Researchers say their case report highlights the difficulties faced when treating drug-resistant TB in children.
Now 5 years old, the child is in good overall health and is in full remission, according to the report, though she will continue to be monitored for a further 2 years.
By describing how they successfully treated the child, as well as the obstacles they faced, the report authors hope they can shed light on how to successfully treat other children with the disease.
Caused by the bacteria Mycobacterium tuberculosis, tuberculosis (TB) is estimated to cause illness among more than 10 million people worldwide each year, and around 1.5 million die from the disease annually.
TB is an airborne disease that most commonly attacks the lungs, causing coughing - including coughing up blood - chest pain, weakness or fatigue, fever, chills, night sweats, loss of appetite and weight loss. If untreated, TB can be fatal.
While TB can occur in any country, last year, the majority of cases occurred in India, Indonesia, Nigeria, Pakistan, People's Republic of China and South Africa.
The challenges of treating children with drug-resistant TB
TB is a curable disease, but it is becoming increasingly challenging to treat. M. tuberculosis is resistant to most drugs currently used to treat it, and its resistance is growing; the World Health Organization (WHO) estimate that around 480,000 people developed multidrug-resistant TB last year.
Report author Dr. Sanjay Jain - TB expert and pediatrician at Johns Hopkins Children's Center - notes that while drug-resistant TB is difficult to treat in general, it is particularly challenging to treat in children.
They explain that children have less TB bacteria in their bodies than adults, which makes the disease tricky to detect and delays diagnosis.
What is more, the authors note that there is lack of diagnostic tools for drug-resistant TB, lack of reliable markers to assess children's response to drugs for TB, as well as lack of child-friendly drugs for TB that meet their physiologic and metabolic requirements.
In their report, Dr. Jain and colleagues describe the challenges they faced when attempting to diagnose and treat a child with a rare form of multidrug-resistant TB.
Case 'highlights need for swifter, more reliable diagnostic techniques'
After returning from a 3-month trip to India, the 2-year-old child was brought to Johns Hopkins Hospital with relentless fever and general sickness.
Initial tests - including urine and blood tests and a throat swab - showed no signs of infection. However, a chest X-ray showed the child had a suspicious spot on her lung, prompting further examination.
- Last year, 9,421 cases of TB were reported in the US
- There were 555 deaths from TB in the US in 2013
- There were 91 cases of multidrug-resistant TB in the country last year.
Doctors then conducted a gastric aspiration, which involves removing swallowed mucus from the gut for testing. While the tests came back negative for TB, the doctors decided to proceed with treatment for the disease.
"Preliminary test results are notoriously unreliable and this case provides a perfect illustration of the need for swifter and more reliable techniques," notes Dr. Jain.
When the same tests were conducted 4 weeks later, as suspected, they showed the child was positive for TB.
With standard treatment for the disease, the child's symptoms improved rapidly. However, from a repeat X-ray, the doctors found the child showed persistent lung inflammation. Dr. Jain says this emphasizes the view that clinical symptoms of TB in children can be misleading.
Further laboratory tests revealed that the child had extensive drug-resistant TB (XDR TB) - a rare form of multidrug-resistant TB that is resistant to almost all first- and second-line drugs for the disease. All in all, it took 12 weeks to conclusively diagnose the child, according to the report authors.
At the time of XDR TB diagnosis, the child's condition worsened. Her fever returned, and a CT (computed tomography) scan showed worsened lung inflammation and death of lung tissue.
As a result, doctors initiated a novel treatment involving a combination of five TB drugs and vitamin B6. However, the authors note that they came across another problem at this point; there was no way to monitor how TB bacteria were responding to such treatment.
Low-dose CT imaging helped monitor treatment response
Clinical symptoms would be a poor indicator of treatment response, the doctors reasoned, and lab tests would take weeks - time they did not have, since the child's condition was rapidly worsening. As such, they turned to child-friendly, low-dose CT scans - a technique that is becoming more widely used for children.
"In the absence of reliable biomarkers for pediatric TB, the acute need for rapid readouts of treatment response and the dangers of treatment failure, we felt a CT scan was our best option," explains Dr. Jain.
The doctors conducted repeat CT scans over a 6-month period - delivered at doses comparable to 2-3 months of radiation from the natural environment - which allowed them to effectively monitor disease progression and how TB bacteria was responding to the novel combination treatment.
Within weeks of initiating treatment, the child's physical symptoms of XDR TB improved. The CT scans echoed treatment success, showing a clearing of mucus in the lungs.
Dr. Jain says this opposes the popular notion that CT scans lag behind physical symptoms of the disease, and the case report indicates CT imaging is a useful tool for monitoring treatment response in children with drug-resistant TB.
Commenting on the report, Antonio Sastre, program director at the National Institute of Biomedical Imaging and Bioengineering - part of the National Institutes of Health, who helped fund the study - says:
"Many factors made this a challenging case, including how physicians would monitor on a timely basis whether the drugs had reduced or eliminated the bacteria.
The effective use of CT monitoring was first shown in the laboratory, with mice, and low-radiation CT imaging has provided a readily translatable solution for this case."
Three years later, the child is now healthy and in remission, though Dr. Jain says the case is "a wake-up call to the realities of TB."
Last month, Medical News Today reported on a study published in The Lancet, in which researchers warned we are going to face worse TB epidemics unless more is done to fight the disease on a global scale.