A severely malnourished young girl, about one and a half years old, was brought to the out-patient department of a busy teaching hospital with symptoms of fever, cough and lethargy for about 10 days. Pneumonia was suspected and confirmed by a chest x-Ray and she was given a course of antibiotics and asked to return for follow-up after a week.
Her frantic mother brought her back to the emergency room after 4 days – by then, she was unconscious and despite all efforts, died the next day. Tests done then showed that she had TB meningitis or TB of the brain in addition to the infection in her lung.
This incident, which I witnessed, has always served as a grim reminder to me, that TB in children is not only poorly understood and mis-diagnosed, but often has little room for error and can progress very rapidly in the young child leading to long-term disability or death, as it did in this case.
Worldwide, at least 1 million TB cases occur each year in children under 15 years of age, 75 per cent of these occur in 22 high burden countries. In 2009, India had the highest number of TB cases in the world (approximately 2 million new patients), suggesting that the prevalence in children is also likely to be high.
The true burden of TB in children is unknown because of the lack of child-friendly diagnostic tools and inadequate surveillance and reporting of childhood TB cases. This is a disease where the infection in children is directly related to the prevalence in adults, as it spreads by airborne droplet infection and close contact.
While about half of all Indians have silent or “latent” TB infection, only a small fraction (10 per cent) develop signs and symptoms in their lifetime, in the rest the bacteria seem to live quietly, in harmony with the host. Whether the infection flares up into disease depends on many things, notably the body's immunity and if that is defective due to HIV or malnutrition or diabetes, then TB gets the upper hand in the battle with the immune system. Age is another important factor and children below 2 or 3 years old not only have a higher risk of developing disease, it is often more severe and widespread.
Pneumonia or infection of the lungs is a leading killer of children, world-wide, accounting for about 20 per cent of deaths in under-five children. Recent studies in Africa showed that TB was a common cause of “pneumonia” in both HIV infected and uninfected children – it was detected only when a special effort was made as part of a research study.
It is likely that more children will be correctly diagnosed if TB is considered as a cause of other common childhood infections. However, it is important to note that the correct tests need to be performed and interpreted properly — another challenge as x-Rays in children are notoriously difficult to read and prone to reader bias.
Perhaps due to the lack of a “gold standard” diagnostic test in children (the sputum test serves as one in adults), a number of unnecessary and useless tests are performed, contributing to a bigger hole in the pocket of the parent, but little else! It has been estimated that in India alone, 15 million dollars are spent annually on serological (ELISA) tests for TB – resources that could be better spent, considering there is no evidence that these tests are useful.
Children with TB infection today represent the reservoir of TB disease tomorrow.
If the global goal of eliminating TB by 2050 is to be met, treatment and prevention of TB in children needs as much attention as in adults. Unfortunately, BCG, the only licensed TB vaccine, has limited efficacy against the most common forms of childhood TB and its effect is of limited duration.
There are several clinical trials ongoing to test newer vaccines for TB, but it will take 8-10 years for a more efficacious vaccine to be available for wide use. Mostclinical trials for new TB drugs and drug combinations (that will be effective against both drug sensitive and drug resistant TB) are being conducted in adults and do not include children.
While there are obvious ethical as well as practical and logistical issues that need to be addressed while conducting trials in children, excluding them only ensures that they do not benefit from advances in diagnostics, new drugs or preventive strategies. Scientists and researchers need to do a better job of raising awareness, educating and engaging with the community about clinical trials in general and trials in children, in particular, especially since most participants in TB clinical trials tend to be poorly educated and socially disadvantaged.
The National TB Control Program is one of the largest and most successful public health programs in the world, providing high quality services to over 1.4 million patients every year.
However, screening of household contacts of adult TB patients and provision of preventive drugs to young children must receive higher priority. As India moves towards universal access to prevention, diagnosis and treatment of TB, the little ones amongst us must not be forgotten.
The author is Coordinator, Research Special Programme for Research and Training in Tropical Diseases, WHO, Geneva