Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
It was recently announced that new estimates indicated over 650,000 children develop tuberculosis (TB) every year in the 22 countries with a high burden of the disease (HBCs). Which countries are these and why are so many children developing TB in these areas?
The 22 HBCs are: Afghanistan, Bangladesh, Brazil, Cambodia, China, DR Congo, Ethiopia, India, Indonesia, Kenya, Mozambique, Myanmar, Nigeria, Pakistan, Philippines, Russia, South Africa, Thailand, Uganda, Tanzania, Vietnam, and Zimbabwe.
These countries are thought to have the highest total TB incidence in all age groups. Some countries have only moderate per capita incidence but extremely large populations; other smaller countries make it onto the list because they have very intense TB epidemics, often exacerbated by high rates of HIV infection.
As for children, the risk of a randomly chosen child becoming infected by the TB bacillus correlates with the per capita community prevalence of TB among adults (who are likely to be more infectious). So the total number of children developing TB in a country is driven by how common TB is where they live, and how many children there are to be infected (determined by demography and population size).
The new estimates are almost 25% higher than the total number of new cases worldwide estimated by WHO in 2012 (530,000). How can this be accounted for?
The first thing to say is that our estimates come with large uncertainty ranges, which include the WHO figures. As you say though, our central estimates are somewhat higher, and this is because of our different methodology.
Most estimates of TB burden are based on the number of cases notified, inflating this number to account for under-diagnosis and under-reporting. With adults, there are data to help quantify each of these sources of shortfall. For children, under-diagnosis and under-reporting are likely to be more severe, and data to assess their level are scant.
We took a different, complementary approach that avoided working with the notification data for children: we started with the adult prevalence estimates, and modelled the risks of infection and progression to disease for children living in these countries. This side steps the need to determine the gap between incidence and notifications, but at the price of greater uncertainty due to our imperfect knowledge about the infection and progression processes.
The truth is we have a substantially worse idea about the burden of TB in children compared to adults. Moving forwards, better reporting, and data from epidemiological studies will hopefully improve all these approaches, helping us converge on the more the more complete and accurate picture of childhood TB we need.
Why has pediatric case reporting historically varied widely between countries?
The reasons are as varied as the countries. I can't claim an intimate knowledge of the health systems of the 22 countries in our study. However, I suspect common factors include a feeling that the difficulties in diagnosing childhood TB make the numbers very unreliable, and therefore of less use; and a sense that TB in children is less significant for public health due to it's lower typical infectiousness.
How can we prevent children being infected with TB in HBCs?
Preventing TB infection in children largely equates to lowering rates of TB in adults and finding new TB cases sooner.
How to best achieve this is a big question in itself, but key elements probably include improved diagnostic tests and processes, lowering the barriers to seeking care and improving retention of patients in the care pathway, and greater use of ART and IPT in people living with HIV.
Active screening for TB in groups or areas with particularly high TB prevalence probably also has a role, where resources allow.
Why are children often ignored in TB control efforts and how important is the quantification of the burden of TB in children?
I think children have received less attention in TB control efforts because they are less likely to be infectious to other people. However, they are particularly vulnerable to progression to disease following infection, and are more likely to have serious forms of TB like TB meningitis and miliary TB.
Measures aimed at preventing TB in children therefore stand to gain much in terms of averted disability and life-years lost, even if they do not influence the TB epidemic in adults. Of course, infected children may go on to develop disease as adults, so there will be some influence.
Conversely, TB control efforts in adults may have a poorly quantified extra benefit from the averted cases of TB in children.
Ultimately, rational allocation of resources and choice of intervention approaches relies on accurate quantification of disease burden. Burden estimates are increasingly used to allocate funding, and motivate research and investment directions. Finally, without good numbers, it is hard to set targets and monitor progress.
What impact do you think these new estimates will have?
I hope these estimates will increase awareness of TB in children as a public health issue and feed into on-going work to improve our understanding of its burden worldwide.
What further action is needed to tackle TB in children in HBCs?
Apart from achieving better general TB control to reduce children’s risk of infection, more use of isoniazid preventive therapy to avoid the development of disease in exposed children could be made.
Improved diagnosis would enable appropriate treatment. Our study suggests in the region of 15 million children were sharing a household with a TB case in these countries in 2010, and these children are potentially identifiable and at particular risk of infection and disease.
Neonatal BCG vaccination coverage is above 90% in most of these countries, but there are a few where coverage is substantially lower. BCG vaccination can help lower chances of developing the most severe forms of disease in children.
Where can readers find more information?
Our study has been published in the Lancet Global Health (http://www.thelancet.com/journals/langlo/article/PIIS2214-109X%2814%2970245-1/abstract) which is open access.
About Dr Peter Dodd
Dr Peter Dodd is currently a research associate in health economic modelling in the School of Health and Related Research at the University of Sheffield, UK. He is an infectious disease modeller, and has mainly worked on tuberculosis, especially in high HIV prevalence settings.
He was previously based at Imperial College London and the London School of Hygiene and Tropical Medicine.
His interests include the use of modelling to interpret RCTs and other epidemiological data, modelling approaches to burden estimation, and methods to fairly represent uncertainty in infectious disease models (particularly with relevance to cost-effectiveness analysis).