A lab technician analyzing a blood sample in the medical laboratory at Nukus MDR TB hospital, Karakalpakstan, Uzbekistan. Photo © Ernst Fischer
The very costly and complex treatment for multidrug-resistant tuberculosis is only accessible to a very small minority among the millions of people affected by the disease worldwide. What's worse, those who have started taking the medicine are subjected to devastating side effects, and barely half of them end up recovering. In the Doctors Without Borders/Médecins Sans Frontières (MSF) program in the separatist republic of Abkhazia in Georgia, day after day MSF sees how toxic the treatment is, and must deal with the lack of tools to properly treat people living with multidrug-resistant tuberculosis.
Kirukhim was the first patient undergoing treatment in August 2001, in the program MSF designed to look after multidrug-resistant tuberculosis (MDR-TB) in Abkhazia. Because he was homeless, he stayed in the hospital for nearly four years, duly following his treatment, swallowing handfuls of medication day after day. He went through relapses and remissions, endured the treatment's devastating side effects and only the hope that he would be cured kept him from sinking into depression. But nothing worked.
"After nearly four years of treatment, his TB test became positive once more," remembers Dr. Cathy Hewison from MSF's medical department. "We had to declare therapeutic failure. After so much effort, it was an extremely painful decision for the patient and for the team. In August 2005, following two months of palliative care, Kirukhim died."
The extreme difficulty in treating multidrug-resistant tuberculosis
In total, 89 patients started treatment to fight MDR-TB in the MSF program in Abkhazia. Thankfully, all did not meet the same fate as Kirukhim. Thirteen patients are considered cured. Forty-five of them are still undergoing treatment, with the hope of overcoming the disease. But one-third of the patients has either died or defaulted from treatment. This high proportion demonstrates how extremely difficult it is to treat MDR-TB.
To start with, over two months go by between the first meeting with a patient and the time when the MDR-TB diagnosis can be given. Dr. Hewison explains, "the required tests are very complex and no laboratory is capable of conducting them in the countries we operate in." For our program in Abkhazia, samples must be taken all the way to Rome! "While waiting for the results, for lack of an alternative, we prescribe the standard treatment against the simple form of tuberculosis, without knowing if it is adapted and even risking resistance development."
At least two years of constraining treatment, under direct observation...
Once MDR-TB is identified with certainty, it is indispensable to talk with the patient and his or her caregivers. "We tell them the treatment is very long, with very severe side effects, and important constraints," says Dr. Hewison. "Upon starting a treatment, the patient must know he will not be able to work, sleep with his spouse, or play with his children for a long period of time. If the person accepts those rules, he or she signs a contract whereby the person promises to respect them."
The treatment can then start. The intensive phase, which takes place in the hospital, lasts a minimum of six months. The patient takes a mix of five drugs, which means one painful injection per day and a handful of tablets every morning and afternoon. The subsequent phase lasts at least 18 months. The injections stop, but the number of tablets doesn't go down. Hospitalization isn't indispensable, but since medication is always taken under direct observation—which forces the patient to come twice a day into the hospital—going away is out of the question. In Abkhazia, patients who aren't from Sukhumi (the capital, where the MSF project is based) thus cannot go back home.
As toxic and violent as chemotherapy
"The length of the treatment makes it extremely difficult. But most of all, it's important to realize that it's as drastic and toxic as chemotherapy used against cancer," says Dr. Hewison. Side effects are not only unpleasant; they're unbearable and can be dangerous. Several molecules have terrible gastric effects, trigger nausea, cause the kidneys and liver to malfunction, and lead to severe anorexia. When tuberculosis isn't the cause of weight loss among patients, the medication itself risks weakening them. The treatment can also trigger severe joint pain. In order to counter those side effects, the only solution is adding more tablets to the already extremely high daily pill count. Cycloserine, another type of medication used against MDR-TB, may lead to serious psychiatric problems (depression, suicide, and psychosis).
"One of our patients sliced open his stomach with a knife because he thought a monster was inside it. We must look out for the slightest sign (paranoia, hallucination, epilepsy...) in order to immediately stop giving cycloserine and treat the psychosis," says Dr. Hewison. When certain types of medication must be stopped due to overly severe side effects—more than a third of all patients stop taking at least one of the molecules during the treatment—there is no alternative solution. "We then replace it with two second-line antibiotics, without being certain it's truly efficient. But it's the only chance there is."
The chances of success are too low, research must be urgently revived
In the world today, no one knows exactly how many people are affected by MDR-TB. The World Health Organization speaks of 2 million cases and 425,000 more people infected each year. Because of the treatment's complexity and cost, only a very small portion of all patients has access to it. Of those that begin a treatment, barely half will end up recovering. This frightening observation highlights how urgently research must be re-launched in order to properly treat patients and prevent MDR-TB from spreading.