Tuberculosis (TB) is hard to diagnose in children, especially very young ones. This is because it is difficult for children to cough up the sputum required to perform the gold standard molecular TB test. Even if they do manage to cough up sputum, there may not be enough TB bacteria in it for a positive diagnosis since children's sputum harbours fewer bugs than that of adults.
Because of this, explains Dr Megan Palmer, medical director of the Desmond Tutu TB Centre PK Unit at the Brooklyn Chest Hospital, TB in children is often diagnosed by looking for the presence of symptoms and signs of TB (such as cough, fever, sweating, lethargy, poor appetite, and poor growth), identifying that the child has been in close contact with another person with TB, and seeing signs of TB on a chest X-ray. TB in kids is thus often diagnosed without a positive molecular or other direct test for the bug.
"We hope that there will be a better diagnostic test for TB in children in the future so that all children with TB can be diagnosed early and access treatment and care because TB is curable," says Palmer.
There are several new TB tests and diagnostic approaches currently being researched or piloted. Spotlight recently reported on an experimental finger-prick blood test - apart from blood, urine, stool and saliva might also have potential. Meanwhile, several pilot projects in South Africa are testing the use of new mobile X-ray screening technology and the Department of Health has started offering molecular tests to people who are asymptomatic but considered to be at high risk of TB - although this still relies on sputum, which limits the potential usefulness for children. A urine test is being used to test for TB in people living with HIV who have severely compromised immune systems.
Just like X-rays have made something of a comeback with the development of new, safer mobile X-ray screening technology, the role of ultrasound in TB diagnosis may also be set to change. Ultrasound is an imaging technology that makes use of sound waves.
Expanded role for ultrasound?
"In the last few years, researchers have been exploring whether ultrasound of the lungs can be used as an alternative to chest X-ray to look for signs of TB in both adults and children," says Palmer.
This could be important since lung (pulmonary) TB is the most common form of TB by some distance.
Palmer explains that ultrasound is already the imaging method of choice for diagnosing abdominal TB in children - as well as being used to detect pneumonia. She says it is currently only available at hospitals (referral centres) and not at clinics.
"Pulmonary TB is the commonest form of TB in children and this is where the use of lung ultrasound is being explored," says Palmer. "Lung ultrasound will not be available in routine healthcare facilities until more research has been done to prove that it is a useful tool to diagnose TB. If studies show that lung ultrasound is useful [for diagnosing] TB in children, then ultrasound devices will need to be procured and healthcare workers will need to be trained to use them before this becomes widely available."
Palmer says that both chest X-rays and lung ultrasound are safe and painless for the child.
"Chest X-ray does include a radiation dose, but this is not a meaningful risk unless multiple chest X-rays are taken in a short period of time," she says. "Lung ultrasound has the potential benefit of being able to be performed at a patient's bedside without the need for referral to an X-ray department, however, this will only become a realised benefit if ultrasound devices are made widely available and healthcare workers are trained to use them. This is currently not the case in South Africa."
Early days
But as Palmer and others point out, the evidence and technology are not yet there to support the widespread use of ultrasound to detect pulmonary TB in children.
A paper published in March that she co-authored concluded that "thoracic ultrasound may have a potential role in screening and diagnosis of TB [but] if it proves to be a useful tool, implementation challenges will need to be addressed before it can be deployed effectively". Apart from challenges with training people to use ultrasound devices and interpret images, the study also suggested that some wrinkles have to be flattened out with the ultrasound devices they tested.
But even with better ultrasound devices, it just isn't known yet exactly how well ultrasound will compare with X-rays and to what extent a more portable hand-held ultrasound device may or may not offer benefits over less wieldy X-ray machines.
Professor Heather Zar, Chair of the Department of Paediatrics and Child Health at Red Cross Children's Hospital and Director of the SAMRC Unit on Child and Adolescent Health at the University of Cape Town describes the use of lung ultrasound as "promising but by no means definitive".
"It is difficult (especially in young children) to detect the commonest form of pulmonary TB, which is enlarged lymph nodes in the chest. It can pick up complications like fluid around the lung but can't really distinguish TB from other causes of pneumonia," Zar explains. She says it may also be useful to see a response to TB treatment by repeating the ultrasound a few weeks into treatment.
Zar says that ultrasound is useful to look for TB in other sites such as the liver or spleen - which can be easily missed. "HIV-infected children are at greater risk [for developing] disseminated disease, so detecting TB in the liver or spleen, for example, may be especially important in this group."
Detecting TB lymphadenopathy
Professor Savvas Andronikou, Professor of Paediatric Radiology at the Perelman School of Medicine, University of Pennsylvania, says it is possible to see TB lymphadenopathy (a form of extrapulmonary TB) with ultrasound and make a diagnosis. "Using chest X-rays for detecting lymphadenopathy [the fingerprint of paediatric pulmonary TB] is flawed," he says.
"X-rays are not accurate, nor reliable for this. The current WHO guideline suggests that a chest X-ray detection of severe TB in the visualisation of airway compression or cavities makes a difference in length of treatment. I would therefore use both techniques at present and even consider more high-end techniques too. Imaging can add a lot of value in diagnosis and classification for treatment, detection of complications, and follow-up for response to treatment," he says, adding that all modalities are useful but ultrasound is the only one they can really take successfully to the patient. "It [ultrasound] requires technical skills and an onsite operator in close contact with the patient. However, it is an affordable technology that has been improved in the development of high-quality mobile units - both in laptop and handheld styles. Therefore, the imaging can go to the patient as opposed to the patient having to visit a high-end hospital in a city where big X-ray equipment needs to be housed, operated, and maintained properly," he says. "Mobile X-ray may work, but it's not necessarily the best option," says Andronikou.
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A simple diagnostic test for children
While ultrasound is clearly useful in some instances, and while ongoing and future research might well justify its wider use, it seems unlikely to be a silver bullet for TB detection in children.
Andronikou believes that the future is a diagnostic test in children for TB that is a lot simpler, can be automated, and does not require imaging, in other words, something like a point of care lab test (probably of blood, urine, stool or saliva).
"Imaging could then detect complications of TB maybe or assist in TB that is resistant to treatment. Ultrasound would play a role in that. We can modify what we do accordingly and use imaging to classify treatment subgroups as suggested by the new WHO guideline. At present, ultrasound is only partially useful for this," says Andronikou.
