World TB Day highlights challenges—and hope

Man receiving tuberculosis drugs
Man receiving tuberculosis drugs

USAID Asia / Flickr cc

On this World Tuberculosis (TB) Day, global health leaders are warning that the COVID-19 pandemic is threatening to derail efforts to reduce the burden of what was, until recently, the world's top infectious cause of death.

According to preliminary data from 84 countries compiled by the World Health Organization (WHO), an estimated 1.4 million fewer people received TB care in 2020 than in 2019, as TB case notifications fell by 21% globally. The decline in TB case notifications in 10 high-burden countries was 28%, with the biggest declines seen in Indonesia (42%), South Africa (41%), the Philippines (37%), and India (25%).

Fewer case notifications means fewer TB patients being diagnosed and receiving proper care. The agency estimates that more than a half million excess TB deaths could result from the decline in case notifications, which would set back TB mortality to what it was in 2010. In 2019, an estimated 1.4 million died from TB-related illness.

The drop-off is linked to COVID-19 lockdowns and restrictions that have disrupted TB diagnosis, treatment, and prevention services around the world, particularly those in high-burden countries, where many TB patients already face hurdles to timely diagnosis and quality treatment and care. Even before COVID-19 pandemic, WHO officials note, nearly 30% of people with TB were not receiving proper treatment because of barriers in accessing care.

"The impact of the COVID-19 pandemic has been severe," Tereza Kasaeva, MD, PhD, director of the WHO's Global TB Programme, said at a press conference earlier this week.  "While we struggle to overcome the COVID-19 pandemic together, we should not neglect the millions of people suffering and dying from TB."

COVID-19 has also had more direct impacts on TB patients. According to the Stop TB Partnership, data emerging from India and South Africa show that people coinfected with TB and COVID-19 have three times higher mortality than people infected with TB alone.

To increase detection, diagnosis, and treatment of TB among vulnerable populations, the WHO today announced new guidelines to scale up systematic screening to rapidly identify TB patients. The guidance aims to help countries identify populations at highest risk of infection, such as those who live with TB patients or who have HIV, and the locations most affected. The WHO is recommending use of rapid molecular tests, chest radiography, and other tools to aid in systematic screening efforts.

"Systematic screening is critical to ensure we can detect TB early in the people who need it, while also identifying people who could benefit from TB preventive treatment," Kasaeva said.

Shorter, more effective treatment for 'worst kinds' of TB

Amid the dire news about the pandemic's impact on TB diagnosis and treatment, however, TB advocacy groups do have some reason to cheer. Chief among them is the effort to address the lengthy, toxic, and largely ineffective treatments for highly drug-resistant TB.

Since the US Food and Drug Administration (FDA) approval of the anti-TB drug pretomanid in 2019 as part of a three-drug, 6-month oral treatment regimen for patients with extensively drug-resistant TB (XDR-TB) or those with multidrug-resistant TB (MDR-TB) that is treatment intolerant or nonresponsive, a growing number of countries have started providing the regimen to the patients who need it.

That's significant because the BPaL (bedaquiline, pretomanid, and linezolid) regimen is a major improvement over the standard regimens for highly drug-resistant TB, which last 18 to 24 months and include multiple antibiotics, some of which need to be injected and can have severe side effects, and have a poor success rate.

In addition to being shorter and less toxic, data from the phase 3 Nix-TB trial demonstrated a success rate of 90% for the BPaL regimen at 6 month follow-up, and a recent analysis found that success rate was sustained at 2 years. The overall treatment success rate reported in 2018 for the standard XDR-TB regimen was 39%, according to the WHO.

"It's a transformative change, when it comes to treatment of the worst kinds of TB," Sandeep Juneja, senior vice president of market access at TB Alliance, told CIDRAP News. Pretomanid was developed by TB Alliance, which has been working with partners since the FDA approval to accelerate global approval and access to the BPaL regimen.

And now more patients with the worst kinds of TB will have access to it. Pretomanid has been made available to 150 low- and middle-income countries through the Stop TB Partnership's Global Drug Facility, and TB Alliance has reached commercialization agreements with international manufacturing partners to promote competitive and sustainable pricing of the new regimen.

Per WHO guidelines introduced in 2019, countries can use the BPaL regimen under operational research conditions, which require patients to be monitored and tracked carefully. According to TB Alliance, more than 28 countries have procured the regimen or will soon be providing it to patients under those guidelines.

"It's gathering momentum pretty rapidly in many countries now," Juneja said. "There are several countries that have already commenced putting patients on [BPaL] treatment under operational research conditions, and many others are gearing up to start that."

Among the early adopters of the BPaL regimen were countries with a high burden of XDR-TB, like Ukraine and South Africa. But Junejal said countries less affected by XDR-TB are also planning to use the regimen under operational research conditions.

More research on shorter treatments for MDR-TB

Improving treatment options for drug-resistant TB is one element of the WHO's End TB strategy, which calls for an 80% reduction in overall TB incidence, and a 90% reduction in TB deaths, by 2030. According to the WHO's latest global TB report, and estimated 465,000 people developed MDR-TB or rifampicin-resistant TB in 2019.

In addition to supporting the shorter BPaL regimen for XDR-TB patients, the WHO has since 2018 recommended shorter MDR-TB regimens that prioritize newer medications and oral drugs over older, injectable drugs.

"Treatment is from two to three times shorter if countries follow our latest recommendations…[and] can be provided at home or the community, without unnecessary visits to healthcare facilities," Kasaeva said.

And research into shorter, simpler treatments for MDR-TB patients continues. Medecins Sans Frontieres (MSF) announced today that a phase 2/3 clinical trial testing a 6-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin against standard MDR-TB treatments—which last 9 to 20 months—stopped enrolling patients last week after the independent data safety and monitoring board indicated the shorter regimen was better. The conclusion was based on an interim analysis of 242 patients at trial sites in Belarus, South Africa, and Uzbekistan.

MSF says it's preparing a dataset to share with the WHO and will publish the results in a peer-reviewed journal in the coming months.

"The findings could transform the way we treat patients with drug-resistant forms of TB worldwide, who have been neglected for too long," trial steering committee member David Moore, MD, of the London School of Hygiene and Tropical Medicine said in an MSF press release.

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