Has childhood TB come of age?

It seems so. Close on the heels of the WHO Global Tuberculosis Report 2012 releasing some data on childhood tuberculosis for the first time, one plenary at the recently concluded 43rd Union World Conference on Lung Health in Kuala Lumpur was dedicated to Childhood TB: We Need to Do More.
Childhood TB (CTB) is finally on the public health agenda and children are now being recognized as a vulnerable group in the field of TB. The increase in childhood TB is an indication of the failure of the control of TB epidemic and an indication of household TB dynamics, as well as the emergence of transmitted Multidrug Resistant (MDR) TB.
The disease presents itself with high (albeit preventable and treatable) morbidity and mortality in the youngsters. An estimated 490,000 children are falling ill with TB every year and 200 are dying of it every day (the actual numbers would be much more).
In her plenary address, Dr. Anneke Hesseling, Director of the Paediatric TB Research Program at the Desmond Tutu TB Center at Stellenbosch University in Cape Town, called for making CTB more accessible and less complicated by linking knowledge to practice; developing/applying new diagnostic tools and child friendly pediatric formulations of drugs; and adding another I— Integration of family based approach to the existing 3 Is— Intensified case finds, Isoniazid preventive therapy and Infection control.
According to Professor Simon Schaaf, a specialist on childhood tuberculosis at Stellenbosch University, although children make up about 10-20% of the TB burden and we see about 56,000 to 97,000 children with MDR TB, reporting of these cases is very low. He said that “early detection could lead to less aggressive MDR TB treatment in children with shorter duration and fewer drugs without injections, provided there is no resistance to second line drugs. In a study in South Africa involving the largest cohort of pediatric cases with confirmed MDR TB, 149 children (32 were HIV positive too) were started on treatment. The overall cure rate was over 90% and 2nd line ATT was generally well tolerated with few side effects.”
While talking to Citizen News Service — CNS, Dr. Soumya Swaminathan, scientist at the National Institute for Research in Tuberculosis, Chennai, rued that in India, not only are there more and more cases of extra pulmonary TB, but MDR TB in children is also on the rise and studies have shown that rates of MDR TB in children are same as that in adults. It is another thing that we do not find these cases and we do not diagnose them as there are very few centers that can diagnose MDR TB in children.
She said: “It is unfortunate that there are hardly any child friendly formulations of the existing drugs available for Drug Sensitive TB in the market. For second line drugs we have nothing — no children’s formulation — and that is where the pharmaceutical companies really have to do something. There is hardly any awareness in the population about TB. Mass media campaigns can help in educating the public about it. There has to be more literacy on TB in doctors too.”
As Dr. Luis Cuevas, professor at Liverpool School of Tropical Medicine, rightly urged that, “Diagnostic tests should be rapid, efficient, and sensitive and be accessible at low costs. Sample specimens should be more child friendly with minimum invasiveness (like stool and urine). So, more research is needed on collecting multiple samples on one day from different anatomical sites, which could be pooled and tested with one test by the Gene Xpert (GX).”
There are exciting things are indeed happening around developing more child friendly diagnostics and treatments. Dr. Mark Nicol from the University of Capetown spoke about the potentially exciting possibility of using stool samples, instead of sputum, to detect TB especially in children. He informed that “in one study conducted on 123 children at the University of Cape Town, testing of stool sample by GeneXpert (GX) gave a correct detection rate of 47% and specificity of 98%. This was a simple study using very small stool volumes — only .075gm of stool went into the GX test. But if we could use 1 gm of stool then I think we can identify a much larger number of cases. More diagnostic studies with more explicit recommendations are needed on pooling of scarce samples (without getting a dilution effect), optimizing protocols for non-respiratory samples, and use of GX for diagnosing Extra Pulmonary TB in children.”
Dr. Carl Mendel of Global Alliance for TB Drug Development (TB Alliance) talked about the triple A strategy of TB Alliance — developing new and better drugs/regimens for TB that are Affordable, Adapted, and made widely Available. He explained: “The existing framework of development of new TB drugs for children and adolescents is to match the pharmacokinetics (PK) in children with that in adults, once safety and efficacy of a new drug/regimen has been demonstrated in adults. The general consensus is that if a drug is safe and effective in adults it will be effective in children, and so efficacy studies are not required in children. However additional information for safety has to be done in smaller studies involving children. We propose to conduct single dose and PK studies (based on adult dose and PK modeling) in hospitalized children of all age groups from 0 to 16 years old simultaneously, who are already receiving background therapy for TB, and then adjust the dose after the few initial studies. This would be followed by multiple dose studies simultaneously in all age groups. In this way we can get to all young children as quickly as possible, and then do longer term smaller and manageable efficacy studies in different age groups to fix the dosage. In the case of developing drug regimens, the PK is done in context with the individual drugs. We feel that the right time to study a new drug in children is once we have a two months safety and efficacy data in a few hundred adults. With this aggressive approach we would be able to provide recommendations for use of new TB drugs in children and also register new drugs much more quickly.”
In an interview given to CNS, Kolleen Bouchane, director of ACTION, expressed her happiness that childhood TB is now receiving more attention and that maternal and child health agenda is going up. She said: “Children living with and dying of TB is a tragedy but it also gives us an opportunity for entry into the household to find more people who have TB through reverse contact tracing. MDR-TB in children is another under accounted and underrepresented galloping issue — with intolerably painful and very long duration drug regimens. There are still no universal standardized pediatric formulations that are easy to take and children are still popping up pills. Another important point is that pneumonia and TB are often misdiagnosed with each other and hence mistreated in children. So we have these two leading killers of children that are in competition with each other in a strange way in a child’s body. This is a good time to accelerate work on both pneumonia and TB and talk about solutions for combating these two diseases simultaneously. So we need to use the existing tools in a better way and get serious about children in new research for new diagnostics, new drugs and finally a vaccine.”
Lack of political will; inadequate funding and research; and failure to include children in National TB programs, act as barriers to save lives from CTB. To remove these barriers we must prioritize to make use of the available tools, integrate TB services with other health programs and develop child friendly diagnostics, drugs and vaccines. TB is still taken as an adult disease and many health care providers rarely consider it as a cause of childhood illness and death. We have to find and treat more children for TB through community based programs by applying a family centered approach.