The global fight against tuberculosis (TB) has failed children: most TB programmes under-diagnose, under-treat or completely leave children with TB out, despite the increase in paediatric TB, and rising numbers of children who are infected with drug-resistant forms of TB strains, according to new research.
A new report, released by Médecins Sans Frontières (MSF), found that 93 percent of children who are tested for TB using the most commonly used testing method, are deemed not to have the disease, despite later being confirmed to have it.
The study, presented at the Union World Conference on Lung Health in Kuala Lumpur, draws upon data collected over three years from over 2,000 children with TB in 13 MSF projects across six countries, including Myanmar and Zimbabwe.
Children co-infected with HIV and TB were at a greater risk of dying than children with TB, and while more than half the whole cohort had pulmonary TB, only 6.4 percent had tested positive for TB with the most commonly-used test (coughing up a sample of sputum to be checked under the microscope for bacteria).
A tricky diagnosis
But the report acknowledged that diagnosing TB in children is far more problematic. Most children, especially the youngest, cannot produce enough sputum for these tests. And even when they can, sputum-based tests do not detect paucibacillary or extrapulmonary TB that occurs more frequently in children.
“In an attempt to get adequate samples, health workers are forced to use invasive and painful measures, involving forcing vapour into their lungs to make them cough up sputum, or sucking out sputum from their stomach,” said Martina Casenghi, scientific advisor for MSF’s Access Campaign.
"The ideal test for children would be a test that does not rely on sputum… The ideal test would be something not requiring laboratory infrastructure [something like a urine pregnancy test] and that uses an easy to obtain sample such as urine, stool, finger prick blood test, etc. This ideal is not specific to children as it would help diagnose other difficult cases such as HIV co-infected or extrapulmonary TB," Grania Brigden, TB adviser for MSF’s Access Campaign, told IRIN/PlusNews.
Although new diagnostic tools such as the GeneXpert test could mean much more rapid diagnosis of paediatric TB, it still has its limitations as it also relies on sputum samples, the report noted.
Nevertheless, "GeneXpert is a start, as it is an improvement from smear microscopy, especially if you use it on samples obtained from nasopharahgeal aspirate or induced sputum, and for that reason although it is not the perfect test we still feel that it has a role to play in improving diagnosis in children. It also can potentially aid in the diagnosis of drug-resistant TB in children," Brigden added.
According to the report, one of the main barriers to developing a TB test that works in children has been the lack of a gold standard to assess performance of new diagnostic tools. "However, consensus on the methodological approaches to follow for evaluating new diagnostic tests in children has recently been reached... These new approaches should be implemented rapidly so that the rate of progress can be accelerated."
Getting the dosage right
To make things worse, paediatric drug formulations and international treatment guidance for children remain inadequate, MSF found. In 2009, the World Health Organization (WHO) released revised dosage guidelines for TB in children, but the formulations available on the market today are still not tailored to deliver the new dosages.
"And a slow response on the part of WHO to release recommended drug strengths and the composition of new fixed-dose combination (FDC) drugs has meant that, despite two years having passed since new dosage guidelines were issued, no new FDC drugs for children have been developed to correspond to the new doses. Until that happens, treatment providers are struggling to provide children the new doses through complex interim dosing recommendations," the report noted.
MSF urged WHO to provide clear guidance to drug manufacturers on needed fixed-dose combinations of first-line drugs to support implementation of the new WHO-recommended dosages.
TB affects nearly a million children globally every year, and up to 130,000 die annually from this preventable and curable disease.