17 April 2024 by Limpho Sello

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Dr. Llang Maama, the Ministry of Health’s TB and Leprosy Manager says lab technicians are being trained to perform genome sequencing. Photo Credit: Limpho Sello.

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At just 26 years old, *Mapoulo battled tuberculosis (TB) through five treatment attempts. From 2020 to 2022, she experienced five failed TB treatments, prompting local laboratory technologists like Mooko Matobo to seek solutions internationally.

Matobo, serving as the Principal Laboratory Technologist at the National TB Reference Laboratory for the Ministry of Health, shared Mapoulo’s story at the TB scientific symposium held on April 4, 2024, in Maseru.

This symposium was part of the activities organized by Lesotho’s Ministry of Health to mark World TB Day, celebrated annually on March 24. During the event, Matobo revealed that Mapoulo was first diagnosed with TB at the Likotsi Filter Clinic in Maseru in 2020. After completing her six-month TB treatment successfully, she was declared healthy.

“In 2021, she was diagnosed with TB again and started on the same treatment as in 2020,” Matobo explained.

Regrettably, Matobo added that Mapoulo stopped her treatment prematurely during her second attempt.

By August 2021, she was diagnosed with TB for the third time. She received another TB treatment in May 2022, and her fifth unsuccessful treatment was confirmed in September 2022.

Matobo explained that Lesotho uses a machine called GeneXpert MTB/RIF Ultra to test if someone has TB. The machine also detects both TB and Rifampicin – one of the medicines used to treat TB.

Matobo said they tested the patient’s sample using a special test. She said they discovered that one medicine, Isoniazid (INH), did not work, but another one called Rifapentine worked. Also, they found that another medicine, Streptomycin, worked, but Isoniazid did not.

Why Isn’t Mapoulo’s treatment working?

On April 16, 2024, Matobo told Uncensored News that Mapoulo’s treatments did not work because she had a mutation called I491F. This mutation made the GeneXpert test not able to detect this mutation properly, so the test did not work well.

Because of this, Matobo said Mapoulo kept getting sick even after trying treatment multiple times. She explained that currently in Lesotho, TB diagnosis is only done using the GeneXpert machine.

Partners in Health (PIH) says GeneXpert is a closed-system polymerase chain reaction (PCR) machine that allows laboratory technicians to perform automated, cartridge-based PCR–the gold standard for many diagnostic lab tests.

According to PIH, with GeneXpert, a PCR test can be done within hours by inserting a cartridge specific to the disease into the machine. The machine then detects and amplifies specific genetic material (DNA or RNA) to confirm whether the disease is present or not in the sample.

Matobo explained that this machine cannot detect the I491F mutation, which is why the patient’s treatment failed—it was escaping detection by the GeneXpert.

“The I491F mutation in RPBO gene is not a target for GeneXpert but confers a rifampicin resistance,” Matobo explained.

She added: “We need to monitor patients who don’t improve with the first-line TB treatment that includes Rifampicin. Some resistant TB strains might not be detected by the GeneXpert.”

Matobo explained that TB can be hard to treat or take a long time for several reasons. She said these reasons include patients stopping their TB treatment when they feel better or for no reason, receiving poor-quality treatment, being misdiagnosed, or waiting too long to go to the clinic.

However, in Mapoulo’s case, Matobo said treatment failed because the GeneXpert could not detect that specific mutation in her TB germs.

Looking for help in Germany

With five failed treatments tests, Lesotho looked for help in Borstel, Germany.
In this country, doctors use a method called Genomic Sequencing – a process of figuring out the order of tiny building blocks in our genes.

Matobo explained that genomic sequencing gave them clear answers about what the problem was, helping them find out what the GeneXpert had been missing all along.

She quickly added that Lesotho does not have genomic sequencing, so the country have to send samples to Borstel for more testing.

Although this process takes time, with an estimated three-month wait for results, it is an important step that helps Matobo and her colleagues understand why patients like Mapoulo kept getting TB.

“With the genotype analysis, we sent 129 DNA samples to Borstel for sequencing. Of these, 95 were successful, 40 needed to be done again, and 20 were excluded because of poor quality.

“These samples came from both the cut TB samples and routine samples from the ministry. Overall, most of the analyses were successful, and the cluster rate of the samples was not very high,” Matobo explained.

Meanwhile, Dr. Llang Maama, the Ministry of Health’s TB and Leprosy Manager, told Uncensored News that the issue Lesotho faces with GeneXpert missing some cases is a common challenge for many countries using GeneXpert.

Truenat, another TB testing machine, uses chip-based and real-time micro-polymerase chain reaction (PCR) to detect TB and rifampicin resistance using DNA from a sputum sample in just an hour.

While Dr Maama noted that Truenat is not necessarily more advanced than GeneXpert, she said: “We need it in the Lesotho especially to cover remote areas of the country.”

She said its portability allows clinicians to easily carry it to where people will be screened for TB.

“There is a potential of getting at least one or two for the country. They are going to be very helpful in our campaigns because we can take them to our campaigns to screen them on site and get results immediately.”

She added, “We’ve requested a mobile testing unit for the new budget. While it’s the same equipment, this version can be moved to different locations for on-site testing.”

 Lesotho records high TB mortality rates

The 2023 World Health Organisation (WHO) Global TB report says that TB is the leading cause of death worldwide from a single germ. The report shows that Lesotho is one of the 30 countries with the highest TB rates, with an estimated 661 cases per 100,000 people in 2022.

In Lesotho, the death rate from TB is high, with an estimated 225 deaths per 100,000 people in 2022. About 3.2 percent of new TB cases and 6.8 percent of those receiving treatment again are estimated to have drug-resistant TB.

“TB is the leading cause of death among people with HIV, and it’s also a major reason for drug-resistant infections that lead to deaths,” Matobo explained.

She added, “Approcximately 400,000 new TB cases are resistant to Rifampicin, which is a major factor leading to multidrug-resistant tuberculosis (MDR-TB). Additionally, around 200,000 people die from MDR-TB. So, we need to recognize that MDR-TB is a key component of the global challenge of antimicrobial resistance.”

The Centers for Disease Control and Prevention states that MDR-TB is resistant to isoniazid, rifampin, a fluoroquinolone, and either a second-line injectable (like amikacin, capreomycin, or kanamycin) or bedaquiline and linezolid.

She said the main issue with TB diagnosis is that many cases go undetected, including MDR and XDR-TB cases. She quoted Jhpiego’s Monthomeng Matete saying most patients are tested for MDR when they first get TB.

“Additionally, out of 14 people with MDR-TB, which is 15 percent, and one person with XDR-TB, which is one percent, three of the MDR-TB patients have the I491F mutation strain. This strain escapes detection by the GeneXpert,” Matobo explained.

Lesotho to soon introduce advanced TB testing

Dr Richard Banda, WHO Country Representative. Photo Credit: Limpho Sello.

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On April 10, 2024, Dr Maama told Uncensored News that there is an urgent need for technological upgrades like genome sequencing. This technology allows the country to analyse TB bacteria deeply, going into its DNA depths that the GeneXpert cannot detect.

“Genome testing is crucial, and we are at an advanced stage to implement it in the country. Lab technicians are being trained to perform genome sequencing, learning about the bacteria’s patterns and behavior,” Dr. Maama explained.

She added that as diseases and their bacteria and viruses change over time, technology needs to be updated to stay ahead.

“The same goes for effective drugs, as bacteria can change. That is why we are able to monitor the effectiveness of the drugs we use. Science can’t stand still because bacteria keep changing, and our drugs can influence how they behave,” she said.

Meanwhile, Lesotho marked World TB Day on April 6, 2024, in Ha Abia. During the event, Dr. Richard Banda, the World Health Organisation Country Representative, affirmed his office’s commitment to supporting Lesotho with TB treatment guidelines.

“We will continue to support the country by updating TB treatment guidelines to reflect the latest practices and expanding access to rapid diagnostic tools,” Dr Banda said.

He emphasized that strong political leadership, backed by support from WHO and other partners, is always crucial in the fight against TB.

“I urge leaders at all levels in the country (Lesotho) to intensify their commitment to strengthening health systems, ensuring equitable access to TB care, and scaling up innovative interventions. Meeting TB control targets is crucial for saving lives.”

This story was produced with support from Paballo-ea-Bophelo, a civic group advocating for equal access to healthcare services.