Rendimiento del GeneXpert en el diagnóstico de tuberculosis pulmonar y extrapulmonar en la edad pediátrica / GeneXpert for the diagnosis of pulmonary and extrapulmonary tuberculosis in pediatric patients / GeneXpert para o diagnóstico da tuberculose pulmonar e extrapulmonar em pacientes pediátricos

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Summary: Introduction: the World Health Organization (WHO) recommends molecular biology techniques, such as Xpert MTB/RIF, for the diagnosis of tuberculosis (TB) and for the detection of Rifampicin resistance. In Uruguay, the Xpert MTB/RIF has been used since 2014, and no research papers have yet assessed its performance. A Cochrane review recommends the assessment of the Xpert diagnostic accuracy in difficult to diagnose groups, such as, children, people living with HIV and with extrapulmonary tuberculosis. Objectives: describe cases of TB in children of under 15 years of age in Uruguay during 2018 and 2019 and describe the influence of the various diagnostic tests on the bacteriological confirmation of the disease. Evaluate the performance of the Xpert MTB/RIF for the diagnosis of TB in respiratory and non- respiratory samples using the culture as a reference standard. Compare the performance of GeneXpert with smear microscopy for TB diagnosis. Material and methods: analytical, retrospective study of children of under 15 years of age in Uruguay between January 2018 and June 2019, based on data obtained from the PNC-TB information system. Clinical-epidemiological characteristics of the TB cases were described. Definitions were taken from CHLA-EP, as per WHO recommendations. All respiratory and non-respiratory samples received by the National Reference Laboratory in Tuberculosis of the CHLA-EP from 1/1/2018 to 6/30/2019, entered in the IT system ("TB soft") were analyzed; they belonged to patients with clinical suspicion of TB, studied as contacts, or to TB risk groups (patients with immunodeficiency or at risk of immunosuppression, mainly). All samples underwent smear microscopy and/or Xpert MTB/RIF (according to the CHLA-EP protocol) and culture. The detection of Rifampicin resistance in the Xpert was compared with first- line drug sensitivity tests using molecular methods made from the cultures. The sensitivity, specificity, PPV and NPV of GeneXpert and ZN microscopy were calculated using Mycobacterium tuberculosis culture as gold standard. We calculated the Xpert positive and negative likelihood ratio (LR). Results: 67 patients under 15 years of age were diagnosed with TB, and 46% cases were bacteriologically confirmed. A total of 1670 samples were analyzed; 82% respiratory and 17% non-respiratory. A total of 32 samples showed a positive culture for M. tuberculosis (14 respiratory and 18 non- respiratory). One rifampicin resistance sample was detected in the Xpert that was not confirmed in the culture. The sensitivity of Xpert for all samples was 80%; the specificity 99,5%; PPV 80%; NPV 99,5%. In the case of smear microscopy for all samples: S 44,4%, specificity 99,4%, PPV 70,6%; NPV 98,2%. Respiratory samples: Xpert S 100%; E 99,4%; PPV 66,7%; NPV 100%. Bacilloscopy: S 72,7%; E 99,6%; PPV 72,7%; NPV 99,6%. Non-respiratory samples: Xpert S: 66,7%; E 100%; PPV 100%; NPV 97,9%. Bacilloscopy: S 25%; E 98,8%; PPV 66,7%; NPV 93,2%. The LR + of the Xpert for all samples was 160 and the LR - 0,2. Conclusions: TB in children under 15 remains difficult to diagnose. Bacteriological confirmation was attempted in 88% of TB cases, and almost 50% showed positive results by some bacteriological technique. The Xpert showed a good sensitivity and specificity profile in both respiratory and non-respiratory samples, similar to those reported in international papers. The main contribution in relation to smear microscopy is the greater sensitivity for the diagnosis of TB in children under 15 years of age. The Xpert is very useful for TB diagnosis when it is positive, although it does not ensure we can rule out the disease in case of negative results.

Resumo: Introdução: a Organização Mundial da Saúde (OMS) recomenda técnicas de biologia molecular, como o Xpert MTB / RIF para o diagnóstico de tuberculose (TB) e para a detecção de resistência à Rifampicina. No Uruguai, o Xpert MTB / RIF é usado desde 2014, e o seu desempenho ainda não tem sido avaliado. Uma revisão recente da Cochrane promove que pesquisas futuras devem avaliar a precisão diagnóstica do Xpert, em grupos difíceis de diagnosticar, como crianças, pessoas vivendo com HIV e pessoas com tuberculose extrapulmonar. Objetivos: descrever os casos de tuberculose em crianças menores de 15 anos no Uruguai nos anos 2018-2019 e a contribuição dos diferentes testes de diagnóstico na confirmação bacteriológica da doença. Avaliar o desempenho do Xpert MTB / RIF para o diagnóstico de TB em amostras respiratórias e não respiratórias de pacientes menores de 15 anos, utilizando a cultura como padrão de referência. Comparar o desempenho do GeneXpert com a baciloscopia para o diagnóstico da TB. Material e métodos: estudo analítico e retrospectivo de crianças menores de 15 anos estudadas para TB no Uruguai entre janeiro de 2018 e junho de 2019, utilizando a base em dados do sistema informático PNC-TB. Descrevemos as características clínico-epidemiológicas dos casos de TB. As definições foram retiradas do CHLA-EP de acordo com as recomendações da OMS. Todas as amostras respiratórias e não respiratórias recebidas pelo Laboratório Nacional de Referência (LNR) em Tuberculose do CHLA-EP de 01/01/2018 a 30/06/2019, inseridas no sistema computacional (TB Soft), corresponderam a pacientes com suspeita clínica de TB, estudados como contatos ou na detecção de TB em grupos de risco (pacientes com imunodeficiências ou com risco de imunossupressão, principalmente). As amostras foram realizadas por esfregaço (baciloscopia) e/ou Xpert MTB/RIF (de acordo com o protocolo CHLA-EP) e por cultura. A detecção da resistência à Rifampicina no Xpert foi comparada com os testes de sensibilidade a drogas de primeira linha (PSD), utilizando os métodos moleculares das culturas. A sensibilidade, especificidade, PPV e NPV do Xpert e esfregaço foram calculados usando a cultura como padrão de referência. Calculamos a razão de verossimilhança positiva e negativa (LR) do Xpert. Resultados: 67 crianças menores de 15 anos foram diagnosticadas com TB, e 46% dos casos foram confirmados bacteriologicamente. 1670 amostras foram analisadas; 82% respiratórias e 17% não respiratórias. 32 amostras tiveram uma cultura positiva para M. tuberculosis (14 respiratórias e 18 não respiratórias). A sensibilidade (S) do Xpert para todas as amostras foi de 80% (IC95% 37,5-96,3), especificidade (E) 99,5% (IC95% 97,3-99,9), PPV 80% (37,5-96,3), NPV 99,5% (97,3-99,9). Baciloscopia: S de 46,1% (28,7-64,5), E 99,5% (98,7-99,8), PPV 75% (50,5-89,8), VPL 98,3% (97,2-99). Amostras respiratórias: Xpert S 100%; E 99,3% VPP 66% e VPN 100%. Baciloscopia: S 66,6%, E 99,8%, PPV 80%, NPV 99,7%. Amostras não respiratórias: Xpert S: 66,6%, E 100%, PPV 100%, NPV 97,9%; Esfregaço S: 25%, E 99,3%, PPV 80%, NPV 93%. O LR + do Xpert para todas as amostras foi de 160 e o LR - 0,2. Conclusões: a TB em crianças menores de 15 anos é ainda difícil de diagnosticar. Tentamos a confirmação bacteriológica em 88% dos casos de TB, e quase 50% deles tiveram resultados positivos utilizando alguma técnica bacteriológica. O Xpert mostrou um bom perfil de sensibilidade e especificidade em amostras respiratórias e não respiratórias, semelhante ao relatado em papers internacionais. A principal contribuição em relação à baciloscopia é a maior sensibilidade para o diagnóstico de TB em menores de 15 anos. O Xpert é muito útil para o diagnóstico de TB em caso de ser positivo, embora não permita descartar a doença em casos negativos.

Effectiveness of the 7-valent pneumococcal conjugate vaccine against vaccine-type invasive disease among children in Uruguay: an evaluation using existing data.

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine immunization program in Uruguay in March 2008 with a 2-dose primary series (given at 2 and 4 months) plus a booster (at 12 months) and a catch-up campaign (two doses given at 15 and 17 months). We used a case-control methodology and existing laboratory surveillance and immunization registry data from Uruguay to evaluate PCV7 effectiveness against vaccine-type invasive pneumococcal disease (VT-IPD). Cases of VT-IPD (with pneumococcus obtained from a normally sterile site) were identified through the National Reference Laboratory. Age- and neighborhood-matched controls were obtained through a national immunization registry in which all children are enrolled at birth regardless of vaccine receipt; all eligible controls were included. Immunization status of cases and controls was assessed through the immunization registry, and conditional logistic regression was used to calculate PCV7 effectiveness. Between April 2008 and February 2010, 44 cases of VT-IPD among children<5 years were identified; 43 (98%) of those children were located in the registry. Among located case patients, 7 (16.3%) were age-eligible to have received at least one dose of PCV7. A total of 637 matched controls were included. Vaccine effectiveness was 91.3% (95% CI: 46.4, 98.6) for ≥ 1 PCV7 doses and 94.8% (95% CI: 43.1, 99.5) for ≥ 2 PCV7 doses. Using existing data we demonstrated high effectiveness of PCV7 against VT-IPD in Uruguay-a middle-income country using a 2-dose primary series plus a booster dose and a limited catch-up campaign. These data also highlight the utility of surveillance and high-quality immunization registries for evaluating the effectiveness of vaccines.

Assessment of the quality of immunization data produced by the national individual registration system in Uruguay, 2006.

OBJECTIVE: The nominal registration system of Uruguay's national immunization program (NIP) tracks administered vaccines on a paper form filled out after each vaccination and collated into a national database, thus allowing for individual follow-up. This study performed a comprehensive assessment of the quality of Uruguay's immunization data in November 2006 to evaluate the validity of the information and to confirm the high national immunization coverage reported by the program. METHODS: The research team analyzed the concordance of the operational-level numerators (infant immunization data from 18 public and private vaccination centers in six country departments) with department- and national-level data, and compared the national-level (NIP) infant denominators with other official sources. A standardized questionnaire was used to evaluate system performance at the operational (vaccination center), department, and national level. Rapid house-to-house monitoring was conducted to generate additional coverage estimates. RESULTS: Numerator accuracy throughout the data flow was 100%, and national-level denominators appeared to be exhaustive. Overall system performance was excellent (proper archiving and recording of form data, sufficient supply of forms, timely flow of information, adequate defaulter tracing practices and computer system security). The main weaknesses were the degree of data analysis and feedback to peripheral levels. House-to-house monitoring showed high overall immunization coverage (97%). CONCLUSION: Uruguay's NIP registration system produces remarkably reliable information, ensuring valid measurement of immunization coverage. In addition, by allowing for monitoring of each child's current vaccination status, it facilitates management of interventions designed to reduce vaccination default and thus helps achieve the country's high level of coverage.

Assessment of the quality of immunization data produced by the national individual registration system in Uruguay, 2006 / Evaluación de la calidad de los datos de vacunación generados por el sistema nacional de registro individual en Uruguay, 2006

OBJECTIVE: The nominal registration system of Uruguay's national immunization program (NIP) tracks administered vaccines on a paper form filled out after each vaccination and collated into a national database, thus allowing for individual follow-up. This study performed a comprehensive assessment of the quality of Uruguay's immunization data in November 2006 to evaluate the validity of the information and to confirm the high national immunization coverage reported by the program. METHODS: The research team analyzed the concordance of the operational-level numerators (infant immunization data from 18 public and private vaccination centers in six country departments) with department- and national-level data, and compared the national-level (NIP) infant denominators with other official sources. A standardized questionnaire was used to evaluate system performance at the operational (vaccination center), department, and national level. Rapid house-to-house monitoring was conducted to generate additional coverage estimates. RESULTS: Numerator accuracy throughout the data flow was 100 percent, and national-level denominators appeared to be exhaustive. Overall system performance was excellent (proper archiving and recording of form data, sufficient supply of forms, timely flow of information, adequate defaulter tracing practices and computer system security). The main weaknesses were the degree of data analysis and feedback to peripheral levels. House-to-house monitoring showed high overall immunization coverage (97 percent). CONCLUSION: Uruguay's NIP registration system produces remarkably reliable information, ensuring valid measurement of immunization coverage. In addition, by allowing for monitoring of each child's current vaccination status, it facilitates management of interventions designed to reduce vaccination default and thus helps achieve the country's high level of coverage.

OBJETIVOS: El sistema de registro nominal del programa nacional de vacunación (PNV) de Uruguay registra las vacunas administradas en un modelo en papel que se llena después de cada vacunación y se introduce en una base de datos nacional, lo que permite el seguimiento individual. En este estudio, realizado en noviembre de 2006, se hizo un análisis integral de la calidad de los datos de vacunación en Uruguay para evaluar la validez de la información y confirmar la alta cobertura nacional de vacunación informada por el programa. MÉTODOS: Se analizó la concordancia de los numeradores operacionales (datos de vacunación infantil de 18 centros de vacunación públicos y privados de seis departamentos del país) con los datos departamentales y nacionales, y se compararon los denominadores del PNV infantil a nivel nacional con los de otras fuentes oficiales. Se empleó un cuestionario estandarizado para evaluar el desempeño del sistema en los niveles operacional (centros de vacunación), departamental y nacional. Se realizó un monitoreo rápido de casa en casa para obtener estimados adicionales de la cobertura. RESULTADOS: La precisión de los numeradores en todo el flujo de datos fue de 100 por ciento y los denominadores a nivel nacional al parecer eran exhaustivos. El desempeño general del sistema fue excelente (archivo y registro adecuados de los datos, suministro suficiente de modelos, flujo oportuno de información, práctica adecuada de rastreo de fallas y sistema apropiado de seguridad informática). Las principales debilidades fueron el grado de análisis de los datos y la retroalimentación a las instancias periféricas. El monitoreo de casa en casa mostró una alta cobertura general de vacunación (97 por ciento). CONCLUSIONES: El sistema uruguayo de registro del PNV genera una información notablemente confiable, lo que asegura la validez de la medición de la cobertura de vacunación. Además, al permitir el monitoreo del estado de vacunación actual ...