Decentralisation of child tuberculosis services increases case finding and uptake of preventive therapy in Uganda.

BACKGROUND: A lack of capacity to diagnose tuberculosis (TB) in children at peripheral health facilities and limited contact screening and management contribute to low case finding in TB-endemic settings. OBJECTIVE: To evaluate the implementation of a pilot project that strengthened diagnosis, treatment and prevention of child TB at peripheral health facilities in Uganda. METHODS: In June 2015, health care workers at peripheral health facilities were trained to diagnose and treat child TB. Community health care workers were trained to screen household TB contacts. Before-and-after analysis as well as comparisons with non-intervention districts were used to evaluate impact on caseload and treatment outcomes. RESULTS: By December 2016, the average number of children (age < 15 years) diagnosed with TB increased from 45 to 108 per quarter. The proportion of child TB among all TB cases increased from 8.8% to 15%, and the proportion completing treatment increased from 65% to 82%. Of 2270 child TB contacts screened, 55 (2.4%) were diagnosed with TB. Of 910 eligible child contacts, 670 (74%) started preventive therapy, 569 (85%) of whom completed therapy. CONCLUSION: The strengthening of child TB services at peripheral health facilities in Uganda was associated with increased case finding, improved treatment outcomes and the successful implementation of contact screening and management.

Integration of childhood TB into guidelines for the management of acute malnutrition in high burden countries.

Introduction: Childhood tuberculosis (TB) and undernutrition are major global public health challenges. In 2015, although an estimated 1 million children aged <15 years developed TB, the majority of the cases remain undiagnosed, partly due to a lack of awareness and capacity by providers who serve as the first point of care for sick children. This calls for better integration of TB with child health and nutrition services. TB can cause or worsen undernutrition, and undernutrition increases the risk of TB. Methods: Guidelines for the management of acute malnutrition from 17 high TB burden countries were reviewed to gather information on TB symptom screening, exposure history, and treatment. Results: Seven (41%) countries recommend routine TB screening among children with acute malnutrition, and six (35%) recommend obtaining a TB exposure history. Conclusion: TB screening is not consistently included in guidelines for acute malnutrition in high TB burden countries. Routine TB risk assessment, especially history of TB exposure, among acutely malnourished children, combined with improved linkages with TB services, would help increase TB case finding and could impact outcomes. Operational research on how best to integrate services at different levels of the health care system is needed.

Cadre: La tuberculose (TB) de l'enfance et la malnutrition sont des défis majeurs de santé publique dans le monde. On estime qu'un million d'enfants âgés de <15 ans ont eu une TB en 2015, mais la majorité des cas sont restés non diagnostiqués, en partie à cause du manque de connaissance et de capacité des prestataires de soins qui sont le premier point de contact pour les enfants malades ; ceci demande une meilleure intégration de la TB avec les services de santé de l'enfant et de nutrition. La TB peut causer ou aggraver la malnutrition et la malnutrition augmente le risque de TB.Methodes: Les directives pour la prise en charge de la malnutrition aiguë de 17 pays durement frappés par la TB ont été revues afin de rassembler des informations relatives au dépistage des symptômes de TB, des antécédents d'exposition et de traitement.Résultats: Sept (41%) pays recommandent un dépistage de routine de la TB parmi les enfants ayant une malnutrition aiguë et six (35%) recommandent de rechercher des antécédents d'exposition à la TB.Conclusion: Le dépistage de la TB n'est pas systématiquement inclus dans les directives relatives à la malnutrition aiguë dans les pays durement frappés par la TB. Une évaluation de routine du risque de TB, particulièrement des antécédents d'exposition à la TB, parmi les enfants atteints de malnutrition aiguë, combinée à de meilleurs liens avec les services de TB contribuerait à augmenter la découverte des cas de TB et améliorer leur évolution. Une recherche opérationnelle sur la meilleure façon d'intégrer les services à différents niveaux du système de santé est nécessaire.

Marco de referencia: La tuberculosis (TB) durante la infancia y la desnutrición representan graves problemas de salud pública en el mundo. Se estima que un millón de niños de edad de <15 años contrajeron la TB en el 2015, pero la mayoría de los casos permaneció sin diagnóstico, debido en parte a la falta de sensibilización y a la escasa capacidad de los profesionales de salud que atienden en primera línea a los niños enfermos; esta situación exige una mejor integración de los servicios de atención de la TB y los servicios que se ocupan de la salud y la nutrición de los niños. La TB puede causar o agravar la desnutrición y esta a su vez aumenta el riesgo de contraer la TB.Métodos: Se analizaron las directrices de manejo de la desnutrición aguda de 17 países con alta carga de morbilidad por TB, con el objeto de reunir información sobre la detección sistemática de los síntomas, los antecedentes de exposición y el tratamiento de la TB.Resultados: Siete países recomendaban la detección sistemática de la TB en la práctica corriente en los niños con desnutrición aguda (41%) y seis países recomendaban obtener los antecedentes de exposición a la enfermedad (35%).Conclusión: La recomendación de la detección sistemática de la TB no es constante en las directrices de manejo de la desnutrición en los países con alta carga de morbilidad por esta enfermedad. La práctica corriente de una evaluación del riesgo de TB, sobre todo de los antecedentes de exposición en los niños aquejados de desnutrición aguda, aunada a mejores vínculos con los servicios de atención de la TB contribuiría a aumentar el rendimiento de la búsqueda de casos y mejorar los desenlaces. Sería muy útil realizar investigaciones operativas sobre la mejor manera de integrar los servicios en los diferentes niveles del sistema de atención de salud.

Adoption of revised dosage recommendations for childhood tuberculosis in countries with different childhood tuberculosis burdens.

BACKGROUND AND OBJECTIVE: In 2010, the World Health Organization (WHO) published revised dosage recommendations for the treatment of tuberculosis (TB) in children. The aim of the survey was to assess whether countries adopt these new dosage recommendations, as well as to identify challenges in the management and treatment of childhood TB. In addition, countries were asked to provide 2010 surveillance data on childhood TB. DESIGN: A survey questionnaire was developed and broadly disseminated to National Tuberculosis Programmes or people with close links to them. RESULTS: Among the 34 countries that responded to the survey, the proportion of total national TB caseload reported in children in 2010 ranged from 0.67% to 23.6%. The data on new cases reported to this survey varied from data provided to the WHO global TB database. Most countries had childhood TB guidelines in place, and half had adopted the new dosage recommendations. Countries reported a number of challenges related to the implementation of the new recommendations and general management of childhood TB. CONCLUSIONS: Despite the adoption of the new dosage recommendations, their implementation is complicated by the lack of appropriate fixed-dose combinations. In addition, accurate and consistent estimates of the global burden of childhood TB remained a major challenge. Technical assistance and support to countries is needed to improve childhood TB activities.

Interferon-gamma release assays and childhood tuberculosis: systematic review and meta-analysis.

BACKGROUND: Children infected with Mycobacterium tuberculosis have significant risk of developing tuberculosis(TB) and can therefore benefit from preventive therapy. OBJECTIVE: To assess the value of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST)in the diagnosis of TB infection and disease in children. METHODS: Thirty-three studies were included, assessing commercial IGRAs (QuantiFERON®-TB [QFT] andT-SPOT.®TB) and TST. Reference standards for infection were incident TB or TB exposure. Test performance for disease diagnosis was evaluated in studies assessing children with confirmed and/or clinically diagnosed TB,compared to children where TB was excluded. RESULTS: Two small studies measured incident TB in children tested with QFT and found weak positive predictive value. Association of test response with exposure-categorized dichotomously or as a gradient-was similar for all tests. The sensitivity and specificity of all tests were similar in diagnosing the disease. Stratified analysis suggested lower sensitivity for all tests in young or human immuno deficiency virus infected children. CONCLUSIONS: Available data suggest that TST and IGRAs have similar accuracy for the detection of TB infection or the diagnosis of disease in children. Heterogeneous methodology limited the comparability of studies and the interpretation of results. A rigorous, standardized approach to evaluate TB diagnostic tests in children is needed.

The Union and Médecins Sans Frontières approach to operational research.

Operational research (OR) has become a hot topic at national meetings, international conferences and donor fora. The International Union Against Tuberculosis and Lung Disease (The Union) and Médecins Sans Frontières (MSF) Operational Centre Brussels strongly promote and implement OR with colleagues in low- and middle-income countries. Here we describe how the two organisations define OR, and explain the guiding principles and methodology that underpin the strategy for developing and expanding OR in those countries. We articulate The Union's and MSF's approach to supporting OR, highlighting the main synergies and differences. Then, using the Malawi National Tuberculosis Control Programme as an example, we show how OR can be embedded within tuberculosis control activities, leading to changes in policy and practice at the national level. We discuss the difficult, yet vitally important, issue of capacity building, and share our vision of a new paradigm of product-related training and performance-based OR fellowships as two ways of developing the necessary skills at country level to ensure research is actually performed. Finally, we highlight the need to consider and incorporate into practice the ethical components of OR. This is a key moment to be involved in OR. We are confident that in partnership with interested stakeholders, including the World Health Organization, we can stimulate the implementation of quality, relevant OR as an integral part of health service delivery that in turn will lead to better health for people, particularly for those living in the poorer parts of the world.

Interferon-gamma release assays for the detection of Mycobacterium tuberculosis infection in children with cancer.

SETTING: The paediatric oncology unit at Tygerberg Children's Hospital, South Africa. OBJECTIVES: To assess the use of the tuberculin skin test (TST) and two commercial interferon-gamma release assays (IGRAs) for the detection of Mycobacterium tuberculosis infection in children with cancer before initiating chemotherapy treatment. DESIGN: Prospective hospital-based study, including children newly diagnosed with cancer; all underwent TST and IGRA testing. RESULTS: Of the 34 children enrolled, seven (17.6%) tested positive with either test: TST (3/7, 8.8%), T-SPOT.TB (n = 6, 17.6%) and QuantiFERON-TB Gold In-Tube (QFT-G; n = 3, 8.8%). T-SPOT.TB assay results were negative in 17 (50.0%) and indeterminate in four (11.8%) children. Six T-SPOT.TB tests could not be completed due to low cell counts (<100,000 per well), and one clotted. QFT-G results were negative in 26 (76.5%) and indeterminate in five (14.7%). CONCLUSIONS: TST and IGRAs were frequently discordant, with fewer positive results than expected. T-SPOT.TB produced more positive results, but inadequate cell counts were a particular problem. The sample size was too small to comment with confidence on test accuracy. All latent TB infection tests appear to perform sub-optimally in this group of children, and therefore none of them can be used in isolation to confirm or disprove TB infection.

Short-term reproducibility of a commercial interferon gamma release assay.

Interferon gamma release assays (IGRAs) have been shown to be sensitive and highly specific for the detection of immune memory against Mycobacterium tuberculosis. Little is known about the reproducibility and within-person variability of these assays. Various aspects of short-term reproducibility of a commercial IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT) assay, were assessed. The QFT-IT assay was performed twice within 3 days in 27 health care workers in Cape Town, South Africa. Two sets of tests were performed by different operators on day 1, and one set was performed on day 3. Aspects such as interoperator, intraoperator, day-to-day variability, and test-retest variability as well as different the storage methods of plasma were investigated. Seventeen of 27 (63%) of participants had at least one positive QFT-IT text; six had discordant results. The agreement of all aspects studied was high, with kappa values between 0.82 and 1.00 for dichotomous measures, and interclass correlations (ICC) of 0.809 to 0.965 were observed for continuous gamma interferon (IFN-gamma) measures. The variability of the magnitude of response was highest comparing measures obtained from individuals on different days (ICC of 0.809). The magnitude of the IFN-gamma responses between assays performed for individual participants was variable, with ranges from 0.03 to 11 IU/ml, resulting is discordant results for five participants. The results indicate that the QFT-IT assay is a robust and highly reproducible assay. Considerable intraindividual variability occurs in the magnitude of IFN-gamma responses, which may influence the interpretation of serial measures.

[Characteristics of childhood tuberculosis]. / Besonderheiten der Kindertuberkulose.

In spite of a decline in the western industrialised countries, tuberculosis remains one of the commonest causes of childhood mortality in the world. In most cases, children become infected by adults in their immediate environment. The clinical manifestation as a consequence of the primary infection reflects the community transmission of tuberculosis. Children with untreated infection remain a lifelong pool for future disease and therefore infectivity. Thus, prevention and therapy of latent tuberculosis infection are fundamental duties of the public health system. The risk of developing active disease following infection with MYCOBACTERIUM TUBERCULOSIS is especially high in children. Compared to adults, childhood tuberculosis manifests differently and is often more severe. At the same time, the diagnosis is complicated by the unspecific clinical presentation and difficulty of culture confirmation in children. This article gives an overview of the special features of the epidemiology, clinical presentation, diagnosis and management of childhood tuberculosis.

Interferon-gamma release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis.

BACKGROUND: Diagnosis of childhood tuberculosis (TB) is challenging. The widely used tuberculin skin test (TST) may produce -positive results because of cross-reactivity with nontuberculous mycobacteria or bacille Calmette-Guerin vaccination, resulting in unnecessary treatment. Two recently developed interferon- gamma release assays (IGRAs) show good diagnostic accuracy for active TB in adults; pediatric data are limited, particularly in areas with a low incidence of TB. We assessed the diagnostic accuracy of IGRAs for TB in children in an area with a low incidence of TB. METHODS: In a hospital-based study, the diagnostic accuracy of the TST and 2 IGRAs (T SPOT-TB [T-SPOT; Oxford Immunotec] and QuantiFERON-TB Gold In-Tube [QFT-IT; Cellestis]) were assessed in a cohort of 73 children (median age, 39 months); 28 children with bacteriologically confirmed TB were compared with children without TB (23 with bacteriologically confirmed nontuberculous mycobacterial lymphadenitis and 22 with other nonmycobacterial respiratory tract infections). RESULTS: The specificity for TB of QFT-IT was 100% (95% confidence interval [CI], 91%-100%), and the specificity of T-SPOT was 98% (95% CI, 87%-100%), both of which were considerably higher than the specificity of TST (58%; 95% CI, 42%-73%). The specificity of the TST was 10.5% (95% CI, 1%-33%) in children with nontuberculous mycobacterial lymphadenitis and was 100% (95% CI, 83%-100%) in children with other nonmycobacterial respiratory tract infections. The sensitivity of both QFT-IT and T-SPOT was 93% (95% CI, 77%-99%), and the sensitivity of the TST was 100% (95% CI, 88%-100%). Agreement between the IGRAs was 95.6% ( kappa =0.91); 6.8% of the IGRAs showed indeterminate results. CONCLUSIONS: Both IGRAs showed high diagnostic value in bacteriologically confirmed childhood TB. Their advantage in this study, when performed in addition to the TST, was the ability to distinguish -positive TST results caused by nontuberculous mycobacterial disease, thereby reducing overdiagnosis of TB and guiding clinical management.