For patients waiting for XDR-TB treatment in Romania, someday never comes

In March 2014, Jonathan Stillo, a member of TB Europe Coalition’s Steering Committee, participated in the joint World Health Organization (WHO) and European Centre for Disease Control (ECDC) National Tuberculosis (TB) Program Review in Romania on a team of eleven international and fifteen national experts. This blog does not necessarily reflect the positions of WHO or ECDC and should be seen as one research and advocacy expert’s opinion that is informed by eight years of working in Romania. The published 2014 review of Romania’s TB program should be available in early autumn.

Right now, 30,000 Romanians have various forms of TB. This is by far the largest number in the European Union (EU), accounting for about 25% of all cases in member states. Over the past ten years, the overall TB incidence in Romania has dropped steadily. However, even after this reduction, Romania’s TB incidence and prevalence eclipse all other EU countries. The Romanian incidence rate is presently more than five times the EU average and about twenty times higher than low incidence countries such as Germany. Romania also has the largest number of drug resistant TB cases in the EU. About 1,500 people are living now with Multi-Drug Resistant (MDR) or Extensively Drug Resistant (XDR) TB, but only about 20% of these patients are able to receive treatment that meets international standards through the country’s Global Fund grant. This has resulted in a national MDR-TB treatment success rate of 20% which is among the lowest recorded in the world, and actually similar to the historical “spontaneous cure rates” of patients who receive no medication at all.

The international community are extremely concerned about TB in Romania. Romania is presently writing a new TB strategy and its Global Fund concept note. It is my hope that what emerges will be a bold, comprehensive, and sustainable plan. High-level commitment and responsibility for the problem are necessary and must come from within, not from outside of Romania. Now is the time for the Romanian government to take aggressive action by supporting the Romanian Ministry of Health and National TB Program. This action by the Romanian government could single-handedly bring the entire European Union closer to TB elimination. It should be noted that while TB is a problem requiring political commitment, it is not an issue to be politicized. There are individual supporters of TB control in many parties, but none has yet to turn this support into tangible funding from the Ministry of Finance necessary to address the large funding gap.

One of the main recommendations of the 2014 WHO/ECDC TB program review is “Ensure an effective centralized procurement and the uninterrupted supply of all internationally recommended anti-TB drugs (first, second and third line), including for their compassionate use…” There is well-documented evidence of local second-line drug stockouts and national shortages which have led to treatment interruptions and may be contributing to the creation of the cases of XDR-TB—a problem highlighted in the 2014 WHO/ECDC review findings. It will require more than outside funding to address internal delays and blockages of drug registration, approvals, procurement and distribution.  The persistence of drug supply issues suggests that the poor MDR-TB treatment success rates can be expected to continue in the future—perhaps for two years[1] after an appropriate amount and uninterrupted supply of these crucial medications become available. This includes second-line injectable drugs such as amikacin/kanamycin of which stockouts were identified in 2009 in the WHO/ECDC TB review and shortages have been the norm in the years since.

The TB situation in Romania is dire. In addition to drug shortages, directly observed therapy is unavailable in much of the country’s rural areas where 45% of the population lives. Only half of TB cases ever receive first-line drug susceptibility testing and results usually take several months. This is not the fault of Romanian TB doctors, most of whom are dedicated to their patients, nor the Ministry of Health, which is constrained by the smallest budget as a percent of Gross Domestic Product (GDP) in the EU.  Furthermore, the Romanian National TB Program and Ministry of Health are constrained because of the politics surrounding the sort of major structural reforms that will be necessary to address the challenges in Romania’s health system—especially aging infrastructure and staff and a geographic maldistribution of services that denies many of the 45% of the population living in rural areas access to basic health care. More effort should be dedicated to providing robust primary and preventative care that is patient-centered and accessible to all, regardless of location or income level. Because TB, and especially M/XDR-TB is a major cross-border health threat, no compromises should be made when it comes to finding and curing patients and preventing their relapse. There is ample evidence to show that this is a smart investment (eg. a 2013 by Diel, R. et al that conservatively estimates the economic costs of TB in the EU at 5.9 billion euros per year.)

Another major challenge the WHO/ECDC review team identified is infection control. “Patients are unnecessarily admitted and kept in hospital for a long time, sharing the same environment with non-TB patients and other TB patients regardless of their infectious status. These are conditions for nosocomial transmission of TB among patients and hospital staff and potential for litigations and financial compensations by the hospital administration.” Weak infection control measures pose a clear danger to both patients and staff. That TB patients mix regularly mix with non-TB pulmonology patients in shared dining facilities, bathrooms and other common areas, places those without TB at great risk for developing TB, especially those with conditions such as silicosis which is known to increase TB risk. Patients who were positive, negative, and with different or unknown levels of drug resistance (MDR, pre-XDR and XDR) were placed together. This makes it possible for patients to become infected with different strains of TB, that are resistant to the medications they are taking. In fact, many patients have told me they are afraid of this possibility. The way forward for Romania should include options for patients who do not require such long periods of hospitalization. This means strengthening local capacity for DOT and adopting a more flexible approach where savings from reduced hospitalization could be used to strengthen community care.

Romanian TB patients’ need for social, economic, and psychological support is poorly met yet of critical importance. Earlier this month, The Romanian Angel Appeal and the Association for the Support of MDR-TB Patients published research that examined these needs from the perspectives of both patients and caregivers. Because the Romanian National TB program receives only a fraction of the funding that experts estimate it needs to properly diagnose and treat patient, advocacy, education and destigmatization activities are neglected, unless funded by outside sources. Despite the dramatic situation of patients with MDR and XDR dying without the proper medications, civil society has been relatively quiet, at least in part due to the limited funding available for “softer” advocacy activities. Consequently, many decision makers in Romania are not convinced of the seriousness of the issue, instead incorrectly believing that the disease is a Roma (gypsy) problem, or that it will fix itself as the country develops economically.

A number of international organizations treat XDR-TB with great success in high burden places such as Partners in Health in Tomsk, Russia and Médecins Sans Frontières in Khayelitsha, South Africa. These projects might be seen as proof of concept that even in resource limited settings, with appropriate diagnosis, treatment support, and collaboration, XDR is curable—not just by NGOs, but also by an increasing number of national TB programs. Health authorities in other European countries have been treating and curing XDR-TB for years. Notable examples include the Netherlands, France, and Italy, which has generously treated numerous Romanians with XDR-TB, all of whom would almost certainly be dead with the treatment options presently available in Romania. Even much poorer Moldova has begun treating XDR-TB patients using linezolid earlier this year.

Sending Romanians with MDR and XDR-TB to other countries is not a sustainable solution. They deserve access to the same quality of treatment as other EU citizens. Elena, a 34-year old XDR-TB patient from a small village in the north of Romania has not yet been sent elsewhere. Instead, she is in Romania, a European Union and NATO member, the 31st wealthiest country in the world, but by the admission of some of the top TB doctors in the country, at least two generations behind in both diagnostics and treatment of drug-resistant TB.

Elena has four children and like others in her village, she struggles to survive by growing what she can on a small plot of land and receiving a small welfare benefit from the mayor’s office. She told me that the children’s father had left them. When Elena was pregnant, she went to the hospital for a checkup, and was told that she had TB. She was shocked and didn’t know anything about the disease. She remained hospitalized for months, but was not responding to standard treatment. After several months her 1st line DST results showed she had MDR-TB. She was then transferred to one of Romania’s two MDR-TB treatment centers which receive second-line medications through the Global Fund grant. Two months after she arrived, she was still positive and when her 2nd line DST results came back, she found that she was infected with XDR-TB. The previous hospitalizations and months of treatment had been for nothing- a waste of money for Romania and a great economic and personal cost to Elena. When I met her, nine months had passed since she was diagnosed.  She wept as she described missing her little boy’s first year of school. Her brother is trying to help the family, but they lost both parents to cancer recently and have few to turn to.

After more than six months of receiving drugs that she was resistant to, Elena’s real battle with XDR-TB began. Presently, Romania does not provide many of the drugs that are used to treat XDR successfully around the world such as linezolid, clofazamine, and imipenem-cilastatin. These drugs are not miracle cures. They have terrible side effects,  but are among the only options for patients with highly resistant TB (see Treatment Action Group’s new TB drug guide for easy to understand explanations of each) Right now, the only way for a Romanian XDR-TB patient to get access to these life-saving drugs is to seek treatment in another EU country or to get the drugs themselves, usually by buying them on the internet or having them brought from another country. The doctors at Romania’s two MDR centers have world-class skills and are committed to curing their all of their patients. However, they can do little without the right medicines. Until the drugs arrive, all they can do is ask their patients to wait. It is an unethical situation that infringes upon the human rights of TB patients and undermines the Hippocratic Oath and professionalism of Romania’s caring and gifted TB doctors who know that patients like Elena are curable.

Three months ago, I told Elena that soon new drugs would come to Romania through the Global Fund and Norwegian grants and that these drugs would be much stronger than what she was receiving then. However, “soon” in public health terms is often too late for individual patients. It has been one year since Elena was first diagnosed with TB, but effective treatment for her still has not arrived and will not many months. If there is one thing I have learned from researching tuberculosis in Romania for the past eight years, it is that there have never been a shortage of plans, strategies and promises. I have spent years believing that someday soon, everything will change. However, for Romanians with XDR-TB, except for the lucky few who get on a bus or a plane and become medical refugees, throwing themselves at the mercy of other European countries, someday never comes. How long can patients like Elena wait? And if she dies, what will the promise of future XDR-TB treatment be worth to the four orphans she will leave behind?

[1] MDR-TB treatment success rates are reported after 24 months of treatment.

Source: TB Europe Coalition