TB programs, trials pause as COVID-19 spreads

India has the highest burden of TB cases at over 2.3 million a year, and many TB drug suppliers and manufacturing sites are based in India. Due to the lockdown in the country since March 24, production capacity has been affected, leading to a shortage of supply to the National TB Elimination Programme. But this also has an extended impact on TB treatment across the world.

“If they go ahead with this, [it] will be really really bad,” said Dr. Lucica Ditiu, executive director of the Stop TB Partnership, which does pooled procurement of medicines and other TB products under its Global Drug Facility.

Ditiu said the organization has written to the ministry to ensure the supply of anti-TB drugs overseas, and was told; “they are still looking into it.”

“We hope it will not happen but we will know in the coming days,” she told Devex.

This latest policy consideration in India adds to an already difficult operating environment for the TB community globally. The World Health Organization has called on countries and organizations to step up response against TB amid the coronavirus pandemic. But putting that into practice has been challenging.

Health care workers and TB experts have told Devex COVID-19 has significantly disrupted TB programs, particularly in some of the highest-burden countries.

Services diverted for COVID-19

TB services have stopped in some localities, due to overburdened hospitals and health worker shortages, said Jeff Carl Estioco, national TB program nurse coordinator for Metro Manila. A number of health staff in-charge of providing TB services in the capital have been asked to help in COVID-19 quarantine facilities, while others, exposed to the virus, have had to go under quarantine.

Some hospitals in Manila that used to cater to a large number of TB patients have also become COVID-19 referral centers. A number of medical laboratories that used to process TB specimens have also stopped operations.

There’s also a decrease in TB case notifications for the first quarter of 2020 in Metro Manila. Reported cases were over 4,000, a significant drop compared to over 14,000 cases in the first quarter of 2019, although Estioco argued this may well be due to manpower shortages and overburdened staff unable to properly file case reports. He added unvalidated reports put the numbers for the first quarter of 2020 at over 11,000.

“My biggest concern is the provision of direct services to TB patients. That’s number one, as the pandemic has halved these efforts. Second is the exposure of frontline health workers to COVID-19. And third is how we’ll be able to recover patients lost to follow-up during this pandemic,” he said.

Multidrug-resistant TB patients often don’t want to continue their treatment due to adverse drug side effects, he said. Plans to implement a shorter, all-oral TB treatment for these patients were disrupted by the lockdown, although efforts are underway to orient patients on this regimen online.

India, too, shares a similar situation. Daily TB case notifications in the country are down 80% following the national lockdown, according to the findings of a rapid assessment conducted by the Stop TB Partnership in several TB high-burden countries.

A decline in case notifications is understandable, as the lockdown meant people are unable to move from point A to point B, said Jamhoih Tonsing, regional director of the International Union Against Tuberculosis and Lung Disease in Southeast Asia. In addition, most health facilities’ priority is patients suspected of COVID-19.

Restrictions on movement

While some community volunteers are still able to move around, this differs across countries.

“How [authorities] interpret and enforce lockdowns ... determine how easily we can move around,” Tonsing said.

But fears of COVID-19 have also led some to stay at home.

“There are people who are willing to [move around], but you’re right not everybody wants to move about. They’re scared. They’re anxious. And rightly so. This is a disease we know little about,” Tonsing said.

In Indonesia, efforts to decentralize patients’ access to TB services to primary health care facilities have been met with challenges. Some patients live closer to some of the big hospitals that have become COVID-19 facilities. Multidrug-resistant TB patients also require injections in their treatment regimen.

A regulation has been in place to shift MDR-TB patients to an all-oral regimen, but this was implemented gradually, said Esty Febriani, TB technical adviser of the Lembaga Kesehatan Nahdlatul Ulama, a Muslim organization working in 61 districts across 10 provinces in Indonesia, supporting the government’s national TB program.

In addition, some hospitals still have stocks of the injectable agent in the old TB regimen, and some patients experience adverse side effects from the all-oral TB treatment, she added.

Suvanand Sahu, deputy executive director at the Stop TB Partnership, said countries need to be more proactive in diagnosing TB patients. Delayed diagnosis will spread TB among households.

He said the organization has started thinking of conducting modeling studies post-COVID-19 that would answer the questions: 1. What is the impact of COVID on TB mortality and incidents? and 2. What needs to happen post-COVID-19 to catch up on TB response in high burden countries?

Heads of states and government representatives committed to a set of targets for 2022 at the U.N. High-Level Meeting on TB in September 2018. However, “we expect that in 2020 progress will not be there. So catch up is needed,” he said.

TB trial activities ‘on hold’

COVID-19 also has an impact on TB clinical trials.

The endTB initiative, a partnership between Partners In Health, Médecins sans Frontières, Interactive Research and Development, and UNITAID, launched in 2016 a phase 3, randomized clinical trial evaluating the efficacy and safety of new drugs bedaquiline and delamanid in combination with existing TB drugs for the treatment of MDR-TB. It is a multicountry trial that includes locations in South Africa and India.

Clinical trial activities in Khayelitsha, a township in Cape Town, South Africa, are ongoing despite the detection of local transmission of COVID-19 there. But this is only for patients already enrolled in the trial, said Dr. Gabriella Ferlazzo, senior TB advisor with MSF's Southern Africa Medical Unit.

“We did not have to put them on hold, as it is a therapeutic trial, in which the benefit for patients to continue receiving their treatment and follow-up as part of the trial, is considered to [outweigh] any risk due to the COVID epidemics,” she told Devex over email.

The continuation of the trial is essential and has received approval from local authorities, she said, although they had to modify some of their activities to ensure patient and staff safety from COVID-19 infection. This included, for instance, increased use of digital technology as part of patient monitoring, counseling, and follow-up.

But new enrolments for the trial “have been put on hold,” Ferlazzo said.

Plans to start recruitment for a similar trial in Mumbai and Pune in India was also postponed to a later date when the COVID-19 situation “will hopefully calm down.”

“The trial had not officially started in India, prior to COVID, but everything was ready for it!” she said.

Grania Brigden, director of The Union’s TB department, said any delays on TB research and development are a concern, although there is also a need to ensure that continuing trials does not put individuals involved at increased risk of exposure to COVID-19.

Experts have for so long raised concerns on the limited funding funneled to TB research and development. However, the pipeline has been “relatively good” for the past 3-5 years, Brigden said, as new treatment options and TB vaccine developments emerge.

Lessons for TB

The TB community is finding some opportunities amid the challenges of continuing TB programs. This includes embracing technology.

Last week, The Union in India launched a new project on DR-TB to build the capacity of clinicians and health care providers at district health facilities to better manage DR-TB patients. The project was supposed to launch in March and was delayed because of the lockdown, but they found they can do it online, Tonsing said.

There were also concerns of delays in the submission of a Global Fund proposal, slated for May, “but things are moving on,” she said.

“TB has been a very old program, and people have been very conservative in the TB community. I hope we become more technology savvy,” she said.

Febriani shared a similar realization. With movement restrictions in place, community volunteers in Indonesia have resorted to using the platform Whatsapp to contact households of TB index cases as well as follow up on treatment adherence of DR-TB patients. And there are plans to provide these patients with smartphones if they don’t have one.

“Indonesia is one of the countries where usage of smartphones is very high, but I think the problem is we just realized right now [its benefits]. We adopt this kind of mechanism because we have no choice. Before the pandemic we have so many choices,” Febriani said, adding that the use of mobile phones is something she thinks will be included in their TB program even post-pandemic.

And just as countries use existing TB tools for COVID-19, any research on COVID-19 should also consider how it can be repurposed for TB, Brigden said. In addition, she said: “as we scale up response to COVID-19, it’s important to think of scaling up the fight against TB. We should try to use this as an opportunity to fight against TB, and not have an either-or situation.”

Esiotico is hopeful that people’s awareness of infection prevention measures from the COVID-19 pandemic, such as proper hand-washing, will carry over after the pandemic, aiding the fight against TB.

“I hope a study will be conducted after 5 years to assess learnings from COVID-19 in relation to the implementation of the TB program,” he said.

Source: Devex