The harsh reality of multidrug-resistant TB in children

At four months old, Ziggy Intal was in and out of the hospital in 2022. He was initially diagnosed and treated for pneumonia, but recurring symptoms of fever and cough led his physicians to test him for tuberculosis.

They first did a skin test and an X-ray. Then they did a sputum or phlegm test that revealed he has multidrug-resistant TB or MDR-TB, a more serious form of the disease that can’t be treated with standard TB drugs isoniazid and rifampicin and requires a long treatment period of 15 months.

The Philippines has one of the highest numbers of people with TB, accounting for 7% of the global burden. The government recorded 612,002 cases of TB last year, up from 435,890 in 2022. MDR-TB cases stood at 6,911. Children account for 1.7% of the MDR-TB burden in the country, up from 1.3% in 2022.

Ziggy’s diagnosis came as a surprise as none of his family members had TB. Though the source of his illness remains a mystery, his diagnosis helped put him on treatment, which isn’t always the case for children suffering from TB.

Hard to find

More than 1 million children aged zero to 14 years old fall sick with TB yearly, but less than half of these cases get diagnosed or reported, according to the World Health Organization. This means over half a million children aren’t getting the treatment they need.

The numbers are similarly stark for children who suffer from MDR-TB or rifampicin-resistant tuberculosis. Only about 12-16% of children and young adolescents with MDR-TB or RR-TB were diagnosed and treated in 2022.

Children under 5 years old account for the largest undiagnosed age group, likely due to the difficulties in diagnosing them. Cases of TB in kids as young as Ziggy are hard to catch, and doctors often have to tap into their detective skills to properly assess whether a child has TB and to ensure they provide the right treatment.

Doctors look for common symptoms of TB such as weight loss, coughing, and fever. But to confirm the presence of TB, they request a bacteriologic examination where specimens of mucus and gastric contents are tested in the lab.

However, the tests are challenging. Kids usually have a lower bacterial load than adults. They also don’t know how to expel sputum, which is needed to test for the TB bacteria. An alternative is gastric aspiration, an uncomfortable procedure where a tube is inserted in the nose to reach the stomach to obtain the fluid needed to test for TB. But it can lead to false negative results, as gastric acid can kill the bacteria even before it reaches the lab. These difficulties can lead to low detection of TB in children and misdiagnosis.

In Ziggy’s case, it took three hospitalizations in three different hospitals before he was diagnosed with TB.

Maricel Magno, his grandaunt, is a TB coordinator but also failed to suspect his grandson’s illness as TB. “It's very ironic,” she said.

In 2020, WHO recommended the use of stool samples to diagnose TB in children, an easier and painless method. But it’s not yet in use in the Philippines, according to Dr. Irene Flores, TB specialist at the Jose B. Lingad Memorial General Hospital in San Fernando City, Pampanga where Ziggy had his treatment.

“That’s why you really need to know a patient’s history and their contacts. It’s in the TB guidelines that one shouldn’t just rely on symptoms, bacteriologic examination, and X-ray when assessing a child, but also their contacts,” Flores said.

If a child tested negative for TB but has clinical symptoms and has known exposure, such as to a parent with drug-resistant TB, then treatment should be given as there’s a high likelihood that the child has been infected, she said.

A debilitating disease

Russel Cabral, 12, was diagnosed with MDR-TB in mid-2023. By the time he was brought to the hospital, he had a persistent cough, was no longer speaking and was bedridden for months. He lost so much weight and could no longer walk.

Months prior, Russel was already coughing blood. But his father, Marcelo Cabral, refused to have him confined and intubated in the hospital. Instead, he asked the doctor for medicines to treat Russel’s coughing.

But Russel’s condition didn’t improve. When a good samaritan who serves as a bible study coordinator in their neighborhood in Santo Tomas, Pampanga, visited Russel, she found him in a severe condition and took the initiative to get him medical help.

“He could no longer walk. … They had to carry him to and from the bathroom [when he needs to use it],” Princess Guinto told Devex. “[I told them] we can't just wait and let him die like this.”

Their initial suspicion was that Russel suffered a stroke.

But he was diagnosed with MDR-TB in the same hospital where Ziggy was diagnosed and treated for TB.

Flores suspects he may have gotten the infection from his father Marcelo, who two years prior also was diagnosed with MDR-TB. But at that time, family members had no symptoms of the disease.

It’s not uncommon for active TB disease to develop two years after exposure, she said.

“That’s why monitoring is very important. The person with TB disease is not your only patient, but the entire family,” she added.

The long road to treatment

Adding to the challenge of diagnosis is treatment. The duration of treatment is painfully long for children with MDR-TB, and they are at risk of suffering from adverse side effects that can be hard to catch.

Ziggy and Russel had to take four different medications daily for 15 months. They also needed to undergo multiple tests while on treatment — blood extractions, gastric aspirate, X-rays — to monitor whether the treatment was working or the disease was relapsing.

Doctors also had to monitor them for optic neuritis, a condition that can cause eye pain and vision loss and is a common side effect of one of the MDR-TB drugs.

However, another challenge is that neither Ziggy nor Russel can read.

For Russel, Flores uses an ophthalmological chart, called the Tumbling E chart, to assess his vision. “He would just tell me the direction of the letters, as he could not read them,” she said.

In Ziggy’s case, his doctors sought the aid of ophthalmologists, who found some swelling in his optic nerve. It’s unclear whether it’s linezolid induced or by the antibiotics Ziggy took from prior hospitalizations. But for his safety, his doctors decided to change his treatment regimen.

In 2022, WHO recommended a shorter treatment regimen, called BPaL, for patients with MDR-TB. But the recommendation does not yet include children under 15 years old.

“Sometimes it pains me to think that they don’t qualify yet [for BPaL]. But we have to follow the guidelines,” Flores said. She hopes it will eventually become available and proven safe for children and young adolescents.

Last December, Ziggy completed his 15-month treatment. Flores said he is required to have a follow-up checkup at six and 12 months. This is standard protocol for all patients to ensure the sustained success of treatment.

But Russel still has six to seven months left for his medications. If he fails to complete his treatment, he could suffer from extensively drug-resistant TB, which is even harder to treat.

“I told him to be patient so he can overcome his illness,” Marcelo said. It’s a long road to recovery, but he is grateful that his son is now doing well.

“I thought he wouldn’t be able to recover. But God didn’t abandon us,” Marcelo said. “[Russel] is now laughing and he can again play outside.”

Source: Devex