BISHKEK, Kyrgyzstan — When Eremina found out she had multidrug-resistant tuberculosis in 2017 and was headed to hospital, she was convinced she’d never go home. Two of her relatives with TB had disappeared into decrepit old sanatoriums about 17 years ago, and they had spent years getting treatment before eventually dying there. “So I said goodbye to everyone,” she said.
But she eventually recovered — spending just two months in hospital and receiving outpatient care for another seven months.
Those were nine long months: “I had to lie down and wait for the medicine to work through me. I could only get up from bed in the late afternoon,” she said.
A 48-year-old who lives alone and subsists on the money she makes from odd jobs in house repair, Eremina was unable to work, and couldn’t afford to buy food or pay her electricity bill. But the treatment itself was free of cost, and she’s now back at work.
“Drug-resistant TB is a huge global health security issue and it is one of the most significant challenges in responding to the TB epidemic.”— Cheri Vincent, division chief for TB at the Office of Infectious Disease, USAID
Eremina’s successful treatment reflects a number of changes that began in the region in early 2017 and a new method of treating MDR-TB, which is caused by bacteria resistant to at least two first-line treatment drugs.
This approach has been made possible in the region by the U.S. Agency for International Development, along with their Dutch technical partner, KNCV Tuberculosis Foundation. And it reflects USAID’s TB strategy worldwide, which is twofold: focusing on local capacity building in order to ultimately rely on local solutions and resources; as well as funding research and development to move to a purely oral treatment regimen in concordance with the latest World Health Organization guidelines.
In Kyrgyzstan and other post-Soviet states, USAID’s strategy to defeat TB includes cutting health care expenditures — in part by putting an end to interminable hospital stays. What this looks like on the ground is shortened treatment regimens for drug-resistant TB, and limiting hospital stays to two months or until patients are no longer contagious, with treatment continued on an outpatient basis and supplemented with support and follow-up by social workers.
MDR-TB patients diagnosed for the first time, like Eremina, now undergo a nine-month regimen, down from the two-year-long “standard regimen,” which featured toxic chemotherapy drugs and could run up to 14,000 pills plus daily injections for six months. Patients who are resistant to the most potent drugs available — those with extensively drug-resistant TB or XDR-TB — are now administered an "individualized regimen" which is tailored to their drug sensitivity tests, and spans 18-24 months.
A high-burden country for drug-resistant TB
Kyrgyzstan is one of 30 countries in the world grappling with the highest burden of multidrug-resistant tuberculosis. Of the 30 countries designated by WHO as “high-burden countries” for this hard-to-treat strain of the disease, about a third are post-Soviet states. The disease costs the Kyrgyz government around $12 million a year to treat. USAID Kyrgyzstan Mission Director Gary Linden said around 8,000 new cases of TB crop up in the country every year, of which 1,300 have a drug-resistant form of the disease.
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Drug-resistant tuberculosis cases are exponentially more expensive to treat and account for over one-third of the world’s deaths attributable to antimicrobial resistance. Which is why tackling the problem worldwide is a “huge priority,” according to Cheri Vincent, division chief for TB at the Office of Infectious Disease at USAID, which has been involved in fighting the disease for 25 years.
“Drug-resistant TB is a huge global health security issue and it is one of the most significant challenges in responding to the TB epidemic,” Vincent said.
When the drug resistance problem was first detected in the 1990s, the most urgent issue was surveillance and early diagnosis. “USAID and the U.S. government were among the first to support countries to introduce diagnosis and treatment of drug-resistant TB,” she added.
With so many of the drugs to treat TB bringing on side-effects that range from the unpleasant — nausea, rashes, a lurid tan — to the intolerable — hearing loss, psychosis — drop-off rates pose a huge risk to the worldwide efforts to eradicate the disease by 2030, and the ambitious targets that high-burden countries such as Kyrgyzstan committed to at the first U.N. High-level Meeting on Tuberculosis held last September.
“Our goal, along with the broader TB community, is to develop a three-drug, all-oral regimen for MDR-TB in the next five years,” Vincent explained. “We have several promising combinations that we’re studying, and we’re hopeful. But obviously, we’ll have to let the evidence speak for itself.”
Improved results, improved compliance
In Bishkek, USAID’s Linden is very pleased with the initial results of the new approach. Linden says that preliminary results from the first cohort treated with the new regimen started early in 2017 suggest a dramatically improved success rate. For MDR-TB patients, the success rate has gone from 53% to 80%, and for XDR-TB patients, it’s gone from a mere 11% to 88%.
“Before, almost 1 in 4 patients was defaulting treatment due to the long, toxic standard treatment course,” Linden said. “But two years after the introduction of new TB drugs and new treatment methods, the rates of patients who discontinue treatment has decreased from 25% to just 7-8%.”
But even the lower dropout rates can be dangerous, leading organizations such as USAID and KNCV to introduce measures to boost compliance. These include individualized case management with active monitoring of side effects, and directly observed treatment, which ensures that low-income patients and those who live far from hospitals can send daily video-dispatches of themselves taking all their pills.
Under this program, phones are loaned to patients who don’t have them for the duration of their treatment. “This is part of our strategy to reduce the barriers that prevent patients from staying on treatment,” Linden added.
USAID and KNCV also provide additional post-care support for high-risk patients, many of whom also have HIV or hepatitis B. USAID and the Red Cross also arrange food donation programs for TB patients. “They need to double or triple their caloric intake for the medication to be effective — which is not cheap,” Linden explained.
Under USAID’s current Administrator Mark Green, doing more with less is a guiding principle for the organization. This in part hinges on the “path to self-reliance.” In the longer term, this means allowing governments to invest more of their own resources for TB control programs. In the medium term, this means advising local governments to seek local solutions, and to follow more cost-effective policies, USAID officials said.
“What we’re finding now is that shorter hospital stays and shorter regimens both increase treatment adherence.”— Totugul Murzabekova, project coordinator, Challenge TB
The biggest change that this policy has had in Kyrgyzstan is the closure of Soviet-style TB hospitals, and redeploying the savings to fund the push toward case management and outpatient care.
“Before, TB patients used to spend about seven years under treatment and observation in these Soviet-style hospitals,” recalled Totugul Murzabekova, a TB physician who works as a project coordinator with USAID’s Challenge TB program, in conjunction with KNCV. These places had a dining hall, a few wards, showers, and common toilets, and no individual wards. What passed for infection control was moving people from an “active” group to a “recovering” group — making the hospitals ripe grounds for TB to develop, case managers said.
“Also, they were expensive, as they provided free food, medicine, and drugs,” Murzabekova added. “What we’re finding now is that shorter hospital stays and shorter regimens both increase treatment adherence.”
Historically, TB has not received the same political and social pressure for government and scientific action that other diseases — such as HIV/AIDS — have had. That might be beginning to change, some experts say.
According to Nora Madrigal, USAID’s health and education office director in Kyrgyzstan, the TB Optimization Plan, adopted in 2017, drove down the number of beds set aside for TB patients from 3,350 to 2,335 in 2018, while the number of non-TB patients hospitalized in TB hospitals fell by 75%. Overall, TB hospitalizations fell by 41%. The reduction in hospitalization, Madrigal said, saved the government $1 million in 2018.
“These funds, along with current and future savings, will be used to fund incentive payments per treated case for health care workers, hospital renovations, scale up outpatient treatment at primary health care facilities and support the purchase of TB drugs, and purchase consumables and reagents for TB laboratory diagnostics,” Madrigal added.
Gaps and weaknesses
With resource-intensive methods like individualized case management being the most effective way to tackle drug resistance, funding remains the biggest challenge in lower middle-income countries including Kyrgyzstan.
USAID officials pointed out that leveraging domestic resources is crucial, regardless of their intention to decrease funding for international aid, as 80% of the worldwide funding for tackling TB comes from domestic sources. Not all countries, however, have the resources to invest in TB. While countries such as those from BRICS are taking on a bigger share of their TB programs, others still rely largely on external resources such as the Global Fund to Fight AIDS, Tuberculosis and Malaria.
There are also significant gaps in funding for research and development of shorter regimens and new drugs. In its 2018 Global Tuberculosis Report, WHO pointed out that while funding for tuberculosis research peaked at $724 million in 2016, it is still only 36% of the estimated requirement of $2 billion per year.
“That’s even combining domestic sources, the U.S. government, and the Global Fund,” Vincent said. “So we’re trying to fill that gap, and help countries meet their ambitious UNGA targets.”
Stigma and discrimination remain a huge challenge too, particularly with many patients coming from marginalized groups, such as prisoners and migrants. According to WHO data, an estimated 3.6 million tuberculosis patients were “missing” in 2017 — they went undiagnosed, untreated, or their cases went unnotified or uncounted by their governments.
While the global rate of TB incidence has been falling at the rate of 2% annually, and mortality at 3%, according to WHO, aid agencies acknowledge that only a technological breakthrough can ensure the disease can be eradicated altogether.
“We have a ways to go and we’re not going to be able to achieve our targets without new tools and new drugs,” Vincent said. “So we have been working with other partners, investing in new tools, new treatments, new regimens, and helping with access programs for new drugs.”
Editor's note: The reporter traveled to Kyrgyzstan with the support of KNCV. Devex retains full editorial independence and responsibility for this content.