were: miliar, 39 patients; pleural, 4: of lymph nodes, 3; osteoarticular, 2, and meningitis, 2 cases. 49% of patients were 15-59 years old, 28% more than 59; males 64% and 65% coming from country areas. Ziehl Neelsen (ZN) smear was positive in 22% of 59 sputums of pulmonary TB and 20.2% of 94 extrapulmonary TB samples: mycobacteria culture positive in 14.3% of 14 pulmonary TB sputum, and 29.6% of 54 extrapulmonary TB samples. The media days into hospital/yard was 4-26 and the media days to begin tuberculosis treatment/yard was 4-8. In summary there are important request for TB medical care to universitary hospital, however the diagnosis is difficult and takes a long time while mycobacteria can be transmitted to hospital contacts. It is necessary to get a better efficiency of diagnostic tests in the hospital and appropriated survey of the cases that begin treatment.

Tuberculosis en el Hospital Universitario San José, Popayán, 1998-2000

La tuberculosis es problema de salud pública. La Ley 100 de 1993 trajo cambios importantes en los programas de prevención, los cuales debieron asumirlos los municipios y las empresas prestadoras de salud. El programa para el control de la tuberculosis no es ajeno a esta situación; se han registrado menos búsquedas y exámenes de sintomáticos respiratorios. En esta nueva situación se necesita evaluar el manejo de la enfermedad en un hospital estatal de III nivel; por esta razón se adelantó un estudio descriptivo, retrospectivo, del perfil clínico, epidemiológico y de atención médica de los casos atendidos en el Hospital Universitario San José de Popayán en 2 años, mediante la revisión de las historias clínicas y los archivos de laboratorio. El Hospital Universitario San José informó 187 casos. De los 120 (64,2%) incluidos en el estudio, 89 fueron de tuberculosis, 27 con diagnóstico indeterminado y 4 no fueron tuberculosis. De los 89 casos con tuberculosis, 39 (43,8%) eran pulmonares y 50 (56,2%) extrapulmonar; 39 eran de tuberculosis miliar, 4 pleural, 3 ganglionar, 2 osteoarticular y 2 meníngea. El 49% tenía 15 a 59 años y 28%, 60 o más; 64% era de sexo masculino y 65% del área rural. La coloración de Ziehl Neelsen fue positiva en 22% de 59 esputos de casos de tuberculosis pulmonar y en 20,2% de 94 muestras de tuberculosis extrapulmonar. El cultivo fue positivo en 14,3% de 14 esputos de tuberculosis pulmonar y en 29,6% de 54 muestras de tuberculosis extrapulmonar. El promedio de días de hospitalización/sala fue de 4 a 26 y el promedio días de estancia/sala, antes del tratamiento de 4 a 8. Existe una importante demanda de atención médica por tuberculosis al Hospital Universitario San José. Se observa deficiencia en el abordaje diagnóstico y en el seguimiento y demora para el inicio del tratamiento. Se sugieren estrategias para mejorar el manejo.

Tuberculosis in the San José University Hospital in Popayán, Colombia, 1998-2000 TB is a public health problem in the world. In Colombia the Health 100 Law caused changes in prevention programs. The TB control program was compromised too. The actions in relation with active looking and examination of respiratory symptomatic people has been lowering. This retrospective study describes the clinical, epidemiological and medical care characteristics of tuberculosis patients attended in the Hospital Universitario San José de Popayán. The clinical expedients and laboratory registers were investigated. 120 cases of 187 registered patients were included; finally only 89 were tuberculosis cases: 39 pulmonary (43.8%) and 50 extrapulmonary (56.2%). The extrapulmonary forms were: miliar, 39 patients; pleural, 4: of lymhp nodes, 3; osteoarticular, 2, and meningitis, 2 cases. 49% of patients were 15-59 years old, 28% more than 59; males 64% and 65% coming from country areas. Ziehl Neelsen (ZN) smear was positive in 22% of 59 sputums of pulmonary TB and 20.2% of 94 extrapulmonary TB samples: mycobacteria culture positive in 14.3 % of 14 pulmonary TB sputum, and 29.6% of 54 extrapulmonary TB samples. The media days into hospital/yard was 4-26 and the media days to begin tuberculosis treatment/yard was 4-8. In summary there are important request for TB medical care to universitary hospital, however the diagnosis is difficult and takes a long time while mycobacteria can be transmitted to hospital contacts. It is necessary to get a better efficiency of diagnostic tests in the hospital and appropriated survey of the cases that begin treatment.