MANILA — The World Health Organization has issued new guidelines for expanding testing and improving the treatment times for people with latent tuberculosis infection.
The move is in response to countries’ request for guidance on how to scale up preventative measures for people who may not currently show symptoms of illness, but are susceptible to incurring and developing active TB infection. That includes those living with HIV and those who are HIV negative but are exposed or in contact with patients with pulmonary and multidrug resistant, or MDR, TB.
Of the 30 countries identified by WHO as having high burden of HIV-associated TB, only 12 are currently providing preventive treatment among people with HIV. In addition, only 13 percent of 1.3 million children vulnerable to the disease received preventive treatment in 2016.
“We hope the new guidelines will disrupt the status quo in many countries and leapfrog global implementation of TB prevention efforts,” said Dr. Haileyesus Getahun, coordinator for TB/HIV and community engagement from the WHO’s global TB program, in a news release.
The guideline is hoped to provide an additional boost in efforts to reduce TB burden worldwide, and comes in the lead-up to what advocates hope will be the most important political meeting on the disease to date — the first United Nations high-level meeting on TB. The meeting has yet to be scheduled, but advocates hope it will take place in September during the U.N. General Assembly.
“We can’t continue to allow governments and … global health leaders to promise ending TB by 2030 … as long as they’re not even putting their best foot forward in the course of the next 12 months, or even 12 weeks.”— Sharonnan Lynch, HIV and TB policy adviser for Médecins Sans Frontières
While the agenda and modalities are still being negotiated, many expect the meeting will result in a political declaration in which heads of state commit to increasing investments in TB and in meeting measurable targets that would help move them closer to ending the TB epidemic.
There have been only four health threats that received equivalent political attention in the past in the form of U.N. high-level meetings — Ebola, HIV and AIDS, antimicrobial resistance, and noncommunicable diseases. That TB has at last warranted its own U.N. high-level meeting has many health workers hoping a disease that has been relatively neglected will at last have a fighting chance, particularly when it comes to finding better diagnostic tools and treatment options.
“The benefit of these events is you get [a chance to get] countries to sign on a dotted line to time-bound, measurable, and appropriate commitments about what’s going to happen in their countries, not just globally,” Sharonnan Lynch, HIV and TB policy adviser for Médecins Sans Frontières’ Access Campaign, told Devex. “The second thing is by having a spotlight, you know people will take that spotlight and would want to give themselves a [chance to] shine, and that means their company or their country.”
In Moscow last year, the disease got a boost from the first WHO Global Ministerial Conference on TB, where governments committed to the contents of the Moscow Declaration to End TB, which includes mobilizing sufficient and sustainable financing to develop and implement national TB policies and strategies, including research and innovation; strengthening surveillance systems; developing a multisectoral accountability framework; and scaling up TB prevention, diagnosis, treatment and care, including response to drug resistant TB, across communities.
But come September — if the meeting is indeed scheduled to coincide with the U.N. General Assembly — advocates want more solid, actionable commitments, not lofty goals backed by empty promises.
“What we cannot allow at the U.N. high-level meeting or the lead up to it is for governments simply to say they are committed to end TB, or that they promise to end TB by 2030, and that’s the end of it. Instead, they must commit that next month they will test and treat more people than the month before,” Lynch said. “We do not buy the junk promises of ending TB by 2030. In fact, it’s a bit of a smokescreen to eventually obscure the reality, which is that national governments are behind in terms of implementing the best tools that we have. They’re behind in terms of scaling up WHO recommended TB testing, treatment, and prevention. We can’t continue to allow governments and, I have to state, global health leaders to promise ending TB by 2030 or whatever it takes, as long as they’re not even putting their best foot forward in the course of the next 12 months, or even 12 weeks.”
A call for increased detection rates, better diagnostics
Most deaths associated with TB are preventable with early diagnosis and treatment, but there remain huge gaps in this area. In WHO’s 2017 Global TB report, 6.3 million new cases of TB were reported in 2016, up from 6.1 million in 2015. However, this only accounts for 61 percent of the estimated TB incidence cases worldwide, meaning there are about 4 million undiagnosed patients who are not receiving the appropriate care and treatment they need. And the trend has been almost the same for the past five years, with the number of people being diagnosed each year increasing only slightly and most of it due to increased notifications in a few high-burden countries such as India.
Lynch said this shows the world is “failing at the first step” in reducing TB, which is about diagnosing people.
There are a number of factors contributing to the poor detection rates, but one of them is lack of a robust, catch-all, diagnostic tool, said the MSF HIV/TB policy expert.
“What we really need is a rapid point of care, similar to HIV, that can be used in the frontlines, at the lowest level of care and at the community level,” Lynch said. “However, we don’t have that.”
There are several diagnostic tools used for TB detection globally. One of them is a urine-based rapid diagnostic tool that has an estimated cost of $3.50 and that is easy to administer. However, as this only works with people with compromised immune systems such as people with HIV or those who are extremely ill, Lynch said government interest has been minimal.
“I think the reason is that if there’s not a test that works for everyone, then governments aren’t interested,” she said. “However, given that it works for the sickest people, and given that the sickest people die of TB, it’s kind of worth it, isn’t it?”
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Most of the diagnostic tools being used at point of care is still TB microscopy, where patients’ sputum is put under a microscope to count the TB bacteria. However, this is limited in that it can only detect certain forms of TB, such as those found in the lungs — or what doctors calls pulmonary TB — and in people with uncompromised immune systems. Another means to diagnose TB is through culture, but its turnaround time takes anywhere between 4-6 weeks.
Chest X-rays are helpful in providing early indications for patients suspected with TB, but experts note this requires a fluid test to confirm diagnosis.
More recently, a so-called revolutionary rapid molecular testing tool has been put out in the market. Called the GeneXpert, the testing machine has quick turnaround, better accuracy rates, and can detect different forms of TB, including among people with HIV and those suffering from rifampicin-resistant TB, one of the most common drugs for TB treatment.
But the machine is quite expensive and has several requirements. One of the commonly used GeneXpert machines costs about $17,000. It also requires electricity to use, as well as trained laboratory staff and trained repair workers.
“We thought that was a public health revolution, [but] I’ve seen machines not plugged in. I’ve seen machines still wrapped in plastic. I’ve seen machines sitting idle because there are no cartridges, or machines [that] are idle because they’ve broken down and they haven’t been serviced,” Lynch said. “[And] if you look at the reality, the number of people shockingly diagnosed with TB has not gone up with the advent of this machine. So what needs to happen is people need to look seriously at, do we have a test everywhere where we should? Because that machine should be at every district level in high-burden TB contexts. Do we have a strong sample transport system? And is this machine being maintained and serviced?”
The case for better treatment meds
One of the oldest diseases known to mankind, TB remains stubbornly intractable. And with the advent of drug resistant TB bacteria, treatment success rates require ever more vigilance, even with increased government efforts. And even when good policy is in place, it can be tricky to translate that into perfect practice.
Every Tuesday, patients line up outside a white and green painted facility located within the vicinity of Rizal Medical Center, one of the general hospitals in Metropolitan Manila managed by the Department of Health. On its walls, a familiar sign reads: TB-DOTS, or short for a TB facility implementing the WHO recommended strategy of directly observed treatment, short-course for TB control.
The facility acts both as a referral and TB treatment provider. It’s one of the many TB-DOTS facilities scattered across the Philippines. Here, medicines for TB are free for the duration of a person’s treatment, and indigent patients are given transportation allowance to go to the facility for their treatment, encouraging them to finish treatment by easing the financial burden.
Under the DOTS strategy, patients are required to go to the facility to take their medicines, or have a health care worker, nurse or relative who will be able to account to the doctor or nurse in charge that the patient did take their medicines.
These treatment terms are important, as the long treatment time for TB can yield unwilling patients. A standard TB treatment lasts for 6 months. For those found with drug-resistant TB, it can vary anywhere between 18 to 24 months, and the number of medicines they need to take each day vary from 10 to 20 tablets.
Barangay [neighborhood] health centers have been designated TB-DOTS facilities to ensure patients have closer access to treatment. Even then, some patients can still fall through the cracks.
Of the 445 confirmed TB cases detected by RMC in its TB-DOTS facility in 2016, only 347 have successfully been managed and referred to other DOTS facilities. In 2017, 174 out of 453 confirmed cases were not registered nor successfully referred to other DOTS facilities. The reasons for this vary, such as patients opting to go to the private sector or lost to follow-up.
This links to calls in the international community for more investments in TB research and development that would lead to the discovery of drugs allowing for shorter TB regimen, particularly for drug resistant TB. About four years ago, two new drugs became available for treating drug resistant TB — delamanid by Japanese pharmaceutical company Otsuka, and bedaquiline by Johnson & Johnson (J&J). However, only few patients have been able to access the drugs.
Bedaquiline was approved by the United States Food and Drug Administration in 2012. Delamanid meanwhile has received “conditional approval” by the European Medicines Agency, meaning it still requires more evidence of effectiveness, though it can be used in some cases following WHO policy guidelines. However, the drugs have only been registered to date in a limited number of countries: Bedaquiline is only registered in 10 out of 30 high-burden MDR countries, while delamanid is registered in two high-burden MDR countries to date. While bedaquiline isn’t formally registered yet to all high-burden MDR-TB countries, J&J has delivered 43,000 courses of the drug to 95 countries, including those where it isn’t yet registered. This was done through different collaborations, including with the Stop TB Global Drug Facility, said Jessica Freifeld, J&J’s director of communications for global public health.
The need for TB warriors
At the TB-DOTS facility in RMC, there are only two nurses in charge of following up on TB patients. During a visit at the hospital one Tuesday afternoon, Ann Beatrice Doloiras, the facility’s TB-BOTS nurse coordinator, was juggling between checking on TB patients, answering new enquiries, and attending to her administrative duties. Every quarter, she reports to the regional Department of Health office on how their facility is faring in managing TB cases, and twice a year she participates in a regional DOH office initiative on TB planning and implementation review.
She is also in charge of making sure their TB medicine supplies are sufficiently stocked and that they are up to date with the latest TB guidelines.
On that Tuesday afternoon, a patient was clinically diagnosed to have TB of the skin, but Doloiras notes they don’t have that guidance in the manual and need to consult with the regional DOH office.
Doloiras has been nurse at the facility for no more than 2 years, but she has proven to be adept at her job, almost memorizing the different regimens that each type of TB patient requires. But with the skills she has developed in TB management, there’s a high chance she may be promoted to take on other hospital tasks, as was the case with her predecessors.
The clerk in charge at the facility, who was also able to furnish patients with answers to common questions such as whether sharing utensils will spread TB infection to other house members, may also be absorbed by the hospital, leaving the position vacant, again.
“If she does well, she gets promoted,” said Dr. Primo Valenzuela, TB-DOTS medical coordinator at RMC, pointing to the problem of high transition rates in some TB programs matched with low application rates.
A number of TB programs, in the Philippines or outside the country, hire contractual staff. In some facilities, at the barangay level, health care workers for TB programs can be volunteers and only receive allowances.
But if TB programs were to improve on contact tracing and patient compliance — two concerns that Dr. Valenzuela and Doloiras note are the main challenges they encounter in their TB control program — then more professionalization of TB health care workers and provision of incentives may be necessary.
But having dedicated, not just more, health care workers, is key.
“No matter the kind of treatment, if you can’t get commitment from patients, then it’s useless,” Doloiras said in Filipino. “On my part, I share with them my experience of going through TB treatment to show that I can empathize with their struggles. Sometimes, all a patient needs is the reassurance that TB is treatable.”
Update, March 1, 2018: This story has been updated to reflect a comment from J&J, including that bedaquiline was approved in Ethiopia last week, bringing the number of high-burden MDR-TB countries where it has received formal registration to 10.