**7. Future prospects**

infection and patients with active dsease is needed; 2) a prognostic test which can be able to predict the risk of latent TB becoming active needs to be established; 3) there is need for a diagnostic test that can be used to serve as a surrogate endpoint of disease which can be used for monitoring drug and vaccine trials in TB. It is envisaged that the basis for these novel diagnostic measures will be biomics, comprising metabolomic, proteomic and transcriptomic profiles in custom-made biosignature. Identification of non invasive biomarkers, especially the molecular assay of M. tuberculosi fragments in urine and the measurement of volatile biomarkers of volatile organic compounds generated by Mycobacteria TB in the breath or the oxidative stress resulting from infection is one step in the right direction. [http://ec.europa.eu/

**6.4. Need for post-exposure vaccines and those effective against all M. tuberculosis strains**

The Bacille Calmette-Guerin (BCG) vaccine is currently the only vaccine in use against tuberculosis. The efficacy of this vaccine is limited to prevention of severe forms of tuberculosis among children and there are lots of problems in cases of TB/ HIV coinfection.The current vaccine candidates are being developed for pre-exposure administration but, considering the fact that one third of the world's population is already infected, there is a serious need for a post-exposure vaccine to prevent re-activation. Another shortcoming with the vaccines in the pipeline is that they can delay clinical TB but cannot achieve sterile eradication. There is need for combination vaccines that can combine the effects of booster vaccines with another generation of vaccines that can act to effect sterilisation at the post-exposure stage. Focus should also be put on the development of a vaccine that can afford protection against the wide range of M. tuberculosis strains, to ensure universal effectiveness.To avoid complications in clinical and epidemiological research, the evaluation of all the vaccines should also deal with confounding factors such as prior BCG vaccination or HIV status and there should be well worked out guidelines for use of these vaccines in children [http//www.ec.europa.eu/research/

When it comes to the current status of clinical, diagnostic and therapeutic strategies, childhood TB has been grossly neglected and there is, therefore need for better and standardized treatment strategy. Although there is a reasonable number of candidates in the discovery and pre-clinical pipeline, there are still gaps between the different stages of TB drug development, and drugs specically targeting paediatric TB are still needed. Most of the drugs in the pipeline use the same mechanisms with the majority aimed at boosting efficacy or shortening the duration, with very few targeingt dormant stages of the bacillus and, therefore, not suitable for eradication of latent infections. Thus urgency for serious research into the development of new drugs and treatment regimens aimed at achieving this therapeutic objective cannot be over emphasised. Dealing with TB/HIV co-infection is another gap that needs serious attention: there is need to develop drugs that can prevent dormant mycobacteria from re-activating in

HIV-positive individuals [http://ec.europa.eu/research/research-eu.

research/research-eu]

416 Tuberculosis - Current Issues in Diagnosis and Management

research-eu]

**6.5. Development of new drugs**

### **7.1. Reducing the burden of childhood tuberculosis**

TB in children presents a number of difficult challenges which will only be solved by a shift in research priorities. Advances in paediatric TB research will provide wider insights and opportunities for TB control. While development of a new vaccine to prevent TB should be the ultimate goal, development of better diagnostics represent one of the most important steps towards improving individual case management and also providing a more robust case definition for much needed drug and vaccine trials for studies on TB epidemiology and correlates of protective immunity in childhood. Data on the epidemiology of childhood TB may in turn help to inform public health policy by providing a window on current transmission and the effectiveness of control strategies and by identifying children with LTBI for chemo‐ prophylaxis to limit the future propagation of the epidemic. Emphasis should be placed on reducing the vulnerability of the community because successful control of the tuberculosis epidemic is the most effective way to reduce the burden of childhood tuberculosis However, this will require a holistic approach with sustainable poverty alleviation as a key element [http://www. ec.europa.eu/research/research-eu].

#### **7.2. Involvement of funders and industry**

Important resources are required for the exploration of pathways leading to TB diagnosticsoriented basic science in pathogen biology, biomarker discovery, systems biology and point of care test development. The current priorities for TB vaccine development are: i) new vaccine candidates that achieve sterile eradication, and that can progress into phase II and phase III trials; ii) vaccine testing in a naïve stage on M. tuberculosis uninfected individuals; iii) vaccines which can achieve post-exposure prophylaxis to those who are already infected (currently 2 billion people); iv) strategies on how to get vaccines from the research bench to the bedside and into the community. Apart from the protective effect of novel vaccine candidates, priority should be given also to their delivery route, formulation (storage, shelf-life and distribution) and utility for HIV-infected individuals, particularly children.

#### **7.3. Back to basic research**

As we talk about nano technology and pin point delivery of drugs it is a shame that 130 years after the Robert Koch's discovery of M. Tuberculosis we still have huge gaps in our under‐ standing of the biology, immunology and pathophysiology of the bacillus. We are, as yet, not able to explain fully the molecular, biochemical and immunological mechanisms that enable TB infection to go on for years and cause severe disease and death. With the availability of state-of-the-art molecular research tools such as functional genomics and metabolomics a paradigm shift towards empahsising basic research could help provide answers to some of the unanswered questions about M.tuberculosis in general, and paediatric TB in particular. The currently available knowledge has proved insufficient when it comes to the rational design of vaccines or other control tools and this has resulted in a lot of trial-and-error approaches. With the HIV virus still elusive, defeating the dual alliance of TB/HIV co-infection has added another diamension in the already complicated war against the resistant strains of M. tuberculosis. Promoting basic research by providing the necessary resources and involving stakehoolders on the political front can provide solutions to some of the outstanding problems if not solving all of them. Where there is will, there is a way [http//ec.europa.eu/research/research-eu].

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Peadiatric Tuberculosis: Is the World Doing Enough?

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#### **7.4. Concluding remarks**

Recent developments for TB diagnostics seem promising fields due to the fact they are fast and minimally invasive, but they have drawbacks of not being validated in diverse populations and improved according to the patient's needs. Refinement of existing tools and development and testing of new tools are urgently required to improve diagnosis and treatment of TB in children. Higher global priority and funding will be required to improve on childhood nutrition and promote improvement in the socioeconomic and environmental condition of communities if we are to have a significant impact on TB transmission to children. [Expand +Clinical Infectious Diseasescid.oxfordjournals.org
