Knowledge, attitudes and practices on childhood TB among healthcare workers.

BACKGROUND: Increasing childhood TB case detection requires the deployment of diagnostic services at peripheral healthcare level. Capacity and readiness of healthcare workers (HCWs) are key to the delivery of innovative approaches.METHODS: In 2019, HCWs from five district hospitals (DHs) and 20 primary healthcare centres (PHCs) in Cambodia, Cameroon, Cote d´Ivoire, Sierra Leone and Uganda completed a self-administered knowledge-attitudes-practices (KAP) questionnaire on childhood TB. We computed knowledge and attitudes as scores and identified HCW characteristics associated with knowledge scores using linear regression.RESULT: Of 636 eligible HCWs, 497 (78%) participated. Median knowledge scores per country ranged between 7.4 and 12.1 (/18). Median attitude scores ranged between 2.8 and 3.3 (/4). Between 13.3% and 34.4% of HCWs reported diagnosing childhood with (presumptive) TB few times a week. Practising at PHC level, being female, being involved in indirect TB care, having a non-permanent position, having no previous research experience and working in Cambodia, Cameroon, Cote d´Ivoire and Sierra Leone as compared to Uganda were associated with a lower knowledge score.CONCLUSION: HCWs had overall limited knowledge, favourable attitudes and little practice of childhood TB diagnosis. Increasing HCW awareness, capacity and skills, and improving access to effective diagnosis are urgently needed.

Integration of TB into child health policies in Africa's high-burden countries: a normative analysis.

Integration of paediatric TB care into decentralised child health services has the potential to reduce the large proportion of childhood TB that remains undiagnosed. We performed a review of national guidelines and policies for TB and child health to evaluate the normative integration of paediatric TB into existing child health programmes in 15 high TB burden countries in Africa. While integration is addressed in 80% of the national strategic plans for TB, the child health strategies insufficiently address TB in their plans to reduce child mortality. Emphasis needs to be put on multi-sectoral collaboration among national health programmes.

Intégrer la prise en charge antituberculeuse de l'enfant aux services de soins pédiatriques décentralisés pourrait permettre de réduire la proportion élevée de cas de TB pédiatriques qui restent non diagnostiqués. Nous avons examiné les politiques et recommandations nationales en matière de TB et de soins pédiatriques afin d'évaluer l'intégration normative de la TB pédiatrique aux programmes de prise en charge pédiatrique existant dans 15 pays africains à forte prévalence de TB. Cette intégration est abordée dans 80% des plans stratégiques nationaux pour la TB, mais les stratégies relatives aux soins pédiatriques ne tiennent pas suffisamment compte de la TB dans leurs plans visant à réduire la mortalité infantile. Il convient de mettre l'accent sur la collaboration multisectorielle entre les programmes de santé nationaux.

Tuberculosis contact investigation and short-course preventive therapy among young children in Africa.

SETTING: The largest cities in Benin, Burkina Faso, Cameroon and Central African Republic.OBJECTIVE: To demonstrate the feasibility and document the effectiveness of household contact investigation and preventive therapy in resource-limited settings.DESIGN: Children under 5 years living at home with adults with bacteriologically confirmed pulmonary tuberculosis (TB) were screened using questionnaire, clinical examination, tuberculin skin test and chest X-ray. Children free of active TB were offered preventive treatment with a 3-month rifampicin-isoniazid (3RH) or 6-month isoniazid (6H) regimen in Benin. Children were followed-up monthly during treatment, then quarterly over 1 year. Costs of transportation, phone contacts and chest X-rays were covered.RESULTS: A total of 1965 children were enrolled, of whom 56 (2.8%) had prevalent TB at inclusion. Among the 1909 children free of TB, 1745 (91%) started preventive therapy, 1642 (94%) of whom completed treatment. Mild adverse reactions, mostly gastrointestinal, were reported in 2% of children. One case of incident TB, possibly due to a late TB infection, was reported after completing the 3RH regimen.CONCLUSION: Contact investigation and preventive therapy were successfully implemented in these resource-limited urban settings in programmatic conditions with few additional resources. The 3RH regimen is a valuable alternative to 6H for preventing TB.

Cost minimization analysis of line probe assay for detection of multidrug-resistant tuberculosis in Arkhangelsk region of Russian Federation.

BACKGROUND: The development of new diagnostic tools allows for faster detection of both tuberculosis (TB) and multidrug-resistant (MDR) TB and should lead to reduced transmission by earlier initiation of anti TB therapy. The research conducted in the Arkhangelsk region of the Russian Federation in 2012-14 included economic evaluation of Line Probe Assay (LPA) implementation in MDR-TB diagnostics compared to existing culture-based diagnostics of Löwenstein Jensen (LJ) and BacTAlert. Clinical superiority of LPA was demonstrated and results were reported elsewhere. STUDY AIM: The PROVE-IT Russia study aimed to report the outcomes of the cost minimization analysis. METHODS: Costs of LPA-based diagnostic algorithm (smear positive (SSm+) and for smear negative (SSm-) culture confirmed TB patients by Bactec MGIT or LJ were compared with conventional culture-based algorithm (LJ-for SSm- and SSm+ patients and BacTAlert-for SSm+ patients). Cost minimization analysis was conducted from the healthcare system, patient and societal perspectives and included the direct and indirect costs to the healthcare system (microscopy and drug susceptibility test (DST), hospitalization, medications obtained from electronic medical records) and non-hospital direct costs (patient's travel cost, additional expenses associated with hospitalization, supplementary medicine and food) collected at the baseline and two subsequent interviews using the WHO-approved questionnaire. RESULTS: Over the period of treatment the LPA-based diagnostic corresponded to lesser direct and indirect costs comparing to the alternative algorithms. For SSm+ LPA-based diagnostics resulted in the costs 4.5 times less (808.21 US$) than LJ (3593.81 US$) and 2.5 times less than BacTAlert liquid culture (2009.61 US$). For SSm- LPA in combination with Bactec MGIT (1480.75 US$) vs LJ (1785.83 US$) showed the highest cost minimization compared to LJ (2566.09 US$). One-way sensitivity analyses of the key parameters and threshold analyses were conducted and demonstrated that the results were robust to variations in the cost of hospitalization, medications and length of stay. CONCLUSION: From the perspective of Russian Federation healthcare system, TB diagnostic algorithms incorporating LPA method proved to be both more clinically effective and less expensive due to reduction in the number of hospital days to the correct MDR-TB diagnosis and treatment initiation. LPA diagnostics comparing conventional culture diagnostic algorithm MDR-TB was a cost minimizing strategy for both patients and healthcare system.

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.

Outcomes from patients with presumed drug resistant tuberculosis in five reference centers in Brazil.

BACKGROUND: The implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries. METHODS: Observational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriate anti-TB treatment, empirical treatment and, the treatment outcomes. RESULTS: Between February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TB cases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to 45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with first line drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7-111.0] days and, for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0-41.2) days. Among 95 patients that were followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%-34.9%) changed or initiated the treatment after DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TB cases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorable outcomes (p = 0.07). CONCLUSIONS: This study shows a high rate of empirical treatment and long delay for DST results. Strategies to speed up the detection and early treatment of drug resistant TB should be prioritized.

Outcomes from patients with presumed drug resistant tuberculosis in five reference centers in Brazil

Background: The implementation of rapid drug susceptibility testing (DST) is a current global priority for TBcontrol. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistanttuberculosis (pDR-TB) evaluated under field conditions in high burden countries.Methods: Observational study of pDR-TB patients referred by primary and secondary health units. TB referencecenters addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culturepositive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by aphysician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriateanti-TB treatment, empirical treatment and, the treatment outcomes.Results: Between February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TBcases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with firstline drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7–111.0] days and,for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0–41.2) days. Among 95 patients thatwere followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%–34.9%) changed or initiated the treatmentafter DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TBcases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorableoutcomes (p = 0.07).Conclusions: This study shows a high rate of empirical treatment and long delay for DST results. Strategies tospeed up the detection and early treatment of drug resistant TB should be prioritized.

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.

Operational implementation and impact of The Union's online childhood TB training course in South Africa.

Novel, effective tuberculosis (TB) training strategies are needed in developing settings to scale up training and improve TB management at facility level. This study evaluated the feasibility of implementing an online childhood TB training course for community-based health-care workers in the Eastern Cape Province, South Africa, and measured its impact on knowledge. Training sessions were convened and participants completed the course independently. A total of 220 primary care participants completed pre- and post-training tests. The mean knowledge increase was 8% (95% confidence interval 7.0-8.8, P < 0.001). The course proved an acceptable, versatile option for decentralised training in childhood TB, provided that the technology requirements can be met.

De nouvelles stratégies efficaces de formation à la tuberculose (TB) sont requises dans les pays en développement afin d'accélérer la formation et d'améliorer la prise en charge de la TB au niveau des structures de santé. Cette étude a évalué la faisabilité de la mise en œuvre d'un cours de formation en ligne à la TB de l'enfant pour les travailleurs de santé en communauté dans la province du Cap Est, Afrique du Sud, et a mesuré l'impact sur les connaissances. Des séances de formation ont été organisées et les participants ont terminé le cours indépendamment. Un total de 220 participants travaillant en soins de santé primaires ont fait les tests avant et après la formation. L'augmentation moyenne des connaissances a été de 8% (intervalle de confiance 95% 7,0­8,8 ; P < 0,001). Le cours s'est avéré une option acceptable et souple pour une formation décentralisée à la TB de l'enfant si les exigences techniques le permettent.

En los entornos poco desarrollados se precisan estrategias de capacitación innovadoras y eficaces en materia de tuberculosis (TB) con el objeto de ampliar la escala de las iniciativas de formación y mejorar la coordinación asistencial de la TB en los establecimientos de salud. El objetivo del estudio fue evaluar la factibilidad de poner en práctica un curso de capacitación en línea sobre la TB en la niñez dirigido a los agentes de salud comunitarios en la Provincia Oriental del Cabo en Suráfrica y medir su repercusión sobre el nivel de conocimientos de los profesionales. Se convocaron sesiones de formación y luego los participantes completaron por su cuenta el curso. Doscientos veinte profesionales de atención primaria participantes completaron los cuestionarios antes y después de la capacitación. Se observó un progreso promedio de los conocimientos de 8% (intervalo de confianza del 95% 7,0­8,8; P < 0,001). Se demostró que el curso representa una opción aceptable y versátil de formación descentralizada sobre la TB en la niñez, siempre y cuando se puedan cumplir los requisitos tecnológicos.

[Recommendations for therapy, chemoprevention and chemoprophylaxis of tuberculosis in adults and children. German Central Committee against Tuberculosis (DZK), German Respiratory Society (DGP)]. / Empfehlungen zur Therapie, Chemoprävention und Chemoprophylaxe der Tuberkulose im Erwachsenen- und Kindesalter. Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose (DZK), Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (DGP).

Several new international recommendations have been published since the German Central Committee against Tuberculosis (DZK) published its recommendations for drug treatment of tuberculosis (TB) in 2001 and for chemoprevention of latent tuberculosis infection (LTBI) in 2004. These international publications have been integrated in the present new recommendations which describe both the treatment of active TB and preventive treatment, pointing out specific adaptations for Germany. Separate sections deal with the current management of mono-, poly-, and multiresistance or drug intolerance, of TB in children, of different forms of extrapulmonary TB, of LTBI and of special situations such as HIV infection, renal or hepatic insufficiency, infection following BCG instillation in bladder cancer or in case of adverse drug reactions. The following aspects differ from the previous recommendations: A three-drug regimen for the so-called fully susceptible minimal TB is no longer recommended in adults. A dosage of 15 mg/kg body weight of ethambutol for adults is regarded as sufficient. Four secondline drugs (supplemented by pyrazinamide, where appropriate) are recommended for multidrug-resistant tuberculosis (MDR-TB). MDR-TB should be treated over a period of at least 20 months, with an injectable drug administered for a minimum of 8 months (initial phase). Ciprofloxacine and ofloxacine are no longer used to treat TB. It is also recommended to offer an HIV test to all TB patients to complement antiretroviral therapy, if necessary, and to adapt the antituberculous therapy accordingly.

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.

Xpert® MTB/RIF for national tuberculosis programmes in low-income countries: when, where and how?

Xpert ® MTB/RIF offers new and important possibilities for the diagnosis of sputum smear-negative tuberculosis (TB) and/or rifampicin (RMP) resistance, and many are encouraging rapid and widespread implementation. This simple test can be implemented almost everywhere, and it provides results within a few hours. In low-income countries (LICs), however, its cost, environmental limitations (stable and regular electricity, adequate room temperature) and difficulties involved in supply and maintenance are major obstacles. While it may be suitable for major reference hospitals, operational research is needed to evaluate the test and its additional yield above high-quality smear microscopy and clinical algorithms before its use at the peripheral level. In the meantime, direct microscopy should remain the initial diagnostic test for TB suspects. In most LICs, the prevalence of RMP resistance among new TB patients is very low; an Xpert MTB/RIF result indicating RMP resistance will thus always need confirmation by another test. In a population at high risk of RMP resistance (> 15%), however, the positive predictive value for RMP resistance by Xpert MTB/RIF is high, and identification of RMP resistance is an excellent proxy for multidrug-resistant TB (MDR-TB). The assay should be widely used for this purpose if, and only if, excellent MDR-TB management is available, both for ethical reasons and to reduce the risk of extensively drug-resistant TB.

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.

[New recommendations for contact tracing in tuberculosis]. / Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose*1.

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.

Making innovations accessible to the poor through implementation research.

Within countries, poorer populations have greater health needs and less access to good medical care than better-off populations. This is particularly true for tuberculosis (TB), the archetypal disease of poverty. Innovations also tend to become available to better-off populations well before they become available to those who need them the most. In a new era of innovations for TB diagnosis and treatment, it is increasingly important not only to be sure that these innovations can work in terms of accuracy and efficacy, but also that they will work, especially for the poor. We argue that after an innovation or a group of innovations has been endorsed, based on demonstrated accuracy and/or efficacy, introduction into routine practice should proceed through implementation by research. Cluster-randomised pragmatic trials are suited to this approach, and permit the prospective collection of evidence needed for full impact assessment according to a previously published framework. The novel approach of linking transmission modelling with operational modelling provides a methodology for expanding and enhancing the range of evidence, and can be used alongside evidence from pragmatic implementation trials. This evidence from routine practice should then be used to ensure that innovations in TB control are used for positive action for all, and particularly the poor.

[New recommendations for contact tracing in tuberculosis. German Central Committee against Tuberculosis]. / Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose. Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose.

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.

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.

Beyond accuracy: creating a comprehensive evidence base for TB diagnostic tools.

The need for a strong and comprehensive evidence base to support decision making with regard to the implementation of new and improved diagnostic tools and approaches has been highlighted by a number of stakeholders; these include members of the New Diagnostics Working Group (NDWG) and the Subgroup for Introducing New Approaches and Tools of the Stop TB Partnership. To compile such evidence in a systematic manner, we have developed an impact assessment framework (IAF) which links evidence on inputs to outcomes. The IAF comprises five interconnected layers: effectiveness analysis, equity analysis, health systems analysis, scale-up analysis and policy analysis. It can be used by new diagnostics developers and other interested research teams to collect as much policy-relevant data as possible prior to, during and after the demonstration phase of tool development. The evidence collated may be used by international and national policy makers to support adoption, implementation and scale-up decisions. The TREAT TB (Technology, Research, Education and Technical Assistance for TB) initiative uses the IAF in its operational research and field evaluations of new tools and approaches for TB diagnosis. It has also been incorporated into the NDWG's recent publication: 'Pathways to better diagnostics for tuberculosis: a blueprint for the development of TB diagnostics'. This article describes the IAF and the process of improving it and suggests next steps in overcoming the challenges in its implementation.

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.

Isoniazid pharmacokinetic studies of the 1960s: considering a higher isoniazid dose in childhood tuberculosis.

Isoniazid (INH) is one of the most important drugs for the treatment of tuberculosis (TB). In the current international recommendations there is still disagreement on the optimal dosage of INH in childhood TB. This paper presents data from 2 studies, one performed in 1960 and the other in 1961, investigating INH serum levels in children of different age groups, not yet presented internationally. Doses were calculated according to bodyweight (BW) as well as according to body surface area (BSA). In the first study, INH serum levels at different time points in children of different age groups were determined after oral INH administration at 5 mg/kg BW. In the second study, INH serum levels were measured once, 4 h after subcutaneous application of 5 mg/kg BW and once, 4 h after subcutaneous application of INH 200 mg/m(2) BSA 1 week later. These data was compared to adult data on INH collected prior to these studies. After application of 5 mg/kg BW oral dose, INH serum levels were much lower in children than in adults at all time points, especially in children younger than 8 y. In contrast, after dosing according to 200 mg/m(2) BSA, similar serum levels were achieved in children and adults. Dose recommendations of INH 5 mg/kg BW in childhood TB lead to lower serum concentrations than those recommended for adults. In children, it appears to be more appropriate to calculate the INH dose on the basis of body surface area rather than bodyweight.